612 results found
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.
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
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
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
Matthews PM, 2013, Clinical imaging in drug development, Drug Discovery and Development: Technology in Transition, Pages: 259-274, ISBN: 9780702042997
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.
Matthews PM, Filippini N, Douaud G, 2012, Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease, ISBN: 9781614991533
In our contribution to this special issue focusing on advances in Alzheimer's disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression. © 2013 The authors and IOS Press. All rights reserved.
Gelineau-Morel R, Tomassini V, Jenkinson M, et al., 2012, The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis, HUMAN BRAIN MAPPING, Vol: 33, Pages: 2802-2814, ISSN: 1065-9471
Tomassini V, Matthews PM, Thompson AJ, et al., 2012, Neuroplasticity and functional recovery in multiple sclerosis, NATURE REVIEWS NEUROLOGY, Vol: 8, Pages: 635-646, ISSN: 1759-4758
Fleming IN, Whelan M, Baxendale R, et al., 2012, Positron emission tomography radiopharmaceutical studies in humans: a guide to regulations for academic researchers, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 33, Pages: 899-906, ISSN: 0143-3636
Allen N, Sudlow C, Downey P, et al., 2012, UK Biobank: Current status and what it means for epidemiology, HEALTH POLICY AND TECHNOLOGY, Vol: 1, Pages: 123-126, ISSN: 2211-8837
Colasanti A, Guo Q, Onega M, et 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
Politis M, Giannetti P, Su P, et 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
Tomassini V, Johansen-Berg H, Jbabdi S, et 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
Strijbis E, Inkster B, Vounou M, et al., 2012, Glutamate gene polymorphisms predict brain volumes in multiple sclerosis, Multiple Sclerosis Journal
Newbould RD, Miller SR, Toms LD, et 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
De Silva A, Salem V, Matthews PM, et 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.
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.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.