Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Medicine

Edmond and Lily Safra Chair and Head of Brain Sciences
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

586 results found

Matthews PM, 2017, Advanced MRI measures like DTI or fMRI should be outcome measures in future clinical trials - NO, Multiple Sclerosis Journal, Vol: 23, Pages: 1456-1458, ISSN: 1352-4585

Deep ultraviolet (DUV) light sources are used to neutralise isolated test masses in highly sensitive space-based gravitational experiments. An example is the LISA Pathfinder charge management system, which uses low-pressure mercury lamps. A future gravitational-wave observatory such as eLISA will use UV light-emitting diodes (UV LEDs), which offer numerous advantages over traditional discharge lamps. Such devices have limited space heritage but are now available from a number of commercial suppliers. Here we report on a test campaign that was carried out to quantify the general properties of three types of commercially available UV LEDs and demonstrate their suitability for use in space. Testing included general electrical and UV output power measurements, spectral stability, pulsed performance and temperature dependence, as well as thermal vacuum, radiation and vibration survivability.

Journal article

Peeters LM, Lamers I, Valkenborg D, Feys P, Somers V, Spooren A, Popescu V, Hens N, Matthews PM, Thalheim C, Van Wijmeersch B, Hellings Net al., 2017, Towards personalized therapy through extensive longitudinal follow-up using a multidisciplinary data infrastructure for people with MS: a-proof-of-concept study, 7th Joint European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)-Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 934-935, ISSN: 1352-4585

Conference paper

Datta G, Colasanti A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Van Vlierberghe E, Van Hecke W, Searle G, Santos-Ribeiro A, Matthews PMet al., 2017, Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis, Brain, Vol: 140, Pages: 2927-2938, ISSN: 1460-2156

Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient’s disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnet

Journal article

Coffey S, Lewandowski AJ, Garratt S, Meijer R, Lynum S, Bedi R, Paterson J, Yaqub M, Noble JA, Neubauer S, Petersen SE, Allen N, Sudlow C, Collins R, Matthews PM, Leeson Pet al., 2017, Protocol and quality assurance for carotid imaging in 100,000 participants of UK Biobank: development and assessment., European Journal of Preventive Cardiology, Vol: 24, Pages: 1799-1806, ISSN: 2047-4873

Background Ultrasound imaging is able to quantify carotid arterial wall structure for the assessment of cerebral and cardiovascular disease risks. We describe a protocol and quality assurance process to enable carotid imaging at large scale that has been developed for the UK Biobank Imaging Enhancement Study of 100,000 individuals. Design An imaging protocol was developed to allow measurement of carotid intima-media thickness from the far wall of both common carotid arteries. Six quality assurance criteria were defined and a web-based interface (Intelligent Ultrasound) was developed to facilitate rapid assessment of images against each criterion. Results and conclusions Excellent inter and intra-observer agreements were obtained for image quality evaluations on a test dataset from 100 individuals. The image quality criteria then were applied in the UK Biobank Imaging Enhancement Study. Data from 2560 participants were evaluated. Feedback of results to the imaging team led to improvement in quality assurance, with quality assurance failures falling from 16.2% in the first two-month period examined to 6.4% in the last. Eighty per cent had all carotid intima-media thickness images graded as of acceptable quality, with at least one image acceptable for 98% of participants. Carotid intima-media thickness measures showed expected associations with increasing age and gender. Carotid imaging can be performed consistently, with semi-automated quality assurance of all scans, in a limited timeframe within a large scale multimodality imaging assessment. Routine feedback of quality control metrics to operators can improve the quality of the data collection.

