While stroke remains the primary cause of death behind heart disease and cancer and the leading cause of serious, long-term disability in the United States (Rosamond et al 2008), decreasing incidence has been attributed to interventions including revascularization and statin therapy (Collins et al 2004). However, administration of proper treatment is limited by inadequacies in modern diagnostic technologies (Dhopra et al 2007). A variety of imaging methods are routinely employed to diagnosis peripheral atherosclerosis, including digital subtraction angiography as well as noninvasive alternatives such as magnetic resonance angiography (MRA) and duplex ultrasound. Although these imaging methods are known to be effective for detecting occlusive plaques associated with pronounced narrowing of the vessel lumen and/or blood flow obstruction, their focus on lumenal features inhibits detection of nonocclusive plaques contained in arterial walls. Furthermore, their ability to predict plaque risk for causing cerebrovascular accident (CVA) has not been well established (Raggi et al 2005). These diagnostic shortcomings result in as many as 50% of high-risk atherosclerotic plaques going undetected (Veller et al 1993), which leads to `sudden stroke'with no advanced warning of underlying disease or the ability to mitigate. On the other hand, overly aggressive plaque risk assessment in the case of stable plaques leads to unnecessary, high-risk invasive procedures that confer no additional benefit over intensive drug therapy (Golledge et al 2007). There is a clear unmet need for a validated atherosclerosis imaging modality that can improve plaque detection and predict rupture risk. To address this need, our laboratory is developing a novel, noninvasive diagnostic atherosclerosis imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - which exploits tissue composition by interrogating tissue material properties. Our preliminary studies show that in vivo ARFI imaging detected occlusive and nonocclusive plaques and described plaque collagen and elastin composition, which are material features relevant to predicting plaque risk (Behler et al 2006), (Behler et al 2007a), (Behler et al 2007b). The long-term goal of this research program is to develop noninvasive ARFI ultrasound for early plaque detection and identification of plaques at high risk for initiating CVA as well as cardiovascular events. The attractiveness of this line of inquiry lies not only in the potential to diminish CVD's enormous human impact by improving screening and enabling early interventions, but also in the potential to monitor existing therapies and develop new ones. As a critical first step toward achieving our long-term goal, the objectives of the proposed research are to demonstrate ARFI imaging for detecting plaques and for assessing their composition and structure in peripheral arteries. We hypothesize that in vivo, transcutaneous ARFI ultrasound is capable of detecting occlusive and nonocclusive plaques in peripheral arteries and of assessing plaque composition. ARFI plaque detection and compositional assessment may be validated in FH pig iliac arteries and in human carotid arteries.

Public Health Relevance

Stroke is the third leading cause of death and the primary cause of serious, long-term disability in the United States. Although timely and appropriate treatment is critical to saving lives, shortcomings in conventional diagnostic imaging technologies prevent advanced warning of the disease and delay therapy. The objectives of this research proposal are to demonstrate a novel ultrasound imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - for improved diagnosis of atherosclerotic plaques and stroke risk.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL092944-03
Application #
8090446
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Buxton, Denis B
Project Start
2009-08-01
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$366,541
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Moore, Christopher J; Caughey, Melissa C; Meyer, Diane O et al. (2018) In Vivo Viscoelastic Response (VisR) Ultrasound for Characterizing Mechanical Anisotropy in Lower-Limb Skeletal Muscles of Boys with and without Duchenne Muscular Dystrophy. Ultrasound Med Biol 44:2519-2530
Hossain, Md Murad; Levy, Benjamin E; Thapa, Diwash et al. (2018) Blind Source Separation-Based Motion Detector for Imaging Super-Paramagnetic Iron Oxide (SPIO) Particles in Magnetomotive Ultrasound Imaging. IEEE Trans Med Imaging 37:2356-2366
Hossain, Md Murad; Selzo, Mallory R; Hinson, Robert M et al. (2018) Evaluating Renal Transplant Status Using Viscoelastic Response (VisR) Ultrasound. Ultrasound Med Biol 44:1573-1584
Torres, Gabriela; Czernuszewicz, Tomasz J; Homeister, Jonathon W et al. (2017) ARFI variance of acceleration (VoA) for noninvasive characterization of human carotid plaques in vivo. Conf Proc IEEE Eng Med Biol Soc 2017:2984-2987
Czernuszewicz, Tomasz J; Homeister, Jonathon W; Caughey, Melissa C et al. (2017) Performance of acoustic radiation force impulse ultrasound imaging for carotid plaque characterization with histologic validation. J Vasc Surg 66:1749-1757.e3
Selzo, Mallory R; Moore, Christopher J; Hossain, Md Murad et al. (2016) On the Quantitative Potential of Viscoelastic Response (VisR) Ultrasound Using the One-Dimensional Mass-Spring-Damper Model. IEEE Trans Ultrason Ferroelectr Freq Control 63:1276-87
Wang, Zhuochen; Li, Sibo; Czernuszewicz, Tomasz J et al. (2016) Design, Fabrication, and Characterization of a Bifrequency Colinear Array. IEEE Trans Ultrason Ferroelectr Freq Control 63:266-74
Czernuszewicz, Tomasz J; Gallippi, Caterina M (2016) On the Feasibility of Quantifying Fibrous Cap Thickness With Acoustic Radiation Force Impulse (ARFI) Ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 63:1262-75
Geist, Rebecca E; DuBois, Chase H; Nichols, Timothy C et al. (2016) Experimental Validation of ARFI Surveillance of Subcutaneous Hemorrhage (ASSH) Using Calibrated Infusions in a Tissue-Mimicking Model and Dogs. Ultrason Imaging 38:346-58
Czernuszewicz, Tomasz J; Homeister, Jonathon W; Caughey, Melissa C et al. (2015) Non-invasive in vivo characterization of human carotid plaques with acoustic radiation force impulse ultrasound: comparison with histology after endarterectomy. Ultrasound Med Biol 41:685-97

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