Imperial College London

ProfessorTaraBarwick

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Practice (Cancer Imaging)
 
 
 
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t.barwick

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
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109 results found

Rockall AG, Li X, Johnson N, Lavdas I, Santhakumaran S, Prevost AT, Punwani S, Goh V, Barwick TD, Bharwani N, Sandhu A, Sidhu H, Plumb A, Burn J, Fagan A, Wengert GJ, Koh D-M, Reczko K, Dou Q, Warwick J, Liu X, Messiou C, Tunariu N, Boavida P, Soneji N, Johnston EW, Kelly-Morland C, De Paepe KN, Sokhi H, Wallitt K, Lakhani A, Russell J, Salib M, Vinnicombe S, Haq A, Aboagye EO, Taylor S, Glocker Bet al., 2023, Development and evaluation of machine learning in whole-body magnetic resonance imaging for detecting metastases in patients with lung or colon cancer: a diagnostic test accuracy study, Investigative Radiology, Vol: 58, Pages: 823-831, ISSN: 0020-9996

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient spec

Journal article

Jesuthasan A, Barwick T, Dixon L, Molloy S, Johnson MR, Tomlinson Jet al., 2023, LGI1 encephalitis and IGG4-related disease. Rare conditions collide, Neurology: Neuroimmunology & Neuroinflammation, Vol: 10, ISSN: 2332-7812

Objectives: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis and IgG4-related disease (IgG4RD) have traditionally been regarded as 2 distinct disease entities.Methods: We detail the presentation, investigations, and management of a patient who showed typical signs and symptoms of LGI1 encephalitis and also found to possess pancreatic changes and a serum profile in keeping with IgG4RD.Results: Serum and CSF analyses at presentation showed a significant hyponatraemia (117 mmol/L), elevated IgG4 concentration (1.73 g/L), and the presence of LGI1 antibodies. MRI revealed symmetrical diffuse T2-weighted hyperintensity and mild swelling throughout both medial temporal lobes. CT of the chest, abdomen and pelvis revealed an edematous, bulky pancreas with loss of lobulation, typical for IgG4RD. A glucocorticoid weaning regimen was commenced, facilitated by 2 rituximab infusions, with the patient showing an effective treatment response. HLA testing confirmed the presence of HLA DRB1 and HLA DQB1 risk alleles.Discussion: This case suggests that there may be shared mechanisms between LGI1 encephalitis and IgG4RD, supported by common risk HLA associations and treatment strategies/responses. To our knowledge, this represents the first instance that LGI1 encephalitis and IgG4RD have been reported in the same patient and emphasizes the continued development of our understanding of the wide range of IgG4-mediated conditions.

Journal article

Aboagye E, Islam S, Inglese M, Grech-Sollars M, Aravind P, Dubash S, Barwick TD, ONeill K, Saleem A, O'Callaghan J, Anchini G, Williams M, Waldman Aet al., 2023, Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 50, Pages: 3982-3995, ISSN: 0340-6997

Purpose:MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study.Methods:Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade – LGG – and higher-grade – HGG – patients). FPIA was injected as an intravenous bolus injection (range 342–368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min.Results:All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG.Conclusion:Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population.

Journal article

Naik M, Hesni S, Tamimi A, Hameed M, Tomlinson J, Poo S, Tam F, Strickland N, Barwick TD, Harvey CJet al., 2023, Imaging manifestations of IgG4-related disease, Clinical Radiology, Vol: 78, Pages: 555-564, ISSN: 0009-9260

IgG4-related disease is a multisystem immune-mediated disorder associated with lesions manifesting an IgG4-rich plasma cell infiltrate and often raised serum IgG4 concentrations. The disease can mimic neoplastic, infective, and inflammatory processes due to features such as development of masses or organ enlargement. Prompt consideration of this diagnosis is essential to avoid unnecessary investigations and offer appropriate treatments, which can include steroids and other immunosuppressive agents. Although histology is typically diagnostic, imaging is critical to assess disease burden, determine biopsy targets, and evaluate response to treatment. Characteristic imaging features can also point towards the diagnosis in the absence of biopsy. This review highlights these features, as well as more atypical findings, grouped by organ or system. Differential diagnoses are emphasised. The full spectrum of imaging methods is discussed. Whole-body imaging with integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) has an evolving role in the detection of multi-organ involvement and subsequent follow-up.

