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基础研究
磁共振T2-mapping定量成像评估兔急性肠系膜上动脉缺血小肠肠壁损伤的实验研究
陈梦莎 祖涵瑜 钟晓飞 李敏敏 曹璋 韩慧婷 曹赫 姜兴岳

Cite this article as: Chen MS, Zu HY, Zhong XF, et al. Experimental study on the evaluation of acute mesenteric artery ischemia in the small intestine wall injury of rabbits by quantitative magnetic resonance T2-mapping technique[J]. Chin J Magn Reson Imaging, 2022, 13(9): 69-74, 80.本文引用格式:陈梦莎, 祖涵瑜, 钟晓飞, 等. 磁共振T2-mapping定量成像评估兔急性肠系膜上动脉缺血小肠肠壁损伤的实验研究[J]. 磁共振成像, 2022, 13(9): 69-74, 80. DOI:10.12015/issn.1674-8034.2022.09.013.


[摘要] 目的 探讨MRI T2-mapping定量成像对监测和评估兔小肠急性肠系膜上动脉缺血(acute mesenteric ischemia, AMI)肠壁损伤的诊断价值。材料与方法 将36只新西兰雄性白兔随机分为实验组(n=18)和对照组(n=18)。实验组行外科手术结扎第2~5支肠系膜动脉弧形血管网以及相应肠管两端供血血管,随后分别于6个时间点(1 h、2 h、3 h、4 h、5 h、6 h)进行MR T2-mapping成像,每个时间点3只。扫描完成后分别对3只兔施行安乐死,取出肠系膜动脉弧形血管网第3分支所供应的肠管病理标本,评估小肠肠壁缺血损伤的严重程度和病理特征变化。对照组进行假手术,开腹不做结扎处理。各个时间点实验组与对照组定量数值的差异采用独立样本t检验,两组各时间点T2值的组内比较采用单因素方差分析,用高斯拟合模型对T2值与缺血时间点进行拟合,显示小肠缺血肠壁的演变规律,并用病理组织学进行相关验证。T2值与缺血时间点间的拟合方程为f(x)=145×exp{-[(x-3.475)/4.297]2},拟合系数R2=0.79。结果 实验组6个时间点的T2值均高于对照组,差异有统计学意义(P<0.05)。实验组中T23h与T21h、T22h、T25h、T26h差异有统计学意义(P<0.05)。随着缺血时间的进展,T2值先升高后降低,前3 h病理表现以水肿炎细胞浸润为主,影像上缺血近3 h时的T23h值达到峰值(151.50±2.90)ms;缺血4 h时肠壁损伤到达肌层,此时出血面积大大增加,T24h值降为(142.50±4.30)ms,此后T2值持续降低。结论 MRI T2-mapping定量成像有助于定量评估AMI小肠肠壁损伤,对于疾病的早期发现具有一定的优势,具有良好的临床应用前景。
[Abstract] Objective To explore the diagnostic value of T2-mapping in quantitatively monitoring and assessing dynamic small intestine wall injury after acute mesenteric artery ischemia (AMI) in a rabbit model by MRI.Materials and Methods Thirty-six New Zealand white rabbits were randomly divided into two groups. The experimental group performed surgical ligation of the arc-shaped vascular network of the 2nd-5th mesenteric artery and the blood supply vessels at both ends of the corresponding intestinal tract, followed by MR T2-mapping imaging at 6 time points (1 h, 2 h, 3 h, 4 h, 5 h, 6 h), 3 rabbits at each time point. After scanning, 3 rabbits were euthanized, and the intestinal pathological specimens supplied by the third branch of the mesenteric artery arc vascular network were taken out to evaluate the severity of ischemic damage to the small intestinal wall and the changes in pathological characteristics. The control group underwent sham operation without ligation. The differences between the quantitative values of the experimental group and the control group at each time point were performed by independent samples t test, and the intra-group comparison of T2 values at each time point between the two groups was performed by one-way analysis of variance. A Gaussian fitting model was used to fit the T2 value to the ischemic time point to show the evolution of the ischemic intestinal wall in the small intestine, which was verified by histopathology. The fitting equation between T2 value and ischemic time point is f(x)=145×exp{-[(x-3.475)/4.297]2}, and the fitting coefficient R2=0.79.Results The T2 values of the experimental group at 6 time points were higher than those of the control group, and the difference was statistically significant (P<0.05). There were statistical differences between T23h and T21h, T22h, T25h and T26h in the experimental group (P<0.05). With the progression of ischemia time, the T2 value first increased and then decreased. The pathological manifestations in the first 3 hours were mainly edema and infiltration of inflammatory cells. The T23h value reached a peak value of (151.50±2.90) ms at nearly 3 hours of ischemia on the image; at 4 h of ischemia, the intestinal wall injury reached the muscle layer, and the bleeding area greatly increased, the T24h value decreased to (142.50±4.30) ms, and the T2 value continued to decrease thereafter.Conclusions MRI T2-mapping technology helps to quantitatively evaluate the small intestinal wall damage in AMI, has certain advantages for early detection of the disease, and has a good clinical application prospect.
[关键词] T2-mapping;定量技术;磁共振成像;急性肠系膜缺血;新西兰兔模型;小肠肠壁损伤
[Keywords] T2-mapping;quantitative techniques;magnetic resonance imaging;acute mesenteric ischemia;rabbit animal model;small bowel wall damage

