3.0T MRI BOLD及ASL-fMRI成像对使用碘对比剂增强后肾脏损害的评价研究
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摘要
研究背景及意义:
含碘对比剂主要经肾脏排泄,近年来,有关碘对比剂引起的肾功能损害引起了学者的广泛关注及研究。碘对比剂注入体内后可使肾功能暂时性、甚至持续丧失,由碘对比剂引起的肾功能损害被称为对比剂肾病。目前使用碘对比剂造成肾脏损害已是医源性急性肾功能衰竭的第三大原因,仅次于手术和低血压;约占所有医源性急性肾功能衰竭的10%,明显增加患者精神及经济负担,亦明显增加社会经济负担。因此,碘对比剂所致肾脏损害的早期发现、早期预防、早期治疗在临床上具有重要的意义。当前,临床上最常用检测肾功能的方法为测量患者血肌酐浓度及变化情况。但有研究表明血肌酐浓度及变化情况对早期肾功能的损害不敏感。因此,寻找新的、敏感的可早期发现、早期诊断及早期预防碘对比剂所致肾脏损害的方法在临床上具有重要意义。
许多研究表明,肾髓质血流的改变在碘对比剂肾病上起重要作用。肾髓质血流发生改变,可以引起髓质氧含量的改变。目前为止,在动物肾脏局部血流及氧含量的研究,均采用有创手段。传统上,测量肾脏髓质血流的方法是应用侵入性激光多普勒探针。但是,在人体肾脏髓质血流的研究中,有创的监测手段很难实施。理想的方法是在生理状态下,采用无创手段监测肾脏髓质血流及氧含量在研究碘对比肾病至关重要,也是人们致力研究的热点。
随着磁共振设备不断进步,功能磁共振成像为许多疾病的早期发现、早期诊断提供了强有力的手段及方法。一些研究表明,血氧水平依赖性磁共振功能成像(Blood Oxygen Level Dependent Function Magnetic Resonance Imaging,BOLD-fMRI)技术能有效的监控肾脏髓质氧代谢的变化。动脉自旋标记磁共振成像技术(Arterial Spin Labeling Function Magnetic Resonance Imaging,ASL-fMRI)不需外源性对比剂,仅利用组织器官自身血流灌注,定量检测组织器官灌注情况。二者是目前常有的功能磁共振成像方法。
目前利用BOLD及ASL-fMRI成像技术对高血压肾病、糖尿病、肾动脉硬化及肾脏肿瘤等疾病的研究已经取得显著效果。研究表明,BOLD及ASL-fMRI技术所测得数据在不同观察者及同一观察者具有良好的重复性。因此,多数学者认为BOLD及ASL-fMRI技术在肾脏疾病的诊断和评价方面具有非常大的潜在价值。不过至今,应用BOLD及ASL-fMRI技术评价使用碘对比剂后肾脏功能损害的研究鲜见文献报道。
本实验利用磁共振功能成像(Function Magnetic Resonance Imaging,fMRI)BOLD及ASL成像技术监测注入碘对比剂后肾脏血流灌注及氧代谢的变化,在生理状况下研究注入碘对比剂后肾脏功能的改变,以评价所致肾功能损害情况,同时探讨无创的、简便的、可行的评估注入碘对比剂后肾功能损害的方法。
研究目的:
1、探讨3.0TMRI BOLD及ASL成像在大鼠正常肾脏的实验研究
2、探讨3.0TMRI-BOLD成像技术在大鼠碘对比剂增强后肾脏损害的实验研究
3、探讨3.0TMRI-ASL成像技术在大鼠碘对比剂增强后肾脏损害的实验研究
4、探讨3.0TMRI-BOLD及ASL成像技术联合应用在评估大鼠碘对比剂增强后肾脏损害的价值。
材料与方法:
1、实验动物及准备
购置29只SD大鼠。雌雄不限,体重在109.60g±14.26g。每只大鼠MRI扫描前禁食禁水4小时,腹腔麻醉后30分钟进行MRI扫描。
2、MRI扫描
2.1 MRI扫描序列及方法
①三平面定位像:横断、矢状及冠状位。
②常规MRI序列:T2WI横断位、T2WI冠状位、T1WI横断位,采用快速旋转回波(fast spin echo,FSE)序列
③BOLD成像序列:冠状位,采用多次快速梯度回波(multilple-fast gradientrecalled echo,MFGRE序列
④ASL,成像序列:冠状位,流动敏感交变反转恢复技术(Flow SensitiveAltemating Inversion Recovery,FAIR),单激发快速自旋回波序列(Single-ShotFast Spin Echo,SSFSE)FAIR-SSFSE,序列
2.2大鼠MRI扫描方法:
设备:采用3.0TMRI扫描仪,50mmbirdcage实验专用动物线圈。采用头先进、仰卧位。
方法:分别于注入碘对比剂前、注入碘对比剂后20分钟,24小时,48小时,72小时,分别进行MRI扫描。注入碘对比剂前作为对照组,扫描序列:T1WI、T2WI、BOLD、FSE-FAIR扫描,扫描时间:约14分12秒;注入碘对比剂后分20分钟,24小时,48小时,72小时实验组,每个时间点扫描T2WI冠状位、BOLD、FSE-FAIR序列;共扫描4次,每次扫描时间:约6分14秒。
3、MRI图像分析
3.1图像质量分析
2位有经验的MR诊断医师分别分析各序列的图像质量,主要包括图像信噪比、对比度、分辨率、伪影以及解剖结构显示情况。
3.2 BOLD图像T2~*值及R2~*值的测量
每侧肾脏扫四层,每层获得8张不同TE时间(2.2ms～14.7ms)的T2~*图像,将所得图像,经工作站functool软件处理,获得T2~*Map图像,在T2~*Map图像测量T2~*值。R2~*值根据公式:R2~*=1/T2~*获得。用均数±标准差((?)±s)表示。
3.3 ASL图像ASL-RBF值的测量
每侧肾脏扫四层,每层获得20张不同图像,将所得图像,经工作站functool-fair软件处理,获得肾脏灌注图像。在肾脏灌注图像测量皮质、外髓及内髓局部血流量值,用均数±标准差((?)±s)表示。
3.4 ROI测量
对同一实验对象每侧肾脏选取兴趣区(ROI),每个ROI大小、形状完全一致。ROI大小为1.5mm~2～2.5 mm~2,ROI至少包含5像素。皮质区测量6～10个ROI,外髓、内髓区测6～10个ROI,用均数±标准差((?)±s)表示。测量选择的层面无变形及伪影,避开肉眼所见大血管及伪影。
4、大鼠肾脏病理观察
每个时间点取三只大鼠,扫描完后,立即取双肾,去包膜,沿肾蒂冠状位切开,与MRI扫描冠状位一致。生理盐水冲洗后立即放入10%福尔马林溶液中固定。肾脏标本按病理检验程序进行常规梯度酒精脱水、二甲苯透明、浸蜡、石蜡包埋,切3um厚的切片,作HE病理常规染色,封片等,分别于80、400倍光学显微镜下观察。
5、统计学分析
应用SPSS16.0统计软件包,数据录入及分析;采用均数±标准差((?)±s),组间比较采用t检验、方差分析,自身前后组比较采用配对t检验,非正态分布或方差不齐采用秩和检验,Person相关分析,不同时点测量值的变化采用折线图表示。
结果
1、实验大鼠结果
29只SD大鼠,分别编为1-29号,雌雄不限。1-3号大鼠进行预实验和参数优化,未行数据记录及分析。纳入实验分析的大鼠共26只,其中雄性12只,雌性14只。在实验过程中,因麻醉意外死亡大鼠退出实验,不列入下个实验时间点。或所得图像信噪比较低,图像质量差影响各值测量者,排除当次实验组。最终,本实验各组实验测量例数及左右肾脏分析例数均不同。右侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小及72小时R2~*值测量分析例数分别为23、22、21、11、6例;右侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时ASL-RBF值测量分析例数分别23,22,20、12、7例。左侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时R2~*值测量分析例数分别22、22、20、11、6例;左侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时ASL-RBF值测量分析例数分别22、22、21、12、7例。
2、图像质量分析
T2WI横断及冠状位图像质量最好,伪影很少,组织结构显示清晰。ASL图像质量较好,伪影较少,组织结构显示清晰;BOLD图像伪影较多,信噪比及分辨率稍低,但不影响图像分析及各值的测量。
3、统计分析结果
