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

 

Mr Noel Caliste +44 (0)20 7594 2855

 
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Location

 

E515Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

533 results found

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

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

Bishop CA, Newbould RD, Lee JSZ, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD, Bishop CA, Newbould RD, Lee JS, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD, Bishop CA, Newbould RD, Lee JSZ, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD, Bishop CA, Newbould RD, Lee JS, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD, Bishop CA, Newbould RD, Lee JSZ, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD, Newbould R, Muraro P, Bishop C, Waldman Aet al., 2017, 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

Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EIA, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews P, Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EIA, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews P, Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EIA, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews P, 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, Pages: jnumed.116.187161-jnumed.116.187161, ISSN: 0161-5505

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, Gafson A, Craner MJ, Matthews PM, Gafson A, Craner MJ, Matthews PM, Gafson A, Craner MJ, Matthews PM, Gafson A, Craner MJ, Matthews PMet al., 2017, Personalised medicine for multiple sclerosis care, MULTIPLE SCLEROSIS JOURNAL, Vol: 23, Pages: 362-369, ISSN: 1352-4585

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

He S, Yong M, Matthews PM, Guo Y, He S, Yong M, Matthews PM, Guo Y, He S, Yong M, Matthews PM, Guo Y, He S, Yong M, Matthews PM, Guo Y, He S, Yong M, Matthews PM, Guo Y, He S, Yong M, Matthews PM, Guo Yet al., 2017, 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. Contact: sijin@ebi.ac.uk.

JOURNAL ARTICLE

Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD, Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD, Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD, Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD, Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD, Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RDet al., 2017, A Comparison of Magnetization Transfer Methods to Assess Brain and Cervical Cord Microstructure in Multiple Sclerosis, JOURNAL OF NEUROIMAGING, Vol: 27, Pages: 221-226, ISSN: 1051-2284

BACKGROUND: Demyelination is a core pathological feature of multiple sclerosis (MS) and spontaneous remyelination appears to be an important mechanism for repair in the disease. Magnetization transfer ratio imaging (MTR) has been used extensively to evaluate demyelination, although limitations to its specificity are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a mixed group of subjects with active MS, to explore their relative sensitivity to pathology relevant to explaining clinical outcomes. METHODS: A total of 134 subjects underwent MRI of their brain and cervical spinal cord. Isotropic 3-dimensional pre- and postcontrast T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) volumes were segmented into brain normal appearing white matter (NAWM), brain WM lesions (WML), normal appearing spinal cord (NASC), and spinal cord lesions. Volumes and metrics for MTR and MTsat histograms were calculated for each region. RESULTS: Significant Spearman correlations were found with the Expanded Disability Status Scale and timed 25-foot walk for the whole brain and WML MTR, but not in that from the NAWM or any cervical spinal cord region. By contrast, the MTsat was correlated with both disability metrics in all these regions in both the brain and spine. CONCLUSIONS: This study extends prior work relating atrophy and lesion load with disability, by characterization of MTsat parameters. MTsat is practical in routine clinical applications and may be more sensitive to tissue damage than MTR for both brain and cervical spinal cord.

JOURNAL ARTICLE

Matthews PM, Matthews PM, 2017, Advanced MRI measures like DTI or fMRI should be outcome measures in future clinical trials - NO., Mult Scler, ISSN: 1352-4585

JOURNAL ARTICLE

Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LAN, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS, Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LA, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS, Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LA, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS, Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LAN, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS, 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 18 kDa translocator protein expression in rodents but not humans, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 37, Pages: 2679-2690, ISSN: 0271-678X

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 (3)H-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

Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafo MR, Nichols TE, Poline J-B, Vul E, Yarkoni T, Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafò MR, Nichols TE, Poline J-B, Vul E, Yarkoni T, Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafò MR, Nichols TE, Poline J-B, Vul E, Yarkoni T, Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafò MR, Nichols TE, Poline J-B, Vul E, Yarkoni T, 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: 1471-003X

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

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

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 JM, BRAINS Brain Imaging in Normal Subjects Expert Working Group, 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 JM, BRAINS Brain Imaging in Normal Subjects Expert Working Group, 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 JM, 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

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.

