Reliable Evaluation of Coronary Artery Disease using Myocardial BOLD MRI with CO2

描述(申请人提供)：在美国，冠状动脉疾病是导致死亡的主要原因。据估计，美国有超过1600万人患有冠状动脉疾病(CAD)，三分之一以上的死亡是由CAD引起的。此外，美国每年有100多万人因冠心病住院。最常见的冠心病会导致冠状动脉狭窄(狭窄)，从而导致供血和供氧心肌减少，导致心肌缺血--一种心肌供氧远远超过可供氧的状态。心肌缺血的存在是主要不良心脏事件(MACE：死亡、心肌梗死和中风)的重要危险因素。适当的早期干预(冠状动脉搭桥术、血管成形术、药物或药物治疗)，根据与稳定的冠心病相关的缺血负担的范围和严重程度来指导，可能有助于降低MACE的风险。因此，一种可靠的、非侵入性的、可重复的确定缺血范围和严重程度的方法在治疗冠心病患者中是非常宝贵的。这项建议的广泛、长期目标是改善冠心病患者的预后。评估临床上有意义的心肌缺血的理想策略应该是完全非侵入性的；也就是说，除了避免心导管术的风险外，它还应该没有电离辐射、外源性造影剂和药物应激剂--既有风险又有副作用。虽然目前的临床标准没有提供许多这些好处，但心肌血氧水平依赖(BOLD)MRI可以满足这些要求中的一些。然而，目前这种方法的广泛应用受到敏感性、特异性不足以及静脉药理(腺苷)压力的需要的限制，所有这些都在临床实践中构成了相当大的限制。在拟议的项目中，我们希望显著提高心肌BOLD MRI的可靠性，使其强大到足以准确定量与临床意义上的CAD相关的缺血体积，而不需要静脉药物应激或外源性造影剂。提出的方法利用(I)个性化的靶向二氧化碳分压变化(PaCO2)作为非侵入性血管活性刺激，(Ii)快速、高分辨率、3T的4D BOLD MRI和(Iii)广义线性模型(GLM)理论来得出统计参数图(SPM)以可靠地检测和量化临床意义 以数据驱动的方式显示缺血心肌体积。这些研究有望为无创、可靠的评价冠心病患者预后的影像策略提供基本的科学依据。

DESCRIPTION (provided by applicant): Coronary artery disease is the leading cause of death in the United States. It is estimated that in excess of 16 million people are living with coronary artery disease (CAD) and more than 1 in three deaths are due to CAD in the US. In addition, more than 1 million people are hospitalized each year in the US because of CAD. The most common form of CAD leads to the narrowing of the coronary arteries (stenosis) resulting in reduced blood flow and oxygen supplied to the heart muscle, results in myocardial ischemia - a condition where the oxygen demand of the myocardium is far in excess of the available supply. The presence of myocardial ischemia is an important risk factor for major adverse cardiac events (MACE: death, myocardial infarction, and stroke). Appropriate early interventions (coronary bypass, angioplasty, pharmacological, or medical therapy) that are guided by the extent and severity of ischemic burden associated with stable CAD may be instrumental in reducing the risk of MACE. Hence a reliable, non-invasive, and repeatable method for determining the extent and severity of ischemia is invaluable in managing patients with CAD. The broad, long-term objective of this proposal is to improve the prognosis of patients with coronary artery disease. An ideal strategy for assessing clinically significant myocardial ischemia would be completely non-invasive; that is, in addition to avoiding the risks of cardiac catheterization, it would be free of ionizing radiation, exogenous contrast media, and pharmacological stress-agents with both risks and side effects. Although the current clinical standards do not provide many of these benefits, a number of these requirements can be met by myocardial Blood-Oxygen-Level-Dependent (BOLD) MRI. However, the widespread use of this approach is currently limited by inadequate sensitivity, specificity, and the need for intravenous pharmacological (adenosine) stress, all of which pose considerable limitations in clinical practice. In the proposed project, we wish to significantly improve the reliability of myocardial BOLD MRI so that is becomes powerful enough to accurately quantify the ischemic volume associated with clinically significant CAD without intravenous pharmacological stress or exogenous contrast media. The proposed method utilizes (i) an individualized targeted change in arterial partial pressure of CO2 (PaCO2) as the non-invasive vasoactive stimulus, (ii) fast, high-resolution, 4D BOLD MRI at 3T and (iii) the generalized linear model (GLM) theory to derive statistical parametric maps (SPM) to reliably detect and quantify the clinically significant ischemic myocardial volume in a data-driven fashion. These studies are expected to provide the fundamental scientific basis for a non-invasive and reliable imaging strategy for evaluating prognosis of patients with coronary artery disease.