糖尿病肾病的多参数MRI研究

发布时间：2018-05-26 14:28

本文选题：糖尿病肾病 + 肾功能　；参考：《第三军医大学》2017年硕士论文

【摘要】：背景与目的:根据国际糖尿病联盟(international diabetes federation,IDF)最新数据,糖尿病(diabetes mellitus,DM)已经发展成为全球性的慢性疾病,2015年全球DM患者达到4.15亿,其中中国患病人数达到1.09亿。由于肾脏是DM的重要靶点器官,40%的患者将发展为糖尿病肾病(diabetic kidney disease,DKD),DKD是糖尿病常见的并发症之一,是目前引起终末期肾病(end-stage renal disease,ESRD)的首要原因。既往的病理生理学研究发现,糖尿病病情演变过程中,肾脏功能受损主要集中于灌注及氧合水平、水分子弥散运动三个方面。糖尿病早期主要是肾脏皮质灌注受累,高血糖作用于肾脏微小血管,激活肾脏代偿机制,使得肾脏的血流供应和肾功能增强,直至代偿消失。同时肾脏氧合水平也呈现出先升高再降低的变化,这与血流灌注基本一直。当病情进展至皮、髓质结构增生甚至纤维化时,集合系统内水分子弥散运动也将受到限制,如不进行及时的治疗,最终进展为ESRD。因肾脏具有强大的代偿能力,糖尿病早期肾脏各项指标仍在正常范围内,导致患者就诊时多已进展至DKD晚期,错过了最佳治疗时间,因此需要我们尽量早期发现、早期诊断。目前临床使用的常规检查多有创或需要使用外源性对比剂,且不能够早期发现异常改变,并且既往对DKD研究多局限于灌注或氧合水平某一方面的改变,缺乏对肾脏功能进行整体、全面的分析。只有充分了解病情演变过程的前提下,才能够对DKD有新的认识,做到早期发现、早期诊断。因此迫切一种需要简单易行的方式,能够从灌注到氧合水平和水分子运动变化的角度,观察糖尿病状态下肾脏的变化过程,并对肾脏功能进行全面的评估。随着影像学技术的进步,出现了很多新的技术方法,如动脉自旋标记(arterial spin labeling,ASL)、血氧水平依赖(blood oxygenation level dependent,BOLD)、弥散张量成像(diffusion tensor imaging,DTI)等功能磁共振(functional magnetic resonance imaging,fMRI)技术,给我们解决上述临床遇到的困境,提供了可靠、无创的技术手段。本研究以这些技术为抓手,根据病情发展演变规律,对比、观察肾脏灌注、氧合水平、水分子弥散运动三个方面的改变,并对肾功能进行影像学评价,寻找他们之间的联系,探讨DKD发展的病理生理机制,为早期发现DKD提供理论支持。材料与方法:1、动脉自旋标记MRI评估糖尿病肾皮质灌注水平的研究纳入50名Ⅱ型糖尿病患者,根据美国肾脏病基金会K/DOQI专家组提出的慢性肾脏病分期建议及糖尿病肾病诊断标准,由我院高年资内分泌医师将50例Ⅱ型糖尿病患者分为三个亚组,分组依据:(1)DKD轻度组(11例):确诊的2型糖尿病患者,伴有大量白蛋白尿[随机晨尿微量白蛋白/肌酐比值(albumin creatinine ratio,ACR)300]和(或)糖尿病视网膜病变伴慢性肾病,估算肾小球率过滤(estimate glomerular filtration rate,eGFR)≥60 ml/min·1.73m~2;(2)DKD中重度组(14例):确诊的2型糖尿病患者,伴有大量白蛋白尿(随机晨尿ACR300)和(或)糖尿病视网膜病变伴慢性肾病,eGFR60 ml/min·1.73m~2;(3)单纯糖尿病(simple diabetes,SD)组(25例):确诊的2型糖尿病患者,尿蛋白检查阴性(随机晨尿ACR30),排除糖尿病视网膜病变及其他慢性肾病。另外招募25性别、年龄相匹配的健康自愿者作为对照。采用德国8通道体部相控阵线圈的Siemens Magnetom Trio 3.0 T超导MRI仪进行MRI扫描,行双肾常规MRI及ASL MRI扫描,使用Matlab R2013a与Image J软件对ASL图像进行后处理得到肾皮质血流值(cortex of renal blood flow,cRBF)。统计分析采用SPSS18.0软件,采用组内相关性(Interclass Correlation Coefficient,ICC)对2名医师测量的cRBF值进行一致性分析,采用单因素方差分析比较各组间cRBF值差异,并采用LSD法进行两两比较,最后利用Pearson相关分析cRBF值与eGFR的相关性。以P0.01有统计学意义。2、BOLD、DTI MRI评估糖尿病肾脏氧合、水分子弥散水平的研究纳入25名单纯糖尿病患者(SD)、20名糖尿病肾病患者(DKD)和26名健康志愿者(NC),三组间性别、年龄、BMI相匹配。于磁共振检查当日早晨收集随机晨尿、静脉血进行生化检验,而后根据MDRD方程计算eGFR值。采用3.0T MR扫描仪行常规T1、T2排除器质性疾病,并采用m GRE序列的BOLD和平面回波(echo-planar imaging,EPI)序列的DTI扫描,获取的图像在Siemens工作站进行后处理,通过划取ROI的方式得到单个肾脏皮、髓质R2*值、FA、ADC值。采用SPSS18.0软件对三组受试者年龄、BMI行单因素方差分析,分析性别差异采用c2检验;分析左、右肾R2*、MCR、FA、ADC值差异采用配对样本t检验,显示无差异就取左、右肾平均值进行后续统计分析;采用单因素方差分析比较各组间R2*、MCR、FA、ADC值差异;采用Pearson相关性分析R2*、MCR、FA、ADC值与eGFR的关系。结果:1、DKD的皮质灌注水平:配对t检验显示四组组内左、右肾cRBF值均无统计学差异,以其平均值作为个体肾脏cRBF值;对两名医师测量的cRBF值进行一致性分析,各组ICC均0.90,说明一致性高。单因素方差分析显示SD组、DKD轻度组、DKD中重度组、对照组间皮质cRBF值存在统计学差异(F=20.66,P0.01),两两比较结果显示DKD中重度组cRBF值明显降低。Pearson相关性分析显示糖尿病患者肾皮质cRBF值与e GFR呈显著正相关(r=0.646,P0.01)。2、DKD的氧合、水分子弥散水平:单因素方差分析显示三组间MCR、髓质FA值存在差异,DKD组MCR值较SD组明显下降(P=0.001),SD组MCR值较NC组明显增高(P=0.018),SD组髓质FA值显著高于NC组(P=0.005),DKD组髓质FA值显著低于SD组(P0.01)和NC组(P=0.011);糖尿病患者MCR值与eGFR正相关性(r=0.545,P0.01),糖尿病患者髓质FA值与eGFR值也呈正相关性(r=0.406,P=0.006)。结论:灌注方面发现DKD中重度组cRBF值显著低于其他组,并且cRBF值可反映肾小球滤过率水平,说明DKD会加重肾功能损伤,ASL能够准确、简便、安全的评估糖尿病患者肾皮质灌注功能。BOLD和DTI MRI中MCR值和FA值较敏感,早于其他参数发现肾脏变化,可以用来评估肾脏功能状态和早期发现肾脏代谢和水分子弥散运动的改变。
[Abstract]:Background and purpose: according to the latest data from the International Diabetes Federation (IDF), the diabetes mellitus (DM) has developed into a global chronic disease. In 2015, the global DM patients reached 415 million, of which the number of Chinese patients reached 109 million. As the kidney is an important target organ for DM, 40% of the patients will send it. Diabetic kidney disease (DKD), DKD is one of the common complications of diabetes and is the primary cause of end-stage renal disease (ESRD). Previous pathophysiological studies have found that renal dysfunction is mainly concentrated on perfusion and oxygenation levels, water molecules in the evolution of diabetes. Three aspects