JOURNAL ARTICLE

Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL, Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL, Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL, Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL, 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, Pages: e0172921-e0172921, ISSN: 1932-6203

Non-alcoholic fatty liver disease and the risk of progression to steatohepatitis, cirrhosis and hepatocellular carcinoma have been identified as major public health concerns. We have demonstrated the feasibility and potential value of measuring liver fat content by magnetic resonance imaging (MRI) in a large population in this study of 4,949 participants (aged 45-73 years) in the UK Biobank imaging enhancement. Despite requirements for only a single (≤3min) scan of each subject, liver fat was able to be measured as the MRI proton density fat fraction (PDFF) with an overall success rate of 96.4%. The overall hepatic fat distribution was centred between 1-2%, and was highly skewed towards higher fat content. The mean PDFF was 3.91%, and median 2.11%. Analysis of PDFF in conjunction with other data fields available from the UK Biobank Resource showed associations of increased liver fat with greater age, BMI, weight gain, high blood pressure and Type 2 diabetes. Subjects with BMI less than 25 kg/m2 had a low risk (5%) of high liver fat (PDFF > 5.5%), whereas in the higher BMI population (>30 kg/m2) the prevalence of high liver fat was approximately 1 in 3. These data suggest that population screening to identify people with high PDFF is possible and could be cost effective. MRI based PDFF is an effective method for this. Finally, although cross sectional, this study suggests the utility of the PDFF measurement within UK Biobank, particularly for applications to elucidating risk factors through associations with prospectively acquired data on clinical outcomes of liver diseases, including non-alcoholic fatty liver disease.

JOURNAL ARTICLE

Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA, Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA, Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA, Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA, Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA, Colasanti A, Guo, Giannetti P, Wall M, Newbould R, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PM, Malik O, Owen D, Young AH, Gunn R, Piccini P, Matthews P, Rabiner Eet al., 2016, Hippocampal Neuroinflammation, Functional Connectivity, and Depressive Symptoms in Multiple Sclerosis, BIOLOGICAL PSYCHIATRY, Vol: 80, Pages: 62-72, ISSN: 0006-3223

BACKGROUND: Depression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [(18)F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging. METHODS: The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [(18)F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [(18)F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS. RESULTS: Patients with MS had an increased hippocampal [(18)F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [(18)F]PBR111 distribution volume ratio. CONCLUSIONS: Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to furth

JOURNAL ARTICLE

Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, O'Byrne KT, Bell JD, Dhillo WS, Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, O'Byrne KT, Bell JD, Dhillo WS, Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, O Byrne KT, Bell JD, Dhillo WS, Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, O'Byrne KT, Bell JD, Dhillo WS, Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, OByrne KT, Bell JD, Dhillo WS, Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM, O'Byrne KT, Bell JD, Dhillo WSet al., 2016, Kisspeptin signaling in the amygdala modulates reproductive hormone secretion, BRAIN STRUCTURE & FUNCTION, Vol: 221, Pages: 2035-2047, ISSN: 1863-2653

Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to hypothalamic centers involved in gonadotropin secretion. We therefore hypothesized that kisspeptin has effects on neuronal activation and reproductive pathways beyond the hypothalamus and particularly within the amygdala. To test this, we mapped brain neuronal activity (using manganese-enhanced MRI) associated with peripheral kisspeptin administration in rodents. We also investigated functional relevance by measuring the gonadotropin response to direct intra-medial amygdala (MeA) administration of kisspeptin and kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked decrease in signal intensity in the amygdala compared to vehicle alone. This was associated with an increase in luteinizing hormone (LH) secretion. In addition, intra-MeA administration of kisspeptin resulted in increased LH secretion, while blocking endogenous kisspeptin signaling within the amygdala by administering intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse frequency. We provide evidence for the first time that neuronal activity within the amygdala is decreased by peripheral kisspeptin administration and that kisspeptin signaling within the amygdala contributes to the modulation of gonadotropin release and pulsatility. Our data suggest that kisspeptin is a 'master regulator' of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion.

JOURNAL ARTICLE

Datta G, Colasanti A, Kalk NJ, Owen DR, Scott G, Rabiner EA, Gunn RN, Lingford-Hughes AR, Malik O, Ciccarelli O, Nicholas R, Battaglini M, Stefano ND, Matthews PMet al., 2016, In vivo translocator protein positron emission tomography imaging detects a heterogeneity of lesion inflammatory activity in multiple sclerosis not evident by MRI., 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 36-37, ISSN: 1352-4585

CONFERENCE PAPER

Datta G, Violante IR, Scott G, Zimmerman K, Santos-Ribeiro A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Matthews PM, Datta G, Violante IR, Scott G, Zimmerman K, Santos-Ribeiro A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Matthews PM, 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., Mult Scler, Pages: 1352458516681504-135245851668150, 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

