Publications
756 results found
Khamis RY, Woollard KJ, Hyde GD, et 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.
Miller KL, Bangerter N, Almagro FA, et al., 2016, UK Biobank: Brain imaging protocols and first data release, ISMRM 24th Annual Meeting
Petersen SE, Matthews PM, Francis JM, et 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.
Matthews PM, 2016, Pharmacological Applications of fMRI, FMRI TECHNIQUES AND PROTOCOLS, 2ND EDITION, Editors: Filippi, Publisher: HUMANA PRESS INC, Pages: 817-831, ISBN: 978-1-4939-5609-8
Maron E, Wall M, Norbury R, et 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.
Colasanti A, Guo, Giannetti P, et 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
Scott G, Hellyer PJ, Ramlackhansingh AF, et 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.
Matthews PM, Sudlow C, 2015, The UK Biobank, BRAIN, Vol: 138, Pages: 3463-3465, ISSN: 0006-8950
Matthews PM, 2015, New drugs and personalized medicine for multiple sclerosis, NATURE REVIEWS NEUROLOGY, Vol: 11, Pages: 614-616, ISSN: 1759-4758
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- Citations: 10
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.
Nie L, Yang X, Matthews P, et al., 2015, Minimum Partial Correlation: An Accurate and Parameter-Free Measure of Functional Connectivity in fMRI, International Conference on Brain Informatics & Health, BIH, Publisher: Springer International Publishing
Colasanti A, Guo Q, Giannetti P, et al., 2015, Hippocampal inflammation and depression in multiple sclerosis: integrating evidence from TSPO PET and resting state fMRI, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 492-493, ISSN: 1477-0970
Datta G, Battaglini M, Scott G, et al., 2015, Positron emission tomography imaging in multiple sclerosis highlights a diffuse inflammatory response in brain that appears normal on conventional magnetic resonance imaging, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 477-478, ISSN: 1477-0970
Matthews PM, 2015, Measuring brain function in multiple sclerosis, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 58-58, ISSN: 1352-4585
Suri S, Mackay CE, Kelly ME, et al., 2015, Reduced cerebrovascular reactivity in young adults carrying the <i>APOE</i> ε4 allele, ALZHEIMERS & DEMENTIA, Vol: 11, Pages: 648-657, ISSN: 1552-5260
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- Citations: 74
Colasanti A, Guo Q, Giannetti P, et al., 2015, Hippocampal Inflammation and Depressive Symptoms are Associated to the Strength of Hippocampal Functional Connectivity in Multiple Sclerosis: A Study with TSPO-PET and Resting-State fMRI, 70th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology, Publisher: ELSEVIER SCIENCE INC, Pages: 115S-116S, ISSN: 0006-3223
Ntusi NAB, Piechnik SK, Francis JM, et al., 2015, Diffuse Myocardial Fibrosis and Inflammation in Rheumatoid Arthritis Insights From CMR T1 Mapping, JACC-CARDIOVASCULAR IMAGING, Vol: 8, Pages: 526-536, ISSN: 1936-878X
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- Citations: 149
Matthews PM, Datta G, 2015, Positron-emission tomography molecular imaging of glia and myelin in drug discovery for multiple sclerosis, EXPERT OPINION ON DRUG DISCOVERY, Vol: 10, Pages: 557-570, ISSN: 1746-0441
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- Citations: 24
Clarke E, Matthews PM, 2015, The OPTIMISE data project: toward improving multiple sclerosis treatment, FUTURE NEUROLOGY, Vol: 10, Pages: 187-190, ISSN: 1479-6708
Russo E, Gunn RN, Khan S, et al., 2015, <SUP>18</SUP>F-FDG-PET Scanning As a Monitoring Tool in Crohn's Disease. A Prospective Study Assessing the Repeatability and Responsiveness of PET Endpoints, 46th Annual Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S435-S435, ISSN: 0016-5085
Russo E, Pendse D, Newbould R, et al., 2015, Diffusion-Weighted MRI As a Monitoring Tool in Crohn's Disease. A Prospective Pilot Study Assessing Its Responsiveness in Patients Receiving Anti-TNF Therapy, 46th Annual Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S434-S435, ISSN: 0016-5085
Matthews P, 2015, Professor Paul Matthews talks 'big data' within multiple sclerosis, NEURODEGENERATIVE DISEASE MANAGEMENT, Vol: 5, Pages: 101-104, ISSN: 1758-2024
Sudlow C, Gallacher J, Allen N, et al., 2015, UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age, PLOS Medicine, Vol: 12, ISSN: 1549-1277
UK Biobank is a very large and detailed prospective study with over 500,000 participantsaged 40–69 years when recruited in 2006–2010.• The study has collected and continues to collect extensive phenotypic and genotypic detailabout its participants, including data from questionnaires, physical measures, sampleassays, accelerometry, multimodal imaging, genome-wide genotyping and longitudinalfollow-up for a wide range of health-related outcomes.• Wide consultation; input from scientific, management, legal, and ethical partners; andindustrial-scale, centralised processes have been essential to the development ofthis resource.• UK Biobank is available for open access, without the need for collaboration, to any bonafide researcher who wishes to use it to conduct health-related research for the benefit ofthe public.
