Best of BJR 2013

BEST OF

BJR

BJR is the agship journal of the British Institute of Radiology. BJR is an international multidisciplinary journal which covers clinical and technical aspects of medical imaging, radiotherapy, oncology, medical physics and radiobiology.

BEST OF

AN INTERNATIONAL JOURNAL OF RADIOLOGY, RADIATION ONCOLOGY AND ALL RELATED SCIENCES

The oldest radiology journal in the world Acceptance to publication 4 weeks Open access option

PUBLISHED BY:

http://birjournals.org

Simultaneous MR and PET in clinical use %LRJUDSK P05 EULQJV D UHYROXWLRQ LQ GLDJQRVWLF LPDJLQJ WR OLIH 6WDWH RI WKH DUW 7 05, DQG FXWWLQJ HGJH PROHFXODU LPDJLQJ DUH IXOO\ LQWHJUDWHG DV RQH 2QO\ 6LHPHQV FDQ EULQJ \RX WKLV JURXQGEUHDNLQJ V\VWHP UHGHILQLQJ WKH ZD\ \RX YLVXDOL]H GLDJQRVH WUHDW DQG PDQDJH GLVHDVH :LWK

WKH SRWHQWLDO RI EUHDWKWDNLQJO\ DFFXUDWH LPDJHV WKDW RSHQ XS QHZ DYHQXHV RI UHVHDUFK DQG HQDEOH H[WUDRUGLQDU\ FOLQLFDO DSSOLFDWLRQV 0ROHFXODU 05 VXSSRUWV RXU MRLQW YLVLRQ IRU KHDOWKFDUH ² WR DGYDQFH GLVHDVH PDQDJHPHQW DQG LPSURYH FDUH IRU DOO SDWLHQWV ZZZVLHPHQV FRP P05

$QVZHUV IRU OLIH

A91CRM-9243-A2-7600

$ 05 $

ZZZ VLHPHQV FRP P05

The more deeply you look, the more clearly you see your patients.

Tumor Analytics – Oncology Solutions from Siemens www.siemens.com/oncology

Tumors are as individual as patients themselves.

At Siemens, we develop imaging, laboratory and IT solutions that help you understand the nature and behavior of individual tumors with amazing depth and clarity and guide their therapy. Tumor Analytics is our term for the advanced technologies that make such understanding and treatment possible.

Tumor Analytics supports you to diagnose cancer earlier and personalize its treatment. By matching the right treatment with the right patient, Tumor Analytics helps improve patient outcomes and reduce the overall cost of oncology care for institutions and societies.

In short: The better you understand and treat your patient’s tumor, the better you can care for your patient.

At the end of the day, that is what Tumor Analytics is all about.

Answers for life.

Contents

Best of BJR

Introduction from the Honorary Editors Review article Breast cancer subtypes: response to radiotherapy and potential radiosensitisation F E Langlands, K Horgan, D D Dodwell and L Smith

Full papers Scapular free flap harvest site: recognising the spectrum of radiographic post-operative appearance D K Powell, F Nwoke, M L Urken, D Buchbinder, A S Jacobson, J E Silberzweig and A S Khorsandi

MR cholangiopancreatography at 3.0 T in children: diagnostic quality and ability in assessment of common paediatric pancreatobiliary pathology A Almehdar and G B Chavhan

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma X-Q Pei, L-Z Liu, Y-H Xiong, R-H Zou, M-S Chen, A-H Li and M-Y Cai

Dose reduction in oncological staging multidetector CT: effect of iterative reconstruction M Karpitschka, D Augart, H-C Becker, M Reiser and A Graser

Cone beam CT guidance provides superior accuracy for complex needle paths compared with CT guidance W M H Busser, S J Braak, J J F¨utterer, M J L van Strijen, Y L Hoogeveen, F De Lange and L J Schultze Kool

Perihilar branching patterns of renal artery and extrarenal length of arterial branches and tumour-feeding arteries on multidetector CT angiography W Y Kang, D J Sung, B J Park, M J Kim, N Y Han, S B Cho, C H Kang and S H Kang

Bowtie filtration for dedicated cone beam CT of the head and neck: a simulation study G Zhang, N Marshall, R Jacobs, Q Liu and H Bosmans

Short communication Positron emission tomography (PET) attenuation correction artefacts in PET/CT and PET/MRI C Buchbender, V Hartung-Knemeyer, M Forsting, G Antoch and T A Heusner © 2013 The Authors. Published by The British Institute of Radiology. This publication is copyright under the Berne Convention and the Universal Copyright Convention. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without the prior permission of the copyright owner. Permission is not, however, required to copy abstracts of papers or articles on condition that a full reference to the source is shown. Multiple copying of the publication without permission is illegal—address enquiries regarding photocopying to the Copyright Licensing Agency, Saffron House, 6-10 Kirby Street, London EC1N 8TS, UK (Tel. +44 (0)20 7400 3100; E-mail: licence@cla.co.uk).

All opinions expressed in the British Journal of Radiology are those of the respective authors and not the publisher. The publisher has taken the utmost care to ensure that the information and data contained in this journal are as accurate as possible at the time of going to press. Nevertheless, the publisher cannot accept any responsibility for errors, omissions or misrepresentations howsoever caused. All liability for loss, disappointment, or damage caused by reliance on the information contained in this journal or the negligence of the publisher is hereby excluded.

Editorial Board HONORARY EDITORS Professor David Bradley

Scientific

Dr Nigel Hoggard

Medical

DEPUTY EDITORS Dr Daniel Birchall Professor Alan Jackson Dr Simon Jackson Professor Stuart Taylor Professor Mechthild Krause Professor Kevin Prise Professor William Vennart Professor Habib Zaidi

Diagnostic Radiology Diagnostic Radiology Diagnostic Radiology Diagnostic Radiology Radiotherapy & Oncology Radiobiology Physics & Technology Physics & Technology

ASSOCIATE EDITORS Abass Alavi Zahir Amin Richard Amos David Butteriss Mark Callaway Alejandro Carabe-Fernandez Isabel Castellano Steve Connor Gary Cook Peter Corr John Curtis Indra Das Marco Durante Jonathan Eatough Tarek El-Diasty Phil Evans Mark Farrugia Nitin Ghonge Rosalind Given-Wilson Giuseppe Guglielmi Stephen Harden Christopher Harvey John Holemans

Peter Hoskins David Howlett Paul Humphries Charles Hutchinson Andrzej Kacperek Elizabeth Krupinski Ranald MacKay Lesley Malone Stewart Martin Kieran McHugh Michael Michell Shinichiro Mori Hilary Moss Ludvig Muren Andrew Nisbet Christopher Njeh Abdul Jalil Nordin Allan Odurny Harpreet Pannu Mike Partridge Tufail Patankar Ruben Pauwels Niall Power

Shonit Punwani Madan Rehani Peter Riley Kevin Robson Carl Roobottom Anju Sahdev Andrew Scarsbrook Nicholas Screaton Andrew Slater Malcolm Sperrin David Sutton Katy Szczepura Alberto Tagliafico Paul Taylor Raman Uberoi Elspeth Whitby John Winder Bernd Wittkop Wai-Lup Wong Hui-Xiong Xu Pat Zanzonico

STATISTICS EDITORS Adam Brentnall Fay Cafferty

BJR is essential reading for radiologists, medical physicists, radiotherapists, radiographers and radiobiologists. Articles included in BJR cover a wide range of subjects, including diagnostic radiology, radiotherapy, oncology, nuclear medicine, ultrasound, radiation physics, radiation protection and radiobiology.

Authors benefit from rapid decisions, constructive peer-review and global dissemination. For more information or to submit your next article to BJR, go to http://bjr.birjournals.org

Subscriptions Institutional subscription are available from Affinity Subscriptions.

T: +44 (0)20 7383 6270 F: +44 (0)20 7383 6402 E: subscriptions@bmjgroup.com

Founded 1897 Incorporated by Royal Charter Patron: Her Majesty The Queen President: Prof. A Jones

Personal subscriptions Personal subscriptions are available by joining the BIR. www.bir.org.uk/join-us/ E: membership@bir.org.uk

The British Institute of Radiology has as its aim to bring together all the professions in radiology and allied medical and scientific disciplines to share knowledge, and educate the public, thereby improving the prevention and detection of disease and the management and treatment of patients.

Particulars of membership and other information can be obtained from the BIR: 48-50 St John Street, London EC1M 4DG, UK www.bir.org.uk T: +44 (0)20 3668 2220

All BJR subscribers also have free access to Imaging Online, the BIR’s review journal. imaging.birjournals.org

Back Issues BJR issues can be ordered from the BIR Publications Department. The price is £70 per issue including postage.

E: publications@bir.org.uk

Advertising Enquires regarding both print and online advertising should be sent to The Point of Difference: 4 Chaseside Avenue, London SW20 8LU, UK T: +44 (0)20 8542 3200 E: info@pointofdiff.eu For more information and advertising rates: www.bir.org.uk/publications/advertising/

Cover image credited as: Cervical spine MRI. © Deanaustinphotography (Dean Hoch) | Dreamstime.com

Submit to BJR RAPID PUBLICATION

INTERNATIONAL EDITORIAL BOARD

OPEN ACCESS OPTION

GLOBAL READERSHIP

HIGH QUALITY

STRINGENT PEER-REVIEW

For more information go to bjr.birjournals.org

$ &7 $

How important is 0.30 mm in CT? SOMATOM Definition Edge – The reference in single source CT www.siemens.com/somatom-definition-edge

0.30 mm can make a diagnostic difference – if you can see it. Siemens designed the SOMATOM Definition Edge with the revolutionary Stellar Detector and TrueSignal Technology. This unique, fully-integrated detector

reduces cross-talk and increases spatial resolution so that details the size of a grain of sand are visible. Minimized noise means outstanding image quality with the potential for lower dose. Now you can see the difference.

Answers for Life.

INTRODUCTION FROM THE HONORARY EDITORS David Bradley, Honorary Editor (Scientific) and Nigel Hoggard, Honorary Editor (Medical)

We hope you enjoy reading this collection of influential articles from recent issues of BJR. BJR is an international, multidisciplinary journal covering the clinical and technical aspects of medical imaging, radiotherapy, oncology, medical physics, radiobiology and the underpinning sciences. Although the disciplines encompassed by BJR are diverse, there is common ground between the medical specialties and the medical sciences represented, enabling readers to keep up to date with advances in related specialties as well as their own.

This collection contains a cross-section of the broad, multidisciplinary content that can be found in BJR. There are two articles reproduced in full and excerpts from seven articles to give you a taster of the great content that can be found in the journal. To read the articles in full, go to the BJR website (http://bjr.birjournals.org) where they have been made free until the end of 2013.

As the oldest scientific journal in the field of radiology and related sciences, BJR has published a number of pioneering articles, including the first description of computed tomography by Godfrey Hounsfield in 1973 [1]. The complete BJR archive, to be launched in 2014, has been digitised from 1896 and will be a valuable historical resource for the community.

“BJR articles are available quicker than ever… after acceptance it appears in its final version within only 4 weeks!”

Not only does BJR have a well-established place in history, it is also at the cutting edge of modern publishing. BIR|Open is BJR’s open access option for any author who chooses or is mandated to publish in this way. Additionally, all papers are published via continuous publication; once an article is in its final form, it is immediately published online in its final citable form. BJR articles are available quicker than ever before—after a paper is accepted for publication, it appears in its final version within only 4 weeks!

2014 will see the relaunch of the journal website for enhanced and more user-friendly content delivery.

BJR is a competitive, accessible, high-quality journal for 21st century radiological sciences.

We hope you will contribute to the continuing success of BJR by reading BJR articles, reviewing papers and submitting your work.

Reference 1. Hounsfield GN. Computerized transverse axial scanning (tomography): Part I. Description of system. Br J Radiol 1973;46:1016–22.

David Bradley

Nigel Hoggard

ARTICLE INFORMATION Received: 21 November 2012

Accepted: 15 January 2013

Š 2013 The Authors

doi: 10.1259/bjr.20120601

Cite this article as: Langlands FE, Horgan K, Dodwell DD, Smith L. Breast cancer subtypes: response to radiotherapy and potential radiosensitisation. Br J Radiol 2013;86:20120601.

REVIEW ARTICLE

Breast cancer subtypes: response to radiotherapy and potential radiosensitisation 1

F E LANGLANDS, MD, MRCS, 2K HORGAN, MD, FRCS, 3D D DODWELL, MD, FRCR and 1L SMITH, BSc, PhD

Section of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, Leeds University, Leeds, UK Department of Breast Surgery, Leeds General Infirmary, Leeds, UK 3 St James’s Institute of Oncology, St James Hospital, Leeds, UK 1

2

Address correspondence to: Dr Laura Smith E-mail: medlsmi@leeds.ac.uk

ABSTRACT Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Over 50% of patients receive RT at some time during the treatment of their disease, equating to over 500 000 patients worldwide receiving RT each year. Unfortunately, not all patients derive therapeutic benefit and some breast cancers are resistant to treatment, as evidenced by distant metastatic spread and local recurrence. Prediction of individual responses to RT may allow a stratified approach to this treatment permitting those patients with radioresistant tumours to receive higher doses of RT (total and/or tumour cavity boost doses) and/or radiosensitising agents to optimise treatment. Also, for those patients unlikely to respond at all, it would prevent harmful side effects occurring for no therapeutic gain. More selective targeting would better direct National Health Service resources, ease the burden on heavily used treatment RT machines and reduce the economic cost of cancer treatment. Unfortunately, there are no robust and validated biomarkers for predicting RT outcome. We review the available literature to determine whether classification of breast cancers according to their molecular profile may be used to predict successful response to, or increased morbidity from, RT. Classspecific biomarkers for targeting by radiosensitising agents are also discussed.

Breast cancer is the most common cancer in females with just over 1 million new diagnoses and some 400 000 deaths recorded worldwide each year (World Health Organization). As such, this

disease represents one of the most serious and costly health issues. Locoregional treatment of breast cancer has evolved over the last two decades not only in the surgical techniques used but also in

F E Langlands, K Horgan, D D Dodwell et al

the use and delivery of radiotherapy (RT). Surgical management has moved towards breast conserving surgery (BCS) and axillary sentinel lymph node biopsy wherever possible. Surgery aims to remove any disease that has been detected in the breast and regional lymph nodes. Surgery does not, however, remove undetected occult deposits of cancer that may remain within the breast, scar, chest wall or remaining lymph nodes. It is these undetected deposits that may lead to locoregional recurrence (LR) and furthermore to distant metastases.

RT has therefore become a well-established adjuvant treatment modality to optimise local control following most BCS [1] and following mastectomy in those patients at high risk of recurrence [2]. According to a recently published National Health Service Breast Screening Programme audit of 17 013 screen-detected breast cancers collected from April 2009 to March 2010, 10 425 (61%) females received adjuvant RT. This includes those diagnosed with both invasive (9223, 88.5%) and non-invasive (1202, 11.5%) breast cancers.

Of the 8739 patients who underwent BCS for invasive breast cancer, 8201 (94%) received RT. These data did not include females who presented to symptomatic breast clinics and indicate the considerable volume of patients requiring and receiving adjuvant RT each year in the UK alone. It is no surprise that there have been capacity issues leading to wide variations in the timelines of availability of RT from country to country, and even within the same country. RT achieves high cure rates where metastatic spread has not occurred [3–5] and offers improvements in overall survival (OS) and disease-free survival (DFS) in patients presenting with distant metastases at diagnosis [6]. A reduction in LR has tumour-related gains and also quality of life benefits, such as a reduction in the physical morbidity and psychological consequences of LR. However, as with all adjuvant therapies, there are recognised short-term (those which happen within ;3 months of completing treatment) and long-term side effects.