De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw F-E, Dichgans M, Doubal F, Duering M, Dufouil C, Duzel E, Fazekas F, Hachinski V, Ikram MA, Linn J, Matthews PM, Mazoyer B, Mok V, Norrving B, O'Brien JT, Pantoni L, Ropele S, Sachdev P, Schmidt R, Seshadri S, Smith EE, Sposato LA, Stephan B, Swartz RH, Tzourio C, van Buchem M, van der Lugt A, van Oostenbrugge R, Vernooij MW, Viswanathan A, Werring D, Wollenweber F, Wardlaw JM, Chabriat H, De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw F-E, Dichgans M, Doubal F, Duering M, Dufouil C, Duzel E, Fazekas F, Hachinski V, Ikram MA, Linn J, Matthews PM, Mazoyer B, Mok V, Norrving B, O'Brien JT, Pantoni L, Ropele S, Sachdev P, Schmidt R, Seshadri S, Smith EE, Sposato LA, Stephan B, Swartz RH, Tzourio C, van Buchem M, van der Lugt A, van Oostenbrugge R, Vernooij MW, Viswanathan A, Werring D, Wollenweber F, Wardlaw JM, Chabriat H, De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw F-E, Dichgans M, Doubal F, Duering M, Dufouil C, Duzel E, Fazekas F, Hachinski V, Ikram MA, Linn J, Matthews PM, Mazoyer B, Mok V, Norrving B, O'Brien JT, Pantoni L, Ropele S, Sachdev P, Schmidt R, Seshadri S, Smith EE, Sposato LA, Stephan B, Swartz RH, Tzourio C, van Buchem M, van der Lugt A, van Oostenbrugge R, Vernooij MW, Viswanathan A, Werring D, Wollenweber F, Wardlaw JM, Chabriat H, De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw F-E, Dichgans M, Doubal F, Duering M, Dufouil C, Duzel E, Fazekas F, Hachinski V, Ikram MA, Linn J, Matthews PM, Mazoyer B, Mok V, Norrving B, OBrien JT, Pantoni L, Ropele S, Sachdev P, Schmidt R, Seshadri S, Smith EE, Sposato LA, Stephan B, Swartz RH, Tzourio C, van Buchem M, van der Lugt A, van Oostenbrugge R, Vernooij MW, Viswanathan A, Werring D, Wollenweber F, Wardlaw JM, Chabriat H, De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuet al., 2016, Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 36, Pages: 1319-1337, ISSN: 0271-678X

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.

JOURNAL ARTICLE

Dong H, Matthews PM, Guo Y, Dong H, Matthews PM, Guo Y, Dong H, Matthews P, Guo Yet al., 2016, A New Soft Material Based In-the-Ear EEG Recording Technique, 38th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC), Publisher: IEEE, Pages: 5709-5712, ISSN: 1557-170X

© 2016 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

Gafson AR, Nicholas R, Giovannoni G, Matthews PMet al., 2016, Plasma cytokine concentration changes in multiple sclerosis patients after treatment with dimethyl fumarate, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 670-671, ISSN: 1352-4585

CONFERENCE PAPER

James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandes HM, Matthews PM, Zarei Met al., 2016, Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning (vol 35C, pg 32, 2016), EUROPEAN PSYCHIATRY, Vol: 38, Pages: 22-22, ISSN: 0924-9338

JOURNAL ARTICLE

James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandez H, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandez H, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandez H, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandez H, Matthews PM, Zarei M, James A, Joyce E, Lunn D, Hough M, Kenny L, Ghataorhe P, Fernandez H, Matthews PM, Zarei Met al., 2016, Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning, EUROPEAN PSYCHIATRY, Vol: 35, Pages: 32-38, ISSN: 0924-9338

BACKGROUND: Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is hypothesised, in part, to reflect functional dysconnectivity between the frontal cortex and the striatum, although structural abnormalities consistent with this hypothesis have not yet been demonstrated in adolescence. OBJECTIVE: To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS. DESIGN: A MRI volumetric and diffusion tensor imaging study. PARTICIPANTS: Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects. OUTCOME MEASURES: Using probabilistic tractography, cortical regions with the highest connection probability for each striatal voxel were determined, and correlated with IQ and specific cognitive functions after co-varying for age and sex. Fractional anisotropy (FA) from individual tracts was a secondary measure. RESULTS: Bayesian Structural Equation modeling of FA from 12 frontostriatal tracts showed processing speed to be an intermediary variable for cognition. AOS patients demonstrated generalised cognitive impairment with specific deficits in verbal learning and memory and in processing speed after correction for IQ. Dorsolateral prefrontal cortex connectivity with the striatum correlated positively with these measures and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdalohippocampal complex, right anterior cingulate cortex, left medial orbitofrontal cortex and right dorsolateral prefrontal cortex. CONCLUSIONS: Frontostriatal dysconnectivity in large WM tracts that can explain core cognitive deficits are evident during adolescence. Processing speed, which is affected by alterations in WM connectivity, appears an intermediary variable in the cognitive deficits seen in schizophrenia.

