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: 10569034
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569034
• 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; Reliability of Results; Reproducibility; Resolution; Scanning; Selection for Treatments; Series; Signal Transduction; Source; Spectrum Analysis; Systolic heart failure; 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.

项目概要 心脏病是美国的首要死因，每年导致超过 60 万人死亡 年。健康的心脏代谢极其活跃，以满足其能量需求， 心脏代谢的改变对心脏功能有重大影响。 新陈代谢与许多心脏病有关，包括心肌病（遗传性心脏病） 肥厚性心肌病、糖尿病性心肌病）、糖尿病、缺血、HFpEF 以及 作为收缩性和舒张性心力衰竭的早期测量。测量和量化心脏 代谢将对诊断、理解和诊断产生重大影响。 治疗这些心脏病，但目前没有可用的方法 直接测量新陈代谢。 该项目旨在开发超极化 13C MRI 作为人体代谢成像 心脏病的评估。该技术利用 13C-丙酮酸盐，最近已被展示 在人类受试者中是安全可行的，并且在心脏中具有良好的初步成像效果。然而， 它仍然需要进一步的开发和体内验证来建立可重复和可靠的 表现。该提案包括 目标 1：开发强大的心脏超极化 13C MRI 方法。我们建议成像 技术发展，包括实时校准、多种代谢物的快速成像 具有整个心脏覆盖，具有偏共振校正的图像重建，以及 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其再现性和可重复性 技术。这些研究包括受试者准备方法的评估、标准化 代谢成像数据与相关血液测量、重测特征 健康志愿者和患者，以及多次注射研究的同一会话重复性。 该提案还包括有针对性的绩效措施，以实现拟议的目标 事态发展。该项目完成后，超极化 13C MRI 具有变革性意义 评估心脏病的潜力，增加量化代谢的新功能 体内。