594 results found
Matthews PM, 2014, An engaging tour through Oxford's medical history, LANCET, Vol: 383, Pages: 1201-1202, ISSN: 0140-6736
Matthews PM, 2014, The virtues of adaptability, MULTIPLE SCLEROSIS JOURNAL, Vol: 20, Pages: 394-396, ISSN: 1352-4585
Khamis R, Woollard K, Hyde G, et al., 2014, NEAR-INFRARED FLUORESCENCE (NIRF) WHOLE BODY AND INTRA-ARTERIAL MOLECULAR IMAGING OF OXIDIZED LDL IN EXPERIMENTAL ATHEROSCLEROSIS, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 63, Pages: A2150-A2150, ISSN: 0735-1097
Newbould RD, Nicholas R, Thomas CL, et al., 2014, Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis, NeuroImage: Clinical, Vol: 4, Pages: 641-648, ISSN: 2213-1582
BackgroundMultiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration.ObjectiveTo determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI.Materials and methodsForty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region.ResultsAll MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes.ConclusionsDespite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.
Ntusi NAB, Piechnik SK, Francis JM, et al., 2014, Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis - a clinical study using myocardial T1-mapping and extracellular volume quantification, Journal of Cardiovascular Magnetic Resonance, Vol: 16, ISSN: 1097-6647
Background:Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc.Methods:19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification.Results:Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices.Conclusions:Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as foca
Matthews PM, Geraghty OC, 2014, Understanding the pharmacology of stroke and multiple sclerosis through imaging, CURRENT OPINION IN PHARMACOLOGY, Vol: 14, Pages: 34-41, ISSN: 1471-4892
Tawakol A, Singh P, Rudd JHF, et al., 2014, Effect of Treatment for 12 Weeks With Rilapladib, a Lipoprotein-Associated Phospholipase A(2) Inhibitor, on Arterial Inflammation as Assessed With F-18-Fluorodeoxyglucose-Positron Emission Tomography Imaging, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 63, Pages: 86-88, ISSN: 0735-1097
Matthews PM, Edison P, Geraghty OC, et al., 2014, The emerging agenda of stratified medicine in neurology, NATURE REVIEWS NEUROLOGY, Vol: 10, Pages: 15-26, ISSN: 1759-4758
Harvey NC, Matthews P, Collins R, et al., 2013, Osteoporosis epidemiology in UK Biobank: a unique opportunity for international researchers, OSTEOPOROSIS INTERNATIONAL, Vol: 24, Pages: 2903-2905, ISSN: 0937-941X
Zarei M, Beckmann CF, Binnewijzend MAA, et al., 2013, Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease (vol 66, pg 28, 2013), NEUROIMAGE, Vol: 83, Pages: 1109-1109, ISSN: 1053-8119
Colasanti A, Owen DR, Grozeva D, et al., 2013, Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa Translocator Protein (TSPO), PSYCHONEUROENDOCRINOLOGY, Vol: 38, Pages: 2826-2829, ISSN: 0306-4530
Wu C, Zhu J, Baeslack J, et al., 2013, Longitudinal Positron Emission Tomography Imaging for Monitoring Myelin Repair in the Spinal Cord, ANNALS OF NEUROLOGY, Vol: 74, Pages: 688-698, ISSN: 0364-5134
Colasanti A, Guo Q, Mulhert N, et al., 2013, [18F]PBR111 binding in lesional and peri-lesional multiple sclerosis white matter, 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS, Publisher: SAGE PUBLICATIONS LTD, Pages: 68-69, ISSN: 1352-4585
Guo Q, Colasanti A, Owen DR, et al., 2013, Quantification of the Specific Translocator Protein Signal of18F-PBR111 in Healthy Humans: A Genetic PolymorphismEffect on In Vivo Binding, Journal of Nuclear Medicine, Vol: 54, Pages: 1-9
PET is used to image active inflammatory processes by targetingthe translocator protein (TSPO). In vitro, second-generation TSPOradioligands, such as PBR111, have been shown to bind to humantissue samples with either high affinity (high-affinity binders, HABs),low affinity (low-affinity binders, LABs), or an intermediate, mixedaffinity (mixed-affinity binders, MABs). We previously explainedthese differences in affinity in human tissue via the rs6971 polymorphismin the TSPO gene and predicted that the specific signalfrom PET ligands in vivo would vary accordingly. In silico modelingpredicted that 18F-PBR111 would have a moderate to high specificto-nonspecific ratio in the normal human brain. To test these predictions,we present