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

585 results found

Colasanti A, Guo Q, Onega M, Giannetti P, Thomas C, Piccini P, Matthews PM, Gunn RN, Rabiner EAet al., 2012, [F-18]PBR111 binding in multiple sclerosis: relationship to age and clinical variables, 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: NATURE PUBLISHING GROUP, Pages: S22-S22, ISSN: 0271-678X

CONFERENCE PAPER

Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini Pet al., 2012, Increased PK11195 PET binding in the cortex of patients with MS correlates with disability, NEUROLOGY, Vol: 79, Pages: 523-530, ISSN: 0028-3878

JOURNAL ARTICLE

Tomassini V, Johansen-Berg H, Jbabdi S, Wise RG, Pozzilli C, Palace J, Matthews PMet al., 2012, Relating Brain Damage to Brain Plasticity in Patients With Multiple Sclerosis, NEUROREHABILITATION AND NEURAL REPAIR, Vol: 26, Pages: 581-593, ISSN: 1545-9683

JOURNAL ARTICLE

Strijbis E, Inkster B, Vounou M, Naegelin Y, Kappos L, Radue EW, Matthews P, Uitdehaag B, Barkhof F, Polman C, Montana G, Geurts Jet al., 2012, Glutamate gene polymorphisms predict brain volumes in multiple sclerosis, Multiple Sclerosis Journal

JOURNAL ARTICLE

Newbould RD, Miller SR, Toms LD, Swann P, Tielbeek JAW, Gold GE, Strachan RK, Taylor PC, Matthews PM, Brown APet al., 2012, T2* measurement of the knee articular cartilage in osteoarthritis at 3T, JOURNAL OF MAGNETIC RESONANCE IMAGING, Vol: 35, Pages: 1422-1429, ISSN: 1053-1807

JOURNAL ARTICLE

De Silva A, Salem V, Matthews PM, Dhillo WSet al., 2012, The Use of Functional MRI to Study Appetite Control in the CNS, EXPERIMENTAL DIABETES RESEARCH, Vol: 2012, ISSN: 1687-5214

Functional magnetic resonance imaging (fMRI) has provided the opportunity to safely investigate the workings of the humanbrain. This paper focuses on its use in the field of human appetitive behaviour and its impact in obesity research. In the presentabsence of any safe or effective centrally acting appetite suppressants, a better understanding of how appetite is controlled is vitalfor the development of new antiobesity pharmacotherapies. Early functional imaging techniques revealed an attenuation of brainreward area activity in response to visual food stimuli when humans are fed—in other words, the physiological state of hungersomehow increases the appeal value of food. Later studies have investigated the action of appetite modulating hormones on thefMRI signal, showing how the attenuation of brain reward region activity that follows feeding can be recreated in the fasted state bythe administration of anorectic gut hormones. Furthermore, differences in brain activity between obese and lean individuals haveprovided clues about the possible aetiology of overeating. The hypothalamus acts as a central gateway modulating homeostatic andnonhomeostatic drives to eat. As fMRI techniques constantly improve, functional data regarding the role of this small but hugelyimportant structure in appetite control is emerging.

JOURNAL ARTICLE

Matthews PM, 2012, An introduction to functional magnetic resonance imaging of the brain, Functional Magnetic Resonance Imaging: An Introduction to Methods, ISBN: 9780192630711

© Oxford University Press 2001. All rights reserved. This chapter provides an overview of functional magnetic resonance imaging (fMRI) methods and applications, highlighting key concepts and strategies, and includes the full range of techniques by which physiological changes accompanying brain activity are defined. It focuses on the changes in blood oxygenation and flow that have been used for the functional magnetic resonance imaging methods. Direct imaging of the blood flow response using perfusion MRI is also discussed. The study furthermore deals with elegant methods that have been developed and allow an extension of this simple concept for one-dimensional imaging into methods for multi-slice two-dimensional or threedimensional imaging. It outlines the major issues in statistical analysis for fMRI and addresses ways in which the data can be prepared for analysis to minimize artefacts and maximize sensitivity for the detection of activation changes. Finally, the chapter discusses the various applications of fMRI in neuroscience.