Journal article

Robinson R, Valindria V, Bai W, Suzuki H, Matthews P, Page C, Rueckert D, Glocker Bet al., 2017, Automatic quality control of cardiac MRI segmentation in large-scale population imaging, Medical Image Computing and Computer Assisted Intervention, Publisher: Springer, ISSN: 0302-9743

The trend towards large-scale studies including populationimaging poses new challenges in terms of quality control (QC). This is aparticular issue when automatic processing tools such as image segmenta-tion methods are employed to derive quantitative measures or biomarkersfor further analyses. Manual inspection and visual QC of each segmen-tation result is not feasible at large scale. However, it is important tobe able to detect when an automatic method fails to avoid inclusionof wrong measurements into subsequent analyses which could otherwiselead to incorrect conclusions. To overcome this challenge, we explorean approach for predicting segmentation quality based on reverse clas-sification accuracy, which enables us to discriminate between successfuland failed cases. We validate this approach on a large cohort of cardiacMRI for which manual QC scores were available. Our results on 7,425cases demonstrate the potential for fully automatic QC in the context oflarge-scale population imaging such as the UK Biobank Imaging Study.

Conference paper

Bai W, Oktay O, Sinclair M, Suzuki H, Rajchl M, Tarroni G, Glocker B, King A, Matthews P, Rueckert Det al., 2017, Semi-supervised learning for network-based cardiac MR image segmentation, Medical Image Computing and Computer Assisted Intervention, Publisher: Springer, ISSN: 0302-9743

Training a fully convolutional network for pixel-wise (or voxel-wise) image segmentation normally requires a large number of trainingimages with corresponding ground truth label maps. However, it is a chal-lenge to obtain such a large training set in the medical imaging domain,where expert annotations are time-consuming and difficult to obtain. Inthis paper, we propose a semi-supervised learning approach, in which asegmentation network is trained from both labelled and unlabelled data.The network parameters and the segmentations for the unlabelled dataare alternately updated. We evaluate the method for short-axis cardiacMR image segmentation and it has demonstrated a high performance,outperforming a baseline supervised method. The mean Dice overlapmetric is 0.92 for the left ventricular cavity, 0.85 for the myocardiumand 0.89 for the right ventricular cavity. It also outperforms a state-of-the-art multi-atlas segmentation method by a large margin and the speedis substantially faster.

Conference paper

Suzuki H, Gao H, Bai W, Evangelou E, Glocker B, O'Regan DP, Elliott P, Matthews PMet al., 2017, Hypertension and white matter microstructures in healthy participants in UK Biobank, Publisher: OXFORD UNIV PRESS, Pages: 248-249, ISSN: 0195-668X

Conference paper

Dong H, Supratak A, Pan W, Wu C, Matthews PM, Guo Yet al., 2017, Mixed neural network approach for temporal sleep stage classification, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol: 26, Pages: 324-333, ISSN: 1534-4320

This paper proposes a practical approach to addressing limitations posed by using of single-channel electroencephalography (EEG) for sleep stage classification. EEG-based characterizations of sleep stage progression contribute the diagnosis and monitoring of the many pathologies of sleep. Several prior reports explored ways of automating the analysis of sleep EEG and of reducing the complexity of the data needed for reliable discrimination of sleep stages at lower cost in the home. However, these reports have involved recordings from electrodes placed on the cranial vertex or occiput, which are both uncomfortable and difficult to position. Previous studies of sleep stage scoring that used only frontal electrodes with a hierarchical decision tree motivated this paper, in which we have taken advantage of rectifier neural network for detecting hierarchical features and long short-term memory (LSTM) network for sequential data learning to optimize classification performance with single-channel recordings. After exploring alternative electrode placements, we found a comfortable configuration of a single-channel EEG on the forehead and have shown that it can be integrated with additional electrodes for simultaneous recording of the electrooculogram (EOG). Evaluation of data from 62 people (with 494 hours sleep) demonstrated better performance of our analytical algorithm than is available from existing approaches with vertex or occipital electrode placements. Use of this recording configuration with neural network deconvolution promises to make clinically indicated home sleep studies practical.