采用SPSS16.0统计软件进行数据统计分析。计数资料计算频数、构成比;计量资料描述均数±标准差((?)±s),非正态分布描述中位数、最大值、最小值,两组间比较采用t检验,多组间比较采用单因素方差分析(One-way ANOVA),各组间两两比较采用LSD法(Least-significant Difference,最小显著差值法),自身前后比较采用配对t检验(Paired-Samples t Test),非正态分布或方差不齐采用秩和检验,person相关分析,显著性水平α=0.05。不同时点测量值的变化采用折线图表示。
3.1左右肾两侧皮质、外髓及内髓在同一实验组R2~*值之间两两比较,采用配对t检验,在相同实验组左右肾皮质、外髓及内髓R2~*值间差异无统计学意义(P＞0.05)。
3.2左右肾两侧皮质、外髓及内髓在同一实验组ASL-RBF值之间两两比较,采用配对t检验,在相同实验组左右肾皮质、外髓及内髓ASL-RBF值间差异无统计学意义(P＞0.05)。
3.3正常对照组大鼠左肾皮质、外髓及内髓R2~*值间比较,表明外髓R2~*值最高,为32.774±3.07second~(-1),三者间两两比较有显著性差异(F=3.357,P=0.041＜0.05),皮质与外髓、内髓无统计学差异(P＞0.05),内、外髓间有统计学差异(P=0.014)。大鼠右肾皮质、外髓及内髓间R2~*值,外髓R2~*值最高为31.76±2.73 second~(-1),两两比较有显著性差异(F=19.961,P=0.000＜0.05)。
3.4大鼠皮髓质R2~*值各组间采用配对t检验分析:大鼠左肾皮质对照组与注入碘对比剂后不同时间各组皮质R2~*值间无显著性差异;左肾内髓对照组R2~*值与24小时组R2~*值间及24小时组与72小时组间R2~*值有显著性差异(P＜0.05),余各组间R2~*值无显著性差异。左肾外髓对照组R2~*值与注入碘对比剂后各时间点各组R2~*值间均有显著性差异(P＜0.05);48小时组与72小时组R2~*值间无统计学差异(P=0.055),与其它组间均有显著性差异(P＜0.05);大鼠右肾皮质对照组R2~*值与20分钟、24小时及48小时各组皮质R2~*值间有显著性差异(P＜0.05);24小时与48小时、72小时各组间皮质R2~*值、48小时与72小时组皮质R2~*值无显著性差异(P＞0.05);右肾外髓对照组与20分钟、24小时及48小时各组外髓R2~*值间有显著性差异(P＜0.05),对照组与72小时组间R2~*值无显著性差异(P=0.106);右肾内髓对照组与20分钟、24小时组R2~*值有显著性差异(P＜0.05),余各组间无显著性差异。
3.5各组间配对t检验分析大鼠皮髓质ASL-RBF值各组间比较:左肾大鼠皮质对照组与各不同时间点皮质ASL-RBF值间无显著性差异(P＞0.05),左肾内髓对照组与注入碘对比剂后20分钟;20分钟组与24、48小时组ASL-RBF值间有显著性差异(P＜0.05),余各组内髓ASL-RBF值间无显著性差异;左肾外髓对照组与注入碘对比剂后20分钟、24、48、72小时各实验组ASL-RBF值间均有显著性差异(P＜0.05),20分钟与24小时组间ASL-RBF值无显著性差异(P=0.216＞0.05);右肾皮质对照组与注入碘对比剂后各组间ASL-RBF值无显著性差异,20分钟组与24小时组、24小时组与72小时组间ASL-RBF值间无显著性差异(P＞0.05),右肾内髓20分钟组与24小时组ASL-RBF值有显著性差异(P=0.003＜0.05),余各组间均无显著性差异(P＞0.05)。
3.6各部位ASL-RBF值与R2~*值间呈负相关性,其中右肾内髓20分钟组两者之间有统计学意义(γ=-0.537,P=0.010);左肾24小时组内髓ASL-RBF值与R2~*值间有统计学意义(γ=-0.637,P=0.003),余各组皮质及外髓ASL-RBF值与R2~*值间均无统计学意义(P＞0.05)。
4、病理结果
取注入碘对比剂前及后20分钟、24小时、48小时及72小时不同时间点大鼠双肾行病理HE染色,于80、400倍光镜下观察发现:
(1)注入碘对比剂20分钟镜下观察见部分区近曲小管上皮细胞浊肿,个别有溶解。部分区域远曲小管管腔变窄,上皮个别细胞溶解、消失,间质血管扩张、少量充血。随着时间推移:
(2)注入碘对比剂24小时镜下观察见肾小球内少量细胞肿胀、未见萎缩及纤维化。部分区域近曲小管和远曲小管上皮细胞浊肿,未见脂肪变性、玻璃样变及坏死等改变。间质多数血管及毛细血管扩张、充血、破裂。
(3)注入碘对比剂48小时镜下观察见肾小球细胞肿胀、萎缩。部分区域近曲小管和远曲小管上皮细胞浊肿,出现脂肪变性、玻璃样变及坏死等改变。间质内多数血管扩张、充血,毛细血管大部分扩张,出血。
(4)注入碘对比剂72小时镜下观察肾小球结构出现纤维化、萎缩。部分区域近曲小管和远曲小管上皮细胞浊肿,未见脂肪变性、玻璃样变及坏死等改变。间质内少量血管扩张、充血。毛细血管少量扩张,出血。
结论:
1、3.0T MRI大鼠肾脏BOLD成像技术,R_2~*值可定量反映注入碘对比剂后肾脏组织的氧含量的变化;
2、3.0T MRI大鼠肾脏ASL成像技术,ASL-RBF值可定量的反映碘注入碘对比剂后肾脏的血流变化;
3、3.0T MRI大鼠肾脏BOLD及ASL-fMRI成像技术可作为碘对比剂肾脏损害的
评价手段
本课题创新之处
首次提出用3.0TMRI BOLD及ASL-fMRI功能成像技术监测注入碘对比剂后肾脏血流量及氧代谢的改变情况,本研究结果分析认为,3.0T MRI BOLD及ASL-fMRI成像技术可作为注入碘对比剂后在生理状况下监测肾脏功能变化的可行性手段。
Research background and significance:
The use of iodinated contrast agents are becoming more widespread,with the increase of intervention surgery and the widespread applications of CT in clinic. Contrast medium induced renal dysfunction had caused widespread concern and research.Renal function maybe lose temporality or even persistently due to the potential side effects of iodinated contrast agent.This damage,known as contrast agent induced nephropathy.At present,kidney damage caused by iodinated contrast agent has been the third main reason of iatrogenic acute renal failure following surgery and low blood pressure,accounting 10%for iatrogenic acute renal failure incidence.And increase mental and economic burden in the patients obviously.At the same time,a marked increase in society financial burden.Early detection and prevention of renal damage due to iodinated contrast agent were very important in clinic.Measuring serum creatinine concentration was the most commonly method for patients of renal damage.But the study shown that serum creatinine changes were not sensitive to early renal function damage.Therefore,the discovery of effective means for early diagnosis of kidney damage caused by iodinated contrast agent had clinical significance.