BOOK CHAPTER

Jezzard P, Matthews PM, Smith SM, 2012, Functional magnetic resonance imaging: An introduction to methods, ISBN: 9780192630711

© Oxford University Press 2001. All rights reserved. This book provides an introduction to functional magnetic resonance imaging (fMRI), the scanning technique that allows the mapping of active processes within the brain. There are six sections to the book, with chapters from an international team. Part I provides a broad overview of the field and sets the context. Part II describes the physiological and physical background to fMRI, including coverage of the hardware required and pulse-sequence selection. Practical issues involving experimental design of the paradigms, psycho-physical stimulus delivery, and subject response are covered in Part III, followed by a comprehensive treatment of data analysis in Part IV. Part V deals with practical applications of the technique in the field of neuroscience and in clinical practice. The final section describes how fMRI can be integrated with other neuro-electromagnetic functional mapping techniques.

BOOK

Inkster B, Rao AW, Ridler K, Filippini N, Whitcher B, Nichols TE, Wetten S, Gibson RA, Borrie M, Kertesz A, Guzman DA, Loy-English I, Williams J, Saemann PG, Auer DP, Holsboer F, Tozzi F, Muglia P, Merlo-Pich E, Matthews PMet al., 2012, Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease, NEUROBIOLOGY OF AGING, Vol: 33, Pages: 457-465, ISSN: 0197-4580

JOURNAL ARTICLE

Filippini N, Nickerson LD, Beckmann CF, Ebmeier KP, Frisoni GB, Matthews PM, Smith SM, Mackay CEet al., 2012, Age-related adaptations of brain function during a memory task are also present at rest, NEUROIMAGE, Vol: 59, Pages: 3821-3828, ISSN: 1053-8119

JOURNAL ARTICLE

Gupta RK, Newbould RD, Matthews PM, 2012, Methods of measuring lung water, Journal of the Intensive Care Society, Vol: 13, Pages: 209-215, ISSN: 1751-1437

Pulmonary oedema can result from both cardiogenic and non-cardiogenic aetiologies and is a cause of considerable morbidity and mortality. Accurate methods of quantifying pulmonary oedema are needed for both clinical and research purposes. Applications could include early recognition, and thus prevention, of impending decompensation in heart failure patients, guidance of fluid management in patients with established pulmonary oedema, and as a pharmacodynamic outcome measure for early clinical trials of drugs for the treatment of pulmonary oedema. Magnetic resonance imaging, computed tomography, positron emission tomography, electrical impedance, and thermodilution methods have all been used with the aim of measuring lung water. These methods differ in their accuracy, cost, ionising radiation dose, invasiveness, portability, and ability to provide dynamic measures. To date, none have been established as a 'gold standard' clinical measurement to improve clinical outcomes or to assist drug development. This review aims to discuss each of these methods in turn, focussing on advantages, limitations, and possible future development and applications. © The Intensive Care Society 2012.

JOURNAL ARTICLE

Salem V, De Silva A, Matthews PM, Dhillo WSet al., 2012, Imaging the neuroendocrinology of appetite., Adipocyte, Vol: 1, Pages: 68-72, ISSN: 2162-3945

Functional magnetic resonance imaging has become a powerful tool to investigate the neuroendocrinology of appetite. In a recent study, we demonstrated that the brain activation pattern seen following the infusion of the anorectic gut hormones PYY3-36and GLP-17-36 amideto fasted individuals resembles the brain activation pattern seen in the physiological satiated state. This commentary discusses the significance of these findings and compares them with other landmark studies in the field, with specific reference to the brain areas involved in appetite regulation. We highlight the importance of this type of research in order to pave the way for the development of efficacious and safe anti-obesity therapies.

JOURNAL ARTICLE

Newbould RD, Miller SR, Tielbeek JAW, Toms LD, Rao AW, Gold GE, Strachan RK, Taylor PC, Matthews PM, Brown APet al., 2012, Reproducibility of sodium MRI measures of articular cartilage of the knee in osteoarthritis, OSTEOARTHRITIS AND CARTILAGE, Vol: 20, Pages: 29-35, ISSN: 1063-4584

JOURNAL ARTICLE

Cole DM, Beckmann CF, Searle GE, Plisson C, Tziortzi AC, Nichols TE, Gunn RN, Matthews PM, Rabiner EA, Beaver JDet al., 2012, Orbitofrontal connectivity with resting-state networks is associated with midbrain dopamine D3 receptor availability, Cereb Cortex, Vol: 22, Pages: 2784-2793, ISSN: 1460-2199