of diffusion movement. Early diabetes is mainly renal cortical perfusion involvement, hyperglycemia acts on the renal tiny blood vessels, activates the renal compensatory mechanism, makes the renal blood supply and renal function enhanced until compensatory disappearance. Meanwhile, the renal oxygenation level also presents a first increase and then decrease, which is basically the same as blood perfusion. When the disease progresses to the skin, the medullary structure and even the fibrosis, the movement of water molecules in the collection system will be restricted, such as no timely treatment, and the final progress is that ESRD. has a strong compensatory capacity for the kidney. We have missed the best time for treatment, so we need to try our best to find early, early diagnosis. At present, the routine routine examination of clinical use is more invasive or needs to use exogenous contrast agent, and it is not able to find abnormal changes in the early stage, and the previous study of DKD is limited to the changes in perfusion or oxygenation, and the lack of renal function. Overall, comprehensive analysis. Only if we fully understand the evolution process of the disease, can we have a new understanding of DKD, early detection and early diagnosis. Therefore, it is urgent to observe the change process of kidney from the angle of perfusion to oxygenation level and water molecular movement, and to observe the change process of kidney in diabetic state. A comprehensive assessment of renal function. With the progress of imaging technology, many new techniques have emerged, such as arterial spin labeling (ASL), blood oxygen level dependence (blood oxygenation level dependent, BOLD), diffusion tensor imaging (diffusion tensor imaging,) and other functional magnetic resonance Nance imaging, fMRI) technology provides us with a reliable, noninvasive technique to solve the predicament encountered above. This study takes these techniques as a grip, according to the law of development and evolution of the disease, contrasts, changes three aspects of renal perfusion, oxygenation level, water molecular diffusion movement, and looks for the imaging evaluation of renal function. The relationship between them is to explore the pathophysiological mechanism of DKD development to provide theoretical support for early detection of DKD. Materials and methods: 1, the study of arterial spin labeling MRI for assessing the level of diabetic renal cortical perfusion was included in 50 patients with type 2 diabetes, according to the staging of chronic kidney disease proposed by the K/ DOQI expert group of the American kidney disease foundation and The diagnostic criteria for diabetic nephropathy were divided into three subgroups of 50 patients with type II diabetes by the senior endocrinologist in our hospital. The group was grouped by: (1) DKD mild group (11 cases): diagnosed type 2 diabetic patients with a large number of albuminuria [random morning urine microalbuminuria / creatinine ratio (albumin creatinine ratio, ACR) 300] and / or diabetic retina The disease was associated with chronic kidney disease (estimate glomerular filtration rate, eGFR) more than 60 ml/min. 1.73m~2; (2) severe DKD group (14 cases): diagnosed type 2 diabetic patients with a large number of albuminuria (random morning urine ACR300) and (or) diabetic retinopathy with chronic kidney disease, eGFR60 ml/min. (3) simple diabetes (3) Simple diabetes, SD) group (25 cases): diagnosed type 2 diabetic patients with negative urinary protein examination (random morning urine ACR30), excluding diabetic retinopathy and other chronic kidney disease. Also recruited 25 sex, age matched healthy volunteers as control. Using the Siemens Magnetom Trio 3 