MRI-Based Renal Oximetry in Early Diabetic Kidney Disease

项目总结 慢性肾脏病(CKD)影响着15%的美国成年人，其特征是肾脏进行性丧失 功能。慢性肾脏病的主要原因是2型糖尿病，高达40%的2型糖尿病患者继续 发展慢性肾脏病。目前的肾功能测量方法在估计肾小球滤过率方面是有限的。 (EGFR)，需要在几个小时内进行多次血液和尿液样本，或在不可逆转的损害后检测疾病 已经发生了。因此，需要一种更好的生物标志物来更早地发现肾功能障碍。 肾组织氧代谢率(MRO2)是直接反映肾功能的合适指标。在动物身上 模型的MRO2已被发现在糖尿病肾病的早期阶段升高。磁共振 成像(MRI)血氧测定仪技术可以非侵入性地量化MRO2。一种广泛使用的量化方法 大脑的MRO2测量引流静脉中的血水横向松弛时间T2，并将 结果通过对静脉血氧饱和度(SvO2)的校准曲线，以及单独扫描获取血液 流速，这是根据Fick原理量化MRO2所需的关键生理参数。这个 提出的研究提出了一种新的基于T2的血氧测定方法，克服了以前基于T2的血氧测定方法的局限性 方法在单次屏气18秒内同时测量SvO2和血流速度。 基于所提出的技术的新的交织策略使得能够在单个 经过。这项拟议研究的假设是，肾脏MRO2将作为一种直接的、定量的标志物 在发展为不可逆转的器官功能障碍之前的早期肾脏疾病。要检验这一假设，请看以下内容 具体目标是：(1)优化基于T2的血氧仪脉冲序列，并对脑MRO2进行量化 用成熟的磁共振血氧测定仪测试其性能。初步研究将在 大脑因为最小的生理运动和可供比较的数据。(2)：将方法转移到 测定健康受试者腹部和肾脏的MRO2，评价方法的精密度。(3)： 进行一项先导性研究，通过以下方法评估肾脏MRO2作为早期糖尿病肾病的标志物 糖尿病前期和2型糖尿病患者肾脏MRO2、EGFR和微量白蛋白尿的定量研究 并与健康参照者进行比较。该方法预计将产生对肾脏新陈代谢的洞察 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 治疗过程中出现肾脏疾病。

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.