陈梦莎 1   祖涵瑜 1   钟晓飞 1   李敏敏 1   曹璋 2   韩慧婷 1   曹赫 1   姜兴岳 1*  

1 滨州医学院附属医院放射科,滨州 256603

2 滨州医学院附属医院病理科,滨州 256603

*姜兴岳,E-mail:xyjiang188@sina.com

作者利益冲突声明:全部作者均声明无利益冲突。


基金项目: 山东省自然科学基金 ZR2018LH015
收稿日期:2022-06-06
接受日期:2022-09-13
中图分类号:R445.2  R-332 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.09.013
本文引用格式:陈梦莎, 祖涵瑜, 钟晓飞, 等. 磁共振T2-mapping定量成像评估兔急性肠系膜上动脉缺血小肠肠壁损伤的实验研究[J]. 磁共振成像, 2022, 13(9): 69-74, 80. DOI:10.12015/issn.1674-8034.2022.09.013

       肠系膜上动脉狭窄、闭塞所造成的肠道缺血是临床上常见的肠缺血类型,约占肠缺血疾病的50%[1],此病的临床表现往往缺乏特异性,使得早期诊断相对困难[2]。然而缺血程度超过肠道的耐受力,将会发生小肠透壁性坏死,并引起腹膜炎等一系列严重的并发症[3];加之缺血所引起的一系列分子机制反应容易引发铁死亡[4],增加了临床诊断与救治的困难。此时由于缺血所造成的肠道损伤已不可逆转,需马上进行手术切除,这将给患者带来极大的痛苦和生命威胁,有关研究[5]表明经广泛肠切除术后的患者常伴有短肠综合征,并且需依赖于肠外营养,大大降低了患者的生活质量。然而患者的预后往往与救治的时间有关[6],因此急需一种可以评估早期缺血,并判断缺血肠壁受累程度的检查技术,以便用于临床治疗方法的优选及术前评估。

