New Instrumentation and Techniques for Hyperpolarized Metabolic and Perfusion MRI

描述(由申请人提供)：超极化(HP)碳-13磁共振已经证明能够显著提高我们对疾病过程的理解，并具有成为监测临床试验和个别患者管理的经济高效的分子成像工具的巨大潜力。我们最近的第一个人阶段临床试验使用了独特的溶解DNP仪器和方法来进行[1-13C]丙酮酸代谢成像。该项目旨在通过开发新的仪器和方法，将临床前多药剂极化研究转化为首例双药剂同时代谢和灌注HP MRI研究，从而向前迈进一大步。该项目旨在开发一种新的MRI方法，根据癌症的遗传/蛋白质组和血流异常来确定癌症的特征，并将该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磁共振成像是一种功能强大的新的分子成像方法，它使用专门的仪器对碳-13丰富、安全、内源性、非放射性的化合物提供超过5个数量级的信号增强。~(13)C-尿素与[~(13)C]丙酮酸的共极化不仅为提高定量准确度提供了内部参照物，而且还提供了一种无电离辐射和其他灌注造影剂的肾毒性影响的同步血流灌注测量方法。该项目旨在翻译和执行第一人称 惠普双试剂灌注和代谢核磁共振，以满足紧迫的临床需求，特别是改善前列腺癌侵袭性和治疗反应的放射学特征。将设计和建造新的硬件/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。还将开发新的磁共振成像采集和分析方法，以获取快速高分辨率的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，以解决明显未得到满足的临床需求。然而，这些双剂HP 13C磁共振技术也具有普遍的适用性，可以推进其他癌症的临床研究，并可能促进包括心脏、肝脏和肾脏疾病在内的广泛的病理研究。

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.