JBR 2010-2 by office

WETTEREN 1

P 702083

Volume 93 Page 45-116 March-April

Bimonthly

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2010

DIAGNOSTIC AND INTERVENTIONAL IMAGING, RELATED IMAGING SCIENCES, AND CONTINUING EDUCATION

ORGANE DE LA SOCIETE ROYALE BELGE DE RADIOLOGIE (SRBR) ORGAAN VAN DE KONINKLIJKE BELGISCHE VERENIGING VOOR RADIOLOGIE (KBVR)

JBR-BTR ♦ 93/2 ♦ 2010 Journal Belge de ♦ Belgisch Tijdschrift voor ♦ RADIOLOGIE

Founded in 1907 A bimonthly journal devoted to diagnostic and interventional imaging, related imaging sciences, and continuing education Contents Imaging of traumatic and non-traumatic emergencies. One approach. S.M. Goldman, L. Wagner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cystic lesions of the female reproductive system. A review. M. Dujardin, A. Schiettecatte, D. Verdries, J. de Mey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical and imaging tools in the early diagnosis of prostate cancer, a review. P. De Visschere, W. Oosterlinck, G. De Meerleer, G. Villeirs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Staging of lung cancer. Do we need a diagnostic CT of the brain after an integrated PET/CT for the detection of brain metastases ? W. De Wever, E. Bruyeer, Ph. Demaerel, G. Wilms, J. Coolen, J. Verschakelen . . . . . . . . . . . . . . . . . . . . . . . . . . Longitudinal cortical split sign as a potential diagnostic feature for cortical osteitis. V. Goosens, F.M. Vanhoenacker, I. Samson, P. Brys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Brodies’s abscess revisited. P.R. Kornaat, M. Camerlinck, F.M. Vanhoenacker, G. De Praeter, H.M. Kroon . . . . . . . . . . . . . . . . . . . . . . . . . . . . Evaluation of peri-tumoral vessels surrounding colorectal liver letastases after intravenous injection of extruded magnetliposomes in rats: correlation with 3T MRI and histopathology. K. Coenegrachts, J. van Werven, L. ter Beek, Z. Mzallassi, M. Bögels, Th. Van Gulik, I. Van Den Berghe, A. Nederveen, J. Stoker, H. Rigauts, St. Soenen, M. De Cuyper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

45 56 62 71 77 81

SPECIAL ARTICLE The capital cost and productivity of MRI in a Belgian setting. C. Obyn, I. Cleemput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CONTINUING EDUCATION MRI spectrum of medial collateral ligament injuries and pitfalls in diagnosis. M. De Maeseneer, M. Shahabpour, C. Pouders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

IMAGES IN CLINICAL RADIOLOGY Arachnoid Pacchioni’s granulation bulging in a transverse sinus of the brain. F.C. Deprez, D. Hernalsteen, P. Bosschaert . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendicular endometriosis mimicking appendicitis. F. Claus, D. Vanbeckevoort, G. De Hertogh, V. Vandecaveye, Ph. Koninckx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Closed loop small bowel occlusion through a congenital defect of the greater omentum. B. Coulier, B. Vander Elst, F. Pierard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute osteomyelitis. M.I. Wessels, M. Baeyaert, J.L. Termote, F.M. Vanhoenacker, A.M. De Schepper, P.M. Parizel . . . . . . . . . . . . . . . Arachnoiditis ossificans. Ph. Bernard, F.M. Vanhoenacker, N. Adam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Fallen fragment sign. J. Van Doninck, F.M. Vanhoenacker,,C. Petré, D. Willemen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treats from the heart. B.J. Emmer, M. Reijnierse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Calcific myonecrosis. J. Peeters, F.M. Vanhoenacker, M. Camerlonck, P.M. Parizel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . An unusual cause of pleuritic chest pain on a CT pulmonary angiogram. J. O’Brien, S. Barrett, W. Torreeggiani . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Intracardiac defect demonstrated by cardiac CTA. O. Ghekiere, J. Djekic, A. Nchimi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendicular diverticulitis in an Amyand’s hernia. B. Coulier, F. Pierard, S. Malbecq . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

104 105 106 107 108 109 110 111 112 113 114

News from the Universities: Prijs Pr Dr Em A.L. Baert 2009-2010 – Algemeen Reglement . . . . . . . . . . . . . . . . . . 103 Forthcoming courses and meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 News from the Museum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiv, xv Instructions to Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ii Subscribers information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . cii Advertising index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ciii The terms used for indexation of subjects were developed by the Radiological Society of North America (RSNA) over a period of years. Their use here is by permission of the RSNA. The terms may not be used in any other index, print or electronic, except by specific permission of RSNA. ◆◆ Indexed in Index Medicus and in Zentralblatt Radiologie. Evaluated for Medline User, EMBASE and CANCERNET. Abstracted in Excerpta Medica Journals. ◆

JBR–BTR, 2010, 93: 45-55.

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES – ONE APPROACH* S.M. Goldman, L.K. Wagner1 Selection and design of the most appropriate imaging studies during an emergency involving pregnant and/or potentially pregnant female has been the topic of numerous recent articles. While radiation dose must be limited to the necessary amount, a cautious application must never be so severe as to compromise the ability to make the correct diagnosis. No one approach suits all facilities or all circumstances. All approaches need to be institution specific, and may be country or continent dependent. In this article we review our approach to this scenario. Key-words: Pregnancy, irradiation in – Trauma.

The fear of radiation in the human population is deep seated and dates back at least as far as the start of the nuclear arms race. It was even present shortly after the discovery of Roentgen’s mysterious X-rays (1). In medicine, the goal is to use radiation wisely and in limited quantities while not permitting unwarranted fear to compromise medical need. The benefits of any study must appropriately exceed the risks and application of diagnostic radiation and must not be so attenuated as to constrain one’s ability to obtain diagnostic information. On the other hand, numerous papers have been published by radiologists and physicists, in the recent few years that have advocated legitimate ways of decreasing patient exposure (2-7). Other articles focus primarily on risks by applying risk factors to large populations with only casual reference to the benefits that that radiation represents to the population (8). In 2009 a US government appointed commission recommended a significant decrease in the number of mammograms performed in the female population, contrary to evidence that suggests that the present recommendations are working to reduce breast cancer mortality (9). This was preceded by a report from the NCRP that medical radiation exposure has increased by a factor of about 6 since 1980 (10); primarily due to increases in the use of CT and cardiological nuclear medicine. While useful information, the media focused on this as a negative change rather than addressing the issues of the benefits that this brought in terms of better management of heart disease or better cancer diagnosis or

improved surgical management of patients, etc. In this article we review our approach to imaging pregnant females in emergency situations. Our management plan is divided into Traumatic and Non-traumatic emergencies. Relative basic science The effects of radiation on human concepti are based on extensive animal studies as well as exposures of the Japanese population to atomic bomb radiation, individuals who had therapeutic radiation for varying forms of pelvic cancer in the female population, radiation accidents from situations like Chernobyl, radiation from pelvimetry, a wide range of diagnostic imaging doses in various situations worldwide, etc. (11). Radiation effects are typically categorized into two types: deterministic and stochastic. Deterministic effects are caused by an accumulation of radiation damage and a minimum level of radiation absorbed dose is required before these types of effects can occur. Once radiation absorbed dose exceeds the required threshold, the likelihood of the event occurring increases with additional dose as does the potential severity of the effect. Radiation-induced malformation in a developing conceptus is a deterministic effect. Stochastic effects can be caused by subcellular changes in a single cell. For example, changes in a critical macromolecular structure caused by a collision with an ionizing particle might convert a normal cell into a cancerous cell. These changes in cells occur as a result of random damage within

From: 1. Department of Radiology, The University of Texas-Houston Medical School. Address for correspondence: Pr S.M. Goldman, Department of Radiology, The University of Texas-Houston Medical School, Houston, USA. E-mail: Catherine.M.Yarborough@uth.tmc.edu * Paper presented at the Annual Symposium of RBRS on November 14, 2009.

the cell. Theoretically, any level of radiation exposure might result in such a critical change, but the likelihood is extremely small. Most such subcellular damage is corrected without consequence by cellular repair mechanisms. Accumulation of more exposure increases the number of random events, resulting in an increased likelihood of converting a normal cell into a neoplastic tissue. For these effects, the only protection is to keep exposure to radiation as low as reasonably possible. Benefits versus risks in imaging the pregnant patient Table I lists estimates of effective doses for various radiological examinations along with the comparable time required to accumulate a similar amount of background radiation exposure (adapted from RSNA/ ACR website). Risk estimates are also available in other articles (12-14). Radiation exposure to the conceptus of a pregnant individual should be divided into two groups: radiation exposure outside the abdomen and radiation exposure that directly exposes the abdomen. Radiation outside the mother’s abdomen, which is of little concern to the management of the conceptus, and can be generally performed without concern in most cases. On the other hand, direct exposure to the abdomen must be seriously evaluated by the requesting physician, and especially by the participating radiologist as to its magnitude and necessity. Abdominal CT especially has potential to expose the conceptus to significant amounts of radiation. First consideration for diagnostic imaging workup must be given to modalities that use no ionizing radiation or that use only low dose radiation. However, in time-critical situations these should not be used when this will lead to a sacrifice of diagnostic accuracy. When higher

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Table I. — Effective doses for radiological examinations. For this procedure

Your effective radiation dose is*:

Comparable to natural background radiation for:

Abdominal region: Computed Tomography (CT) – Abdomen and Pelvis Computed Tomography (CT) – Body Computed Tomography (CT) – Colonography Intravenous Pyelogram (IVP) Radiography – Lower GI Tract Radiography- Upper GI Tract

10 mSV 10 mSv 10 mSv 3 mSv 8 mSv 6 mSv

3 3 3 1 3 2

Bone: Radiography – Spine Radiography – Extremity

1.5 mSv 0.001 mSv

6 months Less than 1 day

2 mSv 6 mSv 4 mSv 7 mSv 1 to 3 mSv 0.1 mSv

8 months 2 years 16 months 2 years 4 months to 1 year 10 days

5-10 yr. old: 1.6 mSv Infant: 0.8 mSv

6 months 3 months

Face and neck: Computed Tomography (CT) – Sinuses

0.6 mSv

2 months

Heart: Cardiac CT for Calcium Scoring

3 mSv

1 year

Men’s Imaging: Bone Densitometry (DEXA)

0.001 mSv

Less than 1 day

Women’s Imaging: Bone Densitometry (DEXA) Galactography Hysterosalpingography Mammography

0.001 mSv 0.7 mSv 1 mSv 0.7 mSv

Less than 1 day 3 months 4 months 3 months

Central Nervous System: Computed Tomography (CT) Computed Tomography (CT) Myelography Computed Tomography (CT) Computed Tomography (CT) Radiography – Chest

– Head – Spine – Chest – Chest Low Dose

Children’s Imaging Voiding Cystourethrogram

years years years year years years

*All CT dose estimates are for single phase studies only.

dose ionizing radiation examinations are needed, consideration should be given to having pre-determined modification to the regular study in order to reduce radiation dose to the conceptus. For example, only single phase studies of the abdomen are advised. Multi-phase CT should almost invariably be avoided. If absolutely necessary, one of the phases should be performed at much reduced technique. Use of Gadolinium (Gd) for MRI is generally discouraged, even in a patient with a normal keratinize and renal function. Gd crosses the placenta and a small amount enters the maternal milk. Although Gd has not been approved in the US, the Contrast Media Safety Committee of the European Society of Uroradiology (ESUR) has not documented any ill effects from its use (15). In considering benefit/risk for the patient, the timing of the examina-

tion with the gestation age is an important factor. The International Commission On Radiological Protection (ICRP) states, “During the first ten days following the onset of a menstrual period; there can be no risk to any conceptus, since no conception has occurred. The risk to a child who has previously been radiated in utero during the remainder of a 4 week period following the onset of menstruation, is likely to be so small that there need be no special limitation on exposures within this period” (16). The most critical period occurs during the second through fifteenth weeks postconception when detriment to the development of organ systems is a risk. Dose limitations are especially critical so that threshold doses for deterministic effects are not approached. Multiple higher dose examinations, such as multiple-phase or multiple singlephase CT studies are usually neces-

sary before these thresholds are approached. The critical threshold is typically quoted as 100 mGy to the conceptus, but doses between 50 and 100 mGy may result in subtle but clearly undesirable effects. Such doses can be reached after 2-3 single-phase CT studies, for example. Doses less that 50 mGy in this period have not been associated with deterministic effects, but stochastic effects (e.g., induced cancer) are still a concern and so dose limitation remains an important practice during this and later stages of gestation (11). Trauma in pregnancy Data resources This paper is the result of many years of work in the field by both authors. In regard to the trauma section, which will follow, one is referred to (14), which is the com-

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES — GOLDMAN et al

bined experience of the University of Texas and the University of Tennessee over a two year period. This data corroborates data from previous studies, and although informally restudied by the authors, the percentages listed under the next section are reasonably accurate, even with the number of emergency room visits in recent years. In regard to non-traumatic emergencies, our experience was derived from reviewing the emergency room trauma registry during a two year period (17). Our impressions since that study are that the percentages of emergencies based on organ systems (liver, brain, etc.) or disease processes (Crohn’s, Ulcerative Colitis, PRESS Syndrome, etc.) remain stable. Nature of the problem Multiple studies, including our own, have shown that 6-7% of all pregnant females have trauma of some consequence (13). Most of these occur in the 3rd trimester. Part of this reflects the increased instability of the mother due to weight distribution changes and hormonal imbalances that effect coagulation patterns, etc. Most of the injuries (2/3) result from falls related to the above. However, over a 1/3 of the injuries appear to be secondary to spousal or other physical abuse. Trauma is the leading cause of maternal mortality (up to 20% of deaths) (12). In a combined study, 595/275,000 patients seen in the emergency room were pregnant

(14). Ninety-two percent were seen after a motor vehicle accident, 25% during the first trimester, 25% in the second trimester, and 50% of the injuries occurred during the 3rd trimester. In our series, 48 (9.1%) had CT examinations of the chest and/or abdomen and pelvis. In regard to the maternal injuries, 19/48 had no maternal injury (40%), 31% (15/48) had non-uterine maternal injuries. Twenty-seven showed combined fetal and maternal injuries. Five mothers died (10.4%) three of which were secondary to brain injuries. The fetal death rate was 33% (11 isolated, 5 due to maternal deaths). Of the fetal deaths, 80% were under 25 weeks, and 20% over 25 weeks. Unfortunately, restraints (e.g., seat belts) of any kind did not appear to change the incidence of outcome. C-sections were performed in 4 of 48, with 3 survivors among the babies (37-39 weeks). The fourth died at 35 weeks from abruptio placenta. Basic fundamentals of trauma management in pregnancy (12-14) There is very little chance of fetal survival without maternal survival. Therefore, all initial efforts must be geared to maintaining maternal survival. As in all traumas, the first hour is the “Golden Hour of Survival”. It is critical to keep the mother alive before the arrival at the hospital. The classic A (airways) B (breathing), C (cardiac) fundamentals need to be maintained and

monitored on route. A special practice is to remember that wherever possible, the mother should be kept with her right side up to alleviate any decrease in venous return from the lower torso/legs that may result from compression of the inferior vena cava (IVC) (Fig. 1). If possible to accomplish without compromising maternal and/or fetal welfare, the patient should be ultimately transferred to a major/medical facility where all the appropriate level of care is available for mother/ baby. During transfer to the major facility, ongoing monitoring should be maintained by the primary response team and should be communicated either verbally or by telecommunication to the accepting hospital. Based on the information, an appropriate group of specialists should be assembled to manage the patient/fetus. It should be noted that the severity of trauma bears no relationship to fetal outcome. Even minor trauma can result in fetal demise. Therefore, conservative management is the true path of valor. Until it can be absolutely ascertained that there is no further chance of the deterioration of the fetus or the mother, the patient should not be discharged from the accepting hospital. This means, even in a stable patient, fetal monitoring needs to be continued for at least several hours. Upon arrival at the receiving hospital, immediate evaluation of the mother must be performed to determine if she is stable; and everything necessary to assure stability

Fig. 1. — Pregnant female in motor vehicle accident (MVA). Fetus aborted in transit. On arrival regular imaging could be performed of the pelvis, as no fetus present. A. Axial CT shows fracture of iliac wing and opening of sacroilliac joint. B. 3D reconstruction performed for possible surgical intervention.

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Fig. 2. â&#x20AC;&#x201D; 21 yr. old pregnant female (fetus 6 weeks old) in MVA. A. CT of the head shows evidence of an intraventricular bleed. Note filing with blood of the posterior horn of the ventricle. Mother stable post CT. B. Uterine U/S shows fetus to be viable on a color Doppler and on wave form images.

must be instituted immediately, if stability cannot be maintained, the patient should be immediately taken to the operating room, etc. Once the mother is stable, an ultrasound evaluation of the fetus is indicated. Evidence of fetal distress, i.e. bradycardia, tachycardia, etc., requires immediate surgical intervention to save the fetus. Based on the clinical situation, appropriate necessary imaging should be obtained to expedite management as efficiently as possi-

Fig. 3. â&#x20AC;&#x201D; 33 yr. old female (fetus 26 weeks) was stable in MVA, but aspirated. Frontal (A) and bilateral (B) views of chest showed LLL collapse. One day later patient went into premature labor. As stated, there is no relationship of the degree of injury to fetal outcome.

ble with appropriate, but necessary radiation used. In this regard, any interventional procedure should be performed by an appropriate level senior staff to exclude unnecessary radiation exposure (Fig. 2). The types of injuries to the chest, extremities, head and neck are generally no different than those seen in non-pregnant patients. For example, intrathoracic injuries include: rib fractures, pneumothorases, hydro-hemothorases, lung contusions, lung collapse, complete bronchial tear, etc.

(Fig. 3). Similarly, the etiology of neurological injuries include; skull fractures, subdural & epidural bleeds, intracerebral bleeds, intraventricular bleeds, intra & extra cord injuries, vertebral injuries, etc. (Fig. 4). The situation is much more serious in regard to abdominal injuries since the enlarged uterus is present. As the uterus expands, the pelvic structures are displaced from the abdominal pelvis into the upper abdomen. Thus, these structures are much more vulnerable to injury dur-

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES — GOLDMAN et al

Fig. 4. — 17 yr. old pregnant female (12 week fetus) in MVA. CT of neck performed as abdomen unremarkable. Study showed anterolisthesis and tilt at C2. Fetus died within 24 hours of study.

A ing later pregnancy than during the first trimester. Similarly, injuries to the spleen and liver also increase because of the increased abdominal pressure as the uterus expands. In regard to injuries outside the pelvis, all necessary imaging techniques can be used in general, without particular fear of the radiation effects to the conceptus. In a later section, we discuss exposure of the female breasts to radiation. In regard to the abdomen, ultrasound should be used first. MRI without Gd, would be ideally the second choice. However, many radiologists are not familiar with the MRI imaging characteristics of trauma in pregnancy, it usually requires obtaining the services of a MRI trained technologist at night from home, the time involved is still significantly increased compared to CT even with the faster scanning techniques and monitoring of an extremely ill patient is difficult, if not impossible, because many of the monitors are metallic. In our practice, a single pass CT is often done (Fig. 5, 6). In fact, where there is any question, a special trauma protocol of the entire patient is often necessary, especially in the non-communicative patient. This is also our approach in the multi-trauma patient. Imaging of non-traumatic emergencies in pregnancy Neurological emergencies One of the most common and serious emergent conditions is

B Fig. 5. — 20 yrs. old pregnant female (17 week fetus) in MVA. Among the findings in this case: A. Multiple splenic tears B. Collapse of a portion of the left lung.

bleeding from intracerebral aneurysms (12/21). This occurs because of fluid overload, the increased elasticity of the blood vessels and the effect of hormones on clotting factors. The diagnosis can readily be made by a contrast CT. Therapeutic intervention with coils should be doable when performed by an experienced interventional neuroradiologist (17). In recent years a whole host of peripartum neurologic disorders have been identified on MRI. These include: posterior reversible edema syndrome (PRESS), Eclamptic Encephalopathy, Postpartum Cerebral Angiography (PCA), Cerebral Brain Thrombosis (CVT) Pituitary Apoplexy, Sheehan Syndrome,

Lymphocytic Adenophypophysitis, a variety of neoplastic disorders, etc. An excellent review appeared in RadioGraphics (18). These latter entities are best diagnosed by MRI. Please again note that Gd has not been approved for pregnant patients in the US, although up to the present, no harmful effects of Gd have been reported (15). Chest abnormalities Pneumonias are probably the most common chest emergency of pregnancy. This relates to the abnormalities in hormones, immune-antibodies, etc. Abdominal shielding is a necessity, we recommend a single

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B Fig. 6. — 24 yrs. old pregnant female in MVA. A. Minor liver laceration B. Image of fetus shows poor contrast uptake of placenta. This is a poor sign for fetal viability. Fetus was ultimately aborted.

frontal projection first, and then making a decision about the necessity of taking a lateral chest. It is claimed that pulmonary emboli occur in pregnancy in a frequency of .07 - .09/1000 (1/2000 deliveries) (17). Exactly where this number comes from is unknown to the authors. PE results from the hyper-coaguable state, increased venous stasis, 50% increase in plasma volume, etc. Controversy exists as to the best and safest method of diagnosis. The advocates of the use of Tc nuclear medicine scans claim less radiation exposure and cite the problem with false positive CT scans. There are clearly institutions that have had great success using nuclear medicine. However, we are among the advocates of the use of CTA for pulmonary embolus. In our initial research (13), we could find only one positive lung scan identifi-

B Fig. 7. — Anterior cerebral artery aneurysm bleed in 27 yr. old pregnant female with twins. A. CT shows blood in ventricles and around frontal lobes. B. Carotid angiogram reveals anterior cerebral aneurysm, which was successfully occluded initially. Patient was only to rebleed one week later and become decerebrate. Mother was kept artificially alive. The twins were delivered by C-section after being felt mature enough.

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES — GOLDMAN et al

Fig. 8. — Classic case of Posterior Reversible Edema Syndrome on MRI (PRESS).

B Fig. 10. — Gallstones in pregnancy diagnosed on US: A. Gallstones seen lying along the posterior, dorsal wall of the gallbladder. B. Study shows several of the stones in the orifice.

Fig. 9. — Cardiomyopathy of pregnancy diagnosed on chest X-ray in the peripartum period. Patient ultimately recovered.

able in any of the major medical institutions in Houston, and calls to several well-known university hospitals outside Houston revealed similar results. Our experience in our affiliated institutions both during the study and to the present has been far from successful in obtaining high positivity on nuclear studies. The radiation dose to the lungs in a single pass CT is more than acceptable and will no doubt decrease in the future. One should be sure that the radiation exposure should not be

decreased as to lose diagnostic accuracy and require yet another examination. There is a concern about the radiation dose to the female breast from CT. Some have recommended the use of radiation absorbing breast shields to be used on female patients. However, technologists must be trained on their use for each machine. The shields must be placed after the positioning radiographic acquisition on some scanners. In effect, they are an attempt to reduce

dose by bypassing the scanners' normal operation. We recommend that faculties look into modifying their protocols to reduce the mAs per rotation by about 10%-20% and apply this to all patients, male and female. This will result in a more efficient method of risk reduction, it will protect the lungs and marrow of both sexes as well as the female breasts, and it will apply to all patients, resulting in a greater overall benefit to the patient population (19, 20, and 21). Another serious chest emergency is the cardiomyopathy of pregnancy; or better described as the peripartum cardiomyopathy (17). This entity develops in the last trimester or even in the month postpartum. It is unclear as to whether the cause is an active myocarditis. Except for the chest x-ray, the diagnosis is made by the responsible clinicians using clinical and laboratory testing. This may include an echocardiogram. Fifty

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Fig. 11. — Hemolytic Anemia Elevated Liver Function and Low Platelets (HELLP) syndrome in 23 year old pregnant female on contrast enhanced CT. Note extensive necrosis of the (R) lobe of the liver. Fig. 12. — CT of a perforated appendix in a 33 yr. old pregnant female who developed RUQ pain with nausea and vomiting one week post partum. U.S. of RUQ showed gallstones. Pain shifted during the subsequent week with development of RLQ pain. A ruptured appendicitis was identified extending laterally and superiorly over the (R) kidney.

gencies (1/1000 – 1/1100) (17). Most often this occurs secondary to cholecystitis. Morbidity and mortality is higher in these patients. Other causes include tetracycline, pre-eclampsia, fatty liver and infection. Gray scan U/S usually will suffice; however, in the situation where complications of pancreatitis develop, MRI and/or enhanced CT may be necessary. In the latter however, again a single pass in the appropriate phase should be obtained. Fig. 13. — A UVJ stone shown 45 in a sagittal view of (L) ureter with classic shadowing on U/S. There was no jet in this case.

percent recover and 50% have a recurrence if they become subsequently pregnant (12). Abdominal emergencies Right upper quadrant emergencies a. Gallbladder emergencies (.08 %). These constitute the 2nd most common abdominal emergencies in pregnancy. U/S, of course, is the study of choice (17). MRI may be of value in select cases in evaluating

the biliary collecting system, and sometimes Tc-HIDA. It is more common in pregnancy than other times, and reflects decreasing emptying, increased smooth muscle relaxation, the relaxant effect of progesterone, increased esterified and free blood cholesterol, decreased bile salt pool, etc. (12). b. Pancreatitis This is the 3rd most common cause of right upper quadrant emer-

c. Hemolytic Anemia Elevated Liver Function and Low Platelets syndrome (HELLP). This most serious acute emergency in pregnancy is often associated with infection. Although one case has been reported as successfully evaluated using nuclear medicine, MRI or CT will best demonstrate the extensive hepatic necrosis (22). d. Appendicitis (007 - .18%) Appendicitis is the most common acute abdominal emergency in pregnancy (17). For diagnostic purposes, we use U/S first. However, especially in the middle and last trimester, the appendix is displaced from its normal position in the Rt. Lower quadrant superiorly, and is often very difficult to identify. Therefore,

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES — GOLDMAN et al

Fig. 15. — 32 yr. old pregnant Crohn’s patient seen for severe pain at an outside hospital 50 miles away. Emergency CT with oral contrast shows free air above the uterus and fluid tracking (L) abdominal gutter. The bowel loops to the (L) and also behind the uterus are thickened. After surgery, a perforated ileum was found and resected.

B Fig. 14. — Two CT cases being performed to evaluate for a ureteral stone. A. Case 1 shows a dilated ureter behind the enlarged uterus. The (R) ureteral stone had passed. B. A (R) ureteral stones is clearly seen at the right UVJ at the trigone.

our personal results with U/S have been less than satisfactory. MRI, ideally, is the next technique of choice (23, 24, and 25). However, our experience is that MRI is often unavailable after hours and obtaining an emergency MRI is difficult during the busy daytime schedule. If either US or MRI is unavailable, a CT is appropriate in these emergency situations. This is especially true when the diagnosis is confusing and may not be due to appendicitis. Therefore, in our experience, we have found CT to be a very useful modality in diagnosing appendicitis. e. Urinary tract pathology Urinary tract problems in pregnancy consist of the normal hydronephrosis of pregnancy, acute renal calculi, acute pyelonephritis and abscess (17). The diagnosis of pyelonephritis can usually be made

clinically. In obscure cases, power Doppler U/S, MRI (24) and contrast enhanced CT are diagnostic. Which is used depends on the clinical situation. These are especially necessary if there is any question of a renal abscess. Nuclear Medicine is very sensitive, but unfortunately, extremely no-specific and, in our experience, not very helpful. The most common problem clinically is the separation between the normal physiological hydronephrosis of pregnancy and a pregnant female who has a urinary tract stone. We try U/S first. One of the difficulties is that the stone may be obscured by the large fetus and its limbs. If U/S is to be used, it is imperative that the operator look for obstructive stones at the UVJ transvaginally. Without it a negative US study is incomplete. MRI has been advocated, but in our experience,

has been less than ideal. We tend to go immediately to a non-contrast CT if the U/S fails; as it readily separates a dilated physiological ureter from an obstructed or non-obstructed ureter with a concurrent stone. f. Obstetrical and gynecological emergencies These include independent torsion of the fallopian tube, rupture of torsion of adnexal masses, ectopic pregnancies, degenerating myomas, abruptio placenta (Ref. Wei), uterine rupture, etc. Adnexal torsion occurs in 10-15% of ovarian masses during pregnancies (as high as 60%) and usually occurs in early pregnancy or the peripartum. Two to five percent of masses rupture during pregnancy. In most cases, U/S will be the study used first. MRI certainly can be used as needed (24, 25). CT should be reserved for use when the diagnosis is obscure and when MRI is unavailable as the backup choice. g. Bowel emergencies These include development of ulcers, Crohn’s disease, ulcerative colitis, toxic megacolon, pseudomembranous colitis, ischemic bowel, etc. Of these, Crohn’s disease is a serious threat to both fetus and mother. Although pregnancies have

JBR–BTR, 2010, 93 (2)

Fig. 16. — A retroperitoneal desmoid was identified in a 28 year old pregnant female on CT. These tend to grow during pregnancy. Patient underwent a successful partial resection.

successfully reached term, exacerbation of the Crohn’s itself, is well documented and may lead to bowel perforation and/or fetal demise. The diagnosis of ulcer disease is best made clinically, i.e. via` endoscopy. Ideally, MRI would be the choice of study for any of the GI emergencies in pregnancy (25, 26). Again, CT will be diagnostic when MRI is unavailable or where the comfort zone of the physician using MRI is low. h. Abdominal tumors Growing angiomyolipomas, adrenal pheochromocytomas, renal carcinomas, etc. can occur in pregnancy, both symptomatic and asymptomatic. In our experience, some of these lesions are actually picked up on a routine U/S during a normal pregnancy, or on an US performed in the emergency room for other reasons (16). MRI or CT, obviously are often needed in the appropriate diagnosis and staging of these patients and in determining whether termination of the pregnancy should be considered. If one is unsure as to whether the pregnancy should be terminated, then MRI would be the study of choice. However, if MRI is felt to be incapable of staging accurately the tumor that has been found, or if it is clear that the pregnancy will be terminated; and then a CT should be performed. In appropriate situations, a PET scan may in fact be preferable to a CT alone. Conclusions This paper presents what we believe is a reasonable approach to the use of radiation in pregnancy. As per international criteria, imaging

radiation should be performed when it is the most efficient, logical method of obtaining a diagnosis. In cases where imaging is needed outside the abdomen, it should be performed as required since there is no practical risk to offset the benefit. In the abdomen, more selective imaging should be performed as appropriate. Key to treating trauma patients who are/or may be pregnant is to remember that maternal survival is sin non of fetal survival. Further, there is no correlation between the severity of trauma and fetal survival. A second major area discussed in this paper is the non-traumatic emergencies. The rationale of our approach to the imaging evaluation for possible pulmonary embolus, cholecystitis, various liver diseases seen in pregnancy, appendicitis, urinary tract infection and stones, adnexal problems, etc. is described.

