Rayne Institute

London, United Kingdom

Rayne Institute

London, United Kingdom
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Noble J.J.,King's College London | Noble J.J.,Guys Hospital | Keevil S.F.,King's College London | Keevil S.F.,Rayne Institute | And 3 more authors.
British Journal of Radiology | Year: 2014

Objective: To compare Dixon-based MRI techniques for intramuscular fat quantification at 3 T with MR spectroscopy (MRS) in vitro and in vivo.Methods: In vitro, two- three- and four-point mDixon (Philips Medical Systems, Best, Netherlands) sequences with 10°, 20° and 30° flip angles were acquired fromseven test phantoms with sunflower oil-water percentages of 0-60% sunflower oil and calculated fat-water ratios compared with MRS. In vivo, two- three- and four-pointmDixon sequences with 10° flip angle were acquired and compared with MRS in the vastus medialis of nine healthy volunteers (aged 30.6±5.3 years; body mass index 22.2±2.6).Results: In vitro, all mDixon sequences correlated significantly with MRS (r>0.97, p<0.002). The measured phantom percentage fat depended significantly on the flip angle (p≤0.001) and mDixon sequence (p=0.005). Flip angle was the dominant factor influencing agreement with MRS. Increasing the flip angle significantly increased the overestimation of the mDixon sequences compared with MRS. In vivo, a significant difference was observed between sequences (p<0.001), with all mDixon sequences overestimating the intramuscular fat content of the vastus medialis muscle compared with MRS. Two-point mDixon agreed best with MRS and had comparable variability with the other mDixon sequences.Conclusion: This study demonstrates that mDixon techniques have good linearity and low variability for use in intramuscular fat quantification. To avoid significant fat overestimation with short repetition time, a low flip angle should be used to reduce T1 effects.Advances in knowledge: This is the first study investigating the optimal mDixon parameters for intramuscular fat quantification compared with MRS in vivo and in vitro. © 2014 The Authors.


Schuster A.,Robert Koch Str. | Schuster A.,German Center for Cardiovascular Research | Schuster A.,Rayne Institute | Hor K.N.,Ohio State University | And 4 more authors.
Circulation: Cardiovascular Imaging | Year: 2016

Heart failure-induced cardiovascular morbidity and mortality constitute a major health problem worldwide and result from diverse pathogeneses, including coronary artery disease, nonischemic cardiomyopathies, and arrhythmias. Assessment of cardiovascular performance is important for early diagnosis and accurate management of patients at risk of heart failure. During the past decade, cardiovascular magnetic resonance myocardial feature tracking has emerged as a useful tool for the quantitative evaluation of cardiovascular function. The method allows quantification of biatrial and biventricular mechanics from measures of deformation: strain, torsion, and dyssynchrony. The purpose of this article is to review the basic principles, clinical applications, accuracy, and reproducibility of cardiovascular magnetic resonance myocardial feature tracking, highlighting the prognostic implications. It will also provide an outlook on how this field might evolve in the future. © 2016 American Heart Association, Inc.


Silva K.D.,King's College London | Foster P.,King's College London | Guilcher A.,St Thomas National Health Service Foundation Trust | Bandara A.,King's College London | And 9 more authors.
Circulation: Cardiovascular Interventions | Year: 2013

Background.Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Methods and Results.Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35plusmn:1.21 μg/L, 56plusmn:11%, and 8.4plusmn:6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with lategadolinium enhancement infarct mass (r=-0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m-2 s-2×105 predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=.0.34; P=0.07). Conclusions.The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization. © 2013 American Heart Association, Inc.


Phinikaridou A.,King's College London | Phinikaridou A.,Rayne Institute | Andia M.E.,King's College London | Indermuehle A.,King's College London | And 7 more authors.
Radiology | Year: 2014

