Diagnostic Imagaing Europe Magazine March 2013

Page 1

DI EUROPE

Diagnosis • Technology • Therapy • Prevention MARCH 2013

Hospital Spotlight Constant technological innovation maintains high repiration of Swiss Breast Care center.

A talk with Dr Martin Sonneschein of the Engeried Klinik, Berne, Switzerland

EUROPE

•C onsensus statement on CT colonography • How to get computeraided diagnosis into the clinic •V ictims of medical Imaging technology (VOMIT) • I mprovement in visualization of prostate cancer with shear wave elastography •O ptical Coherence tomography (OCT) for the diagnosis of non-melanoma skin carcinoma • Imaging News

PET-MRI:

so far, so good

Now the hard bit:

cost/benefit justification

• Industry News • Technology Update • Book Review

­


Connecting for healthier lives

Discover our ECR 2013 program Find out how GE Healthcare is connecting for healthier lives by combining the needs of healthcare professionals and patients for exceptional imaging solutions. Check out our full program at www.gehealthcare.com/ECR2013 Hear from leaders in the fields of MR, breast imaging, and CT at our 3 lunch symposia Visit us at the booth and take the opportunity to: Explore advanced innovations in healthcare technology Immerse yourself in our scientific program focusing on exceptional imaging techniques Engage with our experts during our News Forum sessions Register online or at the booth


DI EUROPE

BY Alan barclay, Ph.D.

FROM THE EDITOR

VOLUME 29, NUMBER 2 EDITORIAL ADVISORY BOARD Andreas Adam, London Frits H. Barneveld Binkhuysen, Amersfoort Filipe Caseiro Alves, Coimbra Maksim Cela, Tirana Katarzyna Gruszczynska, Katowice Andrea Klauser, Innsbruck Gabriele Krombach, Giessen Philippe Lefere, Roeselare Luis Martí-Bonmatí, Valencia Anne Paterson, Belfast Hans Ringertz, Stockholm Valentin E. Sinitsyn, Moscow Thomas J. Vogl, Frankfurt

Richard P. Baum, Bad Berka Elias Brountzos, Athens Carlo Catalano, Rome Patrick Cozzone, Marseille Anne Grethe Jurik, Arhus Gabriel Krestin, Rotterdam Christiane Kuhl, Bonn Heinz U. Lemke, Kuessaberg Thoralf Niendorf, Berlin Anders Persson, Linköping Gustav von Schulthess, Zurich Patrick Veit-Haibach, Lucerne

EDITORIAL STAFF Editor US Consulting Editor Editorial coordinator

Alan Barclay, Ph.D. Greg Freiherr Denise Astbury

Publisher Associate Publisher

David Lansdowne Bob Warren

EDITORIAL Contact Rue des Noisetiers 9, 1421 Ophain, Belgium Tel. +32 479 370 364 E-mail: a.barclay@dieurope.com E-mail: d.astbury@dieurope.com

SUBSCRIBER SERVICES Telephone: +44 1442 877777; Fax: +44 1442 870617 E-mail: d.astbury@dieurope.com

INTERNATIONAL SALES OFFICES Europe & North America

Japan

DI Europe Ltd E-mail: d.lansdowne@dieurope.com Telephone: +(44) 1442 877777 Fax: +(44) 1442 870617 Contact: David Lansdowne Contact: Bob Warren E-mail: b.warren@dieurope.com

Orient Echo Inc. E-mail: mashy@fa2.so-net.ne.jp Telephone: + (81) 3/3235-5961 Fax: + (81) 3/3235-5852 Contact: Masahiko Yoshikawa

China

Korea

Adept Marketing Unit B, 13/f, Por Yen Building, No 478 Castle Peak Road, Cheung Sha Wan, Kowloon, Hong Kong E-mail: adonism@adeptmkg.com.hk Telephone: +852 2891 7117 Fax: +852 2893 2101 Contact: Adonis Mak

Young Media Inc 407 Jinyang Sangga 120-3 Chungmuro 4 ga Chung-Ku, Seoul, Korea 100-863 E-mail: ymedia@chol.com Telephone: +82 2 2273 4819 Fax: +82 2 2273 4866 Contact: Young J. Baek

Article Reprint Sales

DI Europe Ltd Tel: +44 1442 877777 Email: d.astbury@dieurope.com

DIAGNOSTIC IMAGING EUROPE is published eight times a year by DI Europe Ltd Printed by Manson, St-Albans, UK. Annual subscriptions are available for €60 within Europe where it is also sent free of charge to physicians and radiology department heads. Outside of Europe, there is an annual subscription charge of €110 for air mail. Single copy price is €10. Editorial Advisory Board members suggest topics for coverage and answer questions for the editors. They do not conduct a formal peer-review of all manuscripts submitted to DI Europe. Copyright © 2013 DI Europe Ltd. All rights reserved. Reproduction in any form is forbidden without express permission of copyright owner.

DI Europe Ltd 2 Claridge Court Lower Kings Road Berkhamsted, Herts HP4 2AF UK Telephone: +44 1442 877777 Fax: +44 1442 70617

MARCH 2013

Awareness days:

M

aybe it’s just a lack of previous knowledge or yet another example of the syndrome of waiting for a bus for so long that when suddenly three turn up at once it seems as though the law of averages must have been at least temporarily suspended. However since the International Day of Radiology was celebrated in November last year with great — and justifiable— pomp and enthusiasm, it seems that the number of special days dedicated to some worthy medical cause or another has continued to increase. Thus, we have, or maybe always have had — and depending on individual countries, a breast cancer awareness day (this year October 19th), a colorectal cancer day, March 1st —when we are all invited to wear blue for some reason as the symbol of solidarity and understanding of this type of cancer. There is a melanoma Monday ( May 6th), while for prostate cancer there is even a whole month (October) during which we are supposed to be particularly aware of the features of prostate cancer. There are many other health-related awareness days, but most are dedicated to raising awareness of cancer, so as a catch-all of all awareness days there is the world Cancer day, which this year was on 4th February. The majority of such “cancer awareness” campaigns are, as they should be, directed to the general public, in the name of improving general knowledge around a particular disease and dismissing misconceptions about disease. Such efforts are of course entirely laudable — particularly so when they have a chance of making people more aware of what are frequently the most straightforward methods of avoiding many modern diseases, namely by modifying potentially dangerous life-styles. The problem is that a sort of “awareness day” fatigue can set in, similar to the well-known syndrome of compassion fatigue where an initially sympathetic public becomes ultimately indifferent to the sight, for example, of the distended bellies of D I

E U R O P E

all year long

poor, starving African orphans and stop contributing to the charities that try to help. Directed as they are to the general public and particularly to patients suffering from particular diseases, such awareness campaigns are in essence different to the specific campaign for radiology awareness exemplified by the International Day of Radiology (IDoR) last November. The clearly expressed, and totally valid, objective for the IDoR was to promote radiology not just as a profession but as a vital component of the overall health system. Just as the relevance of the awareness of, for example, breast cancer is clearly valid for much more than the special awareness day, so must awareness of the contribution of radiology be communicated for more than just one day a year. This is an on-going matter and one of significance. The fact is that the role of the radiologist is completely unknown or misunderstood by an astonishingly large number of the general public. Alarming as this is, many radiologists console themselves that at least their role is known and appreciated by the medical community at large. With the on-going turf wars between clinical specialists and radiologists such complacency is dangerous. While it is true that the ever-rapid development of modern scanners means that, more and more, clinicians are increasingly dependent on the results of radiological examinations, the fact is that non-radiologists are gaining increased experience in and familiarity with medical imaging in their particular specialty. As Drs McCoubrie and Reid (DIEurope this issue p 44) point out the danger is that the precise roles of clinicians and radiologists can become mixed with clinicians becoming tempted to greedily help themselves to the “investigational chocolate box”. The message is that awareness of radiology and promotion of the discipline should not be limited to a single day but, like all other awareness days, be an on-going constant effort. n 3


®

MARCH 2013

EUROPE

Elastography Currently prostate cancer is diagnosed by a randomized transrectal ultrasound guided biopsy. However, such randomized “blind” biopsies can miss cancer. ShearWave Elastography technique is an automated, user-friendly and quantifiable method for the determination of prostatic tissue stiffness and has been shown to improve significantly the visualization of prostate cancer ������������������������������������������������������������������������������ 51

Front cover image

REPORTS

The development and clinical deployment of hybrid PRT/MRI systems has enabled the assessment of the possibly groundbreaking potential of the approach. Despite this, formidable challenges remain, not the least of which is economic justification.

REGULARS 03| From the Editor

19-22| I ndustry Outlook

New opportunities to advance patient comfort, improve productivity, increase diagnostic accuracy, and provide greater patient involvement are emerging.

28| N ew hands on the wheel

Optical Coherence tomography (OCT) — a new tool for the diagnosis of nonmelanoma skin carcinoma

Page 63

at guerbet

Hand-held echocardiography will not make high-end echocardiography redundant. but has the potential to revolutionize clinical medicine

Steroid receptor ligands as PET imaging agents

Page 70

Page 66

46| C onstant technological

innovation maintains high reputation of Swiss Breast Care Center

49| Mammography in a private radiology practice: a look at the Zola practice in Nantes, France

55| Boo k review

iagnostic Imaging 7th Edition, by AG D Rockall, A Hatrick, P Armstrong & M Wastie

5-12| Imaging News 40-42| I ndustry News

The latest news on which company is doing what.

73-78| Technology update

The second ESGAR consensus statement on CT colonography. . . . . . . 13 Laxative-free colongraphy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Advances in hybrid PET-MR imaging. . . . . . . . . . . . . . . . . . . . . . . . . . 24 How to get computer-aided diagnosis into the clinic . . . . . . . . . . . . . . 31 Promising advances in computer-aided detection of breast cancer. . . . 35 PACS in intensive care units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 VOMIT (Victims of Medical Imaging Technology) and the optimal use of medical imaging technology . . . . . . . . . . . . . . 44 An innovative diagnostic image sharing network. . . . . . . . . . . . . . . . . 54 Emergency imaging with contrast enhanced ultrasound . . . . . . . . . . . 56 Hand-held Echocardiography — a “small” revolution. . . . . . . . . . . . . . 66

Visit us at

DI EUROPE MARCH 2013

D I

E U R O P E

COMING SOON in the Month issue: Computer-aided diagnosis Mammography PACS update

4


IMA GI N G NEWS Prototype second-generation CT scanner substantially reduces radiation exposure Researchers using a newly approved advanced computed tomography (CT) system have been able to significantly reduce radiation exposure in patients undergoing coronary CT angiography (CCTA), according to a new study published in the journal Radiology (Chen et al Radiology 2013; Jan 22). “Radiation exposure during diagnostic imaging is of concern,” said Marcus Y. Chen, M.D., lead author of the study which was carried out in the advanced cardiovascular imaging laboratory at the National Institutes of Health in Bethesda, MD, USA. “Minimizing radiation exposure while maintaining diagnostic-quality scans is clearly feasible with this new second-generation 320–detector row CT scanner.” The study describes the initial coronary angiography results obtained with a prototype 320–detector row CT system recently approved by the U.S. FDA. The new system holds several technical advantages including a gantry rotation time of 275 milliseconds,

wide volume coverage, iterative reconstruction, automated exposure control, and a larger X-ray power generator. For the study, Dr. Chen and colleagues performed contrast–enhanced CCTA with a second-generation 320-slice CT system on 107 adult patients (mean age, 55.4) and compared radiation exposure and image quality to those of CCTA exams previously performed on 100 patients using a first-generation 320-slice scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers. The median radiation dose was 0.93 mSv with the second-generation unit compared to 2.67 mSv with the firstgeneration unit. The median SSDE was 6.0 milligray (mGy) with the secondgeneration unit compared to 13.2 mGy with the first-generation unit. Overall, the radiation dose was less than 0.5

New imaging technique for identifying the age and sex of a corpse Researchers at the University of Granada, Spain, have designed a new computing system that determines the age and sex of a corpse with a reliability of 95%. This system is based on free software called Image and a free

DICOM displayer called K-Pacs. This state-of-the-art system is very different from the traditional macroscopy systems used to evaluate the osteoarticular features of a corpse, and is much faster and user-friendly. The author

mSv for 23 of the 107 CT angiography exams, less than 1 mSv for 58 exams, and less than 4 mSv for 103 exams. All studies were of diagnostic quality, with most having excellent image quality. “The second-generation CT scanner provided excellent image quality over a wide range of body sizes and heart rates at low radiation doses,” Dr. Chen said. “The low dose achieved during CT angiography could be used to minimize overall radiation dose to the patient or to enable additional types of imaging within reasonable radiation doses.” http://tinyurl.com/Chen-et-al-paper of the report describing this study is Manuel López Alcaraz, a researcher at the Forensic Anthropology Laboratory of the University of Granada, in collaboration with professors Miguel Botella López, Inmaculada Alemán Aguilera and Pedro Manuel Garamendi González. The researchers examined 169 DICOM files of CT scans of patients between 17 and 90 years of age supplied by the Castile-La Mancha health service. The researchers examined the sagittal sections of the articular surface of the pubic symphysis and the pubis itself, thus obtaining four sections: two sections of the right and left symphysis, and two sections of the pubis. Imaging techniques were used to analyze sections, histograms of the structures were obtained and the statistical variables of histograms were entered into the Image program to determine how histograms continued on page 06

MARCH 2013

D I

E U R O P E

5


IMAGING NEWS

New imaging method shows insulin producing cells

Internationally, huge resources are being committed to the development of non-invasive imaging methods for study of the number of remaining insulin cells in patients with developing diabetes. However, a major problem in this area of research is to find suitable contrast agents that specifically bind to the insulin producing cells of the pancreas to allow imaging. In this context, the developed Near Infrared OPT technology can play an important role as it enables the evaluation of new contrast agents. It may also be used as a tool to calibrate the non-invasive read

out by e.g. magnetic resonance imaging (MRI). A new imaging method for the study of insulin-producing cells in diabetes among other uses is now being presented by a group of researchers at Umeå University in Sweden in the form of a video in the biomedical video journal, The Journal of Visualized Experiments. Prof Ulf Ahlgren and his associates at the Umeå Center for Molecular Medicine (UCMM) have subsequently elaborated the technology for biomedical imaging with optical projection tomography (OPT. The present findings describe a further development of the OPT technology by going from ordinary visible light to the near-infrared spectrum. Near infrared light is light with longer wavelengths that can more easily penetrate tissue. This adaptation, to be able to also image in near-infrared light, also means that the researchers gain access to a broader range of the light spectrum, making it possible to study more and different cell types in one organ preparation. In the article the scientists exemplify the possibility of simultaneously tracking the insulinproducing islets of Langerhans as well as autoimmune infiltrating cells and the distribution of blood vessels in a model system for type-1 diabetes. http://tinyurl.com/J-Vis-Exp-video http://tinyurl.com/J-Vis-Exp-Paper

Referring physicians prefer delivering radiology results to patients themselves There is considerable interest in improving radiology reporting practices. It has been suggested recently that reporting practices could be improved by more direct involvement of radiologists

in delivering results to patients and by making clear recommendations within the radiology report. The opinions of primary care physicians about these initiatives are not well known. According to a

New imaging technique for identifying the age and sex of a corpse continued from page 05

are related to age and sex. “Age and sex are essential for the identification of corpses, and the pubis is especially relevant for this purpose. In our study, we exploited the great capacity of computer systems to discriminate between the different gray shades in a histogram (the human eye only can discriminate 64) to determine how histograms can provide information about age and sex”, Lopez Alcaraz states. The researcher notes that this technique might be useful in virtopsies or virtual autopsies. “At present, the main drawback of virtual autopsy is that it cannot replace the macroscopic analysis of tissues for the identification of potential pathologies, determining whether an injury was inflicted before or after death, assessing the course of an injury. As the new technique is based on image analysis, it can be applied to virtual autopsy to provide many more answers than traditional analysis methods. The researcher affirms that this is a step forward in the field of Forensic Anthropology. “We should replace traditional osteological methods with new technologies and exploit the advantages of the visual communications and image era”, the researcher states.”We obtained excellent results in the identification of corpses of people older than 50 years, especially in men”, the author notes. http://tinyurl.com/Alcaraz-paper study in the February issue of the Journal of the American College of Radiology, primary care physicians prefer to deliver the results of radiology examinations themselves and feel medico-legally obligated by recommendations within radiology reports. “There is considerable interest in improving radiology reporting practices. However, as radiologists propose measures to improve reporting, it is wise to obtain an understanding of the needs and opinions of the referring physicians, particularly primary care physicians, regarding these measures so that their feedback and ideas can be incorporated into any change in practice,” said Andrew J. Gunn, MD, author of the study. An online survey was distributed to 229 primary care physicians through an internal list server, and continued on page 08

6

D I

E U R O P E

MARCH 2013


IMAGING NEWS

MRI can optimize placement of fistula in hemodialysis of kidney patients Approximately two million people around the world regularly undergo hemodialysis as a result of kidney failure. This usually involves creating a dialysis fistula in the patient’s arm. However this causes complications in as many as 50% of patients, primarily because of changes in blood flow. Researcher Maarten Merkx

of Eindhoven University of Technology (TU/e) in The Netherlands has developed a system that automatically images the blood vessels in the arm and calculates the expected blood flow through the dialysis fistula. This makes it easy for physicians to find the best surgical strategy to insert the dialysis fistula with minimal chance of complications. At present, physicians determine the location for the dialysis fistula using ultrasound images of the arm. The diameter of the blood vessels is measured manually from such images, but this is not very accurate. That makes it difficult to predict the blood flow through the dialysis fistula. If the blood flow through the fistula is too high it can result in heart failure and insufficient circulation through the hand. If the flow rate is too low it can lead to an inefficient dialysis process. These potential problems make more accurate prediction of the blood flow highly desirable.

The research team developed a system that automatically uses an MRI scan calculates the blood flow in the blood vessels of the arm. The results show that the system allows good prediction of the blood-flow effects, caused by the insertion of the dialysis fistula, in virtually all patients and has proved to be much more precise than the present manual method. The system has a maximum error of 3%, compared with at least 20% for the manual method. The system developed by Merkx converts the MRI images into a kind of ‘wiring diagram’ of the blood vessel system in the arm. A physician can see the calculated flow rate at any point in the network, which enables the best place to insert a dialysis fistula to be located. The introduction of Merkx’s technique can lead to a significant reduction in the number of complications arising in hemodialysis. Despite the use of MRI, which is relatively costly, Merkx believes that his technique will ultimately lead to lower costs due to the reduction in the number of complications. http://tinyurl.com/Merkx-paper

fMRI shows connection error in the brains of anorexics When people see pictures of bodies, a whole range of brain regions are active. This network is altered in women with anorexia nervosa. In a functional magnetic resonance imaging study, two regions that are important for the processing of body images were found to be functionally more weakly connected in anorexic women than in healthy women. The greater this “connection error” was, the more overweight the respondents considered themselves. “These alterations in the brain could explain why women with anorexia perceive themselves as fatter, even though they are objectively underweight” says Prof. B Suchan of the Institute of Cognitive Neuroscience at the Ruhr-University in Bochum, Germany in a recent paper in Behavioural Brain Research. The researchers tested ten anorexic and fifteen healthy women of similar age. To start with, all the women judged on the computer which of several different silhouettes corresponded best to their own body shape. Ten control subjects who did not participate in the MRI scan answered the same question by matching a photo of the test subject to the MARCH 2013

right silhouette. Both healthy and anorexic women estimated their body shape differently than outsiders: healthy subjects rated themselves as thinner than the control subjects. Anorexic women on the other hand perceived themselves to be fatter than the control subjects did. In MRI scanners, the researchers then recorded the brain activity of the 25 participants while they observed photos of bodies. Above all, they analyzed the activity in the fusiform body area (FBA) and the extrastriate body area (EBA), because previous studies showed that these brain regions are critical for the perception of bodies. To this end, the neuroscientists from Bochum calculated the so-called effective connectivity between the FBA and EBA in both hemispheres. This is a measure of how much the activity in several brain areas is temporally correlated. A high degree of correlation is indicative of a strong connection. The connection between the FBA and EBA was weaker in women with anorexia nervosa than in healthy women. In addition, the researchers found a negative correlation between the EBA-FBA connection in D I

E U R O P E

the left hemisphere and the misjudgement of body weight: the weaker the effective connectivity between the EBA and FBA was, the fatter the subjects with anorexia falsely estimated themselves to be. “In a previous study we found that there are structural changes in the brains of patients with anorexia”, says Boris Suchan. “They have a lower density of nerve cells in the EBA. The new data show that the network for body processing is also functionally altered.” The EBA, which has a lower cell density in anorexics, is also the area that stood out in the connection analysis: it receives reduced input from the FBA. “These changes could provide a mechanism for the development of anorexia”, says Suchan. http://tinyurl.com/Suchan-paper 7


IMAGING NEWS

Uncovering the neural mechanism underlying drug cravings

Diffuse reflectance spectroscopy for detection of microcalcifications

Addiction may result from abnormal brain circuitry in the frontal cortex, the part of the brain that controls decisionmaking. Researchers from the RIKEN Center for Molecular Imaging Science in Japan collaborating with colleagues from the Montreal Neurological Institute of McGill University in Canada report that the lateral and orbital regions of the frontal cortex interact during the response to a drug-related cue and that aberrant interaction between the two frontal regions may underlie addiction. Their results are published in PNAS (Hayashi et al PNAS 2013 Jan 28). Cues such as the sight of drugs can induce cravings and lead to drug-seeking behaviors and drug use. But cravings are also influenced by other factors, such as drug availability and self-control. To investigate the neural mechanisms involved in cue-induced cravings the researchers studied the brain activity of a group of 10 smokers, following exposure to cigarette cues under two different conditions of cigarette availability. In one experiment cigarettes were available immediately and in the other they were not. The researchers

Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. A recent paper (Soares et al PNAS Jan 2013) describes an approach based on diffuse reflectance spectroscopy for detection of microcalcifications that focuses on variations in optical absorption stemming from the calcified clusters and the associated crosslinking molecules. In the study, diffuse reflectance spectra were acquired ex vivo from 203 sites in fresh biopsy tissue cores from 23 patients undergoing stereotactic breast needle biopsies. By correlating the spectra with the corresponding radiographic and histologic assessment, the authors developed a support vector machine-derived decision algorithm, which shows high diagnostic power (positive predictive value and negative predictive value of 97% and 88%, respectively) for diagnosis of lesions with microcalcifications. The authors attribute their findings to the presence of proteins (such as elastin), and desmosine and isodesmosine crosslinkers in the microcalcifications. It is important to note that the performance of the diffuse reflectance decision algorithm is comparable to one derived from the corresponding Raman spectra, and the considerably higher intensity of the reflectance signal enables the detection of the targeted lesions in a fraction of the spectral acquisition time. The findings create a unique landscape for spectroscopic validation of breast core needle biopsy for the detection of microcalcifications that can substantially improve the likelihood of an adequate, diagnostic biopsy in the first attempt. http://tinyurl.com/Soares-paper

Referring physicians prefer delivering radiology results to patients themselves continued from page 06

responses were collected confidentially. The majority of respondents were satisfied with radiology reporting and recommendations in general. Ninety-five percent of respondents felt that ordering physicians should deliver the results of examinations. No respondents felt that radiologists should deliver results directly to patients. In addition, 94 percent of respondents felt medico-legally obligated by recommendations made by radiologists within their reports. Twenty-three percent of respondents felt more medico-legally obligated if the recommendation is set apart from the clinical impression, while 58 percent of 8

combined the technique of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). The results demonstrate that in smokers the orbitofrontal cortex (OFC) tracks the level of craving while the dorsolateral prefrontal cortex (DPFC) is responsible for integrating drug cues and drug availability. Moreover, the DPFC has the ability to suppress activity in the OFC when the cigarette is unavailable. When the DPFC was inactivated using TMS, both craving and craving-related signals in the OFC became independent of drug availability. The authors of the study conclude that the DPFC incorporates drug cues and knowledge of drug availability to modulate the value signals it transmits to the OFC, where this information is transformed into drug-seeking action. “We demonstrate that in smokers, cravings build up in the OFC upon processing of cigarette cues and availability by the DFPC. What is surprising is that this is a neural circuit involved in decision making and self-control, that normally guides individuals to optimal behaviors in daily life” explained Dr. Hayashi, from RIKEN, who designed and conducted the fMRI and TMS experiments. “This research uncovers the brain circuitry responsible for self-control during reward-seeking choices. It is also consistent with the view that drug addiction is a pathology of decision making.” http://tinyurl.com/Hayashi-paper

respondents felt less medico-legally obligated if qualifying language is added to the recommendation. “Our study suggests primary care physicians prefer to deliver the results of examinations themselves and feel medico-legally obligated by recommendations within radiology reports, even though this seems to be influenced by the wording and location of the recommendations within reports. Radiologists should consider these factors when contemplating changes in reporting practices,” said Gunn. Future research, such as patient focus groups, patient satisfaction surveys, and surveying other medical specialties, is necessary to better delineate and understand these preferences,” said Gunn. http://tinyurl.com/JACR-Gunn-paper D I

E U R O P E

MARCH 2013


.artundwork designbüro

Embracing life

through better medical imaging solutions.

Better medical imaging solutions for the needs of our customers We have been committed to delivering outstanding medical imaging solutions over decades. Original solutions, that have grown out of the groups' expertise and technical know-how, providing innovations that meet equally the Zeitgeist and the needs of our customers and their patients.

Visit us at ECR 2013, booth 320 in Expo C and discover “solution stars in radiology” Hitachi Medical Systems Europe Holding AG · Sumpfstrasse 13 · CH-6300 Zug

www.hitachi-medical-systems.eu


NOW

with ody Whole B on Indicati

...there’s MORE to see

Whole Body Imaging – One solution with Gadovist® 1.0 Q Macrocyclic compound – class with highest stability1 Q Proven efficacy and tolerability2,3 Q Highest T1-shortening per unit volume of Gd-based contrast agents4,5 and excellent contrast quality6 www.bayer.co.uk

Enquiries: 01635 563999 Calls to and from Bayer HealthCare may be recorded December 2012. L.GB.10.2012.0716a All rights reserved. © Bayer plc 2012

▼Gadovist® 1.0 mmol/ml solution for injection (gadobutrol) and ▼Gadovist® 1.0 mmol/ml solution for injection pre-filled syringe/cartridge (gadobutrol) Prescribing Information (Refer to full Summary of Product Characteristics (SmPC) before prescribing) Presentation: Glass vials containing 15ml, or glass prefilled syringes containing 5ml, 7.5ml or 10ml, of gadobutrol 1.0mmol/ml solution for injection (604.72mg gadobutrol/ml). Indications: Adults, adolescents and children aged 2 years and above: Contrast enhancement in cranial and spinal MRI; MRI of liver and kidneys if suspicion or evidence of focal lesions; MRI of pathologies of the whole body and in magnetic resonance angiography (CE-MRA). Posology and administration: Gadovist should only be administered by healthcare professionals experienced in the field of clinical MRI practice. This medicinal product is for intravenous administration only. Give required dose intravenously as bolus injection. Patient should be recumbent during administration. MRI can start immediately after injection. Optimal signal enhancement usually occurs during arterial first pass for CE-MRA and within 15 minutes of injection for CNS indications. Particularly suitable for T1-weighted scanning sequences. Observe patient for at least 30 minutes after administration. Intended for single use only. Visually inspect before use; do not use in case of severe discolouration, occurrence of particulate matter or defective container. Contrast medium not used in one examination must be discarded. Vials: draw up into syringe immediately before use; never pierce rubber stopper more than once. Pre-filled syringe: prepare immediately before administration. CNS indications: Adults: 0.1mmol/kg body weight (equivalent to 0.1ml/kg body weight). A further injection of 0.2ml/kg body weight may be given within 30 minutes of first injection. Whole Body MRI (except MRA): Adults: 0.1 ml/kg body weight. CE-MRA: Adults: Imaging of 1 field of view (FOV): 7.5ml for body weight below 75 kg, 10ml for body weight of 75 kg and higher (corresponding to 0.1-0.15 mmol/kg BW). Imaging of >1 field of view (FOV): 15ml for body weight below 75 kg, 20ml for body weight of 75 kg and higher (corresponding to 0.2-0.3 mmol/kg BW). Impaired renal function: Only use in patients with severe renal impairment (GFR < 30 ml/min/1.73m2), and in patients in perioperative liver transplantation period after careful risk/benefit assessment and if diagnostic information is essential and not available with non-contrast enhanced MRI. If necessary to use Gadovist, dose should not exceed 0.1 mmol/kg body weight. Do not use more than one dose per scan. Do not repeat the dose for at least 7 days. Children and adolescents: For children aged 2 years and above: 0.1 mmol/ kg body weight (equivalent to 0.1ml/kg body weight) for all indications. Not recommended in children below 2 years of age due to lack of data on safety and efficacy. Elderly (65+ years): No dose adjustment, exercise caution. Contra-indications: Hypersensitivity to ingredients. Warnings and precautions: If injecting into veins with a small lumen, adverse effects such as reddening or swelling may occur. Observe usual precautions for MRI (e.g. exclusion of ferro-magnetic objects). Hypersensitivity reactions, including anaphylactoid reactions ranging to shock, have been observed. Appropriate drugs and instruments must be within hand-reach. Hypersensitivity reactions are not predictable, however in patients with an allergic disposition, carefully evaluate risk-benefit ratio. In rare cases, delayed anaphylactoid reactions (after hours to days) have been observed. Prior to administration, it is recommended to screen all patients for renal dysfunction by laboratory testing. Nephrogenic Systemic Fibrosis (NSF) has been reported with gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30ml/min/1.73m2). Patients undergoing liver transplantation are at particular risk due to high incidence of renal failure. Only use in patients with severe renal impairment and those in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI. Haemodialysis shortly after Gadovist administration may be useful in removing Gadovist from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis. As renal clearance may be impaired in the elderly, it is particularly important to screen patients aged 65+ years for renal dysfunction. Use with caution in patients with a low seizure threshold. Gadovist contains less than 1mmol sodium per dose (based on average amount given to a 70kg person), i.e. essentially ‘sodium-free’. Interactions: No studies have been performed. Pregnancy and lactation: Do not use during pregnancy unless the clinical condition of the woman requires use of gadobutrol. Gadolinium containing contrast agents are excreted into breast milk in very small amounts. At clinical doses no effects on the infant are anticipated. Continuing /discontinuing breastfeeding for 24 hours after Gadovist administration should be at the discretion of the doctor and nursing mother. Undesirable effects: Most undesirable effects are of mild to moderate intensity. Common: Nausea, headache. Uncommon: dysgeusia, injection site reactions, feeling hot, dyspnoea*. Rare: Hypersensitivity/ anaphylactoid reactions (e.g. anaphylactoid shock§*†, circulatory collapse§*, respiratory arrest§*†, bronchospasm§, cyanosis§, oropharyngeal swelling§*, hypotension*, blood pressure increased§, chest pain§, urticaria, laryngeal§/face§/eyelid§ oedema, angioedema§, conjunctivitis§, flushing, hyperhidrosis§, cough§, sneezing§, burning sensation§, pallor), loss of consciousness, convulsion. Not known: Cardiac arrest*†, Nephrogenic systemic fibrosis (NSF) (isolated cases). Patients with an allergic disposition more frequently suffer from hypersensitivity reactions. §Hypersensitivity/anaphylactoid reactions identified only post-marketing (frequency not known). *These adverse reactions may have a fatal or lifethreatening outcome. †These reactions are considered the most serious adverse drug reactions. Prescribers should consult the SmPC in relation to other side effects. Overdose: In case of overdose, perform cardiovascular monitoring (including ECG) and control renal function as a measure of precaution. In patients with renal insufficiency, Gadovist can be removed by haemodialysis. After 3 haemodialysis sessions approx. 98% of agent is removed from the body. However, there is no evidence that haemodialysis is suitable for prevention of NSF. Incompatibilities: Do not mix Gadovist with other medicinal products. Legal category: POM Basic NHS Price: 1 x 15ml vial £101.26, 1 x 7.5ml pre-filled syringe £50.63, 5 x 5 ml prefilled syringes £168.77, 5 x 10ml pre-filled syringes £337.54 MA Numbers: 00010/0535 (vials), 00010/0536 (pre-filled syringes) Further information available from: Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA, United Kingdom. Telephone: 01635 563000. Date of preparation: November 2012. Gadovist® is a trademark of the Bayer Group. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Bayer plc. Tel: 01635 563500, Fax: 01635 563703, Email: phdsguk@bayer.co.uk References 1. Frenzel T et al. Invest Radiol 2008;43:817–828. 2. Voth M et al. Invest Radiol 2011;46:663–671. 3. Tombach B, Heindel W. Eur Radiol 2002;12:1550–1556. 4. Rohrer M et al. Invest Radiol 2005;40:715–724. 5. Data on file, Bayer HealthCare. 6. Forsting M. Neuroradiology 2006;48(suppl 2):87.