Animal research and human postmortem evidence highlight the importance of brain dopamine D3 receptor (D3R) function in multiple neuropsychiatric disorders, including addiction. Separate anatomical and functional neuroimaging findings implicate disrupted frontal cortical connectivity with distributed brain networks in processes relevant for these diseases. This potential conjunction between molecular and functional markers has not, however, been tested directly. Here, we used a novel combination of [(11)C]-(+)-PHNO positron emission tomography and resting-state functional magnetic resonance imaging in the same healthy individuals to investigate whether differences in midbrain D3R availability are associated with functional interactions between large-scale networks and regions involved in reward processing and cognition. High midbrain D3R availability was associated with reduced functional connectivity between orbitofrontal cortex (OFC) and networks implicated in cognitive control and salience processing. The opposite pattern was observed in subcortical reward circuitry and the "default mode" network, which showed greater connectivity with OFC in individuals with high D3R availability. These findings demonstrate that differential interactions between OFC and networks implicated in cognitive control and reward are associated with midbrain D3R availability, consistent with the hypothesis that dopamine D3R signaling is an important molecular pathway underlying goal-directed behavior.

JOURNAL ARTICLE

Matthews PM, Rabiner EA, Passchier J, Gunn RNet al., 2012, Positron emission tomography molecular imaging for drug development, Br J Clin Pharmacol, Vol: 73, Pages: 175-186, ISSN: 1365-2125

Human in vivo molecular imaging with positron emission tomography (PET) enables a new kind of 'precision pharmacology', able to address questions central to drug development. Biodistribution studies with drug molecules carrying positron-emitting radioisotopes can test whether a new chemical entity reaches a target tissue compartment (such as the brain) in sufficient amounts to be pharmacologically active. Competition studies, using a radioligand that binds to the target of therapeutic interest with adequate specificity, enable direct assessment of the relationship between drug plasma concentration and target occupancy. Tailored radiotracers can be used to measure relative rates of biological processes, while radioligands specific for tissue markers expected to change with treatment can provide specific pharmacodynamic information. Integrated application of PET and magnetic resonance imaging (MRI) methods allows molecular interactions to be related directly to anatomical or physiological changes in a tissue. Applications of imaging in early drug development can suggest approaches to patient stratification for a personalized medicine able to deliver higher value from a drug after approval. Although imaging experimental medicine adds complexity to early drug development and costs per patient are high, appropriate use can increase returns on R and D investment by improving early decision making to reduce new drug attrition in later stages. We urge that the potential value of a translational molecular imaging strategy be considered routinely and at the earliest stages of new drug development.

JOURNAL ARTICLE

Colasanti A, Searle GE, Long CJ, Hill SP, Reiley RR, Quelch D, Erritzoe D, Tziortzi AC, Reed LJ, Lingford-Hughes AR, Waldman AD, Schruers KR, Matthews PM, Gunn RN, Nutt DJ, Rabiner EAet al., 2012, Endogenous opioid release in the human brain reward system induced by acute amphetamine administration, Biol Psychiatry, Vol: 72, Pages: 371-377, ISSN: 1873-2402

BACKGROUND: We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET). METHODS: Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [(11)C]carfentanil binding from baseline to post-amphetamine scans (DeltaBP(ND)) after the "high" and "ultra-low" amphetamine doses were assessed in 10 regions of interest. RESULTS: [(11)C]carfentanil binding was reduced after the "high" but not the "ultra-low" amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula. CONCLUSIONS: Our findings indicate that oral amphetamine administration induces endogenous opioid release in different areas of human brain, including basal ganglia, frontal cortex areas, and thalamus. The combination of an amphetamine challenge and [(11)C]carfentanil PET is a practical and robust method to probe the opioid system in the living human brain.

JOURNAL ARTICLE

Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, StJean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JPet al., 2012, An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28, J Cereb Blood Flow Metab, Vol: 32, Pages: 1-5, ISSN: 1559-7016

[(11)C]PBR28 binds the 18-kDa Translocator Protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of signal are confounded by large interindividual variability in binding affinity, which displays a trimodal distribution compatible with a codominant genetic trait. Here, we tested directly for an underlying genetic mechanism to explain this. Binding affinity of PBR28 was measured in platelets isolated from 41 human subjects and tested for association with polymorphisms in TSPO and genes encoding other proteins in the TSPO complex. Complete agreement was observed between the TSPO Ala147Thr genotype and PBR28 binding affinity phenotype (P value=3.1 x 10(-13)). The TSPO Ala147Thr polymorphism predicts PBR28 binding affinity in human platelets. As all second-generation TSPO PET radioligands tested hitherto display a trimodal distribution in binding affinity analogous to PBR28, testing for this polymorphism may allow quantitative interpretation of TSPO PET studies with these radioligands.

