糖尿病肾脏微循环障碍及纤维化的早期功能磁共振评价

Diabetes is a chronic disease that poses a serious threat to human health worldwide with its incidence increasing annually in the global population. Long-term diabetes can cause a series of vascular complications, resulting in significantly increased morbidity and mortality. Among microvascular complications, renal damage is the most common cause of end-stage renal disease. Early accurate assessment can help interfere with the development of diabetic nephropathy, however, effective and comprehensive evaluation approaches are lacking. Impaired vascular regulatory capacity and renal hypoxia are presented in the early stage of diabetic renal injury with renal fibrosis running through the entire course of diabetes, eventually leading to renal failure. Renal functional MRI provides a range of renal pathophysiological information, including perfusion, tissue oxygenation, diffusion, tractography, fibrosis. Additionally, functional MRI combining with oxygen/carbon inhalation can further evaluate the capacity of renal vascular regulation. In this study, our aim is to investigate the key pathological features of the early microcirculation disturbance and interstitial fibrosis in early diabetic renal injury. With the assistance of multi-modal and multi-parametric functional MRI, we will screen out highly specific imaging markers to build non-invasive and robust imaging models, which will achieve early and accurate evaluation of diabetic renal injury after further validation in clinical study and animal treatment.

糖尿病是一种严重威胁人类健康的慢性疾病，在全世界的发病率呈逐年上升趋势。长期糖尿病可引起一系列血管并发症，导致疾病致死致残率显著增高。在微血管并发症中，肾脏受损是终末期肾病最常见的病因，早期精确评估有助于及时干预肾病发生发展，但目前缺乏有效的综合评价指标。糖尿病肾脏损伤早期即表现为血管调节功能受损及肾实质缺血缺氧，肾脏纤维化也贯穿糖尿病整个病程，最终导致肾功能衰竭。肾脏功能磁共振能够提供一系列肾脏病理生理学信息，包括灌注、血氧、水分子弥散、小管结构、纤维化，结合氧气/碳合气吸入更可进一步评估肾脏血管调节储备能力。本研究针对糖尿病肾脏早期微循环障碍及纤维化关键病理特征，通过多模态、多参数功能磁共振筛选出高特异性影像标志物，构建无创可重复的综合性影像评价模型，并通过临床研究及动物干预治疗进一步验证模型稳健性，最终实现对糖尿病肾损伤的早期精准影像评价。

糖尿病是一种严重威胁人类健康的内分泌疾病，糖尿病肾病最显著的微血管并发症之一，本研究旨在通过功能磁共振成像评价糖尿病患者肾脏微循环调节障碍及其它病因所致的肾脏早期纤维化。.本研究在东南大学附属中大医院内分泌科及社会中招募88名2型糖尿病患者以及46名健康志愿者，并研究了48只一侧输尿管结扎肾纤维化大鼠。fMRI序列包括双侧肾动脉相位对比法PC-MRA、弥散张量成像DTI、水脂分离技术Dixon成像、以及双侧肾脏斜冠状位T2*加权成像序列。大鼠研究扫描了肾脏灌注加权成像ASL及血氧水平依赖BOLD-MRI。测量肾脏FA值、ADC值、DTI重建得到肾小管长度及数量、肾脏脂肪含量。采集碳合气激发前后肾动脉管径平均横截面积、单位时间平均流量，以及吸气前后肾脏、肝脏T2*信号变化。计算大鼠在VCP治疗前后肾脏RBF及T2*值。使用方差分析、独立样本t检验进行统计学分析。.结果发现伴有微量蛋白尿的糖尿病患者肾脏脂肪分数显著高于对照组，微量蛋白尿组患者肾髓质FA值（0.31±0.06）在所有组内最低；DTI重建得到肾小管长度及数量也显示微量蛋白尿组患者最低。吸入碳合气后，糖尿病肾病患者、糖尿病无肾病患者和健康志愿者三组的肝脏T2*信号较吸入前均显著下降。糖尿病组肾脏T2*信号均呈现下降的表现，分别为糖尿病无肾病患者肾脏T2*信号下降4.7±7.3％（p=0.047）、糖尿病肾病组T2*信号下降13.3±5.8％（p＜0.001）。糖尿病肾病组肾动脉平均面积及平均流量较吸入气体前未见明显变化（p＞0.05）。而糖尿病无肾病组平均面积增加21.1±9.9％、平均流量增加11.5±9.6％。大鼠肾脏早期纤维化时，ASL显著降低伴肾脏缺氧。VCP治疗后，肾脏功能磁共振指标出现显著恢复，ASL显示肾脏灌注提高，BOLD显示缺氧缓解。.综上所述，功能磁共振技术及碳合气激发试验可潜在用于糖尿病肾脏微循环自身调节功能障碍及肾损伤后早期纤维化的检测。