       MRI作为一种无创的检查方式,结合了解剖成像和功能定量成像的优点,能够更加准确地显示缺血肠壁的形态以及功能改变[7]。MRI定量技术的发展为肠道疾病的诊断提供了新的无创检查方法,使检查结果更加直观化[8, 9]。T2-mapping是一种基于快速自旋回波(fast spin echo, FSE)序列的多回波定量技术[10, 11],它的成像原理是指一次射频脉冲激发后采集多个回波,从而得到权重不同的多对比度的图像。此技术利用组织对横向弛豫时间的影响进行成像,检测组织病理改变所造成T2值的变化,从而实现体内成像[12]。而肠系膜动脉缺血所造成的肠壁病理性改变影响组织的横向弛豫时间,进而可以通过T2值诊断缺血性肠壁损伤。目前,T2-mapping技术大多应用于肾缺血以及颅脑缺血等实质性器官缺血类疾病的研究中,很少应用于中空性脏器缺血的研究,本文旨在通过定量T2值研究小肠缺血所造成的肠壁损伤,并实现肠系膜上动脉缺血的早期诊断。

1 材料与方法

1.1 兔肠缺血模型制作及分组

       本实验严格遵守国际通用赫尔辛基宣言,并获得滨州医学院附属医院动物实验委员会批准,批准文号:20190812。实验选用36只(已剔除术中死亡)3~5月龄的新西兰雄性白兔(济南西岭角养殖繁育中心,普通级,NO.370822211100093125),体质量2.0~2.5 kg,饲养室温度20~25℃,湿度60%~70%,光照适宜。将其随机分为实验组(肠缺血组)和对照组(假手术组)两组。实验前24 h禁食,自由饮水。

       实验组:36只兔,全身麻醉选用浓度为10%的水合氯醛(1.5 mL/kg,北京雷根生物技术有限公司)联合浓度25%的乌拉坦(2 mL/kg,军科弘创生物技术有限公司)经耳缘静脉注射给药。之后根据兔麻醉状态每隔2 h进行麻醉补药。将腹部剃毛,用多维聚碘联合酒精进行消毒处理,术前经皮下注射盐酸利多卡因(0.3 mL/kg,上海麦克林生化科技有限公司)进行局部麻醉镇痛,保证术中动物处于全麻状态,经耳缘静脉注射东莨菪碱(0.5 mL/kg,四川省维克奇生物科技有限公司)抑制肠道蠕动,每3 h进行补药一次,最大程度地减少肠蠕动伪影。经腹中线开腹,找到空肠后用玻璃分针分离出其周围的肠系膜上动脉分支血管,用外科手术线结扎第2~5支肠系膜动脉弧形血管网以及相应肠管两端供血血管,保证小肠肠道供血中断,随后缝合。采用腹带固定兔腹部,以降低呼吸运动以及肠道蠕动所带来的图像问题。结扎后分别于1 h、2 h、3 h、4 h、5 h、6 h随机选取3只实验兔进行MRI扫描,并于扫描完成后立刻对三只兔经静脉注射20~50 mL空气施行安乐死,进行病理取材。

       对照组:18只兔,前期手术操作与实验组一致,但不做结扎处理,缝合完毕后进行与实验组时间节点一致的MRI扫描,扫描结束对兔注射20~50 mL空气施行安乐死后取出肠段。

1.2 MRI扫描

       所有的MRI扫描都是在西门子3.0 T(MAGNETOM Skyra)扫描仪上进行,使用8通道兔专用线圈(苏州众志医疗科技有限公司3A81108C RB80);用腹带抑制腹部运动以及呼吸运动。扫描序列包括常规的冠状位T2WI、横轴位T2WI压脂(BLADE)以及定量T2-mapping序列,具体成像参数如表1所示。

表1  MRI序列和参数
Tab. 1  MRI sequences and parameters

1.3 图像处理

       T2-mapping序列图像在西门子工作站(MM Workplace)上处理,不同TE时间对比的解剖图以及T2 map是由T2-mapping序列自动生成。一名10年以上工作经验的放射医师在T2WI图像上选取缺血肠壁放置三个感兴趣区(region of interest, ROI),并将三个ROI复制在T2 map上相同的位置,ROI的放置尽量避开肠道内容物以及积液,取三个ROI的均值作为此缺血时间点的定量T2值。

