Noninvasive Quantification of Renal Oxygen Utilization in Early Kidney Disease

项目摘要/摘要（30行）： 慢性肾脏病（CKD）的特点是肾功能的进行性丧失，是一个主要的危险因素 不良心血管结局的风险。据估计，CKD影响15%的美国成年人。目前的措施 肾功能依赖于计算估计肾小球滤过率（eGFR）公式，需要多个 血液和尿液样本，或检测功能障碍后，不可逆的损害可能已经发生。这些 这些限制突出了对更好的生物标记物的未满足的需求，该生物标记物可以更早地检测肾功能障碍。肾 氧代谢率（MRO 2）是合适的度量，因为它直接代表肾功能和工作负荷。 此外，已发现肾脏MRO 2在糖尿病肾病的早期阶段增加。MRO 2可以 使用磁共振成像血氧定量法（包括基于血氧定量法（SBO）或T2- 血氧饱和度（T2O）。然而，由于血管的限制，SBO不适用于肾脏成像 用于参考相位测量的相邻组织的定向和缺乏。T2O是首选，但目前 基于T2的方法仅测量静脉血氧饱和度（SvO2），需要单独测量 血流速度以量化MRO 2。拟议的研究介绍了一种基于T2的无创血氧测定法， 一种通过同时测量SvO2和血流速度来量化全器官肾脏MRO 2的方法， 这种方法以交错方式进行，从而克服了其他基于T2的方法的局限性。的中心假设 拟议的研究是肾脏MRO2有可能作为肾脏的直接定量标记物， 功能，使糖尿病CKD的早期检测。为了实现这一目标并检验中心假设， 将追求以下具体目标：（1A）开发MRI血氧测定脉冲序列并在体模中进行测试， 评估测量参数的准确性。(1B)实施脉冲序列以量化上级中的SvO2 脑矢状窦和全脑脑MRO 2。初步研究将量化全脑MRO2， 最小的生理和随意运动，以及可与之进行比较的已建立数据的可用性。(2A)设计 并实现用于肾脏成像的脉冲序列以量化肾脏MRO 2，并测试 口服利尿剂的方法。(2B)在糖尿病前期和糖尿病患者中定量肾脏MRO 2并计算eGFR 评估肾脏MRO 2可作为肾功能不全的早期标志物的假设。拟议 定量肾脏MRO2的研究介绍了一种无创定量肾脏MRO2的方法， 作为早期肾脏疾病的准确标记物和用于监测对干预的反应。

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.