IMA GI N G NEWS Identifying abuse of elderly people The high-profile reports that are occasionally presented in the mainstream press regarding the mistreatment of elderly people who are in long-term care homes or hospitals are bad enough, but it is likely that such high-profile cases are in fact only the tip of the iceberg. Studies presented at the recent RSNA congress, by Dr KJ Murphy of the University Heath Network in Toronto Canada suggest that the vast majority of cases of elderly people who are victims of abuse are the result of abuse that takes place in the elderly person’s own home setting where the care is being given by non-professionals.

Even worse, according to Dr Murphy, is the fact only 2 percent of physical elder abuse is reported by clinicians. In the face of this, Dr Murphy and his team carried out a review of the relevant literature to determine whether they could elicit a pattern of both physical and radiologic evidence that could help in identifying elder abuse cases. To aid radiologists in identifying potential cases of elder abuse, the team analysed more than 1,100 cases. They found that in contrast to older adults who had been accidentally injured the most frequent injuries among abused elderly were physical trauma to the face; dental

SPECT/CT studies show oxygen chambers can boost brain repair

Stroke, traumatic injury, and metabolic disorder are major causes of brain damage and permanent disabilities, including motor dysfunction, psychological disorders, memory loss, and more. Current therapy and rehab programs aim to help patients heal, but they often have limited success. Now Dr S Efrati of Tel Aviv University’s Sackler Faculty of Medicine may have found a way to restore a significant amount of neurological function in brain tissue thought to be chronically damaged — even years after initial injury. Theorizing that high levels of oxygen could reinvigorate dormant neurons Dr Efrati recruited post-stroke patients for hyperbaric oxygen therapy (HBOT). Analysis of SPECT/CT brain imaging showed significantly increased neuronal activity after a two-month period of HBOT treatment compared to control periods of non-treatment, reported Dr Efrati (PLoS One.2013; 8 e53716) Patients experienced improvements such as a reversal of paralysis, MARCH 2013

increased sensation, and renewed use of language. These changes can make a world of difference in daily life, helping patients recover their independence and carry out tasks such as bathing, cooking, climbing stairs, or reading a book. According to Dr. Efrati, there are several degrees of brain injury. Neurons impacted by metabolic dysfunction have the energy to stay alive, but not enough to fire electric signals, he explains. HBOT aims to increase the supply of energy to these cells. The brain consumes 20 percent of the body’s oxygen, but that is only enough oxygen to operate five to ten percent of neurons at any one time. The regeneration process requires much more energy. The tenfold increase in oxygen levels during HBOT treatment supplies the necessary energy for rebuilding neuronal connections and stimulating inactive neurons to facilitate the healing process. For their study, the researchers sought post stroke patients whose condition was no longer improving. Treatment consisted of 40 two-hour sessions five times weekly in high pressure chambers containing oxygen-rich air. The results indicate that HBOT treatment can lead to significant improvement in brain function in post stroke patients even at chronically late stages, helping neurons strengthen and build new connections in damaged D I

E U R O P E

trauma; subdural hematoma; eye and larynx trauma; rib fractures and upper extremity injuries. Radiologists need to be aware of the pattern of injuries frequently seen in the abused elderly,” Dr. Murphy said. “More importantly, we need to integrate the physical and radiological findings with the social context of the patient to help identify those at risk”. http://tinyurl.com/Murphy-paper regions. Although the study focuses on patients only through three years poststroke, Dr Efrati has seen similar improvement in patients whose brain injuries occurred up to 20 years before, belying the concept that the brain has a limited window for growth and change. The findings challenge the leading paradigm in that they demonstrate beyond any doubt that neuroplasticity can still be activated for months and years after acute brain injury. The researchers are currently conducting a study on the benefits of HBOT for those with traumatic brain injury. The treatment also has potential as an anti-aging therapy and could be applicable in other disorders such as Alzheimer’s disease and vascular dementia at their early stages. http://tinyurl.com/Efrati-paper

Clarification: In the Imaging News section of the January issue of DI Europe, an item was published on new guidelines to reduce the risk of infection from ultrasound gel. This item was published with an illustrative picture of ultrasound gels manufactured by Parker Laboratories. DI Europe wishes to make it clear that no product from this manufacturer was involved in any case of infection caused by contaminated ultrasound gel.

11


IMA GI N G NEWS Brain bleeding detected by MRI years after incidents of high altitude sickness

Altitude sickness occurs when the body cannot get enough oxygen from the air at high altitudes. This causes symptoms such as a headache, loss of appetite, and trouble sleeping. It happens most often when people who are not used to high altitudes go quickly from lower altitudes to 2500m or higher. The condition is common — some estimates suggest that more than 20% of people visiting the European Alps get it. It is difficult to predict who is likely to suffer, e.g. fitness level does not seem to affect the likelihood of getting altitude sickness. The generally recognized treatment for at least mild altitude sickness is simply to go to a lower altitude.

Now new MRI research shows that mountain climbers who have had a certain type of severe high altitude sickness known as high altitude cerebral edema (HACE) can show traces of bleeding in the brain even years after the initial incident. HACE results from swelling of brain tissue due to leakage of fluids from the capillaries. Symptoms include headache, loss of coordination and decreasing levels of consciousness. HACE is a life-threatening condition. In a presentation at the recent RSNA meeting, Dr M Knauth from the Dept of Neuroradiology in the Goettingen University Medical Center in Germany described the MRI results obtained when his group looked at four sets of mountaineers. These were: climbers with well documented HACE; climbers with a history of high altitude illness; climbers with a history of severe acute mountain sickness (AMS) and climbers with a history of high altitude pulmonary edema. It was found that brain microhemorrhages were only found in the brains of HACE survivors.

The images show magnetic resonance (MR) slices through the brains of two mountaineers. The image on the left is from a mountaineer who climbed to altitudes above 7,000 meters, and the one on the right is from a mountaineer who survived a high altitude cerebral edema (HACE). The arrows point to the corpus callosum brain structure which consists of densely packed nerve fibres connecting the two brain hemispheres. This part of the corpus callosum is normal in the left image, whereas in the right image (HACE survivor) it shows black spots representing multiple small hemorrhages (microhemorrhages).

“It was previously thought that HACE did not leave any traces in the brains of survivors,” Dr. Knauth said. “Our studies show that this is not the case. For several years after, microhemorrhages or microbleeds are visible in the brains of HACE survivors.” Dr Knauth’s group intend to extend their studies and anlyze more deeply their MRI data. In the meantime he thinks that HACE survivors do not need to give up their sport — but should acclimatize very slowly when they next venture into the high mountains. http://tinyurl.com/Knauth-paper

Significance of second trimester ultrasound markers for Down’s syndrome A new analysis has found that some second trimester markers for Down’s syndrome that are detected by ultrasound are more telling than others (Agathokleous M et al Ultrasound Obstet Gynecol. 2012 Dec 3). Screening for Down’s syndrome is offered to all pregnant women in most Western countries, starting out with a background risk based on age. Certain features detected during a second trimester ultrasound exam are potential markers for Down’s syndrome, including dilated brain ventricles, absent or small nose bone, increased thickness of the back of the neck, an abnormal artery to the upper extremities, bright spots in the heart, ‘bright’ bowels, mild kidney swelling, and shortening of an arm bone or 12

thigh bone.To determine how these markers affect risk, Kypros Nicolaides’s group at the Research Centre for Fetal Medicine at King’s College London in UK analyzed all published studies that reported results on second trimester markers for Down’s syndrome between 1995 and 2012. The team found that a few markers carry increased risks. Dilated brain ventricles, increased thickness of the back of the neck, and an abnormal artery to the upper extremities increase the risk by three- to four-fold, and an absent or small nose bone increases the risk by six- to seven-fold. “The detection of any one of the findings during the scan should prompt the sonographer to look for all other markers or abnormalities,” said Prof. Nicolaides. He added that D I

E U R O P E

the study also revealed that if a detailed second trimester ultrasound exam demonstrates the absence of all major markers, the risk of having a baby affected by Down’s syndrome is reduced by more than seven-fold. The findings indicate that the relative importance of ultrasound markers is very different from what has been previously assumed. Prof. Nicolaides noted that the results from this study will be incorporated in obstetric ultrasound scan software that assesses women’s risks for having a child with Down’s syndrome. http://tinyurl.com/Agathokleous-paper MARCH 2013


Colonography by Dr E Neri

The second ESGAR consensus statement on CT colonography

I

n the recent years there has been both a significant technological development and an increase in the clinical implementation of CT Colonography (CTC). The history of CTC can be broken into three basic stages: that of technological development, which took place mainly in the 90s; the stage of clinical validation (approximately over the period 2003-2008), and the phase of diagnostic practice that is currently on-going. CTC is currently experiencing a rapid progression throughout Europe, from mainly academic reference centers that are principally involved in clinical validation, to other hospitals where CT colonography is now used as an alternative to the double-contrast barium enema. However in the absence of guidelines on how to perform bowel preparation, on acquisition of the images, reading of the examination, and not least the reporting, the rapid spread of the technique has been characterized by variable methodological approaches. For this reason, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) has drawn up new guidelines for use by radiologists to ensure the highest quality standards in the performance of the examination [1] . The new guidelines, known as “The second ESGAR consensus statement on CT colonography”, update the first consensus statement published in 2007 The panel of nine experts involved in the new guidelines came from six EU countries (Austria, Belgium, Italy, The Netherlands, Sweden and the UK), and were chosen from the faculty of the ESGAR CT Colonography hands-on workshops. The experts met at least twice a year to draw up a list of statements covering the fundamental aspects of the examination (preparation, insufflation, acquisition, reading and reporting). After the pre;iminary drafting of the statements (86 in all) the experts reached full consensus in 71 statements, although in the remaining 17 statements the level of concordance was still very good. Consensus was made possible by the application of the Delphi methodology, already used by other groups in different fields of radiology. The Table above shows some key recommendations that could have a particular impact in the clinical practice of CT colonography. The full consensus statement is available in Ref 1. The author : Dr Emanuele Neri ESGAR Fellow, Assistant Professor of Radiology, University of Pisa, Italy email: emanuele.neri@med.unipi.it.

MARCH 2013

D I

Reference 1. N eri E et al. The second ESGAR consensus statement on

CT colonography. Eur Radiol. 2013 Mar; 23:720

Acknowledgments

Sincere thanks to ESGAR for support, and to the group of experts comprising the ESGAR CT Colonography Working Group that made possible this important project: Steve Halligan, Mikael Hellström, Philippe Lefere, Thomas Mang, Daniele Regge, Jaap Stoker, Stuart Taylor, Andrea Laghi.

Statement

Practical implication

Automatic distension with CO2 is the method of choice Use of multi-detector row CT scanners is a prerequisite for CTC and maximum collimation should be no more than 2.5mm. Low dose radiation dose without IV contrast should be used for screening

An insufflator should be part of the CTC equipments

Patient preparation and fecal tagging are mandatory for proper detection of polyps and colorectal cancer.

To start a CTC service radiologists should be aware to use multi-detector scanners, and take specific care to the availability of dose reduction protocols.

The reading should integrate 2D and 3D perspectives, and CAD should be used as second reader.

Specific attention should be given to adopt an optimal preparation regimen (efficacy, quality, patient’s acceptance)

CTC should be reported by a radiologist specifically trained in the technique

The use of dedicated workstations for CTC reading, with CAD implementation is strongly recommended

Only radiologists should be responsible for the CTC final report and competence in image CTC has limited diagnostic interpretation will require an value for lesions less than 6mm. However, if detected with accreditation with adequate training. high confidence such lesions might be reported (particularly if ≥ 3), in both symptomatic In practical, if detected with high and asymptomatic patients. confidence, all diminutive polyps should be reported. All polyps of 6mm or larger should be reported in both The experts did not give specific symptomatic and asymptomindications about the patient atic patients. management with the auspice to work on a consensus with gastroenterologists

E U R O P E

13


Colonography by Dr A Slater

Laxative-free CT colonography This article describes the design and results of a study carried out to determine if the introduction of fecal tagging to CT colonography (CTC) makes the examination easier to tolerate or reduces the number of falsepositives. The study analyzed the results obtained when the method of preparation of patients for CTC was changed from a laxative-only procedure to one using a radio-opaque contrast medium without laxative. This latter regimen was well tolerated, producing less diarrhoea than conventional laxative-based techniques. However we did not show that the use of fecal tagging reduced false positives.

C

T Colonography (CTC) was initially introduced using bowel preparation regimens orginally used for barium enema. By necessity, barium enema required a very clean colon, but the superior imaging of CT enables different techniques to be used; the dose of laxatives can be reduced, and patients can have a low residue diet if it is combined with oral iodinated or barium contrast agents that ‘tag’ the faeces in the colon. Over the years since the introduction of CTC, many different regimens have evolved. The ESGAR consensus statement was only able to reach a conclusion that ‘use of tagging agents is acceptable’ and stated that both full laxative and reduced laxative regimens were acceptable [1]. The UK NHS National Patient Safety Agency (NPSA) has recently issued guidelines about how laxative bowel preparations commonly used for CT colonography (CTC) can be prescribed to patients [2]. The guidelines were drawn up after reported incidents of harm from use of these drugs, including one death. It is no longer acceptable for radiology departments to send patients laxative bowel preparation in the post simply based upon the very limited clinical information usually available on a radiology request card. In our department, the result of this has been to make the process of organising CT colonography more cumbersome. Several authors have described using faecal tagging, usually with Gastrografin in addition to laxatives, and a few have used Gastrografin on its own without any laxatives. We therefore undertook to change our preparation for CT colonography from The author :

« .... it is no longer acceptable for radiology departments to send patients laxative bowel preparations through the post simply on the basis of limited clinical information ....» It has been previously proposed that fecal tagging can reduce the numbers of false positives, by enabling residual feces to be more easily distinguished from true pathology. Previous studies have not shown this, but these studies have used small numbers of patients. We therefore sought to compare the false positive rates between tagged and untagged groups, to see if fecal tagging reduces this number.

Andrew Slater

Methods and Materials

Consultant Radiologist

Consecutive patients were identified from before and after the change in bowel preparation. Patients in the Picolax group were asked to take two sachets of Picolax

John Radcliffe Hospital Headley Way, Oxford, UK andrew.slater@ouh.nhs.uk

14

Picolax without fecal tagging, to oral Gastrografin only with no laxatives. [Picolax contains two active ingredients, sodium picosulfate and magnesium citrate, which are both laxatives. Gastrografin — Diatrizoate Meglumine and Diatrizoate Sodium Solution — is a watersoluble iodinated radiopaque contrast medium for oral or rectal administration only.] We compared patient acceptance before and after this change using a questionnaire. We do not have a reference test for all patients to give the true incidence of colonic neoplasia, so are unable to calculate sensitivity and specificity, but can calculate true and false positive rates based upon the results of further investigations, principally carried out by optical colonoscopy and triggered by CTC reports.

D I

E U R O P E

MARCH 2013


Radiology

without boundaries

Agfa HealthCare’s Regional Health portfolio provides radiologists and clinicians with seamless access to the patient’s entire radiology history, irrespective of the originating radiology department, making medical images available across all clinical disciplines as part of the patient’s comprehensive medical record. Moreover, our solutions enable sharing of longitudinal imaging record by connecting 3rd party RIS/PACS systems across all facilities via federated and centralized approaches utilizing state of the art industry standards and techniques allowing an ‘acquire anywhere –report from anywhere’ workflow.

Insight. Delivered.

Learn about Agfa HealthCare at www.agfahealthcare.com


Colonography the day before the examination, and diet was also modified according to these instructions. For the Gastrografin preparation group, patients took 35mL of Diatrizoate dimeglumine (Gastrografin) mixed with a glass of water at 8pm two days before the CT, and another 35mL at 8pm one day before. Diet was modified to avoid high fibre foods. Forty minutes before the CT, patients were asked to drink our department’s standard oral contrast; 15mL Urografin 370 in 750 mL tap water. The CT examination was performed identically for the two groups, and a mechanical insufflator was used to introduce carbon dioxide after intravenous injection of Buscopan 20mg iv. Questionnaires were given to patients attending for CT colonography as they arrived in the radiology department for their examination. Patients completed the questionnaires whilst they waited for their CT examination. The results were compared between the two groups. CTC reports were classified as either normal, or abnormal warranting endoscopic evaluation of a potential colonic abnormality over 10mm.

Correlation with subsequent endoscopic and pathological reports was made, and reported abnormalities were classified as ‘true positive’, ‘false positive’ or ‘insufficient information for evaluation’. The latter were excluded from further analysis. Results

Sixty two patients in each group were given questionnaires. The main differences between the two groups were found to be in the frequency of bowel movements, with Picolax causing 77% of the patients to have five or more bowel motions in the previous day and night, compared to 34% for Gastrografin (P<0.001). This was reflected in perianal soreness, which was experienced in 63% of patients receiving Picolax against 26% for Gastrografin (P<0.001). Patients preferred the experience of drinking Picolax compared to Gastrografin (reported as ‘easy’ for 85% of patients taking Picolax vs 61% for Gastrografin, P< 0.002). This may be due to the strong aniseed flavour of Gastrografin. 112 patients were identified in the Gastrografin preparation group. Of these, nine were correctly

FIGURE 1. A typical CT Colonography image obtained from the Gastrografin preparation regimen. The colon is well distended and contains a small amount of homogeneously tagged fluid.

16

D I

E U R O P E

reported as having colon cancer (true positive). A benign 2cm polyp was correctly reported. There was one false positive diagnosis of malignancy. Endoscopy showed this to be a diverticular stricture. There was one false positive diagnosis of a 10mm polyp. No examinations were considered non-diagnostic. 397 patients were identified in the Picolax preparation group. There were 14 false positive lesions reported as being 10mm or greater. There were 12 true positive cancers, and 16 true positive large polyps. Eight were reported as nondiagnostic due to excessive amounts of retained fecal residue. The positive predictive values for lesions greater than 10mm for Picolax and Gastrografin groups were 67% and 83% respectively. Although the results are not statistically different from each other, the false positive rate was almost twice as large in the Picolax group. A typical image obtained from the Gastrografin regimen is shown in Figure 1. Discussion

Fecal tagging combined with laxatives has been well described, most notably by Pickhardt et al [3]. However, hard evidence of benefit in sensitivity or specificity is lacking. It has been previously suggested that use of fecal tagging would reduce the number of false positives since small amounts of residual fecal material would be more easily distinguished from true pathology. However previous studies have not shown this. Lefere et al [4] found a non-significant increase in specificity when a polyethylene glycol regimen was compared to a single dose of magnesium citrate combined with barium tagging. The first report of the use of iodinated contrast alone without laxatives was by Iannaconne et al [5]. They described use of Gastrografin taken with a low fibre diet at a dose of 100mL per day for two days before CT. This resulted in excellent tagging with good sensitivity for pathology compared to subsequent colonoscopy. The reference colonoscopy used standard laxative preparation and patients reported preferring the Gastrografin technique. Liedenbaum et al [6] report use of CTC without laxatives with iodine tagging only. They used Megluimne-ioxithalamate MARCH 2013


Burning CDs for image exchange takes time and money. And you can’t afford to waste either one. Soon, your patients will be able to help.

VUE MEANS EMPOWERMENT. With MyVue, patients can take control of their own imaging records – viewing their exam data through a secure portal, and granting access to referring physicians, specialists and other care providers.

I N N O V A T I O N. E M P O W E R I N G T E C H N O L O G Y. carestream.com/myvue

For your facility, this could mean less time wasted with CDs, DVDs or films. It can help lower your costs and speed workflow. All while giving patients a role in their own care.

THE FUTURE OF IMAGE EXCHANGE BEGINS WITH YOUR PATIENTS. © Carestream Health, Inc., 2013.

T H E N E W B E N C H M A R K I N H E A L T H C A R E I T.


Colonography (Telebrix) in a dose of 50mL three times per day over 2 days for the first 50 patients, and 3x50mL in one day for the next 50 patients. A low fibre diet was used for both groups, together with 50mL Telebrix 1.5 hours before the examination. A reference standard of subsequent colonoscopy was used to assess the accuracy of pathology detection, the quality of tagging was graded and patient symptoms were evaluated. It was reported that image quality and polyp detection were comparable between the two regimens, but the one-day preparation group had less diarrhoea. Modified preparation CT is an alternative method of investigating the colon that is very easy to tolerate. Several studies have shown that standard CT performed without bowel purgation has reasonable sensitivity for colorectal cancer [7]. Patients are required to drink oral contrast medium (usually Gastrografin) with meals for two days before the scan in order to label feces. No laxatives are administered and the protocol is thus especially suited to frail patients who may be intolerant of full bowel purgation. A supine scan without gas

insufflation is performed and high attenuation tagged feces can be differentiated from the relatively low attenuation bowel wall and related pathology [Figure 2]. No studies have documented whether this dose causes diarrhoea, but as this is advocated as a test for the frail elderly it is reasonable to assume that any diarrhoea caused is mild. It is clear from our results that Gastrografin at a higher dose of 35mL per day does cause some diarrhoea, and therefore that Gastrografin is itself a laxative. However the effects are less than those generated by Picolax. There are several limitations with this study. Clearly randomizing patients to a tagging regimen or a standard regimen would have been preferable. In retrospect it is clear that our sample size is too small to demonstrate a reduction in false positives, but the necessary sample number needed of 1200 per method would be difficult to achieve in practice. An alternative strategy would be to use a polypenriched population. We did not formally grade the quality of tagging achieved, but none of the tagged dataset were considered non-diagnostic.

Conclusion

We have described a simple bowel preparation technique that does not use laxatives, thus bypassing NPSA regulations. This regimen is well tolerated, producing less diarrhoea than conventional laxative-based techniques. We have not shown that use of fecal tagging reduces false positives. Use of mild laxatives not covered by NPSA guidelines may improve the quality of tagging, but at the expense of increased complexity of the regimen. As software develops that can remove tagged feces from a dataset producing ‘virtual cleansing’, the quality of tagging may become more important. Until now such software has been unreliable and prone to producing artefacts. Historically many papers have described the frequent use of Gastrografin, presumably due to the theoretical benefit of its high osmolarity, but it is likely that other iodinated contrast agents will be able to provide equally good results. Agents that do not have the strong aniseed flavour of Gastrografin are likely to be better tolerated by patients. References 1. S tuart A. Taylor, Andrea Laghi, Philippe Lefere, et al. European society of gastrointestinal and abdominal radiology (ESGAR): Consensus statement on CT colonography European Radiology 2007, 17 (2): 575-579 2. R educing risk of harm from oral bowel cleansing solutions. National Patient Safety Agency alert issued 19 February 2009 http://www.nr ls.npsa.nhs.uk/ alerts/?entryid45=59869&p=2 3. P ickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003 Dec 4;349(23):2191-200. 4. Lefere PA, Gryspeerdt SS, Dewyspelaere J, Baekelandt M, Van Holsbeeck BG. Dietary fecal tagging as a cleansing method before CT colonography: initial results polyp detection and patient acceptance. Radiology. 2002 Aug;224(2):393-403. 5. I annaccone R, Laghi A, Catalano C, et al. Computed tomographic colonography without cathartic preparation for the detection of colorectal polyps. Gastroenterology. 2004 Nov;127(5):1300-11. 6. Liedenbaum MH, de Vries AH, Gouw CI, et al. CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes. Eur Radiol. 2010 Feb;20(2):367-76. Epub 2009 Aug 26.

FIGURE 2. A typical image from a Minimal preparation CT of the Colon (MPCT Colon). The colon is filled with tagged faeces, but is not distended. A solid, untagged mass is seen in the right colon, indicating a tumor.

18

D I

E U R O P E

7. G aneshan A, Upponi S, Uberoi R, D’Costa H, Picking C, Bungay H. Minimal-preparation CT colon in detection of colonic cancer, the Oxford experience. Age Ageing 2007;36:48–52.

MARCH 2013


Industry Outlook by Greg Freiherr

Game-changing technologies take aim at MR, ultrasound and PET Dramatically new opportunities to advance patient comfort, improve productivity, increase diagnostic accuracy, and provide greater patient involvement are emerging. These technologies, exemplified by “noiseless” MR scans, wireless ultrasound transducers, and advanced PET/CT biomarkers are hovering on the periphery of radiology and could have a substantial impact on medical practice as early as this year. When they enter – and there is little doubt that they will – these technologies will be game changers.

A

lmost inconceivably, two decades have passed since radiology had such opportunities and, back then, the community was slow to recognize their potential. In the mid-90s, open MR scanners were dismissed by opinion leaders as lacking the power to compete with high-field systems, their images substandard, if not less than diagnostic. Then patients sounded off. Enough of them balked at sliding into conventional high-field systems to spur the development of true high-field scanners, namely Hitachi’s 1.2T Oasis and Philips’ 1T Panorama. But their true impact occurred not in open designs but in the widebore magnets that are today the industry standard.

Noiseless MR

Not adequately addressed has been noise – the other major factor affecting patient comfort. Vendors have tried an assortment of mufflers and baffles to staunch the often jarring, unsettling noises that occur when gradients execute pulse sequences. Only one company, Toshiba, has attempted to turn its engineering efforts in their regard to a sales advantage, promoting its Pianissimo technology as the means for significantly reducing MR noise. Pianissimo seals the gradient coil in a vacuum, dampens sound and vibration with insulation between the vacuum vessel and magnet, and orchestrates pulse sequences designed to minimize noise. GE Healthcare promises more. At the 2012 RSNA meeting, the company marched the curious past a bigger than life-sized picture of a construction worker operating a jackhammer into a glass-walled enclosure labeled simply “Silent Scan.” Inside they watched a video feed from GE’s engineering lab as an MR scanner, The auther Greg Freiherr is head of the US-based firm, the Freiherr group, which specializes in corporate consulting and editorial services for the medical imaging industry email: greg.freiherr@gmail.com

MARCH 2013

D I

outfitted with the company’s experimental Silenz technology, ran through a pulse sequence. A GE demonstrator, standing in front of the Wisconsin-based MR scanner, began with “what you hear – or don’t hear – is the sound of silence by GE Healthcare. Silent Scan is exclusive to GE and no other vendor and just one more way of humanizing the MR experience.” The suggestion of silence was an exaggeration, one acknowledged by the demonstrator who noted that “you can still hear the cold head and the patient blower, but it is really quiet.” A decibel meter in the video showed the noise level at 76 decibels, the same reading as if it were 15 meters from a passing freight train. But GE Richard Hausmann, Ph.D., president and CEO of GE’s global MR business, explained that those 76 decibels were just one dB more than fills an MR suite when the scanner is just idling. The noises that punctuate conventional scans typically spike to 110 decibels, he said. Unlike past efforts that sought to quiet these sounds, GE’s approach is to prevent them from ever happening in the first place. And that could make all the difference. Silent Scan does so with a reconstruction technique and sequences primed for quiet. Data are acquired in an isotropic volume from the center of K space and reconstructed using a proprietary algorithm. Upgrading the installed base may be as simple as adding software. The gradients, according to Hausmann, are standard on the company’s latest MR scanners. Accompanying the video in GE’s glassed enclosure at RSNA were images that looked diagnostic and were acquired in just about the same time with a Silent Scan as the accompanying images achieved with a conventional scan. But the clinical potential of Silent Scan remains to be proven at luminary sites this year, just as the technology itself has yet to be cleared by the FDA. But Hausmann is optimistic. “We are refining the technology further and I would predict it will be an absolutely standard sequence,” he

E U R O P E

19



Industry Outlook

RSNA 2012 visitors flock to a glass enclosure on the GE Healthcare booth in which GE unveiled its Silent Scan, utilizing technology that promises to dramatically cut the noise generated during MR examinations. Image courtesy GE Healthcare.

said. “I would expect a huge benefit for patients in rejection rate (resulting in prematurely ended MR exams) and for techs who have to listen to that noise all day.” Wireless ultrasound

Workloads for sonographers are increasing with no end in sight, a consequence of the aging workforce and a likely widening demand due to the healthcare reforms that are being promised in many countries. Not surprisingly, work-related injury is mounting. Surveys of sonographers, including a benchmark study by the U.S. Society of Diagnostic Medical Sonographers, indicate that a large majority of sonographers are actually scanning while in pain and injuries are forcing many to leave the profession. Repetitive, awkward movements are a major contributor and the cabling that connects scan head to machine is one factor. Advances in miniaturization promise to change that. An experimental ultrasound scanner unveiled at the Siemens RSNA booth in November featured the holy grail of ultrasound transducers – wireless technology. Since the beginning of diagnostic sonography, cables were an essential component, delivering power to the transducer and conveying signals for processing and display at the console. MARCH 2013

Siemens’ Acuson Freestyle instead packs a power source into the handheld transducer and uses an RF transmitter to send signals to a nearby console, mounted up to three meters away from the patient on a cart, table or wall. The initial application of this technology will be for point-of-care scanning, an application that simplifies data acquisition and transmission demands on the transducer as it maximizes the benefits by eliminating a source of biocontamination and provides ease of use in tight quarters. A primary application will be interventional radiology, guiding the

administration of nerve blocks, localizing biopsy targets, and visualizing routes for vascular access. Freestyle uses an advanced synthetic aperture imaging technology, according to the company, designed specifically for wireless signal transmission at high data rates. The integrated hardware-software focuses on individual pixels to create a high-resolution image throughout the field of view. The design minimizes the power needed to run the transducer, which increases battery life. Any of three sealed transducers have been designed to beam raw data for general imaging, vascular and high-frequency applications, such as musculoskeletal and nerve imaging. An ultra-wideband radio technology, operating at a 7.8 Gigahertz, is designed to work in a RF rich environment free from interference by other electronics. Because these probes are completely sealed, they can be totally immersed in germ-killing solutions, making them simple to sterilize. With no cables to snag surrounding equipment, wireless point-of-care ultrasound will appeal to staff in operating rooms, critical care units, cath labs and emergency rooms, where space is tight and medical devices are all around. “It’s about being more streamlined and controlling the environment and increasing confidence in protecting the patient from infection,” said Michael G. Canon, vice president and general

Wireless transducers offer unfettered access to the patient when doing point-of-care scanning with Siemens’ work-in-progress Acuson Freestyle ultrasound system. Immediate applications may be found where space is tight, particularly in operating rooms, critical care units, cath labs and emergency rooms. Image courtesy Siemens Healthcare.

D I

E U R O P E

21


Industry Outlook manager of point-of-care solutions in ultrasound. Advanced PET/CT biomarkers.

Nuclear medicine has languished for decades, beholden to the arrival of biotracers that would open the door to new applications. The closest it came was fluodeoxyglucose, the F-18 spiked sugar molecule that made positron imaging the nuclear darling of the early 2000s. The industry had all but counted PET out when researchers at the University of Pittsburgh spliced it with CT and the hybrid took off around the globe as the standard for patient assessment for many types of cancer. After a brief run-up, however, during which any institution with a reputation for advanced imaging bought into PET, demand for PET/CTs nosedived, a victim of market saturation achieved only about five years after PET/CT was commercialized. With installed systems running far under capacity, the installed base and makers of PET/CT systems have hoped for a new generation of biotracers that would sop up the excess time available on operating systems. Last year Eli Lilly released the first of that generation, florbetapir, known by the trade name Amyvid). Approved last year by the FDA for use in cognitively impaired patients who are being assessed for Alzheimer’s disease, florbetapir attaches to the betaamyloid molecule that forms plaques associated with the development of Alzheimer’s disease.