RADIOTHERAPY SIDE EFFECTS By far, the most common short-term side effects subsequent to RT are those of skin erythema and fatigue, which can occur in up to 100% of patients [3, 7].

Following this, late side effects include telangectasia (31.4%) and impaired cosmesis with fibrosis (6.7%) [3, 7–9]. Arm lymphoedema and shoulder stiffness are other long-term side effects that can impact on patients’ everyday activities [3, 8]. Post-operative breast RT can

2 of 10

bjr.birjournals.org

also damage the underlying chest organs, namely the lungs and heart. Pulmonary effects include radiationinduced pneumonitis and fibrosis [10]. Radiation pneumonitis is an acute exudative inflammatory process, typically occurring within 1–4 months after RT, which follows the initial damage of cells in the alveolar space (pneumocytes, fibroblasts, endothelial cells and macrophages; [11]). Pulmonary fibrosis is a late injury due to interstitial damage involving the parenchyma and pleura [12]. Radiation damage can also cause endothelial cell damage and atherosclerosis [13], myocardial ischemia and fibrosis [14]. Complications, such as acute pericarditis, pericardial effusion and arrhythmias, can also develop in patients and, in some cases, can occur up to 20 years post treatment. Over the last few decades, there has been an increased recognition of the late side effects of RT. Thus, the introduction of modern techniques (including image-based planning and directed therapies) has reduced irradiation doses to the heart and lungs. However, since some of the more severe late side effects of RT can occur many years following exposure, the full potential benefits of these changes is uncertain, and other possible significant adverse effects have yet to be reported in the literature.

CRITERIA FOR SELECTING PATIENTS FOR RADIOTHERAPY Although RT is used routinely following BCS, many patients could be effectively treated with breast surgery alone without RT. Despite this, there is currently insufficient knowledge to enable the selection of patients who do not need RT. Studies have been unsuccessful in attempting to identify a low-risk group with a ,5% chance of local relapse in whom RT can be reasonably omitted [15]. At the present time, it is therefore recommended that RT should be considered for all patients undergoing BCS, even those with low-grade nodenegative disease. Likewise, not all patients derive therapeutic benefit since some breast cancers are refractory to this treatment, as evidenced by distant metastatic spread and LR. At present, decisions regarding who receives RT are based on clinical factors, stages, morphology-based pathological indicators and type of surgery rather than molecular profiles predictive of likely RT sensitivity. As a result, all breast cancer patients are currently treated with the same RT regimen, irrespective of whether their tumours are likely to respond or not. A more informed approach to identify individual responses would allow a stratified approach, allowing

Br J Radiol;86:20120601

Breast cancer subtypes and response to radiotherapy

those patients unlikely to respond to receive higher doses of RT (total dose and/or tumour cavity boost dose) and/ or radiosensitising agents to increase the efficacy of their treatment. Those patients unlikely to respond at all could be spared from the associated iatrogenesis. This could have a positive impact on breast cancer mortality rates worldwide, ease burden on heavily used treatment machines and reduce the economic cost of cancer treatment.

BIOMARKERS FOR PREDICTING RESPONSE TO RADIOTHERAPY Oncological therapies continue to be developed and are increasingly more specific and targeted towards cancer biomarkers. Prognostic and predictive biomarkers are the two major types of cancer biomarkers, and it is important to recognise that there is a clear distinction between these terms. Prognostic biomarkers are intrinsic factors that provide information about a patient’s overall cancer outcome regardless of therapy.

Such biomarkers may be used by physicians to select those high-risk patients who may benefit from more aggressive treatment. However, such biomarkers are unable to highlight those patients that will derive a clinical benefit from a given therapy. On the other hand, predictive biomarkers provide information regarding the probability of therapeutic benefit from a specific treatment [16]. Well-known examples of these include the oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), which are used to predict response to endocrine therapy and trastuzumab, respectively. However, it is also possible that biomarkers can be both prognostic and predictive.

Several potential predictive biomarkers that may correlate with RT response have been identified [17–19]. In breast cancers, expression levels of Holliday junction recognition protein (HJURP) mRNA can predict patient survival after RT [17] and high cytoplasmic expression of peroxiredoxin-I correlated with increased LRs after RT [18]. However, in most cases, predictive and prognostic information from potential biomarkers has not been separated. Unpublished work from our group has shown that high proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 (PSMD9) expression is significantly associated with an increased incidence of LR in a cohort of breast cancer patients receiving adjuvant RT (log rank p50.02) but not in those treated without RT, indicating that this protein might represent a predictive biomarker for RT response.

3 of 10

bjr.birjournals.org

Review article

However, none of these biomarkers is currently used to guide treatment decisions within the clinic owing to a lack of large-scale randomised control trials in this area.

BREAST CANCER SUBTYPES AND RESPONSE TO RADIOTHERAPY It is well known that breast cancer is not a single disease but rather a collection of diseases with diverse histopathologies and gene expression profiles. Gene expression profiles have enabled the classification of breast cancers into subtypes that were not apparent using more traditional histopathological criteria [19]. Correlating gene expression patterns in the different breast cancer subtypes to clinical, pathological and outcome data has supported the idea that breast cancer subtypes have strong differences in cell biology and tumour behaviour and can be treated as separate diseases.

Although gene expression profiling remains the gold standard for classification, this is not currently feasible for large-scale clinical applications, and so, within the clinic, the system of defining subtypes still relies on the more traditional histopathological methods to assess expression of three common molecular markers; ER, progesterone receptor (PR) and HER2 [20–23]. The luminal subtypes (luminal A and luminal B) encompass the hormone receptor (ER and PR) positive breast cancers [22]. The HER2 subtype consists of those breast cancers expressing low levels of hormone receptors but overexpressing HER2. The basal-like subtype is typically categorised by routine immunohistochemistry as triple negative breast cancer owing to very low or negligible expression levels of ER, PR and HER2 [20–23]. Importantly, we acknowledge that, although most basallike breast cancers have a triple negative phenotype and the vast majority of triple negative cancers comprise basal-like breast cancers, these are not synonymous [24]. However, in the absence of a more suitable marker for the classification of basal-like breast cancers for the purpose of this review, we will define this subtype in accordance with Schneider et al [25] by referring to basal-like breast cancers when gene expression profiling or more sophisticated immunophenotypes were used for identification and triple negative breast cancer when analyses were limited to clinical assays.

It is clear that the heterogeneous nature of breast cancer accounts for different outcomes among women diagnosed with this disease. For example, luminal subtypes are associated with a more favourable prognosis,

Br J Radiol;86:20120601

F E Langlands, K Horgan, D D Dodwell et al

whereas HER2 and basal-like subtypes are associated with significantly worse recurrence rates and diminished OS [21–23, 26]. This was confirmed by Wang et al (2011) [27], who conducted a retrospective analysis of 2118 primary operable breast cancer patients and found that molecular subtype could robustly identify the risk of recurrence with luminal A tumours having the lowest rate of relapse (12.7%, p,0.001), whereas luminal B, HER2 and basal-like subtypes were associated with higher rates of relapse (15.7%, 19.1%, 20.1%). It is also clear that such heterogeneity accounts for variations in response to therapy. However, the question remains as to whether these breast cancer subtypes may be used to predict response to RT or whether specific subtypes may benefit from radiosensitising agents to enhance the efficacy of this treatment. Data from our in vitro studies have shown that breast cancer cell lines representing the different subtypes exhibit differential inherent sensitivities to ionising radiation [28], which suggests that this may certainly be feasible. A clear advantage of being able to exploit these markers for selecting patients for RT is that their expression is already routinely analysed within the clinic for diagnostic and prognostic purposes and also for selecting patients for other breast cancer therapies.

LUMINAL SUBTYPES In 2008, Nguyen et al [29] studied 793 consecutive patients with invasive breast cancer who received BCS followed by RT and reported LR incidences of 0.8% for luminal A, 1.5% for luminal B, 8.4% for HER2 and 7.1% for triple-negative cancers. Kyndi et al [30] also found a significantly improved OS rate after postmastectomy RT (PMRT) only among patients characterised by good prognostic markers (ER/PR positivity and HER2 negativity), whereas no significant OS improvements after PMRT were found among ER/PRnegative and HER2-positive patients. Furthermore, a significantly improved survival rate was reported for patients with hormone-receptor-positive and HER2negative tumours (resembling tumours of the luminal A subtype), who received PMRT when compared with those who received no RT [30]. This suggests that RT is particularly effective for breast cancers of the luminal phenotype, especially that of luminal A. This was confirmed by Wang et al [27] who found that, for breast tumours of the luminal A subtype, adjuvant RT reduces the risk of relapse (p50.005). It has been proposed that these tumours may be particularly sensitive to RT as a result of their dependence on oestrogen [30].

4 of 10 bjr.birjournals.org

Oestrogen acts to accelerate G1 to S phase transition of the cell cycle which, hypothetically, could leave tumour cells with less time to repair DNA damage caused by RT, thereby inducing apoptosis [30].

HER2 SUBTYPE The association between HER2 receptor status and patient response to RT remains unclear. Several groups have reported an increased risk of LR for breast tumours overexpressing HER2 following RT [29, 31]. In contrast, HER2 status alone failed to predict any significant survival benefits after PMRT in a cohort of 1000 breast cancer patients randomly assigned to receive this treatment [30]. However, when HER2 positivity was combined with ER/PR negativity, there was an increased probability of LR (p50.01) and distant metastasis (p50.02) after PMRT, indicating possible radioresistance associated with the HER2 positive subtype [30]. A functional role for HER2 in mediating response to RT has been shown in several in vitro studies. In 1993, Pirollo et al [32] transfected NIH 3T3 cells with genomic HER2 DNA isolated from an oesophageal cancer, which were insensitive to RT. Transfected NIH 3T3 cells exhibited a marked increase in their level of radioresistance, demonstrating that HER2 expression can influence response to RT. Likewise, a recombinant humanised monoclonal antibody raised against HER2 (4D5) was found to reverse the radioresistant phenotypes of HER2 overexpressing breast cancer cell lines by modulating the repair of radiationinduced DNA damage [33].

In vivo studies using HER2 overexpressing human breast cancer xenografts also demonstrated marked enhancement of radiation efficacy when given with this anti-HER2 receptor antibody. Mice treated with radiation or the anti-HER2 antibody alone showed no reduction in tumour size or remission. However, when combining radiation and anti-HER2 antibody therapies, there were marked reductions in tumour growth, and all animals receiving both treatments showed complete tumour remission [33]. Use of adjuvant trastuzumab for the treatment of HER21 early breast cancers has been evaluated in several large multicentre, randomised clinical trials, including the HERceptin Adjuvant (HERA) study. Data show that adjuvant trastuzumab significantly extends both OS and DFS, and these patients are now routinely treated with adjuvant trastuzumab. Many of the published studies related to breast

Br J Radiol;86:20120601

Breast cancer subtypes and response to radiotherapy

cancer subtypes and response to RT did not include patients who received this treatment. This means that, in the future, we may see an even smaller number of LRs and distant disease events in this subtype. Nevertheless, the data above implicate the activation of this signal transduction pathway with radioresistance highlighting additional downstream targets which, when inhibited in combination with HER2, may further increase the efficacy of RT for this subtype.

The HER2 receptor is composed of an extracellular ligand binding domain, a single transmembrane domain and an intracellular domain with tyrosine kinase activity.

Trastuzumab selectively binds to the ligand-binding domain, thereby suppressing HER2 activity. Inhibition of the tyrosine kinase domain represents another therapeutic strategy for suppression of HER2 activity, and several orally bio-available, low-molecular weight tyrosine kinase inhibitors (TKIs) are now also in clinical use. Examples include gefitinib, erlotinib and lapatinib.

These TKIs show potent radiosensitising activity and are currently being studied in Phase I/II clinical trials in various primary solid tumours [34–36]. TKIs have also been shown to act synergistically with trastuzumab, enhancing cell death in response to treatment [37]. Thus, combining these agents may further increase the efficacy of RT for breast cancers of the HER2 subtype.

Targeting additional downstream players within this signalling pathway may also act to increase RT efficacy for these breast cancers. Examples include the inhibition of Ras, Raf and/or MEK, and several molecules are currently in clinical trials as potential radiosensitisers [38–40].

The enzyme farnesyltransferase is involved in the initial post-translational modification of Ras that allows it to become associated with the plasma membrane and become active in signal transduction. Farnesyltransferase inhibition represents a promising strategy for radiosensitisation and was effective in Phase I studies in non-small cell lung cancer and cancers of the head and neck [38]. These agents may serve to further increase the efficacy of RT when used in combination with trastuzumab for the treatment of HER2 overexpressing breast cancers.

TRIPLE-NEGATIVE BREAST CANCER A triple-negative phenotype is significantly associated with an increased risk of LR, distant metastasis and

5 of 10

bjr.birjournals.org

Review article

increased overall mortality in patients treated with RT [29, 30]. This is quite surprising given that this is the type of breast cancer that BRCA-1 and -2 mutation carriers generally develop [26, 41]. Approximately 19.5% of triple-negative patients carry BRCA mutations [42].

BRCA mutation carriers are defective in DNA repair; therefore, it would be expected that these tumours might exhibit extreme sensitivity rather than insensitivity to RT. One possible explanation for this unexpected response to RT is that these tumours might possess compensatory DNA repair mechanisms that are more effective at dealing with radiation-induced DNA damage.

Triple-negative breast cancers represent the most problematic subtype with regard to effective management as, unlike luminal and HER2 positive breast cancers, there are no effective treatment targets. Since the majority of triple-negative cancers comprise basal-like breast cancers, then the identification of a basal-like specific marker would be invaluable both in terms of classification and identifying potential radiosensitising agents. Analyses performed by Nielsen et al [43] on tumours previously used in gene expression profiling studies [22] revealed that basal-like breast cancers express high levels of cytokeratin 5/6, epidermal growth factor receptor (EGFR) and c-kit. These results were found to correlate well with immunohistochemical patterns. It was therefore suggested that basal-like breast cancers might be better identified within the clinic by selecting cases that are ER negative, HER2 negative/low and cytokeratin 5/6 positive and/or EGFR positive [43].

The positive expression of these additional markers within this subtype also highlights potential therapeutic targets for the radiosensitisation of these breast cancers.

In particular, EGFR is a member of the HER family of receptors, along with HER2. In combination with RT, basal-like breast cancers may therefore benefit from the concurrent administration of TKIs and/or the signal transduction inhibitors described previously. Furthermore, EGFR can also be selectively inhibited using monoclonal antibody therapy. Cetuximab is a monoclonal antibody that binds to the EGFR with high specificity and with a higher affinity than epidermal growth factors, thus blocking ligand-induced phosphorylation and activation of EGFR [44]. The radiosensitising properties of cetuximab have been well demonstrated in

Br J Radiol;86:20120601

F E Langlands, K Horgan, D D Dodwell et al

solid tumours, and it appears to sensitise tumour cells to ionising radiation, either through increasing the proportion of cells in the radiosensitive G1 phase of the cell cycle while decreasing the proportion in the radioresistant S phase [45] or through restoration of apoptosis [46] or even anti-angiogenic mechanisms [47]. Bonner et al [48] found that the median duration of OS was 49.0 months among patients with locoregionally advanced head and neck cancers treated with RT plus cetuximab and 29.3 months among those treated with RT alone (hazard ratio 0.73, 95% CI 0.56–0.95; p50.018). The 5-year OS rate was 45.6% in the combined treatment group and 36.4% in the RT alone group. This agent has therefore recently been approved for use in combination with RT for the treatment of locally advanced squamous cell carcinoma of the head and neck. Although cetuximab is not routinely considered for the treatment of breast cancer patients, it may well prove effective in the management of basal-like breast tumours.