Many studies have shown that the blood flow of kidney medulla play an important role in contrast agent induced nephropathy.Changes in medullary blood flow,thus giving rise to changes in oxygen content medulla.Invasive means were always used for the research of renal blood flow and oxygen content in animals. Invasive laser Doppler probe were used for measurement of renal medullary blood flow traditionally.Invasive means of monitoring kidney in humans were difficult to implement and impractical method.The use of non-invasive means of monitoring renal medullary blood flow and oxygen content of iodinated contrast agent induced nephropathy at physiological conditions was essential.
With the advance of magnetic resonance equipment,functional magnetic resonance imaging provides a powerful means for the early detection of many diseases.Some studies had shown that blood oxygen level dependent function magnetic resonance imaging(BOLD-fMRI) technology could monitor the changes in oxygen metabolism of renal medulla effectively.Arterial Spin Labeling function magnetic resonance imaging(ASL-fMRI) could detect the perfusion of tissues and organs quantitatively without exogenous contrast agents,using only their own blood flow.
At present,the research has made significant results,useing BOLD and ASL imaging technologys to kidney diseases such as hypertensive nephrosis,diabetes, arteriosclerosis of renal and kidney cancer.Therefore,BOLD and ASL technique had a very large potential value in diagnosis and evaluation of kidney disease.Nowadays, there were very little research literature about the application of BOLD and ASL technology in evaluating kidney function after using iodinated contrast agent.
Using functional MRI imaging BOLD and ASL technology to monitor renal function such as perfusion and oxygen metabolism changes in physical condition after injection of iodinated contrast agent,proviced non-invasive,simple and feasible means for the study of kidney disease.
objective:
1.To discuss the experimental research of normal kidney in rat with 3.0T BOLD and ASL function magetic resonence imaging.
2.To discuss the experimental research of injury in the rat kidney after injection iodinated contrast agent with 3.0T fMRI-BOLD imaging.
3.To discuss the experimental research of injury in the rat kidney after injection iodinated contrast agent with 3.0T fMRI-ASL imaging.
Materials and methods:
1.Preparation of laboratory animals
To purchase 29 SD rats,with weight of 109.60g±14.26g.Each rat was fasting and water deprivation for 4 hours before MRI scaning.The MRI scans were performed after intraperitoneal anesthesia in 30 minutes later.Each time point 3 rats were executed to check renal pathological observation.
2.MRI scan
2.1 Scan Sequence
①Three planar orientation:transverse,sagittal and coronal.
②Conventional MRI sequences:T2WI axial,T2WI coronal,T1WI axial,fast spin echo(FSE) sequence.
③BOLD imaging sequences:coronal,(multiple fast gradient recalled echo,MFGRE) sequence.
④ASL imaging sequences:coronal,flow sensitive alternating inversion recovery, FAIR),(single-shot fast spin echo,SSFSE),FAIR-SSFSE sequence.
2.2 MRI Scanning Method
Used epuipment:3.0T MRI scanner,50mmbirdcage experimental animals dedicated coil.Head first,in supine position.MRI scans were performed before and after 20mins, 24hrs,48hrs,72hrs of injection iodinated contrast agent.The former as the control group.The scanning sequences were T1WI,T2WI,BOLD,ASL-FAIR.The scanning time was 14 mintues and 12 seconds.4 times MRI scanning were performed at each time point with T2WI coronal,BOLD,ASL-FAIR after injection iodinated contrast agent.Each scanning time was 6 minutes and 14 seconds.
3.MRI Images Analysis
3.1 Image Quality Analysis
2 experienced MR diagnosis of physicians respectively analyzed the image quality of each sequence,including the image sinal to noise ratio,contrast,resolution, artifacts and whether or not the anatomical structure could be demonstracted clearly.
3.2 The T2*value and R2*value measurements IN BOLD imaging
The four-layer scanning was performed on each kidney,with each layer received 8 different T2* images of different TE time(2.2ms～14.7ms).All the images were submitted to obtain T2* Map image by functool software on workstation.The T2* value was measured on T2*Map image.R2 * values in accordance with the formula: R2*=1/T2*,With mean±standard deviation.
3.3 The ASL-RBF value measurement of ASL imaging
The four-layer scanning was performed on each kidney,with each layer received 20 different images.All the images were submitted to access renal perfusion images by functool-fair software on ADW4.3 workstation.The blood flow value of cortex,outer medullary and inner medullary were measured on renal perfusion,with mean±standard deviation.
3.4 ROI Measurement
The region of interest(ROI) selected on each kidney of the same experimental subject had the same size and shape.Each ROI had the area of 1.5mm~2～2.5mm~2, contained at least 5 pixels.6-10 ROIs were measured on cortex and medulla,with the average±standard deviation.The ROIs of placement avoid distortion,artifact and large vessels.