Holding back the wider adoption of Amyvid is a dearth of reimbursement and less than effective treatment for Alzheimer’s disease. A case can be made that differential diagnosis, or just ruling out Alzheimer’s, can point diagnosticians to underlying causes that might be better treated. There’s also active research underway to develop improved treatments for Alzheimer’s – and that is where new biotracers may also have an effect. Merck is one company pursuing such treatment. Its experimental Alzheimer’s drug MK-8931 inhibits BACE (Beta-site of APP cleaving enzyme), an enzyme critical to the production of amyloid. Late last year Merck announced plans to use an experimental PET agent in a Phase II/III clinical trial of MK-8931. The PET agent, [18F]flutemetamol, is being developed by GE Healthcare to visualize amyloid. In the Merck trials, this radiopharmaceutical is expected to document whether the Merck agent is having a therapeutic effect versus placebo in a controlled study of patients with mild-to-moderate Alzheimer’s. GE’s ultimate goal, however, is to market flutametamol as a diagnostic aid for patients suspected of having Alzheimer’s. Data already obtained in Phase III studies point to the utility of flutemetamol, demonstrating up to 86% sensitivity and 92% specificity in the visual detection of amyloid. The GE agent has the potential to “help doctors rule out Alzheimer’s disease by reliably showing the absence of

Beta-amyloid in cortical grey matter (left panel) bind the PET radiotracer florbetapir , indicating a high likelihood of Alzheimer’s disease, whereas low uptake of the tracer in cortical grey matter(right panel) suggests absence of the disease. Florbetapir, approved last year by the FDA for use in patients with cognitive impairment, is the first in an expected wave of new PET biotracers. Images courtesy of Eli Lilly and Company and Avid Radiopharmaceuticals

22

D I

E U R O P E

amyloid deposits in patients with unexplained loss of cognitive function,” said Jonathan Allis, general manager, PET, GE Healthcare Medical Diagnostics. In the years to come, other PET agents now in early stage development may prove useful in the diagnosis of neurological diseases other than dementia, as well as disease of the heart and coronaries. Advanced agents may even be used to identify patients at risk of developing acute events. Using radiotracers licensed from Massachusetts General Hospital, startup company FluoroPharma is testing PET radiopharmaceuticals designed to gauge myocardial perfusion, distinguish ischemic from infracted heart tissue, and identify in blood vessels vulnerable plaques that may rupture to cause heart attack or stroke. A word of caution

As with all new technologies, enthusiasm for these biotracers and other potentially game-changing technologies must be tempered. Even if GE’s Silent Scan pans out in the months ahead and other vendors follow with similar technologies, MR will not be truly silent, at least not in the foreseeable future. And there may be diagnostic or workflow trade-offs associated with such quieter scans, trade-offs as yet unknown and possibly undetected until extensive clinical experience is gained. Wireless ultrasound, now clearly within grasp, is limited in application to point-of-care scanning with its relatively simple architecture, at least compared to premium radiology and echo systems. Typically breakthroughs spur future breaches of other, more difficult barriers, but they have yet to be achieved and the hurdles still to be surmised. Nowhere is this truer than with the long-awaited arrival of the next generation of biotracers that promise to expand the use of PET beyond oncology. Alzheimer’s and CAD diagnostics, if they live up to their potential, could exert a huge impact on the practice of medicine, literally changing the diagnostic landscape of nuclear medicine. But today all they have is potential. Each type of technology is a possible game changer, as each may change the practice of medicine. And each is exciting in its own right, but only for what it has yet to do, not for what it has done so far. MARCH 2013


Ultravist ® (iopromide) Prescribing Information (Refer to Summary of Product Characteristics (SmPC) before prescribing) Presentation: Intravascular injections of nonionic iopromide in strengths of 150mg, 240mg, 300mg and 370mg of iodine/ml. Indications: For diagnostic use only. Delineation of the vascular and renal systems and of body cavities. Posology and administration: Adults Intravenous urography: minimum doses: Ultravist 370: 0.8ml/kg body weight; Ultravist 300: 1ml/kg body weight; Ultravist 240: 1.3ml/kg body weight. Children Intravenous urography: see SmPC. Adults Computed tomography: Cranial CT: Ultravist 240: 1.5-2.5ml/kg body weight; Ultravist 300: 1-2ml/kg body weight; Ultravist 370: 1-1.5ml/kg body weight. Whole-body CT: Dosage and administration rate depend on investigation and scanner. Adults Angiography: depends on age, weight, cardiac output, general condition, clinical problem, examination technique and the nature and volume of the vascular region to be investigated. (see SmPC). Adults Checking function of dialysis shunt: Ultravist 150: 10ml. Paediatric population: young infants (age < 1 year) and especially newborns are susceptible to electrolyte imbalance and haemodynamic alterations. Care should be taken regarding the dose of contrast medium to be given, the technical performance of the radiological procedure and the patient status. Renal impairment: to reduce the risk of additional contrast media-induced renal impairment in patients with pre-existing renal impairment, the minimum possible dose should be used. Hepatic impairment: no dosage adjustment is necessary. Elderly: possibility of reduced renal function should be considered. Contra-indications: Uncontrolled thyrotoxicosis. Warnings and precautions: Can be associated with anaphylactoid/hypersensitivity reactions, ensure preparedness for institution of emergency measures. Allergy-like reactions from mild to severe possible, mostly within 30 min, but delayed reactions (hours to days) may occur. Particularly careful risk/benefit judgement required for patients with: known hypersensitivity to Ultravist or its excipients; previous reaction to any contrast medium or; history of bronchial asthma or allergic disorders (increased risk). Pre-medicate with corticosteroids if necessary. To minimise risk: administer Ultravist to recumbent patients; observe patients closely for 15 minutes and keep them in hospital for at least one hour after the last injection. Patients on beta-blockers may be resistant to the effects of beta agonists. If severe reaction occurs, patients with cardiovascular disease are more susceptible to serious or fatal outcomes. Caution in patients with: known/suspected hyperthyroidism or goitre, monitor thyroid function in neonates exposed via mother or during neonatal period. Caution in patients with cerebral arteriosclerosis, pulmonary emphysema, poor general health, renal insufficiency, dehydration, diabetes mellitus, multiple myeloma/ paraproteinaemia, repetitive and / or large doses of Ultravist. Nephrotoxicity may occur or rarely acute renal failure. Ensure adequate hydration of patients; correct water or electrolyte imbalances before administration. With cardiac or severe coronary artery disease, increased risk of haemodynamic changes or arrhythmia. Intravascular injection may precipitate pulmonary oedema in patients with heart failure. Increased risk of neurological complications in patients with seizure history or CNS disorders. Caution in patients with reduced seizure threshold. May aggravate the symptoms of myasthenia gravis. Flush intravascular catheters frequently with physiological saline (if possible with addition of heparin) and minimise procedure length to minimise procedure-related thromboembolism risk. Patients with phaeochromocytoma may be at increased risk of developing a hypertensive crisis. Minimise excitement, anxiety and pain. Do not use in myelography. Sensitivity testing is not recommended. Interactions: Consider interruption of biguanides treatment prior to Ultravist administration as a precaution against development of lactic acidosis. Prevalence of delayed reactions higher in patients who have received interleukin-2. Diagnosis and treatment of thyroid disorders with thyrotropic radioisotopes may be impeded for up to several weeks due to reduced radioisotope uptake. Pregnancy and lactation: Adequate and well-controlled studies in pregnant women have not been conducted. Safety for nursed infants has not been investigated. Effects on ability to drive and use machines: Driving or operating machinery is not advisable for 30 minutes after the last injection. Undesirable effects: Common: dizziness, headache, dysgeusia, blurred/disturbed vision, chest pain/ discomfort, hypertension, vasodilatation, vomiting, nausea, pain, injection site reactions (e.g. oedema, soft tissue injury post extravasation), feeling hot. Serious side effects: cf – Warnings and Precautions – in addition: Hypersensitivity/ anaphylactoid reactions (anaphylactoid shock§*, respiratory arrest§*, bronchospasm*, laryngeal*/pharyngeal* or mucosal oedema, laryngeal/pharyngeal spasm§, asthma§*, angioedema), vasovagal reactions, arrhythmia*, dyspnoea*, cardiac arrest*, myocardial ischaemia*/infarction*, thyrotoxic crisis, thyroid disorder, coma*, cerebral ischaemia/infarction*, stroke*, brain oedema*, convulsion*, transient cortical blindness (IV use only), loss of consciousness, amnesia, paresis/paralysis, hearing disorders, cardiac failure*, bradycardia*, tachycardia, cyanosis*, hypotension*, shock*, thromboembolic events (IV use), pulmonary oedema*, respiratory insufficiency*, aspiration*, bullous conditions (e.g. Stevens-Johnson syndrome or Lyell syndrome), compartment syndrome due to extravasation (IV use), renal impairment/ acute renal failure (IV use). § Reactions identified only during post-marketing surveillance (frequency not known). *These adverse reactions may have a fatal or life-threatening outcome and are considered the most serious adverse drug reactions. Prescribers should consult the SmPC in relation to other side effects. Overdose: Symptoms may include fluid and electrolyte imbalance, renal failure, cardiovascular and pulmonary complications. Monitoring of fluids, electrolytes and renal function recommended in case of intravascular overdosage. Treatment of overdose should be directed towards the support of vital functions. Ultravist is dialysable. Incompatibilities: Because of possible precipitation, X-ray contrast media and prophylactic agents must not be injected as mixed solutions. Special Precautions for Storage: Protect from light and X-rays. Legal Classification: POM Package Quantities and Basic NHS Price: Ultravist 150 10 x 50ml bottles £101.57 Ultravist 240 10 x 50ml £145.86 Ultravist 300 10 x 20ml £124.63 10 x 50ml £182.03 1 x 100ml £36.16 1 x 200ml £71.98 Ultravist 370 10 x 50ml £224.94 1 x 100ml £44.68 1 x 200ml £88.78 MA Numbers: Ultravist 150: 00010/0564 Ultravist 240: 00010/0565 Ultravist 300: 00010/0566 Ultravist 370: 00010/0567 Further information available from: Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA, Telephone: (01635) 563000 Date of preparation: August 2012 Ultravist® is a trademark of the Bayer Group. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Bayer plc. Tel.: 01635 563500, Fax.: 01635 563703, Email: phdsguk@bayer.co.uk References 1. For details and full range of indications please refer to the Summary of Product Characteristics.

A Well-Balanced Contrast Medium

With a right mix of osmolality, viscosity and iodine concentration, Ultravist® delivers contrast for high-quality imaging results.1

www.bayer.co.uk Enquiries: 01635 563000 Calls to and from Bayer HealthCare may be recorded Date of preparation: October 2012. L.GB.10.2012.0951 All rights reserved. © Bayer plc 2012


Molecular Imaging by Dr H Zaidi

Advances in hybrid PET-MR imaging The development and clinical deployment of hybrid PRT/MRI systems has enabled the assessment of the possibly ground-breaking potential of the approach. Despite this, formidable challenges remain, not the least of which is economic justification. This article reviews the potential clinical role of hybrid PET/MR systems, describes the currently available equipment and their applications as well as the issues needing to be resolved Rationale for and potential clinical role of hybrid PET-MR imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) have become prevailing medical imaging techniques and have proven to be valuable clinical and research tools. However, the inability of PET to provide anatomical information and the difficulties of anatomical MRI to provide molecular signals is considered a major limitation of standalone PET and MR systems [1]. This has motivated the development of software approaches to align PET images with CT or MRI anatomical images [2]. This task proved to be successful in the brain but not in other parts of the body such as the thorax and upper abdomen where the non-rigid motion between the two images owing to different breathing patterns resulting from differences in acquisition times make the registration task difficult to achieve in these regions. In this context, the development of combined SPECT/ CT and PET/CT scanners for clinical imaging rendered possible the acquisition of both structural and functional images [3, 4]. Even though CT has well established benefits in oncological imaging, an extremely attractive substitute to PET/CT is to combine PET with MRI, since the repertoire of MR examinations is greatly complementary to PET [5]. The author : Habib Zaidi, Ph. D., P.D. is at 1D ivision of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva, Switzerland 2G eneva Neuroscience Center, Geneva University, Geneva, CH-1211 Switzerland 3D epartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Correspondence to Habib Zaidi, PhD, PD Division of Nuclear Medicine, Geneva University Hospital, CH-1211 Geneva Switzerland. Tel +41 22 3727258; Fax +41 22 3727169 email: habib.zaidi@hcuge.ch

24

D I

The combination of PET and MRI, enabling truly simultaneous acquisition, bridges the gap between molecular and systems diagnosis. Since PET and MRI offer richly complementary functionality and sensitivity, integration into a combined system offering simultaneous acquisition will capitalize the strengths of each. Moreover, the dual-modality system would enable the exploitation of the superiority of MR spectroscopy (MRS) to gauge regional biochemical content and to measure the metabolic status or the presence of neoplasia and other diseases [6-8]. Figure 1 shows representative clinical whole-body PET/CT and PET/MR images of a lung cancer patient acquired sequentially on two combined systems, namely the Biograph TrueV (Siemens Healthcare) and the Ingenuity TF PET/MRI (Philips Healthcare). The PET/CT study started 30 mins following injection of 370 MBq of 18F-FDG followed by PET/MRI which was begun about 70 mins later. The lesion detected at PET/ CT was also identified by PET/MRI, with small difference between PET/CT and PET/MRI uptake ratios owing to differences in uptake time. However, the better soft tissue contrast observed on MRI is obvious and further emphasizes the ineffectiveness of PET/CT in some indications, and so emphasizes the potential role of PET/MRI. The clinical role of hybrid PET/MR imaging is currently encompassing a wide variety of applications and is being performed in some facilities equipped with this technology to answer important clinical questions including those in oncology [6-8], cardiology [8, 9], neurology and psychiatry [10]. Nowadays, a plethora of novel tracers are used routinely for assessing tumour metabolism and other biological and physiological parameters associated with many diseases [11, 12]. These have clearly demonstrated the enormous potential of emerging hybrid technologies in the field of molecular imaging. Some opinions are emerging which advocate the potential benefits of simultaneous PET/MR

E U R O P E

MARCH 2013


MRI

PET

PET-MRI

FIGURE 1. Representative clinical whole-body PET (left), PET/CT (middle) and PET/MR (right) images of the same patient acquired sequentially (~70 min time difference) on two combined systems (Siemens Biograph Hirez TrueV and Philips Ingenuity TF PET/MRI, respectively) following injection of 370 MBq of 18F-FDG. Courtesy of Geneva University Hospital.

imaging over PET/CT technology in terms of improvement of tissue characterization. However, many challenging issues still need to be addressed. These include the clinical relevance and clinical/economic justification for this technology. 2. A dvances in hybrid PET-MRI systems

Following the pioneering work and early attempts initiated in the 1990s [13, 14], different trends for PET-MR system design have emerged during the last decade [15-17]. The simplest design follows the configuration adopted for PET/CT where the PET and MR scanners are arranged in tandem, thus enabling sequential data acquisition in space and time. These systems were designed in expectation of the availability of mature and economically viable simultaneous wholebody PET/MRI systems [18]. Two such systems were developed and are now commercially available. The first is the Ingenuity TF PET/MRI (Philips Healthcare, Best, The Netherlands), with time-of-flight Gemini TF PET and Achieva 3T X-series MRI systems, allowing for sequential acquisition of coregistered PET and MR images. The characterisation of the MARCH 2013

PET subsystem demonstrated no compromise of system performance caused by the presence of the strong MR magnet [19]. In our facility, the system is being mostly used for clinical oncology, focusing on breast cancer, head and neck cancer and prostate cancer. Figure 2 shows a representative PET/MRI study for staging of breast cancer. An alternative proposed by General Electric (GE Healthcare, Waukesha, WI, USA) enabling trimodality imaging (PET/CT/-MRI) uses sequential acquisition on two separate scanners (PET/ CT and MR) located in adjacent rooms with a mobile bed that can shuttle the patient from one scanner to the other [20]. This latter solution has the advantage that the two scanners can be operated separately in case of high workload, but presents a major drawback and logistical challenge in terms of coordinating patient transfer from one scanner to the other, and represents a higher risk of patient motion between the two examinations. This design also requires the acquisition of a CT scan for attenuation correction of the PET data, thus resulting in additional radiation dose to the patient. The most attractive design option is to perform the PET and MRI examinations simultaneously in space and D I

E U R O P E

time. This solution has brought to the “insert” concept adopted for both preclinical [21] and brain PET-MR systems design [22], where a small axial size PET insert fits inside a standard MRI scanner. A more challenging solution is the “fully integrated” version, where a dedicated whole body PET scanner is built in a dedicated MRI scanner. This is the most promising option that that can bring to a genuine step forward the adoption of combined PET/MRI systems in clinical diagnosis, therapy and follow-up. The mMR whole-body PET/MRI system (Siemens Healthcare, Erlangen, Germany) is one example of an integrated compact hybrid system. The system was recently deployed in a number of facilities located in Europe and the US for assessment and validation in clinical and research settings [23, 24]. 3. Futuristic outlook

The recent introduction of hybrid PET/MRI technology is viewed as a major breakthrough having the potential to prompt a ground-breaking paradigm shift in diagnostic imaging and modernize clinical practice. A number of active research groups in academic and corporate settings are concentrating their efforts towards the 25


Molecular Imaging MRI

PET

PET-MRI

FIGURE 2. Whole body PET/MR study for staging of breast cancer. From left to right, axial planes of low resolution T1-weighted MR scan used for localization and tissue attenuation correction, PET image showing a hypermetabolic lesion of the left breast and fused PET and MR images.

development of stable and compact PET/MRI systems enabling simultaneous imaging using the most highly sophisticated molecular imaging technologies available today. However, despite the many promising aspects of PET/MRI, many challenges are still facing the success and widespread adoption of this technology, the most relevant being its clinical relevance and economical viability within modern healthcare systems where cost and justification play a pivotal role. The likely clinical deployment of different configurations of hybrid PET/MRI systems in the near future will enable comparative effectiveness research to be performed in order to justify the need for simultaneous PET/MRI as opposed to sequential or even software-based PET/MR image fusion. In addition, the qualifications required of interpreting nuclear medicine physicians and radiologists, residents in training, technologists, and medical physicists will need to be defined and harmonized by interdisciplinary groups representing the various professional societies involved. Finally, new reimbursement guidelines for PET/MRI will also have to be established prior to clinical implementation. For this technology to realize its full potential, the quantitative capabilities of PET/MRI still require major improvements and validation. The anatomical information provided by MR is currently used with some limitations for attenuation compensation but could also be useful for many other tasks including, motion detection and correction 26

[25], image reconstruction [26], and partial volume correction [27]. Despite the many worthwhile research efforts, the commercial solutions provided for MR-guided attenuation correction are still not satisfactory. As such, this will remain a very hot and active research topic within the next few years. References 1. P ichler BJ, Kolb A, Nagele T, Schlemmer HP. PET/ MRI: paving the way for the next generation of clinical multimodality imaging applications. J Nucl Med. 2010;51:333-36. 2. Hill DL, Batchelor PG, Holden M, Hawkes DJ. Medical image registration. Phys Med Biol. 2001;46:R1-45. 3. Hasegawa BH, Gingold EL, Reilly SM, Liew SC, Cann CE. Description of a simultaneous emission-transmission CT system. Proc SPIE. 1990;1231:50-60. 4. Beyer T, Townsend D, Brun T, Kinahan P, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000;41:1369290. 5. Zaidi H, Mawlawi O. Simultaneous PET/MR will replace PET/CT as the molecular multimodality imaging platform of choice. Med Phys. 2007;34:1525-28. 6. Buchbender C, Heusner TA, Lauenstein TC, Bockisch A, Antoch G. Oncologic PET/MRI, Part 1: Tumors of the brain, head and neck, chest, abdomen, and pelvis. J Nucl Med. 2012;53:928-38. 7. Buchbender C, Heusner TA, Lauenstein TC, Bockisch A, Antoch G. Oncologic PET/MRI, part 2: bone tumors, soft-tissue tumors, melanoma, and lymphoma. J Nucl Med. 2012;53:1244-52. 8. von Schulthess GK, Kuhn FP, Kaufmann P, VeitHaibach P. Clinical positron emission tomography/magnetic resonance imaging applications. Semin Nucl Med. 2013;43:3-10. 9. Wehrl HF, Sauter AW, Judenhofer MS, Pichler BJ. Combined PET/MR imaging-technology and applications. Technol Cancer Res Treat. 2010;9:5-20. 10. Catana C, Drzezga A, Heiss W-D, Rosen BR. PET/MRI for neurologic applications. J Nucl Med. 2012;53:1916-25. 11. Valliant JF. A bridge not too far: Linking disciplines through molecular imaging probes. J Nucl Med. 2010;51:1258-68. 12. Wester H-J. Nuclear imaging probes: from bench

D I

E U R O P E

to bedside. Clin Cancer Res. 2007;13:3470-81. 13. C hristensen NL, Hammer BE, Heil BG, Fetterly K. Positron emission tomography within a magnetic field using photomultiplier tubes and lightguides. Phys Med Biol. 1995;40:691-97. 14. Shao Y, Cherry SR, Farahani K, Meadors K. Simultaneous PET and MR imaging. Phys Med Biol. 1997;42:1965-70. 15. Delso G, Ziegler S. PET/MRI system design. Eur J Nuc Med Mol Imaging. 2009;36:86-92. 16. Zaidi H, Del Guerra A. An outlook on future design of hybrid PET/MRI systems. Med Phys. 2011;38:5667-89. 17. Vaska P, Cao T. The state of instrumentation for combined positron emission tomography and magnetic resonance imaging. Semin Nucl Med. 2013;43:11-18. 18. Torigian D, Zaidi H, Saboury B, Udupa J, Kwee T, Karp J, et al. PET-MRI: Technical aspects and potential clinical applications. Radiology 2013 in press 19. Zaidi H, Ojha N, Morich M, Griesmer J, Hu Z, Maniawski P, et al. Design and performance evaluation of a whole-body Ingenuity TF PET-MRI system. Phys Med Biol. 2011;56:3091-106. 20. Veit-Haibach P, Kuhn F, Wiesinger F, Delso G, von Schulthess G. PET–MR imaging using a trimodality PET/CT–MR system with a dedicated shuttle in clinical routine. Magn Reson Mat Phys Biol Med. 2013:in press. 21. Judenhofer MS, Wehrl HF, Newport DF, Catana C, Siegel SB, Becker M, et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med. 2008;14:459-65. 22. Kolb A, Wehrl HF, Hofmann M, Judenhofer MS, Eriksson L, Ladebeck R, et al. Technical performance evaluation of a human brain PET/MRI system. Eur Radiol. 2012;22:1776-88. 23. Delso G, Furst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med. 2011;52:1914-22. 24. Drzezga A, Souvatzoglou M, Eiber M, Beer A, Ziegler S, Furst S, et al. First clinical experience of integrated whole-body MR/PET. Comparison to PET/CT in patients with oncological diagnoses. J Nucl Med. 2012;53:845-55. 25. Ouyang J, Li Q, El Fakhri G. Magnetic resonance-based motion correction for positron emission tomography imaging. Semin Nucl Med. 2013;43:60-67. 26. Bai B, Li Q, Leahy RM. Magnetic resonance-guided positron emission tomography image reconstruction. Semin Nucl Med. 2013;43:30-44.

MARCH 2013


Cardiovascular and Interventional Radiological Society of Europe

r e t s i g e R ! w o n

ECIO 2013 Fourth European Conference on Interventional Oncology June 19-22 Budapest | Hungary

www.ecio.org

C RSE


The DI Europe Interview New hands on the wheel at Guerbet: a talk with Yves l’ Epine, CEO of the French-based contrast media company

After a mere 18 months in charge of the contrast media company Guerbet, Yves L’Epine looks as though he is already making his presence felt. With significant sales growth in 2012 and good prospects for this year, the cherry on Guerbet’s cake looks like being the 2013 introduction onto the US market of the company’s flagship product, the gadolinium-based agent Dotarem. After a few years of decline, Guerbet’s stock price on the Paris stock exchange is now again reaching historic highs. We talk to Guerbet’s CEO.

A cardiologist by training and with extensive experience in business and management in the pharmaceutical industry, plus a dynamic personality, 53 year old Yves L’Epine has all the qualities to lead Guerbet.

Q. Judging by the figures,

Guerbet seems to be thriving since you came on board. What’s the secret?

No secret but a lot of hard work and making the correct decisions as to what our priorities should be. Of course as a publicly quoted company, it’s important that the financial figures are satisfactory but in a way that is just a reflection of more important underlying features. These are that, on the one hand, our customers, especially those in our key markets, are increasingly using our products and that, on the other hand, we are able to master our production costs and provide the products at attractive prices. It’s true that for the moment Europe is our stronghold market and sales growth in this market is particularly enouraging. The global market for 28

radiology contrast agents is dominated by the US and European markets which together make up approximately 70% of the world market. This is split over the various modalities, with X-ray contrast agents making up nearly half of the market, nuclear medicine contrast agents approximately 33% of the market and MRI comprising approximately 15%. At Guerbet we don’t really follow this pattern of market breakdown since although we have products for all the modalities, we are proportionally more focussed on MRI as well as having exciting new possibilities in products for use in interventional radiology. Of course we make no pretence about the fact that we are entirely and solely involved in the field of radiology contrast agents with all the constraints and advantages that brings. However despite the special characteristics of the field these don’t hold any fears for me, thanks to my professional background.

Q. Which is?

I originally trained as a cardiologist and interventional radiologist but was relatively soon tempted to make a career in business, so I put myself through a European business school [INSEAD outside Paris, France]. That led me into the world of the pharmaceutical industry, starting with Sandoz, its merger with Ciba Geigy to form Novartis, then progressively head of Takeda’s French subsidiary, and most recently Abbot. One great advantage of this is that, prior to becoming CEO of Guerbet, I’ve thus had exposure to the way of thinking of European, Japanese and American companies in the pharmaceutical business. Of course, the pharmaceutical business has many features in common to the contrast agent business, such as the manner in which the products are regulated and approved by the appropriate authorities, e.g. the FDA in the States and the EMEA in Europe.

Q. But you said that the con-

trast agent business had its own special characteristics.

With a particularly good safety/efficacy profile for Dotarem, especially as far as the risk of NSF is concerned, the company is awaiting a response from the United States FDA. After encouraging results from Phase III clinical trials, this is expected by the end of March 2013. One indication which is expected to be approved is in central nervous system pathologies such as brain tumors. More than half of all MRI scans in the US are carried out for this indication.

D I

E U R O P E

Yes, one obvious one being that although radiology contrast agents may be regulated as pharmaceutical agents, their clinical purpose is of course quite different. Pharmaceutical products are used to induce a therapeutic effect, whereas radiology contrast agents are designed to enhance the diagnostic power of the images, which of course can also be really important. Also, most often contrast agents are only administered on a MARCH 2013


“one-shot” basis while therapeutic drugs can be given on a regular, chronic basis. Despite this difference in typical usage, the toxicological safety criteria that the regulatory agencies apply are the same for both types of products. It can sometimes seem tough that we in the contrast agent business have to provide toxicology data showing the safety of our products being used in ways that are unlikely to ever be applied in practice. However there’s no point in moaning about this — that’s the way it is. Anyway the safety profile of our products is excellent.

Q. What about gadolinium-induced nephrogenic systemic fibrosis (NSF)?

It’s true that, very rarely, there can be side-effects — and unfortunately sometimes quite serious — resulting from the leakage of Gadolinium ions from the molecule that chelates the ion. In patients with renal insufficiency this can sometimes give rise to nephrogenic systemic fibrosis (NSF) . The simplest way to avoid the possible complication is a straightforward test to check correct renal function in patients that could be susceptible. Studies of the correlation between the structure of gadolinium-containing chelating molecules and their likelihood of releasing free Gd show that this is low whenever the Gd ion is caged in a macrocyclic and ionic molecule. This is exactly the structure of gadoteric acid which is the basis of our Dotarem product. In practice this theoretical safety profile has been verified by the fact that there is no single agent case of NSF reported with Dotarem, after 23 years of clinical experience in 72 countries throughout the world. It is this background of safety data which makes us confident that the current application now being considered by the FDA authorities in the USA will be successful and end up in us being able to market Dotarem in the States. We expect the answer from the FDA by March 20th. The indication we expect to be approved is in the central nervous system, e.g. the visualization of brain tumors. MRI scans of the central nervous system alone account for more than half the scans carried out in the US. MARCH 2013

Q. You’ve talked a lot about your

MRI contrast agents and the United States market but what about other products and, for that matter, other geographical markets ?

No company claiming to be a major player in the contrast agents field can afford not to have a complete presence in all the major markets with products covering the major areas, and Guerbet does this. That said, we clearly have priorities where we focus particular attention. These priorities are both in geographical market areas and in product lines. Overall the market, which globally is currently worth more or less 6 billion Euros has several factors which, business-wise, can be considered to be positive. To start with there is the well-documented demographic trends of the ageing population which are accompanied by an inevitable increase in healthcare intervention, including of course radiology. Added to this there is the long-heralded advent of personalized medicine which will also bring with it increased requirements for detailed evaluation (not just radiological) of the patient. Of course there are also aspects of the market which are more challenging. As well as the ever-present pressure by governments to reduce the financial burden of healthcare, which affects everybody, the contrast media business has its own special issues. For example advances in technology such as in CT scanners mean that high quality images can be obtained with lower amounts of contrast media. Another issue is the cost of raw materials. Iodine, which is at the base of all X-ray contrast media is traded in a market, much like other raw materials such as silver, copper, tin, etc. Over the past few years the price of iodine has increased dramatically. Likewise, but to a lesser extent, the price of gadolinium, at the heart of MRI contrast agents has increased significantly.

Q. So how do you meet these challenges ?

Some things, such as the price of iodine are outwith our control. What we can do is to keep a constant control of other costs. Our production facilities — three in France and one in Brazil — are now benefitting from D I

E U R O P E

Paradoxically, one of Guerbet’s products with the brightest future prospects is one of the oldest of the company’s products — albeit in brand new applications. Lipiodol, which consists of iodinated ethyl esters of fatty acids derived from poppy seed oil, was discovered in 1901 by Marcel Guerbet, father of the founder of the Guerbet company. It has been used since as long ago as 1926 as a radiological iodinated contrast agent particularly X-ray examination of lymph vessels. More recently, a modern version of the product is being used in an interventional radiological application, the vascular chemoembolization — in combination with surgical glues of tumors such as hepatocellular carcinoma.

the considerable investment that we have made over the last few years, culminating in nearly 30 million Euros in 2012 alone. From the marketing point of view, we have to fix our priorities. By avoiding the trap of trying to be all things to all men, we then focus on these priorities. For example, as I said the impending approval of Dotarem in the US means that the States will become a high priority for us. In the X-ray contrast media market in Europe we will focus primarily on our main markets — by the way, although we are a French company the vast majority of our sales are outside France. From the product development point of view we deliberately don’t chase after every new product possibility but ruthlessly focus on a few key new molecule projects. In the technology field, one area that we intend to focus on is that of interventional radiology. It’s a paradox that a derivative of one of our oldest products is now finding brand new applications. Lipiodol, which consists of iodinated ethyl esters of fatty acids derived from poppy seed oil, was discovered by Marcel Guerbet, father of André who founded the Guerbet company as long ago as 1926. It has been used since then as a radiological iodinated contrast agent. Now it is being used in certain countries for the chemoembolization of certain tumors such as hepatocellular carcinoma. In this application certain cytotoxic drugs are added to the Lipiodol, which is used a bit like liposomes to carry the drug into the liver. The blood vessels are then blocked to allow more contact time of the drug with the tumor. Encouraging results have been achieved with this approach. 29


CAD by Prof. Bram Van Ginneken

How to get Computer-Aided Diagnosis into the clinic Computer-Aided Diagnosis (CAD) tools are not yet widely used in clinical practice. This article discusses why and identifies the hurdles to be overcome before CAD can thrive.