10.

11.

12.

13.

14.

References 1. Grigg, E.R.N.: The Trail of the Invisible Light. Springfield, IL. Charles C. Thomas, 1965. 2. Gray J.E., Hoffman A.D., Peterson H.A.: Reduction of radiation exposure during radiography for scoliosis. J Bone Joint Surg Am, 1983, 65: 5-12. 3. Ardran G.M., Coates R., Dickson R.A., Dixon-Brown A., Harding F.M.: Assessment of scoliosis in children: low dose radiographic technique. Br J Radiol, 1980, 53: 146-147, 4. Cohen M.D.: Pediatric CT Radiation Dose: How Low Can You Go? AJR, 2009, 192: 1292-1303. 5. Singh S., Kalra M.K., Moore M.A., et al.: Dose Reduction and Compliance

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with Pediatric CT Protocols Adapted to Patient Size, Clinical Indication, and Number of Prior Studies. Radiology, 2009, 252, 200-208. Miller D.L., Balter S., Wagner L.K., et al.: Quality improvement guidelines for recording patient radiation dose in the medical record. J Vasc Interv Radiol, 2004, 15: 423-429. Hirshfeld J.W. Jr., Balter S., Brinker J.A., et al.: ACCF/AHA/HRS/ SCAI clinical competence statement on physician knowledge to optimize patient safety and image quality in fluoroscopically guided invasive cardiovascular procedures: a report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training. J Am Coll Cardiol, 2004, 44: 2259-2282. Brenner, D.J., Hall, E.J.: Computed tomography – an increasing source of radiation exposure. New Eng J Med, 2007, 237: 2277-2284. U.S. Preventive Services Task Force. January 2010. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstfab. htm). Mettler F.A., Bhargavan M., Faulkner K.: Radiologic and Nuclear Medicine Studies in the United States and Worldwide: Frequency, Radiation Dose, and Comparison with other Radiation Sources – 1950-2007. Radiology, 2009, 253: 520-531. American College of Radiology. ACR Practice Guideline for Imaging Pregnant or Potentially Pregnant Adolescents and Women with Ionizing Radiation , American College of Radiology, Reston, Virginia, 2008. Goldman S.M.: Overview of emergency radiological management of the pregnant patient, especially the traumatized pregnant patient. Emerg Radiol, 2000, 198 – 205. Goldman S.M., Wagner L.K.: Radiologic Management of Abdominal Trauma in Pregnancy. AJR, 1996, 166: 763-767. Lowdermilk C., Gavant M.L., Qaisi W., West O.C., Goldman S.: Screening Helical CT for Evaluation of Blunt Traumatic Injury in the Pregnant Patients. RadioGraphics, 1999, 19: S243-Z255. Webb J.A., Thomsen H.S., Morcos S.K., et al.: The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol, 2005, 15: 1234-1240. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 70; 1991. Thompson S.K., Goldman S.M., Shah K.B., Wagner L.K., et al.: Acute non-traumatic maternal illnesses in pregnancy: Imaging approaches. Emerg Radiol, 2005, 11 (4): 199-212. Zak I.T., Dulai H.S., Kish K.K.: Imaging of Neurologic Disorders Associated with Pregnancy and the Postpartum Period. RadioGraphics, 2007, 27: 95108.

IMAGING OF TRAUMATIC AND NON-TRAUMATIC EMERGENCIES — GOLDMAN et al 19. Groves A.M., Yates S.J., Win T., Kayani I., et al.: CT Pulmonary Angiography versus VentilationPerfusion Scintigraphy in Pregnancy: Implications from a UK Survey of Doctors’ Knowledge of Radiation Exposure. Radiology, 2006, 240 (3): 765-770. 20. Ridge C.A., McDermott S., Freyne B., Brennan D.J., Collins C.D., Skehan S.J.: Pulmonary Embolism in Pregnancy: Comparison of Pulmonary CT Angiography and Lung Scintigraphy. AJR, 2009, 193: 12231227. 21. Pahade J.K., Litmanovich D., Pedrosa I., et al.: Quality Initiatives. Imaging Pregnant Patients with

Suspected Pulmonary Embolism: What the Radiologist Needs to Know. RadioGraphics, 2009, 29: 639-654. 22. Ong E.M.W., Drukteinis J.S., Peters H.E., Mortele K.J.: Multimodality imaging of hepato-biliary disorders in pregnancy: a pictorial essay. Emerg Radiol, 2009, 16: 357-363. 23. Cobben L.P., Groot I., Haans L., Blickman J.G., Puylaert J.: MRI for Clinically Suspected Appendicitis During Pregnancy. AJR, 2004, 193: 671-675. 24. Birchard K.R., Brown M.A., Hyslop W.B., Firat Z., Semelka R.C.: MRI of Acute Abdominal and Pelvic Pain in Pregnant Patients. AJR, 2005, 184: 452-458.

25. Pedrosa I, Zeikus E.A., Levine D., Rofsky N.M.: MR Imaging of Acute Right Lower Quadrant pain in Pregnant and Nonpregnant Patients. RadioGraphics, 2007, 27: 721-753. 26. Hogan B.A., Brown C.J., Brown J.A.: Cecal volvulus in pregnancy: report of a case and review of the safety and utility of medical diagnostic imaging in the assessment of the acute abdomen during pregnancy. Emerg Radiol, 2008, 15: 127-131. 27. Smith D.P., Goldman S.M., Beggs D.S., Lanign P.: Renal cell carcinoma in pregnancy: Report of 3 cases and review of literature. Obstetrics Gynecology, 1994, 83: 818-820

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JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 56-61.

CYSTIC LESIONS OF THE FEMALE REPRODUCTIVE SYSTEM: A REVIEW* M. Dujardin, A. Schiettecatte, D. Verdries, J. de Mey1 In order to avoid unnecessary therapy or treatment delay, it is important for the radiologist to be aware of the wide range of differential diagnoses for cystic lesions of the female reproductive system. This paper gives an overview of radiological findings in the variety of physiologic and pathologic cysts which may be encountered in this field. Key-words: Pelvic organs, cysts.

Lesions of the female reproductive system comprise a large number of physiologic and pathologic cysts. In order to avoid unnecessary therapy or treatment delay, it is important for the radiologist to be aware of the wide range of differential diagnoses in this particular field. Since clinical symptoms of pelvic cystic lesions are often non-specific, a correct state-of-the-art radiological work-up is all the more important. Transabdominal and more specific transvaginal ultrasound (TVUS) are definitely the first line exams in the work-up of lesions of the female reproductive system, because of three major advantages: convenience, low-invasiveness and cost effectiveness. Magnetic resonance imaging (MRI) on the other hand is known to be a valuable adjunctive modality for the cystic lesion workup (1). High-resolution multi-planar MRI imaging using a dedicated phased array coil allows detailed anatomic pelvic evaluation. Moreover, MRI is considered an ideal additional modality in this area because of its superb soft-tissue contrast, its lack of radiation exposure and high sensitivity for fluid detection. In our opinion, CT should be reserved for oncological staging and emergency settings where the quick availability of MRI is lacking. The use of contrast should carefully be considered for each patient individually, since not every physiological cyst requires a contrast enhanced study. Contrast enhanced dynamic MRI studies however offer great help in detecting and characterizing solid vascularized components of pelvic neoplasms and peritoneal spread of malignant disease. Therefore, the use of contrast offers

great advantage in diagnosing and staging tumorous lesions in this complex area. In this article, we discuss the radiological findings for pelvic cystic lesions in the female reproductive context and emphasize some key points each radiologist should be familiar with. The cystic findings discussed include vaginal cysts type embryonic cysts, inclusion cysts and bartholin gland cysts, uterine endometrial, as well as myometrial cysts, cervical benign and malignant cystic lesions, the non-significant paraovarian cysts, physiological and complex ovarian cysts and the wide variety of benign, borderline and malignant ovarian tumors. Finally, we end by emphasizing some acute problems, that may be of interest for the radiologist in an on-call setting. Vaginal cysts Vaginal cysts may be embryologic or acquired. Acquired vaginal inclusion cysts or epidermal inclusion cysts can form at a given site following former trauma or surgery. MĂźllerian and Gartner cysts, both embryonic cysts, are typically located in the anterolateral vagina. Usually, they present as asymptomatic simple cysts with sizes ranging from 1 to 7 cm (2). Occasionally, they cause a variety of symptoms such as pain, dyspareunia, voiding complaints, sense of vaginal pressure, or a palpable mass (3). While the commonest type, the MĂźllerian cyst, is a remnant of the paramesonephric duct, the Gartner cyst originates from the mesonephric duct. Distinction between the two embryologic cysts can only be made by means of histological examina-

From: Department of Radiology, UZ Brussel, Brussels, Belgium. Address for correspondence: Dr M. Dujardin, Department of Radiology, UZ Brussel, Laerbeeklaan 101, B-1090 Brussel, Belgium. E-mail: martine.dujardin@gmail.com * Paper presented at the RBRS Annual Symposium, Ghent, 14.11.2009.

tion, but is not clinically significant as both cysts are managed in a similar fashion: large symptomatic cysts are usually excised (4). It is however important for the radiologist to be aware of the association between Gartner cyst and metanephric abnormalities such as unilateral renal agenesis, renal hypoplasia and ectopic ureteral insertion (5). High resolution multiplanar T2weighted MRI imaging is the modality of choice for evaluating such vaginal cysts, as it exhibits the cystic nature of the lesions and differentiates them from urethral diverticula. Signal intensity on T1-weighted imaging without contrast varies from low to high, depending on the mucine or hemorrhagic content. No contrast enhancement is to be expected. The most frequently encountered cyst on cross sectional imaging, the bartholin cyst, is typically located more posteriorly and caudally, in the posterolateral introitus and medial to the labia minora. Bartholin gland cysts are typically retention cysts from chronic inflammation, which leads to ductal obstruction from pus or thick mucus within the bartholin glands. In a bartholin cyst varying contents of mucin and hemorrhage may lead to spontaneous high signal intensity on T1 (Fig. 1). Whenever superimposed infection occurs, it presents as air-fluid levels within the cyst and an irregular rim enhancement on CT or MRI. Uterine cysts Occasionally in the elderly, ultrasound (US) or MRI reveals a cystic gland dilatation combined with endometrial atrophy: cystic endometrial atrophy (Fig. 2). The endometrium presents in such case as a very thin atrophic layer of 4 to 5 mm. Cystic endometrial hyperplasia, on the other hand, is characterized by similar small endometrial cysts in an evenly thickened endometrium of over 5 to 6 mm. Both entities are not premalignant, provided the endometrium is evenly echogenic.

CYSTIC LESIONS OF THE FEMALE REPRODUCTIVE SYSTEM — DUJARDIN et al

Fig. 1. — Follow-up MRI in the context of cervix carcinoma in a 80-year old female: unenhanced sagittal T1-weighted (A) and T2-weighted (B) images made in the context of a follow-up for cervix carcinoma in complete remission shows fluid accumulation in the uterus (*) caused by cervical stenosis post radiotherapy. The hyperintense cystic lesion at the introitus (arrow) which is hyperintense on T1 and hypointense on T2 is an uncomplicated bartholin cyst and an incidental finding. Hypointensity on T2 is caused by a hemorrhagic content of this cyst.

Fig. 2. — Sagittal T2-weighted image in a 81-year old woman in the context of a staging for rectal carcinoma: incidentally, the small endometrial cysts of cystic endometrial atrophy are present throughout the uterus.

Junctional zone myometrial cysts can be encountered in the uterus and are highly specific for adenomyosis. These small and easy to depict myometrial cysts may be the first to draw attention on either US or MRI to the associated thickened junctional layer of ⱖ 12 mm in adenomyosis. Such high T2-weighted signal intensity cysts within the junctional zone may have high signal intensity on native T1-weighted imaging as well and are in fact trapped endometrial glands. Cervical cysts On cross sectional imaging of the cervix, common retention cysts are a typical incidental finding and range from a few mm to 4 cm. They are called nabothian cysts and typically present as a sharply delineated cervical cyst, without contrast enhancement (Fig. 3). Signal intensity is high on T2-weighted imaging, while high signal intensity on unenhanced T1weighted imaging can occasionally be produced by the presence of protein content or hemorrhage. A tunnel cluster is a special type or cluster of nabothian cysts that we may encounter as a complex multicystic mass filling the endocervical channel (6). Moreover, there exists an overlap in imaging characteristics between such a tunnel cluster, a severe endocervical hyperplasia and a cervical polyp. Unfortunately, since imaging findings overlap, exact differentiation of the latter three benign

Fig. 3. — Contrast enhanced CT in venous phase (A) and corresponding T2-weighted high resolution MR image at 3T shows a typical nabothian cyst in the cervix (arrow) with clear cystic content and sharp edges and without any contrast enhancement.

entities with adenoma malignum, a rare minimally invasive adenocarcinoma, is occasionally difficult (7). Besides a watery discharge, which is the most common initial symptom of adenoma malignum, solid components in the deep cervical stroma with enhancement in a complex multicystic mass filling the endocervical channel are suspicious of adenoma malignum (7, 8). Paraovarian cysts Paraovarian cysts like paraöphoron, epoophoron and hydatids of Morgagni or appendices vesiculosae, the latter being attached

to the fringes of the tube, are merely an incidental MRI finding and present as thin walled unilocular simple cysts filled with clear serous fluid. They are of low significance to the radiologist, since they are harmless. Physiological and functional ovarian cysts The Graafian or dominant follicle is found at mid cycle and its size ranges up to 25 mm (1). After ovulation, the corpus luteum remains and is typically a cystic structure of less than 15 mm. While follicles and the dominant follicle are anechoic and thin walled, corpus luteum is typical-

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Fig. 4. — Contrast enhanced CT in the venous phase in a young female performed to exclude acute appendicitis in an emergency setting, reveals a thick walled somewhat collapsed cystic structure in the right ovary (arrow). In this corpus luteum, contrast enhancement in the thick wall is evident. An intrauterine device is also present.

ly presenting with a thick and occasionally convoluted and enhancing wall (Fig. 4). Some degree of blood content, producing scattered internal echoes, is also frequent. If conception does not occur, the corpus luteum involutes into the corpus albicans, which we do not see on imaging. It is important for clarity not to refer to these physiological cystic findings as cysts, but to use the term follicle. A true follicle cyst on the other hand develops when the follicle fails to regress or ovulate, and is typically a 3 to 8 cm unilocular thin walled cyst, that may contain a small amount of blood (9). When the corpus luteum fails to regress after ovulation, which can be seen during the end luteal phase or during pregnancy, it turns into a 2.5 to 6 cm thick walled cyst (10), which is prone to bleed (Fig. 5) and may even reach up to 15 cm in pregnancy. The thick cyst wall may exhibit slightly increased intensity on unenhanced T1-weighted images and relatively low signal intensity on T2-weighted images. Avid enhancement of the cyst wall, reflecting increased vascularity of the thick luteinized cell layer (1), can occur. We should take into account that not only the corpus luteum and corpus luteum cyst but all these

physiological cysts may present on cross sectional imaging with a contrast enhancing wall. Information about the patient’s menstrual cycle at the time of imaging is mandatory in order to be able to differentiate follicle, dominant follicle, corpus luteum, follicular cyst and corpus luteum cyst, since diagnosis of such entities relies on the date in the menstrual phase. Also, since a follicular cyst of more than 5 cm may be indistinguishable from a neoplastic cyst, such as serous cystadenoma, monitoring by follow up TVUS (1) is advocated. Indeed, unlike neoplastic cysts, physiological cysts will regress usually within two menstrual cycles. Theca lutein cysts or hyperstimulation cysts are associated with abnormal high levels of bHCG (human chorionic gonadotropine) as in multiple gestations, trophoblastic disease and most commonly due to pharmacologic hyperstimulation. The TVUS signs for theca luteine cysts are enlarged ovaries of > 5 cm in association with multiple follicular cysts, corpora lutea and edematous stroma. The key imaging finding to make the differentiation with multilocular bilateral cystic ovarian tumor is the uniform size of each locule in theca lutein cyst (11).

Fig. 5. — T2-weighted (A), unenhanced (B) and enhanced (C) T1-weighted images in a 19-year old female with a history of Von Willebrand factor deficit and presenting with acute abdominal pain caused by a ruptured hemorrhagic corpus luteum cyst: a somewhat thicker walled large ovarian cyst is seen on the left as well as high signal intensity free fluid on T1 (arrow, B). The bottom content of the cyst is hypointense on T2 (A) and hyperintense on T1 (B), which is typical for an organized hematoma. A clear enhancement (C) can be seen in the cyst wall, which presents with an interruption (arrow, C). The absence of papillary projections and enhancement of the internal structure of the cyst exclude malignancy.

Complex ovarian cysts: endometrioma Endometriosis is defined as the presence of extrauterine endo-

CYSTIC LESIONS OF THE FEMALE REPRODUCTIVE SYSTEM â&#x20AC;&#x201D; DUJARDIN et al

changes, while on T2 the cyst compound will be low signal intensity with high signal intensity mural nodules (1). Cystic ovarian tumors

Fig. 6. â&#x20AC;&#x201D; T2-weighted (A), unenhanced T1-weighted (B, D), and enhanced T1-weighted image in the venous phase (C) in a 61-year old woman with a persistent ovarian cyst on the left. The internal structure of the cyst shows heterogeneous hypointensity on T2 (A) and hyperintensity on T1 (B), consistent with internal hematoma. High signal intensity on native T1 is consistent with hematosalpinx (arrow, D). Contrast enhanced T1 (C) seems to demonstrate papillary projections on the anterior and left cyst wall, which lead to the preoperative diagnosis of malignant cystic tumor type mucinous cystadenocarcinoma. However, pathology of the adnexectomy specimen revealed an endometrioma, without malignancy.

metrial tissue. The most common location of pelvic endometriosis is the ovarian endometrioma, a complex cyst containing blood products. Endometriomas are usually multiple and do not disappear in 2 month TVUS follow-up, in contrast to a unilateral hemorrhagic follicular or corpus luteum cyst. Characteristic sonograhic features of endometriomas are diffuse low-level internal echoes, multilocularity and hyperechoic foci in the wall (12). On US, no color Doppler signals are to be expected in this complex cyst. The various stages of the blood products in the endometrioma cause the typical MRI findings: high signal intensity on unenhanced T1-weighted imaging and low signal intensity on T2. This phenomenon is called shading (1). It is important to perform fat saturation techniques on MRI in order to distinguish this high signal intensity on unenhanced T1

from fat presence. Occasionally, it can be difficult to differentiate a complex endometrioma from a malignant ovarian tumor (Fig. 6). Because of the risk in endometrioma of developing a secondary neoplasm, it is mandatory to look for solid enhancing components on the endometrioma cyst wall, which are suspicious of malignant transformation. 1% of endometriomas undergo malignant transformation into endometrioid adenocarcinoma and clearcell carcinoma (1). Decidual changes of an endometrioma cyst wall during pregnancy may resemble solid malignant components. These decidual changes can however be distinguished, since they present with similar signal intensity on MRI as normal endometrium on all MRI sequences: on unenhanced T1, a high signal intensity endometrioma cyst will present with low signal intensity from pregnancy decidual

Cystic ovarian tumors are classified on the basis of tumor origin as epithelial, germ cell and sex cord stromal tumors. The subtypes of epithelial tumors include serous, mucinous, endometrioid and clear cell tumors. They represent 60% of all ovarian and 85% of malignant ovarian neoplasms (13) and their prevalence increases with age, peaking in the sixth and seventh decade of life (14). Of all malignant ovarian tumors, 50% are serous and only 10% are mucinous epithelial tumors (15). In general, serous lesions tend to be smaller, unilocular, thin walled and malignant and may mimic functional cysts, whereas mucinous tumors are mostly benign, larger and typically present with a multilocular, stained glass or honeycomb-like locular appearance (15). CT attenuation or MRI signal intensity of the different locules is variable (Fig. 7), due to the difference in degree of mucinous or proteinous cyst content (15). Commonly, serous epithelial tumors are more frequently bilateral and may exhibit psammomatous calcifications. Mucinous epithelial tumors, on the other hand, are mostly unilateral and rarely present with some linear calcifications (15). Mucinous adenocarcinoma can rupture and is associated with pseudomyxoma peritonei. In spite of the considerable overlap in morphologic characteristics and corresponding imaging features, that in many cases prevents definitive preoperative characterization as benign or malignant, besides the obvious presence of either ascitis, peritoneal implants and adenopathies, features suggestive of malignancy in a cyst are: solid elements and either endocystic or exocystic papillary projections, wall and/or septation thickness of more than 3 mm and color flow in the solid components (15). Although rare, endometrioid carcinoma is the most common tumor arising from endometriosis, followed by clear cell tumor. It is associated with endometrial hyperplasia. Unfortunately, imaging findings are non-specific and are those of a large complex cystic mass with solid components (15).

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should immediately be followed by CA125 determination and surgical exploration. Off course, in the elderly, the individual patient constitution should be taken into account. Acute problems

Fig. 7. â&#x20AC;&#x201D; 85-year-old female with an anatomopathologically proven cystadenocarcinoma. Venous phase CT (A) shows a multiloculated septated cystic mass with enhancing solid vegetations on the cyst wall (arrow, A). Sagittal T2-weighted image (B) and axial T1-weighted image without (C) and with contrast (D) reveal the same findings. In B (arrow), some ascitis is present. Some locule contents seem of higher signal intensity (C), which is suggestive of a mucinous content. T1-weighted enhanced image (D) at the same level as CT (A) reveals similar solid parts in the cysts wall (arrows). The anterior cyst wall contrast enhancing exocystic papillary projections are more easily depicted on MRI (D) compared to CT (A).

The mature teratoma or dermoid cyst is the most common ovarian mass in children. It is a predominantly cystic germ cell tumor, containing fat or dense calcifications with a bilateral presentation in 8-25% of the cases. Most mature cystic teratomas can be diagnosed at US, although a variety of appearances, characterized by echogenic sebaceous material and calcification, is possible. Sebum and hair compounds present as echogenic components on US. MRI and CT are able to demonstrate the fat component of the tumor well, which is diagnostic (Fig. 8). Since fat presents as high signal intensity on both T1 and T2-weighted imaging, fat saturation technique allows easy confirmation of this high signal intensity compounds as fat (16). Besides the most common malignant sex cord stromal tumor (15), a granulosa cell tumor is also the most common estrogen producing ovarian tumor. Imaging findings vary

widely from solid to multilocular and the tumor may present as a multicystic lesion with enhancing solid portions (15). It is most important not to misdiagnose physiologic changes of the ovary as pathologic cysts. On the other hand, we should be aware that ovarian masses in young women could indeed represent malignancy. It is therefore recommended in premenopausal women, that a unilocular thin walled cyst of 2.5 to 6 cm should have follow-up TVUS in two months. Follow-up should take place in the immediate postmenstrual period, when follicular cysts are not to be expected. In unilocular cysts exceeding 6 cm surgery is recommended. In postmenopausal women, a serial follow-up is to be considered in the case of a unilocular nonseptated thin walled cyst of less than 3 cm, while a larger cyst and/or any signs suggestive of malignancy

Ectopic pregnancy, hemorrhage within a cyst with or without cyst rupture and infection are acute problems that can be encountered in emergency radiology. Ectopic pregnancy remains the leading cause of death during the first trimester of pregnancy. The initial evaluation of patients suspected to have an ectopic pregnancy entails a bHCG determination and TVUS. The absence of intrauterine pregnancy beyond 6 weeks menstrual age and elevated bHCG levels are highly suspicious of extrauterine pregnancy. An ectopic pregnancy is 95% tubal (17) and associated with hematosalpinx and/or hemoperitoneum. An adnexal mass that is separate from the ovary is the most common finding of a tubal pregnancy and is seen in up to 89-100% of patients (18). The second most common sign is the tubal ring sign, which describes a hyperechoic ring surrounding the extrauterine gestational sac. A related finding is the ring of fire sign, which is recognized by peripheral hypervascularity of the hyperechoic ring (19) on Color Doppler US. An adnexal mass is more specific for an ectopic pregnancy when it contains a yolk sac or a living embryo or when it moves independently from the ovary (20). Of course, the presence of an embryonic heartbeat within an adnexal mass is pathognomonic. Hemorrhage and cyst rupture occasionally occur in a corpus luteum cyst without predisposition. Ovarian cyst rupture causes an acute pain with sudden onset. Evidently, bleeding disorders are predisposing factors for such an event to occur (Fig. 5). As with ovarian torsion and extrauterine pregnancy, ultrasound is the first-line imaging modality for suspected ovarian cyst hemorrhage or rupture. Bleeding causes a complex pattern of echoes within the cyst. The typical US appearance is that of an enlarged ovary, containing often bizarre mixed echoes caused by blood clot and arranged in a reticular pattern, sometimes likened to a spiderâ&#x20AC;&#x2122;s web. On pressure of the trans vaginal probe, the blood clot within the cyst may seem to wobble in a jelly-like fashion (21). Cyst

CYSTIC LESIONS OF THE FEMALE REPRODUCTIVE SYSTEM — DUJARDIN et al

10. 11.

12. Fig. 8. — Unenhanced uro CT performed in a 30-year old woman in an emergency setting demonstrates the incidental finding of a bilateral mature teratoma. The hypodense fat components are diagnostic and present bilaterally, besides calcification and sebaceous material.

13.

14.

rupture causes the presence of high density free pelvic fluid on CT, with higher signal intensity on unenhanced T1-weighted imaging (Fig. 5). A tubo-ovarian abscess is a multilocular complex mass with debris, septation and irregular thick rim enhancement that may contain fluidfluid levels or gas. When dealing with such an abscess, it is mandatory to explore the contra lateral adnex, since it is usually also affected to a variable degree. On TVUS, an echogenic cyst content with surrounding Color Doppler rim may be an imaging clue. Conclusion TVUS is the initial imaging modality of choice for evaluating cysts of the female reproductive system. In our opinion, CT should be reserved for oncological staging and emergency settings, where the quick availability of MR is lacking. In the case of an inconclusive TVUS, MRI is the adjunctive imaging modality of choice. Nowadays, because of limitations in tumor marker as well as in imaging specificity, some ovarian cancers will not be diagnosed preoperatively. In the future, diagnosis

may be more fine tuned using stateof the art MRI at 3T with dedicated coils and additional techniques such as diffusion, perfusion and spectroscopy.

15.