Journal article

Aboagye EO, Barwick TD, Haberkorn U, 2023, Radiotheranostics in oncology: Making precision medicine possible, CA-A CANCER JOURNAL FOR CLINICIANS, Vol: 73, Pages: 255-274, ISSN: 0007-9235

Journal article

Bondje S, Kaplan F, Palazzo F, Barwick Tet al., 2023, Resection of an elusive parathyroid adenoma in the aortopulmonary window, BMJ CASE REPORTS, Vol: 16

Journal article

ElGendy K, Barwick T, Auner HW, Chaidos A, Wallitt K, Sergot A, Rockall Aet al., 2022, Repeatability and test-retest reproducibility of mean apparent diffusion coefficient measurements of focal and diffuse disease in relapsed multiple myeloma at 3t whole body diffusion weighted MRI (WB-DW-MRI), The British Journal of Radiology, Vol: 95, ISSN: 0007-1285

Objectives:To assess the test-retest reproducibility and intra/inter observer agreement of Apparent Diffusion Coefficient (ADC) measurements of myeloma lesions using WB-DW-MRI at 3T MRI.Methods:Following ethical approval, eleven consenting patients with relapsed multiple myeloma were prospectively recruited and underwent baseline WB-DW-MRI. For a single bed position, axial DWI was repeated after a short interval to permit test- retest measurements.Mean ADC measurement was performed by two experienced observers. Intra and inter observer agreement and test-retest reproducibility were assessed, using coefficient of variation (CV) and interclass correlation coefficient (ICC) measures, for diffuse and focal lesions (small ≤10 mm and large >10 mm).Results:Forty seven sites of disease were outlined (23 focal, 24 diffuse) in different bed positions (pelvis = 22, thorax = 20, head and neck = 5). For all lesions, there was excellent intra observer agreement with ICC of 0.99 (0.98–0.99) and COV of 5%. For inter observer agreement, ICC was 0.89 (0.8–0.934) and COV was 17%. There was poor inter observer agreement for diffuse (ICC = 0.46) and small lesions (ICC = 0.54).For test-retest reproducibility, excellent ICC (0.916) and COV (14.5%) values for mean ADC measurements were observed. ICCs of test-retest were similar between focal lesions (0.83) and diffuse infiltration (0.80), while ICCs were higher in pelvic (0.95) compared to thoracic (0.81) region and in small (0.96) compared to large (0.8) lesions.Conclusions:ADC measurements of focal lesions in multiple myeloma are repeatable and reproducible, while there is more variation in ADC measurements of the diffuse disease in patients with multiple myeloma.Advances in knowledge:Mean ADC measurements are repeatable and reproducible in focal lesions in multiple myeloma, while the ADC measurements of diffuse disease in multiple myeloma are more subject to variation. The evidence supports the future pot

Journal article

Qaiser T, Winzeck S, Barfoot T, Barwick T, Doran SJ, Kaiser MF, Wedlake L, Tunariu N, Koh D-M, Messiou C, Rockall A, Glocker Bet al., 2021, Multiple instance learning with auxiliary task weighting for multiple myeloma classification, International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), Publisher: Springer, Pages: 786-796, ISSN: 0302-9743

Whole body magnetic resonance imaging (WB-MRI) is the recommended modality for diagnosis of multiple myeloma (MM). WB-MRI is used to detect sites of disease across the entire skeletal system, but it requires significant expertise and is time-consuming to report due to the great number of images. To aid radiological reading, we propose an auxiliary task-based multiple instance learning approach (ATMIL) for MM classification with the ability to localize sites of disease. This approach is appealing as it only requires patient-level annotations where an attention mechanism is used to identify local regions with active disease. We borrow ideas from multi-task learning and define an auxiliary task with adaptive reweighting to support and improve learning efficiency in the presence of data scarcity. We validate our approach on both synthetic and real multi-center clinical data. We show that the MIL attention module provides a mechanism to localize bone regions while the adaptive reweighting of the auxiliary task considerably improves the performance.