Comninos AN, Anastasovska J, Sahuri-Arisoylu M, et al., 2015, Kisspeptin signaling in the amygdala modulates reproductive hormone secretion, Brain Structure & Function, Vol: 221, Pages: 2035-2047, ISSN: 1863-2661
Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to hypothalamic centers involved in gonadotropin secretion. We therefore hypothesized that kisspeptin has effects on neuronal activation and reproductive pathways beyond the hypothalamus and particularly within the amygdala. To test this, we mapped brain neuronal activity (using manganese-enhanced MRI) associated with peripheral kisspeptin administration in rodents. We also investigated functional relevance by measuring the gonadotropin response to direct intra-medial amygdala (MeA) administration of kisspeptin and kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked decrease in signal intensity in the amygdala compared to vehicle alone. This was associated with an increase in luteinizing hormone (LH) secretion. In addition, intra-MeA administration of kisspeptin resulted in increased LH secretion, while blocking endogenous kisspeptin signaling within the amygdala by administering intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse frequency. We provide evidence for the first time that neuronal activity within the amygdala is decreased by peripheral kisspeptin administration and that kisspeptin signaling within the amygdala contributes to the modulation of gonadotropin release and pulsatility. Our data suggest that kisspeptin is a ‘master regulator’ of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion.
Ntusi NA, Sever E, Lockey J, et al., 2015, Abnormal myocardial perfusion correlates with impaired systolic strain and diastolic strain rate in systemic lupus erythematosus: A cardiovascular magnetic resonance study, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
Ntusi NA, Sever E, Lockey J, et al., 2015, Impaired myocardial perfusion is associated with extracellular volume expansion, disease activity and impaired strain and strain rate in systemic sclerosis: A cardiovascular magnetic resonance study, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
Ntusi NA, Sever E, Lockey J, et al., 2015, Impaired myocardial perfusion in rheumatoid arthritis is associated with impaired strain, strain rate, disease activity and myocardial oedema: A cardiovascular magnetic resonance study, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
Ntusi NA, Holloway C, Francis JM, et al., 2015, Impaired energetics and normal myocardial lipids in rheumatoid arthritis and systemic lupus erythematosus: A phosphorous and proton magnetic resonance spectroscopy and cardiovascular magnetic resonance study, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
Shields GS, Coissi GS, Jimenez-Royo P, et al., 2015, BIOENERGETICS AND INTERMUSCULAR FAT IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE-ASSOCIATED QUADRICEPS WEAKNESS, MUSCLE & NERVE, Vol: 51, Pages: 214-221, ISSN: 0148-639X
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- Citations: 20
Jacobs HIL, Wiese S, van de Ven V, et al., 2015, Relevance of parahippocampal-locus coeruleus connectivity to memory in early dementia, NEUROBIOLOGY OF AGING, Vol: 36, Pages: 618-626, ISSN: 0197-4580
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- Citations: 53
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