The inhibition of poly[adenosine diphosphate (ADP)ribose] polymerase (PARP) is a further novel radiosensitising strategy, which may increase the efficacy of RT in patients with triple-negative breast cancers. As previously mentioned, these cancers are more commonly found in individuals who have deleterious mutations in the BRCA gene [25, 41]. BRCA mutation carriers who lose the remaining wild-type allele exhibit inefficient homologous recombination DNA repair causing an accumulation of genetic aberrations, which drive carcinogenesis. The PARP enzymes play a key role in the repair of DNA single-strand breaks (SSBs) through the repair of base excisions, which are normally repaired by error-free homologous recombination [49].

In cells deficient in this repair mechanism, inhibition of PARP enzymes results in the generation of irreparable DNA SSBs that cause the accumulation of DNA double-strand breaks (DSBs), which trigger apoptosis [50]. There are at least five PARP inhibitors that are in clinical trials, and two of these agents, BSI-201 (BiPar Pharmaceuticals) and olaparib (Astra Zeneca), have been evaluated in Phase II trials in women with BRCA1 mutations who have metastatic breast cancer [51]. Furthermore, niraparib (MK-4827; Merck) has been shown to radiosensitise a variety of human tumour xenografts with differing p53 status, including the triplenegative MDA-MB-231 human breast carcinoma [52].

Thus, combining these agents with RT appears

6 of 10 bjr.birjournals.org

promising, but clinical trials to test the efficacy and toxicity of this combination are warranted.

POTENTIAL CAVEATS FOR CONSIDERATION Studies aimed at determining patient response to RT and identifying factors influencing response suffer from the complexity of establishing the appropriate cohorts of breast tumours for analysis. This is owing to the heterogeneous nature of the disease and the many different treatment modalities available for its effective management. Single modality adjuvant RT in the absence of systemic therapy for the treatment of breast cancer is uncommon and is only administered to lowrisk patients where the risk of LR is low. Large patient numbers are therefore needed in prospective clinical trials. This becomes even more of an issue when separating these patients further into individual subtypes. As such, many of the published studies include those patients receiving additional treatments alongside RT. For example, in the study conducted by Nguyen et al [29], 90% of the patient cohort also received adjuvant systemic therapy as well as RT. Under these circumstances, it becomes difficult to dissect whether LRs are the direct result of radioresistance or resistance to the other treatment modalities given.

Furthermore, LR after BCS and RT is low in all subtypes and was found to be ,10% in the study conducted by Nguyen et al [29], again highlighting the need for large patient numbers for accurate data interpretation.

The question also remains as to whether certain subtypes are just more biologically “aggressive”. HER2 and triple-negative phenotypes are not only associated with a higher risk of LR following RT but are also associated with higher grade, larger size, nodal positivity, younger age at presentation and a higher rate of distant metastases—all of which influence prognosis. Likewise, it remains unknown whether LRs are simply the result of a lack of alternative therapies available for some subtypes, e.g. triple-negative breast cancers. It is also possible that ER/PR negativity defines radioresistance rather than any intrinsic characteristics associated with the HER2 and triple-negative breast cancers. If this is true, the discovery of new radiosensitising strategies will be problematic, as it is more difficult to target a lack of expression than it is to target specific biomarkers known to influence response. For these reasons, there will continue to be limited treatment options for the

Br J Radiol;86:20120601

Breast cancer subtypes and response to radiotherapy

Review article

ER/PR-negative breast cancer patients for the foreseeable future.

Specific subtypes are also subject to more difficult classification based on the expression of only ER, PR and HER2. As described previously, the triple-negative phenotype is often used as a proxy for the basal-like breast cancers owing to the absence of a basal-like specific biomarker. Although the triple negative phenotype greatly enriches for basal-like breast cancers, a recent study has shown that, using this proxy, some basal-like breast tumours are missed and some nonbasal-like cancers are included compared with classifications based on gene expression profiles [53]. Thus, some patients may not be offered the most optimal treatments using the triple-negative phenotype to predict response to a particular agent. At present, it is also difficult to say that some radiosensitising agents will only be efficient for the treatment of specific subtypes of breast cancers. For example, an overexpression of EGFR is not only associated with the basal-like phenotype but is also inversely related to the expression of ER [54]. Therefore, some of the EGFR-specific therapies (e.g. cetuximab) may also be effective for the radiosensitisation of those breast cancers lacking ER expression. This not only includes the basal-like breast cancers but also those breast cancers of the HER2 subtype. Likewise, HER21 luminal B breast cancers may also benefit from the radiosensitising effects of trastuzumab and/or EGFR inhibitors. Since breast cancer is not a single disease, and with the recent discovery of further subtypes [55], treating tumours individually may ultimately prove more beneficial, owing to their unique genotypes, but is not yet feasible and presents profound biostatistical challenges.

Furthermore, classification based on receptor expression can only approximate the underlying genotype.

This may have profound ramifications when using these

classifications to predict whether or not breast tumours may benefit from certain radiosensitising agents. Agents targeting HER2 and/or EGFR would not be effective for the treatment of those breast tumours exhibiting mutations in key downstream players of these pathways.

For example, mutations in the K-Ras gene have been implicated with resistance to EGFR-TKIs in non-small cell lung cancer [56]. Unfortunately, this information cannot be inferred by the immunohistochemical pattern of these receptors.

CONCLUSION RT remains an important treatment for the local control of breast cancers, yet there are currently no valid predictive factors that reliably identify patients who would derive greater than average benefit from this treatment and treatment decisions are still made on the basis of stage and standard histopathological criteria. We have entered into an era in which molecular markers, gene expression profiling and other molecular prognostic indicators are being investigated as a means of individualising adjuvant systemic therapies, and this same approach should be applied to RT. The challenge now will be to apply identified biomarkers to the different breast cancer subtypes to predict RT outcome using techniques already utilised within the clinic. Indeed, the evidence suggests that subtypes do exhibit differential responses to RT, with HER2 and triplenegative breast cancers responding less well compared with luminal cancers. There may also be certain characteristics associated with specific subgroups that may be targeted by radiosensitising agents to increase the efficacy of RT, which can only benefit patients in the future.

ACKNOWLEDGMENTS This work was supported by Breast Cancer Campaign and by the Breast Cancer Research Action Group of Leeds General Infirmary.

REFERENCES 1.

Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and surgery in early breast cancer. An overview of the

7 of 10

bjr.birjournals.org

2.

randomized trials. N Engl J Med 1995;333:1444–55.

Eifel P, Axelson JA, Costa J, Crowley J, Curran W Jr, Deshler A,

et al. National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer.

Br J Radiol;86:20120601

F E Langlands, K Horgan, D D Dodwell et al

3.

4.

5.

6.

7.

8.

9.

J Natl Cancer Inst 2001;93: 979–89.

Hoskin P, ed. Radiotherapy in practice: external beam therapy.

Oxford, UK: Oxford University Press; 2006.

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.

Lancet 2005;366:2087–106.

Overgaard M, Nielsen H, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol 2007;82:247–53.

Ly BH, Nguyen NP, Vinh-Hung V, Rapiti E, Vlastos G. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit? Breast Cancer Res Treat 2010;119:537–45.

Whelan T, Levine M, Julian J, Kirkbride P, Skingley P. The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trail.

Cancer 2000;88:2260–6.

Holli K, Saaristo R, Isola J, Joensuu H, Hakama M. Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: results of a randomised study. Br J Cancer 2001;84:164–9.

Lilla C, Ambrosone C, Kropp S, Helmbold I, Schmezer P, von Fournier D, et al. Predictive factors for late normal tissue complications following radiotherapy for breast cancer. Breast Cancer Res Treat 2007;106:143–50.

8 of 10

bjr.birjournals.org

10. Davis SD, Yankelevitz DF, Henschke CI. Radiation effects on the lung: clinical features, pathology, and imaging findings. Am J Roentgenol 1992;159:1157–64. ´ A, 11. Ja´en J, V´azquez G, Alonso E, Leon Guerrero R, Almansa J. Changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study. Int J Radiat Oncol Biol Phys 2006;65:1381–8.

12. Krengli M, Sacco M, Loi G, Masini L, Ferrante D, Gambaro G, et al.

Pulmonary changes after radiotherapy for conservative treatment of breast cancer: a prospective study. Int J Radiat Oncol Biol Phys 2008;70:1460–7.

13. Schultz-Hector S, Trott KR. Radiation-induced cardiovascular diseases: is the epidemiologic evidence compatible with the radiobiologic data? Int J Radiat Oncol Biol Phys 2007;67:10–18.

14. Bird BR, Swain SM. Cardiac toxicity in breast cancer survivors: review of potential cardiac problems.

Clin Cancer Res 2008;14:14–24.

15. Clark RM, McCulloch PB, Levine MN, Lipa M, Wilkinson RH, Mahoney LJ, et al. Randomised clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer.

J Natl Cancer Inst 1992;84:683–9.

16. Stadler W. Fuzzy thinking on biomarkers. Urol Oncol 2007;25: 97–100.

17. Hu Z, Huang G, Sadanandam A, Gu S, Lenburg M, Pai M, et al. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer. Breast Cancer Res 2010;12:R18.

18. Woolston CM, Storr SJ, Ellis IO, Morgan DA, Martin SG. Expression of thioredoxin system and related

19.

20.

21.

22.

23.

24.

25.

26.

peroxiredoxin proteins is associated with clinical outcome in radiotherapy treated early stage breast cancer. Radiother Oncol 2011;100: 308–13.

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000;406: 747–52.

Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005;23:7350–60.

Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al.

Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.

Proc Natl Acad Sci U S A 2001;98: 10869–74.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al.

Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100:8418–23.

Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, et al.

Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003;100:10393–8.

Rakha EA, Tan DS, Foulkes WD, Ellis IO, Tutt A, Nielsen TO, et al.

Are triple-negative tumours and basal-like breast cancer synonymous?

Breast Cancer Res 2007;9:404.

Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, et al. Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res 2008;14:8010–18.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes,

Br J Radiol;86:20120601

Breast cancer subtypes and response to radiotherapy

27.

28.

29.

30.

31.

32.

and survival in the Carolina breast cancer study. JAMA 2006;295: 2492–502.

Wang Y, Yin Q, Yu Q, Zhang J, Liu Z, Wang S, et al. A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments. Breast Cancer Res Treat 2011;130:489–98.

Smith L, Qutob O, Watson MB, Beavis AW, Potts D, Welham K, et al. Proteomic identification of putative biomarkers of radiotherapy resistance: a possible role for the 26S proteasome. Neoplasia 2009;11:1194–207.

Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 2008;26: 2373–8.

Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen H, Overgaard J, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol 2008;26:1419–26.

St˚al O, Sullivan S, Wingren S, Skoog L, Rutqvist L, Carstensen J, et al. c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer. Eur J Cancer 1995;31A: 2185–90.

Pirollo KF, Tong YA, Villegas Z, Chen Y, Chang EH. Oncogenetransformed NIH 3T3 cells display radiation resistance levels indicative of a signal transduction pathway leading to the radiation-resistant phenotype. Radiat Res 1993;135: 234–3.

9 of 10 bjr.birjournals.org

33. Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/ neu receptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999;59:1347–55.

34. Broniscer A, Baker SJ, Stewart CF, Merchant TE, Laningham FH, Schaiquevich P, et al. Phase I and pharmacokinetic studies of erlotinib administered concurrently with radiotherapy for children, adolescents, and young adults with highgrade glioma. Clin Cancer Res 2009;15:701–7.

35. Joensuu G, Joensuu T, Nokisalmi P, Reddy C, Isola J, Ruutu M, et al.

A Phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer. Int J Radiat Oncol Biol Phys 2010;78:42–9.

36. Harrington KJ, El-Hariry IA, Holford CS, Lusinchi A, Nutting CM, Rosine D, et al. Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck.

J Clin Oncol 2009;27:1100–7.

37. Normanno N, Campiglio M, De LA, Somenzi G, Maiello M, Ciardiello F, et al. Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth.

Ann Oncol 2002;13:65–72.

38. Brunner TB, Gupta AK, Shi Y, Hahn SM, Muschel RJ, McKenna WG, et al. Farnesyltransferase inhibitors as radiation sensitizers.

Int J Radiat Biol 2003;79:569–76.

39. Hsieh CH, Jeng KS, Lin CC, Chen CK, Liu CP, Lin CP, et al. Combination of sorafenib and intensity modulated radiotherapy for

Review article

40.

41.

42.

43.

44.

45.

46.

unresectable hepatocellular carcinoma. Clin Drug Investig 2009;29: 65–71.

Shannon AM, Telfer BA, Smith PD, Babur M, Logie A, Wilkinson RW, et al. The mitogen-activated protein/extracellular signalregulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts. Clin Cancer Res 2009; 15:6619–29.

Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple negative breast cancer. Clin Breast Cancer 2009;9:S73–81.

Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptornegative breast cancer. Clin Cancer Res 2011;17:1082–9.

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al.

Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10: 5367–74.

Baselga J. Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 2002;7:2–8.

Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res 2000;6:2166–74.

Ciardiello F, Caputo R, Troiani T, Borriello G, Kandimalla ER, Agrawal S, et al. Antisense oligonucleotides targeting the epidermal growth factor receptor inhibit

Br J Radiol;86:20120601

F E Langlands, K Horgan, D D Dodwell et al

proliferation, induce apoptosis, and cooperate with cytotoxic drugs in human cancer cell lines. Int J Cancer 2001;93:172–8.

47. Baumann M, Krause M, Dikomey E, Dittmann K, D¨orr W, KastenPisula U, et al. EGFR targeted anticancer drugs in radiotherapy: preclinical evaluation of mechanisms.

Radiother Oncol 2007;83:238–48.

48. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur R, et al.

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximabinduced rash and survival. Lancet Oncol 2010;11:21–8.

49. Dantzer F, de La Rubia G, M´enissierDe Murcia J, Hostomsky Z, de Murcia G, Schreiber V. Base excision repair is impaired in mammalian cells lacking Poly(ADP-

10 of 10 bjr.birjournals.org

50.

51.

52.

53.

ribose) polymerase-1. Biochemistry 2000;39:7559–69.

Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair.

J Clin Oncol 2008;26:3785–90.

Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al.

Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009;361:123–34.

Wang L, Mason KA, Ang KK, Buchholz T, Valdecanas D, Mathur A, et al. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation. Invest New Drugs 2012; 30:2113–20.

Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P, et al.

How basal are triple-negative breast cancers? Int J Cancer 2008;123: 236–40.

54. Bossuyt V, Fadare O, Martel M, Ocal IT, Burtness B, Moinfar F, et al. Remarkably high frequency of EGFR expression in breast carcinomas with squamous differentiation.

Int J Surg Pathol 2005;13:319–27.

55. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda O, Dunning MJ, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012:486:346–52.

56. Massarelli E, Varella-Garcia M, Tang X, Xavier A, Ozburn N, Liu D, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 2007;13: 2890–6.

Br J Radiol;86:20120601

© 2013 The Authors

ARTICLE INFORMATION Received: 12 November 2012

Revised: 8 January 2013

Accepted: 10 January 2013

doi: 10.1259/bjr.20120574

Cite this article as: Powell DK, Nwoke F, Urken ML, Buchbinder D, Jacobson AS, Silberzweig JE, et al. Scapular free flap harvest site: recognising the spectrum of radiographic post-operative appearance. Br J Radiol 2013;86:20120574.