here the analysis and modeling of 18F-PBR111data in healthy humans. Methods: Twenty-one subjects (9 HABs, 8MABs, and 4 LABs), 28–62 y old, genotyped for the rs6971 polymorphism,underwent 120-min PET scans with arterial samplingafter a bolus injection of 18F-PBR111. Compartmental models andLogan graphical methods enabled estimation of the total volume ofdistribution (VT) in regions of interest (ROIs). To evaluate the specificsignal, we developed 2 methods to estimate the nondisplaceablevolume of distribution (VND): the first assumed that the in vitro affinityratio of 18F-PBR111 in HABs relative to LABs (4-fold) is preserved invivo; the second modeled the difference in the HAB and MAB signalsin the context of an occupancy plot. Results: A 2-tissue-compartmentmodel described the data well, and a significant differencewas found between the VT of HABs, MABs, and LABs across allROIs examined (P , 0.05). We also found a significant correlationbetween VT and age for both HABs and MABs in most ROIs. Theaverage VND estimated by the 2 methods was 1.18 6 0.35 (methodI: VND 5 0.93, method II: VND 5 1.42), implying that the 18F-PBR111BPND was 2.78 6 0.46 in HABs, 1.48 6 0.28 in MABs, and 0.51 60.17 in LABs and that the in vivo affinity ratio was simil
Kandel ER, Markram H, Matthews PM, et al., 2013, VIEWPOINT Neuroscience thinks big (and collaboratively), NATURE REVIEWS NEUROSCIENCE, Vol: 14, Pages: 659-664, ISSN: 1471-003X
Matthews PM, Coatney R, Alsaid H, et al., 2013, Technologies: preclinical imaging for drug development., Drug Discov Today Technol, Vol: 10, Pages: e343-e350
Preclinical imaging with magnetic resonance imaging (MRI), computerised tomography (CT), ultrasound (US), positron emission tomography (PET) or single-photon emission computed tomography (SPECT) enable non-invasive measures of tissue structure, function or metabolism in vivo. The technologies can add value to preclinical studies by enabling dynamic pharmacological observations on the same animal and because of possibilities for relatively direct clinical translation. Potential benefits from the application of preclinical imaging should be considered routinely in drug development.
Newbould RD, Miller SR, Upadhyay N, et al., 2013, T1-Weighted Sodium MRI of the Articulator Cartilage in Osteoarthritis: A Cross Sectional and Longitudinal Study, PLOS One, Vol: 8, ISSN: 1932-6203
Khamis R, Woollard K, Chang SH, et al., 2013, The Near Infra-Red (NIRF) molecular imaging of oxidised LDL in atherosclerosis with the native autoantibody LO1, and its molecularly expressed cysteine-tagged Fab construct (LO1-Fab-cys), Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 29-29, ISSN: 0195-668X
Petersen SE, Matthews PM, Bamberg F, et al., 2013, Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, Vol: 15, ISSN: 1097-6647
UK Biobank is a prospective cohort study with 500,000 participants aged 40 to 69. Recently an enhanced imagingstudy received funding. Cardiovascular magnetic resonance (CMR) will be part of a multi-organ, multi-modalityimaging visit in 3–4 dedicated UK Biobank imaging centres that will acquire and store imaging data from 100,000participants (subject to successful piloting). In each of UK Biobank’s dedicated bespoke imaging centres, it isproposed that 15–20 participants will undergo a 2 to 3 hour visit per day, seven days a week over a period of5–6 years. The imaging modalities will include brain MRI at 3 Tesla, CMR and abdominal MRI at 1.5 Tesla, carotidultrasound and DEXA scans using carefully selected protocols. We reviewed the rationale, challenges and proposedapproaches for concise phenotyping using CMR on such a large scale. Here, we discuss the benefits of this imagingstudy and review existing and planned population based cardiovascular imaging in prospective cohort studies. Wewill evaluate the CMR protocol, feasibility, process optimisation and costs. Procedures for incidental findings, qualitycontrol and data processing and analysis are also presented. As is the case for all other data in the UK Biobankresource, this database of images and related information will be made available through UK Biobank’s AccessProcedures to researchers (irrespective of their country of origin and whether they are academic or commercial)for health-related research that is in the public interest.
