Coronary Atherosclerotic Plaque Vascularization Assessed by Computed Tomography

描述(由申请人提供)： 对急性冠状动脉事件(心肌梗死和心脏性猝死)进行充分的风险评估对于有效地分配资源用于预防措施非常重要。多探测器计算机断层扫描(MDCT)技术的进步将其应用从传统的放射成像扩展到心脏应用，使无创冠状动脉成像能够以高诊断精度检测阻塞性冠状动脉疾病。除了冠状动脉疾病的简单解剖学特征外，人们对探索冠状动脉粥样硬化斑块的代谢活性也非常感兴趣，因为它可以告诉我们哪些斑块容易或不容易引发急性冠状动脉事件。评估动脉粥样硬化斑块代谢活性的一个既定指标是斑块内新生血管的存在和程度。使用MRI的研究证明了检测人颈动脉斑块中新生血管的可行性，但在小得多的冠状动脉斑块中没有这种评估的数据。与MRI相比，多层螺旋CT具有更好的空间分辨率，因此更适合于详细的冠状动脉成像。我们假设，高代谢活性的动脉粥样硬化斑块将有别于较不活跃的斑块，这是因为血管形成较多的组织中增强了对比剂摄取。为了验证这一假设，我们建议使用多层螺旋CT对动物模型中的冠状动脉进行成像，并进行组织病理学比较。具体地说，我们将对9只患有诱导性冠状动脉粥样硬化和新生血管的猪进行多层螺旋CT扫描，并使用一种新的、标准化的组织X射线衰减分析来分析图像。在第二步，我们将使用微型CT进行冠状动脉的体外成像。与常规多层螺旋CT相比，Micro CT具有更高的空间分辨率，但不能用于临床。如果MDCT未能检测到血管形成较多或较少的冠状动脉粥样硬化斑块之间组织密度的实际差异，Micro CT可能会证实我们的假设。最后，我们将MDCT和Micro CT检测到的血管的存在和程度与组织病理学结果进行比较。这一建议的意义在于有可能确定一种新的方法，使用广泛可用的工具来检测代谢更活跃、可能更脆弱的冠状动脉粥样硬化斑块，即与更高的冠状动脉事件风险相关的斑块。因此，这项建议可能会显著提高我们识别急性冠状动脉事件风险增加的患者的能力，这可能立即适用于许多患者。 公共卫生相关性： 本研究旨在开发一种利用计算机断层扫描(CT)来表征心脏动脉斑块生物学活性的方法。这项研究中提出的方法可能有助于确定哪些患者最有可能从心脏动脉斑块积聚的特定治疗中受益，哪些患者不太可能受益。因此，这项研究可能有助于更有效地分配资源，减少患者不必要的治疗风险，并减轻我们医疗保健系统的经济负担。

DESCRIPTION (provided by applicant): Adequate risk assessment for acute coronary events (myocardial infarction and sudden cardiac death) is important for efficiently allocating resources for preventative measures. Advances in multi- detector computed tomography (MDCT) technology have expanded its use from traditional radiologic imaging to cardiac applications that enabled non-invasive coronary angiography with high diagnostic accuracy for detecting obstructive coronary artery disease. In addition to mere anatomic characteristics of coronary artery disease, there is immense interest in exploring the metabolic activity of coronary atherosclerotic plaque as it may inform us which plaques are or are not prone to trigger acute coronary events. An established target for assessing atherosclerotic plaque metabolic activity is the presence and extent of neovascularization within plaques. Investigations using MRI demonstrated the feasibility of detecting neovascularization in human carotid artery plaques but no data for such assessment are available in the much smaller coronary artery plaques. MDCT has superior spatial resolution compared to MRI and thus appears better positioned for detailed coronary artery imaging. We hypothesized that highly metabolically active atherosclerotic plaques will be distinct from less active plaques due to enhanced contrast uptake in tissue with greater vascularization. To test this hypothesis, we propose to image coronary arteries in an animal model using MDCT with histopathologic comparison. Specifically, we will perform MDCT in 9 pigs with induced coronary atherosclerosis and neovascularization and analyze images using a novel, normalized analysis of tissue X-ray attenuation. In a second step, we will use micro CT for ex vivo imaging of coronary arteries. Micro CT has superior spatial resolution compared to conventional MDCT but it is not available for clinical use. Micro CT may confirm our hypothesis in case MDCT fails to detect an actual difference in tissue attenuation among coronary atherosclerotic plaques of greater or lesser vascularization. Finally, we will compare the presence and degree of vascularization as detected by MDCT and micro CT with the results of histopathology. The significance of this proposal lies in the possibility of identifying a novel method for detecting coronary atherosclerotic plaques that are more metabolically active and possibly vulnerable, i.e., associated with higher coronary event risk, using tools that are widely available. This proposal, therefore, may lead to a significant advancement in our ability to identify patients at increased risk from acute coronary events which may be immediately applicable to many patients. PUBLIC HEALTH RELEVANCE: This research intends to develop a method for characterizing the biologic activity of plaque in heart arteries seen by computed tomography (CT). The methods proposed in this research may help identifying patients who are most likely to benefit from specific treatments for plaque build-up in their heart arteries and those who are not likely to benefit. Therefore, this research may help allocate resources more efficiently, reduce unnecessary treatment risks for patients, and decrease the financial burden on our health care system.