1.4 病理取材

       MRI扫描结束后对兔施行安乐死,切开腹壁,结合缺血程度选取靠近结扎肠段的中间肠管,即切除实验组与对照组肠系膜弧形血管网第3支血管供应区的肠管,放入10%甲醛水溶液中进行浸泡,标本在甲醛水溶液中保存超过48 h。48 h后将标本进行石蜡包埋处理、切片、HE染色。两名5年以上工作经验的诊断医师采用双盲法随机对病理图像进行诊断评估,评估的病理特征为水肿面积、出血面积、炎性浸润面积三个。评分标准[12]:0分为正常;1分为病理特征面积<25%;2分为25%≤病理特征面积<50%;3分为50%≤病理特征面积<75%;4分为病理特征面积≥75%。

1.5 统计学分析

       数据统计学分析使用GraphPad Prism 9.0和MATLAB R2018b软件,以P<0.05为差异有统计学意义。所有统计数据均用均数±标准差(x¯±s)表示,各组T2值采用Shapiro-Wilk检验法进行正态性检验。对照组与实验组6个节点肠壁的T2值的组间比较采用独立样本t检验比较差异。两组各时间点的T2值的组内多重比较采用单因素方差分析检验。T2值与缺血时间点之间的拟合采用高斯模型拟合。两名诊断医师对病理的评分结果采用Kappa一致性检验(0<Kappa≤0.4为一致性较差;0.4<Kappa≤0.75为一致性中等;0.75<Kappa≤1为一致性良好)。实验组各缺血点的病理特征评分与对照组的比较采用Kruskal-Wallis非参数秩和检验,并采用FDR法校正P值。采用Spearman秩相关分别评估缺血1~3 h和4~6 h的肠壁病理特征评分与缺血时间的相关性。

2 结果

2.1 新西兰兔正常小肠及缺血肠段形态学评估

       新西兰兔对照组与实验组肠壁的形态学变化如图1所示。对照组:兔的肠壁红润,肠系膜血管走行良好,未见肠壁扩张(图1A)。实验组:肠缺血1 h时,兔肠壁颜色变深,肠系膜血管充血,肠壁轻微肿胀(图1B);缺血3 h时,兔肠壁颜色变为深红色,肠管肿胀明显(图1C);缺血4 h,兔肠壁颜色进一步加深,可见出血点,肠管扩张明显,可看到腹腔积液(图1D);缺血6 h时,兔肠壁颜色变为黑紫色,弹性减弱,系膜出血严重(图1E)。

图1  正常及不同缺血时间肠管形态学表现。1A所示为新西兰兔正常肠管,肠壁红润,肠系膜血管走行良好,未见肠壁扩张。1B~1E所示分别为新西兰兔缺血1 h、3 h、4 h、6 h 肠壁的形态学变化,大体可见肠管颜色随着缺血时间逐渐加深,颜色由红润变为黑紫色。
Fig. 1  Morphological manifestations of bowel in normal and different ischemic time. 1A shows the normal intestinal tube of a rabbit, the intestinal wall is ruddy, the mesenteric blood vessels run well, and there is no intestinal wall expansion. 1B-1E show the morphological changes of the intestinal wall of rabbits at 1 h, 3 h, 4 h, and 6 h after ischemia, the color of the bowel gradually deepened with the time of ischemia, and the color changed from ruddy to black and purple.

2.2 MRI常规影像学评估

       对兔正常小肠与缺血小肠的冠状位和横轴位T2WI图像的影像学评估结果见图2。缺血1 h时肠管出现轻微扩张,肠壁肿胀不明显,肠壁结构完整,T2WI上肠壁信号强度轻微增高,未见肠腔积液;缺血2 h时肠腔比1 h肿胀明显,其他征象与1 h无差异;缺血3 h时肠腔积液明显呈明显高信号,并出现明显扩张,肠壁肿胀结构破坏;缺血4 h时肠腔积液持续存在,肠壁结构不清晰;缺血5~6 h时肠管进一步扩张,肠腔积液明显,肠壁呈混杂高信号。

