Hyperpolarized Carbon-13 Metabolic MRI of the Human Heart

人类心脏的超极化碳 13 代谢 MRI

• 批准号: 10369320
• 负责人: Maria Roselle Abraham
• 金额: $ 48.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369320
• 关键词: Address; Bicarbonates; Blood; Calibration; Carbohydrates; Carbon; Cardiac; Cardiomyopathies; Cardiovascular system; Cause of Death; Cessation of life; Clinical Research; Contrast Media; Data; Development; Diabetes Mellitus; Diagnosis; Diastolic heart failure; Evaluation; Exercise; Fatty Acids; Glucose; Glycolysis; Heart; Heart Diseases; Heart failure; Human; Hypertrophic Cardiomyopathy; Image; Imaging Techniques; Imaging technology; Inherited; Injections; Intervention; Ionizing radiation; Ischemia; Ketone Bodies; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Monitor; Morphologic artifacts; Motion; Myocardium; Oral; Pathogenesis; Patients; Performance; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Preparation; Protocols documentation; Pyruvate; RF coil; Reproducibility; Resolution; Scanning; Selection for Treatments; Series; Signal Transduction; Source; Spectrum Analysis; Techniques; Technology; Testing; Time; Translations; Validation; anaerobic glycolysis; clinical imaging; diabetic cardiomyopathy; experimental study; fatty acid metabolism; healthy volunteer; heart function; heart imaging; heart metabolism; human imaging; human subject; image reconstruction; imaging approach; imaging modality; imaging platform; imaging study; improved; in vivo; magnetic field; metabolic imaging; metabolomics; novel; pharmacokinetic model; physiologic model; reconstruction; response; single photon emission computed tomography; technology development; treatment response

Project Summary Heart disease is the leading cause of death in the US, resulting in over 600,000 deaths per year. The healthy heart is extremely metabolically active in order to supply its energetic needs, and alterations in cardiac metabolism have significant consequences for heart function. Metabolism is implicated in many heart diseases, including cardiomyopathies (hereditary hypertrophic cardiomyopathy, diabetic cardiomyopathy), diabetes, ischemia, HFpEF, and also as an early measure of systolic and diastolic heart failure. Measuring and quantifying heart metabolism would have significant implications on the diagnosis, understanding and management of these heart diseases, but there are no methods currently available to perform direct measurements of metabolism. This project aims to develop hyperpolarized 13C MRI as a human metabolic imaging for assessments of heart disease. This technology, utilizing 13C-pyruvate, has recently been shown to be safe and feasible in human subjects, with promising initial imaging in the heart. However, it still requires further development and in vivo validation to establish repeatable and reliable performance. This proposal includes Aim 1: Develop robust cardiac hyperpolarized 13C MRI methods. We propose imaging technology developments including real-time calibrations, fast imaging of multiple metabolites with whole heart coverage, image reconstructions with off-resonance correction, and cardiovascular signal models for quantifying metabolism. Aim 2: Perform in vivo validations in human subjects. We propose a series of studies that will establish robust imaging protocols and characterize the reproducibility and repeatability of this technique. These studies include evaluation of subject preparation methods, normalization of metabolic imaging data with correlative blood measurements, test-retest characterizations in healthy volunteers and patients, and same-session repeatability for multiple injection studies. The proposal also includes targeted performance measures to achieve with the proposed developments. Upon completion of this project, hyperpolarized 13C MRI has transformative potential for assessing heart diseases, adding new capabilities for quantifying metabolism in vivo.

项目摘要 心脏病是美国死亡的主要原因，导致超过60万人死亡 年。健康的心脏非常代谢，以满足其能量需求， 心脏代谢的改变对心脏功能产生重大影响。 代谢与许多心脏病有关，包括心肌病（遗传 肥厚性心肌病，糖尿病心肌病），糖尿病，缺血，HFPEF，也是 作为收缩期和舒张期心力衰竭的早期度量。测量和量化心脏 代谢将对诊断，理解和 这些心脏病的管理，但目前没有可用的方法 直接测量代谢。 该项目旨在开发超极化13C MRI作为人类代谢成像 评估心脏病。最近已经显示了使用13C-丙酮酸的技术 在人类受试者中安全可行，并有希望的最初成像。然而， 它仍然需要进一步的开发和体内验证才能建立可重复且可靠的 表现。该建议包括 AIM 1：开发强大的心脏超极化13C MRI方法。我们提出成像 技术发展，包括实时校准，多个代谢物的快速成像 具有全心覆盖范围，具有非谐振校正的图像重建，并且 用于量化代谢的心血管信号模型。 目标2：在人类受试者中进行体内验证。我们提出了一系列研究 建立强大的成像协议并表征此的可重复性和可重复性 技术。这些研究包括评估主题准备方法，正常化 具有相关血液测量结果的代谢成像数据，重测的重测 健康的志愿者和患者，以及多次注射研究的相同会议重复性。 该提案还包括针对拟议的目标绩效指标 发展。该项目完成后，超极化13C MRI具有变换 评估心脏病的潜力，增加了量化代谢的新能力 体内。