Current clinical criteria for treatment of atherosclerotic plaque or atheromas, has focused primarily on percent stenosis of the vessel. However, percent stenosis does not identify plaque prone to rupture that may release emboli into the blood stream of the sensitive cerebral vasculature. These 'vulnerable'plaques are particularly prone to produce sudden major problems, such as a heart attack or stroke. Atheromas become vulnerable if they grow rapidly and have only a thin fibrous cap separating the soft lipid pool and other plaque constituents from the bloodstream. Structural stability of carotid plaque is a result of its chemical composition, cellular material and new vessel formation. Various studies have indicated that pulsatile pressure induced due to blood flow may rupture the thin cap overlying lipid rich lesions, leading to subsequent thrombosis and plaque rupture. Plaque vulnerability is therefore determined primarily by the mechanical (elastic) properties of the vessel wall and plaque composition. Ultrasound-based strain imaging can provide a means of identifying vulnerable plaque. A novel approach to strain imaging, where pulsation of blood through the carotid artery is used to induce tissue displacements for strain imaging, will be developed and evaluated. We propose the use of three 'strain indices'namely;maximum accumulated axial strain, maximum lateral displacement and strain, and shear strains in plaque over the cardiac cycle as measures of plaque vulnerability. To obtain the normal and shear strain tensors, we propose to utilize beam-steered radiofrequency data acquired along different angular insonification directions to compute the displacement vectors and subsequently the strain tensors. We will also incorporate a modified dynamic 2D multi-level cross-correlation method to track local displacements with the angular data acquired. Our preliminary results demonstrate the ability to differentiate between soft and stiffer plaque noninvasively. The long term objectives are to provide a non-invasive measurement of patients at risk for plaque rupture, expanding upon the current criteria for treatment for atherosclerotic risk based on focal transient ischemic attacks or strokes. The limited in-vivo study on patients will be complimented by a similar analysis on a control group of age-matched volunteers to determine the significance of the 'strain indices'for discrimination of vulnerable plaque. Finally, the entire excised plaque core following carotid endarterectomy will be further evaluated using histological analysis at the same in-vivo transverse cross-sections (based on measurements from the flow- divider) where strain imaging was performed to better understand plaque composition and structure (along with microulcerations and neovascularity) to the information displayed on the normal and shear strain images.

Public Health Relevance

Ultrasound-based strain imaging can provide a means of identifying vulnerable plaque. A novel approach to strain imaging, where pulsation of blood through the carotid artery is used to induce tissue displacements for strain imaging, will be developed and evaluated. One of the goals of this research is to help determine patients at risk for stroke, while excluding patients with manageable risk from undergoing surgery, both of which would dramatically reduce healthcare costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB010098-01
Application #
7773096
Study Section
Special Emphasis Panel (ZRG1-SBIB-S (91))
Program Officer
Lopez, Hector
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$222,750
Indirect Cost
Name
University of Wisconsin Madison
Department
Physics
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Meshram, N H; Varghese, T; Mitchell, C C et al. (2017) Quantification of carotid artery plaque stability with multiple region of interest based ultrasound strain indices and relationship with cognition. Phys Med Biol 62:6341-6360
Wang, Xiao; Jackson, Daren C; Mitchell, Carol C et al. (2016) Classification of Symptomatic and Asymptomatic Patients with and without Cognitive Decline Using Non-invasive Carotid Plaque Strain Indices as Biomarkers. Ultrasound Med Biol 42:909-18
Wang, X; Mitchell, C C; Varghese, T et al. (2016) Improved Correlation of Strain Indices with Cognitive Dysfunction with Inclusion of Adventitial Layer with Carotid Plaque. Ultrason Imaging 38:194-208
Ma, Chi; Wang, Xiao; Varghese, Tomy (2016) Segmental Analysis of Cardiac Short-Axis Views Using Lagrangian Radial and Circumferential Strain. Ultrason Imaging 38:363-383
Ma, Chi; Varghese, Tomy (2014) Analysis of 2-d ultrasound cardiac strain imaging using joint probability density functions. Ultrasound Med Biol 40:1118-32
Wang, Xiao; Jackson, Daren C; Varghese, Tomy et al. (2014) Correlation of cognitive function with ultrasound strain indices in carotid plaque. Ultrasound Med Biol 40:78-89
Wang, X; Jackson, D C; Mitchell, C C et al. (2014) Estimation of ultrasound strain indices in carotid plaque and correlation to cognitive dysfunction. Conf Proc IEEE Eng Med Biol Soc 2014:5627-30
Ma, Chi; Varghese, Tomy (2013) Comparison of cardiac displacement and strain imaging using ultrasound radiofrequency and envelope signals. Ultrasonics 53:782-92
McCormick, Matthew M; Varghese, Tomy (2013) An approach to unbiased subsample interpolation for motion tracking. Ultrason Imaging 35:76-87
Ge, Wenqi; Krueger, Christian G; Weichmann, Ashley et al. (2012) Displacement and strain estimation for evaluation of arterial wall stiffness using a familial hypercholesterolemia swine model of atherosclerosis. Med Phys 39:4483-92

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