4.Pathological Observation
3 mice were selected on each time point.The kidneies were fetched immediatedly after scanning.The capsules were removed and discissioed along the renal pedicle coronal.and then were fixed in 10%formalin solution after washing with normal saline.The kidney specimens were procedured by alcohol dehydration,xylene transparent,Baptist wax and paraffin-embedded by routine pathological examination,which were cut 3um thick slices for conventional pathological HE staining,mount and so on.Then were observed under 80,400 times microscope respectively,some specimens had photograph.
5.Statistical Analysis
Data entry and analysis were performed by SPSS16.0 statistical software using mean±standard deviation,inter-group comparison using t test,variance analysis, before and after the group used their own matching t test,non-normal distribution or variance of arrhythmia using rank sum test.Different time point measurements of changes in the use of line graph.
Results
1.The Experimental Results
29 SD rats,number as 1th to 29th respectively,13 male and 16 female among the total.Rats No.1 to 3 were used to preliminary test,datas were not recorded.The test includes 26 Rats.The rats were abandoned for anesthetic death.Some images were ruled out for the bad quality.The test analysis different cases in different groups.
2.Image Quality Analysis
2.1 Transverse and coronal T2 weighted image had the best quality without any artifacts,and showed a clear tissue structure.ASL image is better,with a few artifacts, and also showed a clear tissue structure.More artifacts could be seen in BOLD image, the signal to noise ratio and resolution were comparatively lower,but image analysis and measurements were not affected.
3.Statistical Analysis Results
3.1 There were significant differenct of R2* values in cortex,epiopticon and opticon of both kidney,intercomparison t test,The same group is no significant difference (P＜0.05).
3.2 There were significant differenct of ASL-RBF values in cortex,epiopticon and opticon of both kidney,intercomparison t test,The same group is no significant difference(P＜0.05).
3.3 R2* values compared between normal control rats.To left kidney:R2* values in peripticon were of the highest(32.77±3.07second-1),but there were significant difference(P=0.041＜0.05) between renal cortex,peripticon and opticon intercomparison among them.To right kidney:The highest R2* values was 31.76±2.73 second-1 in peripticon,there were significant difference(P＜0.05) between renal cortex,peripticon and opticon intercomparison.
3.4 Rat's medulla and cortex R2* values intercomparison between time groups with paired t-test:(1).To left kidney:There was no significant difference between rat's R2* values of renal cortex in control group and in each different time group after injection of iodinated contrast agent.R2* values of opticon were significant difference between control group and 24 hours group,24 hours group and 72 hours group(P＜0.05),but there were not significant difference between other groups.R2* values in peripticon,Significant difference could be found between control group and each different groups after injection of iodinated contrast agent(P＜0.05);no significant difference between 48 hours and 72 hours group(P=0.055),but there were significant difference between other groups(P＜0.05).(2).To right kidney:The R2* values in cortex of control group were significantly different to 20 minutes,24 hours and 48 hours group(P＜0.05);there were no significant difference between 24 hours group and 48 hours,72 hours,between 48 hours and 72 hours(P＜0.05).R2* values in peripticon significant difference could be found between control group and 20 minutes,24 hours,48 hours group(P＜0.05),but between control group and 72 hours, no significant difference(P=0.106).R2* values in opticon,significant difference could be found between control group and 20 minutes,24 hours group(P＜0.05),but no significant difference between others.
3.5 Intercomparison of ASL-RBF values in rats medulla and cortex between each groups with paired t-test:(1).To left kidney:There was no significant difference between ASL-RBF values of renal cortex in control group and in each different time group after injection of iodinated contrast agent(P＞0.05).ASL-RBF values of opticon were significant differenct between control group and 20 minutes group,20 minutes group and 24 hours,48 hours group(P＜0.05),and no significant difference between other groups.ASL-RBF values in peripticon,Significant difference could be found between control group and 20 minutes,24 hours,48 hoursand 72 hours groups (P＜0.05);no significant difference between 20 minutes group and 24 hours group(P =0.216).(2).To right kidney:There was no significant difference between ASL-RBF values of renal cortex in control group and in each different time group(P＞0.05), Significant difference could be found between 20 minutes group and 24 hours,48 hours group and 72 hours(P＞0.05).ASL-RBF values of opticon were significant differenct between 20 minutes group and 24 hours group(P=0.003),and no significant difference between other groups(P＞0.05).
3.6 The R2* value and ASL-RBFvalue were negative correlation in renal cortex, peripticon and opticon of Experimental Group.The R2* value and ASL-RBFvalue were significant difference in 24hr group opticon.There were no significant difference in others groups(P＞0.05)
4 Pathological Results
Pathology HE staining were done to both kidney of different time group rats, contained pre-injection of iodinated contrast agent and 20 minutes,24 hours,48 hours,72 hours after injection iodinated contrast agent.Observed under light microscope by 80,400 times,findings as follow:20 minutes after injection iodinated contrast agent,part of the proximal convoluted tubule epithelial cells cloudy swelling, a few could be seen dissolved,part of the distal convoluted tubule lumens narrowing, also a few epithelium dissolved and disappeared,interstitial substance angiectasis, lightly congestion.Over time:24 hours after injection,small amounts cellular swelling were observed in glomerulus,but no atrophy and fibrosis.Part of proximal and distal convoluted tubule epithelial cells cloudy swelling,no fatty degeneration, hyalinization,cellular necrosis,and so on.The majority of interstitial blood vessels and telangiectasia,congestion,rupture.48 hours after injection,glomerulus cells swelling,atrophy could be seen,part of proximal tubule and distal convoluted tubule epithelial cells cloudy swelling,fatty degeneration,hyaline degeneration and necrosis, occurred.The majority of interstitial vasodilation,hyperemia,most of the expansion of capillary bleeding.72 hours,glomerulus structure occurred fibrosis,atrophy.Part of proximal tubule and distal convoluted tubule epithelial cells cloudy swelling,no steatosis,hyaline degeneration and necrosis changes.A small amount of interstitial vasodilator,congestive.a few capillary a had expansion,hemorrhage.
Conclusions:
1.3.0 TMRI rat kidney BOLD imaging technology,R2* values can reflect the changes of oxygen content quantitatively in the kidney tissue after contrast agent injected.
2.3.0T MRI rat kidney ASL imaging technique,ASL-RBF values can reflect the changes of blood flow quantitatively in the kidney after contrast agent injected.
3.The combination of 3.0T MRI BOLD and ASL-fMRI imaging technology can be more accurately reflect the kidney perfusion and oxygen metabolism changes in rat kidney after iodinated contrast agent injection,and can be used as the evaluation of kidney damage by iodinated contrast agent.
Innovations Of The Subject
First proposed using 3.0T MRI BOLD and ASL-fMRI functional imaging techniques to monitor the kidney blood flow and oxygen metabolism changes after injection iodinated contrast agent.To consider that 3.0T MRI BOLD and ASL-fMRI imaging techniques can be used to monitoring the Change of renal function after injection of iodinated contrast agent feasibility at physiological conditions.
