Atherosclerotic plaque disruption leading to thrombosis has traditionally been studied as a rupture of a thin fibrous cap over a lipid-laden necrotic core. However, two noteworthy categories of plaques that do not rupture have presented themselves: 1) in mice, plaque rupture is rare if not absent, and 2) in humans, some plaques erode and form a thrombus without rupturing. Current understanding of the biomechanical differences between plaques that rupture and those that do not is incomplete. In this research, we used patient-specific computational biomechanics tools to study differences among these groups. Lesion-specific solid mechanical modeling of murine plaques revealed that the relative distribution of stresses differs considerably between mice and man. In human vulnerable plaques, peak stresses are on the thin fibrous cap over a necrotic core, but in mice the highest stresses are in the media and adventitia, away from the plaque. Whereas atherosclerotic human arteries usually experience neointima formation around the entire circumference of the vessel, mouse plaques tend to be punctate and adjacent lesion-free regions. The difference in mechanical environment suggests that plaque rupture, if possible in mice, is likely not driven by mechanics in the same manner as humans. Similar mechanical modeling of human ruptured and eroded plaques and comparison to histological staining revealed that ruptured plaques exhibit increased levels of inflammatory markers in response to strain in ruptured plaques, but no such response was observed in plaque erosion. This suggests that treatment of inflammation, a current paradigm for care of atherosclerotic patients, may not be an effective approach to mediate plaque erosion. Computational fluid dynamics modeling of patients with plaque erosion revealed no relation between wall shear stress magnitude or direction, further suggesting that the mechanism of plaque erosion differs considerably from that of plaque rupture. Together, these findings suggest that biomechanics can help explain why not all plaques rupture and that different clinical approaches are necessary to address different phenotypes of lesions.

Cardiovascular Disease (CVD) continues to be the leading cause of death in western countries according to the statistics update by the American Heart Association. Atherosclerosis is estimated to be responsible for a large portion of CVD and affects 60 million people in the United States. Accurate diagnosis is crucial for proper treatment planning. Currently, the clinical standard screening technique for diagnosing atherosclerosis is x-ray angiography, which reveals the residual lumen size. X-ray angiographic images possess good resolution and contrast, however, lumen size is not always a proper criterion given the positive remodeling nature of atherosclerotic plaques. In the past decade, it has been shown that most plaques responsible for a fatal or nonfatal myocardial infarction are less than 70% stenosed. Clinical data support the idea that plaques producing non-flow-limiting stenoses account for more cases of plaque rupture and thrombosis than plaques producing a more severe stenosis. Due to this fact, plaque itself must be imaged in order to assess its vulnerability. A wealth of literature suggests that multicontrast MRI has the potential of characterizing plaque constituents, and thus is a promising technique for plaque imaging. Because of the technical difficulties associated with in-vivo plaque imaging and the fact that our research was aimed at developing new methodologies, our approaches was to image excised coronary arteries under simulated in-vivo conditions in a tissue culture chamber. It is shown by this research that automatic plaque characterization techniques developed under ex-vivo conditions still apply for in-vivo studies. Based on this finding, an automatic plaque characterization technique using multicontrast MRI was developed. Furthermore, "shared k-space" reconstruction techniques were interrogated to assess their feasibility in accelerating multicontrast MRI acquisition. Results show that these techniques are promising in accelerating multicontrast MRI acquisitions.

Not available / text

No description available.

No description available.

Thesis (Ph. D.)--University of Canterbury, 2008. / Typescript (photocopy). Includes bibliographical references (p. 211-250). Also available via the World Wide Web.

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Hanjoong Jo; Committee Member: Ajit P. Yoganathan; Committee Member: Andrew P. Kowalczyk; Committee Member: David G. Harrison; Committee Member: Kathy K. Griendling

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 109-125.

No description available.

A vast majority of heart attacks occur due to rapid progression of plaque buildup in the coronary arteries that supply blood to the heart muscles. The diseased arteries can be treated with drugs delivered locally to vulnerable plaques—ones that may rupture and release emboli, resulting in the formation of thrombus, or blood clot that can cause blockage of the arterial lumen. In designing these local drug delivery devices, important issues regarding drug distribution and targeting need to be addressed to ensure device design optimization as physiological forces can cause the local concentration to be very different from mean drug tissue concentration estimated from in vitro experiments and animal studies. Therefore, the main objective of this work was to develop a computational tool-set to support the design of a catheter-based local drug delivery system that uses nanoparticles as drug carriers by simulating drug transport and quantifying local drug distribution in coronary artery walls. Toward this end, a three dimensional mathematical model of coupled transport of drug and drug-encapsulated nanoparticles was developed and solved numerically by applying finite element based isogeometric analysis that uses NURBS-based techniques to describe the artery wall geometry. To gain insight into the parametric sensitivity of drug distribution, a study of the effect of Damkohler number and Peclet number was carried out. The tool was then applied to a three-dimensional idealized multilayered model of the coronary artery wall under healthy and diseased condition. Preliminary results indicated that use of realistic geometry is essential in creating physiological flow features and transport forces necessary for developing catheter-based drug delivery design procedures. Hence, simulations were run on a patient-specific coronary artery wall segment with a typical atherosclerotic plaque characterized by a lipid pool encased by a thin fibrous cap. Results show that plaque heterogeneity and artery wall inhomogeneity have a considerable effect on drug distribution. The computational tool-set developed was able to successfully capture trends observed in local drug delivery by incorporating a multitude of relevant physiological phenomena, and thus demonstrated its potential utility in optimizing drug design parameters including delivery location, nanoparticle surface properties and drug release rate. / text