Journal article

Edison P, Mayers J, Calsolaro V, Fan Z, Turton S, Venkataraman A, Femminella G, Gunn R, Rabiner E, Matthews P, Tyacke R, Nutt Det al., 2017, Dementia Platform U.K. Experimental medicine: human in vivo astroglial activation in early Alzheimer’s disease, Alzheimer's and Dementia, Vol: 13, Pages: P1073-P1074, ISSN: 1552-5260

Journal article

Nie L, Yang X, Matthews PM, Xu ZW, Guo YKet al., 2017, Inferring functional connectivity in fMRI using minimum partial correlation, International Journal of Automation and Computing, Vol: 14, Pages: 371-385, ISSN: 1751-8520

Functional connectivity has emerged as a promising approach to study the functional organisation of the brain and to define features for prediction of brain state. The most widely used method for inferring functional connectivity is Pearson-s correlation, but it cannot differentiate direct and indirect effects. This disadvantage is often avoided by computing the partial correlation between two regions controlling all other regions, but this method suffers from Berkson-s paradox. Some advanced methods, such as regularised inverse covariance, have been applied. However, these methods usually depend on some parameters. Here we propose use of minimum partial correlation as a parameter-free measure for the skeleton of functional connectivity in functional magnetic resonance imaging (fMRI). The minimum partial correlation between two regions is the minimum of absolute values of partial correlations by controlling all possible subsets of other regions. Theoretically, there is a direct effect between two regions if and only if their minimum partial correlation is non-zero under faithfulness and Gaussian assumptions. The elastic PC-algorithm is designed to efficiently approximate minimum partial correlation within a computational time budget. The simulation study shows that the proposed method outperforms o thers in most cases and its application is illustrated using a resting-state fMRI dataset from the human connectome project.

Journal article

Owen DRJ, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhir H, Peferoen LAN, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CSet al., 2017, Pro-inflammatory activation of primary microglia and macrophages increases 18kDa Translocator Protein (TSPO) expression in rodents but not humans, Journal of Cerebral Blood Flow and Metabolism, Vol: 37, Pages: 2679-2690, ISSN: 1559-7016

The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58–1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45–0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49–0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.

Journal article

Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas ELet al., 2017, Correction: Characterisation of liver fat in the UK Biobank cohort, PLoS ONE, Vol: 12, Pages: e0176867-e0176867, ISSN: 1932-6203

[This corrects the article DOI: 10.1371/journal.pone.0172921.].

Journal article

Matthews PM, Datta G, Colasanti A, KALK N, Owen D, Scott G, Rabiner E, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nei L, Battaglini M, Stefano Net al., [(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis., Journal of Nuclear Medicine, ISSN: 1535-5667

Journal article

Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EI, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews Pet al., 2017, [(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis., J Nucl Med

Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands ((11)C-PBR28 or (18)F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region). White matter lesions (WML) were classified as "active" (DVR highest in the lesion), "peripherally active" (peri-lesional DVR highest), "inactive" (DVR highest in surrounding normal appearing white matter, NAWM) or "undifferentiated" (similar DVR across lesion, peri-lesional and NAWM volumes). Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4x10-11). A higher proportion of lesions were inactive in patients with SPMS (35 %) than RRMS (23 %), but active lesions were found in all patients, including those on highly efficacious treatments. Conclusion: TSPO radioligand uptake was increased in brains of MS patients relative to healthy controls with two TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation.

Journal article

Gafson A, Craner MJ, Matthews PM, 2017, Personalised medicine for multiple sclerosis care., Multiple Sclerosis Journal, Vol: 23, Pages: 362-369, ISSN: 1477-0970

Treatments with a range of efficacy and risk of adverse events have become available for the management of multiple sclerosis (MS). However, now the heterogeneity of clinical expression and responses to treatment pose major challenges to improving patient care. Selecting and managing the drug best balancing benefit and risk demands a new focus on the individual patient. Personalised medicine for MS is based on improving the precision of diagnosis for each patient in order to capture prognosis and provide an evidence-based framework for predicting treatment response and personalising patient monitoring. It involves development of predictive models involving the integration of clinical and biological data with an understanding of the impact of disease on the lives of individual patients. Here, we provide a brief, selective review of challenges to personalisation of the management of MS and suggest an agenda for stakeholder engagement and research to address them.

