The long-term goal of this project is to identify characteristic features of the vulnerable plaque, defined as an atherosclerotic lesion that poses an increased risk for thromboembolic complications. In this proposal, we plan to study mechanisms that may lead to the development of the vulnerable plaque using high resolution MRI. To achieve these goals, we will serially examine a cohort of subjects with moderate carotid stenosis to identify changes in the MRI appearance of the artery as it evolves from a clinically silent, stable plaque to a symptomatic, culprit lesion. Histological studies suggest that the vulnerable plaque is characterized by thinning and rupture of the fibrous cap that overlies the thrombogenic necrotic core. Other studies also suggest an important role for plaque neovasculature. Neovessels within plaque are believed to represent a pathway for macrophage infiltration, and these macrophages have been shown to express matrix metalloproteinases that can weaken the fibrous cap. Previous studies have shown that MRI is capable of precisely measuring plaque volume, distinguish thick fibrous caps from thin or ruptured caps, and identify regions with plaque neovasculature.
The specific aims of this study are: 1. Test the hypothesis that fibrous cap thinning and rupture precedes increase in plaque volume 2. Test the hypothesis that plaques with increased neovasculature are more likely progress from a thick cap to a thin or ruptured cap lesion, and are more likely to demonstrate progression in plaque volume 3. Test the hypothesis that progression from a thick cap to a thin or disrupted cap lesion correlates with the onset of an ischemic neurological event or histological evidence of cap thinning or rupture. A better understanding of the mechanisms leading to the development of the vulnerable plaque may provide new targets for therapy. Furthermore, identification of additional high-risk plaque features, other than the degree of lumen stenosis, may lead to better selection of patients for intervention, such as carotid endarterectomy, and result in overall reduction in health care costs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL073401-01
Application #
6602315
Study Section
Special Emphasis Panel (ZRG1-CCVS (01))
Program Officer
Wassef, Momtaz K
Project Start
2003-06-01
Project End
2007-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$570,586
Indirect Cost
Name
University of Washington
Department
Surgery
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Daemen, Mat J; Ferguson, Marina S; Gijsen, Frank J et al. (2016) Carotid plaque fissure: An underestimated source of intraplaque hemorrhage. Atherosclerosis 254:102-108
Xu, Dongxiang; Hippe, Daniel S; Underhill, Hunter R et al. (2014) Prediction of high-risk plaque development and plaque progression with the carotid atherosclerosis score. JACC Cardiovasc Imaging 7:366-73
Tang, Dalin; Kamm, Roger D; Yang, Chun et al. (2014) Image-based modeling for better understanding and assessment of atherosclerotic plaque progression and vulnerability: data, modeling, validation, uncertainty and predictions. J Biomech 47:834-46
Tang, Dalin; Yang, Chun; Canton, Gador et al. (2013) Correlations between carotid plaque progression and mechanical stresses change sign over time: a patient follow up study using MRI and 3D FSI models. Biomed Eng Online 12:105
Canton, Gador; Chiu, Bernard; Chen, Huijun et al. (2013) A framework for the co-registration of hemodynamic forces and atherosclerotic plaque components. Physiol Meas 34:977-90
Kerwin, William S; Hatsukami, Thomas; Yuan, Chun et al. (2013) MRI of carotid atherosclerosis. AJR Am J Roentgenol 200:W304-13
Sun, Jie; Underhill, Hunter R; Hippe, Daniel S et al. (2012) Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: a long-term time course study. JACC Cardiovasc Imaging 5:798-804
Makhijani, Mahender K; Balu, Niranjan; Yamada, Kiyofumi et al. (2012) Accelerated 3D MERGE carotid imaging using compressed sensing with a hidden Markov tree model. J Magn Reson Imaging 36:1194-202
Balu, Niranjan; Yarnykh, Vasily L; Chu, Baocheng et al. (2011) Carotid plaque assessment using fast 3D isotropic resolution black-blood MRI. Magn Reson Med 65:627-37
Yang, Chun; Canton, Gador; Yuan, Chun et al. (2011) Impact of flow rates in a cardiac cycle on correlations between advanced human carotid plaque progression and mechanical flow shear stress and plaque wall stress. Biomed Eng Online 10:61

Showing the most recent 10 out of 30 publications