Independent Scientist: ARFI and RWI Ultrasound for Improved Atherosclerosis Imagi

描述(申请人提供)：尽管中风仍然是美国第三大致死原因，仅次于心脏病和癌症，也是导致严重、长期残疾的主要原因，但发病率的下降归因于包括血管重建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管理。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阻碍了对动脉壁中包含的非闭塞斑块的检测。此外，他们预测导致脑血管意外(CVA)的斑块风险的能力还没有确定。有一个明显的未得到满足的需求，验证动脉粥样硬化成像方式，可以改善斑块检测和预测破裂风险。为了满足这一需求，我们的实验室正在开发基于声辐射力的新型成像方法，该方法可以询问组织成分和结构特征，这些特征表明破裂风险。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，即声辐射力脉冲(ARFI)超声，用于动脉粥样硬化的诊断。我们现在建议探索一种新的基于声辐射力的方法，即重新影响波成像(RWI)，以改进ARFI对斑块成分和结构的描绘。我们假设，在活体内，经皮ARFI和RWI超声能够检测周围动脉闭塞和非闭塞的斑块，并评估斑块的成分和结构。正在进行的R01研究追求三个具体目标：1)明确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猪的斑块成分和结构，以及3)建立ARFI成像描绘人类的斑块及其组成和结构。我们现在提出了一个发展RWI技术的新目标：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中斑块成分和结构的分辨能力。在提高成像敏感性和特异度方面，单独使用RWI和作为ARFI辅助检查的RWI将与单独使用ARFI进行比较。这位PI接受了电气工程和超声波物理学方面的培训，但她建议在组织中机械波传播的物理学方面进行额外的培训，以实现目标4的最大能力。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.