T

en years or so ago, the future for Computer-Aided Diagnosis, or CAD, looked bright. In 1998, the first product to analyze a medical image had received approval from the United States Food and Drug Administration. In the early 2000s, US insurance companies started to reimburse the use, in mammography of this CAD technology, the so-called R2 ImageChecker. The widespread expectation at the time was that many other applications would quickly follow and that this would be the beginning of an era where computers and radiologists would read images together. Industry opened dedicated CAD research labs, the number of papers on CAD grew fourfold in ten years, and a new conference was started. And indeed, most mammograms in the United States are now processed by CAD. But in other areas, and in mammography in Europe, computers are still not widely used to help physicians in the interpretation of medical images. Why is this? The answer is not simple, because there are multiple conditions that must be fulfilled before CAD can thrive [1]. In this article I will discuss one wrong and three correct explanations, and I will argue that the future of CAD still looks bright. “IT IS TOO DIFFICULT TO BUILD INTELLIGENT COMPUTERS”

This explanation is wrong, but it is understandable that radiologists have come to this conclusion over the years. Industry has simply brought too many CAD products to market that are not working well enough to be of clinical use. Consider lung nodule volumetry in CT as an example. De Hoop et al. [2] published a direct comparison of six commercially available algorithms for volumetry of solid lung nodules. Three commercial systems produced an inadequate segmentation in 22% to 30% of all cases. This is not an isolated example. There are many CAD systems for sale that suffer from high numbers of false positives at only moderate sensitivity levels. In general, however, computers are becoming intelligent very rapidly. We are seeing breakthroughs in machine learning all around us. The two most prominent examples are IBM The author : Prof. Van Ginneken is Chair of the Diagnostic Image Analysis Group, Department of Radiology, Radboud University Nijmegen Medical Centre, The Netherlands. e-mail: b.vanginneken@rad.umcn.nl.

MARCH 2013

D I

Watson and the Google Car. Watson is a computer system that can answer general questions posed in natural language [3]. Watson beat top human players in the popular quiz Jeopardy in 2011. The Google Cars have driven hundreds of thousands of miles without human intervention, under wide varying conditions, among other traffic. This technology is expected to be commercially available within a decade [4]. In both cases, nobody expected a few years ago that something like this was possible [5]. In both cases a top team of around twenty researchers, backed by a company that takes innovation seriously, developed these technologies in around five years only. From a technological point of view, this shows that serious investment in building intelligent computers pays off. Also in radiology, there are success stories. One of the systems in the study of De Hoop [2] mentioned earlier, actually produced an adequate segmentation in 98% of all cases. Or consider bone age assessment, as determined from a radiograph of the left hand and wrist. Many attempts to automate this have been made, starting in 1992 with CASAS from Tanner and Gibbons [6]. CASAS was thoroughly evaluated and found to reduce inter-observer variability, but the software was cumbersome to use because each bone had to be located manually. Moreover, performance of automated staging of bones was lackluster. Thus, CASAS was never widely used. Recently, Thodberg introduced BoneXpert [7], a program that is fully automatic and processes an image in about five seconds on standard PC hardware (Figure). It locates the borders of fifteen bones in the radiograph and assigns an intrinsic bone age to thirteen bones. A machine learning model estimates the Greulich and Pyle bone age from these intrinsic bone ages. Evaluation studies have elegantly shown that when those cases where the computer and human experts disagree are blindly reexamined, the error was in most cases made by the humans [8]. CAD AS A “SPELLCHECKER” IS NOT WHAT WE NEED

Most CAD systems on the market today provide radiologists with markers, or prompts, around suspicious regions in the image, that warrant a closer look. This paradigm of “CAD as a spellchecker” became the norm in the early days of CAD, when the FDA developed a procedure for approving such systems and CAD systems were not performing well enough to be more than a mere spellchecker. It is highly doubtful, however, that simply providing the radiologist with candidate lesions is the most effective way to

E U R O P E

30


See us at ECR 2013, Booth 8 - Extension Expo A

TM

terarecon.com/cloud

Experience iNtuition online, for FREE. Sign up today at terarecon.com/cloud. Award-Winning Advanced Visualization, direct to your browser. Finding Viewer

Patient Name: FaceOffˆRECIST_1.1

PATIENT ID: 001

Finding Viewer 05/05/2010

07/13/2010

09/01/2010

1. Lymph 1 (Target)

Distance: 27.4 mm Slice #: 57

Distance: 11.9 mm (-57%) Slice #: 30

Distance: 10.9 mm (-60%) Slice #: 39

2. Lesion1 (Target)

Distance: 12.0 mm Slice #: 39

Distance: 12.0 mm (0.0%) Slice #: 12

Slice #: 16

3. Lymph2 (Target)

Distance: 34.9 mm Slice #: 59

Distance: 20.0 mm (-43.%) Slice #: 31

4. Lesion2 (Target)

Distance: 12.2 mm Slice #: 34

Distance: 9.92 mm (-18%) Slice #: 7

5. Lesion3 (Target)

Distance: 36.6 mm Slice #: 36

Distance: 40.6 mm (11%) Slice #: 9

5 Target Lesions

5 Target Lesions SUM (RECIST ): 94.5 mm

Distance: 13.2 mm (9.6%)

10/21/2010

Distance: 25.8 mm (-5.8%) Slice #: 10

Distance: 11.8 mm (-1.8%)

Slice #: 16

6. Lesion4 (Non Target)

7. Lesion5 (Non Target)

SUM (RECIST ): 123 mm

Unmatch

Show Filter

iNtuitionCLOUD – Public and Private TeraRecon is the first and only provider of true thin-client advanced visualization in the Cloud. The runaway success of the public iNtuitionCLOUD has proven the power and capability of TeraRecon’s cloud technology, which is completely self-contained and not reliant on any third-party service for cloud hosting services. As a result, an equally-capable Private iNtuitionCLOUD is possible, with all security and access controls remaining within the healthcare enterprise.

info@terarecon.com | www.terarecon.com | +49 69 9510 3520 | 0800 837 2732

iNtuition and the iNtuition logo are trademarks of TeraRecon, Inc. Copyright© 2013 TeraRecon, Inc. All rights reserved. 022513AQ-A/DIE-A1


CAD achieve the goal of CAD: increase sensitivity without a corresponding loss of specificity and without increasing reading time. Our clinical experience so far shows that it is harder for the radiologist to differentiate between true and false positive markers than one would expect. Dependant on the mindset of an individual reader, he will dismiss true positive CAD candidate lesions or accept false positive markers. And to achieve high sensitivity and mark the lesions that are actually likely to be missed by radiologists, CAD systems produce a lot of false positive markers, many more than a radiologist would do. This undermines radiologists’ faith in the software, and could be the reason why many researchers believe that CAD for mass detection in mammograms is not yet good enough to be useful [9]. Another option is to provide “CAD on demand”: instead of showing markers automatically, the user can click on suspicious regions and immediately obtain the opinion, in terms of a numerical score, of the computer. A recent study [10] showed that CAD on demand for the detection of masses in mammography was more effective than the use of classical CAD markers. However, both markers and CAD on demand increased reading time from about 40 to 50 seconds per case. In the long term CAD solutions that do not increase reading time would be preferable, like the completely automatic analysis of BoneXpert or automatic volumetric segmentation of tumors to replace cumbersome manual diameter measurements according to RECIST criteria in oncology applications. In both these examples, only a quick glance from humans would be needed to make sure the analysis was carried out reliably. CAD SUFFERS FROM POOR INTEGRATION IN RADIOLOGISTS’ WORKFLOW

This is absolutely true, and a lot of work is needed to solve this. Radiologists will only use CAD if it is seamlessly integrated in their workflow. The output of the algorithm should be available within their reading environment, typically a PACS workstation. The result should be pre-computed, or computed very quickly at the push of a single button. The first steps in this direction are being made. Several vendors are marketing CAD servers, computers within the network of the 32

radiology department that inspect the DICOM descriptors of all studies, process relevant scans in the background and store CAD results as DICOM structured reports. In theory, CAD results stored in a standardized format could be displayed by any workstation, but in practice this is not yet the case. Integrating quantitative CAD tools in a diagnostic workstation is more complicated than including CAD detection markers that only require static display. This is especially true if user interaction is deemed necessary. Automatic inclusion of the quantitative information in the radiological report is essential. “THERE IS NO GOOD BUSINESS MODEL FOR CAD TOOLS”

A major limitation of workflow integration of CAD tools today is the lack of open standards. Radiologists, as workstation users, together with patient advocacy groups and regulatory agencies, should insist that vendors allow interoperability, so that the manufacturer of your nodule detection algorithm does not need to be the same as the company from which you buy your scanner or PACS software. Workstation vendors should realize that their product has more value if it allows integration of any CAD product, even a product from a competitor. Compare diagnostic workstations with smart phones: both Apple and Android phone manufacturers have created a highly successful market for small applications that enhance a phone’s capabilities. This materialized because they opened their systems to software created by third party companies, instead of bundling only their own software. All parties, phone manufacturers, third party developers and end users, benefit. If such a market were created for diagnostic workstations, even simple CAD applications that under the current situation would not be profitable to develop could be deployed widely and save radiologists’ time. An example is the automatic determination of the cardio-thoracic ratio on chest radiographs. Automating such a measurement is feasible [11] but this CAD application is too small to be marketed as a stand-alone product. However, as a plugin or “app” it might be widely used. SUMMARY

Developing computer algorithms that analyze medical images with a performance level comparable to that of D I

E U R O P E

human experts is not impossible. It just requires considerable effort and worldclass expertise in image processing, machine learning, and radiology: we need a proper business model for CAD before these investments will be made. A related issue is that integration in clinical workflow poses many practical challenges. Radiologists must urge manufacturers to open their PACS workstations for third party CAD software developers. They should be able to download and directly use CAD software in their own PACS environment, as easily as they can today download small applications that enhance the capabilities of their mobile phone. The number of potential CAD applications is huge and if the right incentives are put in place, CAD will certainly thrive. Radiologists will become more productive, make fewer errors, and will have more time to spend on the more complex, challenging cases. REFERENCES: 1. B. van Ginneken, C.M. Schaefer-Prokop, M. Prokop. Computer-aided Diagnosis: How to Move from the Laboratory to the Clinic, Radiology, 2011;261:719-32. 2. B. de Hoop, H. Gietema, B. van Ginneken et al. A comparison of six software packages for evaluation of solid lung nodules using semiautomated volumetry: what is the minimum increase in size to detect growth in repeated CT examinations. Eur Radiol 2009;19:800-8. 3. D. Ferrucci, E. Brown, J. Chu-Carroll, et al. Building Watson: An Overview of the DeepQA Project. AI Magazine, Fall 2010. 4. Look, no hands. The Economist, September 1, 2012. 5. Race Against the Machine: How the Digital Revolution is Accelerating Innovation, Driving Productivity, and Irreversibly Transforming Employment and the Economy”, E. Brynjolfsson and A. McAfee. Digital Frontier Press, 2011. 6. J.M. Tanner, D. Oshman, G. Lindgren et al. Reliability and validity of computer-assisted estimates of TannerWhitehouse skeletal maturity (CASAS): comparison with the manual method. Horm Res 1994;42:288-94. 7. H.H. Thodberg, S. Kreiborg, A. Juul, et al. The BoneXpert method for automated determination of skeletal maturity. IEEE Trans Med Imaging 2009;28:52-66. 8. R .R. van Rijn, M.H. Lequin, H.H. Thodberg. Automatic determination of Greulich and Pyle bone age in healthy Dutch children. Pediatr Radiol 2009;39:591-7. 9. R.M. Nishikawa, M. Kallergi, C.G. Orton. Computeraided detection, in its present form, is not an effective aid for screening mammography. Med Phys 2006;33:811-4. 10. R. Hupse, M. Samulski, M.B. Lobbes, et al. Computeraided Detection of Masses at Mammography: Interactive Decision Support versus Prompts, Radiology 2013;266:123-9. 11. B. van Ginneken, M.B. Stegmann, M. Loog. Segmentation of anatomical structures in chest radiographs using supervised methods: a comparative study on a public database. Med Imag Anal 2006;10:19-40.

MARCH 2013


Come to feel the Evolution at:

Visit us at Expo B booth n. 205

Your needs, our passion. Giotto Tomo is 2 Generation Tomosynthesis: nd

the only system in the world with Step and Shoot Tube Motion, variable angles, and variable dose. These characteristics ensure the highest image quality with low dose! It is the cutting edge approach to lesion visualization!

Giotto Image Mammography & Prone biopsy 2-in-1: the only system for mammography and prone biopsy using the same detector for both procedures. This reduces missed micro calcifications during stereotactic biopsies.

Prone biopsy

Via Sagittario, 5 - 40037 Pontecchio Marconi Bologna Italy - Tel +39 051 84.68.51

w w w. i m s i t a l y. c o m imscomm@imsitaly.com


7 4 E N JU

3 1 0 2 R A G ES BARCESLOPNAIAN

an Europe Society ointestinal r of Gast ominal d and Ab gy Radiolo

Meeting President: Prof. Carmen Ayuso, Barcelona/ES

CT COLONOGRAPHY HANDS-ON WORKSHOPS 2013 18th Hands-on Workshop on CT Colonography April 18 – 20, Copenhagen, Denmark Workshop organisers Philippe Lefere, Carsten Lauridsen

19th Hands-on Workshop on CT Colonography October 2 – 4, Vienna, Austria Workshop organiser Thomas Mang

LIVER IMAGING WORKSHOP 2013 13th Liver Imaging Workshop September 19 – 20, Stockholm, Sweden Workshop organiser Lennart Blomqvist

PANCREAS WORKSHOP 2013 May 10 – 11, Lisbon, Portugal Workshop organiser Celso Matos

ESGAR/ESCP BOWEL IMAGING WORKSHOP 2013

in association with

October 24 – 25, Amsterdam, The Netherlands Workshop organisers Regina Beets-Tan, Najib Haboubi, Jaap Stoker

Information on all ESGAR Activities can be found on www.esgar.org


CAD by R. Bird

Refining technology, renewing hope: promising advances in Computer Aided Detection of breast cancer

T

he World Health Organization calls early detection “the cornerstone of breast cancer control”[1]. After years of technological improvements, Computer Aided Detection (CAD) systems are poised to build on that cornerstone: a new generation of CAD technology is currently improving radiologists’ effectiveness in finding cancer and distinguishing cancer from non-cancer. CAD systems help radiologists zero in on potential pathologies by automatically identifying areas of a mammogram that are consistent with breast cancer. Designed to detect suspicious masses, architectural distortions, and microcalcifications in breast tissue, some of these systems also employ comparisons with the contralateral breast to locate asymmetries. With their potential to save time and help to make radiologist more effective, they may soon become indispensable in the search for breast cancer. Early CAD systems were the subject of controversy, with studies questioning their effectiveness [2]. However, a comprehensive reader study of recently introduced CAD technology confirms a significant change for the better. For the first time, an FDA study has shown that a new approach to CAD leads to improvements in radiologist sensitivity to breast cancer as well as in radiologist ability to differentiate between breast cancer and non-cancerous states. These technological strides should translate directly into better health outcomes for women.

«....For the first time, an FDA study has shown that a new approach to CAD leads to improvements in radiologist sensitivity to breast cancer as well as in the radiologist’s ability to differentiate between breast cancer and non-cancer...» promising and problematic at the same time. The hope was the at it would help radiologists to more effectively detect breast cancers and potentially save lives. That vision seemed unrealistic after an influential study published in the New England Journal of Medicine stated that CAD interpretation of mammograms was less accurate than interpretation without a computer’s help [3].

A Brief History of CAD

Looking back to 1998, when CAD for mammography was making its debut, the technology seemed both The author : Rives Bird is Director of Clinical Affairs VuCOMP, Inc., Plano, Texas. USA Rives Bird has a broad range of experience in engineering, R&D and clinical settings, spanning over 20 years. His background includes pivotal involvement in a variety of mammography technologies as well as other clinical applications. Rives holds a BA is Physics from Wake Forest University, and did his graduate work at the Bowman Gray School of Medicine. FIGURE 1. A very small mass detection with associated architectural distortion.

He can be reached at rives.bird@vucomp.com

MARCH 2013

D I

E U R O P E

35


CAD The U.S. Food and Drug Administration (FDA) responded strongly to such concerns. In 2007, the FDA re-evaluated the process to clear a CAD device for market. After public comment and considerable deliberation, the FDA established guidance for “designing and conducting clinical performance assessment studies” that would support premarket submissions to the FDA [4]. The final guidelines, issued in July 2012, further specified that guidance. Recommending the use of comprehensive reader studies to demonstrate device effectiveness, they note that “performance metrics based on the receiver operating characteristic (ROC) curve or variant of ROC … in addition to sensitivity and specificity at a clinical action point will be likely candidates as study endpoints” [5].

«...In the past, CAD systems have typically depended on “black-box” learning technologies such as neural networks… there is another option for CAD today....” Recent Reader Study Validates New Generation of CAD Systems

Designed and conducted according to the FDA’s final guidelines, a study of physicians using VuCOMP’s M-Vu CAD system has recently met its study endpoints. Led by principal investigator Dr. Etta Pisano of the University of North Carolina at Chapel Hill, the comprehensive reader study concluded that physicians using this CAD system

were more effective at reading mammograms, and that the system increased their ability to discriminate between cancer and non-cancer [6]. A Different Approach to Image Analysis

In the past, CAD systems have typically depended on “black-box” learning technologies such as neural networks. By processing a vast number of examples and encoding the emergent patterns in a set of numbers, neural networks are ablke to “learn”. However the problem with this type of technology is that engineers do not precisely know what the computer is encoding—hence the term “black box.” Without this knowledge, engineers have a hard time identifying the source of any problems arising during the development process. Are there hidden biases in the example cases, for instance? What if examples of non-cancer cases come from a clinic that overexposes its mammograms, and examples of cancer cases from another clinic that uses proper exposure? In that (admittedly simplified) scenario, since a black-box learns all it knows from the examples it is given, the system might learn that overexposure means “normal,” while proper exposure means “cancer.” This would of course degrade actual performance—and without being able to clearly understand what was learned, the developer might never discover why. There is another option for CAD makers today. In contrast to “black-box” systems, decision technology can be oriented towards the important types of visual structures that appear in mammograms. With this technology, developers can construct mathematical formulae that represent the concepts underlying these structures to map closely to our own human understanding. The automated intelligence thus performs its reasoning using mathematical constructs that an engineer can interpret more intuitively. The benefits of this approach are obvious: because a problem can be traced to a particular concept flaw, the system can be improved more quickly and with relative ease. The net result is that the technology can be pushed to greater levels of performance than approaches based upon more obscure reasoning. Systems using decision technology are not only better equipped to adapt to clinical realities now; they will be more responsive to clinical needs in the future. ReferEnces 1. h ttp://www.who.int/cancer/detection/breastcancer/en/index.html 2. “ Study Refuting CAD Effectiveness in Mammography Sparks Debate,” Radiological Society of North America (1 Oct. 2011). http://www.rsna. org/NewsDetail.aspx?id=2535 3. Fenton JJ, Taplin SH, et al. Influence of Computer-Aided Detection on Performance of Screening Mammography. NEJM, Vol. 356, No. 14. April 5, 2007 4. “ Draft Guidance for Industr y and FDA Staff: Clinical Performance Assessment: Considerations for Computer Assisted Detection Devices Applied to Radiology Images and Radiology Device Data – Premarket Approval (PMA) and Premarket Notification [510(k)] Submissions” (21 Oct. 2009), 7. 5. G uidance for Industry and FDA Staff: Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device Data - Premarket Approval (PMA) and Premarket Notification [510(k)] Submissions” (3 July 2012), 9. 6. S SED Data http://www.accessdata.fda.gov/cdrh_docs/pdf10/ P100005b.pdf

FIGURE 2. A detected microcalcification cluster.

36

D I

E U R O P E

MARCH 2013


ECR 2013 VIENNA Saturday, March 9 12:30-13:30 Room E1

are invited!

Bracco Satellite Symposium

Personalized CT Imaging: a Patient Centric Approach Chairman Prof. Mathias Prokop; Radboud University Nijmegen Medical Centre, The Netherlands

Tailoring CT exams: when and how? C. Loewe

How to balance radiation dose and diagnostic yield? H.C. Becker

What if the patient is at risk? M.F. Bellin Faculty Dr. Christian Loewe; Medical University of Vienna, Austria Dr. Hans-Christoph Becker; Grosshadern Clinic Center, Munich, Germany Prof. Marie-France Bellin; H么pitaux Universitaires Paris-Sud, Paris, France

Bracco. The contrast imaging specialists.


PACS in the ICU by Dr A Georgiou

PACS and its effect on clinical work, communication and organisation in Intensive Care Units: an overview of the evidence

Picture Archiving Communication Systems (PACS) can be described as an information communication technology (ICT) that replaces previous filmbased systems by providing a centralised digital repository for the storage, communication and archiving of imaging data (e.g., those from x-rays, MRIs, ultrasound and CT scans) This paper outlines some of the key findings of a systematic review relating to the impact of PACS on clinical work practices in the hospital Intensive Care Unit (ICU) [1, 2]

P

ACS has developed dramatically over the last few decades, and its uptake across health systems has continued to expand. PACS is a contributor to major transformations in the practice of radiology, not least as a component of the future integrated electronic medical record (EMR). This itself incorporates technologies such as Radiology Information Systems (RIS – imaging databases that can incorporate scheduling, result reporting and image tracking capabilities), Computerised Provider Order Entry (CPOE – electronic ordering) systems and Decision Support Systems (DSS) [3]. The EMR is expected to make a substantial contribution to the delivery of seamless information exchange across the hospital and broader healthcare service, thus helping to optimize the efficiency and effectiveness of patient care. It would seem logical therefore to expect dramatic evidence of the impact of sophisticated technologies like PACS, particularly in hospital settings like the Intensive Care Unit (ICU), which undertakes high volumes of imaging studies with complex (and urgent) data requirements across multiple information sources. However, prior to our review there had not been a thorough evaluation of the evidence of the effect of PACS on clinical work practices in the ICU [1]. We thus set out to systematically review all the quantitative peer The author : Dr Andrew Georgiou is at Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, University of New South Wales, Sydney 2052, Australia. Email: a.georgiou@unsw.edu.au;

38

D I

reviewed literature published between 1980 and 2010, to investigate changes in the nature of the technology and the corresponding effect on work processes. We searched all the major clinical and medical databases such as Medline, Embase and the SPIE Digital Library as a means of identifying the core benefits associated with PACS in ICU settings. The scope of the evidence base

Our systematic review identified 16 papers representing 11 studies, nine of which came from the USA and two from the United Kingdom. The majority of the studies were conducted before 2000, but three were published after 2000. We found no randomized controlled trials in the literature, but did locate three studies which employed a before-and-after study methodology. The majority of papers came from two US research groups – eight from the University of Pennsylvania Medical Center and five from the Duke University Medical Center in North Carolina. Five key performance indicators were identified [1]. They related to the following key areas of ICU clinical work practice: • the time from when an image is taken to when it is available; • the time from when an image is taken to when it is accessed by an ICU physician; • the time(s) of day that it was reviewed; • the time an image-based clinical action is taken; • the frequency and types of communication that are undertaken between ICU clinicians and the medical imaging department.

E U R O P E

MARCH 2013


What the evidence reveals

The existing evidence showed that PACS is associated with faster access to images with reported improvements in the availability of images of up to 30 minutes for routine examinations [4 ]. These positive findings were mirrored in the results of surveys of ICU staff which showed that up to 90% of users believed that, with PACS, images were available sooner than previously, and 72% perceived that there were no longer problems with lost images [5].

“.... the existence of PACS alone will not automatically lead to more timely processes if PACS is not supplemented by even simple things like electronic flags to signal the availability of images....� There were improvements in the time taken for ICU physicians to review images, with one study revealing that the mean time from image exposure to image viewing was 39 minutes in a surgical intensive care unit with PACS, compared to 78 minutes in a medical intensive care unit without PACS [6]. These findings also corresponded with survey results which reported that the majority of PACS users believed the use of a workstation led to more efficient decision making relating to patient management [5]. The evidence also showed the potential for PACS to affect clinician viewing patterns, with one study reporting that prior to PACS, images were mostly viewed at the daily afternoon conference with radiology, but after PACS implementation, ICU clinicians viewed images earlier, and more evenly across the day [7]. In contrast to these findings of the effect of PACS on efficiency and timeliness, the prevailing evidence about the impact of PACS on communication patterns within the ICU and across the hospital, was inconsistent, with some finding that showed that PACS had resulted in a reduction in communication between radiologists and physicians [8]. Results

Our systematic review had some unanticipated results. We were surprised by the scantiness of the existing evidence base. Eleven studies is not a huge evidence base, particularly considering that they come from a limited number of sites across only two countries. It is a finding that broadly parallels those from other reviews about the impact of health IT on medical imaging services [3]. We also expected to find a lot more recent studies given the substantial uptake of PACS in ICUs since 2000 MARCH 2013

D I

[1]. The existing research does not represent a substantial up-to-date repository of generalizable evidence about the role of PACS in ICU settings. Nevertheless, the findings do point to the substantial potential for PACS to contribute to improvements in the efficiency of clinical work processes, with corresponding effects on the timeliness of clinical decision making and patient care. The same cannot be said about the area of communication practices, particularly as it relates to relationships between clinicians and radiologists, work procedures and practices. Here the evidence base is variable and inconclusive, pointing to the need for greater research attention to some of the key socio-technical aspects of health IT design, implementation and utilisation, particularly as they relate to how multidisciplinary clinical work is planned, organized, synchronised and prioritized. For instance, as was noted in our systematic review, the existence of PACS alone will not automatically lead to more timely processes if PACS is not supplemented by even simple things like electronic flags to signal the availability of images [1]. The successful design and implementation of information and communication technologies requires anticipation of the expected changes and disruption to existing work practices and relationships. The introduction of innovative new technologies with the capacity to build on the PACS platform (e.g., voice recognition software and teleradiology technologies) will continue to have a big effect on how work is practiced across the ICU, medical imaging and hospital interface [9]. It is a challenge that cannot be avoided, but should be planned and prepared for. References 1. H ains I, Georgiou A, Westbrook J. The impact of PACS on clinician work practices in the intensive care unit: a systematic review of the literature. Journal of the American Medical Informatics Association 2012;19(4):506-13. 2. Faggioni L, Neri E, Castellana C, Caramella D, Bartolozzi C. The future of PACS in healthcare enterprises. European Journal of Radiology 2010. 3. G eorgiou A, Prgomet M, Markewycz A, Adams E, Westbrook J. The impact of computerized provider order entry systems on medical imaging services: a systematic review Journal of the American Medical Informatics Association 2011;18:335-40. 4. Watkins J, Weatherburn G, Bryan S. The impact of a picture archiving and communication system (PACS) upon an intensive care unit. European Journal of Radiology 2000;34(1):3-8. 5. C ox B, Dawe N. Evaluation of the impact of a PACS system on an intensive care unit. Journal of Management in Medicine 2002;16(2/3):199205. 6. H umphrey LM, Fitzpatrick K, Atallah N, Ravin CE. Time comparison of intensive care units with and without digital viewing systems. Journal of Digital Imaging 1993;6(1):37-41. 7. D e Simone D, Kundel H, Arenson R, Seshadri S, Brikman I, Khalsa S, et al. Effect of a digital imaging network on physician behavior in an intensive care unit. Radiology 1988;169(1):41-44. 8. R edfern RO, Kundel HL, Polansky M, Langlotz CP, Lanken PN, Brikman I, et al. Image workstation in a medical intensive care unit changes viewing patterns and timing of image-based clinical actions in routine portable chest radiographs. In: Jost R, Dwyer III S, editors. Medical Imaging 1996: PACS Design and Evaluation. Newport Beach, CA, USA: SPIE, 1996:298-306. 9. Tan SL, Lewis RA. Picture archiving and communication systems: a multicentre survey of users experience and satisfaction. European Journal of Radiology 2010;75(3):406-10.

E U R O P E

39


INDUSTRY NEWS Renowned US cancer hospital and research center joins R & D consortium to improve radiotherapy treatment

It has recently been announced that the renowned University of Texas MD Anderson cancer center (Houston, Texas, USA) has agreed to join a research consortium whose objective is to advance the development of an innovative image-guided treatment technology for cancer care. MD Anderson is the second university member of the research consortium, which will ultimately comprise leading radiation oncology centers and clinicians, and already includes the University Medical Center Utrecht in The Netherlands. Industrial partners are the Swedish company Elekta and the Dutch company Philips. The technology being developed merges radiation therapy and magnetic resonance imaging technology in a single system. The combination of state-of-the-art MRI with a cutting edge radiation therapy system should provide physicians with exceptional images of a patient’s soft tissues and tumor during radiation therapy. This breakthrough innovation also aims to

enable clinicians to adapt treatment delivery in real time for the most precise cancer treatments possible. “The special capabilities of the MRI-guided radiation therapy system – MR-based soft tissue imaging performed simultaneously with treatment delivery – could revolutionize cancer care,” says Jay Hoey, Executive VP, Elekta North America. “Patients are the ultimate winners, because MR imaging will help put the therapeutic radiation right on target, with the potential to avoid exposure to normal tissues. My colleagues at Elekta, Philips and University Medical Center Utrecht are delighted to welcome MD Anderson to the research consortium, which will profit immensely from this center’s highcaliber medical, technological and patient care expertise.” “MRI is the gold standard modality for imaging soft tissues, and MR imaging of the cancer during radiation therapy could provide the health care team with the ability to optimize treatment while reducing toxicity,” said Steven J. Frank, M.D., Associate Professor of Radiation Oncology and Director of Advanced Technologies at MD Anderson. “Our collaborative research will focus on what this combination could mean for patients in the future. As a leading innovator in cancer care, the University of Texas MD Anderson Cancer Center will bring our unique expertise to help realize the promise of more targeted cancer treatments and transform the way healthcare is delivered today.”

