Rupture-prone plaque diagnosis by IVUS-guided time-resolved spectroscopy

通过 IVUS 引导的时间分辨光谱诊断易破裂斑块

• 批准号: 7626779
• 负责人: Laura Marcu
• 金额: $ 36.34万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626779
• 关键词: Address; Anatomy; Animal Model; Aorta; Applications Grants; Arterial Fatty Streak; Beds; Biochemistry; Carotid Artery Plaques; Carotid Endarterectomy; Catheters; Cells; Classification; Clinical; Collaborations; Collagen; Computer software; Coronary; Coronary artery; Data Collection; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Elastin; Evaluation; Fiber Optics; Fluorescence Spectroscopy; Frequencies; Funding; Grant; Histopathology; Human; Inflammation; Inflammatory; Injury; Intravascular Ultrasonography; Investigation; Ischemia; Lasers; Lesion; Limb structure; Lipids; Location; Measurement; Methodology; Microanatomy; Microscope; Monitor; Morphology; Myocardial Infarction; Operative Surgical Procedures; Patients; Recording of previous events; Reporting; Research; Research Design; Research Infrastructure; Research Personnel; Resolution; Rupture; Schedule; Screening procedure; Specificity; Spectrum Analysis; Staging; Stenosis; Stroke; Symptoms; System; Techniques; Technology; Testing; Thick; Thrombosis; Time; Translational Research; Ultrasonics; United States National Institutes of Health; Vascular remodeling; Visual; Work; analytical method; base; clinical practice; cost; design; evaluation/testing; high risk; human subject; in vivo; instrumentation; programs; prototype; reconstruction; research study; tool; Address; Anatomy; Animal Model; Aorta; Applications Grants; Arterial Fatty Streak; Beds; Biochemistry; Carotid Artery Plaques; Carotid Endarterectomy; Catheters; Cells; Classification; Clinical; Collaborations; Collagen; Computer software; Coronary; Coronary artery; Data Collection; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Elastin; Evaluation; Fiber Optics; Fluorescence Spectroscopy; Frequencies; Funding; Grant; Histopathology; Human; Inflammation; Inflammatory; Injury; Intravascular Ultrasonography; Investigation; Ischemia; Lasers; Lesion; Limb structure; Lipids; Location; Measurement; Methodology; Microanatomy; Microscope; Monitor; Morphology; Myocardial Infarction; Operative Surgical Procedures; Patients; Recording of previous events; Reporting; Research; Research Design; Research Infrastructure; Research Personnel; Resolution; Rupture; Schedule; Screening procedure; Specificity; Spectrum Analysis; Staging; Stenosis; Stroke; Symptoms; System; Techniques; Technology; Testing; Thick; Thrombosis; Time; Translational Research; Ultrasonics; United States National Institutes of Health; Vascular remodeling; Visual; Work; analytical method; base; clinical practice; cost; design; evaluation/testing; high risk; human subject; in vivo; instrumentation; programs; prototype; reconstruction; research study; tool

