小肠缺血再灌注损伤的多层螺旋CT灌注成像研究

发布时间：2018-02-03 16:09

本文关键词：小肠体层摄影术 x线计算机 CT灌注成像动物模型小肠缺血再灌注损伤体层摄影术 X线计算机 CT灌注成像动物模型小肠缺血再灌注损伤肠系膜动脉体层摄影术 X线计算机组织病理学动物模型小肠缺血再灌注损伤　出处：《复旦大学》2014年博士论文　论文类型：学位论文

【摘要】：第一部分小肠多层螺旋CT灌注成像的可行性研究目的评价多层螺旋CT (MSCT)灌注成像定量评价小肠血流动力学的可行性。材料和方法15只巴马猪肌注氯胺酮、阿托品麻醉后固定,腹带加压控制呼吸伪影,采用Somatom Definition AS 128层螺旋CT,选定中腹部小肠最大范围层面作为灌注扫描层面,采用Abdomen VPCT Long灌注扫描模式,灌注采集覆盖范围16.8cm。高压注射器经耳缘静脉自动注射碘普罗胺(370mgI/ml) 50ml,注射速率为5mL/s,同等速率追加生理盐水30ml。扫描时间54.08s。图像后处理及测量由两名医师在影像诊断工作站独立完成,将图像放大2倍左右,在血流量(BF)或血容量(BV)图像上选取肠壁的感兴趣区(ROI),通过灌注后处理软件获得BF、BV、平均通过时间(MTT)、表面通透性(PS)灌注伪彩图,测量空肠和回肠肠壁的各灌注参数值。比较空肠和回肠各灌注参数差异,应用Bland-Altman一致性分析来评价两位医师测量结果可重复性。结果猪肠道解剖与人类相似,各灌注图显示小肠血流灌注丰富、分布基本均匀。小肠时间密度曲线(TDC)呈前期整体上升、中后期整体平台的趋势。空肠和回肠各灌注参数值如下：BF为(35.57±7.12)ml/100ml/min和(33.81±8.96)ml/100ml/min, BV为(10.56±1.40) ml/100ml和(9.83±1.58) ml/100ml, MTT为(19.54±3.77)s和(21.02±4.46)s,PS为(22.25±5.71)ml/100ml/min和(23.69±4.53)nl/100ml/min。空肠的BF和BV值略高于回肠,PS和MTT值略低于回肠,但差异均无统计学意义(p=0.463、0.284、0.464和0.720)。两位医师测量结果具有很好的一致性(差值均数分别为0.7907、0.0068、-0.3139和0.745)。结论应用MSCT灌注成像评价小肠血流动力学是可行的,小肠血供丰富,空回肠灌注参数值无明显差异。第二部分小肠缺血再灌注损伤的多层螺旋CT灌注成像研究目的探讨MSCT灌注成像评价急性小肠缺血再灌注损伤(IRI)的价值。材料和方法巴马猪48头,随机分为IRI 1h、2h、3h、4h四个实验组(每组n=6)及相应时间点的假手术组(每组n=5)和单纯缺血组(n=4)。实验组开腹用血管夹夹闭肠系膜上动脉(SMA)主干2h后松开,再灌注分别为1h、2h、3h和4h;单侧缺血组夹闭SMA 2h不进行再灌注；假手术组仅开腹和分离SMA主干。造模结束后行MSCT灌注扫描,设备、扫描方案、图像分析、测量和观察指标同第一部分。扫描结束后处死动物,用玻片刮取回肠粘膜冷冻,留取新鲜组织标本,测定丙二醛(MDA)含量以及超氧化物歧化酶(SOD)活性；取远端小肠组织HE染色后评价组织损伤程度。比较各组间灌注参数差异,评价血流动力学参数与MDA和SOD的相关性。结果IRI 4h组BF值低于假手术组[(18.832±4.687)VS (31.014±7.039) ml/100ml/min, p=0.018]; IRI 2h、3h、4h组BV值低于假手术组(4.624±0.668) VS (9.160±1.887) ml/100ml, p=0.003; (5.015±1.203) VS(9.310±1.466)ml/100ml, p=0.000; (3.376±0.826)VS(9.188±0.785)ml/100ml, p=0.000];四组IRI的MTT值与假手术组相比均具有统计学差异(p值分别为0.000、0.000、0.011、0.008)；IRI 3h和IRI 4h组的PS值与假手术组相比有统计学差异(p值分别为0.001和0.000)。四组IRI间BF、BV、PS值差异均具有统计学意义(F=9.965、10.856和5.511,p=0.005、0.000和0.007),MTT值差异则无统计学意义(F=1.760, p=0.191)。BF和BV值与MDA值呈显著负相关(r=-0.714, p=0.000; r=-0.713, p=0.000),与SOD值呈显著正相关(r=0.641,p=0.001; r=0.677, p=0.000)。与缺血组相比,再灌注后肠粘膜损伤没有明显加重。结论MSCT灌注成像能够准确反映小肠IRI及其动态演变过程,与生化标志物具有良好的相关性,是评价急性小肠IRI的有效方法。第三部分小肠缺血再灌注损伤的多层螺旋CT表现与病理对照研究目的探讨小肠缺血再灌注损伤(IRI)的MSCT表现及与肠粘膜损伤相关性。材料和方法巴马猪20头,随机分为IRI1h、2h、3h和4h四组(每组n=5),IRI造模方法同第二部分。采用128层螺旋CT机,术前3天及术后即刻行全腹平扫、动脉期和门脉期双期增强扫描。增强采用高压注射器经耳缘静脉注射碘普罗胺(370mgI/ml),剂量2ml/kg,注射速率为3mL/s,延迟时间分别为38s及72s,观察和比较手术前后肠系膜密度、肠壁强化、肠管扩张及肠腔积液情况。扫描结束后处死动物,取远端小肠组织HE染色后光镜下观察组织病理学改变。结果肠系膜密度增高仅见于IRI 4h组。IRI 1h、2h和3h组动脉期和静脉期强化值均与术前相仿,差异均无明显统计学意义(动脉期p=0.340、0.810和0.169;静脉期p=0.608、0.659和0.343)；IRI 4h组动脉期和静脉期强化值均较术前明显下降,但动脉期差异无明显统计学意义(p=0.071)；静脉期差异有统计学意义(p=0.013)。15头实验动物出现肠腔扩张及积液,以IRI 4h最为明显,但无统计学差异。