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

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• 批准号: 10115625
• 负责人: James A Bankson
• 金额: $ 64.92万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10115625
• 关键词: 3-Dimensional; Address; Affect; Algorithmic Analysis; Biochemical Process; Biopsy; California; Cancer Center; Cancer Etiology; Cancer Patient; Cessation of life; Chemicals; Clinical; Clinical Trials; Clinical assessments; Complex; Conduct Clinical Trials; Contrast Media; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Drug Kinetics; Enzymes; Evaluation; Excision; Future; Gland; Goals; Gold; Histopathology; Human; Image; Image Enhancement; Imaging Phantoms; Imaging Techniques; Indolent; Infrastructure; Institution; Investigation; Kinetics; Lead; Life; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Maryland; Measurement; Metabolic; Metabolism; Methods; Modeling; Nuclear; Oncologist; Patients; Performance; Phase; Phase I Clinical Trials; Physicians; Process; Prostate; Prostatectomy; Protocols documentation; Pyruvate; Quality of life; Radical Prostatectomy; Reproducibility; Resolution; Role; Running; Safety; San Francisco; Scientist; Sensitivity and Specificity; Site; Techniques; Technology; Testing; Therapeutic; Three-Dimensional Imaging; Translating; Translations; Tumor stage; Universities; Visualization; Work; base; clinical examination; cohort; cost; cost outcomes; design; feasibility trial; image reconstruction; imaging biomarker; imaging capabilities; imaging modality; imaging scientist; improved; improved outcome; in vivo; insight; men; metabolic imaging; minimally invasive; mortality risk; multi-site trial; overtreatment; patient population; pharmacokinetic model; reconstruction; safety and feasibility; simulation; spatiotemporal; temporal measurement; tumor; tumor metabolism

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.

项目摘要 当前评估前列腺癌的方法，前列腺癌是男性癌症死亡的第二大原因， 不要充分区分侵略性和懒惰疾病。过度或不足 由于次优的诊断，可能导致不必要的生命损失或质量下降的毁灭性下降 生活。更好地评估疾病侵略性的新方法可以大大降低长期成本 并改善受到前列腺癌影响的男性的生活质量。动态核极化（DNP） [1-13c] - 丙酮酸提供对磁性读数的敏感性提高10,000倍 共振，可以在体内深入了解生物化学过程，并以空前的时空分辨率进行体内。 丙酮酸位于由许多癌症影响的代谢中的分支点：化学转化 即使在常氧性条件下，丙酮酸到乳酸的乳酸通常也会被癌症上调。 HP丙酮酸是 通过已证明与疾病侵略性相关的酶转化为HP乳酸。因此， HP丙酮酸和乳酸的代谢MR成像提供了前所未有的新窗口 对疾病和侵略性的最小侵入性诊断评估的机会。最近 加利福尼亚大学旧金山分校的同事们进行的I期临床试验证明了 HP丙酮酸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表明疾病成功可视化，但 提供有限的空间覆盖范围和时空分辨率。我们的目标是开发和翻译新 HP 13C MR代谢成像的获取和分析策略，可提供必要的覆盖范围 和解决方案，以便对多个机构的前列腺癌患者进行强有力的临床评估。 MD Anderson癌症中心和UCSF之间的这种合作伙伴关系在两个机构中利用专业知识 开发和翻译新的成像技术，以满足当前未满足的临床需求 前列腺癌的管理。这项工作将以三个目标进行。首先，我们将开发新的 加速的动态3D成像方法，在整个腺体上支持<0.5cm3图像分辨率，沿着 具有一类新的动态多光谱成像幻象来表征和验证 成像序列的性能。在第二个目标中，我们将完善并整合药代动力学 （PK）用于定量评估KPL的分析算法，KPL，肿瘤的成像生物标志物 代谢，并利用PK模型进一步改善了HP 13C前列腺的时空分辨率 癌症检查通过受约束的图像重建。在最终目标中，我们将评估灵敏度，特异性， 以及使用重测范式的这些测量值的可重复性，并通过比较 具有金色标准的组织病理学成像。到该项目结束时，我们将实施 强大的新成像方法，并对灵敏度，特异性和 HP 13C代谢MRI的可重复性，提供关键数据以帮助指导未来的临床试验 评估该技术的临床作用。