Conference paper

Rockall A, Barwick T, Wilson W, Singh N, Bharwani N, Sohaib A, Nobbenhuis M, Warbey V, Miquel M, Koh D-M, De Paepe KN, Martin-Hirsch P, Ghaem-Maghami S, Fotopoulou C, Stringfellow H, Sundar S, Manchanda R, Sahdev A, Hackshaw A, Cook GJ, MAPPING Study Groupet al., 2021, Diagnostic accuracy of FEC-PET/CT, FDG-PET/CT and diffusion-weighted MRI in detection of nodal metastases in surgically treated endometrial and cervical carcinoma, Clinical Cancer Research, Vol: 27, Pages: 6457-6466, ISSN: 1078-0432

Purpose:Pre-operative nodal staging is important for planning treatment in cervical cancer (CC) and endometrial cancer (EC) but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-Fluoro-deoxy-glucose-(FDG)-PET/CT and diffusion-weighted-MRI (DW-MRI) with conventional morphological MRI.Experimetal Design:A prospective, multicentre observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centres. FEC-PET/CT, FDG-PET/CT and DW-MRI were compared to nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable CC stage=>1B1 or EC (grade 3 any stage with myometrial invasion or grade 1-2 stage=>II). Results:Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT, and 60 underwent FEC-PET/CT. 267 nodal regions in 118 women were strictly correlated at histology (nodal positivity rate 25%). Sensitivity per-patient (n=118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT were 40%*, 53%, 53%, 63%* and 67% for all cases (*p=0.016); 10%, 10%, 20%, 30% and 25% in CC (n=40); 65%, 75%, 70%, 80% and 88% in EC (n=78). FDG-PET/CT outperformed nodal size (p=0.006) and size ratio (p=0.04) for per-region sensitivity. False positive rates were all <10%. Conclusions:All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different to other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.

Journal article

Connor M, Dubash S, Bass E, Tam H, Barwick T, Vincent K, Winkler M, Ahmed Het al., 2021, Clinical translation of positive metastases identified on prostate-specific membrane antigen positron emission tomography/computed tomography imaging in the management of de novo synchronous oligometastatic prostate cancer, European Urology Focus, Vol: 7, Pages: 951-954, ISSN: 2405-4569

Recent randomised evidence supports the diagnostic superiority of prostate-specific membrane antigen (PSMA) PET/CT, over conventional imaging, in the detection of distant occult metastasis in men with newly diagnosed high-risk prostate cancer. This may result in a rise in the detection of de novo synchronous hormone-sensitive “oligometastatic” prostate cancer. We outline the evidence supporting PSMA PET/CT imaging in primary staging. We also discuss the translation of positive areas, with a high probability of distant metastasis, into clinical therapeutic targets for metastasis-directed interventions. Finally, we highlight the role of PSMA PET/CT as an imaging biomarker. This may have future utility in disease monitoring and prediction of response to systemic, local cytoreductive and metastasis-directed interventions. Patient Summary: A new whole-body scan can accurately detect cancer deposits, in men in whom distant prostate cancer spread is suspected. This may be useful to monitor and predict response to drug therapy, treatments to the prostate and cancer deposits.