JOURNAL ARTICLE

Stagg CJ, Bachtiar V, O'Shea J, Allman C, Bosnell RA, Kischka U, Matthews PM, Johansen-Berg Het al., 2011, Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke, BRAIN, Vol: 135, Pages: 276-284, ISSN: 0006-8950

Transcranial direct current stimulation, a form of non-invasive brain stimulation, is showing increasing promise as an adjuncttherapy in rehabilitation following stroke. However, although significant behavioural improvements have been reported inproof-of-principle studies, the underlying mechanisms are poorly understood. The rationale for transcranial direct current stimu-lation as therapy for stroke is that therapeutic stimulation paradigms increase activity in ipsilesional motor cortical areas, butthis has not previously been directly tested for conventional electrode placements. This study was performed to test directlywhether increases in ipsilesional cortical activation with transcranial direct current stimulation are associated with behaviouralimprovements in chronic stroke patients. Patients at least 6 months post-first stroke participated in a behavioural experiment(n= 13) or a functional magnetic resonance imaging experiment (n= 11), each investigating the effects of three stimulationconditions in separate sessions: anodal stimulation to the ipsilesional hemisphere; cathodal stimulation to the contralesionalhemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the ipsilesional hemisphere led to significant improve-ments (5–10%) in response times with the affected hand in both experiments. This improvement was associated with anincrease in movement-related cortical activity in the stimulated primary motor cortex and functionally interconnected regions.Cathodal (inhibitory) stimulation to the contralesional hemisphere led to a functional improvement only when compared withsham stimulation. We show for the first time that the significant behavioural improvements produced by anodal stimulationto the ipsilesional hemisphere are associated with a functionally relevant increase in activity within the ipsilesional primary

JOURNAL ARTICLE

Zarei M, Mataix-Cols D, Heyman I, Hough M, Doherty J, Burge L, Winmill L, Nijhawan S, Matthews PM, James Aet al., 2011, Changes in Gray Matter Volume and White Matter Microstructure in Adolescents with Obsessive-Compulsive Disorder, BIOLOGICAL PSYCHIATRY, Vol: 70, Pages: 1083-1090, ISSN: 0006-3223

JOURNAL ARTICLE

Tzimopoulou S, Cunningham VJ, Nichols TE, Searle G, Bird NP, Mistry P, Dixon IJ, Hallett WA, Whitcher B, Brown AP, Zvartau-Hind M, Lotay N, Lai RYK, Castiglia M, Jeter B, Matthews JC, Chen K, Bandy D, Reiman EM, Gold M, Rabiner EA, Matthews PMet al., 2011, Validation and pilot application of [ <sup>18</sup>F]FDG-PET in evaluation of a metabolic therapy for Alzheimer's disease, Advances in Alzheimer's Disease, Vol: 2, Pages: 627-642, ISSN: 2210-5727

Here we describe methods for application of quantitative fluorodeoxyglucose positron emission tomography ([ 18F]FDG-PET) measures of brain glucose metabolism in multi-centre clinical trials for Alzheimer's disease. We validated methods and demonstrated their use in the context of a treatment trial with the PPARγ agonist Rosiglitazone XR versus placebo in mild to moderate AD patients. Novel quantitative indices related to the combined forward rate constant for [ 18F]FDG uptake \(({K}-{i}^{index})\) and to the rate of cerebral glucose utilization \((CM{R}-{glu}^{index})\) were applied. Active treatment was associated with a sustained but not statistically significant trend from the first month for higher mean values in both. However, neither these nor another analytical approach recently validated using data from the Alzheimer's Disease Neuroimaging Initiative suggested that active treatment decreased the progression of decline in brain glucose metabolism. Rates of brain atrophy were similar between active and placebo groups and measures of cognition also did not demonstrate clear group differences. Our study demonstrates the feasibility of using [ 18F]FDG-PET as part of a multi-centre therapeutics trial and describes new measures that can be employed. It suggests that Rosiglitazone is associated with an early increase in whole brain glucose utilisation, but not with any biological or clinical evidence for slowing progression over the period of study in the selected patient group. © 2011 The authors and IOS Press. All rights reserved.

