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: 10503631
• 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/10503631
• 关键词: Adopted; Aerobic; Affect; Anatomy; Animal Model; Award; Biological Markers; Blood; Blood flow; Breathing; Cardiac; Cardiac health; Catheterization; Chronic; Classification; Clinical; Consumption; Contrast Media; Coronary Arteriosclerosis; Coronary Circulation; Coronary sinus structure; Cyclotrons; Data; Dependence; Development; Diastole; Disease; Disease Surveillance; Dose; Early Diagnosis; Early Intervention; Energy Metabolism; Epidemic; Family suidae; Flowmetry; Foundations; Functional disorder; Gold; Guidelines; Heart; Heart Rate; Heart failure; Hospitalization; Image; Impairment; Ionizing radiation; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mechanics; 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; Pharmacology; Phase; Physiologic pulse; Play; Population; Positron-Emission Tomography; Preventive; Preventive treatment; Procedures; Prognosis; Publications; Research Personnel; Resolution; Rest; Risk; Role; Secondary to; Societies; Staging; Stress; Systole; Techniques; Testing; Time; Treatment Efficacy; Treatment Failure; Venous; Work; base; blood oxygen level dependent; cardiac magnetic resonance imaging; cardiogenesis; career; clinical practice; efficacy evaluation; heart function; heart metabolism; heart motion; high risk; imaging modality; improved; mortality risk; novel; novel therapeutic intervention; novel therapeutics; oxidation; 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.

摘要 心脏能量消耗是心脏功能的核心决定因素。它的损害是 心力衰竭（HF）的标志，每年占近400亿美元的医疗费用 并且是住院的最常见原因。在HF病理生理学中， 心肌的收缩力与伴随的能量降低不匹配 消费这导致机械收缩和能量之间的解耦 心脏的消耗，其驱动心脏的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改变可以提供关键信息 心脏健康和指导新的治疗HF正在开发中的干预措施。 由于心脏几乎完全依赖于有氧氧化， 心脏能量学的改变来自侵入性测量的整个心脏心肌氧 消耗量（MVO 2）。然而，侵入性导管插入术不是重复的实用方法 监测可疑人群中的疾病或监测治疗效果。 因此，存在对能够实现可重复的非侵入性方法的未满足的需求。 心脏能量学的定量评估。已作出重大努力， 开发用于MVO 2测量的非侵入性技术，特别是基于正电子 发射断层扫描（PET）和磁共振波谱（MRS）。但他们 由于主要的技术/实践限制，没有进入临床竞技场。一个替代 这种方法克服了PET的关键限制和长期存在的技术挑战， MRS用于估计MVO 2，采用磁共振血氧测定法。然而，这需要 在快速运动的脑内同步可靠地绘制定量MR参数 冠状窦，这对于今天的CMR技术几乎是不可能的。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， 同时推导冠状窦血氧饱和度和心肌血流量用于MVO 2 测量.我们将测试开发的方法在检测受损的心脏能量 在心力衰竭动物模型中的消耗水平。该方法预计将 无创量化心脏能量消耗，无电离辐射，外源性 造影剂。因此，为（1）早期检测和分类奠定了基础 （2）无创性手术的HF预后，以及（3）纵向 监测HF进展，以指导新型HF治疗的开发。