Journal article

Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas ELet al., 2017, Characterisation of liver fat in the UK Biobank cohort, PLOS ONE, Vol: 12, ISSN: 1932-6203

Non-alcoholicfattyliverdiseaseandtheriskof progressionto steatohepatitis,cirrhosisandhepatocellularcarcinomahavebeenidentifiedasmajorpublichealthconcerns.Wehavedemonstratedthefeasibilityandpotentialvalueof measuringliverfatcontentbymagneticresonanceimaging(MRI)in a largepopulationin thisstudyof 4,949participants(aged45–73years)in theUKBiobankimagingenhancement. Despiterequirementsforonlya single( 3min)scanof eachsubject,liverfatwasableto bemeasuredastheMRIprotondensityfatfraction(PDFF)withanoverallsuccessrateof 96.4%.Theoverallhepaticfatdistributionwascentredbetween1–2%,andwashighlyskewedtowardshigherfatcontent.ThemeanPDFFwas3.91%,andmedian2.11%.Analysisof PDFFin conjunctionwithotherdatafieldsavailablefromtheUKBiobankResourceshowedassociationsof increasedliverfatwithgreaterage,BMI,weightgain,highbloodpressureandType2 diabetes.SubjectswithBMIlessthan25kg/m2hada lowrisk(5%)of highliverfat(PDFF>5.5%),whereasin thehigherBMIpopulation(>30kg/m2) theprevalenceof highliverfatwasapproximately1 in 3. Thesedatasuggestthatpopulationscreeningto identifypeoplewithhighPDFFis possibleandcouldbecosteffective.MRIbasedPDFFis aneffectivemethodforthis.Finally,althoughcrosssectional,thisstudysuggeststheutilityof thePDFFmeasurement withinUKBiobank,particularlyforapplicationsto elucidatingriskfactorsthroughassociationswithprospec-tivelyacquireddataonclinicaloutcomesof liverdiseases,includingnon-alcoholicfattyliverdisease.

Journal article

Shenkin SD, Pernet C, Nichols TE, Poline J-B, Matthews PM, van der Lugt A, Mackay C, Lanyon L, Mazoyer B, Boardman JP, Thompson PM, Fox N, Marcus DS, Sheikh A, Cox SR, Anblagan D, Job DE, Dickie DA, Rodriguez D, Wardlaw JMet al., 2017, Improving data availability for brain image biobanking in healthy subjects: Practice-based suggestions from an international multidisciplinary working group, NEUROIMAGE, Vol: 153, Pages: 399-409, ISSN: 1053-8119

Journal article

Giovannoni G, Cutter G, Sormani MP, Belachew S, Hyde R, Koendgen H, Knappertz V, Tomic D, Leppert D, Herndon R, Wheeler-Kingshott CAM, Ciccarelli O, Selwood D, di Cantogno EV, Ben-Amor A-F, Matthews P, Carassiti D, Baker D, Schmierer Ket al., 2017, Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses., Mult Scler Relat Disord, Vol: 12, Pages: 70-78

Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials.

Journal article

Kalk NJ, Guo Q, Owen D, Cherian R, Erritzoe D, Gilmour A, Ribeiro AS, McGonigle J, Waldman A, Matthews P, Cavanagh J, McInnes I, Dar K, Gunn R, Rabiner EA, Lingford-Hughes ARet al., 2017, Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [(11)C]PBR28 PET study, Translational Psychiatry, Vol: 7, ISSN: 2158-3188

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [(11)C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [(11)C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [(11)C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [(11)C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [(11)C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

Journal article

Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafo MR, Nichols TE, Poline J-B, Vul E, Yarkoni Tet al., 2017, Scanning the horizon: towards transparent and reproducible neuroimaging research, Nature Reviews Neuroscience, Vol: 18, Pages: 115-126, ISSN: 1471-0048

Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions that are drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.