References 16. 1. Tamai K., Koyama T., Saga T., et al.: MR features of physiologic and benign consitions of the ovary. Eur Radiol, 2006, 16: 2700-2711. 2. Hwang J.H., Jeong Oh M., Woo Lee N., Young Hur J., Wan Lee K., Kwan Lee J.: Multiple vaginal Mullerian cysts: a case report and review of literature. Arch Gynecol Obstet, 2009, 280: 137-139. 3. Eilber K.S., Raz S.: Benign cystic lesions of the vagina: a literature review. J Urol, 2003, 170: 717-722. 4. Prasad S.R., Menias C.O., Narra V.R., et al.: Cross-sectional imaging of the female urethra: technique and results. Radiographics, 2005, 25: 749761. 5. Currarino G.: Single vaginal ectopic ureter and Gartner’s duct cyst with ipsilateral renal hypoplasia and dysplasia (or agenesis). J Urol, 1982, 128: 988-993. 6. Kurman R.J., Norris H.J., Wilkinson E.: Tumors of the cervix. In: Atlas of tumor pathology: tumors of the cervix, vagina and vulva. Armed

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Forces Institute of Pathology, Washington DC, 1992. Doi T., Yamashita Y., Yasunaga T., et al.: Adenoma malignum: MR imaging and pathologic study. Radiology, 1997, 204: 39-42. Yamashita Y., Takahashi M., Katabuchi H., Fukumatsu Y., Miyazaki K., Okamura H.: Adenoma malignum: MR appearances mimicking nabothian cysts. Am J Roentgenol, 1994, 162: 649-650. Outwater E.K., Mitchell D.G.: Normal ovaries and functional cysts: MR appearance. Radiology, 1996, 198: 397-402. Rosai J.: Female reproductive system. Ackerman’s surgical pathology. 8th edition, St Louis, 1996. Ghossain M.A., Buy J.N., Ruiz A., et al.: Hyperreactio luteinalis in a normal pregnancy: sonographic and MRI findings. J Magn Reson Imaging, 1998, 8: 1203-1206. Kinkel K., Frei K.A., Balleyguier C., Chapron C.: Diagnosis of endometriosis with imaging: a review. Eur Radiol, 2006, 16: 285-298. Russel P.: Surface epithelial-stromal tumors of the ovary. In: Blaustein’s pathology of the female genital tract. 4th edition. Edited by Kurman R.J., Springer-Verlag, New York, 1994, pp 705-782. Koonings P.P., Campbell K., Mishell D.R., Grimes D.A.: Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol, 1989, 74: 921-926. Jung S.E., Mun Lee J., Eun Rha S., Young Byun J., Im Jung J., Tai Hahn S.: CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. Radiographics, 2002, 22: 1305-1325. Outwater E.K., Siegelman E.S., Hunt J.L.: Ovarian teratomas: tumor types and imaging characteristics. Radiographics, 2001, 21: 475-490. Lin E.P., Bhatt S., Vikram V.S.: Diagnostic clues to ectopic pregnancy. Radiographics, 2008, 28: 16611671. Atri M., Leduc C., Gillett P., et al.: Role of endovaginal sonography in the diagnosis and management of ectopic pregnancy. Radiographics, 1996, 16: 755-774. Pellerito J.S., Taylor K.J., QuedensCase C., et al.: Ectopic pregnancy: evaluation with endovaginal color flow imaging. Radiology, 1992, 183: 407-411. Blaivas M., Lyon M.: Reliability of adnexal mass mobility in distinguishing possible ectopic pregnancy from corpus luteum cysts. J Ultrasound Med, 2005, 24: 599-603. Bottomley C., Bourne T.: Diagnosis and management of ovarian cyst accidents. Best Practice and Research Clinical Obstetrics and Gyneacology, 2009, 23: 711-724.

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CLINICAL AND IMAGING TOOLS IN THE EARLY DIAGNOSIS OF PROSTATE CANCER, A REVIEW* P. De Visschere1, W. Oosterlinck2, G. De Meerleer3, G. Villeirs1 Measurement of serum Prostate Specific Antigen (PSA) level is useful to detect early prostate cancer. PSA-screening may reduce the mortality rate from prostate cancer, but this is associated with a high rate of overdiagnosis and overtreatment. To improve the detection of clinically significant cancers, several auxiliary clinical and imaging tools can be used. The absolute PSA value can be complemented with parameters such as PSA velocity, PSA density and free/total PSA. Transrectal Ultrasound (TRUS) has only moderate accuracy in the detection of prostate carcinoma, but is very useful in the estimation of prostate volume and thus calculation of PSA-density. The role of Magnetic Resonance Imaging (MRI) in diagnosis and staging of prostate carcinoma is rapidly increasing. Morphologic T2weighted MR images (T2-WI), preferably with an endorectal coil, depict the prostatic anatomy with high resolution and can detect tumoral areas within the peripheral zone of the prostate. Addition of MR spectroscopic imaging (MRSI), dynamic contrast enhanced MRI (DCE-MRI) and/or diffusion weighted imaging (DWI) further increase the diagnostic performance of MRI. The gold standard for diagnosis of prostate carcinoma is histological assessment obtained by transrectal ultrasound-guided systematic core needle biopsy. In the future, imaging-based targeted biopsies may improve the biopsy yield and decrease the number of biopsy cores. Computed Tomography (CT) and positron emission tomography (PET) have no value in early prostate cancer detection and the indications are limited to lymph node staging and detection of distant metastases.

Introduction

Clinical tools

Prostate cancer is one of the most common tumors in Western countries, but not all detected cancers will become symptomatic during the patient’s lifetime if left untreated (13). Treatment selection is based on prognostic factors such as serum Prostate Specific Antigen (PSA) level, histological grading (Gleason score), tumor size, clinical staging (TNM classification) and the patient’s life expectancy and co-morbidity (1, 4, 5). On the basis of these variables, patients may be either allocated to active treatment (radical prostatectomy, radiotherapy, minimally invasive surgery) when the tumor is deemed clinically relevant, or to active surveillance when the impact of the prostate cancer on the patient’s life expectancy and quality of life is deemed insignificant. Such allocations obviously require a highly accurate assessment of the abovementioned prognostic factors. In this review article, the role of traditional clinical parameters (PSA, digital rectal examination, histological grading) will be discussed and the increasing role of imaging techniques to improve treatment stratification will be highlighted.

PSA Most prostate carcinomas are detected on the basis of elevated serum PSA, which is up to present the best available test for early detection of prostate carcinoma (36). Its exact cut-off level is agedependent but remains controversial (7). Commonly > 3.0 ng/ml is used as the trigger for further examination (6). Apart from tumoral etiology, PSA levels may also be elevated due to benign prostatic hyperplasia (BPH), acute and chronic prostatitis and recent urologic procedures (1, 4, 7). To improve the differentiation between benign and malignant causes of PSA-elevation, additional parameters such as PSA velocity, PSA density and free/total PSA are frequently used (3, 5). PSA velocity is determined by the evolution of serum PSA over time. If the serum PSA increases > 0.75 ng/ml/year, there is a higher risk of clinically significant prostate cancer (3, 5). PSA density relates serum PSA level to the prostate volume, usually calculated with transrectal ultrasound (TRUS) or magnetic resonance imaging (MRI). A level below 0.15 ng/ml/cc is more suggestive of

From: 1. Department of Radiology (Division of Genitourinary Radiology), 2. Department of Urology, 3. Department of Radiotherapy, Ghent University Hospital, Gent, Belgium. Address for correspondence: P. De Visschere, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. E-mail: pmzgvm@yahoo.com * Paper presented at the Annual Symposium of RBRS in November 14, 2009.

benign prostatic hyperplasia (BPH) than of prostate carcinoma (5, 7). The percentage free/total PSA is used for further risk assessment in the PSArange lower than 10 ng/ml; values above 25% are most frequently associated with BPH, whereas values under 10% are highly suggestive of malignancy, although chronic prostatitis may show similar low percentages (5, 7). The impact of PSA screening on prostate cancer survival remains controversial (4, 6). Recent reports of large-scale randomized studies addressing the issues of population screening for prostate cancer (the Prostate, Lung, Colorectal, Ovarian cancer (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial) have demonstrated that PSA-based screening leads to a significant increase of prostate cancer detection and that numerous patients with prostate cancer are being identified at an earlier and potentially more treatable stage (8). As a result, the mortality rate from prostate cancer can be reduced by about 20%. Unfortunately, this can only be achieved at the cost of a high rate of overdiagnosis and overtreatment (9). To avoid overdetection, the European Guidelines Committee advises no routine PSA testing in patients younger than 50 years, or in patients with a life expectancy of less than 10 years (5, 10). Recently another biomarker, Prostate Cancer Gene 3 (PCA3) has been developed. PCA3 is highly specific for prostate cancer and is not influenced by prostatitis. It has better diagnostic accuracy than PSA for prediction of

CLINICAL AND IMAGING TOOLS IN THE EARLY DIAGNOSIS OF PROSTATE CANCER â&#x20AC;&#x201D; DE VISSCHERE et al

prostate cancer but has not yet been compared to additional parameters such as PSA-density. Moreover, it is expensive and currently not remunerated in Belgium (6, 11-13). Digital Rectal Examination PSA-testing is in daily practice routinely supplemented with a digital rectal examination (DRE), to assess the prostatic shape, symmetry, firmness and nodularity, and to detect grossly enlarged prostate glands (14, 15). DRE primarily detects higher risk tumors and more advanced disease, but since the PSA-era the majority of detected prostate carcinomas is not palpable (1, 2, 4, 8). Although the overall diagnostic sensitivity is quite low and influenced by observer bias, it is nevertheless capable of finding about 15% of cancers that would otherwise go undetected by PSA screening alone (14).

Histology The gold standard for diagnosis of prostate carcinoma is histological assessment (4). Histological specimens are obtained with ultrasoundguided transrectal core needle biopsy when PSA-results, DRE and/or imaging studies are not reassuring. Traditionally, systematic biopsies are performed with 6 to 12 cores, depending on the prostatic volume, but supplemental image-guided targeted biopsies may improve the detection rate of significant cancer and decrease the number of biopsy cores (16). An important histopathologic parameter is the Gleason score. It reflects the grade of differentiation of the prostate cancer and thus correlates with tumor aggressiveness (4, 16, 17). A score of 3 + 4 or lower corresponds to a lessaggressive tumor with lower risk of non-organ confined disease, while a score of 4 + 3 or higher corresponds to a more aggressive tumor with higher clinical significance and mortality risk. Imaging tools Transrectal Ultrasound (TRUS) The prostate can be evaluated with a high-frequency intrarectal ultrasound transducer. The normal prostatic contour is usually clearly depicted and the isoechoic peripheral zone can be differentiated from the heterogeneous central gland (Fig. 1, 2). About 70% of prostate carcinomas are found within the peripheral zone (4, 10) and may be

Fig. 1. â&#x20AC;&#x201D; Zonal anatomy of the prostate. Sagittal (A-D) and axial (E) pictures. The prostate gland is located caudal to the urinary bladder, with the urethra running through it. The seminal vesicles are convoluted cystic structures at the posterolateral sides of the prostate base (blue), draining into the ejaculatory ducts (A). The ejaculatory ducts join the urethra at the prostatic verumontanum. The caudal part of the prostate is called the apex, the cranial part the prostate base. The prostate is divided into a central gland (yellow) (E) and a peripheral zone (red) (C, D, E). The central gland consists of the periurethral glands along the proximal urethra, the paired pear-shaped transition zones (gray) and the central zone, that envelopes the ejaculatory ducts (orange) (B, E). In benign prostatic hyperplasia (BPH) the transition zone enlarges and compresses the central zone, which becomes a surgical pseudocapsule between the central gland and the peripheral zone. The peripheral zone is covered by a thin capsule, known as the true anatomic capsule. Anteriorly, the prostate is covered by the anterior fibromuscular stroma (brown) (D, E). (Reprinted from Villeirs GM, Verstraete KL, De Neve WJ and De Meerleer GO, 2005, Magnetic Resonance Imaging Anatomy of the prostate and periprostatic area: a guide for radiotherapists, Radiotherapy and Oncology, 76, 99-106, copyright ÂŠ 2005, with permission from Elsevier).

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Fig. 2. â&#x20AC;&#x201D; Transrectal ultrasound of the normal prostate in a 59-year old male, transverse (A, C) and sagittal (B, D) sections. The prostate is located caudal to the bladder (B) (C, D). The prostatic contour is clearly depicted and can be used for volume estimation (A, B). The isoechoic peripheral zone may be differentiated from the hypo- or hyperechoic central gland (white arrows) (A). The seminal vesicles present as convoluted hypoechoic structures at both posterolateral sides of the prostate base (SV) (B, C). Sometimes central gland calcifications are visualised, with typical retroacoustic shadow (white star) (A). On sagittal sections the urethra running through the prostate is demonstrated (white arrowheads) (D).

visible as a predominantly hypoechoic area compared to normal peripheral zone tissue (Fig. 3). Tumors in the central gland are usually difficult to detect, because they blend with the heterogeneous central gland background tissue. TRUS is widely available and is relatively cheap, but cannot be used in prostate cancer screening because it has only moderate accuracy for prostate cancer detection in the general population (1, 4, 18, 19). In patients with elevated PSA or an abnormal digital rectal examination (DRE), however, it can be used for initial morphologic assessment of the prostate and seminal vesicles, to measure the prostatic volume (for calculation of PSA density), or for biopsy guidance (1, 4, 18, 19). In an effort to improve the diagnostic accuracy of transrectal ultrasound, a number of ancillary techniques have

been proposed. Tumor neoangiogenesis can be detected with Doppler or Power-Doppler examinations, which are particularly helpful for the detection of isoechoic tumors that would normally be missed with gray-scale ultrasound (4, 10, 18). Intravenous injection of sonographic-contrastmedia consisting of stabilized microbubbles, in conjunction with contrast harmonic techniques may further improve the sensitivity for increased blood perfusion (4, 18, 19). Tissue Harmonic Imaging results in improved spatial and contrast resolution (4, 10), and sono-elastography displays a color-coded qualification of tissue elasticity (4, 10, 18, 19), which helps to increase the positive biopsy yield of elastography-directed biopsies (20). Improved prostate cancer detection has also been reported with Tissue Type Imaging, a new technique which analyzes the

echo-signal spectrum before it is converted into an image (19, 21, 22). Computed Tomography Computed Tomography (CT) has little value in the detection of primary prostate cancer (1, 18). The margins of the lower prostate halve are poorly defined on CT, and the intraprostatic anatomy is not sufficiently demonstrated (1), both on unenhanced or contrast-enhanced CT. CT can therefore not be used for prostate cancer detection and its indications are limited to lymph node staging or detection of distant metastases in patients with known prostate carcinoma (1, 18). Magnetic Resonance Imaging (MRI) The role of MRI in both the diagnosis and staging of prostate carcinoma has evolved tremendously in the past decade. In particular,

CLINICAL AND IMAGING TOOLS IN THE EARLY DIAGNOSIS OF PROSTATE CANCER — DE VISSCHERE et al

COLOR PRINT ?

C the introduction of endorectal-coil imaging and the emergence of functional techniques such as MR spectroscopy (MRSI), dynamic contrastenhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) has boosted the diagnostic accuracy of MRI and its potential to refine the therapeutic decision making process (1, 22). Standard morphologic imaging sequences should include 4 mm transverse, sagittal and coronal fast-T2 weighted images (Fig. 4) for tumor detection, localisation and staging (1, 4), supplemented with a 4 mm transverse breath-hold T1-weighted sequence for detection of post-biopsy intraglandular hemorrhage (Fig. 5) (1, 2, 4, 23). On 1.5T equipment, the use of an endorectal coil in conjunction with a pelvic phased-array coil is highly recommended (1, 2). It significantly increases the signal-to-noise ratio for prostate imaging and markedly improves spatial and contrast resolution. The balloon-covered endorectal coil is inflated with 60cc

Fig. 3. — Transrectal Ultrasound of the prostate in a 65-year old male with prostate carcinoma. A. Transverse section of the midprostate shows a subtle hypoechoic area in the peripheral zone on the left side (white arrows), suspicious for prostate carcinoma. B. Elastographic image of the prostate demonstrates harder consistency of the prostate carcinoma (white arrows) compared to the surrounding normal peripheral zone tissue. C. On Doppler flow examination, the tumor is confirmed as a hypervascular area, due to tumor neovascularity (white arrows).

of air or filled with 40cc of perfluorocarbon (PFC) to increase the magnetic field homogeneity by eliminating the air-tissue interface and reducing susceptibility artifacts (1, 2, 17, 22). Before the examination Scopolamine (Buscopan®) IV is administered to reduce peristaltic motion of the rectum and adjacent bowel segments (17). T2-weighted sequences exquisitely depict the prostatic zonal anatomy and the presence and extent of low signal-intensity prostate carcinoma surrounded by high signal-intensity normal peripheral zone tissue (Fig. 6) (24). Because about 70% of all prostate cancers occur within the peripheral zone, many of them can readily be detected on morphologic T2-weighed images. Nevertheless, a low signal intensity area is not specific for prostate cancer, since benign conditions such as prostatitis, hemorrhage, hyperplastic nodules or post-treatment (hormonal or irradiation) changes may equally show low signal intensity (1, 2, 24,

25). Furthermore, morphologic T2-WI is less accurate for evaluating central gland cancers, unless they show an irregular area of uniform low signalintensity (16, 26). Overall, diagnostic accuracies of about 70% have been reported for morphologic T2-WI in the detection of prostate cancer (24, 27, 28). MR spectroscopy (MRSI) provides information about the relative concentrations of cellular metabolites in the prostate. A three-dimensional data set with spectra from small voxels of 0.5 cc or less is acquired throughout the prostate. MRSI sequences suppress signal contributions from water and fat and measure the relative concentrations of citrate, choline, creatine and polyamines, which resonate at distinct frequencies in the spectrum (1, 24, 29). Citrate is synthesized, stored and secreted by glandular tissue in the prostate and is abundantly available in the normal peripheral zone and in glandular benign prostatic hyperplasia (1) (Fig. 7). In prostate

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Fig. 4. — T2-weighted endorectal coil MR images of the normal prostate in a 63-year old male. A. Transverse section at midprostatic level. The normal zonal anatomy is depicted with high resolution. The central gland shows a heterogeneous low signal intensity (white star), whereas the peripheral zone shows diffuse high signal intensity (black stars), surrounded by a thin rim of low signal intensity, which represents the anatomic or true capsule (white arrows). B. Transverse section through the seminal vesicles. These are demonstrated as convoluted high-signal intensity lobules (white arrows) at both superolateral sides of the prostate. C. Transverse section at level of the prostatic apex. The peripheral zone is demonstrated as high signal intensity tissue (white arrows) surrounding the hypointense external sphincter and urethra. D. Sagittal section showing the prostate (white arrows), caudal to the urinary bladder (black star), and anterior to the rectum with the endorectal coil.

Fig. 5. — Transverse T1-weighted MR image of the prostate in a 75-year-old male 4 weeks after transrectal ultrasound-guided biopsy. Post-biopsy artefacts are demonstrated as high signal intensity foci in the prostate on T1-weighted images (white arrows), as blood demonstrates high signal on these sequences.

Fig. 6. — Transverse T2-weighted MR image in a 77-year-old male with prostate cancer. The tumor is demonstrated as a circumscribed low signalintensity lesion in the peripheral zone of the prostate (white arrows).

CLINICAL AND IMAGING TOOLS IN THE EARLY DIAGNOSIS OF PROSTATE CANCER — DE VISSCHERE et al

B Fig. 7. — MR spectroscopy of the normal prostate in a 67-yearold male. A. On morphologic transverse T2-weighted MR image the peripheral zone shows diffuse high signal intensity, in accordance with healthy prostatic tissue. B. Transverse MR-spectroscopy at the same level of A) shows normal metabolite indices in all voxels throughout the prostate. C. Detail of the encircled voxel in B), demonstrating a dominant citrate peak, and low concentrations of choline and creatine, typical spectrum of non-cancerous tissue.

C carcinoma, however, the citrate level is significantly reduced, in part because of oxidation of citrate (29). Choline is an important constituent in the cell membrane metabolism and its concentration increases in highly cellular areas, such as tumor lesions (29). The contributions of polyamines and creatine are less important. Polyamines are reduced or absent in prostate cancer (30), but on 1,5T clinical MRI scanners, they cannot be entirely resolved from choline and creatine peaks (1). The creatine peak is not substantially different in cancer than in normal peripheral zone tissue and is included in the analysis only to ease the quantification of choline compounds (1, 31). The complimentary changes of these metabolites are used to predict the presence or absence of prostate

cancer by means of the choline-pluscreatine-to-citrate (CC/C) ratio, in which higher ratios are increasingly more suggestive of prostate cancer. Diagnostic accurracies up to 70-90% for MRI combined with MRSI have been reported, yielding a 20% improvement compared to morphologic T2-WI alone (Fig. 8) (24, 28, 29, 32). Interestingly, the CC/C ratio has also been shown to correlate with the Gleason score, therefore MRSI has the potential to non-invasively asses tumor aggressiveness (1, 2, 29). In our own investigation in 356 men with elevated PSA (33) the combination of MRI and MRSI was able to predict the presence or absence of high grade (Gleason 4 + 3 or higher) prostate carcinoma with a sensitivity of 92,7%, and a negative predictive value of 98,5%. This is of particular importance in patients

with persistently elevated PSA and multiple previous negative biopsies, in whom a negative MRI + MRSI may reduce the need for rebiopsy, but a positive MRI + MRSI warrants systematic rebiopsy, supplemented with biopsies targeted at the suspicious areas. Furthermore, the exclusion of high grade tumors with MRI + MRSI may support the choice for active surveillance in a prostate cancer patient in whom active therapy is deemed inappropriate. In dynamic contrast enhanced MRI (DCE-MRI) the prostate is evaluated on serial (every 2-5 sec) 3D GE T1-WI after intravenous bolus injection (0.1 mmol/kg) of a lowmolecular weight contrast agent (Gadolinium chelate) (1, 17). Alternatively, T2*-sequences have been designed that are sensitive to tissue perfusion and blood volume, but up to present there are only limited data on these methods (2, 24). Prostate carcinoma is associated with de novo angiogenesis, increased microvessel density and increased vascular permeability. Most prostate carcinomas show earlier and higher peak enhancement with initial steep slope of the signal intensity – time curve, as well as early washout (1,

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Fig. 8. â&#x20AC;&#x201D; 78-year-old male with prostate carcinoma in the central gland on the left side. A. On T2-weighted MR images there is normal high signal intensity in the peripheral zone. The central gland shows heterogeneous low signal intensity. B. Diffusion weighted MR image at the same level as a) demonstrates no restricted diffusion. C. MR-spectroscopy at the same level as A) and B) reveals reduced citrate levels and high choline levels in several voxels in the central gland on the left side, suspicious for prostate carcinoma. D. Detail of the encircled voxel in C), demonstrating a dominant choline peak and decreased concentration of citrate: typical spectrum of prostate cancer.

17). Several quantitative postprocessing parameters have been developed, such as Ktrans (= transfer constant or the permeability surface area, relating the fraction of contrast agent transferred from blood to the interstitial space), ve (= extravascular extracellular space (EES) or interstitial space) and kep (= rate constant,

representing the efflux from the EES to blood plasma) (1, 17, 23, 27). Most prostate carcinomas show an increased vascular permeability Ktrans and higher kep (17). However, there still appears to be some overlap in the enhancement patterns between tumors and benign conditions such as prostatitis, postbiopsy hemor-

rhage and benign prostatic hyperplasia (27). Accurracies of 70 to 90% have been reported for dynamic contrast enhanced MRI in primary diagnosis of prostate carcinoma, again yielding a 20% improvement compared to morphologic T2-WI alone (17, 27). Diffusion weighted imaging (DWI)

CLINICAL AND IMAGING TOOLS IN THE EARLY DIAGNOSIS OF PROSTATE CANCER — DE VISSCHERE et al

Fig. 9. — 70-year-old patient with prostate cancer in the central gland. A. Morphologic T2-weighted MR image through the midprostate shows normal high signal intensity in the peripheral zone. The central gland shows diffuse low signal intensity. B. Apparent diffusion coefficient map, corresponding to A) demonstrates restricted diffusion on the right side in the central gland. Targeted biopsy under transrectal ultrasound-guidance, confirmed prostate cancer in this area.

provides information about the amount of random ‘Brownian’ movements of water molecules. 4 mm single-shot fat-suppressed echo-planar images (EPI) are acquired at various gradients of diffusion (b-values = 0, 250, 500, 750 and 1000 s/mm²), with calculation of an apparent diffusion coefficient (ADC) (23, 24). The degree of diffusion of protons is dependent on tissue density, cell organisation and binding to macromolecules. Protons are very mobile in normal acinous water-rich glandular tissue, but restricted in their movement in densely packed water-poor tissue such as tumor areas, which contain many hydrophobic cell membranes (24). As a consequence, prostate cancer in both the peripheral zone and transition zone displays significantly lower ADC values compared to benign prostatic tissue (2, 23, 24, 34) (Fig. 9). Increased tumour detection with DWI and a correlation between Gleason score and ADC values have been reported by several authors but the overall diagnostic efficacy still remains unclear (2, 2325, 35-38). Positron Emission Tomography (PET) FDG-PET has a disappointingly low sensitivity for prostate cancer detection, with no difference in tracer uptake between benign prostatic hyperplasia and prostate carcinoma (1). New tracers such as

C Choline and 18F Fluorocholine are promising (18) as they show lower streak artifacts arising from the tracer-filled bladder and their very high sensitivity. Due to their low specificity they are not recommended for detection of primary prostate carcinoma (39-41), but are gaining acceptance in lymph node staging and in treatment follow up in patients with biochemical evidence of recurrence (1). 11

Conclusion Most prostate carcinomas are detected on the basis of elevated serum PSA levels but the gold standard for diagnosis of prostate carcinoma is histological assessment. Transrectal ultrasonography has a low diagnostic yield in detection of prostate carcinoma and is therefore not recommended for screening, but is useful for calculation of prostatic volume and for biopsy guidance. CT and PET are not indicated in the detection of primary prostate cancer and are reserved for lymph node staging and detection of distant metastases. MR imaging, particularly the combination of endorectal coil T2-weighted morphologic imaging with functional MRI techniques such as MR spectroscopy, Diffusion Weighted MRI and Dynamic Contrast Enhanced MRI will undoubtedly play an increasing role in the early detection and characterization of prostate

cancer, especially of high grade tumors. MRI is not a first-line approach for the diagnosis of prostate cancer, but it may improve the diagnostic yield of targeted biopsy, especially in patients with persistently increased PSA levels but negative previous biopsies. Exclusion of high grade cancer is of particular interest in patients with prostate cancer who choose for active surveillance. References 1. Fuchsjager M., Shukla-Dave A., Akin O., Barentsz J., Hricak H.: Prostate cancer imaging. Acta Radiol, 2008, 49: 107-120. 2. Mazaheri Y., Shukla-Dave A., Muellner A., Hricak H.: MR imaging of the prostate in clinical practice. Magma, 2008, 21: 379-392. 3. Catalona W.J., Loeb S.: The PSA era is not over for prostate cancer. Eur Urol, 2005, 48: 541-545. 4. Candefjord S., Ramser K., Lindahl O.A.: Technologies for localization and diagnosis of prostate cancer. J Med Eng Technol, 2009, 33: 585-603. 5. Verbaeys C., Oosterlinck W.: Prostaatspecifiek antigeen (PSA): indicatie, interpretatie en therapeutisch gevolg. Tijdschrift voor Geneeskunde, 2008, 64: 609-613. 6. Schroder F.H., Roobol M.J.: Defining the optimal prostate-specific antigen threshold for the diagnosis of prostate cancer. Curr Opin Urol, 2009, 19: 227-231.

70 7. Catalona W.J., Southwick P.C., Slawin K.M., et al.: Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging. Urology, 2000, 56: 255-260. 8. Shteynshlyuger A., Andriole G.L.: Prostate cancer: to screen or not to screen? Urol Clin North Am, 37: 1-9, Table of Contents. 9. Schroder F.H., Hugosson J., Roobol M.J., et al.: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med, 2009, 360: 1320-1328. 10. Pallwein L., Mitterberger M., Pelzer A., et al.: Ultrasound of prostate cancer: recent advances. Eur Radiol, 2008, 18: 707-715. 11. Lin D.W.: Beyond P.S.A.: utility of novel tumor markers in the setting of elevated PSA. Urol Oncol, 2009, 27: 315-321. 12. Schilling D., de Reijke T., Tombal B., de la Taille A., Hennenlotter J., Stenzl A.: The Prostate Cancer Gene 3 assay: indications for use in clinical practice. BJU Int, 2009, 105: 452-455. 13. Kirby R.S., Fitzpatrick J.M., Irani J.: Prostate cancer diagnosis in the new millennium: strengths and weaknesses of prostate-specific antigen and the discovery and clinical evaluation of prostate cancer gene 3 (PCA3). BJU Int, 2009, 103: 441-445. 14. Kijvikai K.: Digital rectal examination, serum prostatic specific antigen or transrectal ultrasonography: the best tool to guide the treatment of men with benign prostatic hyperplasia. Curr Opin Urol, 2009, 19: 44-48. 15. Bosch J.L., Bohnen A.M., Groeneveld F.P.: Validity of digital rectal examination and serum prostate specific antigen in the estimation of prostate volume in community-based men aged 50 to 78 years: the Krimpen Study. Eur Urol, 2004, 46: 753-759. 16. Lawrentschuk N., Fleshner N.: The role of magnetic resonance imaging in targeting prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels. BJU Int, 2009, 103: 730-733. 17. McMahon C.J., Bloch B.N., Lenkinski R.E., Rofsky N.M.: Dynamic contrast-enhanced MR imaging in the evaluation of patients with prostate cancer. Magn Reson Imaging Clin N Am, 2009, 17: 363-383. 18. Afnan J., Tempany C.M.: Update on prostate imaging. Urol Clin North Am, 37: 23-25, Table of Contents.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93 (2) 19. Gravas S., Mamoulakis C., Rioja J., et al.: Advances in ultrasound technology in oncologic urology. Urol Clin North Am, 2009, 36: 133-145, vii. 20. Pallwein L., Mitterberger M., Struve P., et al.: Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection. Eur Radiol, 2007, 17: 2278-2285. 21. Feleppa E.J., Porter C.R., Ketterling J., et al.: Recent developments in tissuetype imaging (TTI) for planning and monitoring treatment of prostate cancer. Ultrason Imaging, 2004, 26: 163172. 22. Kim C.K., Park B.K.: Update of prostate magnetic resonance imaging at 3 T. J Comput Assist Tomogr, 2008, 32: 163-172. 23. Somford D.M., Futterer J.J., Hambrock T., Barentsz J.O.: Diffusion and perfusion MR imaging of the prostate. Magn Reson Imaging Clin N Am, 2008, 16: 685-695, ix. 24. Seitz M., Shukla-Dave A., Bjartell A., et al.: Functional magnetic resonance imaging in prostate cancer. Eur Urol, 2009, 55: 801-814. 25. Van As N., Charles-Edwards E., Jackson A., et al.: Correlation of diffusion-weighted MRI with whole mount radical prostatectomy specimens. Br J Radiol, 2008, 81: 456-462. 26. Li H., Sugimura K., Kaji Y., et al.: Conventional MRI capabilities in the diagnosis of prostate cancer in the transition zone. AJR Am J Roentgenol, 2006, 186: 729-742. 27. Ocak I., Bernardo M., Metzger G., et al.: Dynamic contrast-enhanced MRI of prostate cancer at 3 T: a study of pharmacokinetic parameters. AJR Am J Roentgenol, 2007, 189: 849. 28. Futterer J.J., Heijmink S.W., Scheenen T.W., et al.: Prostate cancer localization with dynamic contrastenhanced MR imaging and proton MR spectroscopic imaging. Radiology, 2006, 241: 449-458. 29. Kurhanewicz J., Vigneron D.B.: Advances in MR spectroscopy of the prostate. Magn Reson Imaging Clin N Am, 2008, 16: 697-710, ix-x. 30. Shukla-Dave A., Hricak H., Moskowitz C., et al.: Detection of prostate cancer with MR spectroscopic imaging: an expanded paradigm incorporating polyamines. Radiology, 2007, 245: 499-506. 31. Kurhanewicz J., Vigneron D., Hricak H., Narayan P., Carroll P., SJ. N. Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.7-cmÂł) spa-

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JBR–BTR, 2010, 93: 71-76.

