Cardiac Magnetic Resonance Elastography: Imaging Heart Failure Pathophysiology

描述(申请人提供)：100多年来，心肌僵硬一直被认为是心功能的中心参数，是多种疾病的基础。僵硬异常是导致心力衰竭两种主要形式的主要病理原因：1)。全球业务增长 僵硬导致心室充盈不良，导致射血分数正常的心力衰竭(HFNEF)，2)。心肌梗死改变局部僵硬，引发左心室(LV)重构和心力衰竭，并降低射血分数(HFREF)。这两种机制加在一起，占了心力衰竭事件的大部分，而心力衰竭又导致了每年392亿美元的总医疗成本，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，但目前还没有非侵入性方法来评估心肌硬度。这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创造有效治疗该疾病的关键。到目前为止，还没有开发出有效的治疗HFNEF的方法，心力衰竭总体上仍然有大约50%的五年死亡率。我们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，应用于胸壁的非侵入性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，通过一种称为反转的数学过程，将波的位移转换为心肌刚度图。CMRE的每一阶段都很难在薄壁、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、序列和倒置，使CMRE适用于人类。我们将在HFNEF动物模型中验证CMRE硬度测量与体内压力/体积计算的心肌硬度，并在心肌梗死动物模型中验证体外力学测试--心肌梗死是HFREF的最常见原因。如果成功，这项提议将导致CMRE发展成为一种强大的临床和研究工具，用于非侵入性测量心肌硬度。CMRE可以改善心力衰竭的诊断，并可用于指导创造更有效的心力衰竭治疗方法。 与公众健康相关：心肌僵硬是心脏病的一个极其重要的标志。然而，目前只能通过将导管插入心脏并进行压力测量来无创性地测量心脏的硬度。因为这很难做到，所以对心脏僵硬增加引起的疾病的了解有限。特别是，一种非常重要的疾病，即射血分数正常的心力衰竭，一直很难诊断和治疗。一种新型的核磁共振扫描已经被开发出来，可以测量心脏肌肉的硬度。有了这种新的扫描，医生们可能能够诊断出射血分数正常的心力衰竭，并测量心脏对药物的反应。

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. PUBLIC HEALTH RELEVANCE: Stiffness of the heart muscle is an extremely important marker of heart disease. However, the heart's stiffness can currently only be measured invasively by placing a catheter into the heart and making pressure measurements. Because this is difficult to do, there is limited understanding of diseases caused by increased heart stiffness. In particular, a very important disease called heart failure with normal ejection fractin has been hard to diagnose and treat. A new type of MRI scan has been developed that can measure heart muscle stiffness. With this new scan, doctors might be able to diagnose heart failure with normal ejection fraction and measure the heart's response to medication.