Journal article

Arora M, Moura AG, Carmody M, Win Z, Patel NH, Bowen C, Khan SR, Barwick Tet al., 2021, Ipsilateral nodal uptake post COVID-19 vaccination and the impact on interpretation of 18F-FDG PET/CT scans, Publisher: SPRINGER, Pages: S150-S151, ISSN: 1619-7070

Conference paper

Uy CP, Tarkin JM, Gopalan D, Barwick TD, Tombetti E, Youngstein T, Mason JCet al., 2021, The impact of integrated non-invasive imaging in the management of takayasu arteritis, JACC: Cardiovascular Imaging, Vol: 14, Pages: 495-500, ISSN: 1876-7591

Journal article

Kenny LM, Gopalakrishnan GS, Barwick TD, Vaja V, McDevitt SH, Punjani R, Patel NH, Ramakrishnan R, Patel NR, Johnston S, Mansi J, Cook GJ, Gilbert FJ, Aigbirhio FI, Hiscock D, Aboagye EOet al., 2021, Herpet study- PET imaging of HER2 expression in breast cancer using the novel Affibody tracer [18F]GE-226, a first in patient study, San Antonio Breast Cancer Virtual Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Camenzuli C, DiMarco AN, Isaacs KE, Grant Y, Jackson J, Alsafi A, Harvey C, Barwick TD, Tolley N, Palazzo FFet al., 2021, The changing face of reoperative parathyroidectom a single-centre comparison of 147 parathyroid reoperations, ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND, Vol: 103, Pages: 29-34, ISSN: 0035-8843

Journal article

Reed N, Balega J, Barwick T, Buckley L, Burton K, Eminowicz G, Forrest J, Ganesan R, Harrand R, Holland C, Howe T, Ind T, Iyer R, Kaushik S, Music R, Sadozye A, Shanbhag S, Siddiqui N, Syed S, Percival N, Whitham NL, Nordin A, Fotopoulou Cet al., 2021, British Gynaecological Cancer Society (BGCS) cervical cancer guidelines: Recommendations for practice, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 256, Pages: 433-465, ISSN: 0301-2115

Journal article

Barwick T, Orton M, Koh DM, Kaiser M, Rockall A, Tunariu N, Blackledge M, Messiou Cet al., 2021, Repeatability and reproducibility of apparent diffusion coefficient and fat fraction measurement of focal myeloma lesions on whole body magnetic resonance imaging, BRITISH JOURNAL OF RADIOLOGY, Vol: 94, ISSN: 0007-1285

Journal article

Mason J, Dattani R, Barwick T, Wardany G, Gibbons N, Morgan P, Pusey C, Tam F, Tomlinson Jet al., 2020, An international patient centred study of Retroperitoneal Fibrosis, QJM: an international journal of medicine, Vol: hcaa327, ISSN: 1460-2393

BackgroundThe impact that rare chronic disorders, such as retroperitoneal fibrosis (RPF), can have on the physical and psychological aspects of a patient’s health is poorly understood. Patient-related outcome measures and experiences provide a unique opportunity to understand the impact rare chronic disorders have on a patient’s life as well as allowing healthcare providers to compare and improve performance.AimTo understand the physical and psychosocial impact that RPF has upon peoples’ lives.DesignAn international online questionnaire was therefore created to gain insights into how patients with RPF, a rare fibro-inflammatory condition, viewed their health and experiences.MethodsAn international online questionnaire comprising 62 questions/free text options, was designed in collaboration with two patient advocates and the multi-disciplinary Renal Association Rare Disease Registry (RaDaR) RPF Group the questionnaire was anonymous and freely accessible on a GOOGLE Form online platform for 6 months.ResultsA total of 229 patients from 30 countries across 5 continents responded. Four key issues were identified; (i) pain; (ii) therapy-related side effects; (iii) lack of informed doctors/information about their condition and its management; and (iv) psychological burden. Variations in diagnosis and management are highlighted with 55% undergoing a biopsy to reach a diagnosis of RPF; 75% of patients underwent a further interventional procedure with 60% concurrently treated medically.ConclusionThis study will guide further development of clinical and academic multi-disciplinary activity and shows the importance of trying to understand the impact of rare chronic disorders on the physical and psychological aspects of a patient’s health.