STAGING OF LUNG CANCER. DO WE NEED A DIAGNOSTIC CT OF THE BRAIN AFTER AN INTEGRATED PET/CT FOR THE DETECTION OF BRAIN METASTASES? W. De Wever, E. Bruyeer, Ph. Demaerel, G. Wilms, J. Coolen, J. Verschakelen1 Brain CT has been recommended in staging of patients with lung cancer because of its usefulness in the detection of metastases. Purpose of this study is to examine if a diagnostic brain CT (CT1) can be obviated when an integrated PET/CT (PET/CT ) is available. 87 consecutive patients underwent a diagnostic brain CT and a whole-body PET/CT within a period of 3 weeks to stage a known primary tumour. CT examinations were evaluated by two experienced neuroradiologists on the detection of brain lesions (benign and malignant). The results of PET/CT and CT reading were compared and both readings were compared with the clinical results. Statistical analysis was done by measuring sensitivity, specificity, PPV, NPV and accuracy. The relative accuracies were compared by a McNemar (exact) test for correlated proportions. Considering the CT1 as standard of reference, sensitivity, specificity, PPV, NPV and accuracy for the brain CT of PET/CT (CT2) and PET/CT were respectively 83%, 96%, 77%, 97%, 94% and 69%, 98%, 90%, 95%, 94%. Considering the clinical diagnosis as standard of reference these figures were for CT1, CT2 and PET/CT respectively 80%, 100%, 100%, 96%, 96% and 66%, 95%, 77%, 93%, 90% and 66%, 97%, 83%, 93%, 91%. There was no statistical difference between CT1 and CT2. The comparison of the additional CT in PET/CT with a diagnostic CT of the brain did not yield a statistical difference in the detection of brain lesions despite the inferior quality of the CT component of PET/CT. A diagnostic brain CT can be obviated when a PET/CT is available. Key-words: Lung neoplasms, metastases – Brain neoplasms, secondary - Brain, CT.

Lung cancer is a common disease with approximately 1.3 million new cases per year worldwide and is the leading cause of death in many countries (1, 2). Lung cancer is the commonest primary source of brain metastases (3). The detection of brain metastases at the time of diagnosis of lung cancer has important therapeutic complications. Surgical removal is rarely indicated, but occasionally, in carefully selected patients, it can reduce neurological impairment and prolong survival (4). Incidence rates of brain metastases from lung carcinoma that have been reported in the literature range from as low as 9.7% to as high as 54% (5). An optimal staging is important to determine the best possible therapeutic option, to clarify operability and to have an idea about the outcome for the patient. The ideal staging investigation should be inexpensive and easy to perform, have high sensitivity and specificity, provide accurate results that reflect the patient’s true clinical state, and yet cause minimal patient discomfort and morbidity (6).

The role of Computed Tomography (CT) in screening for cerebral metastases in potentially surgically resectable bronchogenic carcinoma patients has been actively debated for decades. MultiDetector CT has substantially reduced examination time, as well as enabled high-quality multiplanar reconstructions. The use of MRI has contributed to a higher detection rate of central nervous system metastases (5). The clinical gold standard, MRI, provides excellent anatomic details. Standard T1- and T2-weighted MRI is highly sensitive in determining the size and location of brain lesions, as well as mass effect, oedema, haemorrhage, necrosis, and signs of increased intracranial pressure (7). The efficacy of Positron Emission Tomography (PET) in depicting cerebral metastases is controversial. The sensitivity of PET in revealing cerebral metastases in patients with malignancy has been reported at 6882% when compared with anatomic imaging (8). The specificity of PET in evaluating cerebral abnormalities is

less clear than its sensitivity. In one study published in 1996 with 402 lung cancer patients, researchers reported a 38% specificity of PET alone when compared with anatomic imaging (9). PET/CT is a new anatomometabolic imaging technique. The first integrated PET/CT machine came into clinical practice in 1998, when a prototype was installed at the University of Pittsburgh Medical Centre (10, 11). PET/CT is the combination of two different examination techniques in one machine: CT giving anatomic information and PET giving metabolic information. Due to the concept of integrated PET/CT the technique of the CT component is somewhat different of that of a diagnostic CT of chest, abdomen and brain, and this can influence the quality of the CT images (12). A CT scan of the brain is included in an integrated PET/CT study. The quality of this brain scan is inferior compared to a diagnostic CT of the brain but may detect metastatic disease. The purpose of our study is to examine if a diagnostic brain CT (CT1) can be obviated when an integrated PET/CT is available. Patients and methods

From: Department of Radiology, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Address for correspondence: Dr W. De Wever, M.D., Department of Radiology, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: walter.dewever@uzleuven.be

Patients Between February 2004 and June 2006, 123 patients with a malignant

JBR–BTR, 2010, 93 (2)

Table I. — Etiology of the primary tumour. Primary tumour Lung Abdominal Urogenital Breast Neurological

Number

Primary tumour

Number

49 6 2 5 2

Oesophagus Haematological Melanoma Unknown

6 13 3 1

primary tumour underwent a whole body integrated PET/CT and a dedicated CT of the brain as part of their staging procedure with a time interval no longer than 3 weeks. After selecting those patients who received an integrated PET/CT and a dedicated CT, both with IV contrast administration, 87 patients (54 men, 33 women, mean age 58 years) were entered into this retrospective study. Forty-nine (56%) patients had primary lung cancer (Table 1). Twenty seven patients (31%) underwent the CT examination of the brain because of neurological symptoms. The final diagnosis of the presence or absence of brain lesions was made by the clinician and was used as the standard reference in this study. This final diagnosis was based on additional MR examination and/or follow-up during 12 months. There were 27 patients (31%) with neurological symptoms, 8 of them had a lung tumour. Methods All PET/CT studies were acquired on a dual-modality PET/CT tomograph (Biograph LSO Duo; Siemens Medical Solutions, Erlangen, Germany). The CT component of the Biograph LSO duo corresponds to a Somatom Emotion Duo (Siemens Medical Solutions, Erlangen, Germany), a 2-row spiral CT system with a maximum continuous scan time of 100 sec. and a maximum rotation speed of 75 rpm. CT images were acquired with 85 mAs, 130 kV, slice thickness of 5 mm, and table feed of 12 mm per rotation. The scanning area for CT was defined on a CT topogram. Whole body spiral CT was performed starting with the head and subsequently covering the neck, thorax, abdomen, and pelvis. To ensure diagnostic CT image quality, 120 mL of a contrast agent containing 300 mg iodine per ml was administered intravenously using an automated injector (1.6 mL/sec, scan delay 100 sec). CT was performed during breath hold at expiration tidal volume.

The PET component of the integrated PET/CT is based on an ECAT ACCEL (Siemens Medical Solutions, Erlangen, Germany), a full ring Lutetium ortho silicate (LSO) based PET system with an in plane spatial resolution of 4.6 mm and an axial field of view of 15.5 cm for each bed position. The scanning area for PET was defined on the CT topogram. Non attenuation and attenuationcorrected images were made. PET imaging was done 75 minutes after injection of FDG which in general gives a good balance between the duration of the examination and the amount of FDG-uptake necessary for interpretation. Patients had been instructed to fast for a minimum of 4 hours prior to starting the examination. Blood samples collected before the injection of the radioactive tracer ensured blood glucose levels in the normal range. The diagnostic CT of the brain (CT1) was done using the following scan parameters: 380 mAs, 120 kV, and sequential scan protocol. At the skull base a slice thickness of 2.4 mm, a collimation of 24 x 1.2 mm, a feed of 28.5 mm, and a rotation time of 4 sec. were used. At the brain: these figures were respectively 9.0 mm, 30 x 0.6 mm, 18 mm and 4 sec. Both CT1 and the brain CT part of the PET/CT (CT2) were evaluated by two experienced neuroradiologists searching for suspected brain lesions (brain metastases or primary tumours). The time interval between the evaluations of the 2 CT examinations was at least 2 weeks and conclusions were reached by consensus. The readers were blinded to the clinical information and to the images of the other CT study. The PET/CT of the brain was evaluated by a general radiologist and a nuclear medicine physician in consensus. If CT and/or PET were suggestive for a brain tumour or metastasis, the PET/CT was considered as positive. The results of CT2 and PET/CT were correlated with those of the diagnostic CT1 which

was used at that moment as standard of reference. The results of CT1, CT2 and PET/CT were also correlated with the final diagnosis. The sensitivity, specificity, accuracy and predictive values of CT1, CT2 and PET/CT were calculated using the standard definitions. The relative accuracies were compared by a Mac Nemar (exact) test for correlated proportions (with 95% confidence interval). Results The final diagnosis, made by the clinician and based on additional MR examination and/or follow-up during 12 months included 15 patients (17%) with malignant brain lesions (12 brain metastases, 3 primary brain tumours), 12 patients (14%) with benign brain lesions (ischemic lesions) and 60 patients (69%) without lesions. In the group of patients with a lung tumour (49 patients), 6 (12%) patients had malignant brain lesions (all brain metastases), 6 patients (12%) had benign brain lesions and 37 patients (76%) had no lesions. In the group of patients with a lung tumour, there were only 8 patients (16%) with clinical neurological symptoms. Four of these patients showed brain metastases, the other 4 patients didn’t show brain lesions. CT1 showed 12 patients with malignant lesions (Fig. 1). There were 3 false negatives with CT1. In the group of patients with a lung tumour (49 patients), CT1 demonstrated 5 patients with malignant lesions (1 false negative), all brain metastases. CT1 detected all the patients with a lung tumour with neurological symptoms who had brain metastases. CT2 showed 10 patients with malignant lesions. There were 5 false negatives with CT2. In the group of patients with a lung tumour CT2 demonstrated 4 patients with malignant lesions, there were 2 false negatives (Fig. 2). The four patients with malignant brain lesions detected with CT2, were also those patients with a lung tumour and with neurological symptoms. PET/CT showed 10 patients with malignant lesions. There were 5 false negatives and 2 false positives with PET/CT. In the group of patients with a lung tumour PET/CT demonstrated 3 patients with malignant lesions, there were 3 false negatives. Sensitivity, specificity, predictive values and accuracy of CT2 and PET/CT to detect patients with malignant brain lesions were first

STAGING OF LUNG CANCER — DE WEVER et al

Fig. 1. — 67-year-old man with SCLC in the left upper lobe. Patient developed neurological symptoms. Diagnostic brain CT (upper row) showed multiple brain metastases: two right cerebellar, one right frontal and one left frontal. All these metastases are surrounded by oedema. The CT of the integrated PET/CT (lower row) showed also brain metastases but could not demonstrate one right cerebellar metastasis (first image). The quality of the CT of the PET/CT is inferior of this of a diagnostic brain CT: lesser contrast opacification and also the surrounded oedema is not so clear visualised, however this can be due to the treatment with corticosteroids in the short time between diagnostic brain CT and integrated PET/CT.

Fig. 2. — 53-year-old woman with oatcell carcinoma with extensive disease. Patient had also brain metastasis. Diagnostic CT of the brain (A) was true positive showing a right cerebellar brain metastasis. This metastasis was not visualised on the brain CT of the integrated PET/CT (B) due to the inferior quality of this CT.

calculated by considering CT1 as the standard of reference and secondly by considering the final diagnosis as standard of reference (Table II). The relative accuracies are summarized in Table III. We couldn’t find a statistically significant difference between CT1 and CT2.

Discussion Recently, it has been shown that in tumour staging of patients with lung cancer, analysis of PET/CT images is superior to the analysis of CT images alone or PET images alone, and to the combined analysis

of PET and CT images viewed side by side (13). CT images from PET/CT made with our PET/CT protocol have a lower image (Fig. 1 and 2). The quality of CT and PET/CT images depends on different parameters. Some parameters used for PET/CT, such as CT dose and the use of

JBRâ&#x20AC;&#x201C;BTR, 2010, 93 (2)

Table II. â&#x20AC;&#x201D; Sensitivity, Specificity, predictive values and accuracy of CT1, CT2 and PET/CT for the detection of malignant brain lesions. %

Sensitivity

Specificity

PPV

NPV

Accuracy

96 98

77 90

97 95

94 94

97 100

80 100

97 95

96 96

94 94

90 88

94 88

92 88

100 95 97

100 77 83

96 93 93

96 90 91

100 97 100

100 80 100

97 95 93

98 94 93

100 93 93

100 90 90

88 82 82

92 85 85

CT1 as standard of reference All patients with a primary tumour 83 CT2 69 Integrated PET/CT Patients with a lung tumour CT2 80 Integrated PET/CT 60 Patients with neurological symptoms CT2 90 Integrated PET/CT 80 Final diagnosis as standard of reference All patients with a primary tumour 80 CT1 CT2 66 Integrated PET/CT 66 Patients with a lung tumour CT1 83 CT2 66 Integrated PET/CT 50 Patients with neurological symptoms CT1 83 CT2 75 Integrated PET/CT 75 CT1: diagnostic CT of the brain CT2: brain CT part of the integrated PET/CT.

intravenous (IV) contrast media, that influence image quality, are different from those used for a diagnostic CT (12). An important question is which CT dose has to be chosen for the integrated PET/CT protocol. For a diagnostic CT a dose of about 140 kV and 120 mAs is normally used to obtain images with optimal quality. Due to the concept of PET/CT, this dose cannot be generated with the first PET/CT scanners like ours. Hany et al. (14) compared different CT doses. In this study, 21% of all lesions were classified as undecided with PET alone and could therefore not be specified. By using low-dose CT (10-40 mAs) for image co-registration, an additional 7% of all lesions could be classified. The reduction in false-negative and falsepositive results significantly increased the accuracy of PET/CT. When an 80 mAs CT was used, the number of undecided lesions was reduced to 12%. However, using a 120 mAs CT did not further improve lesion classification. Therefore, the authors concluded that PET 80 mAs CT should be used for optimal reduction of the number of undecided lesions. However there are no studies who compares a diagnostic CT of

the brain with the brain CT part of a PET/CT in the detection of brain metastases in the staging of patients with a known primary tumour. In this study we tried to examine if we can obviate a diagnostic CT of the brain if a total-body PET/CT is available. Brain metastases are a common way of general dissemination of lung cancer. The incidence of brain metastases in the initial staging of patients with primary lung cancer has been reported to be between 12% and 18% (15, 16). Also in our study, 12 % of the patients with a lung tumour had brain metastases. The signs and symptoms of brain metastasis are related to the involved brain area. Most patients present with headache or focal neurological deficits. Common focal symptoms include muscle weakness, gait disturbances, visual field defects and aphasia (17) and these symptoms justify further investigation. Preoperative evaluation and follow-up with diagnostic imaging for brain metastases in asymptomatic patients remains a controversial issue (18, 19). International guidelines for staging a lung tumour are proposed by the American Thoracic Society / European Respiratory Society (20).

Several authors have recommended that brain CT must be performed in the staging of lung cancer because of its usefulness in the detection of occult metastases (21). Other authors have advocated that the routine use of brain CT is not warranted in patients without neurological signs or symptoms because of the marginal cost-effectiveness (22, 23). In this setting, it is interesting to know whether the brain CT part of the whole-body PET/CT is able to detect symptomatic and occult brain metastases because this brain CT is part of the examination in many institution and has no additional cost. Therapeutic management of patients with brain metastases includes whole-brain radiotherapy, stereotactic radiosurgery, surgery, and chemotherapy. To select the appropriate therapy, the physician must consider the extent of the brain metastasis, including the number of brain metastases, their size, location, and histology (24). Different studies are made to compare the usefulness of MRI and CT in the detection of brain metastases during preoperative evaluation and postoperative follow-up. Yokoi found in his study

STAGING OF LUNG CANCER â&#x20AC;&#x201D; DE WEVER et al

Table III. â&#x20AC;&#x201D; Relative accuracies of the different imaging techniques in the detection of malignant brain lesions compared by Mc Nemar exact test (confidential interval 95%). Mc Nemar test

All patients with a known primary tumour

CT2 Integrated PET/CT

Patients Patients with a with neurological lung tumour symptoms

CT1

P = 1,000 P = 0,6831

P = 0,4795 P = 0,4795

P = 0,4795 P = 1,000

CT1: diagnostic CT of the brain CT2: brain CT part of the integrated PET/CT.

that MRI showed a tendency toward a higher preoperative detection rate of brain metastases than CT. The mean maximal diameter of the brain metastases was significantly smaller in the MRI group than in the CT group. However there was no significant difference between the groups in survival time (25). Despite the fact that MRI is the superior test for the detection of brain metastases, CT of the brain has a well-documented accuracy in detecting metastatic lesions and has been described as being of value in the preoperative staging of patients with non-small cell lung cancer who were free of neurological symptoms (3, 26, 27). CT is adequate to exclude brain metastases in most patients but it can miss small lesions especially those who are located in the posterior fossa (28). The CT appearance of brain metastases is non-specific and may mimic other processes, such as infectious disease. Therefore, the CT scan must always be interpreted within the context of the clinical picture of the individual patient, particularly since cancer patients are vulnerable to opportunistic CNS infections or may develop second primaries, which can include primary brain tumours (29). This interpretation within the whole context of the clinical picture was not performed in our study. The readers only knew that the patient had a primary tumour but did not know whether the patients had neurological symptoms or not. Using the final diagnosis as standard of reference we found a sensitivity, specificity, and accuracy for the detection of malignant brain lesions in the global patient group with CT1, CT2 and integrated PET/CT of respectively 80%, 100%, 96% and 66%, 95%, 90% and 66%, 97%, 91%. The results of CT1were better of those of CT2, however we could not find a significant difference between CT1 and

CT2. When we examined only the patients with a lung tumour, these results for CT1 and CT2 were better. Crane et al found in his study a sensitivity of 98% and a PPV of 98% for CT scans in the detection of brain metastases in patients with or without neurological signs or symptoms. However, CT scans were positive in only 6% of the asymptomatic patients (30). Using as reference criteria clinical judgment supported by a strict follow-up evaluation, Ferrigno et al found in his study a sensitivity, specificity, and accuracy of 92%, 99%, and 98% respectively (19). Also using the clinical judgment and the follow-up as standard of reference, we were not able to demonstrate such a high sensitivity (83%). However, the specificity and accuracy in our study were in the same range. When our patients had neurological symptoms, these figures became better. The efficacy of PET in depicting cerebral metastases is controversial. Sensitivities between 68%-82% and specificities of about 83% have been reported when compared with anatomic imaging (7, 29). We did not examine the role of PET only in the detection of brain metastases. In the literature, no detailed information is available about the use of the CT of the brain from a wholebody PET/CT to detect brain metastases. Although in our study no statistical significant difference was found between the diagnostic CT and the CT part of the integrated PET/CT (Table III), the results of the diagnostic CT were somewhat better. The results of the CT part of the integrated PET/CT interpreted apart from the PET information are somewhat better than those of the integrated PET/CT. The reason that PET/CT results are not so good as those of CT1 and CT2 can be found in the fact that CT1 and CT2 where evalu-

ated by experienced neuroradiologists in consensus and that PET/CT was evaluated by a general radiologist and nuclear medicine physician in consensus. Conclusion Brain CT has been recommended in the staging of lung cancer because of its usefulness in the detection of occult metastatic disease. Nevertheless, the routine use of brain CT is probably not warranted in patients without neurological signs or symptoms because of the marginal cost-effectiveness. PET/CT offers an additional CT scan of the brain without additional costs. We have shown that when comparing this CT with a diagnostic CT of the brain, there is no statistically significant difference between these two CT scans in detecting malignant brain lesions, despite the fact that the quality of the CT of the brain of the PET/CT is inferior. So, a diagnostic CT of the brain is very likely not necessary when a whole-body PET/CT has been performed especially in those patients with clinical symptoms. In case of clinical symptoms and a negative PET/CT or in order to obtain a more detailed idea about the multifocality of the brain lesions, an additional MRI of the brain is appropriate. References 1. Janssen-Heijnen M.L., Coebergh J.W.: Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe. Lung Cancer, 2001, 31: 123-137. 2. Schrevens L., Lorent N., Dooms C., Vansteenkiste J.: The role of PET scan in diagnosis, staging, and management of non-small cell lung cancer. Oncologist, 2004, 9: 633-643. 3. Kormas P., Bradshaw J.R., Jeyasingham K.: Preoperative computed tomography of the brain in non-small cell bronchogenic carcinoma. Thorax, 1992, 47: 106-108. 4. Tarver R.D., Richmond B.D., Klatte E.C.: Cerebral metastases from lung carcinoma: neurological and CT correlation. Work in progress. Radiology, 1984, 153: 689-692. 5. Schouten L.J., Rutten J., Huveneers H.A., Twijnstra A.: Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer, 2002, 94: 2698-2705. 6. Sihoe A.D., Yim A.P.: Lung cancer staging. J Surg Res, 2004, 117: 92106.

76 7. Chen W. Clinical applications of PET in brain tumors. J Nucl Med, 2007, 48: 1468-1481. 8. Ludwig V., Komori T., Kolb D., Martin W.H., Sandler M.P., Delbeke D.: Cerebral lesions incidentally detected on 2-deoxy-2-[18F)fluoro-D-glucose positron emission tomography images of patients evaluated for body malignancies. Mol Imaging Biol, 2002, 4: 359-362. 9. Palm I., Hellwig D., Leutz M., Rentz K., Hellwig A., Kirsch C.M., Ukena D., Sybrecht G.W.: (Brain metastases of lung cancer: diagnostic accuracy of positron emission tomography with fluorodeoxyglucose (FDG-PET)). Med Klin (Munich), 1999, 94: 224-227. 10. Beyer T., Townsend D.W., Brun T., Kinahan P.E., Charron M., Roddy R., Jerin J., Young J., Byars L., Nutt R.: A combined PET/CT scanner for clinical oncology. J Nucl Med, 2000, 41: 13691379. 11. Townsend D.W., Beyer T., Blodgett T.M.: PET/CT scanners: a hardware approach to image fusion. Semin Nucl Med, 2003, 33: 193-204. 12. De Wever W., Stroobants S., Verschakelen J.A.: Integrated PET/CT in lung cancer imaging: history and technical aspects. JBR-BTR, 2007, 90: 112-119. 13. De Wever W., Ceyssens S., Mortelmans L., Stroobants S., Marchal G., Bogaert J., Verschakelen J.A.: Additional value of PET-CT in the staging of lung cancer: comparison with CT alone, PET alone and visual correlation of PET and CT. Eur Radiol, 2007, 17: 23-32. 14. Hany T.F., Steinert H.C., Goerres G.W., Buck A., von Schulthess G.K.: PET diagnostic accuracy: improvement with in-line PET-CT system: initial

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results. Radiology, 2002, 225: 575581. Hooper R.G., Tenholder M.F., Underwood G.H., Beechler C.R., Spratling L.: Computed tomographic scanning of the brain in initial staging of bronchogenic carcinoma. Chest, 1984, 85: 774-776. Mintz B.J., Tuhrim S., Alexander S., Yang W.C., Shanzer S.: Intracranial metastases in the initial staging of bronchogenic carcinoma. Chest, 1984, 86: 850-853. Biswas G., Bhagwat R., Khurana R., Menon H., Prasad N., Parikh P.M.: Brain metastasis â&#x20AC;&#x201C; evidence based management. J Cancer Res Ther, 2006, 2: 5-13. Hillers T.K., Sauve M.D., Guyatt G.H.: Analysis of published studies on the detection of extrathoracic metastases in patients presumed to have operable non-small cell lung cancer. Thorax, 1994, 49: 14-19. Silvestri G.A., Littenberg B., Colice G.L.: The clinical evaluation for detecting metastatic lung cancer. A meta-analysis. Am J Respir Crit Care Med, 1995, 152: 225-230. Pretreatment evaluation of nonsmall-cell lung cancer. The American Thoracic Society and The European Respiratory Society. Am J Respir Crit Care Med, 1997, 156: 320-332. Ferrigno D., Buccheri G.: Cranial computed tomography as a part of the initial staging procedures for patients with non-small-cell lung cancer. Chest, 1994, 106: 10251029. Cole F.H., Jr., Thomas J.E., Wilcox A.B., Halford H.H., 3rd.: Cerebral imaging in the asymptomatic preoperative bronchogenic carcinoma patient: is it worthwhile?

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LONGITUDINAL CORTICAL SPLIT SIGN AS A POTENTIAL DIAGNOSTIC FEATURE FOR CORTICAL OSTEITIS V. Goosens1, F.M. Vanhoenacker2, I. Samson3, P. Brys1 Septic cortical osteitis is a rare but distinct type of bone infection that is characterized as a hematogenously seeded infection predominantly or exclusively limited to the cortex. Diagnosis is difficult and often delayed. Combination of clinical and laboratory findings together with the typical radiological findings consisting of vertically orientated cortical osteolysis, the ‘cortical split sign’ and the predominantly cortical disruption at the periosteal side of the cortex may lead to the correct diagnosis. Key-word: Bones, infection.

In adults, subacute and chronic forms of osteomyelitis are frequently encountered, usually secondary to an open injury to bone and surrounding soft tissue. Septic cortical osteitis – however – is a rare subgroup of bone infection caused by hematogenous spread that is predominantly or exclusively limited to the cortex of long tubular bones and usually affecting adolescents and young adults. Diagnosis can be difficult because of the nonspecific clinical findings and sometimes misleading imaging features mimicking a focal bone lesion. The purpose of this paper is to present three cases of septic cortical osteitis, in which the cortical split sign may be a potential useful clue to the correct diagnosis. The literature on the subject is reviewed. Case report Case 1 A 17-year-old, otherwise healthy male student and football player, presented to his general practitioner complaining of a continuous pain in the left leg, causing limping and awaking him at night. Symptoms started abruptly one month previously, without any history of trauma. Clinical examination revealed a firm, slightly painful area at the posterolateral aspect of the left thigh. Laboratory investigation was unremarkable except for a slightly raised C-reactive protein (CRP). Plain radiographs showed a 12 cm long cortical defect paralleling the

long axis of the middiaphyseal femur with a central linear density and faint periosteal reaction (Fig. 1A). Computed tomography (CT) demonstrated a longitudinal osteolysis with central density and partial cortical disruption at the periosteal side of the cortex (Fig. 1BC). Magnetic Resonance (MR) imaging showed an irregularly delineated cortical defect on the posterior side of the femur, surrounded by edema in the bone marrow and periosseous soft tissues. The cortical defect was slightly hyperintense to muscle on T1- and T2-weighted images, with a central linear hypointense focus on both pulse sequences, representing a sequestered bone fragment (Fig. 1D). After administration of intravenous gadolinium contrast, the cortical lesion showed peripheral rim enhancement as well as enhancement of the adjacent soft tissues and bone marrow (Fig. 1E). The diagnosis of chronic cortical osteitis was suggested and surgical debridement was performed. Culture of the obtained tissue was positive for Staphylococcus aureus and histology confirmed the diagnosis of cortical osteitis. Postoperatively, a 6-week course of antibiotics was initiated. The further follow-up was uneventful. Case 2 A 38-year-old female presented to the emergency department with pain in her left upper limb. The symptoms were of insidious onset without his-

From: 1. Department of Radiology, University Hospital, Leuven, 2. Department of Radiology, University Hospital, Antwerp, AZ Sint-Maarten Duffel-Mechelen, 3. Department of Orthopedic Surgery, University Hospital, Leuven, Belgium. Address for correspondence: Dr V. Goosens, M.D., Department of Radiology, University Hospitals, Herestraat 49, B-3000 Leuven, Belgium. E-mail: veerle.goosens@uz.kuleuven.be

tory of trauma, getting worse in recent days. Plain radiographs of the left femur showed a 7 cm long longitudinal intracortical lucency on the anteromedial side of the left femur with preservation of the internal cortical lining, irregular thickening of the outer cortex and disorganized periosteal reaction (Fig. 2A). CT confirmed a longitudinal osteolytic area in the anteromedial cortex containing internal central linear densities, representing calcifications or bone fragments. There were multiple radiolucent defects in the outer cortex and an interrupted periosteal reaction but there was absence of intramedullary extension (Fig. 2B-C). T2-weighted, fat-saturated MRI showed increased signal intensity in the cortex with focal outer cortical disruption and associated soft tissue and bone marrow edema (Fig. 2D-E). Surgical debridement was performed and histological and laboratory findings confirmed the diagnosis of cortical osteitis. After a 3 month period of antibiotic treatment, there was a complete clinical recovery. Case 3 A 30-year-old male recreational football player presented with gradually worsening pain in his right upper leg since three weeks. As in the two previous cases, plain radiographs and CT revealed a 6 cm long longitudinal cortical osteolysis with a central linear density surrounded by faint periosteal reaction (Fig. 3A). Partial cortical disruption at the periosteal side of the cortex was better evaluated on CT (Fig. 3B-C). MRI showed an irregularly delineated cortical defect, surrounded by extensive bone marrow edema and peri-osseous soft tissue edema (Fig. 3D). Histological examination after surgical debridement confirmed the diagnosis of cortical osteitis.

