Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Brain Sciences

Edmond and Lily Safra Chair. Head of Department
 
 
 
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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

594 results found

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

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

Matthews PM, 2016, Pharmacological applications of fMRI, Neuromethods, Pages: 817-831

© Springer Science+Business Media New York 2016. Increasing societal expectations for new drugs, lack of confidence in short-term endpoints related to long- term outcomes for chronic neurological and psychiatric diseases and rising costs of development in an increasing cost-constrained market all have created a sense of crisis in CNS drug development. New approaches are needed. For some time, the potential of clinical functional imaging for more confident progression from preclinical to clinical development stages has been recognized. Pharmacological functional MRI (fMRI), which refers specifically to applications of fMRI to questions in drug development, provides one set of these tools. With related structural MRI measures, relatively high resolution data concerning target, disease-relevant pathophysiology and effects of therapeutic interventions can be related to brain functional anatomy. In this chapter, current and potential applications of pharmacological fMRI for target validation, patient stratification and characterization of therapeutic molecule pharmacokinetics and pharmacodynamics are reviewed. Challenges to better realizing the promise of pharmacological fMRI will be discussed. The review concludes that there is a strong rationale for greater use of pharmacological fMRI particularly for early phase studies, but also outlines the need for preclinical and early clinical development to be more seamlessly integrated, for greater harmonization of clinical imaging methodologies and for sharing of data to facilitate these goals.

Book chapter

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

Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RDet al., 2016, A compararison of magnetization transfer methods to assess brain and cervical cord microstructure in multiple sclerosis, Journal of Neuroimaging, Vol: 27, Pages: 221-226, ISSN: 1552-6569

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, Hampshire A, 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

Poldrack RA, Baker CI, Durnez J, Gorgolewski KJ, Matthews PM, Munafò M, Nichols TE, Poline J-B, Vul E, Yarkoni Tet al., 2016, Scanning the Horizon: Towards transparent and reproducible neuroimaging research, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>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 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 lack of direct replication apply to many fields, but perhaps particularly to fMRI. 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 answers to neuroscientific questions.</jats:p>

Working paper

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: 1461-7285

Journal article

Nie L, Matthews PM, Guo Y, 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 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 non-uniformly 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

Scott G, Gunn RN, Matthews PM, Sharp DJet al., 2016, Minocycline reduces microglial activation after traumatic brain injury measured using [11C]-PBR28 positron emission tomography, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 686-687, ISSN: 1362-301X

Conference paper

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

De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw FE, 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 Het al., 2016, Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease., Journal of Cerebral Blood Flow & 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

Tiwari AD, Wu C, Zhu J, Zhang S, Zhu J, Wang WR, Zhang J, Tatsuoka C, Matthews PM, Miller RH, Wang Yet al., 2016, Design, Synthesis, and Evaluation of Fluorinated Radioligands for Myelin Imaging, Journal of Medicinal Chemistry, Vol: 59, Pages: 3705-3718, ISSN: 0022-2623

Journal article

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: 1778-3585

Journal article

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, Practical Neurology, Vol: 16, Pages: 279-287, ISSN: 1474-7766

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

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) approachfor the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonalautoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye toyield 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 focallocalization within the aortic arch and its branches, as detected by fluorescence moleculartomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocalmicroscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites ofatherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMPactivity (MMPSense-645-FAST), both probes produced statistically significant increases inNIRF signal in the Ldlr-/- model in relation to duration of HF diet. When withdrawing the HFdiet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less markedthan the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization wassuccessfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detectioncatheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parentantibody in murine atheroma showing promise for future translation.

Journal article

Vera JH, Guo Q, Cole JH, Boasso A, Greathead L, Kelleher P, Rabiner EA, Kalk N, Bishop C, Gunn RN, Matthews PM, Winston Aet al., 2016, Neuroinflammation in treated HIV-positive individuals: A TSPO PET study., Neurology, Vol: 86, Pages: 1425-1432, ISSN: 1526-632X

OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.

