Development of large-field-of-view hyperpolarized MRI

大视场超极化MRI的发展

• 批准号: 10531899
• 负责人: Charles H. Cunningham
• 金额: $ 57.12万
• 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/10531899
• 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; Lesion; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Metabolic; Metabolism; Metastatic Prostate Cancer; Methods; Monitor; Motivation; Mutation; Oncogenic; PSA level; Pathology; Patients; Perfusion; 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; bone; cancer site; cancer therapy; castration resistant prostate cancer; cohort; design; first-in-human; follow-up; human study; image reconstruction; imaging biomarker; imaging capabilities; 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; transmission process; 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.

项目总结/文摘