Development of large-field-of-view hyperpolarized MRI

大视场超极化MRI的发展

基本信息

批准号：
9887898
负责人：
Charles H. Cunningham
金额：
$ 67.38万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
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/9887898
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

项目摘要

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对非手术治疗反应的临床评估往往不够充分，因为研究表明。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，去势抵抗性前列腺超过 90% 的癌症 (CRPC) 会导致骨病变，但临床仍迫切需要这种药物。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，有可能改变通过利用 13C 标记的内源性底物，我们研究了体内代谢。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在前列腺癌的情况下，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不幸的是，我们目前观察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。强大的平台能够对前列腺癌患者的转移性疾病进行成像。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，第一组将进行成像。使用 HP [1-13C] 丙酮酸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野 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。