DESCRIPTION (provided by applicant): The objective of this competitive renewal application is to develop a catheter-based diagnostic technique for localization and characterization of rupture-prone atherosclerotic plaques. We propose to combine into one unique, clinically compatible system (i) our recently developed time-resolved laser-induced fluorescence spectroscopy (TR- LIFS) technique, which provides a direct evaluation of plaque composition, with (ii) high-resolution intravascular ultrasonography (IVUS) which allows a visual reconstruction of plaque microanatomy. The resulting system is to enable detection and monitoring of both compositional and structural features of atherosclerotic lesions which are predictive of plaque rupture. In this application, we consider the current paradigm for understanding the progression of atherosclerotic disease, criteria for defining and detecting vulnerable plaques, and final steps in plaque rupture, to develop an apparatus and associated methodologies for detection of one or a combination of factors associated with plaque vulnerability. Over the past three years, with NIH funding, we have developed a TR-LIFS clinically compatible apparatus (instrumentation and software), tested/validated this apparatus in an in-vivo atherosclerotic animal model, and established the infrastructure and collaborations that allows study of atherosclerotic plaques in patients. Currently, we investigate carotid plaque in patients undergoing carotid endarterectomy using this technique. Our results demonstrate that TR-LIFS can predict accumulation of inflammatory cells in the.plaque fibrous cap, one key marker of plaque vulnerability. In this competitive renewal application we seek to demonstrate the feasibility of TR-LIFS technique for atherosclerotic plaque clinical characterization while developing synergy with high-frequency IVUS for guidance of TR-LIFS investigations and increased specificity of plaque diagnostic. Three specific aims will be addressed: (1) To establish the clinical feasibility of TR-LIFS for diagnosis of rupture- prone plaques by analyzing information from TR-LIFS measurements in patients undergoing carotid endarterectomy. (2) To develop an ultrasonic - guided TR-LIFS prototype that provides information for characterization of both plaque morphology and biochemistry/inflammation at the same location. (3) To design, build and test a diagnostic catheter combining TR-LIFS and ultrasonic (IVUS) detection. The probe will be tested initially on human arterial segments (ex- vivo) and then in an animal model (in-vivo). This study will facilitate direct translation of research findings on carotid plaques and catheter design into clinical practice for identifying and treating those patients who are more likely to have a high-risk plaque prior to any stroke symptoms. Also, the study will serve as paradigm for detection of vulnerable plaques in other arterial beds including coronary arteries.

描述（由申请人提供）：这种竞争性更新应用的目的是开发一种基于导管的诊断技术，用于定位和表征可破裂的动脉粥样硬化斑块。我们建议将最近开发的时间分辨激光诱导的荧光光谱（TR-LIFS）技术合并为一种独特的临床兼容系统（i），该技术可直接评估斑块组成，并具有（ii）高分辨率静脉内术后术（IVUS），允许视觉复发pla pla pla pla pla pla pla plaque plaquque。最终的系统是可以对可预测斑块破裂的动脉粥样硬化病变的组成和结构特征进行检测和监测。在此应用中，我们考虑了当前的范式，以了解动脉粥样硬化疾病的进展，定义和检测易受攻击的斑块的标准以及斑块破裂的最后一步，以开发一种与斑块易受易受关系相关的因素的相关方法和相关方法。在过去的三年中，通过NIH资助，我们开发了一种临床上兼容的设备（仪器和软件），在体内动脉粥样硬化动物模型中测试/验证了该设备，并建立了基础设施和协作，以研究患者的动脉粥样硬化斑块。目前，我们使用此技术研究了接受颈动脉内膜切除术的患者的颈动脉斑块。我们的结果表明，TR-LIF可以预测斑块纤维帽中炎症细胞的积累，这是斑块脆弱性的一个关键标记。在这种竞争性更新应用中，我们试图证明TR-LIFS技术对动脉粥样硬化斑块临床表征的可行性，同时开发具有高频IVU的协同作用，以指导TR-LIFS研究和斑块诊断的特异性。将解决三个具体目标：（1）通过分析接受颈动脉内膜切除术的患者的TR-LIFS测量信息，建立TR-LIFS诊断破裂斑块的临床可行性。 （2）开发一个超声波引导的TR -LIFS原型，该原型提供了在同一位置表征斑块形态和生物化学/炎症的信息。 （3）设计，构建和测试结合TR-LIF和超声波（IVU）检测的诊断导管。该探针最初将在人类动脉片段（Ex-Vivo），然后在动物模型（体内）上进行测试。这项研究将有助于将有关颈动脉斑块和导管设计的研究结果直接转化为临床实践，以识别和治疗那些在任何中风症状之前更有可能患有高风险斑块的患者。此外，该研究将作为检测包括冠状动脉在内的其他动脉床中脆弱斑块的范式。