Wall Shear Stress and Atherosclerotic Plaque Progression

Atherosclerotic plaque is the build-up of lipids, inflammatory cells and fibrotic tissue in the arterial wall. As disease progresses, atherosclerotic plaque progresses into various forms. Depending on their composition, plaques can be generally divided into two categories: stable and vulnerable. Rupture of a vulnerable plaque can lead to the sudden and unpredictable onset of stroke or heart attack. Although risk factors for atherosclerosis, including smoking, diabetes, high blood pressure, hyperlipidemia, genetic susceptibility are systemic in nature, atherosclerosis develops at specific sites of the vasculature, i.e. near curvatures and bifurcations. This is due to the difference in the wall shear stress (WSS) environment. WSS is the frictional force that blood flow applies on the endothelial lining of the arterial wall. Low WSS is known to induce inflammation and plaque initiation, while high WSS is anti-inflammatory and protect against plaque formation. However, the relationship between WSS and plaque vulnerability is not clear. The aim of this thesis was to study the evolution of WSS during plaque progression and determine its correlation to plaque composition using

Contrast-enhanced micro-CT imaging in murine carotid arteries : a new protocol for computing wall shear stress

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis. Methods: A tapering cast was placed around the right common carotid artery (RCCA) of ApoE(-/-) mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA. Results: eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals. Conclusions: eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque

Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition

Contrast-enhanced micro-CT imaging in murine carotid arteries: A new protocol for computing wall shear stress

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atheroscleroti

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effects of food wastes based on different components on digestibility and energy recovery in hydrogen and methane co-production

This study was conducted for four organic fractions (carbohydrates, proteins, cellulose, lipids) at an inoculum concentration of 30 % and a total solid (TS) of 8 % to investigate the effect of the main components of food waste on the performance of the two-stage anaerobic digestion. The results showed that the gas phase products were closely related to the composition of the substrate, with the carbohydrate and lipid groups showing the best hydrogen (154.91 ± 2.39mL/gVS) and methane (381.83 ± 12.691mL/gVS) production performance, respectively. However, the increased protein content predisposes the system to inhibition of gas production, which is mutually supported by changes in the activity of dehydrogenase and coenzyme F420. Butyric acid (53.19 %) dominated the liquid phase products in both stages, indicating that all four organic fractions were butyric acid-based fermentation and that the final soluble chemical oxygen demand degradation reached 72.97 %–82.86 %. The carbohydrate and cellulose groups achieved the best energy recovery performance, with conversion rates exceeding 65 %. The above results can provide a useful reference for the resource utilization of food waste

Asynchronous fracture of hierarchical microstructures in hard domain of thermoplastic polyurethane elastomer: Effect of chain extender

Four chain extenders, 1,3-propanediol (PDO), 2-methyl-1,3-propanediol (MPO), 2,2-dimethyl-1,3-propanediol (NPG) and 2,2,4,4-tetramethyl-1,3-cyclobutanedio (CBDO) are chosen to synthesize model polyurethanes, respectively. Although with similar oxygen distance between the two hydroxyl groups, their volumes increase gradually according to computer simulation. As expected, the degree of microphase separation decreases with the increasing chain extender volume. Except for CBDO based polyurethane, the other three samples show systematic variations in mechanical properties. Various techniques including single-molecule force spectroscopy (SMFS), small-angle X-ray scattering (SAXS) and Fourier transform infrared spectroscopy (FTIR) are employed to investigate the structural changes after tensile break in different length scales. A picture of asynchronous fracture of microstructures during the tensile break of thermoplastic polyurethane elastomers can be obtained by the combination of different analytical methods. It is interesting to note that the macroscopic break may not affect the state of hydrogen bonding or the hard phase network. Sometimes, the hydrogen bonding state changes a lot while the phase network keeps almost the same, or vice versa. (C) 2018 Elsevier Ltd. All rights reserved

A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria

10.1039/c5cc03807cCHEMICAL COMMUNICATIONS516212490-1249