Journal article

Arshad MA, Gitau S, Tam H, Park W-HE, Patel NH, Rockall A, Aboagye EO, Bharwani N, Barwick TDet al., 2020, Optimal method for metabolic tumour volume assessment of cervical cancers with inter-observer agreement on [18F]-fluoro-deoxy-glucose positron emission tomography with computed tomography, European Journal of Nuclear Medicine and Molecular Imaging, Pages: 1-15, ISSN: 0340-6997

PurposeCervical cancer metabolic tumour volume (MTV) derived from [18F]-FDG PET/CT has a role in prognostication and therapy planning. There is no standard method of outlining MTV on [18F]-FDG PET/CT. The aim of this study was to assess the optimal method to outline primary cervical tumours on [18F]-FDG PET/CT using MRI-derived tumour volumes as the reference standard.Methods81 consecutive cervical cancer patients with pre-treatment staging MRI and [18F]-FDG PET/CT imaging were included. MRI volumes were compared with different PET segmentation methods. Method 1 measured MTVs at different SUVmax thresholds ranging from 20 to 60% (MTV20-MTV60) with bladder masking and manual adjustment when required. Method 2 created an isocontour around the tumour prior to different SUVmax thresholds being applied. Method 3 used an automated gradient method. Inter-observer agreement of MTV, following manual adjustment when required, was recorded.ResultsFor method 1, the MTV25 and MTV30 were closest to the MRI volumes for both readers (mean percentage change from MRI volume of 2.9% and 13.4% for MTV25 and − 13.1% and − 2.0% for MTV30 for readers 1 and 2). 70% of lesions required manual adjustment at MTV25 compared with 45% at MTV30. There was excellent inter-observer agreement between MTV30 to MTV60 (ICC ranged from 0.898–0.976 with narrow 95% confidence intervals (CIs)) and moderate agreement at lower thresholds (ICC estimates of 0.534 and 0.617, respectively for the MTV20 and MTV25 with wide 95% CIs). Bladder masking was performed in 86% of cases overall. For method 2, excellent correlation was demonstrated at MTV25 and MTV30 (mean % change from MRI volume of −3.9% and − 8.6% for MTV25 and − 16.9% and 19% for MTV30 for readers 1 and 2, respectively). This method also demonstrated excellent ICC across all thresholds with no manual adjustment. Method 3 demonstrated excellent ICC of 0.96 (95% CI 0.94–0.97) but had a

Journal article

Aboagye E, Sharma R, Inglese M, Dubash S, Lu H, Pinato D, Patel N, Chung A, Sanghera C, Tait A, Mauri F, Crum W, Barwick Tet al., 2020, Monitoring response to transarterial chemoembolization in hepatocellular carcinoma using 18F-Fluorothymidine Positron Emission Tomography, The Journal of Nuclear Medicine, Vol: 61, Pages: 1743-1748, ISSN: 0161-5505

Accurate disease monitoring is essential following transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) due to potential for profound adverse event and large variation in survival outcome. Post-treatment changes on conventional imaging can confound determination of residual/recurrent disease, magnifying the clinical challenge. Based on increased expression of thymidylate synthase (TYMS), thymidine kinase-1 (TK-1) and SLC29A1 (Equilibrative nucleoside transporter 1, ENT1) in HCC compared with liver tissue, we conducted a proof of concept study evaluating the efficacy of 18F-fluorothymidine (18F-FLT)-PET to assess response to TACE. As previous PET studies in HCC have been hampered by high background liver signal, we investigated if a temporal-intensity voxel-clustering (“Kinetic Spatial Filtering”) (KSF) improved lesion detection. Methods: A tissue microarray (TMA) was built from 36 HCC samples and matched surrounding cirrhotic tissue and was stained for thymidine kinase-1 (TK-1). A prospective study was conducted; eighteen patients with a diagnosis of HCC by American Association for the Study of Liver Diseases criteria (AALSD) who were eligible to treatment with TACE were enrolled. Patients underwent baseline conventional imaging and dynamic 18F-FLT-PET/KSF followed by TACE. Repeat imaging was performed 6-8 weeks post TACE. PET parameters were compared with modified-Response Evaluation in Solid Tumours (mRECIST) enhancement-based criteria. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1 and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (p<0.05). The sensitivity of 18F-FLT-PET for baseline HCC detection was 73% (SUVmax of 9.7 ± 3.0; tumour to liver ratio of 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response following TACE by mRECIST criteria was 58% (14 patients with 24 lesions). A 30% reduction in mean 18F-FLT-PET uptake was o

