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.

项目摘要 慢性肾脏病（CKD），影响15%的美国成年人，其特征是肾功能进行性丧失 功能CKD的主要病因是2型糖尿病，高达40%的2型糖尿病患者继续 发展CKD。目前肾功能的测量方法局限于估计肾小球滤过率 （eGFR），需要在几个小时内多次血液和尿液样本，或在不可逆损伤后检测疾病 已经发生了。因此，需要一种更好的生物标志物，可以更早地检测肾功能障碍。 肾氧代谢率（MRO 2）是直接代表肾功能的合适度量。在动物 已经发现，在糖尿病肾病的早期阶段，MRO 2增加。磁共振 成像（MRI）血氧测定技术可以无创地量化MRO 2。一种广泛使用的量化方法 脑的MRO 2测量引流静脉中的血液水横向弛豫时间T2，并将 通过静脉血氧饱和度（SvO2）的校准曲线获得结果，此外还进行单独扫描以采集血液 流速，这是通过Fick原理量化MRO 2所需的关键生理参数。的 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的血氧测定方法的局限性。 方法通过在单个18秒屏气期内同时测量SvO2和血流速度。 基于所提出的技术的新颖交织策略使得能够在单个帧中量化MRO 2。 过去的这项研究的假设是，肾脏MRO 2将作为一种直接的定量标志物， 进展为不可逆器官功能障碍之前的早期肾病。为了验证这一假设， 具体目标如下：（1）优化基于T2的血氧测定脉冲序列并量化脑MRO 2 以测试其相对于成熟的MRI血氧测定方法的性能。初步研究将在 大脑，因为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 对健康人腹部和肾脏的MRO2进行定量，并对该方法的精密度进行评价。(3): 进行一项试点研究，通过以下方式评估肾脏MRO 2作为早期糖尿病肾病的标志物 糖尿病前期和2型糖尿病患者的肾脏MRO 2、eGFR和微量白蛋白尿定量 与健康参考对象进行比较。该方法预计将产生对肾脏代谢的见解， 肾脏疾病的早期阶段，并可能最终提供一种监测糖尿病患者的手段， 治疗期间的肾病。