含碘对比剂主要经肾脏排泄,近年来,有关碘对比剂引起的肾功能损害引起了学者的广泛关注及研究。碘对比剂注入体内后可使肾功能暂时性、甚至持续丧失,由碘对比剂引起的肾功能损害被称为对比剂肾病。目前使用碘对比剂造成肾脏损害已是医源性急性肾功能衰竭的第三大原因,仅次于手术和低血压;约占所有医源性急性肾功能衰竭的10%,明显增加患者精神及经济负担,亦明显增加社会经济负担。因此,碘对比剂所致肾脏损害的早期发现、早期预防、早期治疗在临床上具有重要的意义。当前,临床上最常用检测肾功能的方法为测量患者血肌酐浓度及变化情况。但有研究表明血肌酐浓度及变化情况对早期肾功能的损害不敏感。因此,寻找新的、敏感的可早期发现、早期诊断及早期预防碘对比剂所致肾脏损害的方法在临床上具有重要意义。
许多研究表明,肾髓质血流的改变在碘对比剂肾病上起重要作用。肾髓质血流发生改变,可以引起髓质氧含量的改变。目前为止,在动物肾脏局部血流及氧含量的研究,均采用有创手段。传统上,测量肾脏髓质血流的方法是应用侵入性激光多普勒探针。但是,在人体肾脏髓质血流的研究中,有创的监测手段很难实施。理想的方法是在生理状态下,采用无创手段监测肾脏髓质血流及氧含量在研究碘对比肾病至关重要,也是人们致力研究的热点。
随着磁共振设备不断进步,功能磁共振成像为许多疾病的早期发现、早期诊断提供了强有力的手段及方法。一些研究表明,血氧水平依赖性磁共振功能成像(Blood Oxygen Level Dependent Function Magnetic Resonance Imaging,BOLD-fMRI)技术能有效的监控肾脏髓质氧代谢的变化。动脉自旋标记磁共振成像技术(Arterial Spin Labeling Function Magnetic Resonance Imaging,ASL-fMRI)不需外源性对比剂,仅利用组织器官自身血流灌注,定量检测组织器官灌注情况。二者是目前常有的功能磁共振成像方法。
目前利用BOLD及ASL-fMRI成像技术对高血压肾病、糖尿病、肾动脉硬化及肾脏肿瘤等疾病的研究已经取得显著效果。研究表明,BOLD及ASL-fMRI技术所测得数据在不同观察者及同一观察者具有良好的重复性。因此,多数学者认为BOLD及ASL-fMRI技术在肾脏疾病的诊断和评价方面具有非常大的潜在价值。不过至今,应用BOLD及ASL-fMRI技术评价使用碘对比剂后肾脏功能损害的研究鲜见文献报道。
本实验利用磁共振功能成像(Function Magnetic Resonance Imaging,fMRI)BOLD及ASL成像技术监测注入碘对比剂后肾脏血流灌注及氧代谢的变化,在生理状况下研究注入碘对比剂后肾脏功能的改变,以评价所致肾功能损害情况,同时探讨无创的、简便的、可行的评估注入碘对比剂后肾功能损害的方法。
研究目的:
1、探讨3.0TMRI BOLD及ASL成像在大鼠正常肾脏的实验研究
2、探讨3.0TMRI-BOLD成像技术在大鼠碘对比剂增强后肾脏损害的实验研究
3、探讨3.0TMRI-ASL成像技术在大鼠碘对比剂增强后肾脏损害的实验研究
4、探讨3.0TMRI-BOLD及ASL成像技术联合应用在评估大鼠碘对比剂增强后肾脏损害的价值。
材料与方法:
1、实验动物及准备
购置29只SD大鼠。雌雄不限,体重在109.60g±14.26g。每只大鼠MRI扫描前禁食禁水4小时,腹腔麻醉后30分钟进行MRI扫描。
2、MRI扫描
2.1 MRI扫描序列及方法
①三平面定位像:横断、矢状及冠状位。
②常规MRI序列:T2WI横断位、T2WI冠状位、T1WI横断位,采用快速旋转回波(fast spin echo,FSE)序列
③BOLD成像序列:冠状位,采用多次快速梯度回波(multilple-fast gradientrecalled echo,MFGRE序列
④ASL,成像序列:冠状位,流动敏感交变反转恢复技术(Flow SensitiveAltemating Inversion Recovery,FAIR),单激发快速自旋回波序列(Single-ShotFast Spin Echo,SSFSE)FAIR-SSFSE,序列
2.2大鼠MRI扫描方法:
设备:采用3.0TMRI扫描仪,50mmbirdcage实验专用动物线圈。采用头先进、仰卧位。
方法:分别于注入碘对比剂前、注入碘对比剂后20分钟,24小时,48小时,72小时,分别进行MRI扫描。注入碘对比剂前作为对照组,扫描序列:T1WI、T2WI、BOLD、FSE-FAIR扫描,扫描时间:约14分12秒;注入碘对比剂后分20分钟,24小时,48小时,72小时实验组,每个时间点扫描T2WI冠状位、BOLD、FSE-FAIR序列;共扫描4次,每次扫描时间:约6分14秒。
3、MRI图像分析
3.1图像质量分析
2位有经验的MR诊断医师分别分析各序列的图像质量,主要包括图像信噪比、对比度、分辨率、伪影以及解剖结构显示情况。
3.2 BOLD图像T2~*值及R2~*值的测量
每侧肾脏扫四层,每层获得8张不同TE时间(2.2ms～14.7ms)的T2~*图像,将所得图像,经工作站functool软件处理,获得T2~*Map图像,在T2~*Map图像测量T2~*值。R2~*值根据公式:R2~*=1/T2~*获得。用均数±标准差((?)±s)表示。
3.3 ASL图像ASL-RBF值的测量
每侧肾脏扫四层,每层获得20张不同图像,将所得图像,经工作站functool-fair软件处理,获得肾脏灌注图像。在肾脏灌注图像测量皮质、外髓及内髓局部血流量值,用均数±标准差((?)±s)表示。
3.4 ROI测量
对同一实验对象每侧肾脏选取兴趣区(ROI),每个ROI大小、形状完全一致。ROI大小为1.5mm~2～2.5 mm~2,ROI至少包含5像素。皮质区测量6～10个ROI,外髓、内髓区测6～10个ROI,用均数±标准差((?)±s)表示。测量选择的层面无变形及伪影,避开肉眼所见大血管及伪影。
4、大鼠肾脏病理观察
每个时间点取三只大鼠,扫描完后,立即取双肾,去包膜,沿肾蒂冠状位切开,与MRI扫描冠状位一致。生理盐水冲洗后立即放入10%福尔马林溶液中固定。肾脏标本按病理检验程序进行常规梯度酒精脱水、二甲苯透明、浸蜡、石蜡包埋,切3um厚的切片,作HE病理常规染色,封片等,分别于80、400倍光学显微镜下观察。
5、统计学分析
应用SPSS16.0统计软件包,数据录入及分析;采用均数±标准差((?)±s),组间比较采用t检验、方差分析,自身前后组比较采用配对t检验,非正态分布或方差不齐采用秩和检验,Person相关分析,不同时点测量值的变化采用折线图表示。
结果
1、实验大鼠结果
29只SD大鼠,分别编为1-29号,雌雄不限。1-3号大鼠进行预实验和参数优化,未行数据记录及分析。纳入实验分析的大鼠共26只,其中雄性12只,雌性14只。在实验过程中,因麻醉意外死亡大鼠退出实验,不列入下个实验时间点。或所得图像信噪比较低,图像质量差影响各值测量者,排除当次实验组。最终,本实验各组实验测量例数及左右肾脏分析例数均不同。右侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小及72小时R2~*值测量分析例数分别为23、22、21、11、6例;右侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时ASL-RBF值测量分析例数分别23,22,20、12、7例。左侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时R2~*值测量分析例数分别22、22、20、11、6例;左侧肾脏(注入碘对比剂前)对照组、注入碘对比剂后20分钟、24小时、48小时及72小时ASL-RBF值测量分析例数分别22、22、21、12、7例。
2、图像质量分析
T2WI横断及冠状位图像质量最好,伪影很少,组织结构显示清晰。ASL图像质量较好,伪影较少,组织结构显示清晰;BOLD图像伪影较多,信噪比及分辨率稍低,但不影响图像分析及各值的测量。
3、统计分析结果