图2  兔对照组及实验组肠管的MRI T2WI 及T2-mapping 图比较。第一行与第二行图片是对照组与实验组的冠状位与横轴位T2WI图像,缺血组1 h出现肠管扩张,3 h肠腔中出现积液呈明显高信号,4 h、6 h肠腔积液仍然存在,且肠壁结构模糊。第三行图片是对照组与实验组T2-map图像,缺血1 h、3 h肠壁T2值升高,3 h可见肠腔积液,4 h、6 h肠壁T2值降低。
Fig. 2  Comparison of MRI T2WI and T2-mapping of intestinal canal in rabbits in control and experimental groups. 1st and 2nd row of pictures are the coronal and transverse axial T2WI images of the control group and the experimental group. In the ischemic group, the intestinal tract was dilated at 1 h, and the effusion in the intestinal cavity was obviously high signal at 3 h, and the intestinal effusion still existed at 4 h and 6 h, and the intestinal wall structure is blurred. 3rd row image is the T2-map images of the control group and the experimental group, the T2 value of the intestinal wall increased at 1 h and 3 h of ischemia, the intestinal effusion was seen at 3 h, and the T2 value of the intestinal wall decreased at 4 h and 6 h.

2.3 兔急性缺血肠段的MRI T2值变化

       对照组与实验组各组的T2值满足正态性,检验结果如表2所示。对照组与实验组在手术处理后的各个时间点所测得的兔肠壁磁共振T2值见表3。对照组中6个时间点的肠壁T2值差异无统计学意义(P>0.05)。与对照组相比,实验组1~6 h的T2值均高于对照组,且差异均有统计学意义(P<0.05)(图3A)。缺血肠壁的T2值随着缺血时间的进展呈现先升高后降低的趋势,3 h时T2值达到最高(151.50±2.90)ms。在实验组中,T23h值与T21h、T22h、T25h、T26h差异有统计学意义(P<0.05),T24h值稍有下降,为(142.50±4.30)ms,此后T2值逐渐降低但仍高于对照组。缺血5~6 h时与缺血1~2 h时的T2值差异均无统计学意义(P>0.05)。缺血肠壁T2值与时间点的拟合曲线如图3B所示,两者之间的拟合方程为f(x)=145×exp{-[(x-3.475)/4.297]2},R2=0.79。

图3  不同缺血时间肠壁T2 值的比较。3A为对照组与实验组中新西兰兔不同缺血时间肠壁的T2 值的比较,实验组各时间点肠壁的T2 值均高于对照组。3B为实验组T2 值与缺血时间的拟合曲线,拟合方程为f(x)=145×exp{- [(x-3.475)/4.297]2},R2=0.787。** 代表P<0.01,*** 代表P<0.001,****代表P<0.0001。
Fig. 3  Comparison of intestinal wall T2 values at different ischemia times. 3A is the comparison of the T2 value of the intestinal wall of rabbits in the control group and the experimental group at different ischemia times. The T2 value of the intestinal wall at each time point in the experimental group was higher than that in the control group. 3B is the fitting curve of T2 value and ischemia time in the experimental group, the fitting equation is f(x) = 145×exp{- [(x-3.475)/4.297]2}, R2=0.79. ** represents P<0.01, *** represents P<0.001, **** represents P<0.0001.
表2  对照组与实验组肠壁T2值的正态性检验
Tab. 2  Normality test of intestinal wall T2 value in control group and experimental group
表3  对照组与实验组肠壁T2值的比较
Tab. 3  Comparison of intestinal wall T2 values between the control group and the experimental group

