Development of large-field-of-view hyperpolarized MRI

项目摘要/摘要 前列腺癌，目前男性最常见的癌症，表现出广泛的生物学特征。 多样性。对非手术治疗反应的临床评估通常是不够的，因为研究 已经表明，当依赖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，或根据经直肠超声引导下的活检组织学确诊为癌症。 当进展为转移性癌症时，通常在雄激素剥夺治疗后，去势抵抗前列腺癌 癌症(CRPC)在90%以上的病例中会导致骨骼病变。临床上仍有迫切的需求 前列腺癌存在和反应的分子成像生物标志物的更高的敏感性和特异性 为新疗法干杯。 一项非同寻常的新技术，超极化磁共振(HP MR)，有可能改变 我们询问体内新陈代谢的方式。通过利用13C标记的内源底物，我们 能够非侵入性地成像代谢中间体及其后续的下游产品 常规核磁共振检查。在前列腺癌的背景下，这为研究前列腺癌提供了一个潜在的宝贵工具。 前列腺癌新陈代谢及其调控与肿瘤侵袭性和反应性的关系 治疗性干预。不幸的是，我们目前在可视化大量的 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方法几乎无法访问。 这一创新的学术产业伙伴关系的目标是通过开发一种 大视场HP MRI方法，包括硬件和软件。这项提议将建立一个 强大的平台，能够对前列腺癌患者的转移性疾病进行成像。在这个项目的第一个目标中 建议我们将开发一种新型的13C身体发射线圈和接收系统，能够对腹部进行成像。 同时，我们还将制定收购战略，以利用这一硬件实现快速惠普磁共振成像。 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]丙酮酸评估下游糖酵解的可视化方法，第二种方法使用[2-13C] 丙酮酸成像三氯乙酸循环，这是一项首次人类研究。 该提案的首要目标是构建一种新颖的大视场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 能够提供有关前列腺生物学的信息。

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.