Journal article

He S, Yong M, Matthews PM, Guo Yet al., 2016, tranSMART-XNAT Connector tranSMART-XNAT connector-image selection based on clinical phenotypes and genetic profiles., Bioinformatics, Vol: 33, Pages: 787-788, ISSN: 1367-4803

MOTIVATION: TranSMART has a wide range of functionalities for translational research and a large user community, but it does not support imaging data. In this context, imaging data typically includes 2D or 3D sets of magnitude data and metadata information. Imaging data may summarise complex feature descriptions in a less biased fashion than user defined plain texts and numeric numbers. Imaging data also is contextualised by other data sets and may be analysed jointly with other data that can explain features or their variation. RESULTS: Here we describe the tranSMART-XNAT Connector we have developed. This connector consists of components for data capture, organisation and analysis. Data capture is responsible for imaging capture either from PACS system or directly from an MRI scanner, or from raw data files. Data are organised in a similar fashion as tranSMART and are stored in a format that allows direct analysis within tranSMART. The connector enables selection and download of DICOM images and associated resources using subjects' clinical phenotypic and genotypic criteria. AVAILABILITY AND IMPLEMENTATION: tranSMART-XNAT connector is written in Java/Groovy/Grails. It is maintained and available for download at https://github.com/sh107/transmart-xnat-connector.git

Journal article

Datta G, Violante IR, Scott G, Zimmerman K, Santos-Ribeiro A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Matthews PMet al., 2016, Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis., Multiple Sclerosis, Vol: 23, Pages: 1469-1478, ISSN: 1352-4585

BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied. TSPO PET imaging with [(11)C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). RESULTS: [(11)C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [(11)C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [(11)C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [(11)C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. CONCLUSION: MRS [ myo-inositol] and PET [(11)C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [(11)C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.

Journal article

Dichgans M, Wardlaw J, Smith E, Zietemann V, Seshadri S, Sachdev P, Biessels GJ, Fazekas F, Benavente O, Pantoni L, De Leeuw F, Norrving B, Matthews P, Chen C, Mok V, Duering M, Whiteley W, Shuler K, Alonso A, Black SE, Brayne C, Chabriat H, Cordonnier C, Doubal F, Duzel E, Ewers M, Frayne R, Hachinski V, Ikram MA, Jessen F, Jouvent E, Linn J, O'Brien J, van Oostenbrugge R, Malik R, Mazoyer B, Schmidt R, Sposato LA, Stephan B, Swartz RH, Vernooij M, Viswanathan A, Werring D, Abe K, Allan L, Arba F, Bae H-J, Bath PMW, Bordet R, Breteler M, Choi S, Deary I, DeCarli C, Ebmeier K, Feng L, Greenberg SM, Ihara M, Kalaria R, Kim S, Lim J-S, Lindley RI, Mead G, Murray A, Quinn T, Ritchie C, Sacco R, Salman RA-S, Sprigg N, Sudlow C, Thomas A, van Boxtel M, van der Grond J, van der Lugt A, Yang Y-Het al., 2016, METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research, ALZHEIMERS & DEMENTIA, Vol: 12, Pages: 1235-1249, ISSN: 1552-5260

Journal article

Newbould R, Muraro P, Bishop C, Waldman Aet al., 2016, Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions, NeuroImage-Clinical, Vol: 13, Pages: 9-15, ISSN: 2213-1582

Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between “younger” and “older” onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses.21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors.Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group.These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.

