Sarah C. Vigmostad

Plaque development, vessel curvature, and wall shear stress in coronary arteries assessed by X-ray angiography and intravascular ultrasound

The relationships among vascular geometry, hemodynamics, and plaque development in the coronary arteries are complex and not yet well understood. This paper reports a methodology for the quantitative analysis of in vivo coronary morphology and hemodynamics, with particular emphasis placed on the critical issues of image segmentation and the automated classification of disease severity. We were motivated by the observation that plaque more often developed at the inner curvature of a vessel, presumably due to the relatively lower wall shear stress at these locations. The presented studies are based on our validated methodology for the three-dimensional fusion of intravascular ultrasound (IVUS) and X-ray angiography, introducing a novel approach for IVUS segmentation that incorporates a robust, knowledge-based cost function and a fully optimal, three-dimensional segmentation algorithm. Our first study shows that circumferential plaque distribution depends on local vessel curvature in the majority of vessels. The second study analyzes the correlation between plaque distribution and wall shear stress in a set of 48 in vivo vessel segments. The results were conclusive for both studies, with a stronger correlation of circumferential plaque thickness with local curvature than with wall shear stress. The inverse relationship between local wall shear stress and plaque thickness was significantly more pronounced (p<0.025) in vessel cross sections exhibiting compensatory enlargement (positive remodeling) without luminal narrowing than when the full spectrum of disease severity was considered. The inverse relationship was no longer observed in vessels where less than 35% of vessel cross sections remained without luminal narrowing. The findings of this study confirm, in vivo, the hypothesis that relatively lower wall shear stress is associated with early plaque development.

Fluid dynamic analysis in a human left anterior descending coronary artery with arterial motion.

A computational fluid dynamic (CFD) analysis is presented to describe local flow dynamics in both 3-D spatial and 4-D spatial and temporal domains from reconstructions of intravascular ultrasound (IVUS) and bi-plane angiographic fusion images. A left anterior descending (LAD) coronary artery segment geometry was accurately reconstructed and subsequently its motion was incorporated into the CFD model. The results indicate that the incorporation of motion had appreciable effects on blood flow patterns. The velocity profiles in the region of a stenosis and the circumferential distribution of the axial wall shear stress (WSS) patterns in the vessel are altered with the wall motion introduced in the simulation. The time-averaged axial WSS between simulations of steady flow and unsteady flow without arterial motion were comparable (−0.3 to 13.7 Pa in unsteady flow versus −0.2 to 10.1 Pa in steady flow) while the magnitudes decreased when motion was introduced (0.3–4.5 Pa). The arterial wall motion affects the time-mean WSS and the oscillatory shear index in the coronary vessel fluid dynamics and may provide more realistic predictions on the progression of atherosclerotic disease.

Vocal Fold Elasticity in the Pig, Sheep, and Cow Larynges

Elastic characteristics of the pig, sheep, and cow vocal folds were investigated through a series of in vitro experiments. Sample strips of the vocal-fold tissue were dissected from pig, sheep, and cow vocal folds and mounted inside a saline-filled ergometer chamber that was maintained at 37°C ± 1°C. Sinusoidal elongation was applied on the samples to obtain the passive force measurements. Force and elongation data from the samples were recorded electronically with a dual-servo system (ergometer). Stress-Strain data were compared to characterize the interspecies differences in the elastic properties of vocal folds. Pig vocal folds exhibited the most nonlinear stress-strain relationship, indicating the presence of a high level of collagen fibers. Cow vocal folds had the highest Youngs modulus, but the tissue displayed a nearly linear stress-strain profile. Previous studies of phonation in these three species have indicated that pig larynges have the highest range of phonation frequencies, making them a good candidate for animal studies. The current study provides quantitative data for the elastic properties of the oscillating laryngeal tissue in these species and indicates that nonlinear behavior of these tissues may lead to wider oscillation ranges.

