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

项目摘要 目前用于评估前列腺癌的方法，前列腺癌是男性癌症死亡的第二大常见原因， 不能充分区分侵袭性疾病和惰性疾病。治疗过度或治疗不足 由于次优诊断可能导致不必要的生命损失或医疗质量的毁灭性下降， 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 改善前列腺癌患者的生活质量。动态核极化（DNP） [1- 13 C]-丙酮酸盐提供了大于10，000倍的磁读出灵敏度增加 共振，允许洞察生物化学过程在体内前所未有的时空分辨率。 丙酮酸位于代谢的一个分支点，受许多癌症的影响： 丙酮酸转化为乳酸的过程经常被癌症上调，即使在含氧量正常的条件下。HP丙酮酸是 被证明与疾病侵袭性相关的酶转化为HP乳酸。因此，在本发明中， HP丙酮酸盐和乳酸盐的代谢MR成像提供了一个前所未有的新窗口， 为疾病和侵袭性的微创诊断评估提供了机会。最近的一 由位于旧金山弗朗西斯科的加州大学的同事进行的I期临床试验证明， HP丙酮酸盐用于评估前列腺癌患者的安全性和可行性。成像 在可行性试验中使用的方法证明了对疾病的成功可视化， 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 HP 13 C MR代谢成像的采集和分析策略，提供必要的覆盖范围 和分辨率，从而能够在多个机构对前列腺癌患者进行稳健的临床评估。 MD安德森癌症中心和UCSF之间的这种合作关系利用了两家机构的专业知识 开发和翻译新的成像技术，以解决目前未满足的临床需求， 前列腺癌的治疗这项工作将在三个目标下进行。首先，我们将开发新的 加速的动态3D成像方法，支持整个腺体<0.5 cm 3的图像分辨率，沿着 使用一类新的动态多光谱成像幻影来表征和验证 成像序列的性能。在第二个目标中，我们将完善和整合药代动力学 (PK)用于定量评估肿瘤成像生物标志物kPL的分析算法 代谢，并利用PK模型进一步提高HP 13 C前列腺的时空分辨率 通过约束图像重建进行癌症检查。在最终的目标中，我们将评估灵敏度，特异性， 和重现性，这些测量使用测试-重测范例，并通过比较 用金标准组织病理学成像。到本项目结束时，我们将实施 强大的新成像方法，并进行了首次评估的灵敏度，特异性， HP 13 C代谢MRI的可重复性，提供了关键数据，以帮助指导未来的临床试验， 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.