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

按钮式心脏 MRI 用于心力衰竭心肌能量消耗的无创定量

• 批准号: 10684051
• 负责人: Hsin-Jung Yang
• 金额: $ 78.49万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684051
• 关键词: Adopted; Aerobic; Affect; Anatomy; Animal Model; Award; Biological Markers; Blood; Blood flow; Breathing; Cardiac; Cardiac health; Catheterization; Chronic; Classification; Clinical; Contrast Media; Coronary Arteriosclerosis; Coronary Circulation; Coronary sinus structure; Cyclotrons; Data; Dependence; Development; Diastole; Disease; Disease Surveillance; Dose; Early Diagnosis; Early Intervention; Energy Metabolism; Energy consumption; Family suidae; Flowmetry; Foundations; Functional disorder; Guidelines; Heart; Heart Rate; Heart failure; Hospitalization; Image; Impairment; Ionizing radiation; Journals; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Mechanics; Mediation; Medical Care Costs; Mental Depression; Methods; Modeling; Monitor; Motion; Movement; Myocardial; Myocardial Infarction; Myocardial dysfunction; Myocardium; Needles; Outcome; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Patients; Persons; Phase; Physiologic pulse; Play; Population; Positron-Emission Tomography; Preventive; Preventive treatment; Procedures; Prognosis; Publications; Recommendation; Research Personnel; Resolution; Rest; Risk; Role; Secondary to; Site; Societies; Staging; Stress; Systole; Techniques; Testing; Time; Treatment Efficacy; Treatment Failure; Venous; Work; blood oxygen level dependent; cardiac magnetic resonance imaging; career; clinical practice; efficacy evaluation; heart function; heart metabolism; heart motion; high risk; imaging modality; improved outcome; mortality risk; new epidemic; novel; novel therapeutic intervention; novel therapeutics; oxidation; pharmacologic; prevent; respiratory; screening; targeted treatment; therapy development; tool

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.

抽象的 心脏能源消耗是心脏功能的核心决定因素。它的障碍是 心力衰竭的标志（HF），每年占近400亿美元的医疗费用 这是住院最常见的原因。在HF病理生理学中， 心肌的收缩力与能量伴随抑郁症不匹配 消耗。这导致机械收缩与能量之间的解偶联 心脏的支出，驱动心脏的收缩或舒张功能障碍。因此， 发现HF患者心脏能量的早期改变可以提供关键信息 在心脏健康和指导正在开发的HF的新型治疗干预措施上。 由于心脏几乎完全依赖有氧氧化，因此分期的金标准 心脏能量的改变来自侵入性的全心肌氧气 消费（MVO2）。但是，侵入性导管插入并不是重复的实用方法 可疑人群中疾病的监测或治疗功效的监测。 因此，对无创方法的需求未满足，可以重复重复 心脏能量学的定量评估。已经为 开发用于MVO2测量的无创技术，尤其是基于正电子 发射断层扫描（PET）和磁共振光谱（MRS）。但是，他们有 由于主要的技术/实践局限性，未进入临床领域。另一种 方法，克服了宠物的关键局限性以及长期存在的技术挑战 MRS用于估计MVO2，采用磁共振血氧仪。但是，这需要 快速移动中定量MR参数的同时且可靠的映射 冠状动脉窦，对于当今的CMR技术几乎是不可能的。在这里，我们建议 开发和验证单个，快速，自由呼吸的，运动不敏感的采集 同时推导MVO2的冠状窦氧饱和度和心肌血流 测量。我们将测试开发的方法检测心脏能量受损 具有心力衰竭的动物模型中的消费水平。提出的方法有望 非侵入性地量化心脏能耗，而无需电离辐射和外源性 对比剂。因此，构成（1）早期检测和分类的基础 HF用于目标治疗的HF，（2）无侵入性程序的HF预后，（3）纵向 HF进展的监测以指导新型HF疗法的发展。