Real-time in vivo IVUS/IVPA imaging to detect and characterize vulnerable plaques

描述（由申请人提供）：仅在美国，每年约有50万人死于血管斑块破裂，而血管造影评估认为这些斑块“无关紧要”。现有的筛查和诊断方法不足以在事件发生前识别可能的受害者。因此，临床迫切需要一种诊断成像技术来识别和表征冠状动脉介入治疗过程中动脉粥样硬化斑块的易损性。我们研究计划的总体目标是开发一种体内成像技术-结合血管内超声和光声成像-能够可视化动脉粥样硬化斑块的结构特性和组成。本项目的基本假设是血管内光声（IVPA）成像结合血管内超声（IVUS）成像可在临床上实现，用于检测和确定动脉粥样硬化斑块的易损性。因此，IVUS/IVPA联合成像可以改善干预前计划，辅助干预本身，从而改善干预后结果，降低患者发病率。最重要的是，拟议的IVUS/IVPA成像不会显著改变目前冠状动脉介入治疗的临床方案。为了充分探索IVUS/IVPA成像在介入心脏病学中的能力，必须解决广泛的科学、生物医学工程和临床问题。当前项目的中心主题是在广泛的临床研究之前，开发和测试用于实时体内成像的IVUS/IVPA联合系统的原型。为了实现我们的目标，首先，我们将设计并构建一个实时体内IVUS/IVPA成像系统的原型，该系统由定制的IVUS/IVPA成像导管与电机组件集成，并与脉冲激光源、超声发射器/接收器和微处理器控制单元接口组成。其次，我们将开发必要的信号/图像处理算法来评估血管壁和斑块的解剖特征，以识别和量化动脉粥样硬化斑块内富含脂质的坏死核心。我们将通过对动物模型（兔和猪）和人类冠状动脉解剖样本的离体动脉粥样硬化动脉成像来优化系统硬件和信号/图像处理算法的性能。最后，将使用活体动脉粥样硬化动物模型验证体内实时IVUS/IVPA成像系统的有效性。基于在该项目中收集到的见解，我们将准备进行进一步的大型动物和临床研究，以证明IVUS/IVPA成像系统可能成为介入心脏病学所需的卓越临床成像工具。

DESCRIPTION (provided by applicant): In the United States alone, approximately 500,000 deaths per year are due to ruptured vascular plaques that were considered "insignificant" by angiographic evaluations. Available screening and diagnostic methods are insufficient to identify possible victims before the event occurs. Therefore, there is a definite and urgent clinical need for a diagnostic imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions. The overall goal of our research program is to develop an in vivo imaging technology - combined intravascular ultrasound and photoacoustic imaging - capable of visualizing both structural properties and composition of atherosclerotic plaques. The underlying hypothesis of this project is that intravascular photoacoustic (IVPA) imaging combined with intravascular ultrasound (IVUS) imaging can be implemented clinically and used to detect and determine the vulnerability of atherosclerotic plaques. Therefore, combined IVUS/IVPA imaging can improve pre-intervention planning and assist with the intervention itself, thus improving the post-intervention outcome and reducing patient morbidity. Most importantly, the proposed IVUS/IVPA imaging will not significantly change the current clinical protocol of coronary artery intervention. A wide range of scientific, biomedical engineering, and clinical problems must be addressed to fully explore the capabilities of IVUS/IVPA imaging in interventional cardiology. The central theme of the current project is to develop and test a prototype of the combined IVUS/IVPA system for real-time in vivo imaging prior to extensive clinical studies. To achieve our objective, first we will design an build a prototype of the real-time in vivo IVUS/IVPA imaging system consisting of the custom-built IVUS/IVPA imaging catheters integrated with a motor assembly and interfaced with pulsed laser source, ultrasound transmitter/receiver, and microprocessor control unit. Second, we will develop the signal/image processing algorithms necessary to assess the anatomical features of the vessel wall and plaque to identify and quantify lipid-rich necrotic cores within atheroscleroti plaques. We will optimize the performance of the system hardware and signal/image processing algorithms by imaging ex vivo atherosclerotic arteries from animal models (rabbit and swine) and human coronary artery autopsy samples. Finally, the efficacy of the in vivo real-time IVUS/IVPA imaging system will be validated using live animal models of atherosclerosis. Based on the insights gathered during this project, we will be ready to perform further large animal and clinical studies to demonstrate that the IVUS/IVPA imaging system may become a superior clinical imaging tool needed in interventional cardiology.