Development of large-field-of-view hyperpolarized MRI

大视场超极化MRI的发展

• 批准号: 10162833
• 负责人: Charles H. Cunningham
• 金额: $ 4.03万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162833
• 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 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.

项目摘要/摘要 前列腺癌（目前是男性最常见的癌症）表现出巨大的生物学 多样性。对非手术治疗反应的临床评估通常是不足的，因为作为研究 已经表明，当它们依靠血清前列腺特异性抗原（PSA）水平时，它们会导致不准确 使用转直肠超声引导活检到达癌症的组织学确认后，到达癌症。 通常在转移性癌症（通常在雄激素剥夺治疗后）castrate前列腺 癌症（CRPC）在超过90％的病例中导致骨骼病变。仍然有关键的临床需求 在前列腺癌的存在和反应的分子成像生物标志物中的更高敏感性和特异性 进行新的疗法。 一种非凡的新技术，超极化磁共振（HP MR），有可能改变 我们在体内询问新陈代谢的方式。通过利用13C标记的内源性底物，我们是 它可以非侵入性地对代谢中间体形象及其随后的下游产品图像 常规MRI。在前列腺癌的情况下，这为研究提供了潜在的宝贵工具 前列腺癌代谢及其调节作为肿瘤侵袭性的函数和对 治疗干预。不幸的是，我们目前的能力有限 兴趣，而转移性前列腺癌通常需要可视化腹部和骨骼区域，但 当前的HP MRI方法几乎无法访问。 这种创新的学术工业伙伴关系的目的是通过开发一个 大型视野HP MRI方法，包括硬件和软件。该建议将建立一个 强大的平台可以使前列腺癌患者的转移性疾病成像。在第一个目的 提案我们将开发一种新型的13C身体传输线圈，并接收能够对腹部进行成像的系统。 同时，我们还将制定采集策略，以利用此硬件来快速HP MRI。 最后，我们将在2个转移性前列腺癌患者中验证这种方法。第一个将成像 使用HP [1-13C]丙酮酸评估可视化下游糖酵解的方法，第二种方法是[2-13C] 丙酮酸成像TCA周期以进行首次人类研究。 这是该提议的总体目标，即建立一种针对HP MRI的新颖，大型视野方法 - 包括，包括， 重要的是，硬件和软件都将其应用于癌症中HP丙酮酸代谢的成像 患者为将来使用该技术提供基准，并确定其 能够告知前列腺生物学的能力。