Measurement solutions in the medical field

RAYSAFE THINX

RAYSAFE SOLO

RAYSAFE X2

RAYSAFE Xi

LINEUP FOR QUALITY ASSURANCE AND SERVICE Why have the majority of X-ray manufacturers, physicists and technicians made Unfors RaySafe the leading X-ray QA equipment provider in the world? Because our solutions are built on three key principles: ease of use, speed, and accuracy. Learn more about our complete product range at www.raysafe.com

MARCH 2013

D I

E U R O P E

40


Multi-site hospital signs deal to keep IT solution state-of-the-art

Located near Amersfoort in the Netherlands, the Meander Medical Center is one of the country’s top clinical and training hospital. Its four sites have a total of 982 beds, and handle almost 700,000 outpatient visits per year. The hospital has 3,300 employees and 239 clinicians. The radiology department’s 14 radiologists and 130 staff members carry out 175,000 exams annually. In 2013, the hospital group will move into an impressive, brand-new site, currently under construction. The hospital has just announced that it has signed a major contract with Agfa Healthcare for the upgrade of its current PACS, RIS and nuclear information systems (NIS). These systems will be integrated into a single workflow to provide benefits such as smoother workflow, faster results consolidated patient information and efficient patient turnaround. The deal also includes a Managed Services contract that will keep the solution state-of-theart over time, plus a storage solution. The implementation for the upgraded PACS and new RIS/NIS will be completed in March 2013. Agfa Healthcare Mortsel, Belgium www.agfahealthcare.com

Transforming pleural services in Welsh hospital

According to Dr Helen Davies, Consultant Chest Physician at the University Hospital Llandough (UHL), Cardiff, Wales the quality of the pleural services offered at UHL have been significantly improved by the SonoSite’s S-ICU

ultrasound system. Dr Davies said “UHL provides services to a population of just over 500,000 people in Cardiff and the Vale of Glamorgan, as well as receiving referrals from the whole of South Wales for procedures such as endobronchial ultrasound. Having a dedicated clinic and ultrasound room helps us to treat patients in a more organized, timely manner, which makes a considerable difference. The system itself is straightforward to use and the image quality is good. It is very portable and, if required, can easily be transferred to different areas of the hospital, such as intensive care. Images can also be stored for review, which is ideal for training purposes.” Dr Davies added: “Previously, patients on the ward needing a pleural procedure would be referred to radiology for an ultrasound scan, and then be transferred back to the ward for treatment. Using the S-ICU, we can now

perform an ultrasound scan and guided aspiration at the same time. This is safer for patients and streamlines the process, allowing us to increase the number of pleural procedures performed. It has completely changed what we do, helping to reduce the time from referral to procedure and giving new patients a far swifter diagnosis.” Sonosite Seattle WA, USA www.sonosite.com

Queen of England opens new MRI suite

On 5 February Queen Elizabeth of England officially opened a £3 million MRI suite housing two new GE Healthcare MR scanners at The Queen Elizabeth Hospital, King’s Lynn. The facility is

expected to help significantly improve local diagnostic facilities for patients. The MRI scanner suite has been open to the public since May 2012. The two GE Healthcare scanners installed at the facility, the Optima MR360 1.5T and the Optima MR450w with GEM Suite will help increase capacity for scans, predicted to increase from an annual 6,600 in 2008 to 13,000 per annum within the next few years. The MR450w with GEM Suite has been designed with patient comfort in mind. In particular, the area where the patient lies is wider than in many conventional scanners. In addition, flexible ‘Geometry Embracing Method (GEM)’ coils follow the contours of the patient’s body, allowing easier patient positioning and making for a more relaxed scanning experience. This also makes it easier for radiographers to correctly position their patients leading to a higher quality diagnostic image. The Optima MR360 also combines clear image quality with versatile and userfriendly features, which make it possible to produce high quality images even when scanning challenging areas such as breasts, the heart and blood vessels. It is also energy efficient, using up to 34 percent less power than previous generation MR systems. Karl Blight, General Manager of GE Healthcare UK & Ireland said: “GE Healthcare’s scanners are a key part of this state of the art suite at The Queen Elizabeth Hospital and we are pleased to be part of delivering diagnostic facilities for patients here.” GE Healthcare Little Chalfont, Bucks, UK www.gehealthcare.com/eueu


INDUSTRY NEWS Samsung buys medical imaging company – NeuroLogica

Presenting at ECR 2013 Vienna, Austria Bracco satellite symposium Saturday March 9. 12.30 -13.30 Room E1 Personalized CT Imaging: a Patient Centric Approach Under the chairmanship of Prof. Mathias Prokop of the Raboud University Nijmegen Medical Center in the Netherlands, this symposium will feature three presentations.

One of Neurologica’s most popular products is the Ceretom, a protable head and neck CT scanner.

Samsung’s United States subsidiary of Samsung Electronics Co. Ltd, announced end of January that it would be acquiring NeuroLogica, a leading CT company headquartered in Danvers, MA. Established in 2004, NeuroLogica develops medical imaging products and is known for its world-class portable CT scanners, such as BodyTom and CereTom. Terms of the deal were not disclosed. The acquisition of NeuroLogica is another important step in the expansion of Samsung’s medical imaging business. Samsung will continue to strengthen its capabilities and product portfolio to establish itself as a trusted leader in the health and medical equipment industry. The company plans to leverage its global brand awareness and world-leading technology in consumer electronics, IT and communications with NeuroLogica in order to expand medical imaging business. Samsung Electronics is committed to explore new avenues of growth in the healthcare business by enhancing medical imaging diagnosis, providing innovation to both patients and doctors. Samsung Medison Seoul, Korea www.samsung.com/healthcare MARCH 2013

• Tailoring CT exams Prof Christian Loewe, Professor of Radiology, Medical University Vienna, Austria. The starting point of Prof Loewe’s presentation is that fixed prepared examination protocols are no longer sufficient in modern CT imaging; instead individual adaptation of protocols is necessary. Although individualization of examination protocols in modern CT angiography sounds complex such personalization is now an important requirement of modern patient care and for optimized image results. Discussion should focus therefore not on “if ” or “why”we should tailor the CT examination but only on how we can do so in a safe and time-efficient manner. Defining a “normal” patient based on three BMI groups seems to be an easy way to implement tailoring in daily routine. These three groups can be the basis for the implementation of very simple rules for adaptation of radiation dose and as a consequence contrast injection parameters according to the BMI. Using such very basic recommendations should enable personalized, perfectly tailored CT protocols to become possible. • How to balance radiation dose and

diagnostic yield?

Prof. Hans-Christoph Becker, Grosshadern Clinic, Ludwig-MaximiliansUniversity Munich, Germany Prof Becker’s presentation starts from considering the impact that the increasing utilization of CT has had on the

D I

E U R O P E

increased awareness about the high level of associated radiation exposure. In particular, cardiac CT, which was initially performed with retrospective ECG gating, has raised serious concerns about the risk of cancer caused by diagnostic radiation exposure. Prof Becker points out that modern CT scanners offer a variety of options which allow substantial radiation exposure reduction. These options include special X-ray beam collimators, highly sensitive detectors, and iterative reconstruction. However, while all these options help to reduce radiation exposure, the CT scanners are not yet able by themselves to choose the optimal settings for a given patient or examination. It is therefore all the more important to optimize the settings, e.g. through a combination of high pitch protocols, low tube voltage settings and high iodine contrast infusion. This combination is particularly advantageous for small vessels such as the cerebral, coronary and pulmonary arteries. • What if the patient is at risk? Prof. Marie-France Bellin, Professor of Radiology, University Paris Sud, Hospital Bicêtre-Paul Brousse, France. Prof Bellin points out that while the currently widely used iodinated contrast agents are generally considered efficacious and safe, there are nevertheless potential risks. These can include predictable chemotoxic reactions and unpredictable allergic or pseudoallergic reactions. It is therefore important to identify patients at high risk of such reactions before contrast administration. One method is to use the standardized questionnaire as recommended by the Contrast Media safety Committee of the European Society of Urogenital Radiology (ESUR).

42


Planmed Verity®

Extremity Scanner – New Way to See

Point-of-care 3D extremity imaging Watch Planmed Verity video:

High resolution with low dose Low life-cycle cost More information

www.planmed.com

Planmed Oy Sorvaajankatu 7, 00880 Helsinki, Finland, tel. +358 20 7795 300 fax +358 20 7795 664, ExtremityCT@planmed.com


The practice of radiology by Dr P McCoubrie & Dr JH Reid

VOMIT and the optimal use of medical imaging technology The increasing use of highly sensitive modern imaging technology can be associated with increased false positive rates, the detection of ‘incidentalomas’ that are irrelevant to the presenting complaint. Patients affected have been labelled VOMIT or “Victims Of Medical Imaging Technologies”. We argue that this widely accepted notion is overstated, flawed and preventable.

V

OMIT (victims of modern imaging technology) was first described in a personal view in the British Medical Journal in 2003 [1]. Richard Hayward, a pediatric neurosurgeon at Great Ormond Street Hospital in London, described how ‘innocent pathology’ found on MRI causes worry to the patients and their families. This worry was fuelled by searching for information on the internet and required the specialist to spend considerable time allaying the patients’ fears. This “acronym for our time” has become very popular. Within a decade it has passed into common UK medical parlance. It has now come to encompass all patients who suffer physically and mentally as a result of scan findings that turn out to be a benign condition. The principles underlying VOMIT are now accepted and considered as being beyond question: troublesome incidental findings are an inevitable part of modern radiology. However, we disagree strongly; there are several reasons that VOMIT is a flawed principle. First, it isn’t a new idea. Second, it is a deliberately unpleasant acronym aimed at transferring blame for difficult clinical circumstances. Third, incidental isn’t always trivial. Fourth, VOMIT is overstated but just usually down to poorly performing radiologists. Last, we contend that the rise in incidental findings is due to a rise in inept clinical targeting.

Nothing New Under the Sun

The thinking behind VOMIT is not new. The term “incidentaloma” was first used over thirty years ago [2]. Since this original description of incidentally discovered adrenal lesions, it has become apparent that most organs frequently contain benign masses if you look The Authors:

Shifting the Blame

Compared to the bad old days of diagnosis by exploratory heroic surgery and subsequent necropsy, it is impossible to imagine approaching an acutely ill patient without computed tomography (CT). The accuracy of modern scanners has lead to our clinical colleagues becoming increasingly dependent on their radiological colleagues. Nevertheless radiology can’t always provide a definitive answer and, almost more than any other specialty, our work is open to massive hindsight bias. Diagnoses can be elusive, clinical practice is still challenging. VOMIT is an unpleasant word, conjuring up strongly negative sensations and emotions. But it is a quite deliberately chosen acronym. Why choose such a word? We contend that VOMIT tags the spectre of negative emotion onto otherwise positive and clinically useful scans. Furthermore, the implication is that the obfuscation of radiologists is often the cause for unclear and difficult cases. The poor surgeon or physician is therefore absolved of blame; it is all the radiologist’s fault. We equate this tactic with heroin addicts trying to blame poppy growers in Afghanistan for their habit. Incidental Isn’t Always Trivial

Dr P McCoubrie1 & Dr JH Reid2 1. D epartment of Radiology, Southmead Hospital, Bristol BS10 5NB, UK email: paul.mccoubrie@nbt.nhs.uk 2. D epartment of Radiology, Borders General Hospital, Melrose TD6 9BS, UK email: john.reid@borders.scot.nhs.uk

44

hard enough. Such small masses are often difficult to distinguish from early malignancies. Over forty years ago, that is well before the modern golden age of cross sectional imaging, there were problems with unexpected test results and false positives. An eloquent account of the “Ulysses syndrome” was given by Rang in 1972 [3]. He described patients who “make a long journey through the investigative arts and experience a number of adventures before reaching their point of departure once again”, akin to Ulysses’ 20 years of dramatic exploits on trying to return home after the Trojan War.

D I

It is often forgotten that some ‘incidental’ findings are not innocuous. For example: • Unexpected cancers are relatively common. For example, CT colonography finds unexpected extra-colonic malignancies in 0.6% of patients, that is more than double the rate of colonic tumors [4].

E U R O P E

MARCH 2013


• Significant findings are worthwhile. Over 50% of renal tumors are now found by accident, detected by radiologists during investigations for unrelated symptoms [5]. Moreover, survival from such asymptomatic tumors is better than can be explained by differences in stage, grade or demographics. • ‘Incidental’ is a judgement. Coronary artery calcification on CT used to be thought incidental. However it has been found to be an extremely strong predictor of cardiovascular risk; coronary calcium ‘scoring’ is now a common indication for CT. Poorly Performing Radiologists

Despite the vast majority of patients who benefit from radiology there are unquestionably those who suffer unnecessary anxiety and further testing. No test is 100% sensitive or 100% specific. There will always be false positives. Modern scanners are capable of stunning resolution and have revealed a whole new menagerie of anatomical curiosities. We are able to visualize many diseases at an embryonic stage. The challenge to the radiologist is to differentiate the early signs of disease from pure incidental findings of little clinical import. A good radiologist will do this in a binary fashion and thereby prevent VOMIT at source. Truly benign incidental findings are firmly dismissed; significant incidental findings are highlighted appropriately. An experienced radiologist equivocates only when essential. Borderline findings are specified, the reason for equivocating is highlighted and then a plan for solving the dilemma is suggested. How should individual radiologists reduce their equivocation?

There are several ways: • The radiologist should be an expert in the body part being scanned. Subspecialisation in radiology is an absolute must, despite pressures to maintain ‘general’ radiology skills. • Images should be of the best possible quality. This needs carefully protocolled scans on modern machines controlled by skilled and motivated staff. MARCH 2013

• The radiologist should make time to assess the images fully despite intense time pressures. Proven methods include optimizing slice width and window settings with appropriate use of multi-planar reformatting and 3D imaging [6]. • The major modifiable factor is the production of better written radiology reports. A good radiology report should answer the clinical question in as brief, clear and unambiguous a fashion as possible [7]. Often radiologists ‘hedge”’, that is they avoid the risk of commitment through vague abstruseness. “There appears to be a possible lung nodule” tells much, yet almost nothing. A review of medicolegal cases by Berlin [8] highlighted that vagueness in reporting can easily lead to delayed diagnosis. VOMIT is often caused by ‘hedging’ over benign findings; failure to categorise findings adequately. Inept Clinical Targeting

An insidious phenomenon is permeating modern clinical practice: the ‘rule out’ scan. Wanting to ‘exclude’ diseases heralds a move away from traditional medical diagnostic acumen, based on knowledge and expertise. The heart of western medical thinking, the clinico-pathological method and probabilistic hypothetico-deductive reasoning, is rejected. Diagnostic indecision is embraced “just in case”. It is clinically and morally lazy. Moreover, this negative investigational paradigm should be distinguished from the meritorious desire to investigate a patient fully. ‘Ruling out’ betrays the doctor: patient relationship from within. Inappropriately extensive investigation mimics thorough and hence caring medicine [9]. The truth is that the doctor is transferring risk to the patient under the guise of being thorough. “Ruling out” is defensive medicine, plain and simple. Over-reliance on the technological marvels of modern radiology can cripple the use of the mind and sensory faculties to make diagnosis. The jump from history of presenting complaint to investigation is worrisome. It leads to clinical laziness and progressive clinical deskilling - ‘hyposkillia’. Unfocused testing produce more D I

E U R O P E

VOMIT for simple mathematical reasons. 5% of healthy people are statistically abnormal. If a person has 20 tests, there is a 66% chance of one or more abnormal results. Also, the clinical history will bias interpretation. To explain symptoms, the radiologist is forced to postulate that benign-looking findings could conceivably be symptomatic. Add unfocused tests to an unclear clinical picture and the waters muddy still further. The Way Forward

Radiologists have a hill to climb if they are to avoid VOMIT. They have a heap of personal and departmental challenges to overcome. In addition, they need to intelligently engage with their referring clinical colleagues to encourage best quality medical practice. Otherwise, clinicians are naturally tempted to greedily help themselves to the ‘investigational chocolate box’. Clinicians should be encouraged to use radiology like a precision instrument to confirm specific clinical theses rather than treating it like a club, bludgeoning a diagnosis to death. If the future is approached in a collegiate fashion then patients, clinicians, radiologists and the public purse will benefit. Intelligent use of modern imaging is the only way forward. References 1. Hayward R. VOMIT (victims of modern imaging technology)--an acronym for our times. BMJ 2003; 326(7401):1273. 2. Rang M. The Ulysses syndrome. Can Med Assoc J 1972;106:122–3. 3. Geelhoed GW, Druy EM. Management of the adrenal “incidentaloma”. Surgery 1982;92(5):866. 4. Pickhardt PJ, Kim DH, Meiners RJ, Wyatt KS. Colorectal and Extracolonic Cancers Detected at Screening CT Colonography in 10 286 asymptomatic adults. Radiology 2010; 255(1):838. 5. Palsdottir HB, Hardarson S, Petursdottir V et al. Incidental Detection of Renal Cell Carcinoma is an Independent Prognostic Marker: Results of a LongTerm, Whole Population Study. J Urol 2012;187:48. 6. Horton KM, Johnson PT, Fishman EK. MDCT of the Abdomen: Common Misdiagnoses at a Busy Academic Center. Am J Roentgenol 2010;194(3):660. 7. Wallis A, McCoubrie P. The radiology report — Are we getting the message across? Clin Radiol 2011;66(11):1015. 8. Berlin L. Pitfalls of the vague radiology report. Am J Roentgenol 2000;174(6):1511. 9. MacFadyen RJ. Referral for diagnosis: effectiveness not activity. J R Coll Physicians Edinb 2012;42(1):5.

45


Hospital spotlight Constant technological innovation maintains high reputation of Swiss Breast Care Center The Breast Care Centre at the Engeried Klinik in Berne, Switzerland has a long-standing reputation for being equipped with the latest technology. Already carrying out a large number of breast tomosynthesis examinations, the centre has recently complemented this equipment with the installation of a new tomosynthesis-guided biopsy system. We spoke to Dr Martin Sonnenschein, head radiologist in the Engeried Klinik about the centre in general and the tomosynthesis-guided biopsy system in particular.

Q. F irst of all please tell us a bit about your hospital and the breast care center. Where are you located, how big is the hospital and what population do you serve? How many patients do you see? Screening or diagnostic patients?.

Our institution is a private hospital, known as the Klinik Engeried. We are very proud of the high reputation it has gained over the years for the pioneering use of new technologies in general and in the improvement of women’s breast health in particular. Located in Berne, Switzerland, our 86-bed hospital is considered to be one of the leading private hospitals in Switzerland and is renowned for its center of excellence in women’s health. Women come to our breast center because of the widespread reputation it has as a leader in technology. With 8,000 mammograms being carried out annually we perform twice as many mammograms as any other facility in our province. Over the last four years we have carried out more than 16,000 tomosynthesis breast examinations, using Hologic’s 2D/3D Selenia Dimensions tomosynthesis system. At the moment we only carry out diagnostic examinations but we are planning to start a screening program — this is due to start in the middle of this year.

Dr Martin Sonnenschein is head radiologist at the Breast Care centre at the Engeried Klinik, where the breast tomosynthesis imaging system has now been recently complemented by the installation of a tomo-guided biopsy system.

with the installation of Hologic’s Selenia Dimensions threedimensional breast tomosynthesis system, thus becoming the first hospital in Switzerland and one of only a handful of hospitals in Europe being able to offer this ground-breaking technology at that time. Another “first in the world” innovation was the installation in 2011 of a “C-View” system which allows the creation by a special reconstruction algorithm of synthesized 2D images from a 3D tomosynthesis data set. I call this system “all -in-one-mammography“, because the 3D tomosynthesis is at least equal to spot views, so the need for any additional shots is eliminated.

Q. What about the work flow ? How many radi-

ologists read the images? Procedure in case of doubtful lesions? Recalls?

The challenge we had was how to introduce breast tomosynthesis in practice into the diagnostic work up of the breast taking particular attention to the radiation doses used.

Q. What about the equipment you have to do all this and of course the personnel you have to operate the equipment and interpret the images?

As I said, we have a reputation for the introduction of innovative technology — as long ago as 1998 the Klinik Engeried installed one of the first digital mammography systems in the world. We now have three systems of which two have the capability of carrying out breast tomosynthesis. In 2008, the Klinik Engeried was again a pioneer and led the way 46

D I

Thanks to its reputation for always being at the forefront of technological innovation, the Breast Care centre of the Klinik Engeried in Berne Switzerland attracts women from far afield.

E U R O P E

MARCH 2013


To start with our radiographers routinely take four standard views for each patient. If the breast is dense, or if the patient is perceived to be at high risk or indeed if the radiologist sees any structural changes or doubtful findings, we take additional images using the three dimensional technology. Since we have the C-View system we do a lot more 3D mammograms, because the dose is nearly the same as for a 2D exam alone. We find that tomosynthesis is an excellent tool for the establishment of a better and more reliable diagnosis in difficult cases. We are able to see things better, to detect more — and smaller — cancers of the breast and have a lower recall rate. In our department we have four dedicated radiologists specialized in women’s health so overall all images are routinely double read.

Q. What’s your opinion on breast tomosynthesis ver-

The creation of 1 mm thin slices in the 3D mammogram enables the inner architecture of the breast to be revealed, with reduced tissue overlapping, especially in dense breasts. In this way 3D mammograms help solve problems in the interpretation of 2D mammograms. Images courtesy of Engeried Klinik.

We first integrated breast tomosynthesis into the diagnostic workup procedure in 2008. The creation of 1 mm thin slices in the 3D mammogram enables the inner architecture of the breast to be revealed, with reduced tissue overlapping, especially in dense breasts. In this way 3 D mammograms help us solve problems in the interpretation of 2D mammograms. In our experience, tomosynthesis reduces false-positives, increases sensitivity, increases earlier detection and the detection rate of malignant lesions and generally increases the “reader confidence” in BI-RADS classification. Just about the only disadvantage of tomosynthesis is that it is a little bit more time-consuming for radiographers and radiologists, but overall the benefits far outweigh this drawback.

used the MIV, analogue system from Hologic with the Stereoloc II upright biopsy system. Compared to this earlier upright system we find that the main advantage of the Affirm system is that, thanks to the digital detector, we can assess lesions or microcalcifications better. As for tomosynthesis biopsy the big advantage is that we are now able to biopsy lesions — for example architectural distortion without microcalcifications — that are only seen on tomosynthesis. Because it is easy to handle and dependable, our radiographers love the Affirm system. The fact that we already had and were used to an upright system meant that we didn’t have to change our way of working to incorporate the new tomobiopsy system. The learning curve for our radiographers was easy and we didn’t have any teething troubles.

sus 2D mammography? Are you able to detect more lesions or earlier? Are there any drawbacks and if so do the advantages outweigh the drawbacks?

Q. Now about the taking of biopsies. Prior to your

purchase of the Hologic biopsy system, what did you use for biopsies? Since when have you had the new Hologic equipment ? Any learning curve needed? Teething troubles?

Before the very recent installation of the “Affirm” system in 2012, (which, as of now, is available with tomosynthesis biopsy) we

The Affirm tomosynthesis-guided biopsy system is the most recently installed equipment in the Breast Care Center in Klinik Engeried.

MARCH 2013

D I

Q. And now the key question — has the equipment

met your expectations? Principal advantages? Any unexpected surprises, positive or negative?

Overall, the new tomosynthesis-assisted biopsy system has more than met our expectations and as I said earlier, because we have the C-View system we carry out many more tomosynthesis studies. In practice we find many lesions that are not detected on 2D mammograms and ultrasound, even when we know the location of the lesion. For such cases in the past we had to perform expensive MRI scans and take MRI-guided biopsies but we now expect that tomo-biopsy will solve these problems and so avoid the certain cost- and timeintensive MRI interventions. Additional benefits of tomobiopsy are a dose reduction and a gain of time. In addition, clinically we only have minor breast hematomas, which we attribute to the shorter duration of the intervention. Thus, all-in-all, we are happy with the Affirm system and find it to be a sophisticated, well-developed and rapid system. To such an extent that we no longer think there is a need for a prone table any more, which has the advantage that we should be able to save a bit of precious space.

E U R O P E

47



Breast cancer Mammography in a private radiology practice:

Dr Bruno Scheffer is head of the Zola clinic in Nantes, France, where they have been carrying out mammography examinations for 24 years.

a look at the Zola practice in Nantes, France All too often, most of the news of innovation and progress in radiology seems to come from large university hospitals with high patient throughput and commensurately elevated staffing levels. However, it shouldn’t be forgotten that, taken together, the large number of smaller private radiology practices also make a significant contribution to the overall provision of radiology services. We talked to one such small practice, the “Zola cabinet” located in the Western French city of Nantes. The practice has just invested in the purchase of a new digital mammography system. Radiologist Dr Bruno Scheffer tells us about his practice and his latest equipment

Q. First of all please tell us about

Q. Can you tell us more about this

We are a small but busy private radiology practice with an average throughput of approximately 45 patients per day. The patients are generally referred to us from many general practitioners scattered throughout the city of Nantes and even further afield. The fact that we are located in central, downtown Nantes means that we are easily accessible for the patients. The cases we see range from general radiology and emergency cases but we also see chronic cases and carry out routine screening.

In France, the national breast cancer screening program has fixed itself the objective that every two years at least 80% of women aged between 50 to 74 should have a mammogram. There is an on-going debate about the exact contribution of mammography but surveys have shown that to achieve a reduction of 20-30% in breast cancer mortality at least 70% of the healthy population in this age range should be screened. In practice these screening objectives have not yet been reached and, given that there are approximately more than 40,000 new breast cancer cases diagnosed annually in

your practice

mammography service that you provide.

Q. How are you equipped to do all this?

Well, despite the fact that we are small in size, we are actually quite proud of how well we are equipped. Thus, we have a fully automated room in which we carry out bone, lungs as well as jaw, dental and skull examinations. To handle all these images we have a workstation from the French company Keosys which enables centralisation, visualization and analysis of the images and of course archiving. We have three secretaries who deal efficiently with the administration but I carry out all the actual examinations myself. However, we also have a long tradition in carrying out mammography examinations — we’ve been doing this for more than 24 years now and we have a dedicated room for this part of our practice. MARCH 2013

D I

With its subdued lighting, the design and decoration of the mammography room in th e Zola clinic have been deliberately chosen to put the women patients at their ease.

E U R O P E

49


Breast cancer France, there is a lot of progress still to be made. This general background debate has been sharpened by a recent controversy in France which has been widely reported in the popular press (e.g. in the magazine Lyon Capitale February 2013) under bold headlines such as “Failures in breast cancer screening “ or “Thousands of breast cancers undetected because of problems with mammography equipment”. The controversy relates to the publication last October in France of a report which showed that CR systems were less sensitive than DR or film-based systems in the detection of breast tumors. Of course the danger is that this message may be interpreted by women that all mammography systems aren’t to be trusted. Coming down from the French national level to what happens in our practice, we have been carrying out mammography examinations in our practice for about 24 years. Now we carry out approximately 20 mammography examinations per day. Of all the mammography exams that we carry out, 50% are performed in the context of general screening programs sponsored by health insurance schemes, and 40% are what we call individual screening, i.e. referred to us by the general practitioner or gynecologist. Thus all-in-all, 90% of our mammography exams are for screening. Approximately 5% are diagnostic exams for investigation of clinical symptoms and the remaining 5% are for post-treatment monitoring . In practice, the way we are set up means that we can take enough time to examine the images sufficiently in detail to avoid the need to recall the women. In case of doubtful looking lesions we take additional images and if there are microcalcifications we then carry out exams at higher magnification. In all cases except exclusively lipomatous breasts, we carry out a mode B ultrasound screen. Six years of systematic echographic screening, carried out in no fewer than 16107 mammographies, have enabled us to investigate 271 breast cancers using a Hitachi strain elastography system. Of these cancers, 27% were not seen on mammography. The vital contribution of the HI-RTE elastography system is that it confers a positive predictive value of 82% on the microbiopsy, thus enabling the number of unnecessary biopsies to be reduced significantly. This 50

contrasts with the situation in standard ultrasound screening, where, as several studies have shown, there is a high level of false positives. It is important to note that none of the benign lesions seen on elastography and which were then monitored regularly turned out later to be malignant. If the presence of a lesion is confirmed we will then carry out more thorough examinations and ultimately take a sample of cells by fine needle aspiration. The cytological examination of the sample is carried out immediately in our office and confirmation sought from the central pathology laboratory in the city of Nantes. More recently, as of 2011, we now refer our patients directly to the anticancer centre in Nantes. The protocol for the intrabeam irradiation that they carry out in the anti-cancer centre requires histological confirmation of the lesion.

Q. W hat equipment do you have

for the mammography part of your practice?

We have two ultrasound systems capable of carrying out elastography measurements. As I said earlier, one of these is from Hitachi; the other is from Supersonic. However the most recent acquisition we have made is a Planmed Nuance Excel system, which we acquired in July 2011. We thought long and hard before buying this system but finally opted for it principally because of its image quality and its ergonomic design which means that we can carry out our examinations really rapidly. An additional reason for our choice was that previously we had a “Sophie” mammography unit from Planmed. We’ve had this system for more than 5 years and during this period we’ve never had a single breakdown so we’re impressed by the reliability. The similarity of the new Nuance model to the previous Sophie system also had the advantage that there was no problem in becoming fully familiar with its operation, so we were up and running in no time.

Q. A nd how have you found the new system?

We like it — what we particularly appreciate about it is that it is compact and D I

E U R O P E

The most recent acquisition of the Zola practice in Nantes, France is the Excel Nuance system produced by the Finnish company Planmed. A feature of the system is its superior clinical image quality which is achieved at a low dose level. A novel X-ray tube with proprietary TriFilter technology and an amorphous Selenium (a-Se) flat panel detector with 85 μm pixel size deliver uncompromised image quality without exposure to unnecessary radiation..

easy to use and especially because with it we can carry out our exams very quickly — four mammography images can be taken in four minutes. So far so good. What is also important — especially in the context of the current French mammography controversy that I mentioned earlier — is that since the installation of the Nuance Excel our internal quality controls with target and phantoms have been stable and satisfactory. Likewise, the 6-monthly quality controls carried out by external, independent organizations have also always been satisfactory (as was the Sophie system during the 5 years we used it) .

Q. A nd how do you see future developments?

On a national and regional level I foresee a continuing increase in the number of women being screened for breast cancer, with a continuation of the encouraging trend of a steady decrease in the mortality of the disease. At the level of our practice, I think the next development will be when we get into breast tomosynthesis, which is particularly interesting because of the possibility of increased detection of the number of lesions. MARCH 2013


Ultrasound by Dr G Salomon, Dr L Budaeus, Dr L Durner & Dr K Boehm

Improvement in the visualization of prostate cancer through the use of ShearWave Elastography Prostate cancer is the most common cancer in males with more than 910,000 annual cases worldwide. With early detection, excellent cure rates can be achieved. Today, prostate cancer is diagnosed by a randomized transrectal ultrasound guided biopsy. However, such randomized “blind” biopsies can miss cancer because of the inability of conventional TRUS to visualize small cancerous spots in most cases. Elastography has been shown to improve visualization of prostate cancer. The innovative ShearWave Elastography technique is an automated, user-friendly and quantifiable method fore the determination of prostatic tissue stiffness.

T

he detection of prostate cancer (PCA) has become easier thanks to Prostate Specific Antigen (PSA) testing; the diagnosis of PCA has been shifted towards an earlier stage of the disease. Prostate cancer is, in more than 80 % of the cases, a heterogeneous and multifocal tumor. Conventional ultrasound has limitations to accurately define tumor foci within the prostate. This is due to the fact that most PCA foci are isoechogenic, so in these cases there is no differentiation of benign and malignant tissue. Because of this, a randomized biopsy is performed under ultrasound guidance with at least 10 to 12 biopsy cores, which should

represent all areas of the prostate. Tumors, however, can be missed by this biopsy regimen since it is not a lesiontargeted biopsy. When PSA is rising — which usually occurs in most men — the originally negative biopsy has to be repeated.

The Authors : Dr Georg Salomon1, Dr Lars Budaeus1, Dr L Durner & Dr K Boehm1

2

1. Martini-Clinic – Prostate Cancer Center University Hospital Hamburg Eppendorf Martinistrasse 52 20253 Hamburg Germany 2. Urologische Klinik Dr. Castringius München-Planegg Germeringer Str. 32 82152 Planegg Germany Corresponding author: PD Dr. Georg Salomon

FIGURE 1. (Case #1): Huge area of hard tissue in the mid-right prostate, high suspicion of extracapsular penetration. Highly suspicious (kPascal value 111). Suspicious areas in SWE (red areas) correlate well with final histopathological whole mount of the prostate. Patient data. Age 65 years. PSA: 45 ng/mL. DRE: suspicious on the left side. Final histopathological result: pT3a, NO, RO (left anterior extracapsular extension).

Associate Professor of Urology Martini Clinic Tel: 0049 40 7410 51300 gsalomon@uke.de

MARCH 2013

D I

E U R O P E

51


Ultrasound

FIGURE 2. (Case #2): Mid-left side of the Prostate. ShearWave Elastography shows no hard tissue and no evidence of tumor. Patient data. Age: 69 years. PSA: 4.8 ng/mL. DRE: not suspicious. Number of previous negative biopsies: 3. Biopsy result: no cancer.