T of the German 8 passages phased array coil, superconducting MRI The MRI scan was performed with a double kidney routine MRI and ASL MRI scan. The renal cortical blood flow values were obtained by the Matlab R2013a and Image J software after the post-processing of the ASL images. The cRBF value difference between each group was compared by single factor analysis of variance, and the LSD method was used to compare the cRBF values. Finally, the correlation between cRBF and eGFR was used to analyze the cRBF value of Pearson, BOLD, DTI MRI evaluation of diabetic renal oxygenation, and the study of the water molecular diffusion level was included in the 25 list of pure diabetic patients. People (SD), 20 diabetic nephropathy patients (DKD) and 26 healthy volunteers (NC), three groups of sex, age, and BMI were matched. In the morning of the magnetic resonance examination, random morning urine was collected, venous blood was tested by biochemical test, and then the eGFR value was calculated according to the MDRD equation. The 3.0T MR scanner was used for routine T1, T2 ruled out organic diseases, and m GRE sequence was used. DTI scanning of LD and echo-planar imaging (EPI) sequences, the acquired images were processed after Siemens workstation, single kidney skin, R2* value of medulla, FA, ADC values were obtained by using ROI method. SPSS18.0 software was used for three groups of subjects' age, BMI row mono ANOVA analysis, analysis of gender differences, and analysis left, right The R2*, MCR, FA, and ADC values of the kidney were compared with the paired sample t test. The mean values of left and right kidney were statistically analyzed without difference, and the difference of R2*, MCR, FA, ADC values were compared by single factor analysis of variance, and the relationship between R2*, MCR, and the value of R2* was analyzed by Pearson correlation. Results: 1 There was no statistical difference between the left and right renal cRBF values in the four groups. The average value of the kidney was used as the cRBF value of the individual kidney. The cRBF values measured by two doctors were analyzed, and the ICC was 0.90 in each group. The single factor variance analysis showed that the SD group, the DKD mild group, the DKD medium severe group and the control group were statistically different (F=20.66, P). 0.01), the results of 22 comparison showed that the cRBF value of DKD in the moderate and severe group decreased significantly by the.Pearson correlation analysis. The renal cortical cRBF value was significantly positively correlated with e GFR (r=0.646, P0.01).2, DKD oxygenation and water molecular diffusion level: the single factor variance analysis showed that the three groups were MCR, and the medulla FA values were significantly different. (P=0.001), the value of MCR in group SD was significantly higher than that in group NC (P=0.018), and the FA value of medulla in group SD was significantly higher than that in NC group (P=0.005), and the FA value of medulla in the DKD group was significantly lower than that of the SD group. The cRBF value of DKD medium and severe group was significantly lower than that of other groups, and the cRBF value could reflect the glomerular filtration rate, indicating that DKD would aggravate renal function damage. ASL can be accurate, simple and safe to evaluate the MCR value and FA value of renal cortical perfusion function in diabetic patients,.BOLD and DTI MRI more sensitive than other parameters, which can be used to detect renal changes. Evaluation of renal function and early detection of renal metabolism and diffusion of water molecules.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R587.2;R692.9

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