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Fig. 1. — A. Plain radiographs of the left femur show a longitudinal cortical defect with a central linear density (arrow) and faint periosteal reaction (arrowhead). B. Axial CT image shows a well defined focal osteolysis of the outer cortex, which contains a central linear sequestrum. There is cortical disruption at the periosteal side with periosteal reaction (arrow). C. Sagittal reformatted CT image demonstrates the typical ‘cortical split sign’, consisting of a vertically orientated osteolysis with a central linear sequestrum. D. Coronal fat-suppressed T2-weighted MR image of the femur shows a linear hyperintensity in the medial femoral cortex (arrow) and high signal intensity involving the marrow and surrounding soft tissues representing edema. E. Axial fatsuppressed T1-weighted MR image after intravenous administration of gadolinium contrast depicts rim enhancement of the lesion, with enhancing perilesional soft tissue and bone marrow edema.

Discussion Septic cortical osteitis represents an unusual type of bone infection, first described during the nineteenth century by Gerdy (1). It is characterized as a hematogenously seeded infection predominantly or exclusively limited to the cortex. Only a few case reports have been reported in literature (1, 2). The mechanism of bacterial deposition is thought to be caused by hematogenous spread of septic emboli in the periosteal plexus. These plexuses are derived from the arteries of the neighboring muscles and supply the outer third of the cortex (Fig. 4). Any form of end-capillary obstruction, including a small hematoma caused by minor trauma, could produce an area of avascular necrosis that predisposes to infection (3). These anatomic and patho-

genetic data may explain why cortical disruption occurs predominantly at the periosteal side of the cortex, whereas the endosteum usually remains intact, such as demonstrated in our three cases. Interestingly, two of our patients were soccer players, which favor the hypothesis that minor trauma may contribute to the pathogenesis. The long bones of the lower limb are the most frequent locus of infection. Like in other forms of osteomyelitis, Staphylococcus aureus is the most common causative infective organism. Diagnosis may be challenging because patients present with vague symptoms consisting of local tenderness and minimal or even no fever. Routine laboratory tests are usually nonspecific with normal leukocyte count and slightly elevated CRP. Therefore, the infection is

E often left untreated initially and can progress to a chronic condition resulting in focal bone loss, sequestrum formation, and reactive bone sclerosis. Moreover, the radiologic findings are often nonspecific and depend on the time of presentation. Plain radiographs may reveal a cortical osteolysis along with the long axis of the long bone with a central linear density and limited periosteal reaction. Although ultrasound may demonstrate elevation and/or thickening of the periosteum of more than 3 mm due to pus emanating from the cortex, it provides only limited information about bone changes (3). CT is superior for precise evaluation of the extent of cortical destruction and is the preferred modality for identification of anosseous sequestrum, resulting in the ‘cortical split sign’. Cortical disruption – even subtle – at the periosteal side is also better assessed on CT compared to plain radiography. On the other hand, MRI is far superior to demonstrate asso-

A POTENTIAL DIAGNOSTIC FEATURE FOR CORTICAL OSTEITIS — GOOSENS et al

A A

D B

Fig. 2. — A. Plain radiographs of the left femur show an intracortical lucency on the anteromedial side of the left femur with preservation of the internal cortical lining and thickening of the outer cortex. There is a partially disrupted periosteal reaction (arrow). Note the vertical course of the lesion, parallel to the cortical bone. B. Axial CT image shows a focal cortical osteolysis with central punctiform densities. Note the focal cortical destruction and faint periosteal reaction (arrow). C. Coronal reformatted CT image demonstrates the ‘cortical split sign’. D. Coronal fat-suppressed T2-weighted MR image demonstrates high signal intensity in the medial femoral cortex (arrow), the marrow and surrounding soft tissues. E. Axial fat-suppressed T1-weighted MR image with gadolinium contrast shows enhancement of the focal cortical destruction and associated bone marrow and soft tissue edema.

ciated bone marrow edema and soft tissue inflammation, which is another important clue in the differential diagnosis with noninfectious lesions. Whenever infection is suspected, gadolinium contrast administration is mandatory for evaluation of sinus tracts, fistulas, and soft tissue abscesses.

A bone lesion that consists of a lucent area with a central sclerotic focus has been referred to as the ‘button sequestrum sign’ (4). This sign was first described as a radiological manifestation of eosinophilic granuloma, a localized form of Langerhans’ cell histiocytosis, but this sign may be seen in other

C Fig. 3. — A. Plain radiographs of the right femur show a longitudinal osteolysis in the lateral femoral cortex with central density and faint periosteal reaction (arrow). B. Axial CT image shows a ill defined osteolysis of the outer cortex, which contains a central sequestrum. There is cortical disruption at the periosteal side with faint periosteal reaction. C. Coronal reformatted CT image demonstrates the ‘cortical split sign’. Note the intact endosteal cortex (arrow). D. Coronal fat-suppressed T2-weighted MR image demonstrates an irregularly delineated cortical defect, surrounded by extensive edema in the bone marrow and peri-osseous soft tissues (arrow).

Fig. 4. — Line drawing of the vascular supply of the cortex of a long bone. The outer third of the cortical bone is supplied by periosteal plexuses (1), derived from arteries of neighbouring muscles and soft tissues. These periosteal plexuses form connections with the cortical capillaries (2), derived from medullary branches, which supply the inner two thirds of the cortex.

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entities such as osteomyelitis, fibrosarcoma and lymphoma as well. Other differential diagnoses to be considered in case of a cortical radiolucency with a central density include osteoid osteoma, longitudinal stress fracture and osseous changes associated with calcium hydroxyapatite crystal deposition disease (HADD). Osteoid osteoma (O.O.) appears as a lucent area representing the nidus, which may be uniformly radiolucent or contain variable amounts of calcification, and is surrounded by bone sclerosis. Unlike the osteolysis in cortical osteitis which shows an irregular lining of the inner borders, the lucent area in O.O. has more smooth round margins (5). Moreover, the more extensive length of the cortical osteolysis in our cases argues against O.O. A longitudinal stress fracture can also present as a linear cortical lucency but on axial CT or MR images, the cortical cleft representing the fracture line is visible on multiple adjacent sections. Other secondary findings of a longitudinal stress fracture are eccentric periosteal reaction and new bone formation, eccentric soft tissue edema and a superomedial location relative to the nutrient foramen (6). HADD-associated tendinopathy sometimes may produce bone erosion simulating a radiolucent lesion, but this is not often a diagnostic dilemma because of the characteristic site of the calcification and erosion at a tendinous insertion (7). Treatment of cortical osteitis requires adequate debridement in

addition to long-term systemic antibiotic therapy. In conclusion, cortical osteitis represents a rare subgroup of osteomyelitis. In young patients with non specific complaints, slightly elevated CRP and radiological and CT findings of a vertically orientated cortical osteolysis with the typical ‘cortical split sign’ and cortical disruption at the periosteal side of the cortex, the diagnosis of cortical osteitis should be strongly considered. References 1. 2.

4. 5.

Lagard D., Dupont S., Boutry N., Delfaut E., Cotten A.: Ostéite corticale septique. J Radiol, 2000, 81: 54-58. Picard C., Krug B., Boutsen Y., et al.: An uncommon cause of septic cortical osteitis. Clin Nucl Med, 2007, 32: 624-627. Resnick D., Niwayama G.: Osteomyelitis, septic arthritis and soft tissue infection: Mechanisms and situations. In: Resnick D., editor. Diagnosis of Bone and Joint Disorders. 4rd ed. WB Saunders, Philadelphia, 2002, pp 2377-2624. Krasnokutsky M.V.: The button sequestrum sign. Radiology, 2005, 236: 1026-1027. Pendse N.A., Rastogi H., Bera M.L., Agarwal G., Gulati Y.: Cortical sclerosis with central nidus – report of two cases. Ind J Radiol Imag, 2005, 15:469-472. Craig J.G., Widman D., Van Holsbeeck M.: Longitudinal stress fracture: patterns of edema and the importance of the nutrient foramen. Skeletal Radiol, 2003, 32: 22-27. Hayes C.W., Conway W.F.: Calcium Hydroxyapatite Deposition Disease. Radiographics, 1990, 10: 1031-1048.

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BRODIE’S ABSCESS REVISITED P.R. Kornaat1, M. Camerlinck2, 3, F.M. Vanhoenacker2, 3, G. De Praeter3, H.M. Kroon1 Radiology plays an important role in the diagnosis of a Brodie’s abscess, as can be difficult for a clinician to identify the disease using clinical information alone. A Brodie’s abscess is clinically difficult to diagnose because patients typically have mild local symptoms, few or no constitutional symptoms, and near normal laboratory values. Furthermore, a Brodie’s abscess may mimic various benign and malignant conditions, resulting in delayed diagnosis and treatment. The most frequently made incorrect diagnosis is that of a primary bone tumor. The present pictorial review summarizes imaging clues to the diagnosis of a Brodie’s abscess, such as the serpentine sign on conventional radiographs and the penumbra sign seen on Magnetic Resonance (MR) images. A Brodie’s abscess is difficult to diagnose, however, once diagnosed, it is a curable disease with a 100% cure rate. Key-word: Bones, abscess.

History The original description of a localized bone abscess dates from 1832 and is named after Sir Benjamin Collins Brodie, a surgeon in St. George’s Hospital, London, United Kingdom (Fig. 1). He amputated the leg of a man who had intractable pain for a number of years. Unfortunately, the patient died due to the complications of the amputation. After macroscopic examination of the amputated limb, Brodie described the condition in the tibia as “a cavity the size of a walnut filled with dark-colored pus. The bone immediately surrounding the cavity was whiter and harder than the surrounding bone. The inner surface of the cavity appeared to be highly vascular” (1). Pathogenesis A Brodie’s abscess is a subtype of a subacute osteomyelitis. In a Brodie’s abscess a situation develops where the bacteria and the host defenses are equally matched; the abscess is walled-off, minimizing the systemic response. An osseous infection can be caused by haematogenous spread of organisms to bone or by direct local invasion by bacteria. The organisms reach the bone from a disrupted site elsewhere in the body such as a skin pustule, furuncles, impetigo, infected blisters and burns, or secondary to an infection of another organ system (urogenital infections, enteritis, cholangitis or endocarditis).

Fig. 1. — Sir Benjamin Collins Brodie (1783-1862), British physiologist and surgeon.

Infection has even been suggested to be the outcome of common events such as normally harmless daily teeth brushing. Often the infective focus is not identified. Direct spread to bone can occur from bac-

From: 1. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, 2. Department of Radiology, University Hospital Antwerp UZA, Antwerp, Belgium 3. Department of Radiology, AZ Sint-Maarten, Duffel-Mechelen, Belgium. Address for correspondence: Dr P.R. Kornaat, M.D., Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E-mail: P.R.Kornaat@lumc.nl

terial invasion, e.g. through penetrating wounds or postoperative infection. This route is most likely after contaminated soft tissue trauma, as well as in diabetic patients with plantar ulcers or in bedridden patients with decubitus ulcers (2). The causative organism is usually coagulase-positive Staphylococcus (3). Other organisms encountered are Streptococcus B, in the newborn, Pseudomonas, which is more frequent in drug addicts than in the general population, and

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Salmonella, in patients with diabetes mellitus or sickle cell anemia. Haemophilus influenza, Kingella kingae, Mycobacterium tuberculosis, Spirochaetes, Fungi (Candida, Actinomyces), Viruses and Helminths (e.g. Echinococcus) are also described. However, in almost 50% of cases of a Brodie’s abscess, no organism can be cultured. A Brodie’s abscess is most commonly seen in children and characterized by accumulation of the pathogenic organisms in the terminal arterioles and capillaries of the metaphysis. Metaphyseal locations are most common before closure of the growth plates. After closure, an epiphyseal / metaphyseal abscess is most frequent. Epiphyseal lesions may also occur in older adolescents as the growth plates are closed and vessels cross the closed growth plate, failing to provide a barrier to the epiphysis. Interconnecting infection of the epiphysis and metaphysis is explainable in infants younger than 18 months, when one considers that vascular communication between the epiphysis and metaphysis is present until the age of 18 months, as described by Trueta (4). Another interesting explanation for the localization of subacute osteomyelitis adjacent to the growth plate cartilage is the finding by Speers and Nade that S. aureus has a certain affinity for physeal cartilage (5). Infection develops as the organisms spread into the perivascular interstitial tissue, leading to a leucocytic infiltration that permeates the bone marrow. The dissemination progresses along Volkmann’s canals and through the Haversian system. The infiltration leads to vascular compression and compromised nutrition of the bone marrow. Combined with the effect of the bacterial toxins, this ultimately causes osteonecrosis, leading to the formation of a Brodie’s abscess (6). Clinical Presentation

C Fig. 2. — A. Conventional radiographs show a discrete predominantly osteolytic, geographic, ovoid lesion, with a sclerotic border in the metaphysis of the distal tibia. B. From left to right: coronal T1-weighted, T2-weighted with fat suppression, and post gadolinium T1-weighted images with fat suppression. The images show a typical Brodie’s abscess in the distal metaphysis of the tibia. It contains a small central area with low signal intensities on all sequences, compatible with a sequestrum. The penumbra sign is present, with a high signal intensity rim on the T1-weighted images, corresponding to granulation tissue. The reactive sclerotic border causes a low signal intensity rim on all sequences. Associated bone marrow edema is also present, low signal intensity changes on the T1-weighted images and high signal intensity on T2weighted and post gadolinium images. C. MR images of the distal tibia. From left to right: axial T1-weighted image, axial fat suppressed T2-weighted image, and fat suppressed T1-weighted post gadolinium image. On these axial images a “guirlande” shaped appearance of the Brodie’s abscess is appreciated.

Pain is the most consistent complaint in most patients followed by minimal loss of function or limping. Because the symptoms of a Brodie’s abscess are often vague, an accurate diagnosis is usually delayed, with an average duration of symptoms varying between 1 month and 2 years. A Brodie’s abscess is slightly more common in boys with a 3 to 2 ratio and usually occurs in young patients with an average age of 19.5 years (7). White blood cell count, erythrocyte sedimentation rate, and C-reactive

BRODIE’S ABSCESS REVISITED — KORNAAT et al

B Fig. 4. — A. Conventional radiograph of the knee. A predominantly lucent lesion at the lateral aspect of the epiphysis and metaphysis of the distal femur. Over time a Brodie’s abscess progressively elongates from epiphysis through metaphysis, the “serpentine sign” (white arrows). B. Coronal T2-weighted MR image with fat suppression of the knee. A Brodie’s abscess is appreciated in the lateral aspect of the epiphysis and metaphysis of the distal femur. The abscess is elongated in a snakelike fashion, the “serpentine sign” (white arrowheads).

Fig. 3. — Conventional radiograph of the ankle shows the typical metaphyseal location of a Brodie’s abscess in the distal fibula (white arrow).

protein (CRP) are usually within normal limits or occasionally slightly elevated. Blood culture results are usually negative. The lower limb is affected much more often than the upper limb, and the tibia is affected relatively more often than is the femur. Other sites in which a Brodie’s abscess is frequently reported are the pelvis, the vertebrae, the calcaneus, the clavicle, and the talus. When a Brodie’s abscess occurs in tarsal bones, it usually occurs in the subchondral part or borders the apophysis of the calcaneus. Lesions in the spine occur more often in adults than in children. The patella is rarely involved. Multifocal subacute osteomyelitis is a rare form of subacute osteomyelitis that was reported by Season and Miller and by Rasool (8, 9). It is usually associated with a deficient immune system.

Imaging Conventional radiographs should always be the first step in imaging of a Brodie’s abscess. Typically, a welldemarcated radiolucent lesion with surrounding sclerosis is present within the metaphysis of a long bone (Fig. 2A and 3). A Brodie’s abscess might be tethered to the growth plate, and the cavity progressively elongates, with growth extending from the epiphysis through the metaphysis and even into the diaphysis in a snakelike fashion, resulting in the so-called “serpentine sign” (10) (Fig. 4A, 4B, 5B, 5C). An area of sclerosis may be seen centrally in the lucent lesion, a sequestrum (Fig. 2). In the early stages of osteomyelitis the conventional radiographs are normal, as it takes from 10 to 21 days for an osseous lesion to become visible on conventional radiography, because a 30-50% reduction of bone mass must occur before radiographic change is apparent (11). Unfortunately, a Brodie’s abscess sometimes has a less typical presen-

tation on conventional radiographs showing extensive erosions of cortical bone or periosteal new bone formation. Radiography is also valuable as a primary imaging technique as it can exclude other diagnoses and to monitor therapy. The various radiologic techniques involved in the diagnosis of a Brodie’s abscess are important and complementary, rather than competitive. Bone scintigraphy is rarely indicated unless the diagnosis is unclear and a bone scan is performed as part of a tumor work-up. Also, bone scintigraphy might be helpful for the assessment of multifocal subacute osteomyelitis. Computed tomography (CT) scanning is valuable in detecting lesions in difficult anatomic locations and to differentiate a Brodie’s abscess from osteoid osteoma. CT scan is also superior to conventional radiography or MR imaging for the detection of a sequestrum. Magnetic resonance (MR) imaging is the most sensitive technique to evaluate a Brodie’s abscess

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Fig. 5. — A. Conventional radiographs of the knee. A subtle round radiolucency in the medial site of the proximal tibia metaphysis was missed initially (white arrow). B. Conventional radiographs of the knee, two years later. A radiolucency at the epiphysis and metaphysis of the medial proximal tibia, consistent with a Brodie’s abscess. Note the elongated shape of the Brodie’s abscess, the “serpentine sign”. C. Coronal T1 weighted image of the same patient. Similar to the conventional images, an elongated lesion is seen at the medial site of the proximal tibia epiphysis and metaphysis. D. Axial MR images of the proximal tibia. From left to right: T1-weighted image, fat suppressed T2-weighted image, and post gadolinium fat suppressed T1-weighted image. The images show a Brodie’s abscess with sequestrum formation (black arrow), cloaca (white arrows), sinus tracts (black arrowheads) and soft tissue spread (white arrowhead).

BRODIE’S ABSCESS REVISITED — KORNAAT et al

the lesion showing lower signal intensity than the fatty bone marrow on T1-weighted images. A Brodie’s abscess typically has a “guirlande” shaped appearance (Fig. 2C). A gadolinium-enhanced image depicts a well-circumscribed non-enhancing area with slight rim enhancement. Brodie’s abscess generally appears as a defect without central contrast enhancement; however, the defect can enhance if the abscess cavity is filled with granulation tissue rather than pus. Lesions penetrating the cortex are characterized by signs of intramedullary inflammation as well as some degree of concomitant soft tissue inflammation. Soft tissue or subperiosteal abscesses are more common in children because of the loose periosteum in children (Fig. 6). Classically a Brodie’s abscess can form sinus tracts, a cloaca, and a sequestrum (Fig. 5D). Differential diagnosis

B Fig. 6. — A. Conventional radiographs of the right proximal humerus show a Brodie’s abscess in the proximal metaphysis of the right humerus. Note the lucency at the medial aspect of the proximal humerus metaphysis, consistent with a subperiosteal extension of the abscess (black arrow). B. Coronal MR images of the right proximal humerus. The T1-weighted and fat suppressed T2-weighted image shows the subperiosteal extension of the Brodie’s abscess (white arrows).

(Fig. 2B and 2C). Within the central part of the lesion, signal intensity is decreased on T1-weighted images and increased on T2-weighted images. A characteristic but not pathognomonic finding on MR that supports the diagnosis of a Brodie’s abscess and helps to exclude the presence of a tumor is the penumbra sign (Fig. 2). The penumbra sign does not appear to occur with any great frequency in other osseous conditions (12). The penumbra sign

is characteristically seen on T1weighted MR images as a discrete peripheral zone of marginally higher signal intensity, than the abscess cavity itself. The hyperintensity may be due to the high protein content of the highly vascularized granulation tissue surrounding the abscess cavity. This zone is surrounded by a second layer of low signal intensity rim on all sequences corresponding to sclerotic bone. Finally, there is bone marrow edema surrounding

Osteomyelitis is a known mimic of various diseases, and a Brodie’s abscess is no exception, having all of the presenting signs and symptoms of many bone tumors, both benign and malignant. The classic solitary lesion located in the metaphysis surrounded by reactive new bone presents little difficulty in diagnosis. However, extensive erosions of cortical bone or periosteal new bone formation may add a more ominous dimension. When the lesion is diaphyseal it may be confused with bone infarction or Langerhans cell histiocytosis. When the lesion is located at the diaphysis and associated with an onionskin periosteal reaction, it may be confused with Ewing’s sarcoma, osteosarcoma or lymphoma. An epiphyseal lesion may mimic a chondroblastoma, clear cell sarcoma, fungal osteomyelitis, tuberculous osteomyelitis, aneurysmal bone cyst, pigmented villonodular synovitis (PVNS), degenerative changes, degenerative erosions, intraosseous ganglion, giant cell tumor, or gout, depending upon the age of the patient. Metaphyseal eccentric lesions may have a similar imaging appearance of a nonossifying fibroma or chondromyxoid fibroma, metastatic neuroblastoma, or stress fractures. Brodie’s abscesses, osteoid osteoma, intracortical hemangioma, stress fractures and a cortical desmoid should all be included in the differential diagnosis of an intracortical bone lesion.

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References 1. Brodie B.C.: An account of some cases of chronic abscess of the tibia. Medico Chirurgical Transactions, 1832, 17: 239-249. 2. Resnick D.: Diagnosis of bone and joint disorders, vol III, 4th edition. Printed by Saunders, Philadelphia, 2002, pp 2377-2509. 3. Bohndorf K.: Infection of the appendicular skeleton. Eur Radiol, 2004, 14: E53-E63. 4. Trueta J., Morgan J.D.: The vascular contribution to osteogenesis. I. Studies by the injection method. J Bone Joint Surg Br, 1960, 42-B: 97-109. 5. Speers D.J., Nade S.M.: Ultrastructural studies of adherence

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of Staphylococcus aureus in experimental acute hematogenous osteomyelitis. Infect Immun, 1985, 49 (2): 443-446. Oudjhane K., Azouz E.M.: Imaging of osteomyelitis in children. Radiol. Clin North Am, 2001, 39: 251-266. Lopes T.D., Reinus W.R., Wilson A.J.: Quantitative analysis of the plain radiographic appearance of Brodie’s abscess. Invest Radiol, 1997, 32 (1): 51-58. Season E.H., Miller P.R.: Multifocal subacute pyogenic osteomyelitis in a child. A case report. Clin Orthop Relat Res, 1976, 116: 76-79. Rasool M.N.: Primary subacute haematogenous osteomyelitis in children. J Bone Joint Surg Br, 2001, 83(1): 93-98.

10. Letts R.M.: Subacute osteomyelitis and the growth plate. In: Behaviour of the Growth Plate. Edited by Uhthoff H.K., Wiley J.J., eds. Behavior of the Growth Plate. Printed by Raven Press, New York, 1988, pp 331338. 11. Bonakdarpour A., Gaines V.D.: The radiology of osteomyelitis. Orthop Clin North Am, 1983, 14: 21-33. 12. Grey A.C., Davies A.M., Mangham D.C., et al.: The ‘penumbra sign’ on T1-weighted MR imaging in subacute osteomyelitis: frequency, cause and significance. Clin Radiol, 1998, 53 (8): 587-592.

4IÈME SYMPOSIUM DE SÉNOLOGIE Oostduinkerke 29 et 30 mai 2010 Maison de vacances “Ter Helme”, Kinderlaan 49-51, Oostduinkerke. Radiologues Thèmes: classification de BIRADS, dépistage, l'aisselle Possibilité de pratique de mammographie digitale (inscription séparée nécessaire)

4E SENOLOGISCH SYMPOSIUM Oostduinkerke 29 en 30 mei 2010 Vakantiehuis “Ter Helme”, Kinderlaan 49-51, Oostduinkerke. Radiologen Thema’s: BIRADS-classificatie, screening, de axilla Röntgenlaboranten: positionering (theorie-praktijk), artefacten, fysisch-technische controle, evaluatie meegebrachte mammografieën Information/informatie : Mme L. Van den Broeck: liesbeth.vandenbroeck@uzleuven.be

JBR–BTR, 2010, 93: 87-91.

EVALUATION OF PERI-TUMORAL VESSELS SURROUNDING COLORECTAL LIVER METASTASES AFTER INTRAVENOUS INJECTION OF EXTRUDED MAGNETOLIPOSOMES IN RATS: CORRELATION WITH 3T MRI AND HISTOPATHOLOGY K. Coenegrachts1, J. van Werven2, L. ter Beek3, Z. Mzallassi4, M. Bögels5, Th. van Gulik4, I. Van Den Berghe6, A. Nederveen2, J. Stoker2, H. Rigauts1, S. Soenen7, M. De Cuyper7 Background: Magnetoliposomes have pronounced signal-enhancing effect on T1-weighted (T1w) images of the liver using qualitative analysis which may be benefical for demonstrating peritumoral vasculature. Purpose: To correlate peri-tumoral vasculature (ring-enhancement) surrounding colorectal liver metastases after injection of magnetoliposomes using T1-weighted (T1w) imaging with histopathology in a rat model. Material and Methods: All experiments were approved by the responsible Animal Care Committee. Three rats injected with CC531 coloncarcinoma cells in the portal vein were imaged at 3T using a small diameter four channel coil. The presence of liver metastases, signal intensity changes within intrahepatic vessels, peri-tumoral vasculature (ringenhancement) surrounding liver metastases on T1w imaging and histopathology, and the histopathological distribution of iron particles were evaluated. SS SE-EPI and T1w GE sequences were used. Images were evaluated qualitatively and MRI findings were correlated with histopathology. Results: Fifteen liver metastases were present which were all detected at MRI (mean diameter 2.4 mm (SD 0.8 mm, range 1.5 -4.7 mm)). Ring-enhancement surrounding liver metastases at contrast-enhanced T1w GE sequences was present in all liver metastases. Correlation with histopathology showed the corresponding presence of dilated sinusoids filled with iron particles surrounding the liver metastases. Conclusion: Blood-pooling of iron oxide particles within magnetoliposomes was demonstrated with increased and hyperintensity of vessels after injection of magnetoliposomes. Qualitatively, ring-enhancement surrounding the liver metastases was seen on T1w imaging and corresponded histopathologically with the presence of iron particles (magnetoliposomes) within the dilated sinusoids surrounding the liver metastases. Key-words: Liver neoplasms, secondary – Neoplasms, blood supply.