Purpose: To compare delayed-enhancement (DE) magnetic resonance (MR) imaging with an elastin-specific contrast agent and unenhanced blackblood (BB) MR imaging with regard to vessel wall delineation and assessment of vascular remodeling and to test the prospective value for predicting plaque disruption in a rabbit model of atherosclerosis. Materials and Methods: All procedures were approved by the animal ethics committee. Atherosclerosis was induced in 14 New Zealand White rabbits by means of a 1% cholesterol diet and endothelial denudation. Plaque disruption was triggered with Russell's viper venom and histamine. Animals with atherosclerosis were imaged before triggering to identify plaques and vascular remodeling and after triggering to identify thrombus. Plaques were classified as nondisrupted (stable) or disrupted (vulnerable). Control rabbits fed a regular diet were imaged twice. Unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent, and T1 mapping were used to assess vascular remodeling and calculate the plaque area and vessel wall relaxation rate (R1 = 1/T1). Elastin was quantified by using elastica-van Gieson stain. Group comparisons were analyzed with the Mann-Whitney or paired t test. Agreement between methods was performed with Bland-Altman analysis. Results: Unenhanced T1-weighted BB MR imaging and DE MR imaging showed that, compared with nondisrupted plaques, disrupted plaques had larger plaque area (T1-weighted BB MR imaging: 5.1 mm2 vs 5.7 mm2; DE MR imaging: 6.0 mm2 vs 7.9 mm2; P < .001) and vessel area (T1- weighted BB MR imaging: 11.8 mm2 vs 14.3 mm2; DE MR imaging: 10.8 mm2 vs 13.9 mm2; P < .001) and underwent positive remodeling. Assessment of positive remodeling with DE MR imaging enabled better prediction of plaque disruption compared to that with unenhanced T1-weighted BB imaging (sensitivity: 83.7% vs 58.1%). DE MR imaging showed a stronger agreement with histologic findings, whereas the vessel area was overestimated with unenhanced T1-weighted BB imaging. Conclusion: Compared with unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent enables more accurate assessment of vascular remodeling in the prediction of vulnerable plaque. © RSNA, 2014.


Coleman A.,Rayne Institute | Steel S.,Rayne Institute | Degreeff A.,King's College London | Shennan A.,King's College London
Blood Pressure Monitoring | Year: 2010

Background: The BP11 is currently one of the lowest-cost blood pressure (BP) monitors available in the UK and has sold approximately 1.5 million units since its launch in 2006. As access to home-use BP monitoring increases, it is important that such devices are validated so that consumers and clinicians can be confident of their accuracy. Methods: The device was validated using the European Society of Hypertension International Protocol. Data collection and analysis were carried out under the laboratory standard ISO17025. Adherence to the standard and protocol was audited on-site by the United Kingdom Accreditation Service. Nine sequential same-arm measurements were taken alternating between trained observers and the test device. Minor variations from the protocol are reported. Results: The device passed both phases of the European Society of Hypertension International Protocol. The mean (standard deviation) of the difference between the observers and the device measurements was -1.2 (6.4) mmHg for systolic and 2.1 (6.8) mmHg for diastolic pressures, respectively. Conclusion: The BP11 BP monitor can be recommended for home and professional use in an adult population. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Authier S.,CiToxLAB North America | Pugsley M.K.,Janssen Pharmaceutical | Curtis M.J.,Rayne Institute
Handbook of Experimental Pharmacology | Year: 2015

Evaluation of the effects of a drug on arterial blood pressure is important in nonclinical safety pharmacology assessment. Detecting large and obvious changes in blood pressure is an unchallenging task. Detecting small changes is more difficult, and interpretation of findings requires careful risk/benefit evaluation. Detecting subtle and small changes in blood pressure is important in particular with respect to increases, since blood pressure above the normal range is associated with increased risk of stroke and sudden cardiac death. Cardiovascular safety pharmacology has been preoccupied with drug-induced changes in the electrocardiogram, and by comparison, there has been little in the way of contemporaneous improvements in the level of complexity and sophistication involved in blood pressure assessment. Thus, it is important to understand the nature of drug-induced changes in blood pressure, appreciate the plethora of agents currently used clinically (and over the counter) that alter blood pressure and understand safety pharmacology study design in order to optimize assessment of a new chemical entity (NCE) or biologic agent in this context. © Springer-Verlag Berlin Heidelberg 2015.


Perez-Sanchez C.,Hospital Reina Sofia | Ruiz-Limon P.,Hospital Reina Sofia | Aguirre M.A.,Hospital Reina Sofia | Bertolaccini M.L.,King's College | And 11 more authors.
Blood | Year: 2012