What urologists expect from imaging and biopsy procedures is the detection of prostate cancer at an early stage and an accurate description of all foci within the prostate with different (Gleason) grades of differentiation for best treatment options. In the past 10 years a couple of new innovative ultrasound techniques

(computerized, contrast enhanced and real time elastography) have been introduced to the market and their impact on the detection of early prostate cancer has been evaluated. The major benefit of elastography compared to the other techniques is its ability to provide visualization of suspicious areas and to guide the biopsy

FIGURE 3. (Case #3): Mid-left side of the prostate: small hard suspicious tissue in the peripheral zone. (red, kPascal value: 62). Patient data. Age: 67 years. PSA: 7.5 ng/mL. DRE: enlarged. Number of previous negative biopsies: 2. Biopsy result: Gleason 3+4 in 10 out of 12 cores. Radical prostatectomy: both sides nerve sparing (NeuroSafe). Final histopathological result: pT2x Gleason 3+4, N0, RO.

52

D I

E U R O P E

needle, in real time, to the suspicious and potentially malignant area. Ultrasound-based elastography has been investigated over the years and has had a lot of success for increasing the detection rate of prostate cancer or reducing the number of biopsy samples required. [1-3]. Different companies have used different approaches to the ultrasound elastography technique (strain elastography vs. shear wave elastography). Medical centers have seen an evolution in better image quality with more stable and reproducible results from these techniques. One drawback of real time strain elastography is that there is a significant learning curve to be climbed before reproducible elastograms can be generated. The technique has to be performed by compressing and then decompressing the ultrasound probe to derive a measurement of tissue displacement. Today there are ultrasound scanners on the market, which have the ability to produce elastograms without this “manual” assistance: this technique is called shear wave elastography. While the ultrasound probe is being inserted transrectally, the “elastograms” are generated automatically by the calculation of shear wave velocity as the waves travel through the tissue being examined, thus providing measurements of tissue stiffness and not displacement measurements. There are several different techniques for this type of elastography. The FibroScan system, which is not an ultrasound unit, uses shear waves (transient elastography) to evaluate the advancement of the stiffness of the liver. Another technique is Acoustic Radiation Force Impulse or ARFI technique, also used for the liver. These non real-time techniques only provide a shear wave velocity estimation for a single region of interest and are not currently used in prostate imaging. A shear wave technology that provides specific quantification of tissue elasticity in real-time is ShearWave Elastography, developed by SuperSonic Imagine. This technique measures elasticity in kilopascals and can provide visual representation of tissue stiffness over the entire region of interest in a color-coded map on the ultrasound screen. On a split screen MARCH 2013


the investigator can see the conventional ultrasound B-mode image and the color-coded elastogram at the same time. This enables an anatomical view of the prostate along with the elasticity image of the tissue to guide the biopsy needle. In short, ShearWave Elastography (SWE) is a different elastography technique that can be used for several applications. It automatically generates a real-time, reproducible, fully quantifiable color-coded image of tissue elasticity. Quantification of tissue stiffness

Such quantification can help to increase the chance that a targeted biopsy is positive for cancer. It has been shown that elastographytargeted biopsies have an up to 4.7 times higher chance to be positive for cancer than a randomized biopsy [4]. ShearWave Elastography can not only visualize the tissue stiffness in color but also quantify (in kPa) the stiffness in real time, for several organs including the prostate. Correas et al. reported that

with tissue stiffness higher than 45 to 50 kPa the chance of prostate cancer is very high in patients undergoing a prostate biopsy. The data from Gorreas et al showed a sensitivity of 80 % and a high negative predictive value of up to 90%. Another group (Barr et al.) achieved a negative predictive value of up to 99.6% with a sensitivity of 96.2% and specificity of 96.2%. With a cut-off of 40 kPa the positive biopsy rate for the ShearWave Elastography targeted biopsy was 50%, whereas for randomized biopsy it was 20.8 %. In total 53 men were enrolled in this study. Our group used SWE prior to radical prostatectomy to determine if the ShearWave Elastography threshold had a high accuracy using a cutoff >55 kPa. (Fig 1) We then compared the ShearWave results with the final histopathological results. [Figure 1]. Our results showed the accuracy was around 78 % for all tumor foci. We were also able to verify that ShearWave Elastography targeted biopsies were more likely to be positive compared to randomized biopsies. [Figures 2, 3]

Conclusion

SWE is a non-invasive method to visualize prostate cancer foci with high accuracy, in a user-friendly way. As Steven Kaplan puts it in an editorial comment in the Journal of Urology 2013: “Obviously, large-scale studies with multicenter corroboration need to be performed. Nevertheless, SWE is a potentially promising modality to increase our efficiency in evaluating prostate diseases.” References 1. P allwein, L., et al., Sonoelastography of the prostate: comparison with systematic biopsy findings in 492 patients. European journal of radiology, 2008. 65(2): p. 304-10. 2. Pallwein, L., et al., Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection. European radiology, 2007. 17(9): p. 2278-85. 3. Salomon, G., et al., Evaluation of prostate cancer detection with ultrasound real-time elastography: a comparison with step section pathological analysis after radical prostatectomy. European urology, 2008. 54(6): p. 1354-62. 4. Aigner, F., et al., Value of real-time elastography targeted biopsy for prostate cancer detection in men with prostate specific antigen 1.25 ng/ml or greater and 4.00 ng/ml or less. The Journal of urology, 2010. 184(3): p. 913-7.

What Do You Get with an

UltraFast™ Platform?

Liver – Prostate – Thyroid – Vascular – Musculoskeletal – Abdomen – Gynecology – Breast – Breast 3D – Pediatrics

MARCH 2013

D I

E U R O P E

53


Image sharing An innovative diagnostic image sharing network enabling multi-disciplinary, multi-site

A specialist in musculoskeletal radiology, Dr Phil O’Connor was head of the radiology services provided in the special polyclinic at the main venue of the recent London Olympic Games. The new image sharing network was used to give fast turnaround diagnostic reporting in injuries to athletes competing in the many remote subsidiary venues of the Games.

An innovative clinical ‘networking’ platform, known as PACSMail has been developed to allow diagnostic image and report sharing by multi-disciplinary teams. Driven by high demand from teams who need to work across organizational or national boundaries, the network of professionals using the system is growing rapidly. PACSMail has been particularly successful in the field of orthopedics/sports medicine, for example, which places some special demands on image and report sharing since athletes and their club doctors are highly mobile and often need access to advice from surgeons/radiologists and other specialists who may be some distance from where an injury has taken place. Using an approach similar to that behind social networking systems (it is similar to LinkedIn), PACSMail enables users to invite colleagues to join their networks. Once connected, they can securely share full diagnostic images and associated clinical notes using a standard PC/Internet connection. The system uses state-of-the-art file encryption and is fully DICOMcompliant, so it can either be used to upload scans from CD or can be linked directly to PACS, thus providing a portal for imaging centres to provide access to scans by off-site radiologists and to automatically copy scans and reports on-line to referring clinicians. Diagnostic Imaging Europe wanted to find out more about the system and how it works in practice so we spoke to Dr Phil O’Connor, Consultant MSK radiology specialist at the Leeds NHS Teaching Hospitals Trust who has made widespread use of PACSMail in his busy reporting practice.

Q. F irst of all please tell us a bit about your

radiology practice. Where are you located, and what patients do you provide services to?

I am a Consultant Radiologist at the Leeds Teaching Hospitals NHS Trust which has approximately 2,500 inpatient beds together with critical care and day case beds. The Trust employs over 14,000 staff across six sites, treating around a million patients a year. We have an Agfa RIS/ PACS system. In addition to my NHS work, I also provide radiology services to a wide range of sporting organizations and I was responsible for radiology services at the Olympics games village in London 2012.

tions, PACSMail allows us to quickly and easily share scans and reports with team doctors and we can often provide diagnostic advice within minutes of a scan being completed. PACSMail also enables us to report scans remotely from

Q

. Why do you need PACSMail and how does it help you to deliver these services?

Our in-house RIS/PACS is fine for managing the main hospital workload, but being able to get access to specialist diagnostic imaging expertise is now an increasingly essential part of patient care in clinics that are beyond the reach of our hospital imaging network. In sports medicine, for example, athletes can be injured whilst away from home and getting rapid access to specialist diagnostic advice is often key to maximizing performance outcomes. In these situa 54

D I

The new system has been particularly successful in the field of sports medicine, allowing sports club doctors to send scans for review by remote experts.

E U R O P E

MARCH 2013


imaging departments who do not have MSK specialist on-site. A good example of this was the use of PACSMail by the radiology team I led at the 2012 Olympics which used the service to provide fast turnaround diagnostic reporting for athlete injuries that occurred at events taking place outside the main Olympic venue.

Q. What makes PACSMail different from other image sharing systems?

The key difference between PACSMail and other image sharing systems is that it is designed to enable clinicians to set up their own networks. It is similar in concept to social networking — I can invite and set up a connection with a remote colleague in a few minutes. PACSMail provides email alerts when scans are waiting for review, which can then be accessed and displayed using use the system’s own viewer, or you can export it to a third party viewer such as Osirix. The system has its own RIS/PACS functionality and can be used for single or group practice reporting.

Q. And now the key question — has the system met your expectations? Any surprises, positive or negative?

PACSMail has proved fast and reliable for sports radiology reporting. The Osirix automatic export gives a real edge to PACSMail for Mac giving a workstation like experience to reporting. Not being able to send reports from the Mac version

Book review

of PACSMail is the only downside but I’m sure the company have this in hand.

Q. How do you see the future evolution of the system?

The developer of PACSMail, the company Sybermedica, is currently developing new networks in mainland Europe and in the Middle East and I can see the service becoming a valuable resource for both national and international clinical collaboration. For more information www.sybermedica.com

Tomosynthesis Events at ECR Hologic is sponsoring three tomosynthesis events at ECR

Diagnostic Imaging 7th Edition Includes Wiley E-Text, By Andrea G. Rockall, Andrew Hatrick, Peter Armstrong, Martin Wastie Pub byWiley-Blackwell, 2013, paperback. 520 pages; € 59.40 This book will help medical students, junior doctors, residents and trainee radiologists understand the principles behind interpreting all forms of imaging. Providing a balanced account of all the imaging modalities available — including plain film, ultrasound, computed tomography, magnetic resonance imaging, radionuclide imaging and interventional radiology — it explains the techniques used and the indications for their use. Organized by body system, it covers all anatomical regions. In each region the authors discuss the most suitable imaging technique and provide guidelines for interpretation, illustrating clinical problems with normal and abnormal images. With more than 600 photos, the book is lavishly illustrated.

MARCH 2013

The PACSMail system is a secure medical data communications network enabling clinicians to collaborate via Internet. It is used in the delivery of a range of ‘virtual’ clinical services, allowing those with hands-on responsibility for patient care to access the expertise of remote clinical colleagues.

D I

• A special ECR Satellite Symposium, “Celebrating the Evolution of Tomosynthesis”, on Saturday, March 9 from 14.00 to 15.30 in the Austria Center Vienna, Room C. The symposium will focus on: - The Oslo Tomosynthesis Screening Trial Results. Prof. Per Skaane, Oslo University Hospital Ullevaal, Oslo, Norway - Initial Experience with Tomosynthesis-guided Biopsy Dr. Daniela Bernardi, Division U.O. Senologia Clinical e Screening Mammografico, Dipartimento di Radioliagnostica, Trento, Italy - A Review of the Evolution of Breast Tomosynthesis Andrew Smith, Ph.D., Hologic, Inc., Bedford, MA, USA • Nine 75-minute breast tomosynthesis education sessions from March 7th thru the 10th. Each session includes handson experience reading breast tomosynthesis images in combination with conventional and synthesized 2D images. • Twelve tomosynthesis-guided breast biopsy training workshops. Each workshop will include an overview of the first clinical experiences with vacuum-assisted breast biopsies guided by tomosynthesis prior to a demonstration of a phantom procedure.

E U R O P E

55


Ultrasound by Prof. D . Cokkinos

Emergency imaging with Contrast Enhanced Ultrasound Contrast Enhanced Ultrasound (CEUS) can be carried out in emergency situations. Typical indications include abdominal organ trauma and infarcts, scrotal-penile pathology and blood vessel imaging. This article reviews the underlying principles of CEUS and summarizes the principal indications in emergency situations, safety considerations and limitations.

M

ost Contrast Enhanced Ultrasound (CEUS) examinations are scheduled in advance but stable patients can also undergo emergency scanning, for example for assessing solid abdominal organ injuries and infarcts, blood vessel, scrotal and penile pathology. If an intravenous cannula is already in place, the additional time for carrying out CEUS is less than 10 minutes. Since US contrast agents (USCA) are not excreted by the kidneys, their use is not contraindicated in renal insufficiency; in addition anaphylactoid reactions are extremely rare.

CEUS PRINCIPLES, PHYSICS AND SAFETY

USCA are composed of gas-filled microbubbles coated with a protein, lipid or polymer shell [1]. They are too large to exit the endothelial vessel wall and are therefore limited to the intravascular space[2]. When encountering an ultrasound wave, USCA agents with a low mechanical index (MI) such as Sonovue (sulfur hexafluoride microbubbles in phospholipid shell [3]), oscillate asymmetrically, generating echoes containing harmonic frequencies [4]. These are signals with peaks at frequencies that are multiples of the original frequency. Specific software [5, 6] such as Phase Inversion is needed: two US pulses of constant amplitude but with a 180° phase change in alternate pulses [7] are transmitted sequentially. The US instrument then adds returning signals [8], with almost complete tissue cancellation and a strong USCA signal. Simultaneous split screen view (enhanced image next to baseline image) facilitates orientation. USCA generally behave in a similar fashion to computed tomography (CT) and magnetic resonance (MR) agents. CEUS overcomes color Doppler limitations [9-11], revealing blood flowing at very low speed [1] in vessels as small as 40 μm [12]. In contrast to CT-MR enhancement (observed at specific moments in time), USCA uptake is seen in real time The author : Prof. Demosthenes D Cokkinos Radiology Department, Evangelismos Hospital, Athens, Greece Email: ddcokkinos@yahoo.gr

56

D I

for up to 5-7 minutes. The incidence of anaphylactic reactions (1:7000 or 0.014%) [7, 13, 14], is lower than that of CT agents (0.035%–0.095%) [7, 15, 16]. APPLICATIONS of CEUS in Emergency situations

1. CEUS in abdominal trauma • When and how? Focused Assessment with Sonography for Trauma (FAST) non-enhanced US [17] is the commonest examination method for blunt abdominal trauma imaging [18-20]. The method focusses on fluid detection and has a sensitivity of up to 99% [21-22], but solid organ injuries can easily be overlooked [23], especially if they are isoechoic [24] or in the absence of hemoperitoneum [25, 26]. Contrast enhanced CT is the gold standard technique for the examination of abdominal trauma, but often patients show no or minimal injuries, for example in unilateral localized sports, playground or low-altitude falls [27]. In this scenario, CEUS is useful, and has sensitivities for injury detection of 69% (kidneys), 84% (liver) and 93% (spleen) compared to CT; specificity is over 90% [28]. CEUS has a role in initial emergency imaging of low-energy injuries or follow-up [29]. FAST and full abdominal US are usually performed initially [30, 31]. Upon suspicious indications (abdominal fluid, localized pain, focally altered echogenicity, inhomogeneities stronger than different fat deposit grades) emergency CEUS can be carried out. CEUS images solid organ injuries as non-enhancing areas [27, 32, 33], defining

FIGURE 1. CEUS of the liver (right part of panel a) shows right lobe contusion (arrow). Unenhanced US (left part of panel a) reveals only inhomogeneous echogenicity. Contrast enhanced CT (b) confirms hepatic trauma (arrow) showing that there is excellent correlation between enhanced CT and CEUS .

E U R O P E

MARCH 2013


Explore details at ECR 2013

Extention Expo A

#22

Industry’s Best Specification Industry’s Best Specification WIDE’s new X series LCD Solutions raise the standard in medical imaging by delivering outstanding performance coupled with cutting edge technology. These environmentally friendly and ergonomically designed LCDs exceed industry standards with the new on-Board IQ sensor® bundled with a calibration package for full automatic calibration, conformance, alerting and reporting. Ultra high brightness and contrast ratios, industry leading luminance uniformity performance as well as a 5 year warranty make the X-Series display line the future in medical imaging technology.

New IQ Sensor®

DisplayPort/DVI

PrivateLite®

ECO-Compliance

WIDE EUROPE B.V. | Hullenbergweg 413, 1101 CS Amsterdam, Zuidoost, The Netherlands | Tel: +3120-311-9797 | Fax: +31-20-311-9790 | infoeu@widecorp.com | www.widecorp.com


ISMRM

B R I DGI NG T H E G A P B E T W E E N C L I N I C A L N E E D S AND T E C H N O L O G I C A L S O L U T I O N S

International Society for Magnetic Resonance in Medicine

ATTEND THE LARGEST MEETING DEDICATED TO MAGNETIC RESONANCE IMAGING ISMRM is the premier INTERNATIONAL COMMUNITY of clinicians and scientists in the field of magnetic resonance. The Society hosts an ANNUAL MEETING & EXHIBITION and provides EDUCATIONAL and NETWORKING opportunities to advance knowledge, promote discovery, encourage innovation, IMPROVE WORLD HEALTH and further the CAREERS of its members. Join OVER 6,000 clinicians, physicists, engineers, biochemists, technologists and radiographers from MORE THAN 60 COUNTRIES around the world at THE LARGEST MEETING dedicated to promoting communication, research, development and applications in the field of magnetic resonance in medicine and biology.

WWW.ISMRM.ORG A majority of ISMRM members recommend membership and our annual meeting. Scan this code to find out why! ISMRM

#ISMRM

ISMRM

GET CUTTING-EDGE EDUCATION & GROUND-BREAKING SCIENTIFIC RESEARCH

ISMRM

S

SAVE ON REGISTRATION FEES: REGISTER BY 6 MARCH 2013 GET BEST HOTEL RATES: BOOK BY 7 MARCH 2013

21st Annual Meeting & Exhibition

alt Lake City, Utah, USA 20– 26

A p r i l

2013

“Discovery, Innovation & Application – Advancing MR for Improved Health” SMRT 22nd ANNUAL MEETING “Changing the World through MR Education and Innovation”

20–21 APRIL 2013

ISMRM

COMMUNITY

FOR CLINICIANS AND SCIENTISTS

The International Society for Magnetic Resonance in Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

TO FIND OUT MORE ABOUT UPCOMING PROGRAMS, HOUSING AND REGISTRATION, PLEASE VISIT:

WWW.ISMRM.ORG/13 OR CALL +1 510 841 1899 INTERNATIONAL SOCIETY FOR MAGNETIC RESONANCE IN MEDICINE • 2030 ADDISON STREET • SUITE 700 • BERKELEY • CA 94704 USA


Ultrasound borders, capsular extension and vascular injury [29]. There is excellent correlation with CT [Figure 1]. Contrast extravasation suggests ongoing hemorrhage [32, 34]. Infarcts present as hypoechoic triangular areas with base adjacent to lateral parts of the organ on baseline US, and enhancement defects on CEUS. The dose of contrast agents for hepatic use is 50-100% of that used for focal lesion characterisation (2.4 mL for SonoVue), to avoid concealing small lacerations [27, 29, 35]. The spleen enhances inhomogeneously due to diverse perfusion rates between the red and white pulp. Delayed scanning (i.e. later than 60 sec post-injection) avoids false characterisation of early heterogeneous splenic enhancement as injury [29]. Long splenic uptake (up to 7 min) allows adequate scanning time. The splenic vein tree shows late contrast washout, appearing as defects after 2-3 min post injection, possibly because the spleen acts as a microbubble filter [27]. The vein (tubularly shaped with branching vessels and microbubbles in its lumen) is distinguished from irregular lacerations (with no branches or microbubbles) [Figure 2]. Shattered spleens show ill-defined outlines and abnormal architecture. The kidneys can be assessed by CEUS for a shorter time (up to 2.5 min) [35]. Contusions, lacerations and infarcts appear as filling defects. Hematomas appear as anechoic convex areas. Splenic and renal doses are 25-50% of the hepatic dose [27, 29, 35]. • Multiple abdominal organ assessment for trauma CEUS is primarily performed for unilateral isolated injury [27]. However,

multiple organs can also be imaged. In stable patients with localized injuries diagnosed in the first 2-3 min post administration, the next 2-5 min are used for additional organ scanning, dividing a vial of contrast agents into 2-3 doses. In the left decubitus position, the first dose is used for the right kidney (first 2 minutes) and liver (remaining 3 minutes) [6, 27, 33]. In the right decubitus position, the second dose is used for the left kidney (first 2 minutes) and spleen (remaining 5 minutes). • CEUS or CT for abdominal trauma Stable patients with no or minimal unilateral injuries on CEUS can be observed without need for CT, thus avoiding exposure to radiation, and saving time and money. In multiple injuries, however CEUS should not replace contrast enhanced CT. Critical patients should not be imaged with CEUS but, directly after FAST, sent for CT (if stable) or to surgery (if unstable) [27, 35, 36]. If there are equivocal results on CT (e.g. suboptimal contrast enhancement, artefacts caused by superimposing arms, medical devices or patient motion), CEUS should be used for elucidation [32]. Patients initially examined with CT and who are improving clinically, can then be imaged with CEUS [32], thus resulting in the reduction of the number of repeat CTs, especially important in young patients [37]. 2. Emergency testicular and penile CEUS Emergency scrotal US is carried out to evaluate torsion, trauma, infection and tumors [38]. A full vial of contrast agent (4.8 mL for Sonovue) is needed for best results.

FIGURE 2. B mode US shows ill defined hypoechogenicity in the lower part of the spleen, (arrow in a) referring to an area with no flow in power Doppler (arrow in b). CEUS reveals an enhancement defect (arrow in c) due to trauma (image c is at higher magnification than a and b).

MARCH 2013

D I

E U R O P E

• Torsion Color Doppler US is usually adequate for this but in difficult cases CEUS can confirm the absence of vascularity with suboptimal color imaging (e.g. adolescents with small testes). CEUS has however not been proven to add information in complete torsion [39]. In cases of chronic torsion (i.e. torsion that was initially missed), CEUS detects peritesticular increased vascularity and in incomplete torsion the technique can reveal enhancement discrepancies between normal and abnormal testicle. In intermittent torsion, CEUS shows normal/ increased flow, so helping to differentiate from orchitis [40] and to distinguish rounded segmental infarcts from poorly vascularised tumors [41, 42]. This can increase confidence in unenhanced US [43]. • Trauma of testis and penis Baseline US is adequate for this and can showing testicle border alteration, hemorrhage or infarction, thickened testicular-scrotal wall or ruptured tunica albuginea. CEUS assesses trauma severity, which can possibly be underestimated on unenhanced US [32]. Injuries appear hypoechoic and unenhancing. Ruptured testes, hematoceles and hematomas show abnormal architecture and no enhancement [39]. CEUS improves Color Doppler imaging, defining fracture lines and viable tissue amount [43]. Trauma findings should be followed sonographically until resolution so as not to overlook any underlying neoplasms. In penile trauma there is enlargement and inhomogeneous echogenicity of the corpora cavernosa penis or urethrae, focal contusions and loss of intactness of the surrounding fibrous tissue on unenhanced US. CEUS shows injuries as enhancement defects, thus clarifying or confirming baseline findings. • Testicular infarction Unenhanced US images a wedge shaped area with decreased-absent color flow [44]. CEUS differentiates segmental rounded infarcts from poorly vascularised tumors, detecting ischemic parenchymal lobules separated by normal testicle vessels [45]. Subacute segmental infarctions show peripheral enhancement, gradually decreasing and eventually disappearing with lesion shape change and shrinkage [32]. 59


The CAR 76th Annual Scientific Meeting 76e Congrès scientifique annuel de la CAR APRIL 25 – 28, 2013 | DU 25 AU 28 AVRIL 2013 | LE CENTRE SHERATON | MONTRÉAL, QUÉBEC

Quest for Quality MORE THAN JUST AN IMAGE

La quête de la qualité AU-DELÀ DE L’IMAGE

REGISTRATION NOW OPEN! Register at www.car.ca. Early bird registration ends March 6.

INSCRIPTION MAINTENANT DISPONIBLE!

SCIENTIFIC PROGRAM TRACKS TO INCLUDE:

KEYNOTE SPEAKERS | CONFÉRENCIERS D’HONNEUR

LES SESSIONS DU PROGRAMME SCIENTIFIQUE COMPRENDRONS :

Inscrivez-vous au www.car.ca. Tarif de préinscription en vigueur jusqu’au 6 mars.

Ramin Khorasani, MD, MPH, Brigham and Women’s Hospital Evan Siegelman, MD, Hospital of the University of Pennsylvania

• • • • • • •

Quest for Quality Oncological Imaging Mistakes We All Make Debate – Peer Review: Is It Effective? MSK Live Ultrasound Simulation Workshop Resident Review and Hot Seat Sessions and more…

• • • • •

La quête de la qualité Imagerie en oncologie Erreurs que nous faisons tous Débat – L’évaluation par les pairs : est-elle efficace? Atelier de simulation en matière d’échographie musculosquelettique effectuée sur de vrais modèles • Séances de révision pour les résidents et de mise sur la sellette • et plus encore…

SISTER EVENTS | ÉVÉNEMENTS EN MARGE DU CONGRÈS :

04/23 Two-day ACLS for Radiologists Course | Formation de deux jours en SARC (ACLS) pour les radiologistes (CAR) 04/25 Basic Life Support Course (BLS) | Cours de réanimation cardio-respiratoire (BLS) (Société canadienne-française de radiologie)

613 860-3111

education@car.ca

www.car.ca


Ultrasound • Testicular Infection Epididymo-orchitis begins in the epididymal head or tail [38, 46] disseminating through the rest of the epididymis and testicle. US shows large, echopoor or heterogeneous hypervascular epididymis and testicle, with a sensitivity of up to 100% [47]. On CEUS, abscesses show peripheral and internal septation enhancement, which can potentially be overlooked on unenhanced examination [48]. Central liquefied areas do not enhance [39]. CEUS can differentiate hematomas from tumors and detect spermatic cord vessels thrombosis, especially in funiculitis [32]. 3. Emergency CEUS vessel imaging Since US contrast agents are intravascular, imaging is comparable to angiography, with no nephrotoxicity or exposure to radiation. CEUS usually confirms color Doppler findings or overcomes its limitations (respiratory-cardiac motion artefacts, flow in critical stenosis, slow flow, aliasing, blooming, angle dependence) [49, 50]. CEUS improves the imaging of abdominal aorta aneurysm (AAA), delineating lumen and main branches [32]. When rupture is suspected, the absence of thrombus uptake on CEUS rules out intrathrombus hemorrhage. In intrathrombus leaks, contrast flows from the lumen towards the thrombus. Aortic rupture is seen as contrast extravasation and retroperitoneal hemorrhage [34, 51]. Large blood quantities present as pulsatile contrast exit. Small quantities show continuous flow [34, 51, 52]. CEUS discriminates ruptured aneurysms (which enhance) from pseudoaneurysms with no ongoing hemorrhage (which do not enhance) and helps treatment by guiding thrombin injection during leakage repair [52]. In AA dissection, CEUS shows uptake in both true (earlier) and false (later) lumen, if no thrombosis is present in the false lumen [53] and images possible renal or splenic infarctions [49], but

has not yet been established routinely for emergency imaging. In undiagnosed inferior vena cava IVC thrombus, CEUS delineates the lumen, avoiding motion artefacts and confirms thrombosis suggested on color Doppler. Complicated AAAs with rupture inside the IVC can produce aortocaval fistulas. Although the best imaging methods are CT-MR angiography, CEUS can be useful in unstable cases, revealing blood flowing from aorta to IVC [54]. Emergency CEUS confirms carotid artery obstruction or dissection suggested on color US, improving sensitivity [32] and confidence [Figure 3], differentiates occlusion from tight subocclusive stenosis and outlines endovascular borders in difficult cases. It images pre-stenotic, intra-stenotic and post-stenotic segments of elongated vessels [49-50] and assesses re-stenosis post stenting. In dissection, CEUS increases baseline US accuracy [49, 50], revealing poor but present blood flow (contrary to absent flow in obstruction), suggesting more cephalad occlusion, possibly overlooked on color Doppler US. Superficially located, extremity vessels are easily imaged with CEUS. Thrombosis, embolism, occlusion, pseudoaneurysm etc, suggested on baseline US, can be confirmed. LIMITATIONS

Despite its numerous advantages CEUS has some drawbacks. The results of the technique are operator-dependent and not available worldwide [55]. High value equipment, specific software and are needed. Likewise the technique requires extra time for catheter placement, drug preparation and administration of the agent. CEUS cannot overcome lesion location limitations [32]. Injection of the US contrast agents should be avoided in patients with serious cardiopulmonary disease [56-58].

FIGURE 3. Color Doppler US images pre-obstruction tracing in the left common carotid artery (a) and defines the level of obstruction (arrow in b). CEUS confirms obstruction (arrow in c) and increases examiner’s confidence at 3 in the morning (circled clock in a).

MARCH 2013

D I

E U R O P E

CONCLUSION

There are many indications for the use of CEUS in emergency situations. CEUS should be carried out if a non- enhanced scan is undiagnostic in order to increase confidence in the non-enhanced findings or to decrease the need for further imaging. The technique is easy to learn and quick to perform and, in experienced hands, can solve many diagnostic problems. REFERENCES 1. Morin SH et al. World J Gastroenterol 2007; 13: 963 2. Brannigan M et al. Radiographics 2004; 24: 921 3. Seitz K et al. Ultraschall Med 2010; 31: 492 4. Uhlendorf V et al. Ultrasonics 2000; 38: 81 5. Ripollés T et al. Insights Imaging 2011; 2: 639 6. EFSUMB study group. Ultraschall in Med 2008; 29: 28 7. Wilson SR & Burns PN. Radiology 2010; 257: 24 8. Burns PN et al. Invest Radiol 2000; 35: 58 9. Bauer A & Solbiati L. In: Solbiati L (ed). Contrast-enhanced ultrasound of liver diseases. Springer, Milan 2003; pp: 21 10. Burns P. In: Solbiati L (ed). Contrast-enhanced ultrasound of liver diseases. Springer, Milan 2003; pp: 1-18 11. Correas JM et al. Eur Radiol 2011; 11: 1316 12. Claudon M & Dietrich CF. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS). Ultrasound Med Biol 2013; 39: 187 13. Kitzman DW et al.. Am J Cardiol 2000; 86): 669 14. Piscaglia F & Bolondi L. Ultrasound Med Biol 2006; 32: 1369 15. International Collaborative Study of Severe Anaphylaxis. Pharmacoepidemiol Drug Saf 2003; 12: 195 16. Cochran ST et al. AJR Am J Roentgenol 2001; 17: 1385 17. Scalea TM et al. J Trauma 1999; 46: 466 18. Kretschmer KH et al. Emerg Radiol 1997; 2: 62 19. Yoshii H et al. J Trauma 1998; 45: 45 20. Healy MA et al. ? J Trauma 1996; 40: 875 21. Rozycki GSet al. J Trauma 1995; 39: 492 22. Brown MA et al. J Intensive Care Med 2006; 18: 253 23. Pearl WS & Todd KH. Ann Emerg Med 1996; 27: 353 24. Leen E et al. Eur Radiol Suppl 2004; 14[Suppl 8]: P16 25. Chiu WC et al. J Trauma 1997; 42: 617 26. Shanmuganathan K et al. Radiology 1999; 212: 423 27. Thorelius L Eur Radiol Suppl 2007; 17[Suppl 6]: F107 28. Catalano O et al. Abdom Imaging 2009; 34: 225 29. Afaq A et al. Eur J Emerg Med 2012; 19: 140 30. Yegiyants S et al. Am Surg 2006; 72: 943 31. Brenchley J et al. Emerg Med J 2006; 23: 446 32. Piscaglia F et al. Ultraschall Med 2012; 33:33 33. Valentino Met al. AJR Am J Roentgenol 2006; 186:1361 34. Catalano O et al. Abdom Imaging 2006; 31: 9 35. Cokkinos D et al. Ultraschall Med 2012; 33: 60 36. Valentino M et al. Radiol Med 2009; 114: 1080 37. Manetta R Radiol Med 2009; 114: 771 38. Wittenberg AF et al. Curr Probl Diagn Radiol 2006; 35: 12 39. Moschouris Het al. Int Braz J Urol 2009; 35: 692 40. Alcantra AL & Sethi Y. Emerg Radiol 1998; 5: 394 41. Sriprasad S Br J Radiol 2001; 74: 965 42. Ledwige ME AJR 2002; 179: 775 43. Valentino M et al. Eur Radiol 2011; 21: 1831 44. Bilagi P et al. Eur Radiol 2007; 17: 2810 45. Bertolotto M et al. AJR Am J Roentgenol 2011; 196: 834 46. Gorman B & Caroll BA. In: Rumack CMet al., (eds) Diagnostic ultrasound, 3rd ed. Elsevier Mosby, St Louis, 2005; pp: 849 47. Burks DDet al. Radiology 1990; 175: 815 48. Muttarak M & Lojanapiwat B. Singapore Med J 2005; 46: 352 49. Clevert DA, et al. Clin Hemorheol Microcirc 2009; 43: 129 50. Clevert DA Eur J Radiol 2011; 80: 68 51. Catalano O AJR Am J Roentgenol 2005; 184: 423 52. Martegani A et al. Eur Radiol Suppl 2004; [Suppl 8]: P73. 53. Clevert DAet al. Eur Radiol 2007; 17: 2991 54. Bhatia M et al. Abdom Imaging 2010; 35: 376 55. Beaton Cet al. Eur J Surg Oncol 2010; 36: 43 56. Main ML et al. JACC 2007; 50: 2434 57. US Food and Drug Administration. Available via: http:// www.fda.gov/Safety/MedWatch/ SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm092270.htm. Accessed 6 April 2012. 58. Health Canada. Available via: http://www.hc-sc.gc.ca/dhp-mps/ medeff/advisories-avis/prof/_2008/definity_hpc-cps_2-eng.php. Accessed 6 April 2012.

