Chemical analysis of coronary atherosclerosis 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用于测量活体人类患者冠状动脉粥样硬化斑块的化学和分子组成的设备。测量人类冠状动脉中的化学物质和分子的能力可以提高我们对斑块形成、斑块进展、导致冠状动脉血栓形成的事件以及对药物治疗的反应的了解。冠脉内拉曼光谱是一种很有前途的获取这一信息的技术。利用拉曼光谱，激光照射组织样本，一小部分光将其部分能量传递给组织的化学键。由于能量损失的量是特定于每个单独的化学键，拉曼散射光的光谱可以用来确定组织的化学和分子组成。我们最近开发了一种原型导管，并证明了拉曼光谱可以从活体猪冠状动脉内的单个点获得。在这项计划中，我们将开发下一代拉曼系统和导管，以满足人类使用的要求，并能够沿冠状动脉周围甚至整个冠状动脉节段获得高质量的拉曼光谱图。虽然拉曼光谱已经被证明能够测量许多斑块化学物质和分子，但我们还将研究其测量其他目前被认为导致急性冠状动脉综合征的分子的潜力，包括与坏死性核心病变、细胞外基质和氧化应激相关的分子。最后，我们将在60名患者中进行临床研究，以证明冠状动脉内拉曼光谱的安全性和可行性。这项研究将通过比较从不同冠状动脉疾病表现的患者获得的化学和分子信息来深入了解这种新方法的临床应用。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and validate a device for measuring the chemical and molecular composition of coronary atherosclerotic plaques in living human patients. The ability to measure chemicals and molecules in human coronary arteries could improve our understanding of plaque formation, plaque progression, the events leading to coronary thrombosis, and the response to pharmacologic therapy. Intracoronary Raman spectroscopy is a promising technology for obtaining this information. With Raman spectroscopy, a laser illuminates a tissue sample and a small portion of the light imparts some of its energy to the tissue's chemical bonds. Since the amount of energy lost is specific to each individual chemical bond, the spectrum of the Raman scattered light can be used to determine the tissue's chemical and molecular composition. We have recently developed a prototype catheter and have demonstrated that Raman spectra can be obtained from a single spot within the coronary arteries of living swine. In this proposal, we will develop a next-generation Raman system and catheter that fulfills the requirements for human use and that is capable of obtaining high-quality Raman spectral maps along the circumference of a coronary artery, and possibly even over entire coronary segments. While Raman spectroscopy has already been shown to be capable of measuring many plaque chemicals and molecules, we will additionally investigate its potential to measure other molecules that are currently thought to precipitate acute coronary syndromes, including those associated with necrotic core lesions, the extracellular matrix, and oxidative stress. Finally, we will conduct a clinical study in 60 patients to demonstrate the safety and feasibility of intracoronary Raman spectroscopy. This study will provide insight on the clinical utility of this new method by comparing chemical and molecular information obtained from patients with different presentations of coronary artery disease.