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

Vascular Segmentation Algorithms for Generating 3D Atherosclerotic Measurements

Atherosclerosis manifests as plaques within large arteries of the body and remains as a leading cause of mortality and morbidity in the world. Major cardiovascular events may occur in patients without known preexisting symptoms, thus it is important to monitor progression and regression of the plaque burden in the arteries for evaluating patient\u27s response to therapy. In this dissertation, our main focus is quantification of plaque burden from the carotid and femoral arteries, which are major sites for plaque formation, and are straight forward to image noninvasively due to their superficial location. Recently, 3D measurements of plaque burden have shown to be more sensitive to the changes of plaque burden than one-/two-dimensional measurements. However, despite the advancements of 3D noninvasive imaging technology with rapid acquisition capabilities, and the high sensitivity of the 3D plaque measurements of plaque burden, they are still not widely used due to the inordinate amount of time and effort required to delineate artery walls plus plaque boundaries to obtain 3D measurements from the images. Therefore, the objective of this dissertation is developing novel semi-automated segmentation methods to alleviate measurement burden from the observer for segmentation of the outer wall and lumen boundaries from: (1) 3D carotid ultrasound (US) images, (2) 3D carotid black-blood magnetic resonance (MR) images, and (3) 3D femoral black-blood MR images. Segmentation of the carotid lumen and outer wall from 3DUS images is a challenging task due to low image contrast, for which no method has been previously reported. Initially, we developed a 2D slice-wise segmentation algorithm based on the level set method, which was then extended to 3D. The 3D algorithm required fewer user interactions than manual delineation and the 2D method. The algorithm reduced user time by ≈79% (1.72 vs. 8.3 min) compared to manual segmentation for generating 3D-based measurements with high accuracy (Dice similarity coefficient (DSC)\u3e90%). Secondly, we developed a novel 3D multi-region segmentation algorithm, which simultaneously delineates both the carotid lumen and outer wall surfaces from MR images by evolving two coupled surfaces using a convex max-flow-based technique. The algorithm required user interaction only on a single transverse slice of the 3D image for generating 3D surfaces of the lumen and outer wall. The algorithm was parallelized using graphics processing units (GPU) to increase computational speed, thus reducing user time by 93% (0.78 vs. 12 min) compared to manual segmentation. Moreover, the algorithm yielded high accuracy (DSC \u3e 90%) and high precision (intra-observer CV \u3c 5.6% and inter-observer CV \u3c 6.6%). Finally, we developed and validated an algorithm based on convex max-flow formulation to segment the femoral arteries that enforces a tubular shape prior and an inter-surface consistency of the outer wall and lumen to maintain a minimum separation distance between the two surfaces. The algorithm required the observer to choose only about 11 points on its medial axis of the artery to yield the 3D surfaces of the lumen and outer wall, which reduced the operator time by 97% (1.8 vs. 70-80 min) compared to manual segmentation. Furthermore, the proposed algorithm reported DSC greater than 85% and small intra-observer variability (CV ≈ 6.69%). In conclusion, the development of robust semi-automated algorithms for generating 3D measurements of plaque burden may accelerate translation of 3D measurements to clinical trials and subsequently to clinical care

Simulated hemodynamics in human carotid bifurcation based on Doppler ultrasound data

Background: Atherosclerotic lesions commonly develop at arterial branch sites. Noninvasive carotid artery ultrasound is a well-established and effective method which allows real-time images and measurements of flow velocities. We aimed to develop a methodology for patient-specific computational 3D reconstruction and blood flow simulation based on ultrasound image data.Material and Methods: Subject-specific studies based on the acquisition of a set of longitudinal and sequential cross-sectional ultrasound images and Doppler velocity measurements at common carotid artery (CCA) bifurcation were performed at a university hospital. A developed simulation code of blood flow by the finite element method (FEM) that includes an adequate structured meshing of the common carotid artery bifurcation was used to investigate local flow biomechanics.Results: Hemodynamic simulations of CCA bifurcations for six individuals were analysed. Comparing pairs (Doppler, FEM) of velocity values, Lin's concordance correlation coefficient analysis demonstrated an almost perfect strength of agreement (c = 0.9911), in patients with different degrees of internal carotid artery (ICA) stenosis. Numerical simulations were able to capture areas of low wall shear stress correlated with stagnation zones.Conclusions: Simulated hemodynamic parameters can reproduce the disturbed flow conditions at the bifurcation of CCA and proximal ICA, which play an important role in the development of local atherosclerotic plaques. This novel technology might help to understand the relationship between hemodynamic environment and carotid wall lesions, and have a future impact in carotid stenosis diagnosis and management

An Integrated Visual Analytics System for Studying Clinical Carotid Artery Plaques

Carotid artery plaques can cause arterial vascular diseases such as stroke and myocardial infarction, posing a severe threat to human life. However, the current clinical examination mainly relies on a direct assessment by physicians of patients' clinical indicators and medical images, lacking an integrated visualization tool for analyzing the influencing factors and composition of carotid artery plaques. We have designed an intelligent carotid artery plaque visual analysis system for vascular surgery experts to comprehensively analyze the clinical physiological and imaging indicators of carotid artery diseases. The system mainly includes two functions: First, it displays the correlation between carotid artery plaque and various factors through a series of information visualization methods and integrates the analysis of patient physiological indicator data. Second, it enhances the interface guidance analysis of the inherent correlation between the components of carotid artery plaque through machine learning and displays the spatial distribution of the plaque on medical images. Additionally, we conducted two case studies on carotid artery plaques using real data obtained from a hospital, and the results indicate that our designed carotid analysis system can effectively provide clinical diagnosis and treatment guidance for vascular surgeons