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      In Vitro Shear Stress Measurements Using Particle Image Velocimetry in a Family of Carotid Artery Models: Effect of Stenosis Severity, Plaque Eccentricity, and Ulceration

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          Abstract

          Atherosclerotic disease, and the subsequent complications of thrombosis and plaque rupture, has been associated with local shear stress. In the diseased carotid artery, local variations in shear stress are induced by various geometrical features of the stenotic plaque. Greater stenosis severity, plaque eccentricity (symmetry) and plaque ulceration have been associated with increased risk of cerebrovascular events based on clinical trial studies. Using particle image velocimetry, the levels and patterns of shear stress (derived from both laminar and turbulent phases) were studied for a family of eight matched-geometry models incorporating independently varied plaque features – i.e. stenosis severity up to 70%, one of two forms of plaque eccentricity, and the presence of plaque ulceration). The level of laminar (ensemble-averaged) shear stress increased with increasing stenosis severity resulting in 2–16 Pa for free shear stress (FSS) and approximately double (4–36 Pa) for wall shear stress (WSS). Independent of stenosis severity, marked differences were found in the distribution and extent of shear stress between the concentric and eccentric plaque formations. The maximum WSS, found at the apex of the stenosis, decayed significantly steeper along the outer wall of an eccentric model compared to the concentric counterpart, with a 70% eccentric stenosis having 249% steeper decay coinciding with the large outer-wall recirculation zone. The presence of ulceration (in a 50% eccentric plaque) resulted in both elevated FSS and WSS levels that were sustained longer (∼20 ms) through the systolic phase compared to the non-ulcerated counterpart model, among other notable differences. Reynolds (turbulent) shear stress, elevated around the point of distal jet detachment, became prominent during the systolic deceleration phase and was widely distributed over the large recirculation zone in the eccentric stenoses.

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          A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps.

          In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-mum-diameter) cellular-level microcalcifications in the cap, which heretofore have gone undetected because they lie below the visibility of current in vivo imaging techniques, cause local stress concentrations that lead to interfacial debonding. New theoretical solutions are presented for the local stress concentration around these minute spherical inclusions that predict a nearly 2-fold increase in interfacial stress that is relatively insensitive to the location of the hypothesized microinclusions in the cap. To experimentally confirm the existence of the hypothesized cellular-level microcalcifications, we examined autopsy specimens of coronary atheromatous lesions using in vitro imaging techniques whose resolution far exceeds conventional magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography approaches. These high-resolution imaging modalities, which include confocal microscopy with calcium-specific staining and micro-computed tomography imaging, provide images of cellular-level calcifications within the cap proper. As anticipated, the minute inclusions in the cap are very rare compared with the numerous calcified macrophages observed in the necrotic core. Our mathematical model predicts that inclusions located in an area of high circumferential stress (>300 kPa) in the cap can intensify this stress to nearly 600 kPa when the cap thickness is <65 microm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.
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            High wall shear stress and spatial gradients in vascular pathology: a review.

            Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.
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              Plaque rupture in the carotid artery is localized at the high shear stress region: a case report.

              Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. Summary of Case- We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                9 July 2014
                : 9
                : 7
                : e98209
                Affiliations
                [1 ]Department of Physics and Astronomy, University of Western Ontario, London, ON, Canada
                [2 ]Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada
                [3 ]Department of Surgery, University of Western Ontario, London, ON, Canada
                University of California Berkeley, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SK DWH TLP. Performed the experiments: SK. Analyzed the data: SK JSM. Contributed reagents/materials/analysis tools: SK JSM DWH TLP. Wrote the paper: SK JSM DWH TLP.

                Article
                PONE-D-13-43031
                10.1371/journal.pone.0098209
                4090132
                25007248
                bbc7a840-e73f-49ec-9884-723ebd3d6a20
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 October 2013
                : 30 April 2014
                Page count
                Pages: 19
                Funding
                Financial support is acknowledged from the Canada Foundation for Innovation (PIV system) and Ontario Ministry of Research and Innovation (PIV system, Early Researcher Award), Heart and Stroke Foundation of Ontario (operating grant #T-6427), Natural Sciences and Engineering Research Council of Canada (Discovery Grant), S.K. was partially supported by a Canadian Institutes of Health Research Training Fellowship in Vascular Research. D.W.H. is the Dr. Sandy Kirkley Chair of Musculoskeletal Research in the Schulich School of Medicine and Dentistry. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Fluid Physiology
                Cardiovascular Anatomy
                Biomechanics
                Biological Fluid Mechanics
                Biophysics
                Biotechnology
                Bioengineering
                Biomedical Engineering
                Engineering and Technology
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Imaging
                Hematology
                Hemodynamics
                Medical Physics
                Pulmonology
                Pulmonary Vascular Diseases
                Radiology and Imaging
                Vascular Medicine
                Vascular Diseases
                Peripheral Vascular Disease
                Atherosclerosis
                Physical Sciences
                Physics

                Uncategorized
                Uncategorized

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