采用SPSS16.0统计软件进行数据统计分析。计数资料计算频数、构成比;计量资料描述均数±标准差((?)±s),非正态分布描述中位数、最大值、最小值,两组间比较采用t检验,多组间比较采用单因素方差分析(One-way ANOVA),各组间两两比较采用LSD法(Least-significant Difference,最小显著差值法),自身前后比较采用配对t检验(Paired-Samples t Test),非正态分布或方差不齐采用秩和检验,person相关分析,显著性水平α=0.05。不同时点测量值的变化采用折线图表示。
3.1左右肾两侧皮质、外髓及内髓在同一实验组R2~*值之间两两比较,采用配对t检验,在相同实验组左右肾皮质、外髓及内髓R2~*值间差异无统计学意义(P＞0.05)。
3.2左右肾两侧皮质、外髓及内髓在同一实验组ASL-RBF值之间两两比较,采用配对t检验,在相同实验组左右肾皮质、外髓及内髓ASL-RBF值间差异无统计学意义(P＞0.05)。
3.3正常对照组大鼠左肾皮质、外髓及内髓R2~*值间比较,表明外髓R2~*值最高,为32.774±3.07second~(-1),三者间两两比较有显著性差异(F=3.357,P=0.041＜0.05),皮质与外髓、内髓无统计学差异(P＞0.05),内、外髓间有统计学差异(P=0.014)。大鼠右肾皮质、外髓及内髓间R2~*值,外髓R2~*值最高为31.76±2.73 second~(-1),两两比较有显著性差异(F=19.961,P=0.000＜0.05)。
3.4大鼠皮髓质R2~*值各组间采用配对t检验分析:大鼠左肾皮质对照组与注入碘对比剂后不同时间各组皮质R2~*值间无显著性差异;左肾内髓对照组R2~*值与24小时组R2~*值间及24小时组与72小时组间R2~*值有显著性差异(P＜0.05),余各组间R2~*值无显著性差异。左肾外髓对照组R2~*值与注入碘对比剂后各时间点各组R2~*值间均有显著性差异(P＜0.05);48小时组与72小时组R2~*值间无统计学差异(P=0.055),与其它组间均有显著性差异(P＜0.05);大鼠右肾皮质对照组R2~*值与20分钟、24小时及48小时各组皮质R2~*值间有显著性差异(P＜0.05);24小时与48小时、72小时各组间皮质R2~*值、48小时与72小时组皮质R2~*值无显著性差异(P＞0.05);右肾外髓对照组与20分钟、24小时及48小时各组外髓R2~*值间有显著性差异(P＜0.05),对照组与72小时组间R2~*值无显著性差异(P=0.106);右肾内髓对照组与20分钟、24小时组R2~*值有显著性差异(P＜0.05),余各组间无显著性差异。
3.5各组间配对t检验分析大鼠皮髓质ASL-RBF值各组间比较:左肾大鼠皮质对照组与各不同时间点皮质ASL-RBF值间无显著性差异(P＞0.05),左肾内髓对照组与注入碘对比剂后20分钟;20分钟组与24、48小时组ASL-RBF值间有显著性差异(P＜0.05),余各组内髓ASL-RBF值间无显著性差异;左肾外髓对照组与注入碘对比剂后20分钟、24、48、72小时各实验组ASL-RBF值间均有显著性差异(P＜0.05),20分钟与24小时组间ASL-RBF值无显著性差异(P=0.216＞0.05);右肾皮质对照组与注入碘对比剂后各组间ASL-RBF值无显著性差异,20分钟组与24小时组、24小时组与72小时组间ASL-RBF值间无显著性差异(P＞0.05),右肾内髓20分钟组与24小时组ASL-RBF值有显著性差异(P=0.003＜0.05),余各组间均无显著性差异(P＞0.05)。
3.6各部位ASL-RBF值与R2~*值间呈负相关性,其中右肾内髓20分钟组两者之间有统计学意义(γ=-0.537,P=0.010);左肾24小时组内髓ASL-RBF值与R2~*值间有统计学意义(γ=-0.637,P=0.003),余各组皮质及外髓ASL-RBF值与R2~*值间均无统计学意义(P＞0.05)。
4、病理结果
取注入碘对比剂前及后20分钟、24小时、48小时及72小时不同时间点大鼠双肾行病理HE染色,于80、400倍光镜下观察发现:
(1)注入碘对比剂20分钟镜下观察见部分区近曲小管上皮细胞浊肿,个别有溶解。部分区域远曲小管管腔变窄,上皮个别细胞溶解、消失,间质血管扩张、少量充血。随着时间推移:
(2)注入碘对比剂24小时镜下观察见肾小球内少量细胞肿胀、未见萎缩及纤维化。部分区域近曲小管和远曲小管上皮细胞浊肿,未见脂肪变性、玻璃样变及坏死等改变。间质多数血管及毛细血管扩张、充血、破裂。
(3)注入碘对比剂48小时镜下观察见肾小球细胞肿胀、萎缩。部分区域近曲小管和远曲小管上皮细胞浊肿,出现脂肪变性、玻璃样变及坏死等改变。间质内多数血管扩张、充血,毛细血管大部分扩张,出血。
(4)注入碘对比剂72小时镜下观察肾小球结构出现纤维化、萎缩。部分区域近曲小管和远曲小管上皮细胞浊肿,未见脂肪变性、玻璃样变及坏死等改变。间质内少量血管扩张、充血。毛细血管少量扩张,出血。
结论:
1、3.0T MRI大鼠肾脏BOLD成像技术,R_2~*值可定量反映注入碘对比剂后肾脏组织的氧含量的变化;
2、3.0T MRI大鼠肾脏ASL成像技术,ASL-RBF值可定量的反映碘注入碘对比剂后肾脏的血流变化;
3、3.0T MRI大鼠肾脏BOLD及ASL-fMRI成像技术可作为碘对比剂肾脏损害的
评价手段
本课题创新之处
首次提出用3.0TMRI BOLD及ASL-fMRI功能成像技术监测注入碘对比剂后肾脏血流量及氧代谢的改变情况,本研究结果分析认为,3.0T MRI BOLD及ASL-fMRI成像技术可作为注入碘对比剂后在生理状况下监测肾脏功能变化的可行性手段。
Research background and significance:
The use of iodinated contrast agents are becoming more widespread,with the increase of intervention surgery and the widespread applications of CT in clinic. Contrast medium induced renal dysfunction had caused widespread concern and research.Renal function maybe lose temporality or even persistently due to the potential side effects of iodinated contrast agent.This damage,known as contrast agent induced nephropathy.At present,kidney damage caused by iodinated contrast agent has been the third main reason of iatrogenic acute renal failure following surgery and low blood pressure,accounting 10%for iatrogenic acute renal failure incidence.And increase mental and economic burden in the patients obviously.At the same time,a marked increase in society financial burden.Early detection and prevention of renal damage due to iodinated contrast agent were very important in clinic.Measuring serum creatinine concentration was the most commonly method for patients of renal damage.But the study shown that serum creatinine changes were not sensitive to early renal function damage.Therefore,the discovery of effective means for early diagnosis of kidney damage caused by iodinated contrast agent had clinical significance.
