MRI-Based Renal Oximetry in Early Diabetic Kidney Disease

基于 MRI 的肾血氧饱和度在早期糖尿病肾病中的应用

• 批准号: 10593684
• 负责人: Felix W Wehrli
• 金额: $ 24.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593684
• 关键词: Abdomen; Address; Adult; Affect; Albumins; Albuminuria; Animal Model; Attenuated; Benchmarking; Biological Markers; Blood; Blood Flow Velocity; Blood flow; Brain; Calibration; Cardiovascular Diseases; Cerebrovascular Circulation; Cerebrum; Chronic Kidney Failure; Clinical; Clinical Markers; Creatinine; Data; Development; Diabetes Mellitus; Diabetic Nephropathy; Dialysis procedure; Disease; Disease Progression; Early Diagnosis; Early Intervention; Evaluation; Fick method; Filtration; Functional disorder; Future; Glomerular Filtration Rate; Health; Histology; Hour; Human; Hypoxia; Ionizing radiation; Kidney; Kidney Diseases; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Methods; Microalbuminuria; Monitor; Motion; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Oxygen; Oxygen saturation measurement; Pathologic; Pathway interactions; Patient Monitoring; Patients; Performance; Phase; Physiologic pulse; Physiological; Pilot Projects; Play; Positron-Emission Tomography; Prediabetes syndrome; Prevalence; Public Health; Pulse Oximetry; Relaxation; Renal Tissue; Renal function; Reporting; Reproducibility; Research; Risk Factors; Role; Sampling; Scanning; Serum; Signal Transduction; Site; Subtraction Technique; Superior sagittal sinus; Techniques; Technology; Testing; Time; Tissues; Transplantation Surgery; Type 2 diabetic; Urine; Veins; Venous; Water; Work; blood flow measurement; cardiovascular risk factor; demographics; deoxyhemoglobin; design; diabetic; diabetic patient; human subject; imaging modality; insight; kidney dysfunction; kidney imaging; metabolic rate; novel; radiotracer; renal damage; renal hypoxia; tissue oxygenation

PROJECT SUMMARY Chronic kidney disease (CKD), affecting 15% of US adults, is characterized by a progressive loss of kidney function. The leading cause of CKD is type-2 diabetes mellitus, and up to 40% of type-2 diabetic patients go on to develop CKD. Current measures of kidney function are limited in that they estimate glomerular filtration rate (eGFR), require multiple blood and urine samples over several hours, or detect disease after irreversible damage has already occurred. Thus, there is a need for a better biomarker that can detect kidney dysfunction earlier. Renal metabolic rate of oxygen (MRO2) is a suitable metric that directly represents kidney function. In animal models MRO2 has been found to increase during the early stages of diabetic kidney disease. Magnetic resonance imaging (MRI) oximetric techniques can noninvasively quantify MRO2. A widely used method for quantifying MRO2 of the brain measures blood water transverse relaxation time T2 in a draining vein and converting the result via a calibration curve to venous oxygen saturation (SvO2), in addition to a separate scan to acquire blood flow velocity, which are the key physiological parameters needed to quantify MRO2 via Fick’s principle. The proposed research introduces a new T2-based oximetry method that overcomes the limitations of prior T2-based methods by simultaneously measuring SvO2 and blood flow velocity in a single 18-second breath-hold period. The novel interleaving strategy underlying the proposed technique enables quantification of MRO2 in a single pass. The hypothesis of the proposed research is that renal MRO2 will serve as a direct, quantitative marker of early kidney disease before progression to irreversible organ dysfunction. To test this hypothesis, the following specific aims will be pursued: (1) Optimize the T2-based oximetry pulse sequence and quantify cerebral MRO2 to test its performance against well-established MRI oximetry methods. Initial studies will be performed in the brain because of minimal physiologic motion and availability of data for comparison. (2): Transfer the method to the abdomen and quantify renal MRO2 in healthy human subjects and evaluate the method’s precision. (3): Perform a pilot study to assess renal MRO2 as a marker of early-stage diabetic kidney disease through quantification of renal MRO2, eGFR, and microalbuminuria in prediabetic and type-2 diabetic patients in comparison to healthy reference subjects. The method is projected to yield insights into renal metabolism during the early stages of kidney disease and may eventually provide a means for monitoring patients with diabetic kidney disease during treatment.

项目概要 慢性肾脏病 (CKD) 影响着 15% 的美国成年人，其特点是肾脏逐渐丧失 CKD 的主要原因是 2 型糖尿病，高达 40% 的 2 型糖尿病患者患有该病。 目前的肾功能测量方法仅限于评估肾小球滤过率。 (eGFR)，需要几个小时内的多个血液和尿液样本，或在不可逆转的损伤后检测疾病 因此，需要一种更好的生物标志物来更早地检测肾功能障碍。 肾氧代谢率 (MRO2) 是直接代表动物肾功能的合适指标。 模型 磁共振发现 MRO2 在糖尿病肾病的早期阶段会增加。 成像 (MRI) 血氧测定技术可以无创地量化 MRO2 一种广泛使用的量化方法。 大脑的 MRO2 测量引流静脉中的血水横向弛豫时间 T2，并将 除了单独扫描采集血液外，还可通过静脉血氧饱和度 (SvO2) 校准曲线得出结果 流速，这是通过菲克原理量化 MRO2 所需的关键生理参数。 拟议的研究引入了一种新的基于 T2 的血氧测定方法，该方法克服了先前基于 T2 的局限性 通过在 18 秒屏气时间内同时测量 SvO2 和血流速度的方法。 该技术所采用的新型交错策略能够在一次中对 MRO2 进行量化 该研究的假设是肾脏 MRO2 将作为直接的定量标记。 发展为不可逆器官功能障碍之前的早期肾脏疾病 为了检验这一假设，我们进行了以下分析。 将追求的具体目标： (1) 优化基于 T2 的血氧饱和度脉冲序列并量化脑部 MRO2 初步研究将根据成熟的 MRI 血氧测定方法来测试其性能。 大脑由于最小的生理运动和数据的可用性进行比较（2）：将方法转移到。 腹部并量化健康人肾脏受试者的 MRO2 并评估该方法的精度 (3)： 进行一项试点研究，通过以下方式评估肾脏 MRO2 作为早期糖尿病肾病的标志物： 糖尿病前期和 2 型糖尿病患者肾 MRO2、eGFR 和微量白蛋白尿的定量 与健康参考受试者进行比较，预计该方法可以深入了解肾代谢。 肾脏疾病的早期阶段，最终可能提供一种监测糖尿病患者的方法 治疗期间出现肾脏疾病。