Intracoronary imaging of plaque collagen in patients

描述(由申请人提供)：这项提案的目标是开发和验证一种冠状动脉内成像设备，用于评估患者的斑块胶原含量和结构。急性心肌梗死(AMI)是由不稳定斑块破裂引起的，是世界范围内的主要死亡原因。胶原蛋白和血管平滑肌细胞(VSMCs)共同赋予斑块机械稳定性，这些成分的净减少是导致斑块破裂的原因。因此，正在开发新的药物来有利地改变胶原含量和稳定不稳定的斑块。然而，由于缺乏准确量化患者治疗反应的成像工具，这些药物中的大多数在临床试验中都失败了。通过促进冠状动脉中胶原和vSMC含量以及斑块微观结构的定量测绘，这项建议中开发的技术将促进目前对患者斑块脆弱性的了解，增强药物开发平台，并最终促进冠状动脉疾病的诊断和治疗监测。我们的团队已经开发出冠状动脉内光学频域成像(OFDI)，以实现冠状动脉斑块的高分辨率显微镜检查。对外直接投资正迅速成为全球冠脉内评估的新标准。组织对比度的另一个来源是使用偏振敏感(PS)-OFDI来测量，它检测探测光的偏振状态以评估双折射，这是胶原和血管SMC所表现出的一种材料特性。我们先前已经证明，测量到的双折射与体外动脉粥样硬化斑块中胶原和vSMC的含量密切相关。然而，由于光学系统中的高偏振噪声，现有的PS-OFDI仪器目前在活体冠状动脉内使用是不可靠的。因此，我们的第一个技术目标是克服现有设备的局限性，实现一种先进的PS-OFDI设备，使活着的患者能够进行强大的3D双折射显微镜检查。虽然PS-OFDI提供了亚表面冠状动脉显微镜的优势，但由于光线对坏死灶的穿透性差，它无法评估斑块厚度。最近的临床研究表明，除了斑块的微观结构，血管内超声(IVUS)测量的斑块负荷对于了解斑块易损性和评估药物疗效至关重要。因此，我们的第二个技术目标是开发一种新型的混合式PS-OFDI/IVUS冠状动脉内控制台和导管，它将保持PS-OFDI的优越空间分辨率优势，同时集成IVUS的深度成像能力。因此，在一次扫描中，该设备将测量体内的胶原结构、斑块微结构和斑块负荷。随着技术的发展，我们将进行一项验证研究，以测试PS-OFDI/IVUS设备在动脉粥样硬化猪身上的准确性。然后，我们将遵循与对外直接投资相同的临床转换路径，并进行临床研究，以评估我们新方法的安全性、可行性和实用性。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and validate an intracoronary imaging device for the assessment of plaque collagen content and architecture in patients. Acute myocardial infarction (AMI), caused by the rupture of unstable plaque, is the leading cause of death worldwide. Collagen and vascular smooth muscle cells (vSMCs) together impart mechanical stability to a plaque, and a net reduction in these components is responsible for plaque rupture. Therefore, new drugs are being developed to favorably alter collagen content and stabilize unstable plaques. However, due the absence of imaging tools to accurately quantify treatment response in patients, a majority of these drugs fail in clinical trias. By facilitating the quantitative mapping of collagen and vSMC content, and plaque microstructure in coronary vessels, the technology developed in this proposal will advance current understanding of plaque vulnerability in patients, augment the drug development platform, and ultimately advance diagnosis and treatment monitoring of coronary artery disease. Our team has developed intracoronary optical frequency domain imaging (OFDI) to enable high resolution microscopy of coronary plaques. OFDI is fast becoming the new standard for intracoronary assessment worldwide. An additional source of tissue contrast is measured using polarization sensitive (PS)-OFDI that detects the polarization state of probing light to evaluate birefringence, a material property that is exhibited by collagen and vSMCs. We have previously shown that the measured birefringence is acutely related with collagen and vSMC content in atherosclerotic plaques ex vivo. However, because of high polarimetry noise in the optical system, existing PS-OFDI instrumentation is currently unreliable for intracoronary use in vivo. Therefore, our first technical goal is to overcome the limitations of the existing device and implement an advanced PS-OFDI device that will permit robust 3D birefringence microscopy in living patients. While PS-OFDI provides the advantage of sub-surface coronary microscopy, it is incapable of evaluating plaque thickness due to poor penetration of light through the necrotic core. Recent clinical studies indicate that in addition to plaque microstructure, plaque burden measured by intravascular ultrasound (IVUS) is vital to understanding plaque vulnerability and evaluating drug efficacy. Our second technical goal, therefore, is to develop a novel hybrid PS-OFDI/IVUS intracoronary console and catheter that will maintain the superior spatial resolution advantage of PS-OFDI while integrating the deep imaging capabilities of IVUS. As a result, within a single scan, this device will measure collagen architecture, plaque microstructure and plaque burden in vivo. Following technical development, we will conduct a validation study to test the accuracy of the PS- OFDI/IVUS device in atherosclerotic pigs. We will then follow the same clinical translational pathway that we used for OFDI, and conduct a clinical study to evaluate the safety, feasibility and utility of our new approach.