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: 10543731
• 负责人: Peder Eric Zufall Larson
• 金额: $ 62.22万
• 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/10543731
• 关键词: Address; Benign; Biological Markers; Biopsy; Calibration; Cardiovascular Diseases; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Protocols; Clinical Research; Data; Data Set; Detection; Diagnosis; 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; Patient Selection; 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; Visualization; 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.

项目摘要： 该项目旨在将超极化（HP）13C丙酮酸MRI作为创新的代谢成像转换 无创预测肾脏肿瘤侵袭性的方法，这是一种未满足的临床需求。我们的研究直接 对第19-264款的响应，支持“新兴成像的优化，应用和验证或 生物标志物的方法是专门针对临床应用的”，其目标是“减少过度诊断”，并且 “从非致命疾病中识别致命的癌症”。我们的项目是由肾脏肿瘤事件不断上升的动机， 在很大程度上，随着许多局部肿瘤的偶然发现对成像的利用率增加。 包括良性肾脏肿瘤和恶性肾细胞癌（RCC）。当前的成像或活检 无法可靠地区分良性肿瘤，低级RCC和高级RCC。诊断 模棱两可导致许多懒惰的肿瘤过度诊断，这些肿瘤是不必要的。 手术风险，重要的是，增加了慢性肾脏疾病和相关心血管疾病的风险。 值得注意的是，RCC的检测增加并未转化为癌症特异性死亡的减少。所以， 对新型成像标记的需求很大，可以改善的风险分层 局部肾脏肿瘤可指导患者管理。 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的实时途径特定研究 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 定量地绘制丙酮酸到肽的增加的代谢，通过缝隙脱氢酶途径（A） 可成像的生物标志物与RCC的存在及其侵略性密切相关。我们也有 证明了在患者中获得肾肿瘤的动态HP 13C丙酮酸MRI的可行性， 肿瘤和正常肾脏之间的代谢对比度。在这些有希望的初步数据的基础上，我们现在 提议首次调查HP 13C丙酮酸MRI的价值，以使局部肾脏肿瘤风险分层。 目标1-我们将优化用于肾肿瘤代谢评估的MRI获取策略。目标2-我们将 研究HP 13C丙酮酸MRI的值，以区分良性肿瘤，低级RCC和 高级RCC。我们还将将HP 13C数据与高级1H MRI和放射线学分析进行比较，并开发 多参数模型以评估它是否可以改善预测。目标3-我们将确定可重复性 肾肿瘤的HP 13C丙酮酸MRI，并评估新的分析方法以进一步改善鲁棒性 代谢定量。该项目的成功完成将提供有关HP价值的第一个数据 13C丙酮酸MRI预测肾脏肿瘤侵袭性，并为将来的更大临床研究铺平道路。 HP 13C丙酮酸已经被证明是安全的，我们设想13C代谢成像标记为 纳入最先进的多参数MRI，以减少当前的过度诊断 同时可以尽早发现侵略性RCC，并帮助安全选择患者进行主动监测。