Development of large-field-of-view hyperpolarized MRI

大视场超极化MRI的发展

• 批准号: 10524248
• 负责人: Charles H. Cunningham
• 金额: $ 11.4万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524248
• 关键词: Abdomen; Address; Animals; Benchmarking; Biodiversity; Biological Markers; Biology; Biopsy; Brain; Breast; Cancer Patient; Citric Acid Cycle; Clinic; Clinical; Clinical assessments; Collaborations; Computer software; Data; Development; Disease; Disseminated Malignant Neoplasm; Echo-Planar Imaging; Foundations; Future; Glycolysis; Goals; Heart; Histologic; Human; Human body; Image; Industrialization; Infrastructure; Infusion procedures; Label; Lead; Lesion; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Metabolic; Metabolism; Metastatic Prostate Cancer; Metastatic to; Methods; Monitor; Motivation; Mutation; Oncogenic; PSA level; Pathology; Patients; Pharmacotherapy; Phenotype; Physiologic pulse; Population; Prostate; Pyruvate; Pyruvate Metabolism Pathway; Radioactive Tracers; Research; Research Personnel; Role; Scientist; Sensitivity and Specificity; Site; Support System; Surface; System; Systems Biology; Techniques; Technology; Therapeutic Intervention; Time; Translating; Transrectal Ultrasound; Up-Regulation; Validation; Visualization; Work; androgen deprivation therapy; animal imaging; base; bone; cancer site; cancer therapy; castration resistant prostate cancer; cohort; design; first-in-human; follow-up; human study; image reconstruction; imaging biomarker; imaging modality; improved; in vivo; individualized medicine; industry partner; innovation; interest; men; metabolic abnormality assessment; metabolic imaging; molecular imaging; non-invasive imaging; non-invasive monitor; novel; novel therapeutic intervention; novel therapeutics; patient population; response; serum PSA; software development; tool; treatment effect; treatment planning; treatment response; tumor; tumor metabolism; virtual

PROJECT SUMMARY/ABSTRACT Prostate cancers, currently the most common cancer in men, demonstrate a tremendous range of biologic diversity. Clinical assessments of response to non-surgical therapy are often inadequate because, as studies have shown, they lead to inaccuracies when they rely upon serum prostate specific antigen (PSA) levels reaching a nadir, or upon the histological confirmation of cancer using transrectal ultrasound guided biopsies. When progressing to metastatic cancer, typically after androgen deprivation therapy, castrate resistant prostate cancer (CRPC) results in bone lesions in more than 90% of cases. There remains a critical clinical need for greater sensitivity and specificity in molecular imaging biomarkers of prostate cancer presence and of response to novel therapeutics. An extraordinary new technique, hyperpolarized magnetic resonance (HP MR), has the potential to change the way we interrogate metabolism in vivo. Through the utilization of 13C-labeled endogenous substrates, we are able to non-invasively image a metabolic intermediate and its subsequent downstream products using conventional MRI. In the setting of prostate cancer, this provides a potentially invaluable tool for the study of prostate cancer metabolism and its modulation as a function of tumor aggressiveness and response to therapeutic intervention. Unfortunately, we are currently limited in our ability to visualize large volumes of interest, whereas metastatic prostate cancer typically requires visualization of the abdomen and bone regions, virtually inaccessible to current HP MRI approaches. The objective of this innovative academic industrial partnership is to address this problem by developing a large-field-of-view HP MRI approach, including both hardware and software. This proposal would establish a robust platform to enable the imaging of metastatic disease in prostate cancer patients. In the first aim of this proposal we will develop a novel 13C body transmit coil and receive system capable of imaging the abdomen. In tandem, we will also develop acquisition strategies to take advantage of this hardware for rapid HP MRI. Finally, we will validate this approach in 2 cohorts of metastatic prostate cancer patients. The first will be imaged with HP [1-13C] pyruvate to assess methods to visualize downstream glycolysis and the second with [2-13C] pyruvate to image the TCA cycle for a first-in-human study. It is the overarching goal of this proposal to build a novel, large-field-of-view approach to HP MRI – including, importantly, both hardware and software – and apply it to the imaging of HP pyruvate metabolism in cancer patients so as to provide benchmark for future studies using this technique, and additionally to determine its ability to inform on prostate biology.

项目概要/摘要 前列腺癌是目前男性中最常见的癌症，具有多种生物学特性 多样性。对非手术治疗反应的临床评估通常是不充分的，因为，正如研究 已经表明，当它们依赖于血清前列腺特异性抗原（PSA）水平时，它们会导致不准确 达到最低点，或使用经直肠超声引导活检对癌症进行组织学确认。 当进展为转移性癌症时，通常是在雄激素剥夺治疗后，去势抵抗性前列腺 90% 以上的癌症 (CRPC) 会导致骨病变。临床仍然迫切需要 前列腺癌存在和反应的分子成像生物标志物具有更高的敏感性和特异性 到新的治疗方法。 超极化磁共振 (HP MR) 是一种非凡的新技术，有可能改变 我们研究体内新陈代谢的方式。通过利用 13C 标记的内源底物，我们 能够使用非侵入性方式对代谢中间体及其后续下游产品进行成像 常规 MRI。在前列腺癌的背景下，这为研究提供了一个潜在的宝贵工具。 前列腺癌代谢及其作为肿瘤侵袭性和响应的函数的调节 治疗干预。不幸的是，我们目前可视化大量数据的能力有限。 兴趣，而转移性前列腺癌通常需要腹部和骨骼区域的可视化， 目前的 HP MRI 方法几乎无法实现。 这种创新的学术工业合作伙伴关系的目标是通过开发一种解决这一问题的方法。 大视场 HP MRI 方法，包括硬件和软件。该提案将设立一个 强大的平台能够对前列腺癌患者的转移性疾病进行成像。在本次活动的第一个目标中 根据提案，我们将开发一种新型 13C 人体发射线圈和接收系统，能够对腹部进行成像。 与此同时，我们还将制定采集策略，以利用该硬件进行快速 HP MRI。 最后，我们将在两组转移性前列腺癌患者中验证这种方法。第一个将被成像 使用 HP [1-13C] 丙酮酸来评估下游糖酵解可视化的方法，第二个使用 [2-13C] 丙酮酸对 TCA 循环进行成像，以进行首次人体研究。 该提案的总体目标是建立一种新颖的大视场 HP MRI 方法，包括： 重要的是，硬件和软件 - 并将其应用于癌症中 HP 丙酮酸代谢的成像 以便为未来使用该技术的研究提供基准，并另外确定其 了解前列腺生物学的能力。