Push-Button Cardiac MRI for Non-Invasive Quantification of Myocardial Energy Consumption in Heart Failure

摘要 心脏能量消耗是心脏功能的核心决定因素。其减值幅度为 心力衰竭 (HF) 的标志，每年造成近 400 亿美元的医疗费用 并且是住院的最常见原因。在心力衰竭病理生理学中，抑郁症 心肌的收缩力与伴随的能量抑制不匹配 消费。这导致机械收缩和能量之间的脱钩 心脏的支出，导致心脏收缩或舒张功能障碍。因此， 检测心力衰竭患者心脏能量学的早期变化可以提供重要信息 关注心脏健康并指导正在开发的新型心力衰竭治疗干预措施。 由于心脏几乎完全依赖于有氧氧化，因此分期的黄金标准 心脏能量学的改变来自有创测量的全心心肌氧 消耗量（MVO2）。然而，侵入性导管插入术并不是重复治疗的实用方法。 监测可疑人群的疾病或监测治疗效果。 因此，对于一种能够实现可重复的非侵入性方法的需求尚未得到满足。 心脏能量学的定量评估。已做出重大努力 开发 MVO2 测量的无创技术，特别是基于正电子的技术 发射断层扫描 (PET) 和磁共振波谱 (MRS)。然而，他们有 由于主要的技术/实践限制，未进入临床领域。另一种选择 方法，克服了 PET 的主要局限性和长期存在的技术挑战 用于估算 MVO2 的 MRS 采用磁共振血氧测定法。尽管如此，这需要 在快速移动的情况下同时可靠地绘制定量 MR 参数 冠状窦，这对于今天的 CMR 技术来说几乎是不可能的。在此，我们建议 开发并验证单一、快速、自由呼吸、运动不敏感的采集 同时导出 MVO2 的冠状窦氧饱和度和心肌血流量 测量。我们将测试开发的方法来检测受损的心脏能量 心力衰竭动物模型的消耗水平。所提出的方法预计 无创量化心脏能量消耗，无需电离辐射和外源性 造影剂。因此，为 (1) 早期检测和分类奠定了基础 心力衰竭的目标治疗，(2) 没有侵入性手术的心力衰竭的预后，以及 (3) 纵向 监测心力衰竭进展，以指导新型心力衰竭疗法的开发。

ABSTRACT Cardiac Energy consumption is the central determinant of cardiac function. Its impairment is the hallmark of heart failure (HF), which accounts for nearly $40 billion in medical costs every year and is the most frequent cause of hospitalization. In HF pathophysiology, the depression of contractile force of the myocardium is not matched by a concomitant depression of energy consumption. This results in the uncoupling between mechanical contraction and energy expenditure of the heart, which drives systolic or diastolic dysfunction of the heart. Thus, the detection of early alterations in cardiac energetics in HF patients can provide critical information on heart health and guide novel therapeutic interventions for HF which are under development. Since the heart relies almost exclusively on aerobic oxidation, the gold standard for staging alterations in cardiac energetics is from invasively measured whole heart myocardial oxygen consumption (MVO2). However, invasive catheterization is not a practical way for repeat surveillance of the disease in the suspect population or the monitoring of therapeutic efficacy. Hence there is an unmet need for a noninvasive approach that can enable repeatable quantitative assessment of cardiac energetics. Significant effort has been made towards developing noninvasive techniques for MVO2 measurement, particularly based on positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). However, they have not made it into the clinical arena due to major technical/practical limitations. An alternative approach, which overcomes key limitations of PET and longstanding technical challenges of MRS for estimating MVO2, employs magnetic resonance oximetry. Nonetheless, this requires simultaneous and reliable mapping of quantitative MR parameters in the rapidly moving coronary sinus, which is nearly impossible for the CMR techniques today. Here, we propose to develop and validate a single, fast, free-breathing, motion-insensitive acquisition to simultaneously derive coronary sinus oxygen saturation and myocardial blood flow for MVO2 measurement. We will test the developed method in detecting the impaired cardiac energy consumption level in an animal model with heart failure. The proposed method is expected to quantify cardiac energy consumption noninvasively, without ionizing radiation, and exogenous contrast agents. Accordingly, forming the foundation toward (1) early detection and classification of HF for target treatments, (2) prognosis of HF without invasive procedures, and (3) longitudinal monitoring of HF progression to guide the development of novel HF therapies.