Journal article

Scott GPT, Ramlackhansingh A, Edison P, Hellyer PJ, Cole J, Veronese M, Leech R, Greenwood RJ, Turkheimer F, Gentleman S, Heckemann RA, Matthews PM, Brooks D, Sharp DJet al., 2016, Amyloid pathology and axonal injury after brain trauma, Neurology, Vol: 86, Pages: 821-828, ISSN: 0028-3878

Objective: To image amyloid-β (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer’s disease.Methods: Patients 11 months to 17 years after moderate-severe TBI had 11C-Pittsburgh compound-B (PIB) PET, structural and diffusion MRI and neuropsychological examination. Healthy aged controls and AD patients had PET and structural MRI. Binding potential (BPND) images of 11C-PIB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy (FA), was estimated and correlated with 11C-PIB BPND.Results: 28 participants (9 TBI, 9 controls, 10 AD) were assessed. Increased 11C-PIB BPND was found in TBI versus controls in the posterior cingulate cortex (PCC) and cerebellum. Binding in the PCC increased with decreasing FA of associated white matter tracts, and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions, but increased in the cerebellum. Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathological features of dementia, which may relate to axonal damage produced by the injury.

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 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

Miller KL, Bangerter N, Almagro FA, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Jenkinson M, Andersson J, Griffanti L, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Matthews PM, Smith SMet al., UK Biobank: Brain imaging protocols and first data release, ISMRM 24th Annual Meeting

Conference paper

Maron E, Wall M, Norbury R, Godlewska B, Terbeck S, Cowen P, Matthews P, Nutt DJet al., 2015, Effect of short-term escitalopram treatment on neural activation during emotional processing, Journal of Psychopharmacology, Vol: 30, Pages: 33-39, ISSN: 1461-7285

Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significantreduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have adistinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed toexplore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing,and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantlyreduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrusfollowing escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed thatescitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus andamygdala, an effect that seems to be distinguishable from that of other SSRIs.

Journal article

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., 2015, Hippocampal neuroinflammation, functional connectivity and depressive symptoms in multiple sclerosis, Biological Psychiatry, Vol: 80, Pages: 62-72, ISSN: 1873-2402

BackgroundDepression, 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 [18F]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.MethodsThe 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 [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [18F]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 [18F]PBR111 distribution volume ratio.ConclusionsOur 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 further investigation of t

Journal article

Matthews PM, Sudlow C, 2015, The UK Biobank, BRAIN, Vol: 138, Pages: 3463-3465, ISSN: 0006-8950

Journal article

Scott G, Hellyer PJ, Ramlackhansingh AF, Brooks DJ, Matthews PM, Sharp DJet al., 2015, Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage, Journal of Neuroinflammation, Vol: 12, ISSN: 1742-2094

BackgroundTraumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.FindingsUsing [11C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.ConclusionsThese findings support a link between axonal damage and persistent inflammation after brain injury.

Journal article

Matthews PM, 2015, New drugs and personalized medicine for multiple sclerosis, NATURE REVIEWS NEUROLOGY, Vol: 11, Pages: 614-616, ISSN: 1759-4758

Journal article

Tsinalis O, Matthews PM, Guo Y, 2015, Automatic sleep stage scoring using time-frequency analysis and stacked sparse autoencoders, Annals of Biomedical Engineering, Vol: 44, Pages: 1587-1597, ISSN: 1573-9686

We developed a machine learning methodology for automatic sleep stage scoring. Our time-frequency analysis-based feature extraction is fine-tuned to capture sleep stage-specific signal features as described in the American Academy of Sleep Medicine manual that the human experts follow. We used ensemble learning with an ensemble of stacked sparse autoencoders for classifying the sleep stages. We used class-balanced random sampling across sleep stages for each model in the ensemble to avoid skewed performance in favor of the most represented sleep stages, and addressed the problem of misclassification errors due to class imbalance while significantly improving worst-stage classification. We used an openly available dataset from 20 healthy young adults for evaluation. We used a single channel of EEG from this dataset, which makes our method a suitable candidate for longitudinal monitoring using wearable EEG in real-world settings. Our method has both high overall accuracy (78%, range 75–80%), and high mean \(F_1\)-score (84%, range 82–86%) and mean accuracy across individual sleep stages (86%, range 84–88%) over all subjects. The performance of our method appears to be uncorrelated with the sleep efficiency and percentage of transitional epochs in each recording.

Journal article

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