The exact mechanisms underlying the role of oxidative stress in the pathogenesis and the prothrombotic or proinflammatory status of antiphospholipid syndrome (APS) remain unknown. Here, we investigate the role of oxidative stress and mitochondrial dysfunction in the proatherothrombotic status of APS patients induced by IgG-antiphospholipid antibodies and the beneficial effects of supplementing cells with coenzyme Q10 (CoQ10). A significant increase in relevant prothrombotic and inflammatory parameters in 43 APS patients was found compared with 38 healthy donors. Increased peroxide production, nuclear abundance of Nrf2, antioxidant enzymatic activity, decreased intracellular glutathione, and altered mitochondrial membrane potential were found in monocytes and neutrophils from APS patients. Accelerated atherosclerosis in APS patients was found associated with their inflammatory or oxidative status. CoQ10 preincubation of healthy monocytes before IgG-antiphospholipid antibody treatment decreased oxidative stress, the percentage of cells with altered mitochondrial membrane potential, and the induced expression of tissue factor, VEGF, and Flt1. In addition, CoQ10 significantly improved the ultrastructural preservation of mitochondria and prevented IgG-APS-induced fission mediated by Drp-1 and Fis-1 proteins. In conclusion, the oxidative perturbation in APS patient leukocytes, which is directly related to an inflammatory and proatherothrombotic status, relies on alterations in mitochondrial dynamics and metabolism that may be prevented, reverted, or both by treatment with CoQ 10. © 2012 by The American Society of Hematology.


Jogiya R.,Rayne Institute | Kozerke S.,Rayne Institute | Kozerke S.,ETH Zurich | Morton G.,Rayne Institute | And 6 more authors.
Journal of the American College of Cardiology | Year: 2012

The goal of this study was to determine the diagnostic accuracy of dynamic 3-dimensional (3D) whole heart myocardial perfusion cardiovascular magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) and to establish the correlation between myocardium at risk defined by using the invasive Duke Jeopardy Score (DJS) and noninvasive 3D whole heart myocardial perfusion CMR. 3D whole heart myocardial perfusion CMR overcomes the limited spatial coverage of conventional two-dimensional perfusion CMR methods and allows estimation of the extent of ischemia. The method has shown good diagnostic accuracy for the detection of coronary artery disease (CAD) as defined by using quantitative coronary angiography. However, quantitative coronary angiography does not provide a functional assessment of CAD as available from pressure wirederived FFR. In the catheter laboratory, the DJS can complement FFR to estimate the myocardium at risk. Fifty-three patients referred for angiography underwent rest and adenosine stress 3D whole heart myocardial perfusion CMR at 3-T. Perfusion was scored visually on a patient and coronary territory basis, and ischemic burden was calculated by quantitative segmentation of the volume of hypoenhancement. FFR was measured in vessels with <50% severity stenosis and an FFR <0.75 considered as hemodynamically significant. The DJS was calculated from the coronary angiograms to quantify the myocardium at risk. FFR was measured in 64 of 159 coronary vessels, and 39 had an FFR <0.75. Sensitivity, specificity, and diagnostic accuracy of CMR for the detection of significant CAD were 91%, 90%, and 91%, on a patient basis and 79%, 92%, and 88%, respectively, by coronary territory. There was a strong correlation between the DJS and ischemic burden on CMR (p < 0.0001; Pearson's r = 0.82). 3D whole heart myocardial perfusion CMR accurately detects functionally significant CAD as defined by using FFR and provides an assessment of ischemic burden in agreement with the invasive DJS. The accurate detection of significant CAD combined with an estimation of ischemic burden by using 3D myocardial perfusion CMR holds promise for noninvasive guidance of therapy and risk stratification of patients with CAD. © 2012 American College of Cardiology Foundation.


Fullerton J.N.,Rayne Institute | Singer M.,University College London
Seminars in Respiratory and Critical Care Medicine | Year: 2011

The physiological and biochemical abnormalities that constitute multiple organ failure represent cellular perturbations that, importantly, need to be reconciled with a lack of significant cell death together with availability but impaired utilization of oxygen. In conjunction with the relatively rapid ability of the organ to recover in surviving patients, a paradigm of metabolic shutdown triggered by a decrease in mitochondrial energy production appears increasingly valid. This review discusses data demonstrating temporal changes in oxygen utilization through the septic process, evidence for mitochondrial derangements, and recovery of mitochondrial function preceding clinical recovery. Copyright © 2011 by Thieme Medical Publishers, Inc.


While the current epigenetic drug development is still largely restricted to target DNA methylome, emerging evidence indicates that histone methylome is indeed another major epigenetic determinant for gene expression and frequently deregulated in acute myeloid leukaemia (AML). The recent advances in dissecting the molecular regulation and targeting histone methylome in AML together with the success in developing lead compounds specific to key histone methylation-modifying enzymes have revealed new opportunities for effective leukaemia treatment. In this article, we will review the emerging functions of histone methyltransferases and histone demethylases in AML, especially MLL-rearranged leukaemia. We will also examine recent preclinical and clinical studies that show significant promises of targeting these histone methylation-modifying enzymes for AML treatment.Oncogene advance online publication, 5 September 2016; doi:10.1038/onc.2016.315. © 2016 The Author(s)

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