4D Magnetic Resonance Imaging for Atrial Flow Assessment in Atrial Fibrillation

描述（由申请人提供）：房颤（AF）影响超过220万美国人，预计到2050年将达到1200万人。卒中是房颤最严重的并发症-占房颤患者发生的所有卒中的15-20% -由左心房血栓形成和随后的栓塞引起。房颤卒中预防的重点是在选定的高风险患者中使用华法林抑制血栓形成。虽然华法林对降低中风风险有效，但它也与每年3.4%的大出血风险相关。临床医生利用风险评分来确定从华法令获益的患者。然而，美国胸科医师学会的一个专家小组最近报告说，这些评分的预测价值充其量是中等的。这意味着许多未接受华法林治疗的患者将遭受中风，而许多接受华法林治疗的患者则不必要地暴露在大出血的风险中。这些评分表现欠佳的一个原因是，它们由临床危险因素（例如，年龄在100 - 75岁之间，高血压）组成，这些因素在人群基础上与中风有关，但根据生理学原理，与个体血栓形成没有特别的关系。导致血栓形成的关键因素之一是血瘀。使用超声波的研究已经将左心室低血流标记与中风风险联系起来。然而，这种技术不适合广泛的筛选，并且无法绘制3D流。功能4D心血管磁共振成像（4DcMRI）的新技术结合了时间分辨的3D解剖和3D血流速度信息，可以评估3D血流特征，特别适合于评估LA和右心房（RA）的血瘀。我们将应用该技术来评估LA和RA附件中瘀血或血流模式的差异是否解释了房颤中LA与RA附件血栓形成风险高出约10倍，以及房颤中全身性栓塞与肺栓塞风险高出10倍的原因。我们假设在房颤中有房内血栓形成风险的患者中，LA与RA附件中瘀血和血流模式改变的区域更为常见。我们将a)优化心房颤动患者血流表征的4DcMRI设置；b)开发半自动化分析工具来计算停滞指数和评估三维流动模式；c)比较两组患者的血流模式：1)持续性房颤患者，既往有房栓或血栓栓塞性卒中记录；2) 4年未使用华法林治疗且无LA血栓或血栓栓塞事件史的持续性房颤患者。假设1组和2组LA和RA附属物的瘀型和流型改变指标有显著差异。该项目将有助于确定4DcMRI是否可以用于提供血栓形成风险的生理信息。长期目标是评估对瘀血指标的个体化评估是否可以提供额外的有价值的信息，以建议哪些房颤患者需要华法林治疗，从而减少中风和出血并发症。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) affects over 2.2 million Americans, with projections of 12 million people by 2050. Stroke is the most serious complication of AF -15-20% of all strokes occurring in patients with AF - and results from thrombus formation in the left atrium (LA) and subsequent embolization. Stroke prevention in AF focuses on inhibiting thrombus formation with the use of warfarin in selected high risk patients. Although warfarin is effective at reducing stroke risk, it is also associated with a 3.4% annual risk of major bleeding. Clinicians utilize risk scores to identify patients who benefit from warfarn. However, an expert panel of the American College of Chest Physicians recently reported that the predictive value of these scores is mediocre, at best. This means that many patients who are not receiving warfarin will suffer a stroke while many patients who are treated with warfarin are being unnecessarily exposed to the risk of major bleeding. One reason for the subpar performance of these scores is that they are comprised of clinical risk factors (e.g. age > 75 years, high blood pressure) that are associated with stroke on a population basis but are not specifically related to thrombus formation in an individual based on physiologic principles. One of the key factors responsible for thrombus formation is blood stasis in the LA. Studies using ultrasound have linked markers of low flow in the LA to risk of stroke. However, this technique is not suitable for widespread screening and is unable to map 3D flow. The novel technique of functional 4D cardiovascular magnetic resonance imaging (4DcMRI) incorporating time- resolved 3D anatomy and 3D blood velocity information can assess 3D flow characteristics and is uniquely suited to evaluate blood stasis within the LA and right atrium (RA). We will apply thi technique to evaluate whether differences in stasis or flow patterns in the LA and RA appendages explain the approximately 10-fold greater risk of LA versus RA appendage thrombus formation and the 10-fold greater risk of systemic versus pulmonary embolism in AF. We hypothesize that stasis and regions with altered flow patterns are more common in the LA versus RA appendage in patients with AF at risk for intraatrial thrombus formation. We will a) optimize the 4DcMRI settings for flow characterization in AF patients; b) develop semi-automated analysis tools to calculate indices of stasis and assess 3D flow patterns; and c) compare flow patterns in two groups: 1) patients with persistent AF and documented prior atrial thrombus or thromboembolic stroke; 2) patients with persistent AF for >4 years not treated with warfarin and without history of LA thrombus or thromboembolic event. The hypothesis is that indices of stasis and flow pattern alterations will be significantly different in the LA versus RA appendage in Group 1 versus 2. This project will help determine whether 4DcMRI can be used to provide physiologic information regarding the risk for thrombus formation. The long-term goal is to evaluate whether individualized evaluation of indices of stasis can provide additional valuable information to advise which AF patients require warfarin therapy, thereby reducing both strokes and bleeding complications.