Scapular free flap harvest site: recognising the spectrum of radiographic post-operative appearance D K POWELL, MD, F NWOKE, MD, M L URKEN, MD, D BUCHBINDER, MD, A S JACOBSON, MD, J E SILBERZWEIG, MD and A S KHORSANDI, MD Department of Radiology, Beth Israel Medical Center, New York, NY, USA Address correspondence to: Dr Daniel K. Powell E-mail: dpowell@chpnet.org

Objective: Scapular free flap harvesting for oral cavity cancer reconstruction is an increasingly used and versatile option. We aim to describe the appearance of the scapula harvest site on chest radiograph and CT. Methods: We retrospectively reviewed a surgical database of 82 patients who underwent scapular osteocutaneous flap harvesting for oral cavity cancer reconstruction and had imaging performed at our institution. We searched the picture archiving and communications system for all associated imaging.

Results: Characteristic radiographic appearance in the immediate post-operative period as well as in the remote post-operative period is described, including an upside-down V-shaped paraglenoid notch, rectangular (or triangular) lateral border defects and a sharply pointed inferior scapular body.

Additionally, common CT appearances are discussed, including an abrupt gleno-scapular interval, an absent axillary rim bulge and a Z-shaped scapula.

Conclusion: The altered appearance of the scapular defect following surgical harvest is easily recognised. Although the description of this defect may not alter management and may reasonably be omitted, a radiologist’s comfort with these appearances may potentially enhance the understanding of patient management and recognition of superimposed complications, such as infection.

Advances in knowledge: Scapular osteocutaneous free flap reconstruction is an increasingly used technique after oral cavity surgery.

Very few radiologists reported in our review the surgical scapular defects, and there is apparent ignorance of their appearance.

We described characteristic radiographic and CT signs of scapular free flap harvesting to increase radiologists’ familiarity with these defects, which may provide clinical information and possibly contribute to detection of complications.

D K Powell, F Nwoke, M L Urken et al

The scapular osteocutaneous flap, although first described in the 1980s [1, 2], is increasingly used for reconstruction after head and neck surgery [3, 4].

The flap offers several advantages, including ease of harvesting, an extensive and varied subscapular arterial and venous system (Figure 1a), up to 14 cm of bone, and a multitude of soft tissue as well as bone flaps (Figure 1b). The scapular tip, because of its shape, has been described as ideally suited both for mandibular angle [5] and palatomaxillary [6] reconstruction.

There is increasing recognition among surgeons of the versatility of osteocutaneous scapular free flaps after oral cavity surgery, even outside tertiary care centres.

The option was initially used in patients with multiple surgeries whose traditional donor sites were already used. However, they are increasingly selected because they are ideally suited to repair defects of the lateral mandible that include skin, mucosal or “through-andthrough” soft-tissue loss [3]. When harvesting the bone, the lateral border and inferior angle can be harvested together or separately with independent blood supplies,

Figure 1. (a) Drawing of a posterior view of the scapula demonstrating potential myocutaneous paddles that can be harvested: a more traditional circumflex artery flap (horizontal) and the newer thoracodorsal artery angular branch flap (vertical). (b) Illustrations of the three possible bone flaps, which can be combined with the myocutaneous flaps for various composite flaps. © Jill Gregory, Continuum Health Partners. Permission has been granted by the illustrator to publish this figure.

2 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

Scapular free flap harvest site

based on the subscapular system [1, 2]. The circumflex scapular artery provides a short associated vascular pedicle, and the angular branch of the thoracodorsal artery provides a longer pedicle [4].

Knowledge of normal anatomy (Figure 2a) can improve the detection of surgical defects (Figure 2b). Embryogenesis of the scapula is poorly understood, with some evidence that its portions derive from different elements of the mesoderm, for instance the blade and spine originating from dermomyotomal mesenchyme and the glenoid and coracoid developing from the lateral plate mesoderm [7]. The scapula, or shoulder blade, is a thin, translucent, triangular flat bone of the posterolateral thorax, overlying the second through seventh ribs, and comprising a major portion of the

Figure 2. (a) Normal scapular anatomy. (b) Scapular anatomy with superimposed surgical defects.

shoulder girdle. The anterior or costal surface is referred to as the subscapular fossa. The posterior surface is divided by the scapular spine into a larger infraspinous fossa and a smaller supraspinous fossa. The thick horizontally oriented spine continues laterally as the acromion [Greek (G.) akros, for point]. The adjacent truncated superolateral portion of the scapula, or the lateral angle, is the glenoid tubercle, which contains the glenoid fossa (G. socket) for articulation with the humeral head. The thickest portion of the glenoid is also called the scapular head, and the thinnest portion the scapular neck. Between the glenoid and the acromion is the spinoglenoid (or infraglenoid) notch, running anteromedial and just inferior to the glenoid. The coracoid process (G. korakodes, like a crow’s beak) projects anterolaterally, above the glenoid. The lateral scapular border, also called the axillary border, is the thickest of the borders, bearing more stress than the thinner medial and superior borders. The suprascapular notch is on the superior scapular border at the base of the coracoid process, between the lateral and the middle thirds. The superior and inferior angles mark the extremes of the medial border, where many of the muscles insert [8].

Patients with these flaps commonly receive chest radiographs, both immediately following surgery and later, as well as multiple cross-sectional studies for surveillance and diagnosis, including for suspected pulmonary embolism. The altered appearance of the scapula may be easily overlooked on routine imaging or mistaken for scapular pathology in the absence of appropriate surgical history. Thus, our objective was to describe the appearance of the scapular harvest site on chest radiograph and CT, in the post-operative and later periods, and to assess how these findings have been previously reported at our institution.

METHODS We retrospectively reviewed our surgical database of 82 patients who underwent scapular osteocutaneous flap harvesting for oral cavity cancer reconstruction at our institution between November 2004 and November 2011. We searched our picture archiving and communications system (PACS) for all associated imaging.

We characterised and quantified the early and late appearances of the defects on chest radiograph and cross-sectional imaging, including multiplanar sagittal and coronal reconstructions.

3 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

D K Powell, F Nwoke, M L Urken et al

Figure 3. Two-week post-operative chest radiograph of a 61-year-old female with multifocal oral cancer who had a left scapular free flap oral reconstruction in 2003 and required an additional right scapular free flap reconstruction in 2010 for recurrence. The single radiograph (bisected with different brightness and contrast levels on each side) reveals bilateral paraglenoid notches (thin white arrows) with a discrete lateral scapular border (shallow triangular) defect on the left (first surgery; thick white arrow indicates inferior corner) and a sharply pointed inferior scapular body on the right (second surgery) with early callus formation (thick black arrow).

2 of the 82 patients had bilateral scapular free flaps at different times, effectively increasing our population to 84. The patient population consisted of 40 males and 42 females, ranging in age from 15 to 93 years (mean of 65 and median of 66) at the time of surgery.

At least 12 (12/84514.3%) of the patients underwent segmental mandibular resection and reconstruction owing to osteoradionecrosis of the jaw, and at least 25 (25/ 84529.8%) underwent resection and reconstruction owing to recurrence of disease. Clear history was not available in 23 (23/84527.4%) cases. The remaining 24 patients (24/84528.6%) underwent a primary reconstruction of the oral cavity following initial cancer resection.

This retrospective Health Insurance Portability and Accountability Act-compliant study was performed after the institutional review board deemed the study to be exempt from review, not requiring patient informed consent.

RESULTS At least two portable chest radiographs beginning on post-operative Day 1 were accessible on PACS for all but one patient who had their surgery prior to management at our institution (and only for the second operations in both patients with bilateral defects). 37 patients (37/84544.0%) received delayed follow-up radiographs (defined as at least 1 month post surgery).

39 patients (39/84546.4%) had additional cardiothoracic cross-sectional imaging [chest CT or positron emission tomography (PET) scans] after surgery, including 6 of the patients who did not have delayed radiographs. 7 (7/8458.3%) patients received a chest CT within the first post-operative week for clinical suspicion of pulmonary embolism or pneumonia.

Imaging Nine patients were subsequently imaged with conventional posterior-to-anterior and lateral projections. The indications for these radiographs were largely not provided, but they were typically performed in the outpatient as opposed to inpatient setting. Despite better evaluation of the lungs, the abduction of the scapulae away from the thorax was less suited for the recognition of the scapular resection defect when compared with the portable technique. Lateral radiographs did not prove useful in the identification of a scapular free flap resection.

A characteristic upside-down V-shaped notch immediately medial and slightly caudal to the glenoid tubercle (which we called an upside-down-V paraglenoid

Figure 4. 51-year-old female with oral cavity cancer requiring a right scapular free flap reconstruction with immediate post-operative and 1-year follow-up chest radiographs. An upside-down-V paraglenoid notch is present, both early and late (black arrows), but becomes more conspicuous on the later radiographs. Haziness of the lateral border and the remnant scapular body become better defined upon follow-up, with lateral border callus formation and a sharply pointed inferior scapular body remnant (white arrow).

4 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

Scapular free flap harvest site

notch) was the most recognisable defect on radiographs seen in 100% of patients in the immediate and more remote post-operative periods (Figure 3).

The lateral border of the scapula was ill-deďŹ ned, with varying degrees of lucency in comparison with the wellcorticated, rounded and thickened lateral border of the

normal scapula, in the immediate post-operative period in 100% of patients (Figures 2 and 3). Increased conspicuity of the lateral and inferior scapula, in the later post-operative period, revealed different appearances of the residual bone (relating both to the choice of vascular pedicle and the surgical utility of the inferior tip in reconstruction; Figures 1b and 3).

Figure 5. (a) 29-year-old male with oral cavity cancer requiring a right scapular free flap reconstruction with immediate post-operative and 14-month follow-up chest radiographs. There are paraglenoid notches (thin white arrows) in both radiographs and haziness of the lateral border on the late film, not unlike the case from Figure 2. However, the later studies reveal preservation of the inferior scapular angle and an additional angular notch more inferiorly on the lateral border (thick white arrows), creating a discrete rectangular lateral defect. (b) 70-year-old male with oral cavity cancer requiring scapular free flap reconstruction with immediate and 11-month post-operative chest radiographs. Both radiographs also reveal paraglenoid notches (white arrows) and haziness of the lateral borders, not unlike the case from Figure 2. However, later studies reveal preservation of the inferior scapular angle (black arrow) and an additional angular notch more inferiorly on the lateral border (thick white arrow), creating a discrete triangular lateral border defect. (c) 71-year-old male with mandibular trigone cancer requiring scapular free flap reconstruction with postoperative Day 1 and Day 2 as well as 5-month follow-up chest radiographs. The two immediate post-operative radiographs demonstrate the typical paraglenoid notches (thin white arrows) and haziness of the lateral borders. There is preservation of the inferior scapular angle (thin black arrows) and the entire medial border (white arrowheads). A triangular lateral border defect (thick black arrow) is also seen on the first radiograph (on the left). However, in the second post-operative radiograph and on the later follow-up study (on the right), there is fracture or separation of the inferior angle at the inferior surgical notch with a sharply pointed remnant inferior scapular body and a step-off from the medial border (thick white arrows). Progressive lateral migration of the inferior angle is noted (thin black arrows) with poor visualisation on the late follow-up radiograph (on the right).

5 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

D K Powell, F Nwoke, M L Urken et al

The most common appearance of the inferior border, a sharply pointed remnant inferior scapula (with a somewhat shark-tooth appearance; Figure 4), was seen in 49 patients (49/84558.3%) and was best recognised on follow-up imaging. An additional 6 cases (6/8457.1%) were considered likely to have this feature, allowing for the lack of imaging beyond the first few post-operative days.

This feature was best recognised on early radiographs by the lack of a well-defined and rounded inferior scapular angle, asymmetric in comparison with the contralateral side, seen in a total of 55 cases (55/84565.5%; Figure 4).

A relative generalised lucency of one hemithorax was also an indirect sign of the resection.

Less often, the remnant inferior scapular tip was preserved, seen in 26 cases (26/84531%). In 18 of these cases (18/84521.4%), a second inferior 90° angle notch was perceived on the lateral scapular border, creating a well-defined rectangular defect (Figure 5a). Interestingly, the remnant tip seemed particularly prone to propagation of the defect, or fracture, particularly when there was a more pronounced or deeper triangular lateral wall defect, seen in the remaining 8 of those 26 patients (8/8459.5%; Figure 5b). 3 cases (3/26511.5%), which initially demonstrated this deeper triangular defect, eventually resulted in migrated

inferior tips from propagation of the resection defect, creating an appearance similar to those with tip harvesting and a pointed shark-tooth-appearing inferior scapula body. There was progressive inferolateral migration of the inferior angle on later radiographs (presumably from muscular traction) and diminishing visualisation of the separated inferior portion (Figure 5c).

The most characteristic findings in the axial plane on CT were an abrupt defect interposed between the glenoid tubercle and the body of the scapula (Figure 6) and deficiency of the lateral and inferior borders with loss of the characteristic bulging axillary rim (normally the thickest border; Figure 7). A normal scapular appearance in the axial plane, from craniad to caudad, will never demonstrate a soft tissue interval between the glenoid tubercle and the body of the scapula (owing to the sloping of the lateral border from the lateral angle).

Therefore, the presence of a sharply demarcated defect, medial to the glenoid tubercle (corresponding to the radiographic paraglenoid notch), is particularly suggestive of this surgery, and it was seen in 34 patients (34/39587.2%) who had post-operative CT imaging of the chest. However, this may be present on only one or two slices and is easily missed. As such, inspection of the lateral border of

Figure 6. Axial non-contrast chest CTs in multiple patients with scapular free flap harvesting at remote follow-up: a 70-year-old male at 1-year follow-up (top left), a 70-year-old female at 6-month follow-up (top right), an 81-yearold female at 2-year follow-up (bottom left) and a 76-year-old male at 4-year follow-up (bottom right). There are abrupt well-demarcated defects interposed between the glenoid tubercle and the scapular body (white arrows). No portion of the glenoid tubercle should be seen separate from the scapular body on any cut of an axial scan in the normal anatomy. Note, the fissuring and irregular sclerosis sometimes seen, which can aid in detection (black arrows).

6 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

Scapular free flap harvest site

Figure 7. Axial non-contrast chest CTs in multiple patients with scapular free flap harvesting at remote follow-up: a 70-year-old female at 6-month follow-up (top left), an 81-year-old female at 2-year follow-up (top right) and a 58-year-old female at 16-month follow-up (bottom). There is deficiency of the lateral borders and inferior angles with loss of the normal rounded and bulging lateral border. It is replaced by post-surgical irregular heterogeneous sclerosis and callus formation (arrow). Note the surgical material laterally, which can aid detection.

the scapula for loss of the normally thickened axillary border (which we called an absent axillary bulge) and generalised tapering is important in recognising the defect on CT, as this was present in 100% of patients, to varying degrees. In 2 of the patients (2/5540%) without a glenoscapular interval defect, slight excrescent irregularity of the infero-lateral aspect of the glenoid was seen (Figure 8). This may also serve as an indicator to alert a reader to the possibility of this resection defect.

detection. This feature was pronounced enough to be recognisable on a portable chest radiograph in one patient (Figure 9a). Most often, scapular body irregularity was very slight, with mild healed fracture remodelling, seen in 14 patients (14/39535.9%), requiring a more focused inspection to be recognised (Figure 9b). Extensive mature periostial remodelling was seen in one patient (Figure 9c), presumably from atypical post-surgical callus formation, as there was no historical record of infection.