2.4 病理表现及病理特征评估

       对照组肠壁各层结构无异常(图4A)。实验组:缺血1 h时肠壁表现为黏膜层上皮细胞轻度脱落,部分血管充血扩张,炎性细胞浸润,黏膜层及黏膜下层轻度水肿(图4B);缺血2 h时黏膜层上皮细胞进一步脱落血管扩张明显,炎性细胞数量较之前增多,黏膜下层水肿明显;缺血3 h时可观察到大部分黏膜层上皮细胞脱落并伴有出血,黏膜下层结构疏松并伴有轻度出血,大量炎性细胞浸润于黏膜层和黏膜下层,肌层结构正常(图4C);缺血4 h时部分肌层受累,黏膜层、黏膜下层及肌层结构出血严重,黏膜层正常结构消失(图4D);缺血5 h时较缺血4 h时各层出血进一步加重;缺血6 h时整个肠壁严重出血,肌层受累严重(图4E)。

       两名诊断医师对水肿、出血、炎细胞浸润情况病理评分结果一致性良好(水肿评分Kappa=0.80;出血评分Kappa=0.82;炎细胞浸润评分Kappa=0.82),所有病理评分结果见表4。三种病理评分与缺血时间均具有正相关性(水肿评分r=0.87,P<0.05;出血评分r=0.96,P<0.05;炎细胞浸润评分r=0.93,P<0.05)。水肿评分于缺血3 h时达到3分,且开始与对照组差异有统计学意义(P=0.019)(图5A)。肠壁出血评分于4 h时达到3分,与对照组差异有统计学意义(P=0.017)(图5B)。炎细胞浸润情况于缺血4 h时达到(3.17±0.29)分,与对照组差异有统计学意义(P=0.015)(图5C)。

       at 3 h of ischemia was significantly different from that of the control group, and the scores of hemorrhage and inflammatory cell infiltration were significantly different between the control group at 4 h of ischemia. * represents P<0.05, ** represents P<0.01.

图4  对照组与实验组不同缺血时间病理表现。4A:对照组肠壁各层结构完整,未见异常病理征象(HE ×10);4B:缺血1 h 肠壁黏膜层上皮细胞轻度脱落,炎细胞浸润并伴有轻度水肿,黏膜层和黏膜下层血管扩张(HE ×10);4C:缺血3 h,大部分黏膜层上皮细胞脱落,黏膜层和黏膜下层水肿明显,黏膜下层出血,肌层结构正常(HE ×10);4D:缺血4 h 肠壁黏膜层正常结构消失,上三层出血明显,肌层内可见明显的炎性细胞浸润(HE ×10);4E:缺血6 h 肠壁明显出血,肌层结构破坏明显(HE ×10)。
Fig. 4  Pathological manifestations of different ischemia time in the control group and the experimental group. 4A: In the control group, all layers of the intestinal wall were structurally intact, and no abnormal pathological signs were found (HE ×10); 4B: After 1 h of ischemia, the mucosal epithelial cells of the intestinal wall were slightly sloughed off, inflammatory cells were infiltrated with mild edema, and the mucosal and submucosa blood vessels were dilated (HE ×10); 4C: After 3 h of ischemia, most of the mucosal epithelial cells fell off, the mucosal and submucosa edema was obvious, the submucosa hemorrhage, and the structure of the muscle layer was normal (HE ×10); 4D: After 4 h of ischemia, the normal structure of the intestinal mucosal layer disappeared, the upper three layers of hemorrhage were obvious, and the infiltration of inflammatory cells was obvious in the muscle layer (HE ×10); 4E: After 6 h of ischemia, the intestinal wall was obviously hemorrhaged, and the muscularis structure was obviously destroyed (HE ×10).
图5  对照组与实验组不同缺血时间点病理评分的比较。5A~5C 分别为对照组与实验组的水肿、出血、炎性细胞浸润评分。水肿评分于缺血3 h与对照组差异有统计学意义,出血和炎性细胞浸润评分于缺血4 h 与对照组差异有统计学意义。* 代表P<0.05,**代表P<0.01。
Fig. 5  Comparison of pathological scores between control group and experimental group at different ischemic time points. 5A-5C are the scores of edema, hemorrhage, and inflammatory cell infiltration in the control group and the experimental group, respectively. The score of edema at 3 h of ischemia was significantly different from that of the control group, and the scores of hemorrhage and inflammatory cell infiltration were significantly different between the control group at 4 h of ischemia. * represents P<0.05, ** represents P<0.01.
表4  对照组与实验组病理特征评分
Tab. 4  The pathological feature scores between the control group and the experimental group

