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 影响美国成年人15％的慢性肾脏病（CKD）的特征是肾脏逐渐丧失 功能。 CKD的主要原因是2型糖尿病，多达40％的2型糖尿病患者继续 开发CKD。当前的肾功能量度受到限制，因为它们估计肾小球滤过率 （egfr），需要多个血液和尿液样本，或者在不可逆的损害后检测疾病 已经发生了。这是需要更好的生物标志物，可以早些时候检测到肾脏功能障碍。 氧气的肾脏代谢速率（MRO2）是直接代表肾功能的合适度量。在动物中 在糖尿病肾病的早期阶段，MRO2模型已增加。磁共振 成像（MRI）氧化技术可以非侵入性地量化MRO2。广泛使用的方法来量化 大脑的MRO2测量了排水静脉中的血液横向松弛时间T2并转化 除了单独的扫描以获取血液外，还通过校准曲线到静脉氧饱和度（SVO2）的结果 流速度，这是通过Fick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的血氧仪方法，该方法克服了先前基于T2的局限性 通过简单地测量单个18秒呼吸含量的SVO2和血流速度来进行方法。 所提出的技术的基础的新型交织策略可以在一个单一中量化MRO2 经过。拟议研究的假设是肾脏MRO2将作为直接的定量标记 早期肾脏疾病在发展为不可逆的器官功能障碍之前。为了检验这一假设，以下 将追求具体目的：（1）优化基于T2的血氧蛋白脉冲序列并量化脑MRO2 测试其针对良好的MRI血氧仪方法的性能。初步研究将在 大脑由于生理运动的最小和数据可用性以进行比较。 （2）：将方法转移到 在健康人类受试者中，腹部和量化肾脏MRO2并评估该方法的精度。 （3）： 进行试点研究，以评估肾脏MRO2作为早期糖尿病肾脏疾病的标志 在糖尿病前和2型糖尿病患者中肾脏MRO2，EGFR和微珠尿症的定量 与健康的参考受试者进行比较。该方法预计将在期间对肾脏代谢产生见解 肾脏疾病的早期阶段，有时可能提供一种用于监测糖尿病患者的手段 治疗过程中的肾脏疾病。