Patient-specific bicuspid valve dynamics: Overview of methods and challenges

About 1-2 % of the babies are born with bicuspid aortic valves instead of the normal aortic valve with three leaflets. A significant portion of the patients with the congenital bicuspid valve morphology suffer from aortic valve stenosis and/or ascending aortic dilatation and dissection thus requiring surgical intervention when they are young adults. Patients with bicuspid aortic valves (BAVs) have also been found to develop valvular stenosis earlier than those with the normal aortic valve. This paper overviews current knowledge of BAVs, where several studies have suggested that the mechanical stresses induced on the valve leaflets and the abnormal flow development in the ascending aorta may be an important factor in the diseases of the valve and the aortic root. The long-term goals of the studies being performed in our laboratory are aimed towards potential stratification of bicuspid valve patients who may be at risk for developing these pathologies based on analyzing the hemodynamic environment of these valves using fluid-structure interaction (FSI) modeling. Patient-specific geometry of the normal tri-cuspid and bicuspid valves are reconstructed from real-time 3D ultrasound images and the dynamic analyses performed in order to determine the potential effects of mechanical stresses on the valve leaflet and aortic root pathology. This paper describes the details of the computational tools and discusses challenges with patient-specific modeling.

Multidimensional segmentation of coronary intravascular ultrasound images using knowledge-based methods

In vivo studies of the relationships that exist among vascular geometry, plaque morphology, and hemodynamics have recently been made possible through the development of a system that accurately reconstructs coronary arteries imaged by x-ray angiography and intravascular ultrasound (IVUS) in three dimensions. Currently, the bottleneck of the system is the segmentation of the IVUS images. It is well known that IVUS images contain numerous artifacts from various sources. Previous attempts to create automated IVUS segmentation systems have suffered from either a cost function that does not include enough information, or from a non-optimal segmentation algorithm. The approach presented in this paper seeks to strengthen both of those weaknesses -- first by building a robust, knowledge-based cost function, and then by using a fully optimal, three-dimensional segmentation algorithm. The cost function contains three categories of information: a compendium of learned border patterns, information theoretic and statistical properties related to the imaging physics, and local image features. By combining these criteria in an optimal way, weaknesses associated with cost functions that only try to optimize a single criterion are minimized. This cost function is then used as the input to a fully optimal, three-dimensional, graph search-based segmentation algorithm. The resulting system has been validated against a set of manually traced IVUS image sets. Results did not show any bias, with a mean unsigned luminal border positioning error of 0.180 ± 0.027 mm and an adventitial border positioning error of 0.200 ± 0.069 mm.

Peak Wall Stress Predicts Expansion Rate in Descending Thoracic Aortic Aneurysms

BACKGROUND Aortic diseases, including aortic aneurysms, are the 12th leading cause of death in the United States. The incidence of descending thoracic aortic aneurysms is estimated at 10.4 per 100,000 patient-years. Growing evidence suggests that stress measurements derived from structural analysis of aortic geometries predict clinical outcomes better than diameter alone. METHODS Twenty-five patients undergoing clinical and radiologic surveillance for thoracic aortic aneurysms were retrospectively identified. Custom MATLAB algorithms were employed to extract aortic wall and intraluminal thrombus geometry from computed tomography angiography scans. The resulting reconstructions were loaded with 120 mm Hg of pressure using finite element analysis. Relationships among peak wall stress, aneurysm growth, and clinical outcome were examined. RESULTS The average patient age was 71.6 ± 10.0 years, and average follow-up time was 17.5 ± 9 months (range, 6 to 43). The mean initial aneurysm diameter was 47.8 ± 8.0 mm, and the final diameter was 52.1 ± 10.0 mm. Mean aneurysm growth rate was 2.9 ± 2.4 mm per year. A stronger correlation (r = 0.894) was found between peak wall stress and aneurysm growth rate than between maximal aortic diameter and growth rate (r = 0.531). Aneurysms undergoing surgical intervention had higher peak wall stresses than aneurysms undergoing continued surveillance (300 ± 75 kPa versus 229 ± 47 kPa, p = 0.01). CONCLUSIONS Computational peak wall stress in thoracic aortic aneurysms was found to be strongly correlated with aneurysm expansion rate. Aneurysms requiring surgical intervention had significantly higher peak wall stresses. Peak wall stress may better predict clinical outcome than maximal aneurysmal diameter, and therefore may guide clinical decision-making.