The early detection and therapy of liver metastases is of utmost importance in patients with cancer. Colorectal cancer is a frequent malignancy and is one of a few malignant tumors in which the presence of limited synchronous liver metastases (i.e. occurring at the time of diagnosis of the primary tumor) or metachronous metastases (occurring after diagnosis of the primary tumor) warrants surgical resection (1). Exact knowledge of the number, size, and regional distribution of liver metastases is essential to determine their resectability. To provide this information, radiologists have used computed tomography (CT) – with best results during arterioportography (2, 3) – and superparamagnetic iron oxide (SPIO)-enhanced magnetic res-

onance imaging (MRI) (4-6). SPIOenhanced MRI has high sensitivity that matches that of CT during arterioportography and higher specificity than that of CT during arterioportography (5, 6). The primary advantage of SPIO-enhanced MRI is that, unlike CT during arterioportography, it is noninvasive. SPIO-enhanced MRI is now regarded by many physicians as the best available examination technique in the evaluation of liver metastases (7). SPIO-particles were originally developed as contrast medium for MRI of the liver, where they are administered to improve tumor detection at T2-weighted imaging. Intravenously injected SPIO particles also shorten the T1 relaxation time. The T1-shortening effect is particular-

From: 1. Department of Radiology, AZ St.-Jan Brugge-Oostende AV, Bruges, Belgium, 2. Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands, 3. Philips Healthcare, Eindhoven, The Netherlands, 4. Department of Surgery/Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands, 5. Department of Molecular Cell biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands, 6. Department of Pathology, AZ St.-Jan Brugge-Oostende AV, Bruges, Belgium, 7. Interdisciplinary Research Center, Catholic University Leuven-Campus Kortrijk, Kortrijk, Belgium Address for correspondence: Dr K. Coenegrachts, M.D., Ph.D., Department of Radiology, AZ St.-Jan Brugge-Oostende AV, Ruddershove 10, B-8000 Bruges, Belgium E-mail: kenneth.coenegrachts@azbrugge.be

ly improved for ultrasmall SPIO (USPIO) particles (8-11). For the characterization of malignant focal liver lesions ring-enhancement has already been described as a potential useful sign and optimized demonstration of this enhancement is therefore advantageous (12). In this regards also the blood-pool effect of (U)SPIO particles can be useful. Extruded magnetoliposomes can be fine-tuned so that a higher ratio of T1 shortening to T2 shortening is achieved. Thus, on the basis of these observations, we hypothesized that extruded magnetoliposomes with only a few USPIO grains in their aqueous cavity may generate a pronounced signal-enhancing effect on T1-weighted (T1w) images of the liver. In this pilot study, MRI experiments were performed using a rat model with CC531 colorectal liver metastases. The effect of magnetoliposomes injection for the evaluation of peri-tumoral vessels was qualitatively examined using T1w GE sequences and histopathology. This study was performed to provide a proof-of-principle for using magnetoliposomes as a useful blood-pool agent for the qualitative characterization of liver metastases using magnetoliposomes-enhanced T1w imaging.

Material and methods During previous experiments performing MRI on tubes filled with different concentrations of magnetoliposomes r1 and r2 values were calculated. These values allowed an optimization of the MRI sequences and allowed determining an optimal concentration of iron particles within the magnetoliposome’s interior space (see appendix). All animal experiments were approved by the responsible Animal Care Committee. Three rats injected with CC531 coloncarcinoma cells in the portal vein were imaged at 3T. Animals and procedures Three male Wag/Rij rats (Harlan, Horst, The Netherlands) weighting 250–270g were acclimatized for one week under standardized laboratory conditions in a temperaturecontrolled room with 12-h dark/light cycles. Animals were given free access to water and standard chow (Hope Farms, Woerden, The Netherlands). Especially the evaluation of micrometastases (< 10 mm) are important from a clinical point of view. In this pilot study, liver metastases ranging from 1-10 mm are included for this purpose. The following sequence in manipulations was applied : 1. On day 0 all rats underwent median laparotomy with anesthesia as follows: Isoflurane (Florene, Abbott Laboratories, Queensborough, United Kingdom) anesthesia was used. The rats were placed in an anesthesia chamber and exposed to a gas mixture of 0.3 L/min oxygen, 0.6 L/min air and 2-4% isoflurane (total percentage of oxygen of about 40%). When the rat was completely relaxed it was removed from the chamber and exposed to a gas mixture of 0.75 L/min oxygen, 1.5 L/min nitrous oxide and 2-2.5% isoflurane (total percentage of oxygen of about 40%). By means of a pain stimulus the rat was checked for accurate narcosis. During narcosis the rat was placed on a warming blanket to avoid cooling down. Then, all rats were injected with a dose of 200.000 CC531 coloncarcinoma cells in the portal vein for the induction of colorectal liver metastases. These CC531 coloncarcinoma cells had been in culture for 10 days. The abdomen was closed in two layers using a running 4-0 vicryl suture (Ethicon) and the animals were allowed to wake up.

JBR–BTR, 2010, 93 (2)

2. At day 10 and subsequently on day 15 (as no liver metastases were seen on day 10) two rats were controlled for the presence of liver metastases prior to the injection of magnetoliposomes by using laparascopic inspection. Isoflurane (Florene, Abbott Laboratories, Queensborough, United Kingdom) anesthesia was used for scopic evaluation. These two rats underwent a scopic evaluation (Karl Storz Endoscopy-America Inc., Culver City, California, United States of America) via an abdominal incision of 1 centimeter at day 10 post injection of the CC531 coloncarcinoma cells. This same scopic evaluation was repeated on day 15 as no liver metastases were detected during the first scopic evaluation. The abdomen was closed in two layers using a running 4-0 vicryl suture (Ethicon) and the animals were allowed to wake up. 3. Just before the start of the MRI experiment, all rats were anesthesized with intraperitoneal injection of FFM (0.27 ml/100 gr weight: 1 ml Hypnorm (VetaPharma Ltd, Leeds, United Kingdom), 1 ml Dormicum (Roche bv, Woerden, The Netherlands), 2 ml water (B. Braun, Meisungen, Germany)) and subsequently anesthetized by inhalation of a mixture of O2/air (1:1 v/v, 2 L/min) containing 2-2.5% isoflurane (Florene, Abbott Laboratories, Queensborough, United Kingdom). Then the rats underwent the MRI experiment. Contrast media and doses The magnetoliposomes used here where of the extruded type (13, 14). They consist of large unilamellar vesicles with a diameter of around 100 nm, capturing Fe3O4 nanocores (diameter ~ 2 nm). In practice, a mixture of dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol and the distearoylphosphatidylethanolamine~poly(ethylene glycol)2000 adduct (molar ratio 85/10/5) was incubated with citratecoated Fe3O4 particles having a diameter of about 2 nm (15) and subsequently extruded at room temperature through two polycarbonate filters of 0.1µm pore size. Non-encapsulated magnetic particles where removed by ion-exchange chromatography (type EMD-TMAE). The final contrast agent solution contained 0.073 mmol phospholipid and 7.88 µg Fe3O4 per ml. Based on these values it was calculated that each individual magnetoliposome structure contained approximately 7 magnetite cores.

In all three rats, 0.75 ml of magnetoliposomes were injected in a tail vein immediately followed by 0.5 ml of saline. Both injections were performed by hand injection. MRI imaging protocol All MRI experiments were performed using the 4-channel wrist coil on 3T MRI (Achieva, Philips Medical Systems, Best, The Netherlands). The rats were placed in the head coil in the supine position. At the start of the MRI protocol, a survey and reference scan were performed. Then a SS SE-EPI sequence and a fat-suppressed T1w 3D GE sequence were used before injection of magnetoliposomes. Immediately after intravenous manual bolus injection of 0.8 cc of magnetoliposomes followed by 0.5 ml of saline via the tail vein, the T1w GE sequence was performed in the arterial and venous phases (FS T1w GE sequence performed at start of injection, 1 minute, 3, 5, 10 and 15 minutes after intravenous injection of magnetoliposomes). The BB SE SE-EPI sequence was applied with following parameters: TR: 1200 ms, TE: 50ms, flip angle: 90°, scan plane: axial, NSA (Number of Signal Averages indicates the number of times each (acquired) line in k-space is sampled): 4, FOV (Fieldof-View): 65 mm x 65 mm, scan percentage (is a percentage of phase-encoding values (profiles) of k-space around k = 0 profile): 100%, half scan factor (is a method in which approximately only one half of k-space in the phase-encoding direction is acquired): 1, Act.BW (actual band width): 29,4, ST (slice thickness): 4 mm, SPAIR (SPectral Attenuated Inversion Recovery) TR: 240 ms. The T1w 3D GE sequence was applied with following parameters: TR: 6 ms, TE: 2,9 ms , flip angle: 10°, scan plane: axial, NSA: 4, FOV: 120 mm x 120 mm, scan percentage: 100%, half scan factor: 1, Act.BW: 289,4 , ST (slice thickness): 2 mm, SPAIR TR: 181,2 ms. Sacrifice of the rats and histopathological analysis Immediately after the MRI experiment, the animals were sacrificed during anesthesia and bled to death after resection of the liver. Then all livers were removed for histopathological examination and fixed in 10% buffered formalin for 1 week. All the livers were sliced and macroscopically examined by a

VESSELS SURROUNDING LIVER METASTASES — COENEGRACHTS et al

pathologist having 25 years of experience. All metastatic tumors were located and the largest tumor diameter was measured. Histological sections were made from all metastatic lesions and the surrounding parenchyma. The sections were stained with hematoxylin and eosin and a pearls iron stain. Analysis of the MRI findings with histopathological findings A visual (qualitative) analysis of the SS SE-EPI and T1w GE sequences was performed by an experienced abdominal radiologist (9 years of experience in abdominal MRI). The SS SE-EPI sequence was evaluated for the detection of liver metastases and compared with the (unenhanced and all contrastenhanced) T1w GE sequences concerning liver metastasis detection. The liver metastases detected upon applying the various MRI sequences were correlated with histopathology. The T1w GE sequences were also evaluated for contrast-enhancement of the intrahepatic vessels and for the detection of ring-enhancement surrounding the liver metastases. The T1w GE sequences were correlated with the histopathological findings to evaluate the potential of magnetoliposomes-enhanced T1w GE imaging in characterizing liver metastases. Further the histopathological distribution of the iron particles was evaluated. Statistical analysis For this pilot study only descriptive data presentation was possible. Results The different metastatic lesions showed typical histopathological findings of an adenocarcinoma. In the surrounding liver parenchyma, an accentuated component of blue staining iron was seen on the pearls stain. Histopathology did not detect any additional liver metastases which were not detected by the applied MRI sequences. Compared with T1w GE, the SS SE-EPI sequence detected the maximum number of liver metastases in all three rats. No additional liver metastases were detected using the T1w sequences. Unenhanced T1w GE sequences had too low contrastto-noise ratio for appropriate evaluation of the liver metastases. In rat 1, rat 2 and rat 3 respectively 8, 5 and 2 liver metastases were detected

using the applied MRI sequences. SS SE-EPI detected 3 respectively 2 additional liver metastases in rat 1 respectively rat 2 compared with the T1w sequences. The diameter of the detected liver metastases using MRI ranged from 1.5 mm to 4.7 mm (mean: 2.4 mm ; SD: 0.8 mm). All liver metastases detected on MRI were confirmed by histopathology. Visual (qualitative) evaluation of the MRI examinations showed the appearance of hyperintense signal within the hepatic vessels after injection of magnetoliposomes with persisting hyperintense signal using the delayed contrast-enhanced T1w sequences. Liver metastases were better visualized as hypo-intense lesions using contrast-enhanced T1w sequences compared with unenhanced T1w sequence. Ringenhancement surrounding liver metastases was present in all detected liver metastases using contrastenhanced T1w GE sequences (Fig. 1). Correlation with histopathology (Fig. 1) showed the corresponding presence of dilated sinusoids filled with iron particles surrounding the liver metastases. Neo-angiogenetic vessels within the liver metastases were not visualized by histopathological examination. Discussion In this study CC531 coloncarcinoma cells were used for our rat model as these cells show comparable growth characteristics with human coloncarcinoma cells. The results of this study show that magnetoliposomes-enhanced T1w GE sequences can visualize ring-enhancement at the periphery of the liver metastases. Ring-enhancement on T1w imaging corresponded with the presence of iron particles (blood-pooling of magnetoliposomes) within the dilated sinusoids surrounding the liver metastases on histopathology. Ring-enhancement on T1w sequences was useful for the detection and characterization of liver metastases in this study. Unenhanced SS SE-EPI was the most accurate MRI sequence for the detection of (the smallest) liver metastases. In the literature, a commercially available hepato-specific contrast agent containing SPIO (ferucarbotran (Resovist®)) has already been used for the characterization of colorectal liver metastases (8, 16-18). It appeared that dynamic T1w scanning with ferucabotran significantly improves the differentiation of

benign and malignant focal liver lesions compared with unenhanced MRI and T2w MRI pre/post-ferucarbotran alone. Clinical studies with dynamic T1w GE demonstrated the presence of ring-enhancement surrounding liver metastases. This effect has been explained by neovascularity and blood-pool effects of vessels surrounding malignant focal liver lesions (12, 19). To further improve the T1-effect of the iron-oxide particles in this study, we used smaller iron-oxide particles encapsulated within PEGylated magnetoliposomes to avoid phagocytosis and to allow blood-pooling. In this study, the injection of magnetoliposomes in combination with T1w imaging allowed the characterization of colorectal liver metastases by demonstrating typical ringenhancement surrounding the liver metastases. The persistent hyperintensity on T1w GE of the vessels can be explained by the PEGylation of the magnetoliposomes (“stealth-magnetoliposomes”) leading to increased blood-pooling. Using a blood-pool agent was considered important for this study as the purpose was to evaluate peri-tumoral vessels. Therefore, migration of the magnetoliposomes from the intravascular space to the interstitial space was inhibited. To our knowledge the use of stealth magnetoliposomes using magnetoliposomes-enhanced T1w imaging for the detection and characterization (demonstration of blood-pooling and ring-enhancement surrounding liver metastases) of liver metastases has not been evaluated before. The MRI protocol used in this study consisted of MRI sequences that are already used in clinical practice. In this pilot study CC531 coloncarcinoma cells were used for our rat model as these cells show comparable growth characteristics with human coloncarcinoma cells. This will allow easier extrapolation of our results for future use of the MRI experiments in oncological patients. From table 1 (see appendix) we can see that the ratio of the relaxivities r1/r2 at 3.0T is substantially higher for the magnetoliposomes than for Resovist®. This means that the magnetoliposomes used in this work have a stronger T1 effect relative to T2 compared to Resovist®. It is also shown that the r1/r2 ratio decreases with increasing field strength. Therefore one should be careful to use the commonly cited

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B A

D C Fig. 1. â&#x20AC;&#x201D; Visualization of 6 histologically proven liver metastases. A. displays all 6 liver metastases (white arrows) using SS SE-EPI (b = 10 s/mm2). B. shows the corresponding unenhanced T1w GE sequence having low contrast-to-noise and showing barely the largest liver metastasis. C. shows the corresponding contrastenhanced T1w GE sequence (1 minute post ML injection) showing the largest liver metastasis (white star) with surrounding ring-enhancement. D. shows the corresponding histological image at the level of the largest liver metastasis. Blue iron stain was used. In the lower part a close-up of the liver metastasis is shown. Dilated sinusoids with iron particles (magnetoliposomes; blue particles in the image) are seen surrounding the liver metastasis (magnification factor 20x). The periphery of the liver metastasis is located at the level of the white arrow. E. shows the corresponding histological image at the level of the largest liver metastasis. Blue iron stain was used. In the lower part a detail of the liver metastasis is shown. Dilated sinusoids with iron particles (magnetoliposomes; blue particles in the image) are seen surrounding the liver metastasis (magnification factor 200x). The periphery of the liver metastasis is located at the level of the white arrow.

values of r1 and r2 at 0.47T, since most clinical scanners operate at 1.5T and 3.0T. It should be noted, however, that there is a possible error due to potential nonlinear concentration dependencies of the relaxation rates for these large magnetoliposomes. The solvent was distilled water and no proteins were present like in the case of blood plasma. Proteins may have an effect on the relaxation rates due to possible binding to the contrast agents and increasing the viscosity of the solvent. Visual/qualitative evaluation of (small) focal liver lesions can be dif-

ficult in differentiating true-positive focal liver lesions from false-positive focal liver lesions. Paging through the stack of MRI slices facilitates this task. Further, the visual identification of all the detected lesions was also correlated with other sequences (SS SE-EPI sequence and contrastenhanced T1w sequences). This allowed to differentiate focal liver lesions from intrahepatic vessels. The calculation of lesion-to-liver contrast-to-noise ratio can help in this differentiation although these calculations are less accurate (volume-averaging effect) in small focal liver lesions. Therefore, in this pilot

study only visual/qualitative evaluation (with paging through the MRI images) was used. The persisting ring-enhancement after injection of (blood-pool/stealth) magnetoliposomes supported the characterization of malignant liver lesions (liver metastases). The rather low resolution of the MRI images in this study and the small diameter of the liver metastases in this study made the evaluation of the ringenhancement more difficult. Paging through the stack of images allowed to better appreciate the ringenhancement surrounding the liver metastases. In this study no magnetoliposomes could be detected within the neo-angiogenetic vessels of the liver metastases. This might be caused by the rather small calibre of the studied liver metastases in this study. Further, the use of a pure (100%) blood-pool agent might not be optimal for the detection of these small neo-angiogenetic vessels. For the detection of neo-angiogenesis, it might be interesting to evaluate other magnetoliposomes with different size having blood-pool characteristics but with selective leakage only through neo-angiogenetic vessels. This might allow an indirect measurement of the amount of neoangiogenetic vessels. In conclusion, the T1-effect and blood-pooling of the iron oxide particles within the magnetoliposomes is demonstrated with increased hyperintensity of vessels after injection of magnetoliposomes. Ring-enhancement surrounding the liver metastases is seen using qualitative evaluation of T1w imaging and is caused by the presence of iron particles within the dilated sinusoids surrounding the liver metastases. Further research is needed to optimize these magnetoliposomes and to allow transport of magnetoliposomes to (and through) the neoangiogenetic vessels within the liver metastases. References 1. Schima W., Kulinna C., Langenberger H., Ba-Ssalamah A.: Liver metastases of colorectal cancer: US, CT or MR? Cancer Imaging, 2005, 5: S149-S55. 2. Soyer P., Levesque M., Caudron C., Elias D., Zeitoun G., Roche A.: MRI of liver metastases from colorectal cancer vs CT during arterial portography. J Comput Assist Tomogr, 1993, 17: 6774. 3. Schmidt J., Strotzer M., Fraunhofer S., Boedeker H.,

VESSELS SURROUNDING LIVER METASTASES — COENEGRACHTS et al

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13.

14.

Zirngibl H.: Intraoperative ultrasonography versus helical computed tomography and computed tomography with arterioportography in diagnosing colorectal liver metastases: lesion-by-lesion analysis. World J Surg, 2000, 24: 43-47. Seneterre E., Taourel P., Bouvier Y., et al.: Detection of hepatic metastases: ferumoxides-enhanced MR imaging versus unenhanced MR imaging and CT during arterial portography. Radiology, 1996, 200: 785-792. Vogl T.J., Schwarz W., Blume S., et al.: Preoperative evaluation of malignant liver tumors: comparison of unenhanced and SPIO (Resovist)enhanced MR imaging with biphasic CTAP and intraoperative US. Eur Radiol, 2003, 13: 262-272. Strotzer M., Gmeinwieswer J., Schmidt J., et al.: Diagnosis of liver metastasis from colorectal adenocarcinoma: comparison of spiralCTAP combined with intravenous contrast-enhanced spiral-CT and SPIO-enhanced MR combined with plain MR imaging. Acta Radiol, 1997, 38: 986-992. Nasu K., Kuroki Y., Nawano S., Kuroki S., Tsukamoto T., Yamamoto S., Motoori K., Ueda T.: Hepatic Metastases: Diffusion-weighted Sensitivity-encoding versus SPIOenhanced MR Imaging. Radiology, 2006, 239: 122-130. Saini S., Edelman R., Sharma P., et al.: Blood-pool MR contrast material for detection and characterization of focal hepatic lesions: initial clinical experience with ultrasmall superparamagnetic iron oxide (AMI-227). AJR, 1995, 164: 1147-1152. Saini S., Sharma R., Baron R.L., et al.: Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging. Clin Radiol, 2000, 55: 690-695. Sahani D., Saini S., Sharma R., O’Malley M., Hahn P.: Dynamic T1weighted ferumoxides enhanced MRI for imaging liver hemangiomas: preliminary observations. Abdom Imaging, 2001, 26: 166-170. Müller M., Reimer P., Wiedermann D., et al.: T1-weighted dynamic MRI with new superparamagnetic iron oxide particles (Resovist): results of a phantom study as well as 25 patients. Rofo, 1998, 168: 228-236. Mergo P., Helmberger T., Nicolas A., Ros P.: Ring enhancement in ultrasmall supermagnetic iron oxide MR imaging: a potential new sign for characterization of liver lesions. AJR, 1996,166: 379-384. Sabaté R., Barnadas-Rodríguez R., Callejas-Fernàndez J., et al.: Preparation and characterization of extruded magnetoliposomes. Int J Pharm, 2008, 347: 156-162. Soenen SJH., Hodenius M., De Cuyper M.: Magnetoliposomes : versatile innovative nanocolloids for use

Table I. — Relaxivity values for Resovist® and for the magnetoliposomes. MAGNETOLIPOSOME (3.0T)

® RELAXIVITY IN RESOVIST WATER ref.a ref. b [L*MMOL-1*S-1] (0.47T) (0.47T)

ref. b (3.0T)

[vesicles]

[Fe3O4]

24.7

20.6

4.6

1205

182

163.8

143

1905

288

r1/r2

0.151

0.24

0.032

0.633

Legend: Ref.a: Monograph Resovist, Schering AG, 2002; Ref.b: Rohrer M., Bauer H., Mintorovitch J., Requardt M., Weinmann H.: Invest Radiol, 2005, 40: 715-724.

15.

16.

17.

18.

19.

in biotechnology and biomedicine. Nanomedicine, 2009, 4: 177-191. Hodenius M.A.J., Niendorf T., Krombach G.A., et al.: Synthesis, physicochemical characterization and MR relaxometry of aqueous ferrofluids. J Nanoscience Nanotechnology, 2008, 8: 2399-2409. Reimer P., Jahnke N., Fiebich M., et al.: Hepatic lesion detection and characterization: value of non-enhanced MR imaging, superparamagnetic iron oxide-enhanced MR imaging, and spiral CT-ROC analysis. Radiology, 2000, 217: 152-158. Van Gansbeke D., Metens T., Matos C., et al.: Effects of AMI-25 on liver vessels and tumors on T1-weighted turbo-field-echo images: implications for tumor characterization. J Magn Reson Imaging, 1997, 7: 482-489. Reimer P., Müller M., Marx C., et al.: T1 effects of a bolus-injectable superparamagnetic iron oxide, SH U 555 A: dependence on field strength and plasma concentration – preliminary clinical experience with dynamic T1weighted MR imaging. Radiology, 1998, 209: 831-836. Harisinghani M., Saini S., Weissleder R., et al.: Differentiation of liver hemangiomas from metastases and hepatocellular carcinoma at MR imaging enhanced with blood-pool contrast agent code-7227. Radiology, 1997, 202: 687-691.

Appendix Before the start of this in vivo experiment, we determined the T1 and T2 relaxation times of several sample tubes with a range of concentrations of magnetoliposomes. The T1 times were determined from a standard inversion recovery sequence in a point-resolved spectroscopy sequence for a selected 1 x 1 x 1 cm3 voxel within each sample tube. The MR signal was measured as a function of inversion time

(TI) and fitted off-line to three parameters of the function which described the MR signal recovery. S(TI) = A(1 – Be

– TI c

)

where S(TI) is the MR signal (peak height and peak integral in the spectrum) at an inversion time TI, A is the signal at thermal equilibrium, B is a factor of 2 under perfect experimental conditions when applying a 180 degree RF pulse, and C is the T1 relaxation time. The T1 relaxation times were also determined by a Look-Locker MR protocol and found to be in excellent agreement with the spectroscopy results (unpublished data). The T2 times were determined with a point-resolved spectroscopy sequence within a 1 x 1 x 1 cm3 voxel for each sample tube. The MR signal was measured as a function of the echo-time TE and fitted off-line to three parameters of the function which describes the T2 decay S(TE) = Ae

– TE B

Where S(TE) is the MR signal (peak height and peak integral of the spectrum) at echo-time TE, A is the signal at thermal equilibrium, B is the T2 relaxation time , and C is the baseline noise level to which the signal decays. The repetition time TR in the spectroscopy protocols was chosen sufficiently long to prevent saturation effects, usually around 10 s. Relaxivity values for Resovist® and for the magnetoliposomes used in this study are given in table 1.

JBR–BTR, 2010, 93: 92-96.

SPECIAL ARTICLE THE CAPITAL COST AND PRODUCTIVITY OF MRI IN A BELGIAN SETTING* C. Obyn1, I. Cleemput2 Against the Belgian background of national planning of MRI units and a detailed reimbursement scheme, a study was undertaken to investigate the cost and productivity of MRI units in different investment scenarios and for various operational schedules. This article focuses on capital costs, not operating cost. Using data from a hospital survey and manufacturers, total capital costs per examination were simulated. The survey revealed considerable variation in operational hours, with on average 66 hours per week, resulting in 6 300 examinations per year per unit. Whilst operational hours remained approximately unchanged over the last 8 years, the number of examinations per unit grew by on average 6% per year. Correspondingly, average examination time declined from 45 to 31 minutes. The findings suggest that, mainly due to the increased productivity, capital costs per examination decreased considerably in the examined period. In 2008, the average capital cost per examination is estimated to vary from €23 to €45 for 1.5 Tesla units and from €32 to €62 for 3 Tesla units, assuming an equal examination speed for both types of units. Key-words: Cost-effectiveness – Magnetic resonance (MR).

The supply of medical imaging services may not only be influenced by the medical know-how of the prescribing physicians and radiologists or by the demand of the patients, but also by other factors such as the reimbursement and national infrastructure planning policies. Concerned about the increase in diagnostic imaging expenditures, health care policy makers aim to use the health care financing and national infrastructure planning policy (if any) to encourage efficient delivery of high quality medical imaging. Financing and planning are used to discourage over- or under-use of services but also to avoid providers giving preference to one technique over another for other reasons than those that can be justified by evidence based medicine. In Belgium, the number of MRI units is subject to a national supply constraint. End 2008, 92 units were accredited. This is equivalent to 8.6 units per one million inhabitants. As there is no data available on the appropriateness of current prescriptions and examinations compared to the clinical guidelines, it is not possible to demonstrate under- or overuse of this imaging technique, nor is

it possible to determine the number of units needed at national level that can be scientifically justified. When jurisdictions want to install a national infrastructure planning, it is beyond their ability to fully base it on clinical evidence. What policy makers are able to do, however, is to determine an appropriate financing basis. Therefore detailed data on the investment as well as operational costs of MRI are needed. Against this background, a cost analysis was conducted to assess the total costs of purchasing and running an MRI unit. This article focuses on the evolution of the capital costs and the productivity of the units over the last decade, in order to estimate the evolution in average capital cost per examination over time. The results on the operational costs can be found in the report by Obyn et al. (1). Materials and methods The costing methodology applied in the current cost study is historical costing, as opposed to standard costing, in that it is based on historical and actual cost data of the hospitals instead of standards defined for qualitative, efficient and safe care.

From: 1. Federaal Kenniscentrum voor de Gezondheidszorg (KCE), Brussel, 2. Federaal Kenniscentrum voor de Gezondheidszorg (KCE), Brussel, Belgium. Address for correspondence: C. Obyn, KCE – Federaal Kenniscentrum voor de Gezondheidszorg - Centre fédéral d’expertise des soins de santé – Belgian Health Care Knowledge Centre Administratief Centrum Kruidtuin, Door Building (10e verdieping), Kruidtuinlaan 55, B-1000 Brussels, Belgium. E-mail: caroline.obyn@kce.fgov.be * This article is based on part of the KCE report “Magnetische Resonantie Beeldvorming: kostenstudie / Imagerie par résonance magnétique : analyse de coûts” (1) available on http://www.kce.fgov.be/index_nl.aspx?SGREF=5264&CREF=12925; http://www.kce.fgov.be/index_fr.aspx?SGREF=3465&CREF=12926)

Sources A number of data sources were used, notably a hospital survey and face-to-face meetings with manufacturers. Table I in appendix gives an overview of the sources used per cost item. More details can be found in Obyn et al. (1). Hospital survey In search of reliable MRI cost data, separate questionnaires were sent to the general and financial management and the head of radiology departments of 56 Belgian hospitals with at least one accredited MRI scanner. Table I in appendix provides more detailed statistics on the response rates on the different cost items. The questionnaire sent to the heads of the radiology department contained a question relating to the operational hours, while the questions posed to the financial managers related to financial investment aspects of the services. Manufacturers The three manufacturers active on the Belgian MRI market were contacted: Philips, Siemens and General Electric. Questions posed related to the capital costs and the operational lifetime of the equipment as well as to the technical evolution in MRI over the last decade. Two of the mentioned manufacturers provided precise information that could be used for the analyses. Capital costs Capital costs cover the initial purchase (including installation) of the MRI unit, the upgrades, the building adaptations and the financing of

THE CAPITAL COST AND PRODUCTIVITY OF MRI — OBYN et al

these investments. In order to spread the capital costs over the lifetime of the equipment, an equivalent annual cost was calculated (2). Initial purchase Data on purchase and building adjustment costs were obtained through the hospital survey. For the initial purchase costs, a distinction was made between the purchase of a 1.5 versus a 3 Tesla unit. Building adaptations For building adaptation costs two scenarios were analysed: major versus minor building adjustment requirements. Building adjustment requirements were considered to be major when a new building place was needed, generally in case of a purchase of a first or extra unit or a switch to a higher field strength unit. They were considered to be minor when limited refurbishment of an existing building was sufficient, generally in case of replacement of an older unit without switching to a higher field strength. Based on data from the hospital survey and contacts with manufacturers, a probability distribution was defined for the initial purchase and building adaptation costs, serving as input for the investment cost simulations. Upgrading costs and lifetime of equipment As the MRI technology continues to advance, machines that are up-todate at the time of installation may be considered obsolete within a number of years. Regular upgrades of soft- and hardware are therefore desired. By upgrading an MRI unit, scanning speed and consequently operating efficiency can be increased, imaging quality can be enhanced and clinical capabilities may be expanded. Upgrading costs were obtained from the hospital survey. As most of the units of the responding hospitals were still operational, no average lifetime, nor average upgrade costs, could be determined. Therefore, 4 scenarios were examined: 14 years lifetime of the equipment with a 50% or a 70% upgrade cost after 7 years, 10 years lifetime with a 50% upgrade cost after 5 years and a 7 years lifetime without upgrade investments. Each of these scenarios was analysed for both a 1.5 and a 3 Tesla unit and for both minor and major building adjustment costs.

