Cardiac Magnetic Resonance Elastography: Imaging Heart Failure Pathophysiology

描述（由申请人提供）：100多年来，已知心肌僵硬度是心脏功能的中心参数，是多种疾病的基础。异常僵硬是两种主要形式的心力衰竭的关键病理原因：1）。增加全球 僵硬导致心室充盈不良，导致射血分数正常的心力衰竭（HFNEF），和2）。心肌梗死改变局部僵硬度，触发左心室（LV）重构和射血分数降低的心力衰竭（HFREF）。这两种机制加在一起占了心力衰竭事件的大部分，而心力衰竭每年的总医疗费用为392亿美元，被称为21世纪的“新流行病”。虽然直接测量心肌硬度可能是评估心血管疾病的重要工具，但目前还没有无创方法来评估心肌硬度。对临床研究的影响是深远的，因为非侵入性测量疾病过程是为该疾病创造有效治疗方法的关键。迄今为止，还没有开发出HFNEF的有效治疗方法，总体而言，心力衰竭的五年死亡率仍约为50%。我们的团队开发了一种新的，非侵入性的心肌硬度测量方法，称为心脏磁共振弹性成像（CMRE）。在CMRE中，应用于胸壁的无创机械驱动器将波传输到心肌。与外部施加的波同步的相位梯度磁共振成像脉冲序列对波位移信息进行编码。然后通过称为反演的数学过程将波位移转换为心肌硬度图。CMRE的每个阶段都很难在薄壁、跳动的内部器官（如心脏）中进行。因此，我们建议开发新的CMRE驱动程序，序列和反转，这将使CMRE适用于人类。我们将在HFNEF动物模型中验证CMRE刚度测量与体内压力/体积衍生心肌刚度的关系，并在心肌梗死动物模型中验证CMRE刚度测量与离体力学测试的关系-心肌梗死是HFREF的最常见原因。如果成功的话，这一建议将导致CMRE的发展，作为一个强大的临床和研究工具，心肌硬度的非侵入性测量。CMRE可以改善心力衰竭的诊断，并可用于指导创建更有效的心力衰竭治疗方法。

DESCRIPTION (provided by applicant): For over 100 years, myocardial stiffness has been known to be a central parameter of cardiac function and to underlie multiple diseases. Abnormal stiffness is the key pathologic cause of the two major forms of heart failure: 1). increased global stiffness causes poor ventricular filling, leading to heart failure with normal ejection fraction (HFNEF), and 2). myocardial infarction alters regional stiffness, triggering left ventricular (LV) remodeling and heart failure with reduced ejection fraction (HFREF). Together, these two mechanisms account for the majority of incident heart failure, which in turn accounts for $39.2 billion in overall medical costs per year and has been called "a new epidemic" for the 21st century. Although direct measurement of myocardial stiffness could be an important tool for assessing cardiovascular disease, there is currently no non-invasive method to assess myocardial stiffness. The effect on clinical research has been profound because non-invasively measuring a disease process is key to creating effective treatments for that disease. To date, no effective treatment for HFNEF has been developed and heart failure overall continues to have a five year mortality of approximately 50%. Our group has developed a novel, non-invasive measure of myocardial stiffness called Cardiac Magnetic Resonance Elastography (CMRE). In CMRE, non-invasive mechanical drivers, applied to the chest wall, transmit waves to the myocardium. A phase gradient magnetic resonance imaging pulse sequence, synchronized to the externally-applied waves, encodes the wave displacement information. The wave displacements are then converted to myocardial stiffness maps through a mathematical process called inversion. Each stage of CMRE is difficult to perform in a thin-walled, beating, internal organ such as the heart. Therefore, we propose to develop novel CMRE drivers, sequences and inversions, which will make CMRE applicable in humans. We will validate the CMRE stiffness measurements against in vivo pressure/volume derived myocardial stiffness in an animal model of HFNEF and against ex vivo mechanical testing in an animal model of myocardial infarction -- the most common cause of HFREF. If successful, this proposal would lead to the development of CMRE as a robust clinical and research tool for the non-invasive measurement of myocardial stiffness. CMRE could lead to improved diagnosis in heart failure and could be used to guide creation of more effective heart failure treatments.