Khamis R, Woollard K, Granger D, et al., 2013, IMAGING BEYOND THE LUMEN: NEAR INFRA-RED IN VIVO MOLECULAR IDENTIFICATION OF OXIDISED LDL IN ATHEROSCLEROSIS USING MAB LO1, AND THE GENERATION AND DEVELOPMENT OF ITS MOLECULARLY EXPRESSED CYSTEINE-TAGGED CHIMERIC FAB CONSTRUCT (LO1-FAB-CYS), Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, ISSN: 1355-6037
Ntusi NBA, Francis JM, Matthews PM, et al., 2013, SYSTEMIC LUPUS ERYTHEMATOSUS IS ASSOCIATED WITH IMPAIRED MYOCARDIAL STRAIN AND VASCULAR FUNCTION, INCREMENTAL TO THAT CAUSED BY TRADITIONAL RISK FACTORS: A CARDIOVASCULAR MAGNETIC RESONANCE STUDY, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, ISSN: 1355-6037
Ntusi NBA, Francis JM, Matthews PM, et al., 2013, MYOCARDIAL AND VASCULAR DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS ASSESSED WITH CARDIOVASCULAR MAGNETIC RESONANCE: EVIDENCE OF INCREASED VASCULAR RISK, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A61-U238, ISSN: 1355-6037
Gourraud P-A, Sdika M, Khankhanian P, et al., 2013, A genome-wide association study of brain lesion distribution in multiple sclerosis, BRAIN, Vol: 136, Pages: 1012-1024, ISSN: 0006-8950
Matthews PM, Matthews EA, 2013, Expanding perception through the disordered brain., Lancet, Vol: 381, Pages: 985-986
Zarei M, Beckmann CF, Binnewijzend MAA, et al., 2013, Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease, NEUROIMAGE, Vol: 66, Pages: 28-35, ISSN: 1053-8119
Douaud G, Menke RAL, Gass A, et al., 2013, Brain Microstructure Reveals Early Abnormalities more than Two Years prior to Clinical Progression from Mild Cognitive Impairment to Alzheimer's Disease, JOURNAL OF NEUROSCIENCE, Vol: 33, Pages: 2147-2155, ISSN: 0270-6474
Inkster B, Strijbis EMM, Vounou M, et al., 2013, Histone deacetylase gene variants predict brain volume changes in multiple sclerosis, NEUROBIOLOGY OF AGING, Vol: 34, Pages: 238-247, ISSN: 0197-4580
Matthews PM, Filippini N, Douaud G, 2013, Brain Structural and Functional Connectivity and the Progression of Neuropathology in Alzheimer's Disease, JOURNAL OF ALZHEIMERS DISEASE, Vol: 33, Pages: S163-S172, ISSN: 1387-2877
Owen D, Guo Q, Colasanti A, et al., 2013, Determination of [11C]PBR28 binding potential in vivo: A first human TSPO occupancy study., Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI)
Libri V, Brown AP, Gambarota G, et al., 2012, A Pilot Randomized, Placebo Controlled, Double Blind Phase I Trial of the Novel SIRT1 Activator SRT2104 in Elderly Volunteers, PLoS ONE, Vol: 7, ISSN: 1932-6203
Background:SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD+-dependent deacetylaseinvolved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucosemetabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderlyvolunteers.Methods:Oral doses of 0.5 or 2.0 g SRT2104 or matching placebo were administered once daily for 28 days.Pharmacokinetic samples were collected through 24 hours post-dose on days 1 and 28. Multiple pharmacodynamicendpoints were explored with oral glucose tolerance tests (OGTT), serum lipid profiles, magnetic resonance imaging (MRI)for assessment of whole body visceral and subcutaneous fat, maximal aerobic capacity test and muscle 31P magneticresonance spectroscopy (MRS) for estimation of mitochondrial oxidative capacity.Results:SRT2104 was generally safe and well tolerated. Pharmacokinetic exposure increased less than dose-proportionally.Mean Tmax was 2–4 hours with elimination half-life of 15–20 hours. Serum cholesterol, LDL levels and triglyceridesdecreased with treatment. No significant changes in OGTT responses were observed. 31P MRS showed trends for morerapid calculated adenosine diphosphate (ADP) and phosphocreatine (PCr) recoveries after exercise, consistent withincreased mitochondrial oxidative phosphorylation.Conclusions:SRT2104 can be safely administered in elderly individuals and has biological effects in humans that areconsistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful indose selection for future clinical trials in patients.
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