61



New

technology

by Dr W Alwan, Dr AJ Coleman & Dr KE Lacy

Optical Coherence Tomography (OCT) – a new tool in the diagnosis of non-melanoma skin carcinoma OCT is a high resolution, non-invasive imaging technology that uses nearinfrared light to generate real-time cross-sectional images of tissues. Previously, the technique has been used in industry where its applications include materials testing and imaging. OCT has recognized roles in clinical medicine disciplines such as gastroenterology and cardiology and has most notably been utilized in ophthalmology for the diagnosis and management of retinal disease and glaucoma [1]. Modern OCT systems have evolved greatly in terms of the tissue depth and field of view, and can typically assess tissues to a depth of 1-2 mm with a resolution of between 3-15 micrometres [2,3,4], and are rapidly gaining favour as a new clinical diagnostic imaging modality. Its application in dermatology for non-melanoma skin cancer (NMSC) has showed particular promise and is discussed in this article. Principles of OCT technology

Non-melanoma skin cancer

OCT is analogous to ultrasound (specifically B-scanning mode) except that, rather than sound waves, it relies on the reflection of light signals to generate high-resolution cross-sectional images of tissues such as skin. To acquire an image, a handheld probe is held to the patient’s skin and a beam of near-infrared wavelength (0.7 to 3 micrometres) light is directed towards the tissue. The intensity of back-reflected light will vary dependent on the consistency and composition of the underlying tissue. The technique overcomes the problem of interference of images by minimising the influence of the ‘background’ scattered light through the concept of interferometry. This works by directing the same light source at a reference sample, and a combination of the waveform outputs from this and the sample surface of interest will effectively ‘cancel out’ background scattered photons. This allows light directly reflected from the surface of interest to be used to build up an accurate 2-dimensional image of the tissue of interest.

Non-melanoma skin cancer (NMSC) includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and is the commonest malignancy worldwide. Over 100,000 cases of NMSC were diagnosed in the UK in 2010 [5] and it is thought that NMSC accounts for 70% of the costs of managing skin cancer, despite it being rarely fatal [6,7]. Squamous cell carcinoma is a tumor that has the potential to metastasize, whilst basal cell carcinoma rarely metastasizes but is capable of significant tissue destruction through local invasion. The most important etiological factor in NMSC is chronic exposure to ultraviolet light. Patients are usually elderly and often have multiple suspicious lesions on chronically sun-exposed sites such as the face, nose, ears and hands. Early and accurate diagnosis of malignant lesions is vital and if there is diagnostic uncertainty a skin biopsy is usually undertaken. Given the economic burden and associated patient morbidity of repeated biopsies, coupled with the fact that lesions often occur in cosmetically sensitive areas, the advent of a reliable non-invasive diagnostic tool for NMSC is highly desirable. A study from our unit published this year [8] attempted to assess how OCT images correlated with histological samples taken from patients, in addition to assessing if there are reliable diagnostic OCT features of NMSC. The group also assessed the ability to accurately measure tumor dimensions.

The authors : Dr W Alwan1, Dr AJ Coleman2 & Dr KE Lacy1. 1. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ Hospitals and King’s College London, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, Kings College London, UK 2. Medical Physics Department, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

MARCH 2013

D I

E U R O P E

63


New technology evaluation of suspicious skin lesions and is a familiar tool used widely by Dermatologists. Its role in melanoma diagnosis is well recognized [9]. In this study dermoscopy identified, as previously described, arborizing blood vessels on nodular BCCs. The OCT demonstrated these vessels as dark linear structures and additionally identified dark rings with central sparing that were thought to be consistent with the basaloid cell nests with peripheral palisading. FIGURE 1. Superficial BCC on back. a. Haematoxylin and eosin (H&E) staining of skin biopsy containing a superficial BCC. A typical basaloid cell nest is seen extending from the epidermis (blue arrow). Palisading cells are seen at the edge of the lesion (white arrows). b. OCT scan of same lesion reveals an ovoid structure corresponding to that seen on histology (blue arrow). A corresponding dark band around the edge of the lesion is seen in the same region as palisading cells on the histology (white arrows).

Study design

Seventy-eight patients were included in the study. Eligible patients included were those with a new, clinically suspicious skin lesion of less than 1.5cm diameter referred for a skin biopsy. Twenty-eight lesions were histologically confirmed as malignancies (20 BCCs and 8 SCCs). The remaining lesions were identified as benign naevi, seborrhoeic keratosis and other benign lesions such as fibromas and hemangiomas. Each lesion was assessed by a trained operator using a hand-held OCT probe [VivoSight MDL Ltd., Orpington, UK] before undertaking a skin biopsy which was sent for independent histopathological analysis. The histological specimens were matched with corresponding OCT images from the same patient and the properties of the lesion were assessed for each modality. This included dimensions of the margin between normal and cancerous tissue, deep margin depth and also the optical properties of normal and tumor tissue within well-defined regions. Basal cell carcinoma

Basal cell carcinomas can be clearly visualized using OCT with images that are comparable to histology. Superficial (n=4) [Figure 1], nodular (n=11), pigmented nodular (n=2) and infiltrative BCCs (n=2) were analyzed in the study. In all BCC subtypes dark oval structures seen on OCT were found to be analogous to basaloid cell nests seen on histology [Figure 1a,b]. A dark layer surrounding the margin of the lesion on the OCT image was seen [Figure 1b] within the 64

location of palisading cells on the histology [Figure 1a] where the cells were aligned and appeared elongated with enlarged nuclei. Whilst not exclusive to BCCs, the phenomenon of palisading is a classical histopathological finding for this type of skin tumor. Unlike other subtypes of BCC analyzed, there was no clear dermo-epidermal junction for nodular BCCs on OCT imaging. In addition, a collection of low signal lobular regions surrounded by higher signal bright borders was identified possibly suggestive of a stromal reaction. Quantitatively, the ability of the OCT image to distinguish between normal and malignant tissue was assessed by calculating the margin contrast. By mapping a line between normal and tumor tissue, a value for percentage in greyscale contrast was calculated. All superficial BCCs had a value of margin contrast of >4%, which indicated low signal at the tumor margin compared to the tumor cell nest. A margin contrast of >4% was also seen in most cases of nodular BCCs. Pigmented nodular BCC’s (n=2) did not vary qualitatively in appearance compared from the nonpigmented nodular BCCs, however there was no measurable margin contrast (<4%). The contrast value was also < 4% in both cases of infiltrative BCC. OCT/Dermoscopy correlation

The ability of OCT to view images in any plane can be further utilized to correlate findings with other imaging modalities, such as dermoscopy; where an enface view is used. Dermoscopy uses a magnified light source to facilitate the D I

E U R O P E

Squamous cell carcinoma

Both in situ SCCs (n=5) and an invasive SCC (n=1) were analyzed in our study. OCT images showed bright surface features characteristic of the hyperkeratosis seen on the histology images of SCCs [Figure 2a, b]. There are also changes suggestive of epidermal keratin seen as bright regions on the OCT [Figure 2a,b]. Lesion depth assessment using OCT

OCT was comparable to the goldstandard histopathological technique for measuring tumor depth for lesions that were found to have a deep margin of less than 1 mm. This included all superficial BCCs, 5 nodular BCCs and 2 in situ SCCs. The ability of OCT to assess BCCs of less than 1mm depth has also previously been reported in 2007 [10]. For lesions greater than 1 mm deep, there was a tendency for OCT to underestimate the depth of tumor – this included all the infiltrative BCCs and SCCs. Optical Attenuation Coefficient

Analysis also included the calculation of the optical attenuation co-efficient; a measure of how the intensity of the OCT beam is attenuated by the matter through which it is passing through. In the case of BCC, there was a statistically significant difference between the optical attenuation coeficient (denoted by the character μ) for the tumor tissue and the corresponding stroma (p<0.001). However, despite there being a measured difference in the value of μ for the SCC compared to stroma, this did not reach statistical significance. Plotting the optical attenuation coefficient for all the BCCs and SCCs and the corresponding stroma against the nuclear cytoplasmic ration generated a weak inverse linear correlation. This was interpreted as an MARCH 2013


increase in the nuclear/cytoplasmic ratio with the transition from normal epithelial tissue to malignancy, as reflected by lowering of the OCT signal. Discussion

Our finding of the OCT correlate of palisading in BCCs seen on histology is previously unreported and may help to assist in the identification of BCCs non-invasively. The confirmation of the ability of OCT to assess tumors less than 1mm deep may also be useful for the selection of superficial lesions that are amenable to more conservative topical therapies (e.g. Imiquimod and 5-Fluorouracil) in addition to assessing response to treatment. OCT may also have a role in directing biopsies to improve the yield of tumor diagnosis by identifying high-risk abnormal areas and avoiding normal tissue seen in ‘skip lesions’. The use of OCT in SCCs appears to be less useful, as reported in previous studies[11,12,13,14] , as there is interference shadowing from surface hyperkeratosis which projects brightly on the OCT image. The correlates between OCT and histology are consistent with previous work and has been corroborated in other papers [15]. Additionally, the ability to detect OCT changes suggestive of solar damage, the most important risk factor for NMSC has previously been reported where OCT values for optical attenuation were statistically significantly different between mild sun-damaged skin and severely sun damaged skin [15]. There may be a role for increasing the speed of ex-vivo assessment of BCC samples using OCT excised during Mohs micrographic surgery, which is often protracted due to real-time

processing and interpretation of histopathological sides with conventional haematoxylin and eosin staining [16] Asides from NMSC, OCT may have a role in assessing pigmented melanocytic lesions [17,18]. Conclusion

OCT has characteristic diagnostic features that can highlight lesions that are suspicious for skin malignancy and correlates well with histology. More widespread uptake is only likely to follow with further evidence of its clinical benefits and greater clinician familiarity with characteristic diagnostic features. Data showing its use with other, more recognized modalities such as dermoscopy may help integrate OCT into the clinic setting. Improvements in technical quality of images will help OCT gain wider acceptance. High definition OCT, which offers a greater resolution image compared to conventional OCT, may yield further promise in this respect. It has been shown to be useful in the assessment of actinic keratosis [19] and BCCs [20] Biopsy is the current gold standard but has a high false-positive rate that is accepted given the precautionary approach to skin cancer screening. For patients who deem biopsy unacceptable, identifying ways of risk stratifying lesions in which biopsy may be avoided will be of utmost importance. Consequently OCT is likely to play an increasingly prominent role in tumor diagnostics in the future. REFERENCES 1. J affe GJ, Caprioli J. Optical coherence tomography to detect and manage retinal disease and glaucoma. (Am J Ophthalmol. 2004 Jan;137(1):156-69.) 2. V ivoSight, Michelson Diagnostics web-

FIGURE 2. Invasive SCC on the face a. H&E staining of biopsy of SCC within the skin showing areas representing hyperkeratosis on surface of lesion in addition to keratin within the epidermis (black arrows). b. OCT image shows a bright structure on the surface of the lesion in addition to deeper bright ovoid lesions(white arrows) that may correspond with hyperkeratosis and keratin pearls seen on H&E respectively.

MARCH 2013

D I

E U R O P E

site. http://www.vivosight.com/wp-content/ uploads/2012/11/MICHELSON-TECHNICALSHEET.pdf. Accessed online 1st February 2013. 3. Pierce MC, Strasswimmer J, Park BH, et al. Advances in Optical Coherence Tomography imaging for Dermatology. (J Invest Dermatol 2004; 123: 458-463) 4. Thomlins PH, Adegun O, Hagi-Pavli E, et al. Scattering attenuation microscopy of oral epithelial dysplasia. J Biomed Optics. 2010; 15: 0660031-066003-8) 5. Cancer Research UK website. http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/ skin-cancer/. Accessed online 27th January 2013. 6. Ostergaard A, Lamberg AL, Olsen AB. Epidemiology of non-melanmoma skin cancer. In: Jemec GB, Miech D and Kemeny L. eds. Non-surgical treatment of keratinocyte skin cancer. Berlin: SpringerVerlag, 2010; 15–24. 7. Mogensen M, Jemec GB. Accuracy in the diagnosis of non-melanoma skin cancer. In: Jemec GBE, Miech D and Kemeny L. eds. Non-surgical treatment of keratinocyte skin cancer. Berlin: SpringerVerlag, 2010; 51–72. 8. §Coleman, A. J., Richardson, T. J., Orchard, G., et al. Histological correlates of optical coherence tomography in non-melanoma skin cancer. Skin Research and Technology. 2013; 19: e10–e19. 9. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting (Br J Dermatol. 2008 Sep;159(3):669-76) 10. Olmedo JM, Warschaw KE, Schmitt JM, et al. Correlation of thickness of basal cell carcinoma by optical coherence tomography in vivo and routine histological findings: a pilot study. (Dermatol Surg. 2007; 33:421-426) 11. Gambichler T, Orlikov A, Vasa R et al. In vivo optical coherence tomography of basal cell carcinoma. J Dermatol Sci 2007; 45: 167–173. 12. Jørgensen TM, Tycho A, Mogensen M et al. Machine-learning classification of non-melanoma skin cancers from image features obtained by optical coherence tomography. Skin Res Technol 2008; 14: 364–369. 13. Gambichler T, Moussa G, Kreuter A et al. Applications of optical coherence tomography in dermatology. J Dermatol Sci 2005; 40: 85–94. 14. Korde V, Bonnema G, Xu W et al. Using optical coherence tomography to evaluate skin sun damage and precancer. Laser Surg Med 2007; 39: 687–695. 15. Bechara FG, Gambichler T, Stücker M, et al. Histomorphologic correlation with routine histology and optical coherence tomography. (Skin Research and Technology. 2004; 10: 169-173) 16. Cunha D, Richardson T, Sheth N, et al. Comparison of ex-vivo optical coherence tomography with conventional frozen-section histology for visualising basal cell carcinoma during Mohs micrographic surgery. (British Journal of Dermatology. 2011; 165: 576-580) 17. de Giorgi V, Stante M, Massi D, et al. Possible histopathologic correlates of dermoscopic features in pigmented melanocytic lesions identified by means of optical coherence tomography. (Experimental Dermatology. 2005; 14: 56-59) 18. Gambichler T, Regeniter P, Bechara FG, et al. Characterisation of benign and malignant melanocytic skin lesions using optical coherence tomography in vivo. (J Am Acad Dermatol. 2007; 57: 629-37) 19. Maier T, Braun-Falco M, Laubender RP, et al. Acitinic keratosis in the en-face and slice imaging mode of high definition optical coherence tomography and comparison with histology. (British Journal of Dermatology. 2013; 168: 120-128) 20. Boone MALM, Norrenberg S, Jemec GBE, et al. Imaging of basal cell carcinoma with high definition optical coherence tomography: histomorphological correlation. A pilot study. (British Journal of Dermatology. 2012; 167: 856-864)

65


Ultrasound by Dr C hrstian Prinz

Hand-Held Echocardiography – a “small” revolution Echocardiography with hand-held systems is now feasible in the clinical routine. Despite its advantages (including the financial/cost aspects) the limitations of hand-held echocardiography are such that it will neither make high-end echocardiography nor standard physical examination redundant. It will be a useful tool to complement these established examination methods. Nevertheless, hand held echocardiography has the potential to revolutionize clinical medicine. This article reviews the development of modern hand-held echocardiography systems, their applications and limitations and emphasizes the advantages of thorough training in the use of the systems Historical developments — The stethoscope

From “Hearing” to “Seeing”

The stethoscope is probably the instrument most associated with doctors. Almost no other instrument identifies a person more as a medical professional than the stethoscope dangling around the neck. The word “stethoscope” actually comes from the Greek word “στηθοσκόπιο“ (stēthoskópion), meaning “tó stēthos“ — the chest— and “σκoπέω“ (skopéō), meaning “I am looking or I am observing“. Since the stethoscope is based on acoustic phenomena rather than on a visual evaluation, to be correct, the precise term should actually have been “stethosphone“. In one of the first recorded descriptions of the use of a stethoscope, the French physician, Dr Rene Theophile Hyacinthe Laënnec (1781-1826), tightly rolled up a sheet of paper, placed one end on the precordium (chest) and the other end to his own ear. He was surprised to be able to hear the beating of the heart with greater clarity than he could obtain by direct application of his ear to the chest wall, as was the common practice at the time [1].

Since the introduction of echocardiography more than 50 years ago by Edler and Hertz [2] a continuing revolution and development of the technical capabilities for physical examination has taken place. For the first time the heart and its pathologies could not only be heard, but even seen – a real-time look in the human body was possible (the Greek term of “stēthoskópion” had finally become reality) and the era of visualization was born. Since then cardiac ultrasound has played a key role in clinical practice. There are several advantages that have underpinned the popularity of cardiac ultrasound. These include the absence of exposure to radiation for the patient, the ease of handling and the relative cheapness of the technique, especially when compared with other imaging modalities such as magnetic resonance imaging or computed tomography [3]. Currently the spectrum of the different imaging modalities within echocardiography ranges from M-mode and Doppler-features, through 2- , 3- and 4-D techniques to specialized sub-disciplines such as cardiac deformation imaging or flow-tracking analyses [4, 5]. The increasing processing power of modern computers enables the evaluation of not just anatomic structures, but makes it also possible to gain information about function and causal relationships between morphology and cardiac function. In the last few years the technical progress in this field has been accompanied by an incremental miniaturization of the echocardiography devices. Until now high-end and middle-class ultrasound machines have been physically large and heavy, so limiting their mobility and bedside use. In the late seventies Roelandt and

The author : Dr. Christian Prinz is at Dept. of Cardiology, Heart- and Diabetes Center North RhineWestphalia Ruhr-University Bochum, Bad Oeynhausen, Germany Georgstrasse 11, 32545 Bad Oeynhausen Email: Cchrprinz@aol.com Christian Prinz studied mathematics and physics at the University of Münster (Germany) and medicine at the Universities of Giessen, Berlin and Basel (Switzerland). He was research fellow at the Medical Imaging Research Center of the University of Leuven (Belgium). Now he is at the Department for Cardiology of the Heart- and Diabetes Center, Bad Oeynhausen (Ruhr-University Bochum), Germany.

66

D I

E U R O P E

MARCH 2013


EANM´13

E ur

EANM® o p e an

A s s o ci atio n o f N u cl e a r M e d i

cin e

Annual Congress of the European Association of Nuclear Medicine October 19 –23, 2013 Lyon, France www.eanm.org


Ultrasound

FIGURE 1. This figure shows a recent hand-held echocardiographic device of the size and format of current smart phones. The introduction of such systems facilitates real bedside use (in this example GE VSCAN, GE Healthcare).

colleagues extended the bedside physical examination by integrating an echocardiogram. This was only possible by the development of a (relatively) portable device of sufficient quality (“ultrasonic cardioscope”) [6, 7]. Until now, these hand-carried machines suffered from the fact that they were large and heavy, ranging from approximately 2.5 kg for laptop-sized systems right up to 9 kg.

Depending on their size and weight, the complexity and functions of these devices varied from limited imaging modalities to harmonic imaging and Doppler features. In contrast to such older “hand-carried” ultrasound devices the recent introduction of extremely small and light (< 0.5 kg) hand-held ultrasound scanners allows for the first time an ultrasound machine to be carried in the pocket of the doctor’s white coat, thus facilitating a real bed-side routine usage [Figure 1]. Hitherto the terms “hand-carried ultrasound” or “hand-held ultrasound” were used for both the older and lap-top sized generation of echocardiography machines and for pocket-sized devices with weights under one kilogram. However, a clear distinction between these echocardiographic devices and the newer generation of hand-held devices in actual smart phone size is desirable following the recommendations of the European Association of Echocardiography (EAE) [8]. State of the Art: Hand-Held Echocardiography

Currently the EAE classifies echo machines into four main categories: (1) Fully equipped high-end systems not designed to be moved. (2) Mobile systems with not necessarily all advanced modalities (like 3-D echocardiography) which can be easily

transported inside health-care facilities. (3) Portable machines (lap-top sized) which usually offer all essential modalities for the carrying out of a complete echo study but without advanced modalities. (4) Pocket-size, hand-held imaging devices (pocket echocardiography) Technical abilities of currently available hand-held echocardiography devices

In theory, hand-held echocardiography devices offer just 2D and color Doppler modalities. No spectral Doppler capabilities are available. Basic measurements for distances and areas can be carried out. The total weight of the device and probe together is approximately < 500g. Dedicated software and a docking station are essential for basic off-line measurements and for re-charging the battery in the device. The gain is often adjusted automatically for all depths. An image based “Auto-Cycle” function for the automatic detection of a full heart cycle beginning with end-diastole is offered so that no parallel ECG recording is necessary. Stills, image loops and voice recordings are stored mostly in MP4 format and can be transferred to a PC for off-line analysis [9]. Clinical feasibility and accuracy

The introduction of hand-held echocardiography initiated a debate on the appropriateness of its use in clinical decision-making, mainly due to concerns regarding image quality [Figure 2]. In contrast to the older hand-carried ultrasound machines, almost all recent studies demonstrated the clinical feasibility and accuracy of the new handheld ultrasound devices of real pocket format in different clinical settings by the use of expert echocardiographers [9, 10, 11, 12, 13, 14]. Training in the use of hand-held echocardiography

FIGURE 2. The figure above demonstrates comparable image qualities using high-end echocardiography or a modern hand-held scanner in the same patient.

68

D I

E U R O P E

The EAE does not recommend any specific training for expert (accredited) echocardiographers for the use of pocket-size imaging devices [8]. However, recent studies and my own investigations have shown the desirability of offering a specific training course for cardiologists or other medical professionals who may not be fully conversant with echocardiography [15, 16]. MARCH 2013


Ultrasound Well-designed and thorough training in echocardiography led to a rapid improvement in image acquisition and interpretation over a period of a few weeks. Basic diagnostic findings could be interpreted with high accuracy after even a short training period. However, interpretation of complex findings still remains difficult [16]. For this reason, it is unlikely that hand-held echocardiography will replace high-end echocardiography performed by expert echocardiographers, particularly given the importance of avoiding mis-diagnosis or mis-interpretation of echocardiographic findings. New educational approaches are warranted for the use of hand-held echocardiography, for example as part of a special certification process [17, 18, 19]. Recent studies [9-19] demonstrated that the technical characteristics and image quality from hand-held echocardiography are sufficient for the evaluation of myocardial function, detection of pericardial and/or pleural effusion and for the evaluation of inferior vena cava filling status. Valve disorders, particularly valve regurgitations could be assessed correctly by color Doppler. Due to the lack of spectral Doppler capabilities in current hand-held echocardiographic devices, the assessment of valve stenoses remains a challenge and should therefore remain in the domain of highend echocardiographic imaging [20]. Learning from history

Despite initial severe scepticism by the medical authorities of the time,

Laënnec’s introduction of mediate auscultation using a stethoscope revolutionized the practice of medicine in the 19th century. Laënnec eventually correlated his stethoscopic sounds with postmortem findings of diseases of the chest. His book “De l’auscultation mediate” was translated into English and published in London in 1821. It became a standard diagnostic textbook. Auscultation remained essential for physical examination for almost the next two hundred years until today. However because of the limitations of hand-held echocardiography its introduction will neither make auscultation nor fully equipped high-end echocardiography redundant, just as the introduction of the stethoscope did not make percussion redundant. However, in the hands of welltrained medical professionals the introduction of hand-held echocardiography will allow faster and more accurate clinical diagnoses. Additionally, the technology will probably save precious healthcare resources and also improve medical teaching. It enables for the first time a direct and real-time bedside look into the chest of our patients on top of classical physical examinations and auscultatory findings. However, training in echocardiography is mandatory. Just as Laënnec’s distinguished invention of the stethoscope all these years ago, contributed to significant advances in the diagnosis of chest diseases, small hand-held echocardiography devices look set to bring about a

FIGURE 3. Panel (a) demonstrates the excellent correlation between high-end (EF HIGH) and hand-held echocardiography (EF HAND),in the visual assessment of left ventricular ejection fraction (LV-EF). The examinations — in 320 patients — were carried out by an expert-echocardiographer . Panel (b) shows the Bland-Altman plot.

MARCH 2013

D I

E U R O P E

“small” revolution in the carrying out of examinations in the future. References [1] R oguin A. Rene Theophile Hyacinthe Laënnec (1781-1826): The Man Behind the Stethoscope. CM&R 2006; 3: 230-235 [2] Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of the movements of heart walls. Kungl Fysiografiska Sällskapets i Lund Förhandlingar 1954; 24: 40-58 [3] Picano E. Economic and biological costs of cardiac imaging. Cardiovasc Ultrasound 2005; 3: 13 [4] Lang RM, et al. Three-dimensional echocardiography: the benefits of the additional dimension. J Am Coll Cardiol 2006; 48: 2053-69 [5] Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol 2006; 47: 1313-27 [6] Ligtvoet C, et al. Real time ultrasonic imaging with a hand-held scanner. Part I—technical description. Ultrasound Med Biol. 1978; 4: 91-2 [7] Roelandt JRTC, et al. Ultrasonic real time imaging with a hand-held scanner. Part II--Initial clinical experience. Ultrasound Med Biol 1978; 4: 93-7 [8] Sicari R et al. The use of pocket-size imaging devices: a position statement of the European Association of Echocardiography. Eur J Echo 2011; 12: 85-87 [9] Prinz C, Voigt JU. Diagnostic accuracy of a hand-held ultrasound scanner in routine patients referred for echocardiography. J Am Soc Echocardiogr. 2011; 24: 111-6 [10] Fukuda S et al. Pocket-sized transthoracic echocardiography device for the measurement of cardiac chamber size and function. Circ J 2009; 73:1092–6 [11] Egan M, Ionescu A. The pocket echocardiograph: a useful new tool? Eur J Echocardiogr 2008; 9: 721–5 [12] Cardim N et al. Usefulness of a new miniaturized echocardiographic system in outpatient cardiology consultations as an extension of physical examination. J Am Soc Echocardiogr. 2011; 24: 117-24 [13] Prinz C, et al. Diagnostic performance of handheld echocardiography for the assessment of basic cardiac morphology and function: a validation study in routine cardiac patients. Echocardiography 2012; 29: 887-94 [14] Culp BC, et al. The pocket echocardiograph: validation and feasibility. Echocardiography. 2010; 27: 759-64 [15] Zamorano JL, et al. Echocardiography performed by physicians outside of echo-labs—is it possible? Eur Heart J 2002; 23:908–9 [16] Prinz C et al. The importance of training in echocardiography: a validation study using pocket echocardiography. J Cardiovasc Med (Hagerstown). 2012; 13: 700-7 [17] Popescu BA et al. European Association of Echocardiography. European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography. Eur J Echocardiogr 2009; 10: 893–905. [18] Nihoyannopoulos P, et al. Laboratory Accreditation Committee of the EAE. EAE laboratory standards and accreditation. Eur J Echocardiogr 2007; 8: 80–7 [19] Badano LP. The use of pocket size imaging devices: a position statement by the European Association of Echocardiography. Eur Heart J 2011; 32: 385–392 [20] Zoghbi WA. Echocardiography at the point of care: an ultra sound future. J Am Soc Echocardiogr. 2011; 24: 132-4

69


Molecular imaging by Dr M. C. Oliveira, Dr G. Ribeiro Morais, & Prof T. Thiemann

Steroid receptor ligands as PET imaging agents Estrogen and progesterone receptors are valuable biomarkers in the diagnosis and prognosis of breast tumors as well as in the follow-up of therapeutic response. The design of radiolabelled steroids has been an active area of research because of their well-known value in breast cancer targeting. Some estrogen and progestin-based PET radiotracers have been proposed for steroid receptor imaging. This article reviews recent developments in the field and highlights the most promising PET radiopharmaceuticals for the detection of hormone-responsive breast tumors

B

reast cancer is still one of the most deadly malignancies among women in the Western World, in spite of a decline in mortality rate in recent years [1]. Early detection and accurate staging improves the probability of survival. Mammography is still the diagnostic method that is the most often used, and can allow the cancer to be identified before the appearance of physical symptoms. Ultrasonography and MRI are non-invasive imaging modalities that, together with self-breast and clinical examinations can also be useful in breast cancer detection. However, these techniques only provide information on tissue abnormalities, which may or may not be malignant, and therefore a biopsy is always necessary to confirm whether the abnormal tissue is a carcinoma. Other nuclear imaging modalities, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) do not only give anatomic information but also functional information about primary and metastatic lesions. Estrogen receptors (ER) and progesterone receptors (PR) are found in many breast tumors. These receptors serve as targets for diagnostic imaging and radiotherapy, but can be used as targets for endocrine therapy, too. Knowledge of ER and PR expression within the tumor provides relevant information on the most effective treatment of primary and metastatic breast cancers and can

help to select the patients that may benefit from hormonal therapy. In the case of tumor receptors, the radionuclidebased imaging modalities, PET and SPECT appear to be the only feasible approach for the non-invasive detection of receptor status. This is due to the limited capacity of the receptor binding system that demands a tracer with high specific activity. PET and SPECT are the most sensitive molecular imaging techniques, since they are able to determine concentrations of specific biomolecules as low as in the picomolar range. ESTROGEN AND PROGESTERONE RECEPTORS AS BIOMARKERS IN BREAST CANCER

The growth of breast epithelial cells is a process mediated by estrogens, which manifest their biological activity through a specific, high binding affinity to the ER. This action results in the induction of progesterone receptors, since in target tissues the synthesis of the progesterone

The Authors: Dr M. C. Oliveira1, G. Ribeiro Morais1 & T. Thiemann2 1. M . C. Oliveira and G. Ribeiro Morais are at the Radiopharmaceutical Sciences Group, Campus Tecnol贸gico e Nuclear, Instituto Superior T茅cnico, Lisbon, Portugal. 2. T . Thiemann is Professor of Organic Chemistry at the Faculty of Science, United Arab Emirates University, United Arab Emirates. e-mail: cristinaoliveira@ctn.ist.utl.pt

70

D I

The development of PET radiopharmaceuticals for the detection of hormoneresponsive breast tumors is an active field.