Occasionally, scapular fissuring was seen, to a moderate degree in 7 patients, and minimally in 3 patients (10/39525.6%). Fissuring was extensive enough to involve overriding of medial and lateral portions of a vertical fracture defect in 8 cases (8/39520.5%), which we called a Z-shaped scapula (Figure 9a), enhancing

Some degree of muscular deficiency was also seen in all cases most often related to latissimus dorsi harvesting (Figures 10a,b).

Figure 8. 47-year-old male with squamous cell carcinoma of the oral cavity requiring scapular free flap reconstruction with a 2-year follow-up axial non-contrast CT of the chest demonstrating a rare appearance of the remaining scapula.

There is no defect seen between the glenoid and the scapular body on the axial CT, with only mild excrescence of the infero-lateral aspect of the glenoid (arrow).

The 7 (7/8458.3%) patients receiving early postoperative CT exhibited clean, non-corticated surgical margins and a mild, occasionally moderate, amount of adjacent fat stranding (Figure 11). The surrounding muscle borders were faintly ill-defined, with minimal low attenuation of the muscular bellies, presumably from oedema (Figures 10 and 11). As expected, neither cortical erosion or faint periostitis nor extensive, nodular or enhanced soft tissue swelling was seen (which may potentially be distinguishing features in infection; Table 1).

Although there were distinct changes seen on delayed follow-up CT imaging, such as smoothing and remodelling of the defect margins, it is difficult to make an inference with regard to the natural progression and

7 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

D K Powell, F Nwoke, M L Urken et al

Figure 9. (a) 73-year-old female with maxillary cancer requiring scapular reconstruction. One-year follow-up axial non-contrast CT and 2-month follow-up radiograph reveal a Z-shaped scapula. Overriding healed deformities from vertical propagation of lateral border resection are seen on the radiograph (black arrow) and CT (white arrow). (b) 88-year-old female with squamous cell carcinoma of the retromolar trigone and subsequent osteonecrosis and osteomyelitis of a fibular graft, requiring scapular free flap reconstruction. Four-month follow-up non-contrast axial CT scan shows extensive irregular sclerosis and fissuring, which was occasionally seen and can aid detection (white arrows). (c) 47-year-old male with osteonecrosis of the jaw from oral cavity radiation requiring scapular free flap reconstruction. Follow-up non-contrast axial chest CT shows mature periostial remodelling along the scapular defect on the left (arrow).

timing of healing changes given the small group with early cross-sectional imaging and the variability of later imaging timing. An expected rate of new bone formation and chronic periostial thickening also cannot be reliably estimated.

Although double-oblique maximal intensity projection (Figure 12a) as well as three-dimensional volumerendered reconstructions (Figure 12b) were useful in recognising the defects, they are not practical on routine imaging.

Oblique or paracoronal reconstructed CT images did not successfully approximate the radiographic appearance or allow easy identiďŹ cation of the defects.

Reporting Imaging for the reviewed patients included 884 chest radiographs, 3 shoulder radiographs, 36 chest CTs and

8 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

Scapular free flap harvest site

Figure 10. (a) Contrast-enhanced axial CT scan of a 55-year-old female on post-operative Day 3 after scapular free flap harvesting for recurrent oral cancer.

The latissimus dorsi is absent on the right and preserved on the left (white arrows). Subjacent to the skin staples, there is minimal fat stranding. (b) Contrastenhanced axial CT scan of a 61-year-old female on post-operative Day 5 after scapular free flap harvesting for oral cancer. The latissimus dorsi is largely absent on the right and preserved on the left (white arrows). The deficient remnant right latissimus dorsi is retracted (arrow head) with minimal intramuscular oedema and fat stranding without a markedly shaggy muscle contour or infiltration of the fat to suggest infection.

32 whole-body PET/CTs. These were read by 29, 3, 11 and 4 different radiologists, respectively. However, there was overlap between these groups and a total of 33 different radiologists read post-operative imaging that included the scapula. Only 1 (1/88450.1%) of the original chest radiograph readings described the defect, identifying it as a resection. The report was made by a resident describing a defect on an early post-operative film with limited conspicuity; as such, specific knowledge of the patient’s history is suspected in this case.

The defect was accurately reported on one of the three shoulder radiographs, which provided the clearest views of the scapula and happened to be interpreted by a head and neck radiologist. Four of the CT reports included descriptions of the surgical defects (describing them as “distorted”, “fragmented” or “post-surgical changes”).

In many cases, readers would describe other bone defects or adjacent post-surgical changes but fail to recognise or describe any scapular deformity, even when markedly fragmented. Two faculties described the defects accurately on CT, as partial scapular resections, for a total of 6 descriptions out of 36 reports (6/36516.7%).

1 case out of 32 reports (1/3253.1%) was described on PET/CT. Interestingly, all these descriptions came from different radiologists, and these descriptions were not repeated by subsequently reporting radiologists (except for one of the instances on chest CT). Therefore, 8 (24.2%) of the 33 radiologists recognised and described the defect on one occasion. Only 4 (12.1%) accurately described a resection defect. However, none of the

Figure 11. Post-operative Day 2 contrast-enhanced chest CT of a 73-year-old male after scapular free flap reconstruction of a loose mandibular resection fixation plate for oral cancer. Note the straight, clean surgical margins (black arrows) of the gleno-scapular interval superiorly (on the left image) and the absent axillary bulge inferiorly (on the right image) in this patient ,1 week after surgery.

9 of 11 bjr.birjournals.org

Br J Radiol;86:20120574

D K Powell, F Nwoke, M L Urken et al

Table 1. Characteristic appearances

Characteristic

Frequency (%)

Description

100

Notch immediately medial and caudal to the glenoid, representing superior resection edge

66

Shark-tooth appearance of inferior scapular tip from resection of the angle

21

Second inferior 90° angle notch on the lateral scapular border inferior to the paraglenoid notch, creating a well-defined rectangular defect

Remnant inferior scapular angle

10

Deep and inferior extension of the lateral border resection, creating a triangular defect, with preservation of the inferior scapular angle

Prone to fracture (12% of our population)

Loss of the thickened axillary border. Tapering of the lateral border

Irregular border excrescence (36%), bone fissuring (26%) and periostial reaction/callus formation

87

Sharply demarcated defect interposed between the glenoid tubercle and the body of the scapula

Upside-down V-shaped paraglenoid notch (above)

21

Overriding of medial and lateral portions of a vertical fracture defect of scapular body, creating a Z-shaped appearance

Association

Plain radiograph Upside-down V-shaped paraglenoid notch

Sharply pointed inferior scapular remnant

Rectangular lateral border defects

Triangular lateral border defects

Abrupt gleno-scapular interval (below) Decreased density of the lateral scapular border Generalised lucency of hemi-thorax

CT findings Absent axillary bulge

Abrupt gleno-scapular interval

Z-shaped scapula

100

recognised defects was mistaken for possible acute pathology.

DISCUSSION The rise in prevalence of scapular osteocutaneous flap repairs has been accompanied by an apparent lack of awareness of their appearance among radiologists.

We hope this initial characterisation will alert radiologists to the presence of these defects. Although a description of the defects has no impact on management and may reasonably be omitted, their recognition may provide further history (to the radiologist or other referring clinicians) and will more importantly increase radiologist comfort with the normal post-operative appearances. This, in turn, may lead to better recognition

10 of 11 bjr.birjournals.org

of complications, such as infection. One would not expect metastases to occur in association with this surgical bed, and this has not been reported. However, imaging of complications was not performed for the patients we studied, and it may be interesting to evaluate their characteristic findings in future studies.

CONCLUSIONS On radiograph, we found an upside-down-V paraglenoid notch was present in all cases. A sharply pointed inferior remnant scapular body was seen in up to 65.5% of cases, while a rectangular or triangular defect of the lateral border was seen in 21.4% of cases. This lateral border defect appeared most prone to defect

Br J Radiol;86:20120574

Scapular free flap harvest site

Figure 12. (a) Reconstructed double-oblique maximal intensity projection images of the scapula showing the paraglenoid notches (white arrows) and sharply pointed inferior scapular tips (black arrows). 47-year-old female (in left image) after scapular reconstruction for osteoradionecrosis of the jaw (patient from Figure 9c). 73-year-old male (in right image) on post-operative Day 2 after scapular reconstruction (patient from Figure 11). (b) Threedimensional volume-rendered reconstructions of the posterior thorax and isolated oblique reconstructions of the scapula showing the paraglenoid notches (thick arrows) and sharply pointed inferior scapular remnants (thin arrows).

propagation with fragment displacement, seen in 11.5% of all cases. On axial CT, a gleno-scapular interval was present in 87.2%. Scapular fissuring was seen in 25.6% and overriding healed fracture remodelling,

or a Z-shaped scapula, was seen in 20.5%. Absence of the normal axillary rim bulge was seen in all cases and generalised minimal irregularity was seen in 35.9% of all cases.

REFERENCES 1. Batchelor AG, Sully L. A multiple territory free tissue transfer for reconstruction of a large scalp defect. Br J Plast Surg 1984;37: 76–9.

2. Baker SR, Sullivan MJ. Osteocutaneous free scapular flap for one-stage mandibular reconstruction. Arch Otolaryngol Head Neck Surg 1988; 114:267–77.

3. Takushima A, Harii K, Asato H, Momosawa A, Okazaki M, Nakatsuka T. Choice of osseous and osteocutaneous flaps for mandibular reconstruction. Int J Clin Oncol 2005;10:234–42.

11 of 11 bjr.birjournals.org

4. Deleyiannis FW, Rogers C, Lee E, Russavage J, Gastman B, Dunklebarger J, et al. Reconstruction of the lateral mandibulectomy defect: management based on prognosis and location and volume of soft tissue resection. Laryngoscope 2006; 116:2071–80.

5. Yoo J, Dowthwaite SA, Fung K, Franklin J, Nichols A. A new angle to mandibular reconstruction: the scapular tip free flap. Head Neck Jul 2012. Epub ahead of print. doi: 10.1002/hed.23065 6. Pagedar NA, Gilbert RW, Chan H, Daly MJ, Irish JC, Siewerdsen JH.

Maxillary reconstruction using the scapular tip free flap: A radiologic comparison of 3D morphology.

Head Neck 2012;34:1377–82.

7. Capellini TD, Vaccari G, Ferretti E, Fantini S, He M, Pellegrini M, et al.

Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1. Development 2010;137: 2559–69.

8. Moore KL, Dalley AF. Upper limb. In: Kelly PJ, ed. Clinically oriented anatomy.

4th edn. Philadelphia, PA: Lippincot Williams and Wilkins; 1999. pp. 668–9.

Br J Radiol;86:20120574

Š 2013 The Authors

ARTICLE INFORMATION Received: 15 January 2013

Revised: 25 February 2013

Accepted: 28 February 2013

doi: 10.1259/bjr.20130036

Cite this article as: Almehdar A, Chavhan GB. MR cholangiopancreatography at 3.0 T in children: diagnostic quality and ability in assessment of common paediatric pancreatobiliary pathology. Br J Radiol 2013;86:20130036.

MR cholangiopancreatography at 3.0 T in children: diagnostic quality and ability in assessment of common paediatric pancreatobiliary pathology A ALMEHDAR, MB BS, MD and G B CHAVHAN, MD, DABR Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Address correspondence to: Dr Govind B. Chavhan E-mail: drgovindchavhan@yahoo.com

Objective: To assess the diagnostic quality of MR cholangiopancreatography (MRCP) at 3.0 T in children and to assess its diagnostic ability in answering the clinical query. Also, to determine the frequency of artefacts and anatomic variations in ductal anatomy.

Methods: Consecutive MRCPs performed in children using a 3-T scanner were retrospectively reviewed to note indications, findings, imaging diagnosis, normal variants, quality and artefacts. Analysis was performed based on the final diagnosis assigned by pathology or the combination of clinical, laboratory, imaging features and follow-up to determine whether it was possible to answer the clinical query by MRCP findings.

Results: There were 82 MRCPs performed at 3.0 T on 77 children. 42/82 (51%) MRCPs were of good quality, 35/82 (43%) MRCPs were suboptimal but diagnostic and the remaining 5/82 (6%) MRCPs were nondiagnostic. MRCP answered the clinical query in 61/82 (74%) cases; however, it did not answer the clinical query in 11/82 (14%) cases and was equivocal in 10/82 (12%) cases. There was significant association between the quality of MRCP and the ability of MRCP to answer the clinical query (p,0.0001). 64/82 (78%) MRCP examinations had at least 1 artefact. Variation in the bile duct anatomy was seen in 27/77 (35%) children.

3-T MRCP in children

Conclusion: MRCP performed at 3.0 T is of diagnostic quality in most cases and is able to provide an answer to the clinical query in the majority of cases.

MR cholangiopancreatography (MRCP) is a radiationfree non-invasive imaging tool that is useful for evaluation of a variety of paediatric pancreatobiliary diseases [1–7]. These reported studies were performed using 1.5-T MRI scanners. The inherent improved signal available with 3-T scanners, which were introduced for clinical use in the last decade, is expected to improve the quality of MRCP [8]. MRCP at 3.0 T has been found to be superior in contrast-to-noise ratio and overall image quality in adult healthy volunteers and adult patients [9–12]. Paediatric MRCP is likely to benefit at 3.0 T even more because of the smaller calibre of ducts seen in young children. Its image quality and utility in the evaluation of paediatric pancreatobiliary abnormalities, however, have not been reported so far to the best of our knowledge.

We retrospectively reviewed MRCPs performed in children using a 3-T scanner, with the aim of assessing the diagnostic quality of MRCP at 3.0 T and of assessing its diagnostic ability in answering the clinical questions in a variety of pancreatobiliary diseases. We also reviewed MRCPs to determine the frequency of artefacts and variation in ductal anatomy.

PATIENTS AND METHODS Institutional research ethics board approval was obtained for the study, with waiver for the need for individual patient consent. We retrospectively analysed all MRCPs performed in children on our 3-T scanner between January 2008 and June 2011. The patient list was obtained from a search of our database that records all patients scanned on the 3-T scanner.

MRCP technique All MRI examinations were performed on a 3-T scanner (Achieva; Philips Medical Systems, Best, Netherlands).

Each MRCP included the following sequences. (1) Respiratory-triggered three-dimensional (3D) T2 weighted fast spin echo (FSE) with fat saturation [repetition time (TR) 3168 ms, echo time (TE) 700–900 ms, field of view (FOV) 250–380 mm, matrix 2883288 and slice thickness 2 mm with a 1-mm gap]. (2) Single-shot FSE

2 of 9

bjr.birjournals.org

Advances in knowledge: 3-T MRCP is feasible and useful in the assessment of pancreatobiliary abnormalities in children.

radial slabs in the coronal plane (TR 5764 ms, TE 740 ms, FOV 250–380 mm, matrix 3203320 and slab thickness 30–40 mm). These slabs were acquired with breath-hold in older children and during a shallower phase of respiration in younger children. (3) Coronal and axial single-shot FSE with moderate TE and thin section (TR 3000 ms, TE 160 ms, FOV 250–320 mm, matrix 2563256 and slice thickness 3 mm without any gap). These thin sections with moderate TE are very useful for visualising small ductal anomalies and connections and small biliary stones. (4) Axial T1 weighted fat-saturated T1 weighted high-resolution isotropic volume examination (THRIVE) sequence for pancreas (TR 3.1 ms, TE 1.4 ms, FOV 250–350 mm, matrix 1923192 and slice thickness 3 mm with a gap of 1.5 mm). This sequence shows pancreatic parenchyma as the bright structure in the upper abdomen. Gadolinium-based contrast medium and secretin were not administered.

Imaging review All MRCP images were evaluated independently by a paediatric radiologist (6 years of experience) and a paediatric radiology fellow (2 years of experience).