3 讨论

       兔肠系膜血管网结构与人相近,目前已有多项研究采用兔模型模拟临床肠缺血[13, 14]。本实验采用新西兰兔急性肠系膜动脉缺血模型,探究了缺血肠壁T2值和缺血时间之间的关系,得到了小肠缺血的早期演变规律,证明了T2-mapping技术可以无创动态监测缺血小肠的肠壁损伤程度,并有助于发现早期缺血肠壁的病理变化。随着MRI技术的发展,定量技术已经越来越成熟,其优越性在于受诊断医生主观性影响较小,且能挖掘组织病理改变信息[15, 16],所以对于疾病诊断具有更高的准确性,目前尚没有T2-mapping应用于肠缺血的研究相关报道。

3.1 MRI定量成像技术评估小肠缺血的优势

       肠系膜上动脉缺血的诊断一直被认为是临床上的难题,由于肠道特殊的解剖结构以及呼吸运动的影响使得可应用的检查技术相对受限。计算机断层扫描血管造影(computed tomography angiography, CTA)被认为是检测肠系膜血管缺血的有效方法,但它具有对比剂过敏的风险,且无法评估缺血肠壁损伤程度,对于早期黏膜损伤的诊断更加受限[17, 18],MRI作为一种安全有效的检查手段弥补了CT检查技术的不足。目前,其应用研究大多集中于解剖结构的改变[19, 20]。Rondenet等[21]认为缺血所造成的肠管扩张是肠缺血的重要征象,随着严重程度的进展会出现肠腔积气以及腹腔积液,这往往提示缺血已经累及肌层,而对于缺血早期黏膜层的评估是十分困难的。并且完全凭借解剖结构改变去判断缺血程度缺乏特异性和准确性,MRI定量成像技术的应用提高了对于疾病的诊断效率与准确性[22, 23],它可以更加准确地量化肠壁由于缺血所造成的微小改变,有望成为一种无创诊断小肠缺血的技术。我们使用MRI T2-mapping技术得到了T2值与缺血时间的拟合曲线,从而可以对缺血时间以及疾病的进展进行评估,结合常规T2WI进而更有利于疾病的多方面诊疗。已有相关研究证明MRI定量成像对于缺血肠壁的诊断是有价值的,Zhao等[24]应用定量T1-mapping对比剂增强技术基于缺血缺氧造成Ca2+积聚的机制对于缩短T1弛豫时间的影响进行定量研究,证明了定量成像是一种基于组织微小病理改变的准确成像技术,可以识别出人体肉眼无法察觉的微小改变。而我们实验中所应用的T2-mapping技术在自由呼吸状态就可以实现扫描,有助于不能呼吸配合的患者检查诊断,且无需注入对比剂即可得到对比良好的图像,有望实现临床转化。

