Intracoronary imaging of plaque collagen in patients

患者斑块胶原的冠状动脉内成像

• 批准号: 8842192
• 负责人: Brett E Bouma
• 金额: $ 78.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8842192
• 关键词: Acute myocardial infarction; Address; Architecture; Arterial Fatty Streak; Arteries; Atherosclerosis; Biological Markers; Birefringence; Blood Vessels; Breast Microcalcification; Cardiac Catheterization Procedures; Catheters; Cause of Death; Cholesterol; Clinical; Clinical Research; Clinical Trials; Collagen; Coronary; Coronary Arteriosclerosis; Coronary Vessels; Correlative Study; Country; Development; Devices; Diagnosis; Drug Targeting; Evaluation; Exhibits; Extracellular Matrix; Family suidae; Generations; Goals; Health; Human; Hybrids; Image; Imaging Device; Incidence; Inflammation; Inflammatory; International; Laboratories; Life; Light; Lipids; Maps; Measurement; Measures; Mechanics; Metabolism; Microscopy; Monitor; Morphologic artifacts; Motion; Necrosis; Noise; Optical Coherence Tomography; Optics; Outcome; Pathway interactions; Patients; Penetration; Pharmaceutical Preparations; Property; Proteins; Resolution; Rotation; Rupture; Safety; Scanning; Smooth Muscle Myocytes; Solutions; Source; Structure; Surface; System; Technology; Testing; Thick; Time; Tissues; Ultrasonography; base; drug development; drug efficacy; efficacy trial; high standard; in vivo; innovation; insight; instrumentation; macromolecule; macrophage; novel; novel strategies; novel therapeutic intervention; optical frequency domain imaging; polarimetry; response; tool; treatment response; validation studies

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.

描述（由申请人提供）：本提案的目标是开发和确认用于评估患者斑块胶原蛋白含量和结构的冠状动脉内成像器械。急性心肌梗死（AMI），由不稳定斑块破裂引起，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（vSMC）共同赋予斑块机械稳定性，这些成分的净减少是斑块破裂的原因。因此，正在开发新的药物来有利地改变胶原蛋白含量并稳定不稳定的斑块。然而，由于缺乏成像工具来准确量化患者的治疗反应，这些药物中的大多数在临床试验中失败。通过促进胶原蛋白和vSMC含量以及冠状动脉中斑块微观结构的定量映射，该提案中开发的技术将推进当前对患者斑块脆弱性的理解，增强药物开发平台，并最终推进冠状动脉疾病的诊断和治疗监测。我们的团队开发了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。对外直接投资正在迅速成为全球冠状动脉内评估的新标准。使用偏振敏感（PS）-对外直接投资测量组织对比度的另一个来源，其检测探测光的偏振状态以评估双折射，双折射是胶原和vSMC表现出的材料特性。我们以前已经表明，测得的双折射是急性相关的胶原蛋白和血管平滑肌细胞含量在动脉粥样硬化斑块离体。然而，由于光学系统中的高偏振噪声，现有的PS-OFDI仪器目前在体内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，并实现先进的PS-OFDI设备，该设备将允许活体患者进行强大的3D双折射显微镜检查。虽然PS-OFDI提供了冠状动脉表面下显微镜的优势，但由于光对坏死核心的穿透性差，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，斑块负荷血管内超声（IVUS）测量是至关重要的了解斑块的脆弱性和评价药物疗效。因此，我们的第二个技术目标是开发一种新型的混合PS-OFDI/IVUS冠状动脉内控制台和导管，该控制台和导管将保持PS-OFDI的上级空间分辨率优势，同时集成IVUS的深度成像能力。因此，在单次扫描中，该设备将测量体内胶原结构、斑块微观结构和斑块负荷。在技术开发之后，我们将进行验证研究，以测试PS- OFDI/IVUS设备在动脉粥样硬化猪中的准确性。然后，我们将遵循我们用于对外直接投资的相同临床转化途径，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。