Differences were resolved by consensus reading. Both were aware of the clinical features but were blinded to the final diagnosis. MRCP examinations were reviewed, and the following information was recorded for each examination: clinical indication, diagnostic quality of the examination, major imaging findings, presence and type of artefacts, presence of an abnormal pancreatobiliary junction (PBJ; the junction outside the duodenal wall with presence of a long common channel), anatomic variations in the hepatobiliary tree and the diagnosis based on MRCP (called MRCP diagnosis).

The diagnostic quality of the examination was graded as follows: (1) non-diagnostic (when both 3D FSE and single-shot radial slabs were completely degraded by artefacts); (2) suboptimal but diagnostic (partial degradation by artefacts with large pathology unlikely to be missed but quality not enough to exclude small duct variations, duct wall irregularities or tiny filling defects); and (3) good quality (3D FSE, radial slabs or both are of

Br J Radiol;86:20130036

Š 2013 The Authors

ARTICLE INFORMATION Received: 15 October 2012

Revised: 10 December 2012

Accepted: 19 December 2012

doi: 10.1259/bjr.20120536

Cite this article as: Pei X-Q, Liu L-Z, Xiong Y-H, Zou R-H, Chen M-S, Li A-H, et al. Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma. Br J Radiol 2013;86: 20120536.

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma 1

X-Q PEI, MD, PhD, 1L-Z LIU, MD, PhD, 1Y-H XIONG, MD, 1R-H ZOU, MD, PhD, 2,*M-S CHEN, MD, PhD, *A-H LI, MD and 3M-Y CAI, MD

1,

1 Department of Ultrasound, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China 2 Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China

Address correspondence to: Mrs A-H Li E-mail: lianhua8358@hotmail.com; liah@sysucc.org.cn *M-S Chen and A-H Li contributed equally to this study.

Objective: To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC).

Methods: 34 cases of FNH and 66 cases of HCC (all lesions ,5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software SonoliverÂŽ (ImageArenaTM v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest.

The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS. Results: The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p,0.05), while RT and

Quantitative analysis of CEUS: differentiating FNH from HCC

TTP in FNHs were significantly shorter (p,0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively.

Dynamic contrast-enhanced ultrasonography (CEUS) has noticeably improved the detection and characterisation of focal liver lesions during the past decade [1]. The enhancement patterns of the lesion are evaluated in three vascular phases (the hepatic arterial, portal venous and late phases), where the hepatic arterial phase provides information on the degree and pattern of vascularity and the portal venous and late phases provide important information on the differention between benign and malignant liver lesions [1]. A previous study has shown that CEUS using SonoVue® (Bracco, Milan, Italy) and spiral-CT provides similar diagnostic accuracy in the characterisation of focal liver lesions [2].

The typical enhancement of focal nodular hyperplasia (FNH) on CEUS showed hyperenhancement in the three vascular phases with a stellate vascular and centrifugal enhancement in the arterial phase or a hypoenhancing central scar in the late phase [1, 3–5]. However, these features have not been observed in all cases of FNH, particularly in small lesions. A study on FNH showed that 3 out of 13 lesions (23.1%) were hypoenhancing in the late phase [6] and 3 out of 10 lesions ,3 cm had spoke-wheel patterns and 2 had central scars [4]. There is also a broad variation of stellate vascular enhancement in FNHs with a range from 27.3% to 73.3% and of central scar with a range from 36.4% to 63.3% [3–5]. Thus, it can be difficult to differentiate atypical FNHs from other hypervascular malignant tumours, such as hepatocellular carcinoma (HCC), and hypervascular metastases [3]. Furthermore, a hypoenhancing central scar has been described in fibrolamellar HCC and sclerosing or scirrhous HCC [7, 8], and a central feeding artery with spoke-wheel sign has also been described in two scirrhous HCCs [8].

Hence, a comprehensive approache rather than simply estimating the haemodynamics could be beneficial for differential diagnosis.

2 of 10

bjr.birjournals.org

Conclusion: The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS. Advances in knowledge: Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.

The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which time– intensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9–11].

This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9]. In the present study, CEUS was applied to evaluate enhancing patterns of FNH and HCC; quantitative features of CEUS in the two groups were generated with the analytic software Sonoliver® (TomTec Imaging Systems, Germany) and compared to explore their potential in the differential diagnosis.

Furthermore, the quantitative analysis of CEUS was used to characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS. METHODS AND MATERIALS Patients This study was approved by the institutional ethics committee, and all subjects signed informed consent forms. Between April 2005 and July 2009, a total of 4000 patients at our hospital underwent CEUS. Retrospectively, the patients who met the criteria given below were enrolled in this study: (1) patients with hypervascular liver nodules confirmed by CEUS, (2) those with lesions confirmed as HCC by histology or confirmed as FNH by histology or clinical evidence, (3) those with maximum dimension of lesions ,5 cm, and (4) those with lesions located in a good position for quantitative analysis; furthermore, only those patients without high respiratory motion were enrolled, as this would have led to the quality of fit between the log-compressed signal and the bolus perfusion model being below 80%. An optimum scanning nodule was focused for a patient with two or more nodules. Those patients with HCC who underwent chemotherapy, interventional therapy

Br J Radiol;86:20120536

Cite this article as: Karpitschka M, Augart D, Becker H-C, Reiser M, Graser A. Dose reduction in oncological staging multidetector CT: effect of iterative reconstruction. Br J Radiol 2013;86:20120224.

Dose reduction in oncological staging multidetector CT: effect of iterative reconstruction M KARPITSCHKA,

MD,

D AUGART,

MD,

H-C BECKER,

MD,

M REISER,

MD

and A GRASER,

MD

Department of Clinical Radiology, Grosshadern Clinic, Ludwig-Maximilians-University Munich, Munich, Germany

Objective: To compare radiation exposure and image quality of oncological staging multidetector CT (MDCT) examinations of the chest, abdomen and pelvis with and without iterative reconstruction (IR).

Methods: 40 patients with known malignancy underwent staging CT examinations at two time points. Both CT scans were performed on the same scanner (SOMATOMj Definition Flash, Siemens Healthcare, Forchheim, Germany). For the baseline scan, the tube current–time product was set to 250 mAs [image reconstruction: filtered back projection (FBP)] and for the follow-up scan to 150 mAs [reconstruction: iterative reconstruction (IR)]. Effective radiation doses were estimated based on dose–length products for both baseline and follow-up. Noise measurements in defined regions were compared for FBP and IR. Images were also subjectively evaluated for image quality by three radiologists with different levels of experience.

Results: Dose reduction was 44.4¡8.2% for reduced-dose CT scans with IR compared with baseline with FBP. Image noise was not significantly different between images reconstructed with FBP and IR. The subjective quality of standard-dose FBP images and reduced-dose iteratively reconstructed CT images were identical.

Conclusion: Our results show the dose-reducing potential of IR of CT image data in oncological patients.

Advances in knowledge: The algorithm tested in the present scientific study allows a .45% dose reduction at maintained image quality.

With the advent of more effective first- and secondline cancer treatments, long-term survival of patients with malignant diseases has increased [1]. For example, the overall 5-year survival rate for non-Hodgkin’s lymphoma in the USA has increased from 48% to almost 69% over the past decades, and 10-year survival rates have also improved substantially over the same time [2].

In a clinical setting, CT is used extensively in cancer diagnosis, staging, evaluation of response to treatment and active surveillance for cancer recurrence. As a consequence, patients receive multiple CT examinations during the course of their disease. Over the past 25 years, CT usage has increased 12-fold in the UK and 20-fold in the USA [3, 4]. Overall, the mean effective dose in the USA from all medical X-ray procedures has increased 7-fold over this period [5], with the result that the major proportion of radiation exposure to the population nowadays comes from medical imaging, especially CT imaging. Recent reports on radiation-induced malignancy have sparked new concern and discussion in the medical community as well as among the general public [6–8]. In brief, there is reasonable epidemiological evidence that effective organ doses below 100 mSv result in a very small but non-negligible increase in cancer risk [9–11].

Therefore, CT imaging within a population of younger patients with primary oncological diseases remains a Address correspondence to: Dr Martina Karpitschka, LudwigMaximilians-University Munich, Grosshadern Clinic, Department of Clinical Radiology, Marchionini Str. 15, 81377 Munich, Germany.

E-mail: Martina.Karpitschka@med.uni-muenchen.de

1 of 7

Received 24 April 2012 Revised 3 September 2012 Accepted 10 September 2012 DOI: 10.1259/bjr.20120224 ’ 2013 The British Institute of Radiology

challenge. High image quality is needed for accurate tumour staging to define treatment strategies and to determine prognosis. At the same time, radiation exposure has to be minimised.

The dose associated with a CT scan of the abdomen and pelvis has decreased by a factor of two to three since the 1980s owing to a number of technical innovations [12]. Several recent dose reduction techniques are gaining widespread use. One of the most important technical features is automated exposure control (AEC), which adapts the tube current output and, consequently, the radiation dose to the diameter and attenuation of the patient [13]. Organ-based tube current modulation (TCM) is a new method that has recently been introduced for brain and body imaging [14]. The underlying technique of organ-based TCM reduces the X-ray tube current while the unit is rotating around the patient [15]. These technical features have been successfully implemented to reduce radiation exposure while maintaining image quality [16–18]. Regarding image reconstruction, CT scanners mostly use standard filtered back projection (FBP) methods in which excellent spatial resolution can be achieved, but at the cost of increased image noise.

With regard to image reconstruction and post-processing, a recently developed technology has the potential to further reduce radiation exposure. Iterative reconstruction (IR) techniques have demonstrated the potential to reduce radiation dose while maintaining high image quality [19–22] relative to the currently used FBP Br J Radiol, 86, 20120224

Dose reduction in oncological MDCT

techniques. In contrast to FBP, IR enables a decoupling of spatial resolution and image noise. In IR, a correction loop is introduced into the image reconstruction process, called ‘‘theoretical iterative reconstruction’’. The system creates a synthetic image, computes projections from the image, compares the original projection data and updates the image based on the difference between the calculated and the actual projections, which is very time consuming. IRIS (iterative reconstruction in image space; Siemens Healthcare, Forchheim, Germany) was developed as a method to translate a given number of IR loops into the image space rather than the raw data space, hence avoiding multiple time-consuming iterations of back projection. Information obtained by FBP as an initial image build is used to transform the measured value of each pixel to a new estimate of pixel values. These pixel values are subsequently compared with the ideal Hounsfield unit (HU) number that an image noise model predicts. This process is repeated in successive iterations until the final estimation and ideal pixel values ultimately converge. Using this technique, IRIS is able to selectively identify and subtract image noise, hence avoiding the time-consuming traditional reprojection [15, 23].

Graser et al [24] showed that IR is able to maintain image quality of CT brain scans while radiation exposure is reduced at the same time. However, in body imaging to date there is little evidence to show the potential of IR to reduce dose; to the best of our knowledge, no study exists comparing FBP with IR in one patient population imaged at different time points.

We therefore compared radiation dose and image quality of CT scans of the chest, abdomen and pelvis using two different CT protocols in the same patients with oncological diseases on the same CT scanner: standard-dose contrast-enhanced multidetector CT (MDCT) reconstructed with FBP (sdFBP) at baseline and reduced-dose contrast-enhanced CT reconstructed with IRIS (rdIR) at follow-up.

Methods and materials

and no significant BMI reduction between both CT scans was found (24.0¡0.5 kg m–2 for the first scan vs 23.7¡0.5 kg m–2 during the second scan, p50.7)

MDCT scanning technique All CT scans were performed on a dual-source CT scanner (SOMATOM Definition FLASH) using a 12860.6 mm collimation, a pitch of 1.0 and 120 kVp tube voltage using online dose modulation (CARE Dose4D, Siemens Healthcare). The gantry rotation time was 0.5 s and the reconstructed slice thickness/increment was 5/ 5 mm and 1/0.75 mm. 5 mm reconstructed slice thickness represents a standard value as required by most guidelines for criteria-based reading, e.g. Response Evaluation Criteria in Solid Tumours (RECIST). Therefore, we routinely reconstruct 5 mm axial and coronal slices in our oncological patients. No other slice thickness was used for evaluation in the present study. Acquiring data at thin collimation, e.g. 12860.6 mm, represents the standard of care in modern MDCT in order to allow for isotropic voxel sizes and high-quality multiplannar reconstructions. For reconstruction, common B30f and I30f filters were used (named ‘‘I’’30f because it is used for IR). All CT scans covered the chest, abdomen and pelvis and were obtained 70 s after intravenous injection of 1.9 ml kg21 body weight of a non-ionic contrast agent (IomeronH 400, Bracco Diagnostics, Milan, Italy).

At baseline, standard dose CT scans were obtained at 120 kVp and a reference tube current–time product of 250 mAs with online dose modulation; image data were reconstructed using standard-dose FBP (sdFBP). Dose reduction for follow-up CT scans was achieved by significantly lowering the tube current–time product from 250 to 150 mAs while all other parameters were kept constant. We chose these settings because the first pre-clinical studies had shown that a 40% reduction of the tube current–time product is feasible when image data are reconstructed with IR. The IR algorithm used in this study (IRIS) was installed on our dual-source CT scanner in January 2010.

Patient population Because patients were scheduled for routine CT examinations and a significant dose reduction was expected based on the tube current–time product reduction for the follow-up scans, ethical approval from the Institutional Review Board was not required for this study. A research fellow retrospectively identified adult patients aged over 18 years who were referred for staging examinations of the chest, abdomen and pelvis by the department of oncology between March and October 2010 (n51225). We selected those patients for evaluation (n540) who had been scanned twice on the same scanner (SOMATOMH Definition FLASH, Siemens Healthcare): at baseline before, and at followup after an IR algorithm (IRIS) became available (average time interval between the paired CT examinations 8.0¡0.3 months). The study population consisted of 21 males and 19 females: average age 60¡13 years; range 23–87 years. For each patient, weight and height were recorded for calculation of body mass indices (BMIs), Br J Radiol, 86, 20120224

Radiation exposure The volumetric CT dose indices (CTDIvol) for sdFBP and for rdIR were retrieved from the picture archiving and communication system (PACS; Syngo Imaging 2010, Siemens Healthcare). For the CT scanner used in this study, the accuracy of the manufacturer’s displayed CTDIvol was tested as part of our daily routine quality control. Based on the recorded dose–length product (DLP), the effective dose in millisieverts was estimated using a conversion factor of 0.0015 [25] for both sdFBP and rdIR scans.

Image quality analysis A research fellow who was not involved in data analysis obtained patient-specific quantitative noise measurements for all 40 sdFBP and 40 rdIR CT scans.

The signal (HU) and image noise [HU standard deviation 2 of 7

© 2013 The Authors. Published by the British Institute of Radiology

BJR Received: 29 May 2013

Revised: 29 July 2013

doi: 10.1259/bjr.20130310

Accepted: 31 July 2013

Cite this article as: ¨ tterer JJ, van Strijen MJL, Hoogeveen YL, de Lange F, et al. Cone beam CT guidance provides superior accuracy for Busser WMH, Braak SJ, Fu complex needle paths compared with CT guidance. Br J Radiol 2013;86:20130310.

FULL PAPER

Cone beam CT guidance provides superior accuracy for complex needle paths compared with CT guidance ¨ W M H BUSSER, MSc, 2S J BRAAK, MD, 1J J FUTTERER, MD, PhD, 2M J L VAN STRIJEN, MD, PhD, 1Y L HOOGEVEEN, PhD, F DE LANGE, PhD and 1L J SCHULTZE KOOL, MD, PhD

1 1 1

Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Department of Radiology, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands

2

Address correspondence to: Ms Wendy M H Busser E-mail: w.busser@rad.umcn.nl

Objective: To determine the accuracy of cone beam CT (CBCT) guidance and CT guidance in reaching small targets in relation to needle path complexity in a phantom.

