While stroke remains the third leading cause of death behind heart disease and cancer and the primary cause of serious, long-term disability in the United States, decreasing incidence has been attributed to interventions including revascularization and statin therapy. However, administration of proper treatment is limited by inadequacies in modern diagnostic imaging technologies. These technologies are effective for detecting occlusive plaques associated with pronounced lumenal narrowing (occlusion) and/or blood flow obstruction, but 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) is not established. 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 novel acoustic radiation force-based images methods, which interrogate tissue composition and structure - features that indicate rupture risk. Our on-going R01 research involves developing one acoustic radiation force-based imaging methods, Acoustic Radiation Force Impulse (ARFI) ultrasound, for atherosclerosis diagnosis. We now propose to explore a new acoustic radiation force-based method, Relfected Wave Imaging (RWI), to improve ARFI's delineation of plaque composition and structure. We hypothesize that in vivo, transcutaneous ARFI and RWI ultrasound are capable of detecting occlusive and nonocclusive plaques in peripheral arteries and of assessing plaque composition and structure. The on-going R01 research pursues three specific aims: 1) Define the sensitivity and specificity of ARFI ultrasound for detecting plaques in familial hypercholesterolemic (FH) pigs, 2) Establish that ARFI imaging delineates plaque composition and structure in FH pigs, and 3) Establish that ARFI imaging delineates plaques and their composition and structure in humans. We now propose a new aim to develop RWI technology: 4) Exploit the reflections of acoustic radiation force-induced longitudinal and transverse waves to improve discrimination of plaque composition and structure in Reflected Wave Imaging (RWI). RWI alone and RWI as an adjunct to ARFI will be compared to ARFI alone for improvements in imaging sensitivity and specificity. The PI is trained in electrical engineering and ultrasound physics, but she proposes additional training in the physics of mechanical wave propagation in tissue to pursue aim #4 to her fullest capacity. In addition, the PI proposes training in clinical trials design, execution, and management as well as ethical conduct of research.

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 novel ultrasound imaging technologies - Acoustic Radiation Force Impulse (ARFI) and Reflected Wave Imaging (RWI) 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 Scientist Development Award - Research (K02)
Project #
5K02HL105659-05
Application #
8677959
Study Section
Special Emphasis Panel (ZHL1-CSR-U (O1))
Program Officer
Wang, Wayne C
Project Start
2010-09-15
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$101,800
Indirect Cost
$7,541
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
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
Hossain, Md Murad; Thapa, Diwash; Sierchio, Justin et al. (2016) Blind Source Separation - Based Motion Detector for Sub-Micrometer, Periodic Displacement in Ultrasonic Imaging. IEEE Int Ultrason Symp 2016:
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
Czernuszewicz, Tomasz J; Streeter, Jason E; Dayton, Paul A et al. (2013) Experimental validation of displacement underestimation in ARFI ultrasound. Ultrason Imaging 35:196-213

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