Journal article

Dubash S, Keat N, Kozlowski K, Barnes C, Allott L, Brickute D, Hill S, Huiban M, Barwick T, Kenny L, Aboagye Eet al., 2020, Clinical translation of 18F-fluoropivalate – a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 47, Pages: 2549-2561, ISSN: 1619-7070

BackgroundFatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions.Materials and methodsHealthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1.ResultsAll subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects

Journal article

Bosaily AE-S, Frangou E, Ahmed HU, Emberton M, Punwani S, Kaplan R, Brown LC, Freeman A, Jameson C, Hindley R, Peppercorn D, Thrower A, Winkler M, Barwick T, Stewart V, Burns-Cox N, Burn P, Ghei M, Kumaradevan J, Prasad R, Ash-Miles J, Shergill I, Agarwal S, Rosario D, Salim F, Bott S, Evans H, Henderson A, Ghosh S, Dudderidge T, Smart J, Tung K, Kirkham Aet al., 2020, Additional Value of Dynamic Contrast-enhanced Sequences in Multiparametric Prostate Magnetic Resonance Imaging: Data from the PROMIS Study, EUROPEAN UROLOGY, Vol: 78, Pages: 503-511, ISSN: 0302-2838

Journal article

Salib MY, Russell JHB, Stewart VR, Sudderuddin SA, Barwick TD, Rockall AG, Bharwani Net al., 2020, 2018 FIGO Staging Classification for Cervical Cancer: Added Benefits of Imaging, RADIOGRAPHICS, Vol: 40, Pages: 1807-1822, ISSN: 0271-5333

Journal article

Barwick TD, Castellucci P, 2020, Invited Commentary: Prostate-specific Membrane Antigen PET Response Assessment-Has the Time Come?, RADIOGRAPHICS, Vol: 40, Pages: 1431-1433, ISSN: 0271-5333

Journal article

Dubash S, Inglese M, Mauri F, Kozlowski K, Trivedi P, Arshad M, Challapalli A, Barwick T, Al-Nahhas A, Stanbridge R, Lewanski C, Berry M, Bowen F, Aboagye EOet al., 2020, Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [F-18]fluoromethyl-(1,2-H-2(4))-choline, Theranostics, Vol: 10, Pages: 8677-8690, ISSN: 1838-7640

Purpose: The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited. We investigated such heterogeneity in Non-Small Cell Lung Cancer (NSCLC) with [18F]fluoromethyl-(1,2-2H4) choline ([18F]D4-FCH) and positron emission tomography/computed tomography (PET/CT).Experimental design: [18F]D4-FCH (300.5±72.9MBq [147.60-363.6MBq]) was administered intravenously to 17 newly diagnosed NSCLC patients. PET/CT scans were acquired concurrently with radioactive blood sampling to permit mathematical modelling of blood-tissue transcellular rate constants. Comparisons were made with biopsy-derived choline kinase-α (CHKα) expression and diagnostic [18F]fluorodeoxyglucose ([18F]FDG) scans.Results: Oxidation of [18F]D4-FCH to [18F]D4-fluorobetaine was suppressed (48.58±0.31% parent at 60 min) likely due to the deuterium isotope effect embodied within the design of the radiotracer. Early (5 min) and late (60 min) images showed specific uptake of tracer in all 51 lesions (tumors, lymph nodes and metastases) from 17 patients analyzed. [18F]D4-FCH-derived uptake (SUV60max) in index primary lesions (n=17) ranged between 2.87-10.13; lower than that of [18F]FDG PET [6.89-22.64]. Mathematical modelling demonstrated net irreversible uptake of [18F]D4-FCH at steady-state, and parametric mapping of the entire tumor showed large intratumorally heterogeneity in radiotracer retention, which is likely to have influenced correlations with biopsy-derived CHKα expression.Conclusions: [18F]D4-FCH is detectable in NSCLC with large intratumorally heterogeneity, which could be exploited in the future for targeting localized therapy.