Journal article

Dong H, Matthews P, Guo Y, 2016, A new soft material based in-the-ear EEG recording technique, The 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’16), Publisher: IEEE

Long-term electroencephalogram (EEG) is important for seizure detection, sleep monitoring and etc. In-the- ear EEG device makes such recording robust to noise and privacy protected (invisible to other people). However, the state-of-art techniques suffer from various drawbacks such as customization for specific users, manufacturing difficulties and short life cycle. To address these issues, we proposed silvered glass silicone based in-the-ear electrode which can be manufactured using conventional compression moulding. The material and in-the-ear EEG are evaluated separately, showing that the proposed method is durable, low-cost and easy-to-make.

Conference paper

Russo E, Khan S, Janisch R, Gunn R, Rabiner E, Taylor SA, Matthews P, Orchard Tet al., 2016, Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease., Inflammatory Bowel Diseases, ISSN: 1536-4844

Background: 18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has recently attracted interest for the measurement ofdisease activity in Crohn’s disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activityand its response to treatment in patients with CD.Methods: Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used toassess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity(Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component andunderwent scanning before and 12 weeks after the initiation of anti–tumor necrosis factor alpha therapy. Patients were subcategorized on the basis ofa clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took partin the test–retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures.Results: The sensitivity and specificity of 18F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measurescorrelated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEANdemonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt .0.80 and % variability ,20%) compared with volumedependentFDG-PET measures. A proportion of the FDG signal (10%–30%) was found to originate from the lumen of diseased segments.Conclusions: 18F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.

Journal article

Paley C, Hull H, Ji Y, Toro-Ramos T, Thornton J, Bauer J, Matthews P, Yu A, Navder K, Dorsey K, Gallagher Det al., 2016, Body fat differences by self-reported race/ethnicity in healthy term newborns., Pediatr Obes, Vol: 11, Pages: 361-368

BACKGROUND: Ethnic differences in total body fat (fat mass [FM]) have been reported in adults and children, but the timing of when these differences manifest and whether they are present at birth are unknown. OBJECTIVES: This study aimed to assess whether ethnic differences in body fat are present at birth in healthy infants born at term, where body fat is measured using air displacement plethysmography and fat distribution by skin-fold thickness. METHODS: Data were from a multiracial cross-sectional convenience sample of 332 term infants from four racial or ethnic groups based on maternal self-report (A, Asian; AA, non-Hispanic Black [African-American]; C, non-Hispanic White; and H, Hispanic). The main outcome measure was infant body fat at 1-3 days after birth, with age, birth weight, gestational age and maternal pre-pregnancy weight as covariates. RESULTS: Significant effects for race (P = 0.0011), sex (P = 0.0051) and a race by sex interaction (P = 0.0236) were found. C females had higher FM than C males (P = 0.0001), and AA females had higher FM than AA males (P = 0.0205). C males had less FM than A males (P = 0.0353) and H males (P = 0.0001). CONCLUSION: Race/ethnic and sex differences in FM are present in healthy term newborns. Although the implications of these differences are unclear, studies beginning in utero and birth set the stage for a life course approach to understanding disease later in life.

Journal article

Ricotti V, Evans MR, Sinclair CD, Butler JW, Ridout DA, Hogrel JY, Emira A, Morrow JM, Reilly MM, Hanna MG, Janiczek RL, Matthews PM, Yousry TA, Muntoni F, Thornton JSet al., 2016, Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials., PLOS One, Vol: 11, ISSN: 1932-6203

OBJECTIVE: A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. METHODS: 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. RESULTS: Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001). A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7), accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9) and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8). CONCLUSIONS: These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and func

Journal article

Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JL, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SMet al., 2016, Multimodal population brain imaging in the UK Biobank prospective epidemiological study, Nature Neuroscience, Vol: 19, Pages: 1523-1536, ISSN: 1546-1726

Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank.

Journal article

James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei Met al., 2016, Corrigendum to “Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning” [Eur. Psychiatry 35C (2016) 32–38], European Psychiatry, Vol: 38, Pages: 22-22, ISSN: 1778-3585

Journal article

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