Methods: CBCT guidance combines three-dimensional CBCT imaging with fluoroscopy overlay and needle planning software to provide real-time needle guidance.

The accuracy of needle positioning, quantified as deviation from a target, was assessed for inplane, angulated and double angulated needle paths. Four interventional radiologists reached four targets along the three paths using CBCT and CT guidance. Accuracies were compared between CBCT and CT for each needle path and between the three approaches within both modalities. The effect of user experience in CBCT guidance was also assessed.

Results: Accuracies for CBCT were significantly better than CT for the double angulated needle path (2.2 vs 6.7 mm, p,0.001) for all radiologists. CBCT guidance showed no significant differences between the three

approaches. For CT, deviations increased with increasing needle path complexity from 3.3 mm for the inplane placements to 4.4 mm (p50.007) and 6.7 mm (p,0.001) for the angulated and double angulated CT-guided needle placements, respectively. For double angulated needle paths, experienced CBCT users showed consistently higher accuracies than trained users [1.8 mm (range 1.2–2.2) vs 3.3 mm (range 2.1–7.2) deviation from target, respectively; p50.003].

Conclusion: In terms of accuracy, CBCT is the preferred modality, irrespective of the level of user experience, for more difficult guidance procedures requiring double angulated needle paths as in oncological interventions.

Advances in knowledge: Accuracy of CBCT guidance has not been discussed before. CBCT guidance allows accurate needle placement irrespective of needle path complexity.

For angulated and double-angulated needle paths, CBCT is more accurate than CT guidance.

Needle guidance for puncture or other minimally invasive procedures is increasing in standard interventional radiology practice. In local therapy procedures, such as percutaneous ablations, accurate placement of one or more needles is important in order to provide effective treatment [1]. This is especially the case in treatment or biopsy procedures of small lesions, in which the tip of the needle needs to be placed within a range of millimetres of the target point. Therefore, image guidance plays a significant role in accurate percutaneous needle placement [2].

radiation dose to the patient and operator [4]. Acquiring CT fluoroscopy images to check needle position takes approximately 1 s, time in which the needle cannot be progressed.

Currently, most needle placement procedures are performed using CT guidance, fluoroscopy or ultrasound [3]. CT images provide good visualisation of the target and surrounding tissues. For needle guidance, however, CT has limitations mainly because it does not allow real-time feedback on needle progression. For semi-real-time imaging within the CT scanner, CT-fluoroscopy can be used at the expense of a higher

Fluoroscopy in the angiography suite, however, provides optimal patient accessibility and real-time imaging of needle progression but is limited to two-dimensional visualisation.

A radiation-free technique that also provides real-time imaging is ultrasound. However, the accuracy is operator dependent and, owing to ultrasound’s low penetration depth, the area of use is restricted to superficial targets and moderate-sized patients [3].

New techniques combining cone beam CT (CBCT) and fluoroscopy with dedicated needle guidance software within an angiography C-arm system aim to overcome the disadvantages of CT and allow real-time three-dimensional needle guidance in the interventional suite [5].

Full paper: CBCT guidance accuracy for complex needle paths vs CT guidance

Several authors described the use of this CBCT with navigational tools in various types of procedures [6–19]. Braak et al [8] described the effective patient dose of CBCT guidance procedures to be reduced by 13–42% compared with CT guidance for abdominal and thoracic procedures. Other authors reported diagnostic accuracies of CBCT guidance to be comparable to or higher than other guidance modalities [14–16, 20–22]. However, until now, the accuracy of CBCT guidance for reaching small (millimetre-sized) targets has not been addressed specifically.

BJR

Figure 1. Outline of the interventional three-dimensional abdominal phantom showing an internal target (black dot) and three corresponding needle paths: dotted/dashed line, inplane path; dashed line, angulated path; and solid line, double angulated path. Grey spots represent the corresponding skin entry points. The axes indicate the right (R), head (H) and anterior (A) sides of the phantom.

In clinical practice, the used needle path is determined based on the location of the target tissue and its surrounding structures.

A safe needle path avoids puncturing critical structures such as large vessels or nerves. For CT imaging ease, an inplane needle path is often used. However, this might not always be the safest path. In those cases, a more complex needle path would be more suitable, complicating accurate needle placement.

The purpose of our phantom study was to determine and compare the accuracy of CBCT and CT guidance in reaching small targets by paths with different levels of complexity under standardised conditions.

MATERIALS AND METHODS Phantom To analyse accuracy, a modified model 057 Interventional 3D Abdominal Phantom (CIRS Inc., Norfolk, VA) was used for simulating abdominal needle placements in a standardised setting.

The phantom represents a small adult abdomen (range T9/ T10–L2/L3) and consists of materials mimicking tissues in CT imaging. Four 2.3 mm spheres (CT spots #119; Beekley, Bristol, UK) acting as targets were randomly spread in the phantom. The targets were spread roughly in the centre of the phantom at depths of 84, 98, 117 and 125 mm from the anterior phantom side. This represents a wide range of clinical targets in the abdomen, such as liver or kidney lesions.

Needle placement procedure The procedures were performed using CBCT guidance (XperGuide; Allura Xper FD-20 Angio system, Philips Medical Systems, Best, Netherlands) and CT guidance (Siemens SOMATOM® Sensation 16 CT scanner; Siemens, Erlangen, Germany).

Each of the four targets was reached with an 18G, 20 cm long Trocar EchoTip Needle (COOK Medical, Bloomington, IN) following three paths with different degrees of difficulty (Figure 1). First was an inplane path in which the skin entry point and the target were in the same axial plane and on a vertical line (direction of A-axis, Figure 1). The second path followed an angulated line in one axial plane (R/A plane in Figure 1). For the third and most difficult needle path, the skin entry point and target were located on a double angulated line, which means an angulated needle path crossing several axial scanning slices. Four experienced interventional radiologists (JJF, SJB, MJLVS, LJSK) were asked to reach all four targets along the three paths, as with a clinical procedure, on both modalities. They were allowed to redirect the needle towards the target but without pulling back, as this is not desirable in clinical practice owing to resulting trauma to tissue. All radiologists are experienced users of CT guidance (SJB, JJF, .5 years; MJLVS, LJSK, .10 years). All four had

2 of 6

bjr.birjournals.org

received hands-on training using the CBCT guidance software by a representative of the company and were given the opportunity to practice. There were, however, differences in the level of clinical experience with the guidance software. Two radiologists had performed only a few clinical guidance procedures (i.e. JJF, LJSK, ,10), whereas two (SJB, MJLVS) had performed over 200. A slightly different path was chosen for each puncture to avoid placing the needle in a previously followed path possibly still present in the phantom material. The precise angle of the needle path does not influence or determine the difficulty of the needle placement; however, the direction of the angulation does (inplane angulated vs angulated through several axial planes).

The inplane needle paths had a mean length of 106 mm (range 84–125 mm) and no angulation in the axial plane. The angulated needle paths had a mean length of 142 mm (range 106–167) and angulations in the axial plane of 30°, 50°, 60° or 70° for the different targets. The double angulated needle paths had a mean length of 145 mm (range 128–184 mm) and angulations of 30°, 40° or 50° in the axial plane and 15°, 20° or 25° in the sagittal plane.

Cone beam CT The CBCT guidance procedure commenced with acquisition of a CBCT scan (312 projections over 240°) and reconstruction of a three-dimensional (3D) data set. In this 3D data set, both target and skin entry point were defined by the interventional radiologist so as to create a safe needle path. The 3D data set with planned needle path was subsequently overlaid with the real-time fluoroscopy images and the projection followed the movements of the C-arm [5,6]. This allowed real-time visualisation of needle position and progression towards the target point.

Br J Radiol;86:20130310

Š 2013 The Authors

ARTICLE INFORMATION Received: 27 July 2012

Revised: 6 January 2013

Accepted: 8 January 2013

doi: 10.1259/bjr.20120387

Cite this article as: Kang WY, Sung DJ, Park BJ, Kim MJ, Han NY, Cho SB, et al. Perihilar branching patterns of renal artery and extrarenal length of arterial branches and tumour-feeding arteries on multidetector CT angiography. Br J Radiol 2013;86:20120387.

Perihilar branching patterns of renal artery and extrarenal length of arterial branches and tumour-feeding arteries on multidetector CT angiography 1

W Y KANG, MD, 1D J SUNG, MD, 1B J PARK, MD, 1M J KIM, MD, 1N Y HAN, MD, 1S B CHO, MD, C H KANG, MD and 2S H KANG, MD

1

Department of Radiology, Anam Hospital, College of Medicine, Korea University, Seoul, Republic of Korea Department of Urology, Anam Hospital, College of Medicine, Korea University, Seoul, Republic of Korea

1

2

Address correspondence to: Dr D J Sung E-mail: urorad@korea.ac.kr

Objective: The purpose of our study was to assess the extrarenal length of renal arterial branches and tumour-feeding arteries on multidetector CT (MDCT) angiography, in addition to the perihilar branching patterns, with relevance to segmental artery clamping.

Methods: MDCT angiograms of 64 patients with renal masses ,4 cm were retrospectively reviewed by 2 radiologists. The perihilar branching patterns of the single main renal artery were assessed according to the number of pre-segmental and segmental arteries.

The extrarenal lengths of segmental plus pre-segmental arteries and the tumourfeeding arteries, measured on volumerendered images, were compared according to the vascular segmentation and the tumour location, respectively.

Results: In the 116 kidneys, 1 pre-segmental plus 5 segmental arteries (n548) was the most common branching pattern. The mean extrarenal length of the inferior segmental plus pre-segmental arteries (33.05 mm) and the posterior segmental plus pre-segmental arteries (32.30 mm) was longer than any of the other segmental plus pre-segmental arteries (apical, 23.87 mm; superior, 26.80 mm; middle, 29.23 mm) (p,0.05). The mean extrarenal length of the lower pole tumour-feeding arteries (35.94 mm) was longer than those of the upper and mid-pole tumour-feeding arteries (24.95 mm, 29.62 mm), with significant difference between the lower and the upper pole tumour-feeding arteries (p,0.05).

Conclusion: Tumours in the lower pole, supplied by the inferior or posterior segmental

Extrarenal length of arterial branches and tumour-feeding arteries

artery, may be more amenable to segmental artery clamping.

extrarenal length of tumour-feeding arteries and may help in determining the accessibility for segmental artery clamping.

Advances in knowledge: MDCT angiography with volume rendering can demonstrate the

Nephron-sparing surgery is standard management in selected patients with renal tumours ,4 cm [1].

With advanced surgical techniques, laparoscopic partial nephrectomy has become an accepted alternative for patients with renal tumours [2–6]. Clamping of the main renal artery is a commonly used technique to decrease intraoperative haemorrhage in partial nephrectomy, and renal hilar control provides improved visibility for tumour resection and repair of the renal collecting system [7, 8]. However, this technique causes warm ischaemic injury, affecting renal function after partial nephrectomy. Further, a warm ischaemia time of longer than 20 min can result in significant renal functional loss [7–9].

Graves [10] presented the first detailed description of renal vascular segmentation in 1954 and depicted four renal segments, namely, apical, upper, middle and posterior, supplied by their own segmental arteries with no collateral arterial supply between these segments. However, renal vascular variances have not been well described. Further, the extrarenal division and branching pattern of the renal artery were also disregarded. Renal vascular segmentation suggests that the selective clamping of a segmental renal artery can offer an improved surgical field and decrease the risk of warm ischaemic injury to the whole kidney.

Shao et al [8] reported that segmental artery clamping minimised intraoperative warm ischaemic injury and improved post-operative renal function compared with main renal artery clamping.

Multidetector CT (MDCT) angiography is commonly used to evaluate the renal vascular anatomy and vascular disorders [11]. MDCT angiography is also an excellent tool to display wide variations in the renal vascular system, including tumour-related changes for planning kidney surgery [12].

To our knowledge, there have been no reports describing perihilar branching patterns of the renal artery nor any measuring the length of segmental renal arteries

2 of 10

bjr.birjournals.org

on CT angiography. The aim of this study was to assess the perihilar branching patterns of the renal artery and the extrarenal length of arterial branches and tumourfeeding arteries on MDCT angiography with relevance to segmental artery clamping during nephron-sparing surgery.

METHODS AND MATERIALS Patients Our institutional review board approved this retrospective study. Between March 2007 and February 2011, 380 consecutive patients underwent abdominal MDCT angiography at our institution and a total of 98 patients with a renal mass based on the abdominal CT scan were referred for pre-operative CT angiography. This retrospective study included 64 patients (46 male, 18 female; mean age, 56 years) with renal masses ,4 cm in diameter from the total 98 patients undergoing CT angiography. Among the 64 patients with renal tumours, the diagnosis in 61 patients was confirmed by pathological examination; the diagnosis in 53 patients was renal cell carcinoma, the diagnoses in 7 patients were angiomyolipoma, chronic inflammation, oncocytoma and atypical carcinoid, and the remaining patient showed no pathological diagnosis. The other three patients were lost to follow-up or observed without surgical treatment.

MDCT scanning technique and three-dimensional post processing All patients underwent CT angiography using a 64detector-row scanner (Brilliance 64; Philips Medical Systems, Cleveland, OH). The scanning parameters for CT angiography were 120 kV, 250 mAs with dose modulation (D-Dom; Philips Medical Systems), 6430.625 mm collimation and a rotation time of 0.75 s. The region from the diaphragmatic dome to the iliac crest level was scanned. Scanning was initiated 7 s after a threshold attenuation of 150 HU was reached in the descending aorta at the level of the renal arteries by the use of bolus-tracking software (Bolus Pro Extra; Philips Medical Systems). For each patient, 130 ml of non-ionic contrast

Br J Radiol;86:20120387

© 2013 The Authors. Published by the British Institute of Radiology

BJR Received: 23 December 2012

Revised: 17 May 2013

Accepted: 28 May 2013

doi: 10.1259/bjr.20130002

Cite this article as: Zhang G, Marshall N, Jacobs R, Liu Q, Bosmans H. Bowtie filtration for dedicated cone beam CT of the head and neck: a simulation study. Br J Radiol 2013;86:20130002.

FULL PAPER

Bowtie filtration for dedicated cone beam CT of the head and neck: a simulation study 1,2

G ZHANG, PhD, 1N MARSHALL, PhD, 3R JACOBS, PhD, 2Q LIU, PhD and 1H BOSMANS, PhD

1

Department of Radiology, University Hospitals Leuven, Leuven, Belgium Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China 3 Oral Imaging Center, University Hospitals Leuven, Leuven, Belgium 2

Address correspondence to: Dr Qian Liu E-mail: qianliu@mail.hust.edu.cn

Objective: To investigate the influence of bowtie filtration on dedicated cone beam CT (CBCT) of the head and neck.

Methods: A validated hybrid simulation technique was used to model a commercial CBCT system with offset scanning geometry, 90 kV tube potential and 145375 mm imaging field of view. Three bowtie filters were formulated to produce uniform flux intensity in the projection image of cylindrical objects of diameter 14, 16 and 18 cm.

The influence of these simulated filters was compared with the original flat filtration in terms of the output radiation field, the dose delivered to the object, the scatter distribution in projections and the quality of the reconstructed image.

