Dual-frequency intravascular arrays for functional imaging of atherosclerosis

用于动脉粥样硬化功能成像的双频血管内阵列

• 批准号: 8346523
• 负责人: Xiaoning Jiang
• 金额: $ 51.57万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8346523
• 关键词: Angiography; Arterial Fatty Streak; Arteries; Atherosclerosis; Biological Markers; Calcified; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular system; Catheters; Classification; Clinical assessments; Contrast Media; Coronary Arteriosclerosis; Data; Detection; Development; Devices; Diagnosis; Disease; Disease Progression; Electronics; Elements; Evaluation; Family suidae; Frequencies; Functional Imaging; Functional disorder; Goals; Gray unit of radiation dose; Histology; Histopathology; Image; Imaging Techniques; In Vitro; Infarction; Inflammation; Inflammatory; Ions; Lead; Methods; Microbubbles; Modeling; Morbidity - disease rate; Morphology; Necrosis; Noise; Pathologic Neovascularization; Patients; Penetration; Phase; Physicians; Physiologic pulse; Process; Research; Resolution; Resources; Risk; Roentgen Rays; Rupture; Side; Signal Transduction; Stenosis; Structure; System; Techniques; Technology; Tissues; Transducers; Ultrasonic Transducer; Ultrasonography; United States National Institutes of Health; atherogenesis; base; cardiovascular imaging; design; improved; in vivo; innovation; molecular imaging; molecular marker; mortality; neovascularization; neovasculature; new technology; novel; novel diagnostics; pre-clinical; prototype; response; standard of care; tool; vasa vasorum; virtual

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. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is one of the leading causes of mortality and morbidity - yet technologies to assess atherosclerotic plaque vulnerability are critically lacking. The goal of this project will be to enable new functional imaging approaches fo atherosclerosis using new ultra- broadband, multi-frequency circular arrays produced with micromachined piezoelectric composite (MPC) ultrasound transducer technology. This new intravascular ultrasound technology will enable enhanced imaging of adventitial neovasculature as well as molecular markers of inflammation, and has the potential to have a significant impact in the estimation of the risk of plaque rupture and assessment of atherosclerotic cardiovascular disease.

描述（由申请人提供）：心血管疾病（动脉粥样硬化）是发达国家心血管疾病死亡率和发病率的主要原因。冠状动脉粥样硬化的影像学，更具体地说，无创评估动脉粥样硬化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。x线血管造影和灰度血管内超声（IVUS）目前用于动脉粥样硬化斑块的评估，这两种方法对狭窄程度或斑块形态的信息有限。不幸的是，现在认为这两种特征都不能预测斑块易损性，相反，数据表明导致梗死的动脉粥样硬化斑块通常是非狭窄性的。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心动图，可以提高检测纤维、纤维脂肪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。最近的研究涉及造影剂增强血管血管成像和斑块相关炎症和血管生成生物标志物的分子成像，表明这些造影剂成像技术可以为评估斑块不稳定性提供关键信息。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，设计用于非线性对比成像的IVUS导管是不可用的。最近，一种利用造影剂超宽带响应的高频成像策略在20mhz以上的频率上提供了非常高的信号噪声和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，将采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。采用深度反应离子蚀刻和多层技术，将开发具有8元5mhz和64元40mhz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ivus将在体外模型和离体组织中进行，以评估原型换能器，然后在临床前动脉粥样硬化标准（家族性高胆固醇猪）中进行体内成像。提出的高分辨率IVUS将提供一个强大的创新工具，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的理解，促进新型心血管药物和设备治疗的开发。