Many studies have shown that the blood flow of kidney medulla play an important role in contrast agent induced nephropathy.Changes in medullary blood flow,thus giving rise to changes in oxygen content medulla.Invasive means were always used for the research of renal blood flow and oxygen content in animals. Invasive laser Doppler probe were used for measurement of renal medullary blood flow traditionally.Invasive means of monitoring kidney in humans were difficult to implement and impractical method.The use of non-invasive means of monitoring renal medullary blood flow and oxygen content of iodinated contrast agent induced nephropathy at physiological conditions was essential.
With the advance of magnetic resonance equipment,functional magnetic resonance imaging provides a powerful means for the early detection of many diseases.Some studies had shown that blood oxygen level dependent function magnetic resonance imaging(BOLD-fMRI) technology could monitor the changes in oxygen metabolism of renal medulla effectively.Arterial Spin Labeling function magnetic resonance imaging(ASL-fMRI) could detect the perfusion of tissues and organs quantitatively without exogenous contrast agents,using only their own blood flow.
At present,the research has made significant results,useing BOLD and ASL imaging technologys to kidney diseases such as hypertensive nephrosis,diabetes, arteriosclerosis of renal and kidney cancer.Therefore,BOLD and ASL technique had a very large potential value in diagnosis and evaluation of kidney disease.Nowadays, there were very little research literature about the application of BOLD and ASL technology in evaluating kidney function after using iodinated contrast agent.
Using functional MRI imaging BOLD and ASL technology to monitor renal function such as perfusion and oxygen metabolism changes in physical condition after injection of iodinated contrast agent,proviced non-invasive,simple and feasible means for the study of kidney disease.
objective:
1.To discuss the experimental research of normal kidney in rat with 3.0T BOLD and ASL function magetic resonence imaging.
2.To discuss the experimental research of injury in the rat kidney after injection iodinated contrast agent with 3.0T fMRI-BOLD imaging.
3.To discuss the experimental research of injury in the rat kidney after injection iodinated contrast agent with 3.0T fMRI-ASL imaging.
Materials and methods:
1.Preparation of laboratory animals
To purchase 29 SD rats,with weight of 109.60g±14.26g.Each rat was fasting and water deprivation for 4 hours before MRI scaning.The MRI scans were performed after intraperitoneal anesthesia in 30 minutes later.Each time point 3 rats were executed to check renal pathological observation.
2.MRI scan
2.1 Scan Sequence
①Three planar orientation:transverse,sagittal and coronal.
②Conventional MRI sequences:T2WI axial,T2WI coronal,T1WI axial,fast spin echo(FSE) sequence.
③BOLD imaging sequences:coronal,(multiple fast gradient recalled echo,MFGRE) sequence.
④ASL imaging sequences:coronal,flow sensitive alternating inversion recovery, FAIR),(single-shot fast spin echo,SSFSE),FAIR-SSFSE sequence.
2.2 MRI Scanning Method
Used epuipment:3.0T MRI scanner,50mmbirdcage experimental animals dedicated coil.Head first,in supine position.MRI scans were performed before and after 20mins, 24hrs,48hrs,72hrs of injection iodinated contrast agent.The former as the control group.The scanning sequences were T1WI,T2WI,BOLD,ASL-FAIR.The scanning time was 14 mintues and 12 seconds.4 times MRI scanning were performed at each time point with T2WI coronal,BOLD,ASL-FAIR after injection iodinated contrast agent.Each scanning time was 6 minutes and 14 seconds.
3.MRI Images Analysis
3.1 Image Quality Analysis
2 experienced MR diagnosis of physicians respectively analyzed the image quality of each sequence,including the image sinal to noise ratio,contrast,resolution, artifacts and whether or not the anatomical structure could be demonstracted clearly.
3.2 The T2*value and R2*value measurements IN BOLD imaging
The four-layer scanning was performed on each kidney,with each layer received 8 different T2* images of different TE time(2.2ms～14.7ms).All the images were submitted to obtain T2* Map image by functool software on workstation.The T2* value was measured on T2*Map image.R2 * values in accordance with the formula: R2*=1/T2*,With mean±standard deviation.
3.3 The ASL-RBF value measurement of ASL imaging
The four-layer scanning was performed on each kidney,with each layer received 20 different images.All the images were submitted to access renal perfusion images by functool-fair software on ADW4.3 workstation.The blood flow value of cortex,outer medullary and inner medullary were measured on renal perfusion,with mean±standard deviation.
3.4 ROI Measurement
The region of interest(ROI) selected on each kidney of the same experimental subject had the same size and shape.Each ROI had the area of 1.5mm~2～2.5mm~2, contained at least 5 pixels.6-10 ROIs were measured on cortex and medulla,with the average±standard deviation.The ROIs of placement avoid distortion,artifact and large vessels.
