Noninvasive Quantification of Renal Oxygen Utilization in Early Kidney Disease

项目摘要/摘要(30行)： 慢性肾脏疾病(CKD)的特征是肾功能的进行性丧失，是一个主要的危险因素。 对于心血管疾病的不良后果。据估计，慢性肾脏病影响了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)，需要多次 血液和尿液样本，或检测到功能障碍后，不可逆转的损害可能已经发生。这些 局限性突显了对能够更早发现肾功能障碍的更好生物标志物的需求尚未得到满足。肾 氧代谢率(MRO2)是一个合适的指标，因为它直接代表了肾功能和工作负荷。 此外，已发现肾脏MRO2在糖尿病肾病的早期阶段升高。MRO2可以 使用磁共振成像血氧仪进行量化，包括基于磁感度的血氧仪(SBO)或T2- 基础血氧仪(T2O)。然而，由于血管的限制，SBO不适合用于肾脏成像 定位和缺少用于参考相位测量的邻近组织。T2O是首选选项，但目前 基于T2的方法只测量静脉血氧饱和度(SvO2)，并且需要单独测量 血流速度以量化MRO2。拟议的研究引入了一种基于T2的非侵入性血氧测定仪。 一种同时测量SvO2和血流速度定量全肾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。的中心假说 建议的研究是肾脏MRO2有可能作为肾脏的直接定量标志物。 功能，使早期发现糖尿病CKD成为可能。为了实现这一目标并检验中心假设， 将追求以下具体目标：(1)开发磁共振血氧仪脉冲序列并在模体中进行测试 评估测量参数的准确性。(1B)上级实现SvO2量化的脉冲序列 脑矢状窦和全脑MRO2。初步研究将量化全脑MRO2，因为 最小的生理和自主运动，以及可供比较的已建立的数据。(2A)设计 并实现了用于肾脏成像的脉冲序列以量化肾脏MRO2，并测试了 方法口服利尿剂。(2B)量化糖尿病前期和糖尿病患者的肾脏MRO2并计算EGFR 评价肾脏MRO2可作为肾功能障碍早期标志物的假说。建议数 肾脏MRO2定量研究介绍了一种具有潜力的无创定量肾脏MRO2的方法 应用作为早期肾脏疾病的准确标记物和监测干预反应。

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.