Hyperpolarized Carbon-13 Metabolic MRI of the Human Heart

项目摘要 心脏病是美国死亡的主要原因，每年导致超过60万人死亡。 年健康的心脏代谢非常活跃，以满足其能量需求， 并且心脏代谢的改变对心脏功能具有显著的影响。 代谢与许多心脏病有关，包括心肌病（遗传性 肥厚性心肌病、糖尿病性心肌病）、糖尿病、缺血、HFpEF，以及 作为收缩期和舒张期心力衰竭的早期指标。测量和量化心脏 代谢将对诊断、理解和 这些心脏病的管理，但目前没有方法可以执行 直接测量新陈代谢。 该项目旨在开发超极化13 C MRI作为人体代谢成像， 评估心脏病。这项利用13 C-丙酮酸盐的技术最近已被证明 在人类受试者中是安全可行的，在心脏中具有有希望的初始成像。然而，在这方面， 它仍然需要进一步的开发和体内验证，以建立可重复和可靠的 性能该提案包括 目的1：开发稳健的心脏超极化13 C 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 覆盖整个心脏，进行非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。 目的2：在人类受试者中进行体内确认。我们提出了一系列的研究， 建立强大的成像协议，并表征其再现性和重复性， 法这些研究包括受试者准备方法的评价， 代谢成像数据与相关血液测量， 健康志愿者和患者，以及多次注射研究的相同阶段重复性。 该提案还包括有针对性的绩效措施，以实现拟议的 发展理念该项目完成后，超极化13 C MRI具有变革性 评估心脏病的潜力，增加量化代谢的新能力， vivo.

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.