4.Pathological Observation
3 mice were selected on each time point.The kidneies were fetched immediatedly after scanning.The capsules were removed and discissioed along the renal pedicle coronal.and then were fixed in 10%formalin solution after washing with normal saline.The kidney specimens were procedured by alcohol dehydration,xylene transparent,Baptist wax and paraffin-embedded by routine pathological examination,which were cut 3um thick slices for conventional pathological HE staining,mount and so on.Then were observed under 80,400 times microscope respectively,some specimens had photograph.
5.Statistical Analysis
Data entry and analysis were performed by SPSS16.0 statistical software using mean±standard deviation,inter-group comparison using t test,variance analysis, before and after the group used their own matching t test,non-normal distribution or variance of arrhythmia using rank sum test.Different time point measurements of changes in the use of line graph.
Results
1.The Experimental Results
29 SD rats,number as 1th to 29th respectively,13 male and 16 female among the total.Rats No.1 to 3 were used to preliminary test,datas were not recorded.The test includes 26 Rats.The rats were abandoned for anesthetic death.Some images were ruled out for the bad quality.The test analysis different cases in different groups.
2.Image Quality Analysis
2.1 Transverse and coronal T2 weighted image had the best quality without any artifacts,and showed a clear tissue structure.ASL image is better,with a few artifacts, and also showed a clear tissue structure.More artifacts could be seen in BOLD image, the signal to noise ratio and resolution were comparatively lower,but image analysis and measurements were not affected.
3.Statistical Analysis Results
3.1 There were significant differenct of R2* values in cortex,epiopticon and opticon of both kidney,intercomparison t test,The same group is no significant difference (P＜0.05).
3.2 There were significant differenct of ASL-RBF values in cortex,epiopticon and opticon of both kidney,intercomparison t test,The same group is no significant difference(P＜0.05).
3.3 R2* values compared between normal control rats.To left kidney:R2* values in peripticon were of the highest(32.77±3.07second-1),but there were significant difference(P=0.041＜0.05) between renal cortex,peripticon and opticon intercomparison among them.To right kidney:The highest R2* values was 31.76±2.73 second-1 in peripticon,there were significant difference(P＜0.05) between renal cortex,peripticon and opticon intercomparison.
3.4 Rat's medulla and cortex R2* values intercomparison between time groups with paired t-test:(1).To left kidney:There was no significant difference between rat's R2* values of renal cortex in control group and in each different time group after injection of iodinated contrast agent.R2* values of opticon were significant difference between control group and 24 hours group,24 hours group and 72 hours group(P＜0.05),but there were not significant difference between other groups.R2* values in peripticon,Significant difference could be found between control group and each different groups after injection of iodinated contrast agent(P＜0.05);no significant difference between 48 hours and 72 hours group(P=0.055),but there were significant difference between other groups(P＜0.05).(2).To right kidney:The R2* values in cortex of control group were significantly different to 20 minutes,24 hours and 48 hours group(P＜0.05);there were no significant difference between 24 hours group and 48 hours,72 hours,between 48 hours and 72 hours(P＜0.05).R2* values in peripticon significant difference could be found between control group and 20 minutes,24 hours,48 hours group(P＜0.05),but between control group and 72 hours, no significant difference(P=0.106).R2* values in opticon,significant difference could be found between control group and 20 minutes,24 hours group(P＜0.05),but no significant difference between others.
3.5 Intercomparison of ASL-RBF values in rats medulla and cortex between each groups with paired t-test:(1).To left kidney:There was no significant difference between ASL-RBF values of renal cortex in control group and in each different time group after injection of iodinated contrast agent(P＞0.05).ASL-RBF values of opticon were significant differenct between control group and 20 minutes group,20 minutes group and 24 hours,48 hours group(P＜0.05),and no significant difference between other groups.ASL-RBF values in peripticon,Significant difference could be found between control group and 20 minutes,24 hours,48 hoursand 72 hours groups (P＜0.05);no significant difference between 20 minutes group and 24 hours group(P =0.216).(2).To right kidney:There was no significant difference between ASL-RBF values of renal cortex in control group and in each different time group(P＞0.05), Significant difference could be found between 20 minutes group and 24 hours,48 hours group and 72 hours(P＞0.05).ASL-RBF values of opticon were significant differenct between 20 minutes group and 24 hours group(P=0.003),and no significant difference between other groups(P＞0.05).
3.6 The R2* value and ASL-RBFvalue were negative correlation in renal cortex, peripticon and opticon of Experimental Group.The R2* value and ASL-RBFvalue were significant difference in 24hr group opticon.There were no significant difference in others groups(P＞0.05)
4 Pathological Results
Pathology HE staining were done to both kidney of different time group rats, contained pre-injection of iodinated contrast agent and 20 minutes,24 hours,48 hours,72 hours after injection iodinated contrast agent.Observed under light microscope by 80,400 times,findings as follow:20 minutes after injection iodinated contrast agent,part of the proximal convoluted tubule epithelial cells cloudy swelling, a few could be seen dissolved,part of the distal convoluted tubule lumens narrowing, also a few epithelium dissolved and disappeared,interstitial substance angiectasis, lightly congestion.Over time:24 hours after injection,small amounts cellular swelling were observed in glomerulus,but no atrophy and fibrosis.Part of proximal and distal convoluted tubule epithelial cells cloudy swelling,no fatty degeneration, hyalinization,cellular necrosis,and so on.The majority of interstitial blood vessels and telangiectasia,congestion,rupture.48 hours after injection,glomerulus cells swelling,atrophy could be seen,part of proximal tubule and distal convoluted tubule epithelial cells cloudy swelling,fatty degeneration,hyaline degeneration and necrosis, occurred.The majority of interstitial vasodilation,hyperemia,most of the expansion of capillary bleeding.72 hours,glomerulus structure occurred fibrosis,atrophy.Part of proximal tubule and distal convoluted tubule epithelial cells cloudy swelling,no steatosis,hyaline degeneration and necrosis changes.A small amount of interstitial vasodilator,congestive.a few capillary a had expansion,hemorrhage.
Conclusions:
1.3.0 TMRI rat kidney BOLD imaging technology,R2* values can reflect the changes of oxygen content quantitatively in the kidney tissue after contrast agent injected.
2.3.0T MRI rat kidney ASL imaging technique,ASL-RBF values can reflect the changes of blood flow quantitatively in the kidney after contrast agent injected.
3.The combination of 3.0T MRI BOLD and ASL-fMRI imaging technology can be more accurately reflect the kidney perfusion and oxygen metabolism changes in rat kidney after iodinated contrast agent injection,and can be used as the evaluation of kidney damage by iodinated contrast agent.
Innovations Of The Subject
First proposed using 3.0T MRI BOLD and ASL-fMRI functional imaging techniques to monitor the kidney blood flow and oxygen metabolism changes after injection iodinated contrast agent.To consider that 3.0T MRI BOLD and ASL-fMRI imaging techniques can be used to monitoring the Change of renal function after injection of iodinated contrast agent feasibility at physiological conditions.
引文
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