New Instrumentation and Techniques for Hyperpolarized Metabolic and Perfusion MRI

描述（由申请人提供）：超极化（HP）碳-13 MRI已证明能够显著提高我们对疾病过程的理解，并具有成为用于监测临床试验和个体患者管理的具有成本效益的分子成像工具的巨大潜力。我们最近的首次人体I期临床试验利用独特的溶解DNP仪器和方法进行[1- 13 C]丙酮酸代谢成像。该项目旨在通过开发新的仪器和方法向前迈出重要一步，将临床前多药物极化研究转化为首次人体双药物同时代谢和灌注HP MRI研究。该项目旨在开发一种新的MRI方法，根据癌症的遗传/蛋白质组学和灌注异常来表征癌症，并将这种方法应用于临床前模型，以获得FDA批准所需的初步数据，然后进行初步的人体研究。超极化（HP）碳-13 MRI是一种功能强大的新型分子成像方法，它使用专门的仪器为碳-13富集的、安全的、内源性的、非放射性化合物提供超过5个数量级的信号增强。13 C-尿素与[1- 13 C]丙酮酸盐的共极化不仅提供了提高定量准确度的内部参考，而且还提供了在没有电离辐射和没有其他灌注造影剂的肾毒性效应的情况下进行同时灌注测量的方法。这个项目旨在翻译和执行第一次在人 HP双试剂灌注和代谢MRI可满足迫切的临床需求，特别是改善前列腺癌侵袭性和治疗反应的放射学表征。将设计和构建新的硬件/仪器，以实现首次人体超极化灌注和代谢成像人体研究所需的双试剂功能。还将开发新的MRI采集和分析方法，用于快速采集高分辨率代谢和灌注成像数据。该项目开发的技术将应用于前列腺癌患者，以解决明显未满足的临床需求。然而，这些双试剂HP 13 C MR技术也具有普遍适用性，可用于推进其他癌症的临床研究，并可能用于广泛的病理学，包括心脏病、肝病和肾病。

DESCRIPTION (provided by applicant): Hyperpolarized (HP) carbon-13 MRI has demonstrated the ability to significantly advance our understanding of disease processes and the great potential to become a cost effective molecular imaging tool for monitoring clinical trial and individual patient management. Our recent first-in-man Phase 1 Clinical Trial utilized unique dissolution DNP instrumentation and methods for [1-13C] pyruvate metabolic imaging. The proposed project is designed to take a major step forward by developing new instrumentation and methods to translate preclinical multi-agent polarization studies into first-in-man dual-agent simultaneous metabolic & perfusion HP MRI studies. This project aims to develop a new MRI approach to characterize cancers based on their genetic/proteomic and perfusion abnormalities and apply this method in preclinical models to obtain the required preliminary data for FDA approval and then to conduct initial human studies. Hyperpolarized (HP) carbon-13 MRI is a powerful new molecular imaging method which uses specialized instrumentation to provide signal enhancements of over 5-orders of magnitude for carbon-13 enriched, safe, endogenous, non-radioactive compounds. Co-polarization of 13C-urea with [1-13C] pyruvate provides not only an internal reference for improved quantitative accuracy, but also a method for simultaneous perfusion measurements without ionizing radiation and without the nephrotoxicity effects of other perfusion contrast agents. This project aims to translate and perform first-in-man HP dual-agent perfusion & metabolic MRI to address a pressing clinical need, specifically improved radiological characterization of prostate cancer aggressiveness and treatment response. New hardware/instrumentation will be designed and constructed to enable dual-agent functionality necessary for first-in-man hyperpolarized perfusion and metabolic imaging human studies. Novel MRI acquisition and analysis methods will also be developed for acquiring rapid high resolution metabolic & perfusion imaging data. The techniques developed in this project will be applied in prostate cancer patients to address a clear unmet clinical need. However, these dual-agent HP 13C MR techniques also have general applicability to advance the clinical research of other cancers and potentially a wide range of pathologies including cardiac, liver, and kidney disease.