JOURNAL ARTICLE

Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang S-H, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DO, Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang S-H, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DO, Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang S-H, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DO, Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang S-H, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DO, Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang S-H, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DOet al., 2016, Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approach for the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonal autoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye to yield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions. Injection of LO1-750 into high fat (HF) fed atherosclerotic Ldlr(-/-) mice led to specific focal localization within the aortic arch and its branches, as detected by fluorescence molecular tomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocal microscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites of atherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMP activity (MMPSense-645-FAST), both probes produced statistically significant increases in NIRF signal in the Ldlr(-/-) model in relation to duration of HF diet. Upon withdrawing the HF diet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less marked than the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization was successfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detection catheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parent antibody in murine atheroma showing promise for future translation.

JOURNAL ARTICLE

Lovestone S, Rossor M, Gallacher J, Ritchie C, Burn D, Hyslop PSG, Mackay C, Matthews PM, Ballard C, Georges J, Lovestone S, Rossor M, Gallacher J, Ritchie C, Burn D, Hyslop PSG, Mackay C, Matthews PM, Ballard C, Georges J, Lovestone S, Rossor M, Gallacher J, Ritchie C, Burn D, Hyslop PSG, Mackay C, Matthews PM, Ballard C, Georges J, Lovestone S, Rossor M, Gallacher J, Ritchie C, Burn D, Hyslop PSG, Mackay C, Matthews PM, Ballard C, Georges J, Lovestone S, Rossor M, Gallacher J, Ritchie C, Burn D, Hyslop PS, Mackay C, Matthews PM, Ballard C, Georges Jet al., 2016, Better together for better dementia research and care, LANCET PSYCHIATRY, Vol: 3, Pages: 503-504, ISSN: 2215-0374

JOURNAL ARTICLE

Maron E, Near J, Wallis G, Stokes M, Matthews PM, Nutt DJ, Maron E, Near J, Wallis G, Stokes M, Matthews PM, Nutt DJ, Maron E, Near J, Wallis G, Stokes M, Matthews PM, Nutt DJ, Maron E, Near J, Wallis G, Stokes M, Matthews PM, Nutt DJ, Maron E, Near J, Wallis G, Stokes M, Matthews PM, Nutt DJet al., 2016, A pilot study of the effect of short-term escitalopram treatment on brain metabolites and gamma-oscillations in healthy subjects, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 30, Pages: 579-580, ISSN: 0269-8811

JOURNAL ARTICLE

Matthews PM, Hampshire A, Matthews PM, Hampshire A, Matthews PM, Hampshire A, Matthews PM, Hampshire A, Matthews PM, Hampshire A, Matthews PM, Hampshire Aet al., 2016, Clinical Concepts Emerging from fMRI Functional Connectomics, NEURON, Vol: 91, Pages: 511-528, ISSN: 0896-6273

Recent advances in connectomics have led to a synthesis of perspectives regarding the brain's functional organization that reconciles classical concepts of localized specialization with an appreciation for properties that emerge from interactions across distributed functional networks. This provides a more comprehensive framework for understanding neural mechanisms of normal cognition and disease. Although fMRI has not become a routine clinical tool, research has already had important influences on clinical concepts guiding diagnosis and patient management. Here we review illustrative examples. Studies demonstrating the network plasticity possible in adults and the global consequences of even focal brain injuries or disease both have had substantial impact on modern concepts of disease evolution and expression. Applications of functional connectomics in studies of clinical populations are challenging traditional disease classifications and helping to clarify biological relationships between clinical syndromes (and thus also ways of extending indications for, or "re-purposing," current treatments). Large datasets from prospective, longitudinal studies promise to enable the discovery and validation of functional connectomic biomarkers with the potential to identify people at high risk of disease before clinical onset, at a time when treatments may be most effective. Studies of pain and consciousness have catalyzed reconsiderations of approaches to clinical management, but also have stimulated debate about the clinical meaningfulness of differences in internal perceptual or cognitive states inferred from functional connectomics or other physiological correlates. By way of a closing summary, we offer a personal view of immediate challenges and potential opportunities for clinically relevant applications of fMRI-based functional connectomics.