Financing costs An interest rate of 4.61% was used to estimate financing costs. This rate corresponds with the average 10 year-OLO rate over the period 19982007 (4.46%), increased with 15 basis points as risk premium. Scanning speed The historical evolution of the scanning speed was estimated by combining data from the NIHDI on the number of examinations in Belgium with data on the number of operational MRI units and the average number of operating hours as derived from the hospital survey. Scenarios and uncertainty As described above, multiple scenarios were analysed, in terms of operating hours (55-65-75 hours per week), lifetime of the equipment (710-14 years), upgrade investments (0%-50%-70%) and building adaptations (minor-major). Uncertainty and variability of cost inputs (within each of the scenarios) was taken into account by fitting probability distribution functions to the data and incorporating the distributions instead of mean or median point estimates in the simulations. By running 1000 Monte Carlo simulations, during which input values are drawn at random from the distributions, a probability distribution was obtained for the output, the total capital costs. For this probabilistic analysis, the software package @risk 5.0 (Palisade, London, UK) was used. Appendix Table II shows the distribution functions applied for capital cost inputs. Results Productivity of the units Through the hospital survey, data was obtained on the current and historical weekly operating hours of a Belgian MRI service. The data show that the average operating hours did not change considerably over the last eight years (from 64.7 hrs on average in 1999/2000 to 65.7 hrs in 2007/2008). Summary statistics of the survey results are show in Table I. The number of examinations per unit grew by on average 6% per year (Table II). Correspondingly, the inferred examination time decreased from on average 45 minutes in 1999/2000 to 31 minutes in 2007/2008. This examination time includes imaging, patient positioning, computer set-up, patient dis-

charge and idle time in between two patients. Examination time is not only influenced by the type of the MRI unit (mainly magnetic field strength), but also by case complexity (type of examination and patient), and by the personal preferences of the radiologist with regard to the trade-off between sharpness of images, signal-noise ratio and scanning time. Belgian figures show that the average case-mix in terms of body parts examined and examination setting (hospitalized versus ambulatory) did not change much over the considered period (Table III). These data hence do not support the hypothesis that the increased speed is linked to lower case complexity. The available data rather suggest that the increase in speed is driven by technology advancements (and the accompanying switch to higher magnetic field units) and likely also by improvements in general workflow efficiency. Capital costs Figure 1 shows the cost of purchase over time for 50 MRI units at 28 Belgian hospitals. The figure shows that the responding hospitals most frequently installed a 1.5 Tesla unit, which has currently a lower investment cost than the 3 Tesla units installed by some hospitals more recently. None of the responding hospitals acquired a 1 Tesla unit after 2004. Based on this dataset, the average initial investment costs for a 1.5 Tesla MRI unit slightly decreased from 1999-2000 to 2006-2008 from around €1 300 000 to €1 200 000, second hand units omitted. The small sample size of purchased units (n = 16 respectively n = 5) however precludes firm conclusions. Price information was also obtained from 2 manufacturers for a 1.5 and 3 Tesla MRI unit in 2008. The average sales price for a basic or standard configuration of an MRI unit, which can be used for routine MR imaging in the whole body (neuro, orthopedics, abdomen and angio) and including software and coils for it, was €1 027 0001 for a 1.5 Tesla and € 1 581 000 for a 3 Tesla. With extra options for hardware (mainly specialized coils for specific body parts) and software (such as software for advanced neuro imaging, spectroscopy, soft tissue motion correction etcetera), the upper price would be about €1 378 000 for a

All prices include VAT of 21%.

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Table I. — Number of operational hours per week. 1999/2000

2007/2008

11 64.7 54.0 86.0

20 65.7 52.5 86.0

Response rate (n° of hospitals) Average n° of operational hrs / wk Min n° of operational hrs / wk Max n° of operational hrs / wk Source: hospital survey.

Table II. — Evolution of time required per MRI examination.

N° of examinations per operational MRI unit N° of operating hours per year N° of examinations per hour Time required per MRI examination

1999/2000

2007/2008

4 307 3 235* 1.33 45 min.

6 332 3 285** 1.93 31 min.

* 64.7 hours/week * 50 weeks/year ** 65.7 hours/week * 50 weeks/year.

Table III. — Case mix evolution in terms of body parts: 2000 versus 2007.

Spine Head Limbs Trunk MRA body Mammo Cardiac Functional % ambulatory

2000

2007

31.7% 31.7% 22.3% 9.8% 2.8% 1.4% 0.2% 0.1% 84%

30.3% 26.4% 24.7% 11.0% 4.4% 2.7% 0.5% 0.1% 86%

Source: based on national statistics from NIHDI.

1.5 Tesla unit and about €1 945 000 for a 3 Tesla unit. These prices include first year maintenance and training of nurses and physicians. This data is in line with the data derived from the hospital survey. Table IV shows the results for the building adjustment costs. Within the two categories considered, major versus minor building adjustments, large differences in costs were observed between hospitals. These may be explained by, amongst others, the size and suitability of the location, the used materials, the variations in cages of Faraday and the number of walls needing extra shielding. Figure 2 plots the probabilistic outcomes for the resulting total yearly equivalent capital costs for 1.5 and 3 Tesla units. These costs vary from on average €160 000 (in the scenario 14 yrs – 50% upgrade – minor building adaptations) to €240 000 (7 yrs – 0% upgrade or 10 yrs – 50% upgrade – minor building adaptations) for 1.5 Tesla units. For 3 Tesla units, these average costs vary from €230 000 to €330 000 respectively. These capital costs are one-time, fixed costs. The associated cost per examination therefore depends on the utilization of the unit. Combining the annual capital costs with the different scenarios for operational hours, whilst taking into account an average examination speed of 31 minutes, an average capital cost per examination was obtained ranging from €23 to €45 for 1.5 Tesla units and from €32 to €62 for 3 Tesla units in 2008 (Table V). In 1999/2000, when the average examination speed was still 45 minutes, the average capital cost per examination is estimated to range from €40 to €71 for 1.5 Tesla units2. Discussion and conclusion As the demand for MRI examinations increased over the last years and as the number of MRI units was restricted by the government, Belgian hospitals have been spurred to make the most efficient utilization of the limited resources. The hospital survey highlights that operating hours ranged from 53 to 86 hours per week with an average of 66 hours, resulting in on average 6 300 examinations per year per unit. In a previous Belgian study (3), this productivity appeared the

Fig. 1. — Purchase cost of MRI units. Source: hospital survey.

Cost in nominal terms.

THE CAPITAL COST AND PRODUCTIVITY OF MRI — OBYN et al

Table IV. — Building adjustment costs. Minor building adjustments

Major building adjustments

12 119 458 58 876 0 363 652

21 369 819 413 768 42 926 700 631

Response rate (n° of units) Average cost (€) Median cost (€) Min cost (€) Max cost (€) Source: hospital survey.

Table V. — Capital cost per examination (2007/2008). 1.5 Tesla Operational scenario:

Average capital cost per examination (€)

55 hrs 65 hrs 75 hrs

45 38 33

40 34 29

45 38 33

41 34 30

34 29 25

31 26 23

37 31 27

34 29 25

3 Tesla 55 hrs 65 hrs 75 hrs

61 52 45

55 47 41

62 52 45

57 49 42

47 40 34

43 37 32

51 44 38

48 41 35

14 50% minor

14 70% major

14 70% minor

Investment scenario: Life (yrs) Upgrade % Building adaptations

7 0% major

7 0% minor

Fig. 2. — Equivalent annual capital cost for an MRI unit. Note: Box plot values: center line: mean; box: 25%-75% percentiles; whiskers: 5%-95% percentiles.

10 50% major

10 50% minor

14 50% major

highest in a sample of 8 countries. As a considerable part of the costs are fixed (such as investment costs and maintenance contracts), the longer the operational hours, the lower the cost per examination. Besides operational hours, the time to do an examination obviously is another important parameter to which the cost per examination is very sensitive. In this study, an overall evolution of 45 to 31 minutes was calculated over the last 8 years in Belgium. This evolution inevitably led to a considerable decrease in cost per examination. Looking at the investment data derived from the hospital survey, no major price erosion could be observed for 1.5 Tesla units in the last decade. The major trend seems that more performing MRI technology was bought at roughly the same price level, at least for 1.5 Tesla units. The investment cost of 3 Tesla units is considerably higher, but this higher investment cost is still counterbalanced by the increased productivity over the years. For both 1.5 and 3 Tesla units, the average capital cost per examination (of respectively €23-€45 and €32-€62) now is lower than for a 1.5 unit 8 years ago (€40€71).

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Inevitably, this cost analysis is subject to a number of limitations. It relies on actual cost and operational data as reported by hospitals in a small sample size. Furthermore, no detailed analysis was made of how examination speed depends on case complexity (types of examinations and patients) and on type of MRI units (magnetic field strength). In light of these limitations the presented findings should be interpreted adequately. This study provides information on the costs of investing in an MRI unit in Belgium. The information can

serve as input for decision making at both governmental and hospital level. At governmental level, it can be useful for policy makers who have to design financing mechanisms for these services. At hospital level, it can support discussions on operational and financial management issues. This cost analysis can also be seen as a first step in a broader cost-effectiveness evaluation of the use of MRI. In order to evaluate whether the higher costs of MRI are worth the clinical advantages compared to CT, both costs and advantages of both techniques need to be compared.

References 1.

Obyn C., Cleemput I., Léonard C., Closon J.-P.: Magnetische Resonantie Beeldvorming: kostenstudie. Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE), 2009. 2. Drummond M., Sculpher M., Torrance G., O’Brien B., Stoddart G.: Methods for the economic evaluation of health care programmes: Oxford University Press, 2005. 3. Demaerel P., Hermans R., Verstraete K., et al.: Magnetische Resonantie Beeldvorming. Brussel: Federaal Kenniscentrum voor de gezondheidszorg (KCE), 2006.

Appendix table I. — Detailed overview of sources used for cost analysis. Data

Sources used

Initial investment and upgrading costs

Hospital questionnaire – N° of units bought in 2006-2008: 9 – N° of units bought in 1999-2000: 16 Manufacturers – N° of manufacturers = 2

Building adjustment costs

Hospital questionnaire – N° of hospitals = 22 – N° of units = 33

Operational hours per week

Hospital questionnaire – N° of hospitals = 11 for 1999/2000 – N° of hospitals = 20 for 2007/2008

Appendix table II. — Distribution functions for capital cost input variables. Variable

Lower Bound

Upper Bound

Base Distribution Source Case value (= average)

MR unit investment – 1.5 T3

€1 027 000

€1 378 000

€1 202 500

Uniform

MR unit investment – 3 T

€1 581 000

€1 945 000

€1 763 000

Uniform

Major building adaptation Minor building adaptation

€43 000 €0

€701 000 €364 000

€372 000 €162 000

Uniform Uniform

Manufacturers (lower and upper bound input) Hospital questionnaire

Note that generally first year maintenance is included in this purchase price. This has been taken into account in the equivalent annual investment cost calculation.

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CONTINUING EDUCATION MRI SPECTRUM OF MEDIAL COLLATERAL LIGAMENT INJURIES AND PITFALLS IN DIAGNOSIS M. De Maeseneer1, M. Shahabpour2, C. Pouders3 The medial collateral ligament (MCL) is made up of different components and spans the medial aspect of the knee. With injuries the superficial or deep and posterior components may be involved. A variety of conditions including MCL bursitis, medial osteoarthritis, medial cellulitis, medial bursitis, medial meniscal cyst, meniscocapsular separation, and retinacular tear may present with high signal surrounding the MCL fibers and simulate an MCL tear. Key-words: Knee, ligaments and menisci – Knee, MR.

The MCL is covered by the superficial medial fascia (Fig. 1). The MCL itself is deep to this fascia and is composed of an anterior part and posterior part. The anterior part is loosely attached to the meniscus, and shows a superficial band and deep meniscofemoral and meniscotibial bands (Fig. 2). Anteriorly the MCL is in continuity with the medial retinaculum patellae. The posterior part of the MCL does not show the layered appearance of the anterior part, and in this region only one bandlike structure is apparent (1, 2). MCL tears The present grading system only focuses on the anterior portion of the MCL. In addition only the superficial band is taken into account. A grading system has been proposed for MCL injuries but is limited by the lack of a gold standard (Fig. 3) (3, 4). Indeed MCL injuries are rarely treated surgically and hence correlation with surgical findings is absent. Fluidsensitive sequences are considered ideal to display the characteristics used in the classic grading system. In a grade 1 injury the MCL may appear thickened and surrounded by high signal intensity (Fig. 4). In a grade 2 injuries there is partial disruption of fibers, and in a grade 3 injury there is complete disruption of fibers (Fig. 5). Anatomically only the deep fibers of the MCL may be injured, and it is unclear how to classify this using the present grading system. Also the injury may be confined to the posterior MCL which is not taken into

Fig. 1. — The superficial fascia has been opened (arrows). Note the anterior (A), and posterior (P) portion of the MCL.

From: 1. Division of Radiologic Sciences, Wake Forest University, Winston Salem, NC, USA, 2. Department of Radiology, 3. Department of Experimental Anatomy, Vrije Universiteit Brussel, Brussels, Belgium. Address for correspondence: Dr M. De Maeseneer, Division of Radiologic Sciences, Wake Forest University Hospital, Medical Center Boulevard, Winston Salem, NC 271571088. E-mail: mdemaes2@wfubmc.edu

JBR–BTR, 2010, 93 (2)

C A

D Fig. 2. — A. Coronal anatomical slice. The superficial (S) and deep (D) bands of the MCL can be seen. The deep band is made up of a meniscofemoral and meniscotibial portion. B. Coronal drawing illustrates superficial (S) and deep (D) bands of the MCL. C. Coronal proton density weighted MR image in cadaver. Note fascia (F) and superficial (S) and deep (D) bands of the MCL. D. Spot film of the knee. The superficial MCL can be seen (arrows) outlined by fat. Also note meniscofemoral band (F), meniscotibial band (T) and meniscus (M).

Fig. 3. — Drawing illustrating classification of MCL tears. Sprain on the left (grade 1) with fluid surrounding the MCL. Partial tear in the middle (grade 2) with partial disruption of the MCL, and complete tear on the right (grade 3) with a complete disruption of the MCL.

account in the present grading system. Superiorly, a fascial tear may also extend to the vastus medialis muscle (Fig. 6, 7). In some instances only the deep fibers are involved. (Fig. 8). Sometimes the MCL lesion extends posteriorly (Fig. 9). Posteriorly the lesion may extend to the oblique popliteal ligament which plays a role in knee stability).

MCL bursitis A bursa is present between the superficial and deep bands of the anterior MCL. Sometimes a femoral and a tibial component may be separate from each other (Fig. 10). Although this is a rare event, occasionally the bursa may become distended with fluid. Since the fluid is

MRI SPECTRUM OF MEDIAL COLLATERAL LIGAMENT INJURIES — DE MAESENEER et al

Fig. 4. — Coronal T2 weighted MR with fat saturation. Note fluid superficially and deep to the superficial band of the MCL (arrows) compatible with grade 1 tear (sprain).

Fig. 7. — Corresponding drawing showing extension in vastus medialis (M). Compare to Figure 6.

Fig. 5. — Coronal T2 weighted image with fat saturation. Note complete discontinuity of superficial MCL fibers (arrows) compatible with grade 3 tear. The deep meniscofemoral part is also ruptured.

Fig. 6. — Coronal T2 weighted MR image with fat saturation. Partial tear of the fascia is seen and lesion extends into fibers of the vastus medialis (M).

Fig. 8. — Coronal proton density weighted MR image. Arrows outline normal superficial fascia. Arrowhead points to disrupted deep meniscofemoral band of the MCL.

Fig. 9. — Coronal T2 weighted MR image with fat saturation. Note superficial fascia (F, arrow). Arrows point to injury of posterior part of the MCL showing high signal intensity.

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JBR–BTR, 2010, 93 (2)

located adjacent to the MCL, it could be mistaken as evidence of an MCL tear. The bursa usually becomes distended due to mechanical friction such as in horseback riding and motorcycling. Less commonly rheumatological disorders may cause distention of this bursa. Osteoarthritis Degenerative disease commonly affects the knee joint (Fig. 11). Signs include chondromalacia, subchondral bony edema, meniscal extrusion, and bulging of the MCL (5). Often fluid will accumulate deep to the MCL. This is however a reactive phenomenon and not an indication of an MCL sprain. Medial cellulitis

The soft tissues on the medial aspect of the knee may become affected in an ailment termed medial cellulitis (Fig. 12). This may be a rather focal area of cellulitis or may be more generalized such as in anasarca. The fluid in this instance collects mainly superficial to the medial fascia and hence differentiation from a MCL sprain is thus possible. Medial meniscal tear Meniscal tears are very common on the medial aspect of the knee (Fig. 13). With such tears it is not uncommon to depict reactive fluid deep to the superficial band of the MCL (5). This fluid could be erroneously mistaken for evidence of an MCL sprain. Medial meniscal cyst

B B Fig. 10. — A. Coronal T2 weighted MR image with fat saturation. Fluid is seen filling up the meniscotibial portion of the MCL bursa (arrow) deep to the superficial band of the MCL. In B drawing shows meniscofemoral and meniscotibial part (arrows) of MCL bursa.

Fig. 11. — A. Coronal T2 weighted MR image with fat saturation. Degenerative expulsed meniscus is seen (M) with fluid extending deep to the MCL (arrows). In B drawing shows corresponding findings.

A meniscal cyst usually presents as an oval shaped collection between the superficial and deep MCL (Fig. 14) (6-8). Meniscal cysts are most often associated with a horizontal tear of the meniscus. However, this is not always the case. Occasionally an area of mucoid degeneration may occur in the meniscus without an associated tear. A meniscal cyst is rather rounded or oval shaped whereas an MCL bursa usually appears as an elongated collection adjacent to the femur or tibia or both. When it is located posteromedially it may present as an elongated collection deep to the MCL and be mistaken for evidence of MCL sprain.

MRI SPECTRUM OF MEDIAL COLLATERAL LIGAMENT INJURIES — DE MAESENEER et al

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A A

Fig. 12. — A. Coronal T2 weighted MR image with fat saturation. Note diffuse soft tissue infiltration superficial to the MCL (arrows). In B corresponding drawing shows soft tissue edema (arrows).

Fig. 13. — A. Coronal T2 weighted MR image. Note meniscal tear with fluid superficial and deep to the MCL. In B corresponding drawing shows similar findings (arrows).

B Fig. 14. — A. Coronal proton density weighted MR image. Meniscal cyst is shown adjacent to meniscus and deep to MCL (arrows). In B anatomical drawing shows similar findings.

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Fig. 15. — Coronal T2 weighted MR image. Note fluid superficial to MCL (arrows) in the setting of a patellar dislocation with retinaculum involvement. Note corresponding typical bone contusion at lateral condyle (C).

Fig. 16. — Coronal proton density weighted MR image. Meniscocapsular separation is shown (arrow).

Medial retinaculum tear MCL injury may extend to the medial retinaculum (Fig. 15). The opposite situation also occurs. In patellar dislocation involvement of the retinaculum typically is associated with involvement of MCL fibers (9). In a retinacular tear a typical bone marrow edema pattern may be seen on the lateral condyle. Meniscocapsular separation

Fig. 17. — Coronal proton density weighted MR image. Note tear of meniscofemoral band (F, arrow), a type of meniscocapsular separation and leaking of fluid deep to the MCL (arrow).

With meniscocapsular separation fluid may be detected between the meniscus and the deep bands of the MCL (Fig. 16, 17). This could also be mistaken for evidence of an MCL sprain (10, 11). Deeper involvement may include peripheral meniscal tears. Conclusion MCL injuries present a varied spectrum with involvement of deep and superficial components and also

possible involvement of the posterior MCL. Various soft tissue structures adjacent to the MCL may present with reactive fluid around the components of the MCL and may simulate MCL tears. Acknowledgment We thank Anne Phillips, B.F.A. University of Michigan, for the drawings provided.

References 1. De Maeseneer M., Van Roy F., Lenchik L., Barbaix E., De Ridder F., Osteaux M.: Three Layers of the Medial Capsular and Supporting Structures of the Knee: MR-ImagingAnatomic Correlation. RadioGraphics, 2000, 2: S83-89. 2. Warren F.L., Marchall J.L.: The supporting structures and layers on the medial side of the knee: an anatomical analysis. J Bone Joint Surg Am, 1979, 61: 56-62. 3. Ruiz M.E., Erickson S.J.: Medial and lateral supporting structures of the knee: normal MR imaging anatomy

MRI SPECTRUM OF MEDIAL COLLATERAL LIGAMENT INJURIES — DE MAESENEER et al and pathologic findings. Magn Reson Imaging Clin North Am, 1994, 2: 381399. 4. McNally E.: Knee: Ligaments. In: Imaging of orthopedic Sports Injuries. Edited by Vanhoenacker F.M., Maas M., Gielen J.: Printed by Springer-Verlag, Berlin 2007, pp 283305. 5. Wen D.Y., Propeck T., Kane S.M., Godbee M.T., Rall K.L.: MRI description of knee medial collateral ligament abnormalities in the absence of trauma: edema related to osteoarthritis and medial meniscal tears.

Magn Reson Imaging, 2007, 25: 209214. 6. De Maeseneer M., Shahabpour M., Vanderdood K., Machiels F., De Ridder F., Osteaux M.: MR imaging of meniscal cysts: evaluation of location and extension using a three layer approach. Eur J Radiol, 2001, 39: 117124. 7. Vanhoenacker F.M., Van de Perre S., De Vuyst D., De Schepper A.M.: Cystic lesions around the knee. JBR-BTR, 2003, 86: 302-304. 8. Beaman F.D., Peterson J.J.: MR imaging of cysts, ganglia, and bursae

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about the knee. Radiol Clin North Am, 2007, 45: 969-982. 9. Virolainen H., Visuri T., Kuusela T.: Acute dislocation of the patella: MR findings. Radiology, 1993, 189: 243-246. 10. De Maeseneer M., Shahabpour M., Vanderdood K., Van Roy F., Osteaux M.: Medial meniscocapsular separation: MR imaging criteria and diagnostic pitfalls. Eur J Radiol, 2002, 41: 242-252. 11. Rubin D.A., Britton C.A., Towers J.D., Harner C.D.: Are MR imaging signs of meniscocapsular separation valid? Radiology, 1996, 201: 829-836.

NEWS FROM THE UNIVERSITIES WETENSCHAPPELIJKE PRIJS EM. PROFESSOR DOCTOR A. L. BAERT PERIODE 2009-2010 Artikel 1 Een tweejaarlijkse prijs voor een bedrag van € 2500 wordt opgericht door de stichting “Wetenschappelijke Prijs Em. Prof. Dr. A. L. Baert te Leuven, met als doel het fundamenteel en klinisch wetenschappelijk onderzoek in de radiologie aan te moedigen.

Nederlands (interlinie 1, ca. 47 regels per blz.). Artikel 4 De prijs kan slechts toegekend worden aan een nog niet bekroond werk. De auteur van het bekroonde werk krijgt de titel “Laureaat Wetenschappelijke Prijs Em. Prof. Dr. A. L. Baert”.

Artikel 2 Deze prijs kan worden toegekend aan een radioloog, opgeleid aan één van de vier Nederlandstalige universiteiten in België, op basis van een met goed gevolg verdedigde doctoraatsthesis, door een jury die zal benoemd worden door het stichtingscomité.

Artikel 5 De jury van de prijs is samengesteld uit 7 personen, aangeduid door het stichtingscomité volgens de regels van het intern reglement. Em. Prof. Dr. A. L. Baert is voorzitter van de jury. Het staat de jury vrij de prijs al dan niet toe te kennen.

Artikel 3 Slechts werken die minder dan 2 jaar oud zijn op de datum van hun indiening kunnen in aanmerking worden genomen. Het werk moet opgesteld zijn in het Nederlands of in het Engels, met in beide gevallen, een uitgebreide samenvatting van minstens 15 bladzijden in het

Artikel 6 De gevallen waarin door het reglement van de prijs niet is voorzien of betwistingen die zouden kunnen ontstaan betreffende de interpretatie ervan, de beoordeling van de ontvankelijkheid van de werken en/of van de kandidaten e.a. worden onherroepelijk door de jury beslecht.

Er wordt geen briefwisseling gevoerd over de uitspraak van de jury. Artikel 7 De kandidaten moeten hun werk samen met hun curriculum vitae indienen in 6 gedrukte exemplaren bij Em. Prof. Dr. A.L. Baert en 1 exemplaar bij de secretaris, uiterlijk op 30 september 2010. Het stichtingscomité bepaalt de exacte datum van de toekenning van elke tweejaarlijkse prijs, voorzien in de maand december. De eerste toekenning van de prijs is uitgereikt in december 1998. Em. Prof. Dr. A. L. Baert Voorzitter Trolieberg 58 Dienst radiologie, UZ Leuven 3010 Kessel-Lo Prof. Dr. Ph. Demaerel Secretaris Herestraat 49 3000 Leuven

JBR–BTR, 2010, 93: 104.

IMAGES IN CLINICAL RADIOLOGY Arachnoid Pacchioni’s granulation bulging in a transverse sinus of the brain F.C. Deprez1, D. Hernalsteen2, P. Bosschaert1

A 32-year-old woman was admitted with acute bi-occipital headaches at our emergency room. A head CT study without contrast agent injection was performed to exclude acute cerebral hemorrhage. It revealed a focal well delimited round lacuna in the left transverse sinus, which was confirmed after contrast material injection (Fig. A, transverse and frontal views, black arrow). This anomaly measured 4 mm in diameter, presenting a low mean density of 40 HU (lesser than normal sinus density) and was linked to the sinus upper wall by a small peduncle only visible on sagittal views (Fig. B1, white arrow). MRI series were realized to confirm the diagnosis of a “giant” arachnoid granulation bulging in the left transverse sinus and to exclude a focal thrombosis. The granulation presented a typical low T1-weigthed signal with no contrast enhancement (Fig. B2, sagittal view, white arrow), high T2-weighted signal similar to CSF (Fig. C, sagittal view, white arrow), and the peduncle in connection with the subarachnoid space was clearly visible. No pejorative anomaly was found on the MRI study. Symptomatic headache treatment was therefore proposed to the patient. Comment

Arachnoid granulations (AGs), also known as Pacchioni’s granulations, are small protrusions of the arachnoid into the spinal and cerebral venous sinuses, through dura defects. AGs have a role of passive filtration allowing CSF drainage from the subarachnoid space to the venous system. AGs normally measure a few millimeters but become enlarge with age and can expand into the inner table of the skull or bulge in venous sinuses, most often in the transverse or superior sagittal sinuses and rarely in the straight sinus. AGs are usually fortuitous asymptomatic discoveries but are rarely reported to cause symptoms from venous hypertension secondary to partial sinus occlusion, as proven by dural sinus pressure measurements on both side of the lesion. AGs are commonly encountered on imaging, especially on contrast enhanced CT or MR studies, and must be differentiated from dural sinus thrombosis. Thrombosis is most often most extensive than AGs, involving an entire segment of a sinus or even several sinuses and sometimes extending into cortical veins. Acute thrombosis presents a high density CT signal and usually high T1weighted and low T2-weighted signal on MRI. AGs imaging features are described upper. Differential diagnosis with other intrasinusal tumors such as meningioma, cavernous haemengioma or meninogocele can also be performed by their characteristic imaging features.

1. Department of Radiology, Clinique St-Pierre, Ottignies-LLN, 2. Department of Radiology, Cliniques Universitaires St-Luc, Brussels, Belgium.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 105.

