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）是发达国家心血管死亡率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瘤斑块不稳定性的方法，在诊断和治疗该疾病中至关重要。 X射线血管造影和灰度血管内超声（IVU）目前用于动脉粥样硬化斑块评估，这两种方法都提供了有关狭窄程度或斑块形态的有限信息。不幸的是，现在人们认为这两种特征都不是斑块脆弱性的预测，相反，数据表明导致梗塞的动脉粥样硬化斑块通常是非静态的。新的后处理IVUS技术包括IVUS虚拟组织学，综合反向散射分析和检测学，可以为检测纤维，纤维曲霉和坏死性核心组织提供增强的精度。但是，使用这些后加工技术，IVU成像分辨率，钙化组织中的渗透深度和组织分类挑战仍然是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的能力仍然极为有限。涉及对比度增强的VASA血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的最新研究表明，这些对比成像技术可以提供关键信息以评估斑块不稳定。但是，微泡对比剂的非线性检测策略在其谐振频率附近最有效，该谐振频率通常在1-10 MHz之间，比IVUS成像频率（20-45 MHz）低得多。因此，不可用专为非线性对比度成像设计的IVUS导管。最近，使用造影剂的超宽带响应的最近证明的高频成像策略可在20 MHz以上的频率下为噪声，高分辨率对比度成像提供很高的信号，但需要一种新型的双频率超宽宽带传感器。在这个项目中，这种传感器将使用微机械压电组合（MPC）超声传感器技术设计用于IVU。使用深层反应离子蚀刻和多层化技术，将开发具有8个元素5 MHz和64元素40 MHz组件的双频循环阵列。使用制造的双频率阵列，将开发多通道的多频电子设备用于双模式成像（IVU和对比度增强-IVU）。对比度将在体外幻象和前体组织中进行评估原型传感器，然后在临床前动脉粥样硬化标准中进行体内成像，家族性高胆固醇猪。拟议的高分辨率IVU将提供一种强大而创新的新工具，可为医师提供更准确的动脉粥样硬化诊断，促进对冠状动脉疾病的病理生理学的理解，并促进新颖的心血管药物和装置疗法的发展。 公共卫生相关性：心血管疾病是死亡率和发病率的主要原因之一 - 但是严重缺乏评估动脉粥样硬化斑块脆弱性的技术。该项目的目的是使用新的超宽带，多频圆形阵列启用动脉粥样硬化的新功能成像方法，该阵列由微机械压电复合材料（MPC）超声传感器技术产生。这种新型的血管内超声技术将使增强外膜新血管系统的成像以及炎症的分子标志物，并有可能对估计斑块破裂和评估动脉粥样硬化心血管疾病的风险产生重大影响。