JOURNAL ARTICLE

Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds R, Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds R, Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds R, Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds R, Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds R, Matthews PM, Roncaroli F, Waldman A, Sormani MP, De Stefano N, Giovannoni G, Reynolds Ret al., 2016, A practical review of the neuropathology and neuroimaging of multiple sclerosis., Pract Neurol, Vol: 16, Pages: 279-287, ISSN: 1474-7758

The variability in the severity and clinical course of multiple sclerosis (MS) has as its basis an extreme heterogeneity in the location, nature and extent of pathology in the brain and spinal cord. Understanding the underlying neuropathology and associated pathogenetic mechanisms of the disease helps to communicate the rationale for treatment and disease monitoring to patients. Neuroimaging is an important tool for this: it allows clinicians to relate neuropathological changes to clinical presentations and to monitor the course of their disease. Here, we review MS neuropathology and its imaging correlates to provide a practical guide for using MRI to assess disease severity and treatment responses. This provides a foundation for optimal management of patients based on the principle that they show 'no evidence of disease activity'.

JOURNAL ARTICLE

Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JLR, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu J, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SM, Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JLR, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SM, Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JLR, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SM, Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JLR, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SM, 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: 1097-6256

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

Nie L, Matthews PM, Guo Y, Nie L, Matthews PM, Guo Y, Nie L, Matthews PM, Guo Y, Nie L, Matthews PM, Guo Y, Nie L, Matthews PM, Guo Y, Nie L, Matthews PM, Guo Yet al., 2016, Inferring Individual-Level Variations in the Functional Parcellation of the Cerebral Cortex, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 63, Pages: 2505-2517, ISSN: 0018-9294

OBJECTIVE: Functional parcellation of the cerebral cortex is variable across different subjects or between cognitive states. Ignoring individual-or state-dependent variations in the functional parcellation may lead to inaccurate representations of individual functional connectivity, limiting the precision of interpretations of differences in individual connectivity profiles. However, it is difficult to infer the individual-level variations due to the relatively low robustness of methods for parcellation of individual subjects. METHODS: We propose a method called "joint K-means" to robustly parcellate the cerebral cortex using functional magnetic resonance imaging (fMRI) data for contrasts between two states or subjects that intended to characterize variance in individual functional parcellations. The key idea of the proposed method is to jointly infer parcellations in contrasted datasets by iterative descent, while constraining the similarity of the two pathways in searches for local minima to reduce spurious variations. RESULTS: Parcellations of resting-state fMRI datasets from the Human Connectome Project show that the similarity of parcellations for an individual subject studied on two sessions is greater than that between different subjects. Differences in parcellations between subjects are nonuniformly distributed across the cerebral cortex, with clusters of higher variance in the prefrontal, lateral temporal, and occipito-parietal cortices. This pattern is reproducible across sessions, between groups, and using different numbers of parcels. CONCLUSION: The individual-level variations inferred by the proposed method are plausible and consistent with the previously reported functional connectivity variability. SIGNIFICANCE: The proposed method is a promising tool for investigating relationships between the cerebral functional organization and behavioral differences.

JOURNAL ARTICLE

Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, Young AA, Hudson S, Weale P, Garratt S, Collins R, Piechnik S, Neubauer S, Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, Young AA, Hudson S, Weale P, Garratt S, Collins R, Piechnik S, Neubauer S, Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, Young AA, Hudson S, Weale P, Garratt S, Collins R, Piechnik S, Neubauer S, Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, Young AA, Hudson S, Weale P, Garratt S, Collins R, Piechnik S, Neubauer S, Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, Young AA, Hudson S, Weale P, Garratt S, Collins R, Piechnik S, Neubauer Set al., 2016, UK Biobank's cardiovascular magnetic resonance protocol., Journal of Cardiovascular Magnetic Resonance, Vol: 18, ISSN: 1532-429X

BACKGROUND: UK Biobank's ambitious aim is to perform cardiovascular magnetic resonance (CMR) in 100,000 people previously recruited into this prospective cohort study of half a million 40-69 year-olds. METHODS/DESIGN: We describe the CMR protocol applied in UK Biobank's pilot phase, which will be extended into the main phase with three centres using the same equipment and protocols. The CMR protocol includes white blood CMR (sagittal anatomy, coronary and transverse anatomy), cine CMR (long axis cines, short axis cines of the ventricles, coronal LVOT cine), strain CMR (tagging), flow CMR (aortic valve flow) and parametric CMR (native T1 map). DISCUSSION: This report will serve as a reference to researchers intending to use the UK Biobank resource or to replicate the UK Biobank cardiovascular magnetic resonance protocol in different settings.

JOURNAL ARTICLE

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