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

描述（由申请人提供）：这项竞争性更新申请的目的是开发一种基于导管的诊断技术，用于定位和表征易破裂的动脉粥样硬化斑块。我们建议结合一个独特的，临床兼容的系统：(1)我们最近开发的时间分辨激光诱导荧光光谱（TR- LIFS）技术，该技术提供斑块组成的直接评估；(2)高分辨率血管内超声检查（IVUS），允许斑块微观解剖的视觉重建。由此产生的系统能够检测和监测动脉粥样硬化病变的组成和结构特征，这些特征可以预测斑块破裂。在本应用中，我们考虑了当前理解动脉粥样硬化疾病进展的范例，定义和检测易损斑块的标准，以及斑块破裂的最后步骤，以开发一种检测与斑块易损相关的一个或多个因素的仪器和相关方法。在过去的三年里，在NIH的资助下，我们开发了一种TR-LIFS临床兼容设备（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，并建立了允许研究患者动脉粥样硬化斑块的基础设施和合作。目前，我们使用该技术研究颈动脉内膜切除术患者的颈动脉斑块。我们的研究结果表明，TR-LIFS可以预测炎症细胞的积累。斑块纤维帽，斑块易损性的关键标志。在这个竞争性更新申请中，我们试图证明TR-LIFS技术用于动脉粥样硬化斑块临床表征的可行性，同时开发与高频IVUS的协同作用，以指导TR-LIFS调查和提高斑块诊断的特异性。本研究将涉及三个具体目标：(1)通过分析颈动脉内膜切除术患者的TR-LIFS测量信息，建立TR-LIFS诊断易发破裂斑块的临床可行性。(2)开发超声引导的TR-LIFS原型，为同一位置的斑块形态和生物化学/炎症特征提供信息。(3)设计、制造并测试TR-LIFS与超声（IVUS）检测相结合的诊断导管。该探针将首先在人体动脉段（离体）上进行测试，然后在动物模型（体内）上进行测试。这项研究将有助于将颈动脉斑块和导管设计的研究成果直接转化为临床实践，以识别和治疗那些在卒中症状出现之前更有可能出现高风险斑块的患者。此外，该研究将作为检测其他动脉床（包括冠状动脉）易损斑块的范例。

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.