3.2 MRI T2-mapping技术对早期肠缺血的评估

       早期肠壁的破坏是缺血严重程度的直观表现且与患者的生存能力相关,当缺血局限于黏膜层和黏膜下层时肠缺血处于早期阶段,一旦缺血损伤侵入肌层后患者的预后效果会显著下降[4,25],因此对于缺血损伤肠壁范围的鉴别显得尤为重要[14]。我们的研究表明在缺血早期以黏膜层和黏膜下层的水肿和炎细胞浸润为主,且在缺血1 h时T2值便可表现出异常升高,当缺血达到3 h时水肿评分与对照组差异具有统计学意义,常规T2WI图像上开始出现呈明显高信号肠腔积液,T23h值达到高峰(151.50±2.90)ms。有关缺血性疾病研究中发现了类似的变化趋势,Berritto等[20]在缺血性脑卒中患者的研究中验证了在4.5 h缺血时间窗内患者脑组织T2值相比于正常组织升高,此种现象与含水量有关。T2-mapping技术可以反映组织内水的成分改变所带来的影响[26],而缺血早期由于毛细血管通透性增加所造成的肠壁黏膜上皮细胞水肿将会增大横向弛豫时间,使得病变组织得以鉴别[27]。早期缺血大量炎性细胞浸润,炎性介质被激活[28],会进一步刺激细胞肿胀,引起T2值的升高。因此,我们的研究表明在缺血1~3 h内,肠壁水肿和炎细胞浸润逐渐加重,T21h~T23h值呈现升高的趋势,但此阶段肌层并未受累,是肠壁可逆性损伤救治的关键时期。

3.3 MRI T2-mapping技术对晚期肠缺血的评估

       随着缺血程度的进展,当缺血达到4 h时,此时肠壁破坏侵及肌层,由于缺血缺氧所致血管管壁损伤,黏膜层、黏膜下层及肌层组织出血严重,此时出血病理评分开始与对照组差异具有统计学意义,MRI定量图像中T24h值相较于T23h有轻微的减小,在T2WI像上可观察到肠腔积液持续存在。此时由于动脉供血不足,组织中氧合血红蛋白含量降低,脱氧血红蛋白含量大大增加,脱氧血红蛋白属于顺磁性物质,具有缩短T2弛豫时间的效果,在T2-mapping上表现为T2值的降低[29, 30]。有关急性肠系膜动脉缺血研究中证明缺血肠壁在1~6 h氧合饱和度是逐渐降低的,且在第4 h时下降明显,我们认为这可能是在T2-mapping上T24h值减小的原因[30]。因此当肠壁T2值进展到(142.50±4.30)ms且有下降的趋势时,提示疾病已侵及肌层且伴有严重出血,需引起临床重视。此后T2值进一步降低,提示缺血损伤进一步加重。在缺血6 h时,肠壁发生透壁性坏死,往往提示预后不良,此时各层正常结构消失,肌层发生大片出血,肠壁已发生不可逆性损伤,再灌注救治也毫无意义,需马上进行外科手术切除,这与大多数研究结果一致[19,30]。目前有关基础研究中表明肠道缺血发生后,会有铁质沉积现象,这也是引发铁死亡的关键因素[4],铁质沉积也会降低组织横向弛豫时间,在T2-mapping上表现为T2值变小[31],但在本次研究中没有进行相关证实,还需在以后的研究中完善。综合以上因素,在缺血晚期肠壁的T2值逐渐降低,且T2WI上可观察到肠腔积液,从而与早期缺血肠壁进行区分,这对于临床治疗可以起到指导作用。

3.4 本研究的局限性

       本研究的局限性主要包含以下几点:(1)本研究采用兔模型模拟临床肠系膜动脉缺血,但实验样本数量较少,以后还需大样本的研究及临床探索;(2)尽管本实验中采用腹带束缚以及注射东莨菪碱最大程度减小伪影的影响,但肠道蠕动以及呼吸所造成的伪影对于实验结果仍具有一定的影响;(3)兔小肠肠壁较薄,且肠管内积液对在T2-mapping上ROI的勾画产生一定的影响。

       综上所述,本实验以影像与病理相结合的方法证明MRI T2-mapping定量成像技术是一种有助于诊断和监测肠系膜上动脉缺血肠壁损伤的有效方法。此成像方法对于缺血肠管的生存能力可以起到很好的预测与评估作用,对于手术方案的制订以及患者术后评估具有重要意义,有望成为一种可以评估缺血肠壁严重程度的有效的定量评估检查方法。

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