Chemical analysis of coronary atherosclerosis in patients

描述（由申请人提供）：本提案的目标是开发和验证一种用于测量活体患者冠状动脉粥样硬化斑块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理解。冠状动脉内拉曼光谱是一种很有前途的获取这一信息的技术。利用拉曼光谱学，激光照亮组织样本，一小部分光将其部分能量传递给组织的化学键。由于能量损失的数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导管原型，并证明可以从活猪冠状动脉内的单个点获得拉曼光谱。在本提案中，我们将开发下一代拉曼系统和导管，满足人类使用的要求，能够获得沿冠状动脉周长的高质量拉曼光谱图，甚至可能获得整个冠状动脉段的拉曼光谱图。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，但我们将进一步研究它在测量目前被认为导致急性冠状动脉综合征的其他分子方面的潜力，包括那些与坏死核心病变、细胞外基质和氧化应激相关的分子。最后，我们将对60例患者进行临床研究，以证明冠状动脉内拉曼光谱的安全性和可行性。本研究将通过比较不同冠状动脉疾病患者的化学和分子信息，为这种新方法的临床应用提供见解。

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.