Multi-Site Development & Evaluation of a Quantitative 3D Hyperpolarized C-13 MRI Clinical Prostate Cancer Exam

项目摘要 目前评估前列腺癌的方法是，前列腺癌是男性癌症死亡的第二大原因， 不要充分区分侵袭性疾病和惰性疾病。治疗过度或治疗不足 由于不理想的诊断可能会导致不必要的生命损失或质量的毁灭性下降 生活。更好地评估疾病侵袭性的新方法可以大幅降低长期成本 改善受前列腺癌影响的男性的生活质量。的动态核极化(DNP) [1-13C]-丙酮酸可使磁读数的灵敏度提高10,000倍以上 磁共振，以前所未有的时空分辨率洞察体内的生化过程。 丙酮酸位于新陈代谢的分支点，受许多癌症的影响：化学转化 即使在常氧条件下，丙酮酸到乳酸的比例通常也会因癌症而上调。HP丙酮酸是 已被证明与疾病侵袭性相关的酶将其转化为HP乳酸。因此， HP丙酮酸和乳酸的代谢磁共振成像提供了一个前所未有的新窗口 对疾病和侵袭性进行微创诊断评估的机会。最近 加州大学旧金山分校的同事进行的I期临床试验证明 幽门螺杆菌丙酮酸用于前列腺癌患者评估的安全性和可行性成像 可行性试验中使用的方法显示了疾病的成功可视化，但 提供有限的空间覆盖和时空分辨率。我们的目标是开发和翻译新的 提供必要覆盖范围的HP 13C MR代谢成像的采集和分析策略 以及解决方案，以便在多个机构对前列腺癌患者进行强有力的临床评估。 MD安德森癌症中心和加州大学旧金山分校之间的这种合作伙伴关系利用了这两个机构的专业知识 开发和转化新的成像技术，以满足目前未得到满足的临床需求 前列腺癌的管理。这项工作将在三个目标下进行。首先，我们将发展新的 加速的动态3D成像方法，支持整个腺体的-lt；0.5cm3图像分辨率 利用一类新的动态多光谱成像模体来表征和验证 成像序列的性能。在第二个目标中，我们将提炼和整合药代动力学 用于定量评估肿瘤影像生物标志物KPL的(PK)分析算法 新陈代谢，并利用PK模型进一步提高Hp 13C前列腺的时空分辨率 通过受限图像重建进行癌症检查。在最终目标中，我们将评估敏感性、特异性、 以及这些测量的可重复性，使用重测范式和比较 用黄金标准的组织病理学进行成像。到这个项目结束时，我们将实现 强大的新成像方法，并进行了有史以来首次评估的敏感性、特异性和 HP 13C代谢核磁共振的重复性，为指导未来的临床试验提供了关键数据 评估这项技术的临床作用。

Project Summary Current methods for assessing prostate cancer, the second most common cause of cancer death in men, do not adequately distinguish between aggressive and indolent disease. Over- or under-treatment due to suboptimal diagnostics can lead to unnecessary loss of life or devastating decline in quality of life. New methods that better assess disease aggressiveness could substantially reduce long-term costs and improve the quality of life of men affected by prostate cancer. Dynamic nuclear polarization (DNP) of [1-13C]-pyruvate provides a greater than 10,000-fold increase in sensitivity to readout by magnetic resonance, allowing insight into biochemical processes in vivo with unprecedented spatiotemporal resolution. Pyruvate lies at a branching point in metabolism that is affected by many cancers: the chemical conversion of pyruvate to lactate is often upregulated by cancer, even under normoxic conditions. HP pyruvate is converted into HP lactate by enzymes that have been shown to correlate with disease aggressiveness. Thus, metabolic MR imaging of HP pyruvate and lactate provides an unprecedented new window of opportunity for minimally invasive diagnostic assessment of disease and aggressiveness. A recent Phase I clinical trial conducted by colleagues at the University of California in San Francisco demonstrated the safety and feasibility of HP pyruvate for assessing patients with prostate cancer. The imaging methods that were used in the feasibility trial demonstrated successful visualization of disease, but provided limited spatial coverage and spatiotemporal resolution. Our goal is to develop and translate new acquisition and analysis strategies for HP 13C MR metabolic imaging that provide the necessary coverage and resolution to enable robust clinical assessment of prostate cancer patients at multiple institutions. This partnership between MD Anderson Cancer Center and UCSF leverages expertise at both institutions to develop and translate new imaging techniques to address currently unmet clinical needs in the management of prostate cancer. The work will be carried out in three Aims. First, we will develop new accelerated dynamic 3D imaging methods that support <0.5cm3 image resolution throughout the gland, along with a new class of dynamic multispectral imaging phantoms to characterize and validate the performance of imaging sequences. In the second Aim, we will refine and integrate pharmacokinetic (PK) analysis algorithms for quantitative assessment of kPL, the imaging biomarker for tumor metabolism, and leverage PK models to further improve the spatiotemporal resolution of HP 13C prostate cancer exams by constrained image reconstruction. In the final Aim, we will assess sensitivity, specificity, and reproducibility of these measurements using a test-retest paradigm and by comparison of imaging with gold-standard histopathology. By the end of this project, we will have implemented robust new imaging methods, and conducted first-ever evaluation of the sensitivity, specificity, and reproducibility of HP 13C metabolic MRI, providing crucial data to help guide future clinical trials for assessing the clinical roles of this technology.