Dual-frequency intravascular arrays for functional imaging of atherosclerosis

说明(申请人提供)：心血管疾病(动脉粥样硬化)是发达国家心血管疾病死亡和发病率的主要原因。冠状动脉粥样硬化的成像，更具体地说，是非侵入性评估动脉粥样斑块不稳定性的方法，在这种疾病的诊断和治疗中至关重要。目前，X射线血管造影术和灰阶血管内超声(IVUS)被用于动脉粥样硬化斑块的评估，但这两种方法对斑块狭窄程度或斑块形态提供的信息有限。不幸的是，现在人们认为这两个特征都不能预测斑块的易损性，相反，数据表明导致梗塞的动脉粥样硬化斑块通常是非狭窄的。新的后处理IVUS技术包括IVUS虚拟组织学、集成后向散射分析和掌纹成像，这些技术可以提高检测纤维组织、纤维脂肪组织和坏死核心组织的准确性。然而，IVUS成像分辨率、钙化组织的穿透深度和组织分类挑战仍然是使用这些后处理技术进行更全面的疾病评估的障碍。因此，我们目前评估动脉粥样硬化斑块不稳定性的能力仍然非常有限。最近涉及增强血管成像和斑块相关炎症和血管生成生物标记物的分子成像的最新研究表明，这些对比成像技术可以提供评估斑块不稳定性的关键信息。然而，微泡造影剂的非线性检测策略在其共振频率附近最有效，通常在1-10 MHz之间，远低于IVUS成像频率(20-45 MHz)。因此，为非线性对比成像设计的静脉内超声导管是不可用的。最近展示的一种利用造影剂的超宽带响应的高频成像策略在20 MHz以上的频率下提供非常高的信噪比、高分辨率的对比度成像，但需要一种新型的双频超宽带换能器。在本项目中，将使用微机械压电复合材料(MPC)超声换能器技术为IVUS设计这样的换能器。利用深反应离子刻蚀和多层膜技术，将研制出8元5 MHz、元40 MHz组件的双频圆形阵列。利用制造的双频阵列，将开发用于双模式成像(IVUS和对比度增强IVUS)的多通道、多频率电子设备。对比剂-IVUS将在体外体模和体外组织中进行，以评估原型换能器，然后在临床前动脉粥样硬化标准的体内成像，家族性高胆固醇症猪。拟议的高分辨率血管内超声将提供一个强大和创新的新工具，为医生提供更准确的动脉粥样硬化诊断，促进对冠状动脉疾病病理生理学的理解，并促进新型心血管药物和设备疗法的开发。

DESCRIPTION (provided by applicant): Cardiovascular disease (atherogenesis) is the leading cause of cardiovascular mortality and morbidity in the developed world. The imaging of coronary atherosclerosis, and more specifically, methods to noninvasively assess the instability of atheromatous plaques, is critically important in the diagnosis and treatment of this disease. X-ray angiography and gray scale intravascular ultrasound (IVUS) are currently utilized in atherosclerotic plaque assessment, and both of these methods provide limited information as to the stenosis degree or plaque morphology. Unfortunately, it is now believed that neither feature is predictive of plaque vulnerability, and on the contrary, data suggests that atherosclerotic plaques that lead to infarction are often non-stenotic. New post-processing IVUS techniques include IVUS virtual histology, integrated backscatter analysis, and palpography, which can provide enhanced accuracy for detecting fibrous, fibrofatty, and necrotic core tissue. However, IVUS imaging resolution, penetration depth in calcified tissue, and tissue classification challenges are still obstacles to more comprehensive disease assessment using these post processing techniques. Thus, our current ability for assessing the instability of atherosclerotic plaques remains extremely limited. Recent research involving contrast enhanced vasa vasorum imaging and molecular imaging of plaque- associated inflammatory and angiogenic biomarkers suggests that these contrast imaging techniques can provide critical information to assess plaque instability. However, nonlinear detection strategies for microbubble contrast agents are most effective near their resonant frequency, which is typically between 1-10 MHz, much lower that the IVUS imaging frequency (20-45 MHz). Thus, IVUS catheters designed for nonlinear contrast imagings are not available. A recently demonstrated high-frequency imaging strategy utilizing the ultra- broadband response of contrast agents provides very high signal to noise, high-resolution contrast imaging at frequencies above 20 MHz, but requires a new type of dual-frequency ultra-broadband transducer. In this project, such a transducer will be designed for IVUS using micromachined piezoelectric composite (MPC) ultrasound transducer technology. A dual frequency circular array, with 8-element 5 MHz and 64-element 40 MHz components, will be developed using deep reactive ion etching and multilayering techniques. Multi- channel, multi-frequency electronics will be developed for dual mode imaging (IVUS and contrast enhanced- IVUS) utilizing the fabricated dual frequency arrays. Contrast-IVUS will be performed in in-vitro phantoms and ex-vivo tissue to assess the prototype transducer, followed by in-vivo imaging in the pre-clinical atherosclerotic standard, the familial hypercholesterimic swine. The proposed high-resolution IVUS will provide a powerful and innovative new tool providing physicians more accurate atherosclerosis diagnosis, advancing the understanding of the pathophysiology of coronary artery disease, and facilitating the development of novel cardiovascular drugs and device therapies.