JOURNAL ARTICLE

Patsopoulos NA, de Bakker PIW, 2011, Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci, ANNALS OF NEUROLOGY, Vol: 70, Pages: 897-912, ISSN: 0364-5134

JOURNAL ARTICLE

Narayanan S, Caramanos Z, Matthews PM, Arnold DLet al., 2011, Axonal pathology in patients with multiple sclerosis: Evidence from in vivo proton magnetic resonance spectroscopy, Multiple Sclerosis Therapeutics, Fourth Edition, Pages: 150-164, ISBN: 9780521766272

© Cambridge University Press 2011. Introduction The clinical course of multiple sclerosis (MS) is highly variable, and pathological changes that are seen with the disease are heterogeneous amongst individuals. In recent years, there has been increasing interest in the development of magnetic resonance imaging (MRI) approaches to characterizing the pathological substrates of disability in MS with the objective of developing quantitative in vivo indices of pathology that could provide new insights into the pathogenesis of the disease, as well as provide more specific or sensitive end-points for treatment trials. This chapter reviews results from studies that have used either proton magnetic resonance spectroscopy (1H-MRS, a technique that allows for the acquisition of 1H-MR spectra from single voxels) or 1H-MR spectroscopic imaging (1H-MRSI, a technique that allows for the simultaneous acquisition of 1H-MR spectra from multiple voxels) to measure in vivo chemical pathology associated with impairment of axonal metabolic or structural integrity, and places these results in the context of relevant histopathological investigations. We will focus on an important hypothesis that has developed from these studies: that axonal pathology is central to the final common pathway leading to the progressive disability that is seen in individuals with this disease.

BOOK CHAPTER

De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WSet al., 2011, The Gut Hormones PYY3-36 and GLP-1(7-36) amide Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans, CELL METABOLISM, Vol: 14, Pages: 700-706, ISSN: 1550-4131

JOURNAL ARTICLE

Thomas EL, Makwana A, Newbould R, Rao AW, Gambarota G, Frost G, Delafont B, Mishra RG, Matthews PM, Berk ES, Schwartz SM, Bell JD, Beaver JDet al., 2011, Pragmatic study of orlistat 60mg on abdominal obesity, EUROPEAN JOURNAL OF CLINICAL NUTRITION, Vol: 65, Pages: 1256-1262, ISSN: 0954-3007

JOURNAL ARTICLE

Strijbis EMM, Inkster B, Vounou M, Kappos L, Radu E-W, Matthews PM, Uitdehaag B, Barkhof F, Geurts JJGet al., 2011, The explanatory value of glutamatergic SNPs on combined MRI phenotypes in multiple sclerosis, MULTIPLE SCLEROSIS JOURNAL, Vol: 17, Pages: S114-S115, ISSN: 1352-4585

JOURNAL ARTICLE

Inkster B, Strijbis EMM, Vounou M, Kappos L, Radue EW, Matthews PM, Uitdehaag B, Barkhof F, Polman CH, Montana G, Geurts JJGet al., 2011, Mitochondrial sirtuin gene variants and brain volume changes in patients with multiple sclerosis, MULTIPLE SCLEROSIS JOURNAL, Vol: 17, Pages: S333-S334, ISSN: 1352-4585

JOURNAL ARTICLE

Matthews PM, Rabiner I, Gunn R, 2011, Non-invasive imaging in experimental medicine for drug development, CURRENT OPINION IN PHARMACOLOGY, Vol: 11, Pages: 501-507, ISSN: 1471-4892

JOURNAL ARTICLE

Inkster B, Rao AW, Ridler K, Nichols TE, Saemann PG, Auer DP, Holsboer F, Tozzi F, Muglia P, Merlo-Pich E, Matthews PMet al., 2011, Structural Brain Changes in Patients with Recurrent Major Depressive Disorder Presenting with Anxiety Symptoms, JOURNAL OF NEUROIMAGING, Vol: 21, Pages: 375-382, ISSN: 1051-2284

JOURNAL ARTICLE

Bosnell RA, Kincses T, Stagg CJ, Tomassini V, Kischka U, Jbabdi S, Woolrich MW, Andersson J, Matthews PM, Johansen-Berg Het al., 2011, Motor Practice Promotes Increased Activity in Brain Regions Structurally Disconnected After Subcortical Stroke, NEUROREHABILITATION AND NEURAL REPAIR, Vol: 25, Pages: 607-616, ISSN: 1545-9683

JOURNAL ARTICLE

Roosendaal SD, Bendfeldt K, Vrenken H, Polman CH, Borgwardt S, Radue EW, Kappos L, Pelletier D, Hauser SL, Matthews PM, Barkhof F, Geurts JJGet al., 2011, Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability, MULTIPLE SCLEROSIS JOURNAL, Vol: 17, Pages: 1098-1106, ISSN: 1352-4585

JOURNAL ARTICLE

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