E U R O P E

MARCH 2013


Endocrine therapy response rates at the stage of an advanced progression of the disease average 33% in tumors positive for one hormone receptor and 50-70% in tumors positive for both receptors [8]. ER AND PR PET IMAGING AGENTS UNDER CLINICAL INVESTIGATION

FIGURE 1. Chemical structure of the radioimaging agents discussed: [16α-18F]16α-fluoroestradiol (1, with numbering scheme), [16α-18F]-4,16α-difluoro-11βmethoxyestradiol (2), [21-18F]-21-fluoro-16α17α(R)-(1’-α-furylmethylidene) dioxy]-19-norpregn-4-ene-3,20-dione (3), and [2-18F]-2-fluoro-2-deoxyD-glucose (4).

receptor is an estrogen-controlled process [2]. The overexpression of ER and PR in human tumor cells as well as their binding characteristics, which involve a prolonged retention of the hormone as compared to non-hormonal compounds, provide a favorable mechanism for the localisation of tumors. Research on specific steroid receptor imaging probes for breast tumors has focussed mainly on estrogen-based radiotracers for the evaluation of the ER status, since it is well-known that ERexpressing breast cancer patients may benefit from hormonal therapy. However, in the course of antiestrogen therapy such as tamoxifen, the ER binding sites may be fully occupied by the antiestrogen and its metabolites, resulting in a decreased uptake of the estrogen-based radiotracer by the tumor. In contrast, progesterone receptors in tumors of patients on a tamoxifen regimen should be unoccupied, and their levels might even increase during the antiestrogen therapy [3]. Thus, the response to endocrine therapy can be predicted more accurately after quantification of both ER and PR status [4]. Distinct features of breast cancer can be used to establish a prognosis and to predict the responsiveness of the patient to specific therapies. Together with the standard clinical prognostic factors, well-known molecular biomarkers of breast cancer, such as ER and PR play important roles in determining the tumor response to endocrine therapies and the development of cell resistance to these treatments [5]. The ER subtype α (ERα) is expressed in nearly 70% of breast cancers and is a relevant predictive factor for targeted therapy [6]. Patients with ERα-positive (ERα+) tumors usually have longer overall survival than patients with ERα-negative (ERα-) tumors and are more likely to respond to hormone-based therapies. About one-half of ERα+ tumors are described to be also PRpositive (PR+), and nearly 75% of these hormone responsive tumors (ERα+/PR+) respond positively to endocrine therapy [7]. Hence, knowledge of ERα and PR expression can help to identify the patients that may benefit from endocrine therapy. MARCH 2013

D I

The need for better and more selective probes to non-invasively assess steroid receptor expression in hormone-responsive tumors has encouraged the synthesis and the biological evaluation of several steroid derivatives labelled with positron emitters for ER PET imaging. However, few of them have actually reached the clinical stage [9-11]. Among the radiofluorinated tracers developed for ER PET imaging up till now, the most promising is the estrogen-based 18 F-fluoroestradiol (18F-FES). 18F-FES is relatively easily synthesized [12], has a high specific activity, a high ER binding affinity, a good radiolytic stability and a good chemical stability in vivo. Moreover, it has been shown to exhibit high specific uptake by ERα-rich target tissues and ERα+ mammary tumors in small animal models [13,14]. In addition the potential of 18 F-FES PET to visualize primary breast tumors and distant metastases has been clearly demonstrated in breast cancer patients. Here, a high correlation was found between18F-FES accumulation and ER expression in the tumors, as determined by well-known standard immunohistochemical and receptor assays [15,16]. It has been noted that this can be especially valuable when evaluating patients with recurrent disease. ER PET imaging with 18F-FES can predict the response to hormonal therapy and may help guide treatment selection [17]. For patients with locally or advanced disease, high 18F-FES uptake before primary tamoxifen therapy has been shown to predict a positive response to hormonal therapy [18,19]. Low or absent ER expression in the tumor indicates a very low likelihood of response. [18F]FES is sensitive to image ERα+ tumors with a radiation burden within the normal ranges of other clinical medicinal procedures [20] and complements the information given by [18F]FDG to assess or predict the response of the cancer cells to therapy [15,18]. [18F]FES is currently in phase II of a study on the prediction of response to first line hormone therapy in women with ERα+ metastatic breast cancer [9]. However because 18F-FES is prone to rapid metabolization in the blood, the analogous 4-fluoro-11β-methoxy-16α[18F] fluoroestradiol (4-FMFES) has been synthesized with the fluoro substituent at the 4 ring position to resist metabolic activation, and with a methoxy group at position 11 to reduce non specific binding [21]. The concomitant introduction of a 4-F- and an 11β-methoxy group improves the contrast between target and non-target tissue in small animal models [22] and healthy women [23]. In a Phase II clinical trial, carried out in women with newly diagnosed ERα+ breast cancer before surgery or chemotherapy, 4-FMFES PET imaging showed a higher contrast between the primary lesions and background than 18F-FES PET imaging, demonstrating its

E U R O P E

71


Molecular imaging superior ability to detect ERα+ breast cancer [10]. Hormone-sensitive breast cancer, which occurs more commonly in postmenopausal women and is characterized by longer disease-free and overall survival rates, is less aggressive than the hormone-resistant disease. The presence of PR increases the likelihood of hormone responsiveness, while PR- tumors are less responsive to therapy. This suggests the potential value of non-invasive detection and quantification of PR+ or PR- lesions for an adequate therapeutic outcome. Although they have been studied neither as intensively as ER ligands nor for such a long time, some PR imaging agents, despite showing favorable biological behavior in vitro and in animal models [24], have given disappointing results in humans [25]. The reason for this divergence may be the low PR affinity of the ligands, together with their high metabolic liability and high lipophilicity, which results in high non-receptor binding. Of the various molecules, the progesterone analog 18F-FFNP appears to be the most promising PR imaging agent to date, with high PR binding affinity and moderate lipophilicity. In small animal models, the compound shows highly selective target tissue uptake and high metabolic stability. These findings have encouraged a first-in-human study that was designed to evaluate the safety and dosimetry of 18F-FFNP as well as the feasibility of imaging tumor PRs by PET in breast cancer [11]. 18F-FFNP has been demonstrated to be a safe PET imaging agent, with organ and total-body radiation doses comparable to those from 18F-FES and other commonly used clinical radiopharmaceuticals. 18F-FFNP PET can be used to assess the PR status of individual breast cancer lesions, determining whether antiestrogen therapy is appropriate before initiation of therapy or after first- or second-line endocrine therapy. CONCLUDING REMARKS

PET imaging is a clear advance in the approach to staging and monitoring breast cancer, offering higher accuracy than conventional imaging in the identification of metastases, both in the initial staging and in follow-up of the disease. Thus, while evaluation 72

of ER or PR levels in human breast tumors is currently obtained in vitro by immunohistochemical assays, there is active interest in developing methods to determine these levels by in vivo PET imaging, which can potentially assess receptor densities at all tumor sites, simultaneously and non-invasively. Such data could be used to select patients who are most likely to benefit from endocrine therapies, thereby sparing some the morbidity of radiation and chemotherapy. Forthcoming refinements in scanner technology and development of novel radiopharmaceuticals will probably result in better detection of smaller lesions. Dedicated breast PET/CT or PET/mammography units show promise in improved detection in primary breast cancer, while also providing a method for image guided biopsy. Current research on the molecular basis of cancer will likely provide new agents that may better identify tumors that are not well imaged by 18F-FDG. Alternatively, these agents can be used alongside 18F-FDG [17]. Also, the recent use of a combination of radiopharmaceuticals, such as 18 F-FES and 18F-FFNP [26] for better, more comprehensive profiling of ERα+/ PR+ tumors may gain traction. In conclusion, taken together, the studies described to date indicate that radiolabelled estradiol derivatives are suitable tracers to determine the ER status in breast cancer patients. A variety of ER imaging agents have been and continue to be developed and tested, and clinical PET imaging of ER in breast cancer using 18F-FES is quite advanced. An advantage of 18F-FES over previously developed iodinated tracers is that it allows a quantitative measurement of ER density and occupancy, which may be useful for therapy evaluation and drug development. It should be noted that, thus far, only limited progress has been made with PET imaging of PR. REFERENCES 1) Siegel R, Ward EO, Jemal A. Cancer statistics. CA Cancer J Clin 2011; 61: 212-236 2) Horwitz KB, McGuire WL. Estrogen control of progesterone receptor in human breast cancer. J Biol Chem 1978; 253; 2223-2228 3) Howell A, Harland RNL, Barnes DM, et al. Endocrine therapy for advanced carcinoma of the breast: relationship between the effect of tamoxifen upon concentrations of progesterone receptor and subsequent response to treatment. Cancer Res 1987;47: 300-304 4) Horwitz KB. The structure and function of progesterone receptors in breast cancer. J Steroid Biochem 1987: 27: 447-457

D I

E U R O P E

5) Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: Prognosis and prediction. Endocr Relat Cancer. 2010; 17: R245–R262 6) McGuire WL. Current status of estrogen receptors in human breast cancer. Cancer 1975; 36:638-644 7) McGuire WL, Horwitz KB, Pearson OH et al. Current status of estrogen and progesterone receptors in breast cancer. Cancer 1977; 39: 2934-2947 8) Edwards DP, Chamness GC, McGuire WL. Estrogen and progesterone receptor proteins in breast cancer. Biochim Biophys Acta 1979; 560: 457 – 486 9) ClinicalTrials.gov. NCT00602043: F-18 16 Alpha-FluoroestradiolLabeled Positron Emission Tomography in Predicting Response to First-Line HormoneTherapy in Patients With Stage IV Breast Cancer. http://clinicaltrials.gov/ct2/show/NCT00602043 (Accessed February 14, 2013). 10) Turcotte E, Paquette M, Lavallée E et al. Comparison of 4FMFESPET with FES-PET in a phase II trial to detect estrogen receptorpositive breast cancer: Preliminary results. J Nucl Med 2012; 53: (Supplement 1):281 11) Dehdashti F, Laforest R, Gao F et al. Assessment of Progesterone Receptors in Breast Carcinoma by PET with 21-18F-Fluoro-16a,17a[(R)-(19-a-furylmethylidene)Dioxy]-19-Norpregn-4-Ene-3,20-Dione. J Nucl Med 2012; 53:363-370 12) Kumar P, Mercer J, Doerkson C et al. Clinical production, stability studies and PET imaging with 16a-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients. J Pharm Pharm Sci 2007; 10: 256s – 265s. 13) Kiesewetter DO, Kilbourn MR, Landvatter SW et al. Preparation of four fluorine-18-labeled estrogens and their selective uptakes in target tissues of immature rats. J Nucl Med 1984; 25: 1212-1221 14) Aliaga A, Rousseau J, Ouellette R et al. Breast cancer models to study the expression of estrogen receptors with small animal PET imaging. Nucl Med Biol 2004; 31: 761–770 15) Dehdashti F, Mortimer JE, Siegel BA et al. Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays. J Nucl Med 1995; 36: 1766-1774 16) Peterson LM, Mankoff DA, Lawton T et al. Quantitative Imaging of Estrogen Receptor Expression in Breast Cancer with PET and 18F-Fluoroestradiol. J Nucl Med 2008; 49:367–374 17) Dehdashti F, Mortimer JE, Trinkhaus K et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat 2009; 113: 509 – 517 18) Mortimer JE, Dehdashti F, Siegel, BA et al. Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose and 16alpha[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy. Clin Cancer Res 1996; 2: 933-939 19) Linden HM, Stekhova SA, Link JM et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol 2006; 24: 2793-2799 20) Mankoff DA, Peterson LM, Tewson TJ et al. [18F]Fluoroestradiol Radiation Dosimetry in Human PET Studies. J. Nucl. Med., 2001; 42, 679–684.21) Seimbille Y, Rousseau J, Benard F et al. 18F-labeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptorbinding radiopharmaceuticals Steroids 2002; 67: 765-775.22) Bénard F, Ahmed N, Beauregard JM et al. Biodistribution of fluorinated estradiol derivatives in ER + tumour-bearing mice: impact of substituents, formulation and specific activity. Eur J Nucl Med Mol Imaging 2008; 35: 1473-1479 23) Beauregard JM, Croteau E, Ahmed N et al. Assessment of human biodistribution and dosimetry of 4-fluoro-11β-methoxy-16α-18Ffluoroestradiol using serial whole-body PET/CT. J Nucl Med 2009; 50: 100-107 24) Pomper MG, Katzenellenbogen JA, Welch MJ et al. 21-[18FlFluoro16α-ethyl-19-norprogesterone: Synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography. J Med Chem 1988; 31: 1360-1363 25) Dedashti F, McGuire AM, VanBrocklin HF et al. Assessment of 21-[18Flfluoro-16α-ethyl-19-norprogesterone as a positron-emitting radiopharmaceutical for the detection of progestin receptors in human breast carcinomas. J Nucl Med 1991; 32: 1532-1537 26) Fowler AM, Chan SR, Sharp TL et al. Small animal PET of steroid hormone receptors predicts tumor response to endocrine therapy using a preclinical model of breast cancer. J Nucl Med 2012; 53: 1119-1126

MARCH 2013


TE C H N OLOGY update Research progress on phase-contrast technology for enhanced X-ray images – using existing equipment

The Paul Scherrer Institute in Switzerland.

Scientists from the Paul Scherrer Institute in Switzerland together with researchers from Philips, have developed a new way of significantly enhancing contrast in X-ray images using existing (low-brilliance) X-ray source equipment at standard patient radiation doses. The technology has the potential to visualize structures in, for example, breast tissue, which are difficult to see in standard mammography images. Conventional X-ray imaging produces clear images of certain materials, such as bone tissue, which strongly absorbs the X-rays. However, it is less effective in generating contrasts of different types of soft tissue. Although it is possible to improve the quality of images by using higher doses of X-rays, such high doses are of course potentially more harmful for the patient. As well as being absorbed (which is the basis of standard X-ray images), X-rays are also deflected by tiny amounts (known a refraction) as they pass through the body. The amount of deflection depends on the type of tissue they pass through. In addition X-rays are ‘scattered’ as they pass through the body. The new technique measures the deflection and scattering of the X-rays as they pass through the body. Using advanced imaging processing techniques, this information can be merged with the standard absorption image to create an enhanced, sharper image. By adding three gratings to a standard X-ray imaging device, it is possible to detect X-ray refraction and scattering as well as absorption (which is used in standard X-ray imaging). The first grating, placed near the X-ray source, ensures that the X-rays

MARCH 2013

are aligned. This alignment is lost due to refraction and scattering as the X-rays pass through the body. The second grating and third gratings, placed in front of the X-ray detector, create a so-called ‘interference pattern’ which enables the loss of alignment of the X-rays to be measured, and the refraction and scattering to be derived. Preliminary investigations on five mastectomy samples using the new phase contrast imaging technology have shown an enhancement of general image quality in terms of richness of detail. Contrast and detail in soft tissue, which is typically low in absorption X-ray seemed to be improved. Furthermore, increased visibility of fine image structures was possible. Such structures include ‘micro-calcifications’, early signs of breast cancer, and spiculae, i.e. fine extensions of certain breast tumors spreading into healthy tissue. The new technology is expected to be highly cost-effective, because of its compatibility with conventional X-ray sources, and detection equipment. The technique is currently undergoing laboratory testing on human tissue. More concretely, human mastectomy breasts samples from over 30 patients in Switzerland are being scanned using conventional mammography and phasecontrast mammography. They are then submitted to an international team of radiologists for evaluation. Preliminary results look promising for both screening and diagnostic mammography. If further investigations support the initial findings, steps towards developing a human mammographic prototype scanner may be considered. In combination with Philips’ MicroDose spectral photon-counting mammography solution, the technology has the potential to set the standard for image quality in future digital mammography systems. Philips Eindhoven, The Netherlands www.philips.com

D I

E U R O P E

Workstation desk with 270° Leg Space

The GFS company has been producing efficient workplace solutions and appliances for the medical sector for over 50 years, both as individual items and in large-scale production series. Medical diagnostic facilities throughout the world are now equipped by the company. Among the well-established products with high reputation that the company produces for the medical profession are the Planilux, S-Cape and Eltrono systems. The company’s latest product, the Saltego, is an design optimized “Functional desk”which is a perfect ergonomic combination of technology, design and functionality. All technical features are designed in such a way that flexible working is guaranteed – virtually on all sides and at individually adjustable heights. The desktop’s tilting function accommodates the needs of all those who have rediscovered the advantage of working while standing. Anyone who spends hours working at a desk every day knows how good it is to have maximum freedom of movement at the workplace. The new product makes this possible: leg space and individually adjustable desk heights turn the workplace into an extremely ergonomic, user-friendly place. The desktop’s continuous tilt function from 0 to 15 degrees allows postural variation and thus reduces pressure and stress. The continuously height-adjustable desktop appears to float freely but is in fact supported by a decentralised lifting column. Inside the column, a hydraulic system noiselessly moves even when laden with the heaviest of weights on the desk, such as monitors, files, material samples, etc. GFS, Warstein, Germany www.gfs-warstein.com 73


2013 Euroson 2013 bstracts Call foarvaA ilable on

37. Dreiländertreffen der DEGUM • SGUM • ÖGUM

is .org schall2013 ra lt u . w w w 013 15 April, 2 Deadline:

on Registraati ble on

il is also ava .org schall2013 www.ultra

25th Congress of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB)

Science and Education October 9 – 12, 2013 International Congress Center Stuttgart (ICS), Germany

Bilder / Photos: © fotolia.de

Congress Presidents Andreas Schuler, DEGUM | Fabio Piscaglia, EFSUMB Email: ultraschall2013@helfenstein-klinik.de

www.ultraschall2013.org | www.euroson2013.org


TECHNOLOGY update Flat panel detector now available in the mid-range price segment

Siemens has introduced a new system for the mid-range price segment that can do both full-digital fluoroscopy and radiography. With this 2-in-1 functionality, the new Luminos Fusion with flat panel detector technology allows more effective use of fluoroscopy equipment in routine medical care. The flat panel detector enables faster treatment and patient throughput compared to the mid-range image intensifiers

Web-based advanced PACS

Specializing in software for radiology including teleradiology and PACS products, Voyager Imaging is an Australian-based pioneering medical imaging company. With thousands of users throughout Australia in government and private radiology practices, the company’s products are now being represented throughout international markets by distribution partners in USA, Europe, Africa and the Middle East. The company’s products are used by radiologists, radiographers, sonographers, clinical and medical professionals to provide radiology image acquisition, storage, transmission, reporting and reviewing functions for hospitals and clinics. Product groups include RIS, teleradiology, diagnostic workstations and PACS, supported with options such as integration of 3rd party applications and information systems, DICOM modality worklist and automated CD/DVD burning. Other features are pre-emptive loading of images for fast loading for radiologist lossless images, as well as smart imaging streaming technology for fast delivery of images to referrers thus ensuring fast delivery and display of images for key users connected to the Voyager PACS network. Historically, large scale PACS applications based on legacy technology have been expensive to purchase,

MARCH 2013

that have been available up to now. and which meant a time-consuming process. Taking an X-ray has traditionally meant inserting, removing, and replacing film cartridges. And since the cartridges have to be developed in a laboratory process, patients have to wait longer for results. The Luminos Fusion system with flat panel detector technology is different. Its 43 x 43 cm image surface provides fulldigital, distortion-free X-ray and fluoroscopic images within seconds so that with

implement and maintain. Recent technological developments have enabled a new approach which is providing a new and exciting range of products that provide a vastly more cost effective, scalable and specific set of tools designed to enhance the working methods. Based on these principles, the Voyager PACS is a fully scalable and secure web-based advanced PACS and teleradiology solution that provides image distribution to authorized medical staff via the Internet, Intranets, ISDN and Dial- up. The system uses the company’s proprietary client — the world’s thinnest — to provide users with an almost instantaneous gateway to capture, archive and distribute radiology images via a web interface. Mobile device applications have been released that allow iPad and iPhone users to access their patient reports and images. This application is intuitive and easy to use, and allows fast access and viewing of images and reports. Mac users are supported with its native Mac application for Voyager. The software allows users the option of fully functional tool sets in a native Mac environment, incorporating key features such as preemptive downloading and image streaming functions for fast loading of images for remote users. The company also provides a comprehensive suite of radiology information system (RIS) products for radiology practices and departments.

Voyager Imaging East Hawthorn, Vic, Australia www.intellirad.com.au/

D I

E U R O P E

accelerated treatment, patient throughput can be increased. The higher quality images generated by the flat panel detector give radiologists a better diagnostic foundation than traditional film-based images.. The flat panel detector also takes up less space than image intensifiers and makes it easier for medical personnel to approach the patient Since fluoroscopy patients typically need to fast before an examination employing contrast agents, for example, appointments are generally scheduled in the morning. A 2-in-1 system like Luminos Fusion is available in the afternoon for X-ray imaging, so the equipment can be utilized at greater capacity. Siemens Erlangen, Germany www.medical.siemens.com

Dose monitoring system

Designed to increase patient safety and support efforts to achieve lower patient dose, the RaySafe S1 system is a c l ou d - b a s e d application that collects, add value and share radiology information to different individuals in the diagnostic radiology process. These include referring physicians, radiologists, operators, medical physicists, Radiation Safety Officers (RSO) and medical engineers. Furthermore, the new system gives managers additional insight about the utilization of the radiology department, and support efforts to increase its productivity. The cloud-based solution is prepared for integration in a multi-modality environment within diagnostic radiology, with equipment from different X-ray manufacturers that support the DICOM standard. Raysafe Billdal, Sweden www.raysafe.com 75


TECHNOLOGY update LED Back-lit monitors

EIZO have extended their range of monitors with the launch of the RadiForce GX540, a new 5 megapixel monochrome LCD monitor, and the RadiForce RX440, a new 4 megapixel colour LCD monitor. With the addition of these two models, the company’s RadiForce diagnostic monitor line-up now all come with LED backlights. This technology ensures the stable and reliable performance that is needed in diagnostic monitors while increasing the service life since LEDs deteriorate far slower than traditional CCFL (cold cathode fluorescent lamp) backlights. The new monitors have a 5 year full warranty or 20,000 hours when used at recommended brightness. With the energy-efficient LED backlights, the monitors can thus achieve a reduction in power consumption of approximately 25% compared to the same size monitor with a conventional CCFL backlight. Both monitors include EIZO’s unique Hybrid Gamma

function which automatically distinguishes whether the displayed images are monochrome or color and displays each image in its ideal brightness and grayscale tones. This expands the usability of PACS applications by ensuring that various medical images are optimally displayed simultaneously. An Integrated Front Sensor (IFS) housed within the front bezel measures brightness and grayscale tones and calibrates to the DICOM Part 14 standard. This dramatically cuts monitor quality control workload and maintenance costs Eizo Ishikawa, Japan www.eizo.com/

Radiation dose monitor

Sectra DoseTrack is a complete solution that allows monitoring of patient radiation doses and ensure that they are kept as low as reasonably achievable. By gathering and comparing radiation dose values from radiology examinations already performed, the system provides documentation that helps reduce radiation doses without impacting diagnostic quality. The system automatically collects, stores and monitors the data, which saves valuable time and eliminates the risk of human error in the collection process. The system also enables monitoring of equipment to detect whether an X- ray device is in danger of exposing patients to too much radiation, or to follow up on individual patients to avoid excessive radiation.

76

D I

Sectra DoseTrack allows monitoring of trends for cumulative dose, perform radiation dose benchmarking within or between sites. In addition the system allows database search by patient, modality and examination code, facilitates reporting to regulatory authorities and provides dose notifications. The system supports both the IHE Radiation Exposure Monitoring profile and the DICOM MPPS standard, enabling the connection of almost any modality to gain a complete dose monitoring solution. The system also facilitates benchmarking dose reference levels (DRL) between several healthcare facilities to ensure that policies, procedures and protocols are adequate and being followed to achieve doses as low as possible. SECtra Linkjoping, Sweden www.sectra.com

Smaller format DR detector

Carestream is extending its presence in the wireless digital radiography market with the introduction of the smaller-format 25 cm x 30 cm DRX 2530C Detector (work in progress). The new cesium iodide detector is designed to offer high efficiency for dose sensitive pediatric, orthopedic and general radiology exams. The smaller detector is designed to fit into pediatric incubator trays and offer higher detective quantum efficiency (DQE), which can lead to lower dose requirements than CR cassettes or gadolinium scintillator detectors. The new detector is intended to be used with the company’s DRX-Revolution or Mobile Retrofit Kits for mobile imaging of neonatal or pediatric patients. In orthopedic and general radiology imaging, the smaller detector is designed to aid in positioning for

E U R O P E

MARCH 2013


TECHNOLOGY update tabletop exams such as knee, elbow, skull and other exams that require a patient to hold the detector or requires a smaller field of view. The company is also introducing a new non-motorized option for the DRX-Evolution, a versatile DR system with modular components to meet space, workflow and budget requirements. The new DRX-Evolution Standard-Q offers efficient upgrade to DR capability at an affordable cost. The ergonomically designed wall stand makes standing exams easier with its extensive vertical travel range. In addition, the extra-wide Standard-Q elevating float-top table lowers easily to accommodate stretcher. Carestream Rochester, NY, USA www.carestream.com

Medical displays

The Sony LMD-DM series of high-luminance and highcontrast medical displays offer crystal clear images for critical diagnoses. The monitors are ideal for general diagnosis in mammography, CR/DR, CT, MRI and of course PACS workstations. With improved standards of accuracy, these diagnostic displays reaffirm the commitment Sony is making to the medical industry. The range includes a 5MP diagnostic display; 3MP & 2Mp grayscale displays and a 3MP& 2MP Color displays. Driven by feedback from clinicians for higher quality

and more detailed images, the three and five megapixel monochrome diagnostic displays feature Independent Sub-pixel Drive* technology that is capable of producing three times the resolution of conventional monochrome liquid crystal displays (LCDs). As a result, these displays are ideal for diagnostic studies such as Full Field Digital Mammography (FFDM) where detailed viewing of micro-calcifications is paramount. Each LMD-DM Series display is equipped with an in-built luminance sensor, an ambient light sensor and a luminance control circuit. This enables the display to be optimised depending on the environment the radiology user is working in and the images being displayed. The displays can also be used in portrait and landscape modes and are fully DICOM GSDF compliant. Sony, Tokyo, Japan www.pro.sony.eu/medical.

New Development Gerätebau Felix Schulte.

Visit us at ECR 2013 / Expo E, booth 544

• State-of-the-art workplace for your digital image reading.

• Full flexibility in both sitting and standing positions.

• 270° leg space.

• Individual choice of features and functions.

• Ergonomic and motorized height adjustability.

• Durable and low-maintenance materials.

Gerätebau Felix Schulte info@gfs-warstein.com | www.gfs-warstein.com

MARCH 2013

D I

E U R O P E

77


TECHNOLOGY update Facilitating dose profile measurement

RTI Electronics has introduced the Mover, a computercontroller motorized support for dose profilers that promises to greatly improve the accuracy and speed of test set-up when characterizing the radiation output of any cone beam CT scanner. The new system is designed to overcome the practical and physical challenges encountered by CT technicians when carrying out dosimetry measurements on modern scanners. Many of the latest CT scanners feature wide beam widths that enable patients to be X-rayed in just one rotation, precluding the need to move the patient table – a prerequisite when making CT Dose Index (CTDI) measurements using a point dose detector. In addition, some scanners used for intraoperative analysis do not have an integrated patient table. The Mover provides support for the dose profiler when there is no patient table on which to rest the measurement device and pushes or pulls it through the x-ray field at a constant speed. Crucially, it provides an accurate and easily reproducible way for CT technicians to align the probe in isocentre, potentially providing much faster measurement set-up and a more accurate outcome. Orientation of the Mover can be performed manually or through software. Used in conjunction with RTI’s CT Dose Profiler, software can control both the CT Dose Profiler and the Mover, as well as save data and produce reports on all necessary dose profile parameters, including the true thickness of the beam. In this way, RTI provides a complete solution for making dose profile measurements of any length. The Mover consists of a dose detector holder with a clamp and flexible ball joint that enables easy orientation in horizontal or vertical positions. Optimized for use with the CT Dose Profiler - though it can be used with most dosimeter probes - the Mover has a range of accessories that simplifies set-up for different applications such as Dental Cone Beam CT and general CT scanners, free in air or in phantom measurements. RTI Electronics Mölndal, Sweden www.rti.se

Multifunctional R/F system

The latest product to be introduced by Shimadzu is the Sonialvision G4 R/F system, which in both functionality and operability, table out-performs other R/F systems. Equipped with the largest available FPD at 43 x 43 cm and Shimadzu’s next generation digital imaging platform, the Sonialvision G4 covers the widest possible range of exami-nations, providing inter-departmental hospital capability. Combined with the large longitudinal stroke

78

D I

of Sonialvision, the FPD’s provides an extensive imaging area. In addition, advanced “SUREengine” technology (Shimadzu Ultimate Realtime Enhancement Engine) provides excellent image quality. It enables the natural enhancement of the en-tire image for clearer revealment of all examination areas and small, faint targets. The company’s premium application software offers the most recent improvements for diagnostic imaging including the sup-port of useful applications, such as tomosynthesis for general radio-graphic imaging. This function has also been highly acclaimed in the orthopedic field. In addition many medical personnel are very inter-ested in the further reduction of peripheral metal artifacts in tomosyn-thesis total hip arthroplasty (THA) and total knee arthroplasty (TKA) images.. Slot scanning which needs just the start and end positions to be set is also very useful for long-length image examination in the orthopedic field.. Images can be checked immediately after radiog-raphy has been completed, thereby reducing examination time while improving efficiency. Shimadzu, Duisburg, Germany www.shimadzu.eu

PACS enhancements

Novarad has introduced new radiology technologies into its Diagnostic Suite, which now includes more than a dozen modular radiology technologies that run as either standalone products, or combined into a facility-customized system. The products and product enhancements include: virtual colonoscopy with 3D, multi-frame views, ‘hands-free’ fly through control displaying six simultaneous views, auto zoom and focus on the endoscopic location. For cardiologists, enhancements include vessel finding, cross section and curved MPR vessel view. Screen shot captures are automatically saved to the PACS. Novarad, American Fork, UT, USA www.novarad.net

E U R O P E

MARCH 2013



There’s only

NE.

Only ONE system has proven clinical results, widespread global acceptance and industry accolades – and now with the first ever upright breast tomosynthesis biopsy. Selenia® Dimensions® breast tomosynthesis from Hologic. The Selenia Dimensions system is the only ONE: That features an upright breast biopsy solution for tomosynthesis in addition to traditional stereotactic procedures. That when combined with digital mammography, has been shown to increase cancer detection by 27% and increase invasive cancer detection by 40%. 1 That had a 15% reduction in pre-arbitration false positive rates in a major European study when using 3D mammography plus 2D digital mammography compared to using 2D alone.1 That has over sixty citations in trade publications, abstracts and scientific presentations. For references and additional information e-mail us at tomoinfo@hologic.com.

1

Please visit the Hologic stand #316 at ECR to learn more and don’t miss the ECR Hologic Symposium on Saturday, March 9th 2013 | 14:00 - 15:30 | Room C Hologic Europe www.hologic.com Tel: +32.2.711.4680

© Copyright Hologic 2013 Hologic, Dimensions, Selenia and associated logos are trademarks of Hologic, Inc. and/or its subsidiaries in other countries. This information is intended for medical professionals and is not intended as a product solicitation or promotion where such activities are prohibited. Because Hologic materials are distributed through websites, eBroadcasts and tradeshows, it is not always possible to control where such materials appear. For specific information on what products are available for sale in a particular country, please contact your local Hologic representative or write to womenshealth@hologic.com.


Turn static files into dynamic content formats.

Create a flipbook
Issuu converts static files into: digital portfolios, online yearbooks, online catalogs, digital photo albums and more. Sign up and create your flipbook.