Journal article

Barwick TD, Castellucci P, 2020, Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer, RADIOGRAPHICS, Vol: 40, Pages: 727-730, ISSN: 0271-5333

Journal article

Sharma R, Valls PO, Inglese M, Dubash S, Chen M, Gabra H, Montes A, Challapalli A, Arshad M, Tharakan G, Chambers E, Cole T, Lozano-Kuehne JP, Barwick TD, Aboagye EOet al., 2020, [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 47, Pages: 1239-1251, ISSN: 0340-6997

BACKGROUND: Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. PATIENTS AND METHODS: We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m2). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [18F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. RESULTS: Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki following pazopanib indicating reduced radioligand delivery and retention. CONCLUSIONS: Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti

Journal article

Ordidge KL, Gandy N, Arshad MA, Wallitt K, Soneji N, Khan S, Barwick TDet al., 2020, Interobserver agreement of the visual Herder scale for the assessment of solitary pulmonary nodules on 18F Fluorodeoxyglucose PET/computed tomography, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 41, Pages: 235-240, ISSN: 0143-3636

Journal article

Lai AYT, Riddell A, Barwick T, Boyd K, Rockall A, Kaiser M, Koh D-M, Saffar H, Yusuf S, Messiou Cet al., 2020, Interobserver agreement of whole-body magnetic resonance imaging is superior to whole-body computed tomography for assessing disease burden in patients with multiple myeloma, European Radiology, Vol: 30, Pages: 320-327, ISSN: 0938-7994

ObjectivesWhole-body MRI (WB-MRI) is recommended by the International Myeloma Working Group for all patients with asymptomatic myeloma and solitary plasmacytoma and by the UK NICE guidance for all patients with suspected myeloma. Some centres unable to offer WB-MRI offer low-dose whole-body CT (WB-CT). There are no studies comparing interobserver agreement and disease detection of contemporary WB-MRI (anatomical imaging and DWI) versus WB-CT. Our primary aim is to compare the interobserver agreement between WB-CT and WB-MRI in the diagnosis of myeloma.MethodsConsecutive patients with newly diagnosed myeloma imaged with WB-MRI and WB-CT were prospectively reviewed. For each body region and modality, two experienced and two junior radiologists scored disease burden with final scores by consensus. Intraclass correlation coefficients (ICC), median scores, Wilcoxon signed-rank test and Spearman’s correlation coefficients were calculated.ResultsThere was no significant difference in overall observer scores between WB-MRI and WB-CT (p = 0.87). For experienced observers, interobserver agreement for WB-MRI was superior to WB-CT overall and for each region, without overlap in whole-skeleton confidence intervals (ICC 0.98 versus 0.77, 95%CI 0.96–0.99 versus 0.45–0.91). For inexperienced observers, although there is a trend for a better interobserver score for the whole skeleton on WB-MRI (ICC 0.95, 95%CI 0.72–0.98) than on WB-CT (ICC 0.72, 95%CI 0.34–0.88), the confidence intervals overlap.ConclusionsWB-MRI offers excellent interobserver agreement which is superior to WB-CT for experienced observers. Although the overall burden was similar across both modalities, patients with lower disease burdens where MRI could be advantageous are not included in this series.

Journal article

Hameed M, Sandhu A, Soneji N, Amiras D, Rockall A, Messiou C, Wallitt K, Barwick TDet al., 2020, Pictorial review of whole body MRI in myeloma: emphasis on diffusion-weighted imaging, BRITISH JOURNAL OF RADIOLOGY, Vol: 93, ISSN: 0007-1285

Journal article

Gandy N, Arshad MA, Wallitt KL, Dubash S, Khan S, Barwick TDet al., 2020, Immunotherapy-related adverse effects on <SUP>18</SUP>F-FDG PET/CT imaging, BRITISH JOURNAL OF RADIOLOGY, Vol: 93, ISSN: 0007-1285

Journal article

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