Noninvasive Quantification of Renal Oxygen Utilization in Early Kidney Disease

早期肾脏疾病中肾氧利用的无创定量

• 批准号: 10313057
• 负责人: Rajiv Deshpande
• 金额: $ 5.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313057
• 关键词: Noninvasive; Quantification; Renal; Oxygen; Utilization

Project Summary/Abstract (30 lines): Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function and is a major risk factor for adverse cardiovascular outcomes. It is estimated that CKD affects 15% of US adults. Current measures of kidney function rely on equations to calculate an estimated glomerular filtration rate (eGFR), require multiple blood and urine samples, or detect dysfunction after irreversible damage may already have occurred. These limitations highlight an unmet need for a better biomarker that can detect kidney dysfunction earlier. Renal metabolic rate of oxygen (MRO2) is a suitable metric because it directly represents renal function and workload. Moreover, renal MRO2 has been found to increase during the early stages of diabetic kidney disease. MRO2 can be quantified with magnetic resonance imaging oximetry, including susceptometry-based oximetry (SBO) or T2- based oximetry (T2O). However, SBO is not appropriate for kidney imaging because of restrictions on vessel orientation and lack of adjacent tissue for reference phase measurement. T2O is the preferred option, but current T2-based methods only measure venous oxygen saturation (SvO2) and require a separate measurement of blood flow velocity to quantify MRO2. The proposed research introduces a noninvasive T2-based oximetry method to quantify whole-organ renal MRO2 by simultaneously measuring SvO2 and blood flow velocity in an interleaved manner, thereby overcoming the limitations of other T2-based methods. The central hypothesis of the proposed research is that renal MRO2 has the potential to serve as a direct, quantitative marker of kidney function and enable earlier detection of diabetic CKD. To fulfill this objective and test the central hypothesis, the following specific aims will be pursued: (1A) Develop the MRI oximetry pulse sequence and test in phantoms to assess accuracy of measured parameters. (1B) Implement the pulse sequence to quantify SvO2 in the superior sagittal sinus of the brain and whole-brain cerebral MRO2. Initial studies will quantify whole-brain MRO2 because of minimal physiologic and voluntary motion, and availability of established data to compare with. (2A) Design and implement the pulse sequence for kidney imaging to quantify renal MRO2, and test the performance of the method with an oral diuretic. (2B) Quantify renal MRO2 and calculate eGFR in prediabetic and diabetic patients to evaluate the hypothesis that renal MRO2 can serve as an early marker of kidney dysfunction. The proposed research to quantify renal MRO2 introduces a method to noninvasively quantify renal MRO2 with potential applications as an accurate marker of early-stage kidney disease and for monitoring response to intervention.

项目摘要/摘要（30行）： 慢性肾脏疾病（CKD）的特征是肾功能的逐渐丧失，是主要危险因素 用于不良心血管结局。据估计，CKD影响了15％的美国成年人。当前的措施 肾功能依赖于方程来计算估计的肾小球滤过率（EGFR），需要多个 血液和尿液样本或可能已经发生不可逆损害后发现功能障碍。这些 局限性突出了对更好的生物标志物的未满足需求，该标志物可以早些时候检测到肾脏功能障碍。肾脏 氧的代谢速率（MRO2）是合适的度量标准，因为它直接代表肾功能和工作量。 此外，已经发现肾脏MRO2在糖尿病肾病的早期阶段增加。 mro2可以 用磁共振成像的血氧仪量化，包括基于苏伯测法的血氧仪（SBO）或T2- 基基（T2O）。但是，由于对血管的限制，SBO不适合肾脏成像 方向和缺乏相邻组织进行参考期测量。 T2O是首选选项，但最新 基于T2的方法仅测量静脉氧饱和度（SVO2），需要单独测量 量化MRO2的血流速度。拟议的研究引入了基于T2的非侵入性血氧仪 通过同时测量SVO2和血流速度来量化全器肾Mro2的方法 交错方式，从而克服了其他基于T2的方法的局限性。中心假设 拟议的研究是，肾脏MRO2有可能用作肾脏的直接定量标记 功能并启用早期检测糖尿病CKD。为了实现这一目标并检验中心假设， 将追求以下特定目的：（1A）在幻象中发展MRI氧合脉冲序列并在幻象中进行测试 评估测量参数的准确性。 （1b）实现脉冲序列以量化上级中的SVO2 大脑的矢状窦和全脑大脑MRO2。初步研究将量化全脑MRO2，因为 最小的生理和自愿运动，以及与之相比的已建立数据的可用性。 （2A）设计 并实现肾脏成像的脉冲序列来量化肾脏MRO2，并测试 口服利尿剂的方法。 （2B）量化肾脏MRO2并计算糖尿病前患者的EGFR 为了评估肾脏MRO2可以作为肾功能障碍的早期标志的假设。提议 量化肾脏MRO2的研究引入了一种非侵入性量化肾Mro2的方法 应用是早期肾脏疾病的准确标记，并用于监测对干预的反应。