Results: Compared against flat filtration, dose reduction for the bowtie case, examined as a function of radial

distance within a 16-cm-diameter water cylinder, varied from 8.7% at the centre to 53.8% at the periphery. Scatter reduction, quantified using scatter-to-primary ratio in projection images, was up to 37.6% for a 14-cm-diameter cylindrical contrast phantom. Using the supplied routine image reconstruction, bowtie filtration resulted in comparable noise appearance, contrast resolution and artefact pattern for computational anatomical phantoms, with ,5% difference in contrast-to-noise ratio.

Conclusion: Bowtie filtration can effectively reduce the dose and scatter in CBCT of the head and neck. For better image quality, corresponding modification to the image pre-processing and reconstruction is needed.

Advances in knowledge: The hybrid simulation approach can usefully explore the impact of proposed system component and design changes.

Bowtie filters are widely applied in current mutislice CT and cone beam CT (CBCT) to modulate the output of the radiation source [1–5]. The term “bowtie” applies to a class of filter shapes featuring bilateral symmetry with a thickness that increases with the distance from the centre.

Bowtie filters compensate for the difference in beam path length through the axial plane of the object such that a more uniform fluence can be delivered to the detector.

Owing to this effect, they lower the risk of signal overflow in peripheral detector elements, thus relaxing the requirement on the dynamic range of the detector and allowing better contrast detectability [6]. The use of bowtie filters is known to give a reduction in the radiation dose at the periphery of the imaging field of view (FOV) [1,3]. They have also been found effective in reducing scatter, a major cause of image artefacts [1,3,4]. Furthermore, they have the potential to flatten the scatter distribution, which is beneficial for post-processing scatter correction strategies [7].

Usually, the thickness of a bowtie filter is variable within the axial plane but stays constant over the third dimension

that corresponds to the longitudinal FOV. The large CBCT units for use in image-guided radiotherapy often have different bowtie filters switchable between different exposure settings.

Although the benefits have been well recognised, bowtie filters may not be so useful for systems with a relatively small FOV. In dedicated CBCT of the head and neck, where the FOVs are typically ,20 cm in diameter, flat filtration is commonly applied [8]. The advantages and disadvantages of bowtie filtration for such systems have not been explored. It therefore remains an open question whether the findings regarding bowtie filters in large CBCT systems are still valid, and, if so, what improvements in terms of dose and scatter management can be achieved.

The filters applied on dedicated head and neck CBCT systems are fixed and incorporated within the source assembly, which makes it difficult to assess the effects of different filtration by practical measurement. Computer

Full paper: Bowtie filtration for head and neck CBCT

simulation methods offer a more convenient approach, allowing exploration of parameters for a given imaging system beyond its nominal design [4,7,9]. In a previous paper, we reported a hybrid technique to simulate the complete imaging chain of CBCT [10]. The current paper describes an application of the technique with the objective of modelling a dedicated head and neck CBCT system with only flat filtration, designing and optimising bowtie filters under a given set of presumptions and assessing the resulting system performance. We chose to investigate the Scanora 3D CBCT system (Soredex, PaloDEx Group, Finland).

BJR

Figure 1. Image acquisition geometry of the Scanora 3D cone beam CT system.

METHODS AND MATERIALS In this section, we first introduce the Scanora 3D system and review the outline of the hybrid simulation technique. Next, the simulation model established with the original flat filtration is described, with a focus on measures taken to cope with the socalled “offset” scanning geometry. Then, we propose an approach to design and optimise bowtie filters. Phantoms to be used for evaluation of the system performance are presented last.

Scanora 3D cone beam CT system The Scanora 3D applies an offset scanning technique, which is implemented nowadays as a solution to the growing demand of large FOVs on the one hand and the cost-prohibitive flat panel detectors on the other hand [4,11]. It allows the CBCT system to reconstruct an FOV of some nominal volume using a detector of roughly half the size compared with that in a symmetrical setup. Specifically, the source and the detector rotate in paired circular trajectories while the flat panel detector is offset with respect to the rotation axis, such that the peripheral region of the FOV is imaged by projections in only half of the rotation, namely 180° plus the fan angle, while a small region around the centre of the FOV is covered by all projections. Because of this highly asymmetrical set-up, the projections are also called “half projections”. To avoid ambiguity, the “central beam” mentioned in this text is the one that runs perpendicular from the focal spot to the detector plane. The “inner side” of the half projection refers specifically to the side near the centre of the FOV and the “outer side”, in contrast, is the side corresponding to the periphery of the FOV. Figure 1 shows the image acquisition geometry of the Scanora system. The tube is placed in a direction such that the anode to cathode axis lies orthogonal to the longitudinal FOV. The flat panel detector is the Hamamatsu C10900D (Hamamatsu Photonics®, Hamamatsu City, Japan), with a 6083616 array of 2003200 mm2 pixels. It is offset in the cathode direction, leaving an overlap of ;5 mm for half-projections at opposite angles.

The tube is rotated upwards about the anode to cathode axis by a small angle. Accordingly, the lower bound of the radiation field is slightly below the tube trajectory plane. Two filters are placed in the beam path, each made of a 0.1 mm flat copper sheet. The system operates under a fixed tube potential of 90 kV while the tube current can be adjusted in a range from 4.0 mA to 12.5 mA. The largest FOV is 145375 mm, denoted as width3height, which utilises the entire effective area of the detector and was the focus of our investigation. The paired source–detector movement follows a step-and-shoot (pulsed) pattern, with the half projections distributed evenly over 360°. Under the standard operation

2 of 10

bjr.birjournals.org

mode, the large FOV is associated with 225 half projections, an effective exposure time of 2.25 s and an isotropic voxel resolution of 350 mm in the reconstructed image. The system also supports a high-resolution mode and a panoramic imaging program, which, however, were not considered in this study.

Hybrid simulation technique The simulation technique accounts for the complete imaging chain of a CBCT system via a hybrid approach [10]. The model starts with the X-ray generation, filtration and collimation, delivers a cone beam radiation field, continues with angular projections through a three-dimensional (3D) voxel phantom, calculates the dose distributions in pre-defined regions of interest, produces primary and scatter images separately, applies the measured resolution and noise characteristics of the flat panel detector, follows the image pre-processing procedures and results in a sequence of two-dimensional (2D) projection data ready for volumetric reconstruction. The flowchart of the simulation is presented in Figure 2. This technique is hybrid: it includes both dose- and image-related aspects of the imaging process, splitting the system structure into source, projection and detector, combining deterministic and stochastic methods, making use of the measured detector characteristics as well as different acceleration and variance reduction techniques. The BEAMnrc/EGSnrc code system was employed for the Monte Carlo part [12,13]. The so-called “phase space” was used to keep track of the beam dataflow in the source simulation model and represent the resulting radiation field. The measured resolution and noise characteristics of the detector were described using the modulation transfer function (MTF) and the noise power spectrum (NPS), both of which were used to filter the simulated projection images in the frequency domain. Further details about the hybrid simulation technique can be found in Zhang et al [10].

Br J Radiol;86:20130002

Š 2013 The Authors

ARTICLE INFORMATION Received: 9 November 2012

Revised: 26 February 2013

Accepted: 5 March 2013

doi: 10.1259/bjr.20120570

Cite this article as: Buchbender C, Hartung-Knemeyer V, Forsting M, Antoch G, Heusner TA. Positron emission tomography (PET) attenuation correction artefacts in PET/CT and PET/MRI. Br J Radiol 2013;86:20120570.

SHORT COMMUNICATION

Positron emission tomography (PET) attenuation correction artefacts in PET/CT and PET/MRI 1,2 1,2

C BUCHBENDER, MD, 3V HARTUNG-KNEMEYER, MD, 2M FORSTING, MD, 1G ANTOCH, MD and T A HEUSNER, MD

1 Department of Diagnostic and Interventional Radiology, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany 2 Department of Diagnostic and Interventional Radiology and Neuroradiology, Medical Faculty, University of Duisburg-Essen, Essen, Germany 3 Department of Nuclear Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany

Address correspondence to: Dr Christian Buchbender E-mail: Christian.buchbender@med.uni-duesseldorf.de

Objective: To compare the effect of implanted medical materials on 18F-fludeoxyglucose (18FFDG) positron emission tomography (PET)/ MRI using a Dixon-based segmentation method for MRI-based attenuation correction (MRAC), PET/CT and CT-based attenuation-corrected PET (PETCTAC).

underestimation, overestimation compared with non-corrected images) were compared.

In PETMRAC images, a volume of interest was drawn in the area of the artefact and in a reference site (contralateral body part); the mean and maximum standardised uptake values (SUVmean; SUVmax) were measured.

Methods: 12 patients (8 males and 4 females; age 58611 years) with implanted medical materials prospectively underwent whole-body 18 F-FDG PET/CT and PET/MRI. CT, MRI and MRAC maps as well as PETCTAC and PETMRAC images were reviewed for the presence of artefacts. Their morphology and effect on the estimation of the 18F-FDG uptake (no effect,

Results: Of 27 implanted materials (20 dental fillings, 3 injection ports, 3 hip prostheses and 1 sternal cerclage), 27 (100%) caused artefacts in CT, 19 (70%) in T1 weighted MRI and 17 (63%) in MRAC maps. 20 (74%) caused a visual overestimation of the 18F-FDG uptake in PETCTAC, 2 (7%) caused an underestimation and 5 (19%) had no effect. In PETMRAC, 19 (70%) caused

C Buchbender, V Hartung-Knemeyer, M Forsting et al

spherical extinctions and 8 (30%) had no effect.

Mean values for SUVmean and SUVmax were significantly decreased in artefact-harbouring sites (p,0.001).

Conclusion: Contrary to PET attenuation correction artefacts in PET/CT, which often show an overestimation of the 18F-FDG

Diagnostic imaging in combination with positron emission tomography (PET) requires adequate correction of detected g-rays for the attenuation effect caused by different body tissues. In combined PET/CT, CT data provide opportune information on tissue density, which is rescaled to the annihilation emission energy and used for PET attenuation correction (AC) [1]. Implanted materials, e.g. dental or orthopaedic implants, are often present in patients and lead to artificial AC, resulting in overestimation or underestimation of tracer uptake in PET/CT studies [2–4]. The integration of PET and MRI into one imaging modality (PET/MRI) necessitated MRI-based attenuation correction (MRAC). MRAC relies on either automated pattern recognition of anatomical structures, discriminated by differences in pixel grey values in MR images (atlas-based MRAC method), or tissue classification, for example by using a Dixonbased in- and out-of-phase separation of fat and water (segmentation method) [5,6]. However, the quality of both MRAC methods depends on correct visualisation of the individual anatomy in the MRI source data used for MRAC. Also, in MRI, implanted medical materials cause various artefacts. In tissues adjacent to the foreign material, complete signal loss, signal pile-up, signal dislocation and geometric distortion have been described [7].

Using a Dixon-based MRAC with tissue segmentation for PET/MRI, we encountered severe artefacts owing to implanted medical materials. These artefacts are assumed to lead to bias in PET quantification, with potential impact on diagnostic and therapeutic decisionmaking. Thus, the purpose of this study was to assess the effect of implanted medical materials on Dixonbased MRAC, [18F]-fludeoxyglucose (18F-FDG) PET/ MRI and to compare this effect with 18F-FDG PET/CT. PATIENTS AND METHODS Patients In 12 consecutive oncological patients [8 males and 4 females; age 58611 years (mean 6 standard deviation)] who underwent routine 18F-FDG PET/CT for staging,

2 of 9

bjr.birjournals.org

uptake, MRAC artefacts owing to implanted medical materials in most cases cause an underestimation.

Advances in knowledge: Being aware of the morphology of artefacts owing to implanted medical materials avoids interpretation errors when reading PET/MRI.

PET/MRI was additionally performed on the same day.

Table 1 provides a summary of the patient diagnoses. This study was performed in accordance with the regulations of the local ethics committee.

PET/CT imaging Whole-body (WB) 18F-FDG PET/CT scans were obtained on an mCT™ PET/CT scanner (Siemens Molecular Imaging, Hoffmann Estates, IL). Before imaging, patients fasted for at least 6 h. All patients had blood glucose levels below 150 mg dl21 at the time of 18F-FDG injection. 290645 MBq of 18F-FDG was intravenously injected 60 min before the scan. The CT scan was done with the following parameters. Caudocranial scan direction, field of view (FOV): skull base to upper thighs, 120 kV, automatic mA s21 adjustment (Care Dose 4D™; Siemens Healthcare, Erlangen, Germany; preset: 210 mAs), 5-mm slice thickness, 5-mm increment and pitch 1. PET scan: three-dimensional (3D) mode, 2-min emission time per bed position (45% overlap), reconstruction according to the ordered-subsets expectation Table 1. Summary of patients’ diagnoses

Patient number

Diagnosisa

1

Urothelial carcinoma

2

Lung cancer

3

Thymic cancer

4

Non-Hodgkin lymphoma

5

Lung cancer

6

Sarcoma

7

Renal carcinoma

8

Melanoma

9

Cancer of unknown primary

10

Colorectal carcinoma

11

Renal carcinoma

12

Breast cancer

a

As clinically suspected.

Br J Radiol;86:20120570

Simultaneous MR and PET in clinical use %LRJUDSK P05 EULQJV D UHYROXWLRQ LQ GLDJQRVWLF LPDJLQJ WR OLIH 6WDWH RI WKH DUW 7 05, DQG FXWWLQJ HGJH PROHFXODU LPDJLQJ DUH IXOO\ LQWHJUDWHG DV RQH 2QO\ 6LHPHQV FDQ EULQJ \RX WKLV JURXQGEUHDNLQJ V\VWHP UHGHILQLQJ WKH ZD\ \RX YLVXDOL]H GLDJQRVH WUHDW DQG PDQDJH GLVHDVH :LWK

WKH SRWHQWLDO RI EUHDWKWDNLQJO\ DFFXUDWH LPDJHV WKDW RSHQ XS QHZ DYHQXHV RI UHVHDUFK DQG HQDEOH H[WUDRUGLQDU\ FOLQLFDO DSSOLFDWLRQV 0ROHFXODU 05 VXSSRUWV RXU MRLQW YLVLRQ IRU KHDOWKFDUH ² WR DGYDQFH GLVHDVH PDQDJHPHQW DQG LPSURYH FDUH IRU DOO SDWLHQWV ZZZVLHPHQV FRP P05

$QVZHUV IRU OLIH

A91CRM-9243-A2-7600

$ 05 $

ZZZ VLHPHQV FRP P05

The more deeply you look, the more clearly you see your patients.

Tumor Analytics – Oncology Solutions from Siemens www.siemens.com/oncology

Tumors are as individual as patients themselves.

At Siemens, we develop imaging, laboratory and IT solutions that help you understand the nature and behavior of individual tumors with amazing depth and clarity and guide their therapy. Tumor Analytics is our term for the advanced technologies that make such understanding and treatment possible.

Tumor Analytics supports you to diagnose cancer earlier and personalize its treatment. By matching the right treatment with the right patient, Tumor Analytics helps improve patient outcomes and reduce the overall cost of oncology care for institutions and societies.

In short: The better you understand and treat your patient’s tumor, the better you can care for your patient.

At the end of the day, that is what Tumor Analytics is all about.

Answers for life.

BEST OF

BJR

BJR is the agship journal of the British Institute of Radiology. BJR is an international multidisciplinary journal which covers clinical and technical aspects of medical imaging, radiotherapy, oncology, medical physics and radiobiology.

BEST OF

AN INTERNATIONAL JOURNAL OF RADIOLOGY, RADIATION ONCOLOGY AND ALL RELATED SCIENCES

The oldest radiology journal in the world Acceptance to publication 4 weeks Open access option

PUBLISHED BY:

http://birjournals.org