Translating Hyperpolarized 13C Metabolic MRI to Predict Renal Tumor Aggressiveness

转化超极化 13C 代谢 MRI 来预测肾肿瘤的侵袭性

• 批准号: 10597761
• 负责人: Peder Eric Zufall Larson
• 金额: $ 4.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597761
• 关键词: Address; Benign; Biological Markers; Biopsy; Calibration; Cardiovascular Diseases; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Protocols; Clinical Research; Data; Data Set; Detection; Diagnostic; Disease; Early Diagnosis; Evaluation; Excision; Future; Glycolysis; Goals; Histology; Human; Image; Imaging Techniques; Imaging technology; Incidence; Incidental Discoveries; Indolent; Investigation; Kidney; Kidney Neoplasms; Lactate Dehydrogenase; Link; Local Therapy; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of kidney; Maps; Measures; Mediating; Metabolic; Metabolism; Methods; Modeling; Motivation; Neoplasm Metastasis; Noise; Operative Surgical Procedures; Pathology; Pathway interactions; Patients; Performance; Production; Prognosis; Pyruvate; Pyruvate Metabolism Pathway; RF coil; Reference Standards; Renal Cell Carcinoma; Renal carcinoma; Reproducibility; Risk; Running; Safety; Scanning; Signal Transduction; Testing; Time; Translating; Unnecessary Surgery; Validation; Work; clinical application; cohort; cost; imaging approach; imaging biomarker; improved; innovation; kinetic model; magnetic resonance imaging biomarker; metabolic imaging; metabolomics; molecular imaging; novel; overtreatment; pre-clinical; radiomics; response; risk stratification; standard of care; surgical risk; temporal measurement; tumor; tumor metabolism

Project summary: This project aims to clinically translate hyperpolarized (HP) 13C pyruvate MRI as an innovative metabolic imaging approach for noninvasive prediction of renal tumor aggressiveness, an unmet clinical need. Our study is in direct response to PAR 19-264 that supports “The optimization, application and validation of emerging imaging or biomarker approaches targeted specifically for clinical application”, with the goals to “reduce overdiagnosis”, and “identify lethal cancers from non-lethal disease”. Our project is motivated by the rising incidence of renal tumors, largely due to the increased utilization of imaging with incidental discovery of many localized tumors. These include both benign renal tumors and malignant renal cell carcinomas (RCCs). Current imaging or biopsies cannot reliably differentiate between benign tumors, low grade RCCs, and high grade RCCs. The diagnostic ambiguity has led to an overdiagnosis of many indolent tumors which are unnecessarily treated by surgery with surgical risks, and importantly, increased risk of chronic kidney disease and associated cardiovascular disease. Notably, the increased detection of RCCs has not translated into a decrease in cancer specific death. Therefore, there is a significant unmet need for novel imaging markers that can improve the risk stratification of localized renal tumors to guide patient management. HP 13C MRI is an emerging imaging technology that allows real-time pathway-specific investigation of metabolic processes that were previously inaccessible by imaging. Our pre-clinical data in orthotopic RCC tumor models have shown that HP 13C pyruvate MRI can quantitatively map the increased pyruvate-to-lactate metabolism via the lactate dehydrogenase pathway, an imageable biomarker which is strongly linked to the presence of RCC and its aggressiveness. We have also demonstrated the feasibility of acquiring dynamic HP 13C pyruvate MRI of renal tumors in patients, with excellent metabolic contrast between tumor and normal kidney. Building upon these promising preliminary data, we now propose to investigate for the first time the value of HP 13C pyruvate MRI for risk stratifying localized renal tumors. Aim 1- we will optimize the MRI acquisition strategies for renal tumor metabolic evaluation. Aim 2- we will investigate the value of HP 13C pyruvate MRI for differentiating between benign tumors, low grade RCCs, and high grade RCCs. We will also compare HP 13C data to advanced 1H MRI and radiomics analyses, and develop multi-parametric model to assess whether it can improve the prediction. Aim 3- we will determine the repeatability of HP 13C pyruvate MRI of renal tumors, and evaluate new analysis methods to further improve the robustness of metabolism quantification. Successful completion of this project will provide the first data on the value of HP 13C pyruvate MRI in predicting renal tumor aggressiveness, and will pave the way for future larger clinical studies. HP 13C pyruvate has already been shown to be safe, and we envision the 13C metabolic imaging markers to be incorporated into a state-of-the-art multi-parametric MRI to reduce the current overdiagnosis of indolent tumors while enabling the early detection of aggressive RCCs, and help safely select patients for active surveillance.

项目概要： 该项目旨在将超极化 (HP) 13C 丙酮酸 MRI 作为一种创新的代谢成像进行临床转化 肾肿瘤侵袭性无创预测的方法，这是一个未满足的临床需求。我们的研究是直接的 响应 PAR 19-264，支持“新兴成像或技术的优化、应用和验证” 专门针对临床应用的生物标志物方法”，目标是“减少过度诊断”，以及 “从非致命疾病中识别致命癌症”。我们的项目的动机是肾肿瘤发病率的上升， 这主要是由于成像技术的使用增加以及许多局部肿瘤的偶然发现。这些 包括良性肾肿瘤和恶性肾细胞癌（RCC）。当前成像或活检 无法可靠地区分良性肿瘤、低级别 RCC 和高级别 RCC。诊断 模糊性导致了对许多惰性肿瘤的过度诊断，这些肿瘤不必要地通过手术进行治疗 手术风险，更重要的是，增加慢性肾病和相关心血管疾病的风险。 值得注意的是，肾细胞癌检出率的增加并未转化为癌症特异性死亡的减少。所以， 对可以改善风险分层的新型成像标记物的需求尚未得到满足 局部肾肿瘤指导患者管理。 HP 13C MRI 是一种新兴的成像技术， 允许对以前无法访问的代谢过程进行实时特定途径研究 成像。我们在原位 RCC 肿瘤模型中的临床前数据表明，HP 13C 丙酮酸 MRI 可以 通过乳酸脱氢酶途径定量绘制丙酮酸到乳酸代谢的增加， 与 RCC 的存在及其侵袭性密切相关的可成像生物标志物。我们还有 证明了获取患者肾肿瘤动态 HP 13C 丙酮酸 MRI 的可行性，具有良好的效果 肿瘤和正常肾脏的代谢对比。基于这些有希望的初步数据，我们现在 提议首次研究 HP 13C 丙酮酸 MRI 对局部肾肿瘤风险分层的价值。 目标 1-我们将优化肾肿瘤代谢评估的 MRI 采集策略。目标2-我们会 研究 HP 13C 丙酮酸 MRI 区分良性肿瘤、低级别肾细胞癌和肾细胞癌的价值 高等级碾压混凝土。我们还将 HP 13C 数据与先进的 1H MRI 和放射组学分析进行比较，并开发 多参数模型来评估它是否可以改进预测。目标 3 - 我们将确定重复性 肾肿瘤的 HP 13C 丙酮酸 MRI 的研究，并评估新的分析方法以进一步提高稳健性 代谢定量。该项目的成功完成将提供有关惠普价值的第一份数据 13C丙酮酸MRI可预测肾肿瘤的侵袭性，并将为未来更大规模的临床研究铺平道路。 HP 13C 丙酮酸已被证明是安全的，我们预计 13C 代谢成像标记物将是 纳入最先进的多参数 MRI，以减少当前对惰性肿瘤的过度诊断 同时能够及早发现侵袭性肾细胞癌，并帮助安全地选择患者进行主动监测。