IMAGES IN CLINICAL RADIOLOGY Appendicular endometriosis mimicking appendicitis F. Claus1, D. Vanbeckevoort1, G. De Hertogh2, V. Vandecaveye1, Ph. Koninckx3

A 31-year-old woman presented to the emergency department with right lower quadrant pain. The pain had started three days earlier with increasing intensity postprandially, when walking and in right decubitus position. Completion of her last menstruation was one week before admission. Clinical examination confirmed the right fossa pain with a negative psoas sign. Laboratory findings revealed normal white blood cell count (6.4 x 109/L) and a mild elevation of the CRP (12.6 mg/L). Abdominal ultrasound and CT showed a pathological wall thickening of the appendix extending to the caecum and with infiltration of the peri-appendicular fat and a thickening of the adjacent peritoneal membrane (Fig. A, B). There was no free fluid. Based on the clinical and imaging findings, the tentative diagnosis of appendicitis was made, and a laparascopic appendectomy and a partial caecal resection was performed. Microscopic examination of the appendix showed only minor signs of inflammation, but the presence of fibrous tissue intermixed with endometrial glandular tissue. The latter was confirmed by CK-7 and CD-10 positive staining. Delayed second-look laparascopy showed adhesion of both ovaries towards the uterus and endometriosis sites in the rectovesical excavation and the recto-uterine pouch. Retrospective analysis of the CT-images depicts the close proximity of both ovaries to the uterine body (Fig. C). Comment

Endometriosis is a condition in which endometrial tissue is found outside the uterine cavity. It is typically seen during the reproductive years and the estimated prevalence ranges between 5-10%. Endometriosis is a common finding in women with infertility and the main symptom is (pelvic) pain. Common sites of endometriosis are the ovaries, the recto-uterine pouch, the rectovesical excavation, the posterior broad and uterosacral ligaments, the fallopian tubes and the sigmoid. Appendicular endometriosis is rare with an estimated prevalence 0.05% in the general population and up to 5% in series with female patients presenting with chronic pelvic pain. In the absence of clinical suspicion, the pre-operative diagnosis of appendicular endometriosis is very difficult. Both symptoms and imaging findings are very similar to appendicitis, as illustrated in the case above. Therefore, in reproductive-age women presenting with right lower quadrant pain, no (or only minor) elevated inflammatory blood parameters and pathologic imaging findings of the appendix, endometriosis should be considered in the differential diagnosis. CT has a rather low accuracy in detecting endometriosis, but careful inspection of the pelvis for other implants (e.g. adnexal endometrioma) or adhesions can favour the diagnosis, which can then be confirmed by transvaginal ultrasound, MR imaging or laparascopy.

1. Department of 1. Radiology, 2. Pathology and 3. Gynecology and Obstetrics, University Hospitals Leuven, Leuven, Belgium.

JBR–BTR, 2010, 93: 106.

IMAGES IN CLINICAL RADIOLOGY Closed loop small bowel occlusion through a congenital defect of the greater omentum

★

B. Coulier1, B. Vander Elst1, F. Pierard2

★ A

An 80-year-old male was admitted with a 15-h history of persistent epigastric and peri umbilical pain. Pain had spontaneously appeared during night and awakened the patient. There was neither nausea nor vomiting. Physical examination revealed moderate epigastric and supraumbilical abdominal tenderness. The patient was without surgical antecedent. Laboratory tests were normal. Abdominal ultrasound suspected small bowel subocclusion. Contrast enhanced abdominal MDCT confirmed small bowel sub-occlusion with distension of small bowel loops in the epigastric area, left upper quadrant and left flank. A transitional zone between dilated and collapsed loops was individualised in the infra-umbilical area. During dynamic multiaxial MPR analysis around the point of constriction a typical close loop configuration (Fig. A) was recognised and the diagnosis of internal hernia was proposed. The patient underwent laparatomy and the diagnosis of internal hernia was confirmed. The orifice consisted of a 2 cm congenital defect through the free edge of the greater omentum (Fig. B, white arrowhead). The exact nature of the hernial orifice was retrospectively identified on abdominal MDCT through scrupulous analysis of the surrounding vessels which were recognised as little omental veins (Fig. C) (white arrows on A & C). Comment

Internal hernias are defined by the protrusion of a viscus through a normal or abnormal peritoneal or mesenteric aperture within the confines of the peritoneal cavity. Internal hernias are associated with a high mortality rate, exceeding 50% in some series. The orifice can be either acquired, such as a postsurgical, traumatic or postinflammatory defect, or congenital, including both normal apertures, such as the foramen of Winslow and abnormal apertures arising from anomalies of internal rotation and peritoneal attachment. The general incidence of internal hernias is increasing because of a number of relatively new surgical procedures, including liver transplantation and gastric bypass surgery. A significant increase in hernias is occurring in patients undergoing transmesenteric, transmesocolic, and retroanastomotic surgical procedures. The occurrence of congenital internal hernias is rather rare. They are reported in 0.2%–0.9% of autopsies and in 0.5%–4.1% of cases of intestinal obstruction. The location and relative frequency of internal hernias are as follows: paraduodenal (53%), pericecal (13%), foramen of Winslow, (8%) transmesenteric and transmesocolic (8%), pelvic and supravesical (6), sigmoid mesocolon (6%), and transomental (1–4%). There are two types of transomental hernias. Herniation into the lesser sac may occur through the gastrocolic ligament or through a free greater omentum. The latter is more common, and no sac is present. The hernial orifice is located in the periphery near the free edge and is usually a slitlike opening from 2 to 10 cm in diameter. The cause for omental defect has not been identified, but it has been suggested that most have a congenital origin, although inflammation, trauma, and vascular disorders may also cause omental perforations. Small bowel loops, the cecum, and the sigmoid colon are involved in this defect. The clinical and radiologic findings are almost identical to those of transmesenteric hernias. Imaging studies often play an important role in the diagnosis of internal hernias because they are often difficult to identify clinically. CT has become the first-line imaging technique because of its availability, speed, and multiplanar reformatting capabilities. CT has a high diagnostic accuracy not only in detecting small bowel occlusion but also in defining its severity and aetiology. The latter is determined by meticulous analysis of the transition zone between dilated and collapsed loops, allowing for the correct diagnosis of the cause of the obstruction in 73–95% of cases. Closed loop obstruction is a specific type of obstruction (often found in internal hernias) in which two points along the course of a bowel are obstructed at a single location thus forming a closed loop. In this configuration, two successive dilated segments of bowel (the dilated afferent (black star) loop followed by the closed loop (white star)) are followed by a flattened segment (black arrow) (the efferent loop) and thus there are two adjacent points of narrowing in the small bowel. This is the mechanical situation encountered in internal hernias and in most the orifice will be narrow and both points of constriction will be close. The recognition of the closed loop configuration, dynamic multiaxial MPR (Fig. A) around the point of constriction and a scrupulous analysis and identification of the vessels surrounding this point of constriction were the diagnostic key in the reported case.

★

Departments of 1. Diagnostic Radiology and 2. Abdominal Surgery, Clinique St Luc, Bouge, Belgium.

JBR–BTR, 2010, 93: 107.

IMAGES IN CLINICAL RADIOLOGY Acute osteomyelitis M.I. Wessels1,2, M. Baeyaert1, J.-L. Termote1, F.M. Vanhoenacker2,3, A.M. De Schepper2, P.M. Parizel2

A 4-year-old boy was referred to our department of radiology because of pain in the right shoulder for a few days. Fever had been present for a few weeks before the onset of pain. A radiograph of the right shoulder (Fig. A) showed an ill-defined osteolytic lesion in the proximal diaphysis and metaphysis with extension through the growth cartilage (white arrows), periosteal reaction (black arrow) and soft tissue swelling (short arrows). Axial fat-suppressed intermediate-weighted MR images (Fig. B), revealed marrow edema (high signal intensity) surrounding a focus of intermediate signal intensity (black arrow), focal cortical breakthrough (cloaca) (asterisks) and surrounding soft tissue edema. After administration of gadoliniumcontrast, there was rim enhancement of the bone lesion (white arrow) on the coronal fat-suppressed T1-weighted MR Images (Fig. C). There was also associated soft tissue enhancement. Based on the imaging findings, the diagnosis of acute hematogeneous osteomyelitis was made. After intravenous antibiotics and oral antibiotic treatment for several weeks, radiographs after one, three and six weeks showed gradual regression of the radiographic abnormalities. Comment

Osteomyelitis consists of an infection of the bone and bone marrow. Hematogeneous spread is the most frequent route of contamination. Acute hematogeneous osteomyelitis is more common in the pediatric patient compared to chronic posttraumatic osteomyelitis in the adult patient. Symptoms worsen gradually over several days to a week. Initial symptoms, such as malaise and low-grade fever, may be nonspecific and are usually associated with those of bacteremia. Other symptoms include local bone pain, reduced movement of the affected area and local swelling. The long bones of the femur, tibia and humerus are most often involved. Laboratory tests reveal elevated sedimentation rate, C-reactive protein, and white cells count. The prevalence of acute osteomyelitis in children varies between 1/1000 to 1/5000. It is twice as common in males as females. Staphylococcus aureus is the most common causative organism. Before puberty, the infection starts at the metaphysis. Bacteria may be trapped in the metaphyseal nutrient vessels. Rise in intramedullary pressure due to inflammation and edema leads to local tissue necrosis and breakdown of the trabecular bone structure. Spread of infection occurs along the Haversian canals through the cortex and beneath the periosteal layer. Fragments of necrotic bone may become isolated within the medullary bone (sequestrum). Conventional radiography is often insensitive for early depiction of osteomyelitis. Subtle soft tissue swelling may be seen within 3 days after infection, but bone destruction and periosteal reaction is delayed for a period of 7 days to 2 weeks. MR is the preferred modality for early detection and evaluation of local extension of osteomyelitis. Characteristic findings are bone marrow and soft tissue edema, intramedullary, subperiosteal and soft tissue abscess formation, cloaca (cortical breakthrough), and sequestration. After contrast administration there is enhancement of the affected areas with peripheral enhancement in abscesses and sequestrum. Ultrasound may identify subperiosteal fluid collections. The advantage of ultrasound is that sedation or anesthesia is not required and abscess or fluid collections can be aspirated in a single procedure. Treatment of osteomyelitis consists of intravenous antibiotics or – if unsuccessful – surgical debridement with placement of antibiotic pearls. The prognosis, with early recognition and prompt treatment, is good.

1. Department of Radiology, Heilig Hart Ziekenhuis, Lier, 2. Department of Radiology, University Hospital Antwerp, UZA, University of Antwerp, Edegem, 3. Department of Radiology, AZ Sint-Maarten, Duffel-Mechelen, Duffel, Belgium.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 108.

IMAGES IN CLINICAL RADIOLOGY Arachnoiditis ossificans Ph. Bernard1, F.M. Vanhoenacker1,2, N. Adam3

An 18-year-old female underwent a CT scan and subsequently an MRI scan of the lumbar spine at our department because of chronic low back stiffness and pain, extending in the sacro-iliac and coccygeal regions. The patient had been involved in a car accident one year before. There was no history of previous surgery. CT revealed a spontaneous hyperdensity of the dural sac (Fig. A, black asterisk) and the nerve root sheaths L4 to S1. MRI showed signal loss on both T1- and T2-weighted images of the dural sac (Fig. B-C, white asterisks), and nerve roots suggesting calcification. Furthermore, a plate-like hypo-intense structure was visible at the posterior leptomeninges of the lower thoracic spine (Fig. B-C, white arrows). Treatment with physiotherapy and paralumbar infiltrations was performed resulting in clinical improvement after 6 months. Comment

Arachnoiditis Ossificans (AO) is a rare type of chronic arachnoiditis characterised by the presence of calcification or ossification of the spinal arachnoid, due to proliferative metaplasia of the arachnoid closely enveloping the spinal cord and nerve roots. Although the process may either consist of calcifications or ossifications, the terms arachnoiditis ossificans and calcificans are often used interchangeably. It usually affects the thoracic spine. Isolated involvement of the lumbar spine or cauda equina is very rare. Typically, the lesion extends over fewer than five vertebral levels, but extension over more than ten vertebral levels has been described. Risk factors include previous spinal surgery or trauma, (chemical) meningitis, non-traumatic subarachnoidal hemorrhage, myelography with oil-based contrast agents and injection of intraspinal anesthetic agents. AO may also be idiopathic. In our patient, the previous car accident could be incriminated as potential causative factor. Clinically, there is no distinct symptom complex, but AO is an important, often unrecognized, cause of failed back syndrome, sometimes leading to severe chronic disability and neurological deficit. Plain film imaging is often insensitive for detection of subtle calcifications or ossifications. In extensive cases, radiography may show linear calcifications and ossifications within the spinal canal. On CT, typically hyperdense linear calcifications surrounding or in the dural sac and nerve roots are present. On MRI, these lesions appear usually hypointense on all pulse sequences. In later stage disease, the lesion may contain bone marrow, resulting in a predominant high signal intensity on T1weighted images. Treatment is controversial. Conservative pain management treatment is preferable. In case of progressive neurological deterioration, surgery such as laminectomy combined with dural enlargement and careful resection of soft tissue arachnoiditis to facilitate CSF flow is recommended. However, aggressive removal of periradicular ossification is contra-indicated, because the surgical procedure may cause neurological damage. Furthermore, surgery itself may aggravate the process of arachnoiditis.

1. Department of Radiology, AZ Sint-Maarten, Mechelen-Duffel, Mechelen, 2. Department of Radiology, Antwerp University Hospital, Edegem, 3. Department of Physical Medicine, SintAugustinus Hospital Antwerp, Wilrijk, Belgium.

JBR–BTR, 2010, 93: 109.

IMAGES IN CLINICAL RADIOLOGY Fallen fragment sign J. Van Doninck1, F.M. Vanhoenacker1,2, C. Petré1, D. Willemen1

A 16-year-old boy presented at the emergency room after he fell on his left shoulder while playing American football. Plain radiographs showed a pathological fracture through a well- defined expansile radiolucent lesion within the proximal meta-diaphysis of the left humerus (Fig. A). The lesion caused cortical thinning and contained multiple linear cortical fragments within the central part of the lesion (arrows in Fig. A). Based on the age, location and the plain radiographic characteristics (“fallen fragment sign”), the diagnosis of a solitary bone cyst (SBC) was suggested. Subsequent Magnetic Resonance Imaging (MRI) confirmed the cystic nature of the lesion. Indeed, the lesion was homogeneously hypointense on T1-weighted (WI) images and hyperintense on T2-weighted images (Fig. B) and there was only faint peripheral enhancement of the lesion (Fig. C). There is also minor enhancement at the periosteal side of the medial cortex of the humerus, which can be attributed to pathological fracture. No solid enhancing parts were seen. The lesion contained no internal septations. The patient was treated by immobilisation. Follow-up after ten months showed adequate fracture healing and gradual remodeling of the lesion. Comment

Simple bone cysts (SBC) are benign bone tumors, which are often discovered as incidental findings on plain radiographs or diagnosed after a pathological fracture. They typically occur in the proximal humerus or the femoral neck in children. Although such cysts have also been described in the spine, the pelvis and even in flat bones the metaphyseal region of long bones is a site of predilection. Diagnosis can be made based on the combination of clinical presentation (age of the patient less than 20 years old and skeletal distribution) and plain radiographic findings. The main differential diagnoses on plain radiography include aneurysmal bone cyst (ABC) and fibrous dysplasia. Simple bone cysts typically affect young growing children. During the growth period the lesion may enlarge until skeletal maturity. After fusion of the growth plate, the cyst will stop growing and will spontaneously disappear over years without any radiologic sequela. B On plain radiographs a mild form of septation can be suspected but on macroscopic section these cysts are hollow, fluid-filled and without any obvious partitioning. Therefore, the synonym “unicameral cyst” is often used. They have a sharply marginated radiolucent center surrounded by a dense cortical border of reactive bone. When complicated by a pathologic fracture, the fallen fragment sign on plain films or computed tomography (CT) is highly suggestive for SBC. This sign is explained by displacement of one or more cortical fracture fragments within the dependent zone of the hollow lesion cavity. This sign will not be seen in lesions with internal septations (such as ABC) or lesions containing solid components (such as fibrous dysplasia). It appears in approximately 20% of cases. MR imaging provides more information about the cystic contents and about the relationship of the lesion to the physeal plate. Prolonged T1 and T2 relaxation suggests a cyst, although T1 shortening may occur due to protein content or haemorrhage after a pathologic fracture. Following intravenous injection of C gadolinium chelates, a thin rim of enhancement is seen. Because of the natural evolution of simple bone cysts is spontaneous regression after the growing period of long bones, no therapy is required unless prevention of pathological fractures. When a patient presents with a pathologic fracture, healing of the fracture often will be the trigger for healing of the cyst. Alternative therapeutic options have been suggested ranging from corticoid injection into the cyst to curettage. Recently, percutaneous grafting with allografts or bone substitutes has been described. Malignant transformation of a SBC is extremely rare.

1. Departments of Radiology and Orthopedic Surgery, AZ Sint-Maarten, Duffel-Mechelen, Duffel, Belgium, 2. Department of Radiology, University Hospital Antwerp, UZA, University of Antwerp, Edegem, Belgium.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 110.

IMAGES IN CLINICAL RADIOLOGY Treats from the heart B.J. Emmer, M. Reijnierse1 A 48-year old woman complaining of fatigue and lower back pain since several days, presented at the emergency department with anomic aphasia and fever. The conventional radiograph of the knees revealed mild erosive changes in the left medial compartment with effusion and hand radiographs were unremarkable in the painful right hand but showed some joint space narrowing in the left IP-1 joint, whereas the chest radiograph, CT brain were unremarkable. Blood cultures demonstrated a Staphylococcus aureus sepsis. Lumbar spine MR showed an epidural abscess extending from L1 to L5 with posterior dural compression without signs of spondylodiscitis, as can be seen on the sagittal T1 TSE fat saturated image with intravenous administration of gadolinium (arrow Fig. A). Paravertebral extension of infection was seen on the left side at the L5-S1 level with involvement of the musculus erector spinae on the axial T1 TSE fat saturated image with gadolinium (arrow Fig. B). Transesophageal echocardiography showed vegetations and insufficiency of the mitral valve, consistent with endocarditis. After mitral valve replacement and continuation of antibiotic therapy the patient fully recovered. Comment Musculoskeletal symptoms are common in endocarditis. The most common symptom is arthralgia, usually of the larger joints. Secondly, lower back pain can be present, sometimes with irradiating pain mimicking clinical signs of disc extrusion. These symptoms can precede the diagnosis of endocarditis by several months. They often resolve spontaneously after treatment and an inflammatory and/or immune etiology has been postulated in most cases. Nonetheless, infectious embolic spread to the musculoskeletal system should always be considered in endocarditis regardless of appropriate treatment. The prevalence of endocarditis in patients with spinal infections can be as high as 30%. Depending on the involved compartment, spinal infections can be categorized into three groups: extradural infections (osseous spine, epidural space, facet joints, and paraspinal soft tissues), intradural extramedullary infections and intramedullary infections. The most common pathogen is S. aureus (62-67%) followed by Mycobacterium tuberculosis. The lower thoracic and lumbar spine is the most common site of involvement. Cord compression is the most common presenting symptom in spinal epidural infection. Epidural abscess is almost always located at the posterior portion of the spinal canal. The whole spine should be imaged once spinal infection is suspected, so that multiple level disease can be excluded. Focal abscess formation and paravertebral extension are best evaluated with contrast enhanced MR. Plain radiographic evaluation, generally the initial modality used, is of little value. CT may help to demonstrate paraspinal extension and bone destruction. The sensitivity of MRI for extradural infection varies between 91 and 100% and is the modality of choice. Sagittal views can be used to evaluate cranial or caudal extension. MRI signal depends on the contents of the lesion. Frequently, long segment isohyperintense epidural mass lesion with hypointense thickened, displaced dura on both T1- and T2WI can be seen. Cord compression can be easily detected with MRI. Postcontrast images can help in the differentiation of epidural phlegmon from abscess. Phlegmon has no liquid component or pus with almost uniform enhancement. Abscesses have a liquid component with rim enhancement.

1. Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 111.

IMAGES IN CLINICAL RADIOLOGY Calcific myonecrosis J. Peeters1, F.M. Vanhoenacker1,2, M. Camerlinck1,2, P.M. Parizel1

A 58-year-old man presented with a slowly growing painless mass at the anterolateral aspect of his left lower leg. His past history included a severe neurovascular damage of the left lower leg, due to an accidental dynamite explosion 34 years previously. During surgery following the accident, he developed compartmental ischemia of the left lower leg. Additionally, the involved leg became paralysed and atrophic and he suffered from neuralgic pain and numbness. Initial ultrasound examination showed a liquified mass containing milk of calcium located in the subcutis (Fig. A). Echogenic foci with shadowing were seen within the deeper anterolateral and posterior compartments. Plain radiographs revealed linear, plaque-like soft tissue calcifications, arranged parallel to the long axis in the anterior and posterior deep compartments of the lower leg (Fig. B, curved white arrows). Furthermore, multiple metallic fragments were seen in the soft tissue of left upper and lower leg due to dynamite explosion. (Fig. B, short black arrows). CT clearly demonstrated the rim-like distribution of peripheral calcifications with central intermediate density, suggesting milk of calcium (Fig. C, straight white arrow). The calcific mass was intimately related to the adjacent tibia and fibula cortex (Fig. C, short black arrows). Based on the imaging findings and the clinical history, the diagnosis of calcific myonecrosis was made. Because the lesion remains painless, no further treatment was installed. Comment

Calcific myonecrosis is a condition characterized by latent formation of a dystrophic calcified mass occurring 10 to 64 years after an initial injury of the B lower leg. It typically presents as a slowly enlarging mass in one or more compartments, but location within the anterior compartment of the lower leg is most frequent. It has been suggested that the lesion is a late sequela of compartment syndrome, in which necrotic muscle undergoes central liquefaction and peripheral calcification. Neurovascular compromise seems to be the most important etiopathogenetic factor. Calcific myonecrosis can also occur after common peroneal nerve injury. The mass may enlarge slowly because of repeated intralesional hemorrhage with time. As in most patients with calcific myonecrosis, our patient presented with a visible painless mass representing a late focal enlargement caused by herniation of necrotic tissue through the muscle fascia. Imaging features of calcific myonecrosis have been well described in the literature. Plain radiographs show well-defined mass with linear pattern of calcifications organized around the periphery of the lesion. Sonographic examination demonstrates peripheral, echogenic foci with acoustic shadowing consistent with calcification. The central part of the lesion is hypoechoic and often liquified. CT and MRI more readily identify the typical compartmental distribution. CT shows the predominantly rim-like morphology of the calcifications and may sometimes depict scattered calcifications within the mass, calcium-fluid levels or longstanding, smooth pressure erosions affecting the outer cortex of adjacent bone. On MRI, peripheral calcifications are of low signal intensity on both T1- and T2C Weighted Images(WI). On T2-WI, the mass is often heterogeneous in signal, with areas of bright signal intensity consistent with fluid, while other areas demonstrate intermediate signal intensity. On T1-WI, the central fluid region shows as a homogeneous low signal intensity area. Contrast enhanced CT and/or MRI may demonstrate peripheral enhancement due to anastomosizing small blood vessels around the mass. The distinct radiological features of linear plaque-like calcifications, together with the clinical history of previous closed injury, are helpful to differentiate calcific myonecrosis from other (calcified) soft tissue masses such as sarcomas, myositis ossificans and abscesses. Painless lesions are often left untreated. Ultrasound-guided needle decompression of the cystic mass is a treatment option for the occasionally painful, calcific myonecrosis, with subsequent injection of a mixture of an antibiotic agent and an anesthetic. Surgical debridement remains the most commonly recommended treatment for pain resistant lesions.

1. Department of Radiology, University Hospital Antwerp, UZA, University of Antwerp, 2. Department of Radiology, AZ Sint-Maarten, Duffel-Mechelen, Duffel, Belgium.

JBR–BTR, 2010, 93: 112.

IMAGES IN CLINICAL RADIOLOGY An unusual cause of pleuritic chest pain on a CT pulmonary angiogram J. O’Brien, S. Barrett, W. Torreggiani1

A 41-year-old lady with a history of breast carcinoma, was admitted for investigation of pleuritic chest pain. On examination, there were no focal abnormalities. Her white-cell count was mildly elevated at 12 x 109 cells/l and her biochemical profile was within normal limits. Her chest x-ray was unremarkable. A computed-tomography pulmonary-angiogram (CTPA) was subsequently performed which revealed no evidence of a pulmonary embolus or parenchymal abnormality. On the anterior aspect of the examination within the soft tissues, there were pockets of air visualised, adjacent to the left prosthesis, and when the windows were adjusted, there was a defect of the overlying tissue (Fig. A, B). A soft tissue infection in this area was suggested to the referring team, which was confirmed on examination. This case illustrates an unusual cause of pleuritic chest pain diagnosed on CTPA and the importance of examining extrathoracic structures on each CT examination.

1. Department of Radiology, Adelaide and Meath Incorporating the National Children’s Hospital, Tallaght, Dublin, Ireland.

JBRâ&#x20AC;&#x201C;BTR, 2010, 93: 113.

IMAGES IN CLINICAL RADIOLOGY Intracardiac defect demonstrated by cardiac CTA O. Ghekiere, J. Djekic, A. Nchimi1

A 50-year-old woman with history of multiple pulmonary arteriovenous malformation embolisations caused by hereditary haemorrhagic telangectasia (Rendu-Osler-Weber syndrome), complained of atypical chest pain and dyspnea. Electrcardiographic (ECG) findings were normal and the bicycle stress test was equivocal. ECG-gated 64-row cardiac multidetector computed tomography (MDCT) showed no significant coronary stenosis, but a membranous ventricular septal defect (VSD) (Fig. A, B). Patient responded well to a treatment with beta-adrenergic blocker (Carvedilol 3.125 mg/day), and considering the surgical risks, no attempt to close the VSD was performed. Comment

Congenital intracardiac defects allow communication of blood between the left and right cardiac cavities with left-to-right flow in most cases. The functional impairment caused by intracardiac septal defects primarily depends on the size of the defect, the status of the pulmonary vasculature, and the degree of shunting. Therapeutic options ranged from medical treatment to open or percutaneous closure and depend on the symptoms, the size and the type of defect. In general, the likelihood of success for percutaneous closure of cardiac defect increases with the amount of muscular rim which serves to land the closure device. Cardiac defects include VSD, ASD and atrio-ventricular septal defects. They may occur as an isolated lesion or in combination with other congenital cardiac anomalies. VSD are the most common of these defects and include 4 subtypes: (i) the type I (5%) are located in the outlet portions of the left and right ventricles abutting the conjoined annulus of the aortic and pulmonary valves; (ii) the type II (75%) occur around the membranous septum and the fibrous trigone of the heart; (iii) the type III (10%) are located in the posterior region of the septum beneath the septal leaflet of the tricuspid valve; and the type IV (10%) have entirely muscular rims. In comparison to cardiac echocardiography or magnetic resonance imaging, cardiac gated MDCT may lack functional information, but this case illustrate its capacity to reveal intracardiac defects.

1. Department of Radiology, Cliniques St-Joseph, LiĂ¨ge, Belgium.

JBR–BTR, 2010, 93: 114.

IMAGES IN CLINICAL RADIOLOGY Appendicular diverticulitis in an Amyand’s hernia B. Coulier1, F. Pierard2, S. Malbecq1

A 68-year-old male was referred to our imaging department with a history of pain in the right groin. There was no history of unusual strain and the pain had progressively developed over the last four days. Ultrasound examination of the inguinal area and scrotum (not illustrated) revealed an inguinal hernia containing an unusual tubular structure surrounded by inflammatory fat. Unenhanced MDCT (A, B, C) of the pelvis confirmed an inflammatory inguinoscrotal hernia that was containing a one-eyed inflammatory tubular structure rejoining the caecum in the right iliac fossa. This structure was unambiguously identified as the appendix and it was surrounded by inflammatory mesenteric fat and epiploic appendices and by some fluid. A series of diverticula (black arrow) were also clearly identified along the appendix and at least one of them – containing a gas bubble – appeared particularly inflamed (white arrow). Laboratory tests showed a CRP at 38,2 mg/l. Appendicular diverticulitis – with or without appendicitis – within an inguinal hernia (Amyand’s hernia) was the finally retained diagnosis. The patient underwent classical kelotomy which confirmed the diagnosis of perforating diverticulitis of the appendix. About eight to ten diverticula were visible along the secondary inflamed appendix and at least two were perforated. Comment

The incidence of having a vermiform appendix – normal or inflamed – within an inguinal hernial sac – a condition known as Amyand’s hernia – is very low varying from 0,5 to 1% and only 0,1% of all cases of appendicitis present in an inguinal hernia. It is extremely rare to be able to make a clinical or imaging diagnosis of an Amyand’s hernia preoperatively because when clinical symptoms are associated with an inguinal mass or hernia, the diagnosis of incarceration or strangulation is generally univocally evocated by the clinicians and directly leads to surgical repair. For this reason the diagnosis of Amyand’s hernia is classically always surgical. Appendiceal diverticula are also very rare. Their incidence ranges from 0,004% to 2,1% in appendectomy specimens and from 0,2 to 0,6% from routine autopsies. They can be classified as congenital or acquired. The congenital form is a true diverticulum and is extremely rare. The more prevalent acquired diverticulum is a false diverticulum or pseudodiverticulum consisting of mucosa and submucosa herniated through vascular clefts in the muscular layer. Consequently they are classically found on the mesenteric border of the appendix. Four variations of diverticular disease of the appendix are described, namely appendiceal diverticula without inflammation, acute appendicitis with diverticula, acute appendiceal diverticulitis with acute appendicitis and acute diverticulitis (the reported case). Isolated acute diverticulitis of the appendix is also very rare but perforates more than 4 times as likely as classical appendicitis. Clinically appendicular diverticulitis mimics appendicitis. The coexistence of appendicular diverticulitis and Amyand’s hernia is exceptional and to our kwownledge no previous case has been published.

Departments of 1. Diagnostic Radiology and 2. Abdominal Surgery, Clinique St Luc, Bouge, Belgium.

JBR–BTR, 2010, 93: 115-116.

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