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

描述(由申请人提供)：本次竞争性续展申请的目标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。我们建议将(I)我们最近开发的时间分辨激光诱导荧光光谱(tr-LIFs)技术与(Ii)高分辨率血管内超声(IVUS)相结合，形成一个独特的临床兼容系统，前者可提供斑块成分的直接评估，后者可实现斑块显微解剖的可视化重建。由此产生的系统将能够检测和监测动脉粥样硬化病变的成分和结构特征，这些特征可以预测斑块破裂。在这一应用中，我们考虑了了解动脉粥样硬化性疾病进展的当前范式、定义和检测易损斑块的标准以及斑块破裂的最终步骤，以开发一种设备和相关方法来检测与斑块易损性相关的一个或多个因素。在过去的三年里，在美国国立卫生研究院的资助下，我们开发了一种临床兼容的TR-LIFS仪器(仪器和软件)，在体内动脉粥样硬化动物模型中测试/验证了该仪器，并建立了基础设施和合作，使患者能够研究动脉粥样硬化斑块。目前，我们使用这项技术研究颈动脉内膜切除术患者的颈动脉斑块。我们的结果表明，TR-LIF可以预测斑块纤维帽中炎症细胞的聚集，这是斑块易损性的关键标志之一。在这一竞争性的更新应用中，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，同时发展与高频IVUS的协同作用，以指导TR-LIFs研究，并提高斑块诊断的特异性。将致力于三个具体目标：(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，确定TR-LIFs用于诊断易破裂斑块的临床可行性。(2)开发一种超声引导下的TR-LIFs样机，为同一部位的斑块形态和生化/炎症的特征提供信息。(3)设计、制作和测试一种结合TRLIFs和超声(IVUS)检测的诊断导管。该探头将首先在人体动脉节段上进行测试(体外)，然后在动物模型中进行测试(体内)。这项研究将有助于将有关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出现任何中风症状之前更有可能患有高危斑块的患者。此外，这项研究将作为检测包括冠状动脉在内的其他动脉床上易受攻击的斑块的范例。

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.