Measurement of Vocal Folds Elastic Properties for Continuum Modeling

OBJECTIVE This study aimed to quantify the major elastic properties of human vocal folds lamina propria, including longitudinal and transverse Youngs modulus, shear modulus, and Poissons ratio. METHODS Samples were obtained from cadaveric human larynges that were snap frozen within 48 hours postmortem and kept at -82°F and thawed overnight in saline solution. Once the sample was tested in the longitudinal direction, two special brackets were glued to the side of each sample and the sample was mounted with brackets in the transverse direction. The shear modulus was obtained from samples mounted between two parallel plates applying shear forces. The Poisson ratio was obtained using high-speed video imaging of two-dimensional samples with markers for longitudinal and transverse strain measurements. RESULTS Results indicate that human vocal fold elasticity is very nonlinear with slope that increases 10-15 times from low- to high-strain values. Its average low-strain Youngs modulus is approximately 30 kPa in the longitudinal direction and 1 kPa in the transverse direction. The vocal fold longitudinal shear modulus is in the same order of magnitude of its transverse shear modulus (less than 1 kPa). The average Poisson ratio is approximately 0.57. CONCLUSIONS The present study provides quantitative data for the longitudinal and transverse elastic properties of the human vocal fold tissue and indicates that nonlinear behavior and relative difference of these properties may lead to wide ranges of oscillation frequency and amplitude in human larynges.

Comparison of Left Anterior Descending Coronary Artery Hemodynamics Before and After Angioplasty

Coronary artery disease (CAD) is characterized by the progression of atherosclerosis, a complex pathological process involving the initiation, deposition, development, and breakdown of the plaque. The blood flow mechanics in arteries play a critical role in the targeted locations and progression of atherosclerotic plaque. In coronary arteries with motion during the cardiac contraction and relaxation, the hemodynamic flow field is substantially different from the other arterial sites with predilection of atherosclerosis. In this study, our efforts focused on the effects of arterial motion and local geometry on the hemodynamics of a left anterior descending (LAD) coronary artery before and after clinical intervention to treat the disease. Three-dimensional (3D) arterial segments were reconstructed at 10 phases of the cardiac cycle for both pre- and postintervention based on the fusion of intravascular ultrasound (IVUS) and biplane angiographic images. An arbitrary Lagrangian-Eulerian formulation was used for the computational fluid dynamic analysis. The measured arterial translation was observed to be larger during systole after intervention and more out-of-plane motion was observed before intervention, indicating substantial alterations in the cardiac contraction after angioplasty. The time averaged axial wall shear stress ranged from -0.2 to 9.5 Pa before intervention compared to -0.02 to 3.53 Pa after intervention. Substantial oscillatory shear stress was present in the preintervention flow dynamics compared to that in the postintervention case.

Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study.

Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS) on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH) and transformed prostate cancer cells (PC-3) were used in this study. The Young’s modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared) and immediately after exposure to high (6,400 dyn/cm2) and low (510 dyn/cm2) FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young’s modulus after exposure to high FSS and a ~47% increase in Young’s modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young’s modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young’s modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study investigating the effect of FSS on the mechanical properties of cancer cells in suspension, and may provide significant insights into the mechanism by which some select cancer cells may survive in the circulation, ultimately leading to metastasis at distal sites. Our findings suggest that biomechanical analysis of cancer cells could aid in identifying and diagnosing cancer in the future.

Micro-scale blood particulate dynamics using a non-uniform rational B-spline-based isogeometric analysis

The current research presents a novel method in which blood particulates - biconcave red blood cells (RBCs) and spherical cells are modeled using isogeometric analysis, specifically Non-Uniform Rational B-Splines (NURBS) in 3-D. The use of NURBS ensures that even with a coarse representation, the geometry of the blood particulates maintains an accurate description when subjected to large deformations. The fundamental advantage of this method is the coupling of the geometrical description and the stress analysis of the cell membrane into a single, unified framework. Details on the modeling approach, implementation of boundary conditions and the membrane mechanics analysis using isogeometric modeling are presented, along with validation cases for spherical and biconcave cells. Using NURBS - based isogeometric analysis, the behavior of individual cells in fluid flow is presented and analyzed in different flow regimes using as few as 176 elements for a spherical cell and 220 elements for a biconcave RBC. This work provides a framework for modeling a large number of 3-D deformable biological cells, each with its own geometric description and membrane properties. To the best knowledge of the authors, this is the first application of the NURBS - based isogeometric analysis to model and simulate blood particulates in flow in 3D.