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和发病的主要原因。冠状动脉粥样硬化的成像，更具体地说，无创评估动脉粥样硬化斑块不稳定性的方法，对于这种疾病的诊断和治疗至关重要。 X射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评估，这两种方法提供的有关狭窄程度或斑块形态的信息有限。不幸的是，现在人们认为这两种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、集成反向散射分析和触诊术，可提高检测纤维、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极其有限。最近的研究涉及对比增强血管滋养管成像以及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，该频率通常在 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 导管不可用。最近展示的高频成像策略利用造影剂的超宽带响应，在 20 MHz 以上的频率下提供非常高的信噪比、高分辨率造影成像，但需要新型双频超宽带换能器。在该项目中，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。将使用深反应离子蚀刻和多层技术开发具有 8 元件 5 MHz 和 64 元件 40 MHz 组件的双频圆形阵列。利用所制造的双频阵列，将开发用于双模式成像（IVUS 和对比度增强 IVUS）的多通道、多频率电子器件。将在体外模型和离体组织中进行对比 IVUS 以评估原型换能器，然后在临床前动脉粥样硬化标准（家族性高胆固醇血症猪）中进行体内成像。拟议的高分辨率 IVUS 将提供一种强大且创新的新工具，为医生提供更准确的动脉粥样硬化诊断，增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。 公共卫生相关性：心血管疾病是死亡和发病的主要原因之一，但评估动脉粥样硬化斑块脆弱性的技术却严重缺乏。该项目的目标是利用微机械压电复合材料（MPC）超声换能器技术生产的新型超宽带、多频率圆形阵列，实现动脉粥样硬化的新功能成像方法。这种新的血管内超声技术将能够增强外膜新生血管的成像以及炎症的分子标记，并有可能对评估斑块破裂风险和评估动脉粥样硬化性心血管疾病产生重大影响。