Independent Scientist: ARFI and RWI Ultrasound for Improved Atherosclerosis Imagi

描述（由申请人提供）：在美国，虽然中风仍然是仅次于心脏病和癌症的第三大死亡原因，也是造成严重长期残疾的主要原因，但发病率的下降归因于包括血运重建术和他汀类药物治疗在内的干预措施。然而，现代诊断成像技术的不足限制了适当治疗的实施。这些技术对于检测与明显的管腔狭窄（闭塞）和/或血流阻塞相关的闭塞斑块是有效的，但它们对管腔特征的关注抑制了对动脉壁内非闭塞斑块的检测。此外，它们预测斑块引起脑血管事故（CVA）风险的能力尚未确定。对于一种有效的动脉粥样硬化成像方式，可以提高斑块检测和预测破裂风险，这显然是一个未被满足的需求。为了满足这一需求，我们的实验室正在开发新的基于声辐射力的图像方法，该方法可以询问表明破裂风险的组织组成和结构特征。我们正在进行的R01研究包括开发一种基于声辐射力的成像方法，声辐射力脉冲（ARFI）超声，用于动脉粥样硬化诊断。我们现在建议探索一种新的基于声辐射力的方法，反射波成像（RWI），以改善ARFI对斑块组成和结构的描绘。我们假设在体内，经皮ARFI和RWI超声能够检测外周动脉的闭塞和非闭塞斑块，并评估斑块的组成和结构。正在进行的R01研究有三个具体目标：1)确定ARFI超声检测家族性高胆固醇血症（FH）猪斑块的敏感性和特异性；2)建立ARFI成像描绘FH猪斑块组成和结构；3)建立ARFI成像描绘人类斑块及其组成和结构。我们提出了一个新的发展RWI技术的目标：4)利用声辐射力诱导的纵波和横波的反射来提高反射波成像（RWI）中斑块组成和结构的识别。将RWI单独和RWI辅助ARFI与ARFI单独进行比较，以提高成像灵敏度和特异性。PI接受过电气工程和超声物理方面的培训，但她建议在组织中进行机械波传播物理方面的额外培训，以最大限度地实现目标4。此外，PI还建议对临床试验的设计、执行和管理以及研究的道德行为进行培训。

DESCRIPTION (provided by applicant): 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.