Abstract Objectives The complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific ...computational fluid dynamics (CFD) was used to assess effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS) and oscillatory shear index (OSI) in the thoracic aorta. Methods 45 subjects were divided into 5 groups: Volunteers, AR-TAV, AS-TAV, AS-BAV(RL), AS-BAV(RN), where AR=aortic regurgitation, AS=aortic stenosis, TAV=tricuspid aortic valve, BAV=bicuspid aortic valve, RL=right-left cusp fusion, RN=right-non cusp fusion. Subjects underwent magnetic resonance angiography, with phase-contrast MRI at the sino-tubular junction to define patient-specific inflow velocity profiles. Hemodynamic recordings were used alongside MRI angiographic data to run patient-specific CFD. Results BAV groups had larger mid-ascending aorta diameters (p<0.05). Ascending aorta flow was more eccentric in BAV (Flowasymmetry =78.9±6.5% for AS-BAV(RN), compared to 4.7±2.1% for Volunteers, p<0.05). Helicity was higher in AS-BAV(RL) (p<0.05). Mean WSS was elevated in AS groups, highest in AS-BAV(RN) (37.1±4.0 dyn/cm2 , compared to 9.8±5.4 for Volunteers, p<0.05). The greater curvature of the ascending aorta experienced highest WSS and lowest OSI in AS patients, most significant in AS-BAV(RN) (p<0.05). Conclusions BAV displays eccentric flow with high helicity. Presence of AS, particularly in BAV-RN led to higher WSS and lower OSI in the greater curvature of the ascending aorta. Patient-specific CFD provides non-invasive functional assessment of the thoracic aorta, and may enable development of a personalized approach to diagnosis and management of aortic disease beyond traditional guidelines.
Previous studies have evaluated gene expression in Alzheimer's disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have ...implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD.
Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping ...with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.
This review describes recent advances in the use of magnetic-plasmonic particles (MPPs) for bacteria detection by Surface-Enhanced Raman Scattering (SERS). Pathogenic bacteria pollution has always ...been a major threat to human health and safety. SERS spectroscopy has emerged as a powerful and promising technique for sensitive and selective detection of pathogen bacteria. MPPs are considered as a versatile SERS platform for their excellent plasmonic properties and good magnetic responsiveness. Improved preparation method and typical characterization technique of MPPs are introduced, focusing on the thin and continuous metallic shell covering process. Consequently, the SERS-based sensing methods for bacteria identification were discussed, including the label-free and label-based methods. Finally, an overview of the current state of the field and our perspective on future development directions are given.
Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically ...via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited.
Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean ± SD global myocardial iron causing severe heart failure in 10 patients was 5.98 ± 2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial lnR2* was strongly linearly correlated with lnFe (R²=0.910, P<0.001), leading to Fe=45.0×(T2*)⁻¹·²² for the clinical calibration equation with Fe in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron.
These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.
Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload ...in a young Chinese population with beta TM.
We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload.
The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Liver R2* mapping is often degraded by the low signal-to-noise ratio (SNR) especially in the presence of severe iron. This study aims to improve liver R2* mapping at low SNRs by averaging decay ...curves before the process of curve-fitting. Independently filtering echo images by nonlocal means (NLM) demonstrated improved quality of R2* mapping, but may introduce new errors due to the nonlinear nature of the NLM filter, during which the averaging weights may vary with different image contents at multiple echo times. In addition, the image denoising effect of the NLM may decline when no sufficient similar patches are available. To overcome these drawbacks, we proposed to filter decay curves instead of images. In this novel scheme, decay curves were averaged in a local window, each with a weight assigned according to the curve-similarity measured by the distance between one of the neighboring curves and the targeted one. The proposed method was tested on simulated, phantom and patient data. The results demonstrate that the proposed method can provide more accurate R2* mapping compared with the NLM algorithm, and hence has the potential to improve diagnosis and therapy in patients with liver iron.
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK.
The transferability of the T2* technique for measurement of tissue iron between magnetic resonance (MR) scanners is ...unknown. Heart and liver multi-breath-hold T2* sequences were installed on MR scanners at six different sites. T2* was assessed locally in five or more patients with thalassemia major (n=39), and subjects were re-scanned at the standardization center in London. Inter-center reproducibility of T2* in heart and liver was 5.0% and 7.1%, with mean absolute differences in T2* of 1.3 ms and 0.45 ms, respectively. The MR multi-breath-hold T2* technique for tissue iron quantification is transferable between scanners with good reproducibility.
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