Development of large-field-of-view hyperpolarized MRI

项目总结/摘要 前列腺癌是目前男性中最常见的癌症，其表现出巨大的生物学范围。 多样性对非手术治疗反应的临床评估往往是不够的，因为， 已经表明，当它们依赖于血清前列腺特异性抗原（PSA）水平时， 达到最低点，或在使用经直肠超声引导的活组织检查的癌症的组织学确认时。 当进展为转移性癌症时，通常在雄激素剥夺治疗后， 癌症（CRPC）在超过90%的病例中导致骨病变。临床上仍然需要 前列腺癌存在和反应的分子成像生物标志物的更高灵敏度和特异性 到新的治疗方法。 一种非凡的新技术，超极化磁共振（HP MR），有可能改变 我们研究体内代谢的方式。通过利用13 C标记的内源性底物，我们 能够对代谢中间体及其后续下游产物进行非侵入性成像， 常规MRI。在前列腺癌的情况下，这为研究 前列腺癌代谢及其调节作为肿瘤侵袭性和对 治疗干预不幸的是，我们目前的能力有限，我们可以可视化大量的 感兴趣，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。 这个创新的学术工业伙伴关系的目标是通过开发一个 大视场HP MRI方法，包括硬件和软件。这项建议将建立一个 强大的平台，使前列腺癌患者的转移性疾病的成像。第一个目标是 我们将开发一种新型的13 C身体发射线圈和接收系统，能够对腹部进行成像。 同时，我们还将开发采集策略，以利用该硬件进行快速HP MRI。 最后，我们将在2组转移性前列腺癌患者中验证这种方法。第一个将被成像 与HP [1- 13 C]丙酮酸盐一起评估可视化下游糖酵解的方法，第二个与[2- 13 C] 丙酮酸成像TCA循环的首次人体研究。 本提案的总体目标是为HP MRI构建一种新颖的大视场方法，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 患者，以便为使用该技术的未来研究提供基准，并且另外确定其 前列腺生物学信息的能力。

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.