IRI 1h、2h、3h、4h组肠壁损伤主要局限于粘膜层,有不同程度的脱落和中性粒细胞浸润,间质水肿,毛细血管充血扩张,但各组间肠粘膜损伤病理评分无统计学差异(p=0.797)。结论MSCT能显示IRI的动态演变过程,IRI 1h至3h仅见肠腔扩张和积液,IRI 4h可见肠壁强化值下降和肠系膜水肿。在此过程中肠壁组织病理学损伤改变并无明显进展。第四部分小肠缺血再灌注继发性肺损伤的多层螺旋CT表现及其病理对照研究目的探讨小肠缺血再灌注(IR)继发性肺损伤的MSCT表现及其病理基础。材料和方法巴马猪16头,随机分为IR实验组和假手术组(各8只)。IR实验组用动脉夹夹闭SMA2小时后开放动脉进行再灌注4小时。假手术组仅暴露并分离但不夹闭SMA。两组于术后4h均行全胸部MSCT扫描,扫描准直：0.6mm,重建层厚：1mm；层间距：0.7mmm,视野：294mm；管电压：122kV；管电流：99mAS。在横断位图像观察肺部改变。所有动物于扫描结束后处死,收集支气管肺泡灌洗液(BALF)测定蛋白含量,检测肺通透性指数,计算肺组织湿干重比(W/D)。取肺组织HE染色后光镜下观察组织病理学改变。结果IR实验组有5头猪MSCT见肺部异常,表现为肺野透亮度减低,肺内散在斑片状淡薄磨玻璃密度影,小叶间隔增厚,支气管血管束增粗,肺内网格状高密度影。另3头猪MSCT未见明显异常。光镜下IRI实验组所有5头猪见不同程度的损伤改变,包括肺泡间隔增厚,间质水肿,肺内小血管扩张,其中2例可见肺泡壁破坏、融合、肺泡腔,肺泡壁见及小叶间隔充填炎症细胞、红细胞及渗出液。其他3头动物仅见毛细血管充血和肺间隔水肿。假手术组MSCT未见明显胸部异常征象,光镜下肺组织结构均正常。与假手术组相比,IR实验组肺湿干重比及肺通透性指数明显升高。CT明确诊断肺损伤的敏感度为62.5%,特异度为100%。结论MSCT能够较为准确的显示小肠缺血再灌注继发性肺损伤,可作为临床一站式检查的有效工具。
[Abstract]:The first part of the purpose of the feasibility study of CT perfusion imaging of small intestine multislice spiral evaluation of multislice spiral CT (MSCT) perfusion imaging and quantitative evaluation of the feasibility of small intestinal hemodynamics. Materials and methods 15 pigs intramuscular injection of ketamine, atropine anesthetized, controlled breathing artifact pressurized bellyband, using Somatom Definition AS 128 slice spiral CT, selected in intestines the maximum range of level as the perfusion level, using Abdomen VPCT Long perfusion scan mode, perfusion acquisition coverage of 16.8cm. high pressure syringe via ear vein automatic injection iopromide (370mgI/ml) 50ml, the injection rate is 5mL/s, processing and measuring independently by two doctors at the same rate diagnostic workstation and saline 30ml. scan time 54.08s. after the image magnified images of 2 times, the blood flow (BF) and blood volume (BV) images of selected intestinal wall of interest Area (ROI), by perfusion postprocessing software for BF, BV, mean transit time (MTT), permeability surface (PS) perfusion maps, the perfusion parameters measurement of jejunum and ileum of the intestinal wall. The difference value of the jejunum and ileum of the perfusion parameters, using Bland-Altman consistency analysis to evaluate two doctors measured the results of repeatability. The pig intestinal anatomy and humans, the perfusion maps showed intestinal blood perfusion rich distribution. Small time density curve (TDC) in the early rise in the late of the overall platform trend. The jejunum and ileum of the perfusion parameters were as follows: BF (35.57 + 7.12) and ml/100ml/min (33.81 + 8.96) ml/100ml/min, BV (10.56 + 1.40) ml/100ml and (9.83 + 1.58) ml/100ml, MTT (19.54 + 3.77) s and (21.02 + 4.46) s, PS (22.25 + 5.71) ml/100ml/min and (23.69 + 4.53) nl/100ml/min. jejunal BF and BV value slightly higher than the ileum, PS And the MTT value was slightly lower than the ileum, but the differences were not statistically significant (p=0.463,0.284,0.464 and 0.720). Two doctors measured results have good consistency (difference were respectively 0.7907,0.0068, -0.3139 and 0.745). Conclusion the clinical evaluation of MSCT perfusion imaging of intestinal hemodynamics is feasible, the small intestine with abundant blood supply, jejunoileum perfusion the parameter values had no significant difference. The purpose of CT perfusion imaging on second part of intestine ischemia reperfusion injury on MSCT perfusion imaging evaluation of acute intestinal ischemia reperfusion injury (IRI) value. Materials and methods the 48 pigs were randomly divided into IRI, 1H, 2h, 3h, 4H in experimental group (n = four n=6) sham operation group and the corresponding time points (n = n=5) and ischemia group (n=4). The experimental group open with occlusion of the superior mesenteric artery (SMA) after 2H reperfusion trunk release, respectively 1H, 2h, 3H and 4H; unilateral ischemia group clipping SM A 2h of reperfusion; the sham operation group only laparotomy and isolation of SMA trunk. The end ofmodelthe underwent MSCT perfusion scanning, scanning device, program, image analysis, measurement and observation index is the same as the first part. The animal were sacrificed after the scan, with glass scraping of ileal mucosa specimens from fresh frozen tissue samples, determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity; the extent of tissue damage evaluation of small intestine distal perfusion parameters after HE staining. The differences between groups were compared, correlation evaluation of hemodynamic parameters with MDA and SOD. The IRI 4H group BF value is lower than the sham group [(18.832 + 4.687) VS (31.014 + 7.039) ml/100ml/min, p=0.018]; IRI 2h, 3h, 4H group, BV value is lower than the sham operation group (4.624 + 0.668) VS (9.160 + 1.887) ml/100ml, p=0.003; (5.015 + 1.203) VS (9.310 + 1.466) ml/100ml, p= 0; (3.376 + 0.826) VS (9.188 + 0.785) ml/100ml. P=0.0 00]; four IRI MTT group compared with the sham operation group were statistically significant (P = 0.000,0.000,0.011,0.008); IRI 3H and IRI 4H group PS value was statistically difference compared with the sham operation group (P = 0.001 and 0). Four groups of IRI between BF, BV, PS value difference with statistical significance (F=9.965,10.856 and 5.511, p=0.005,0.000 and 0.007), the MTT value of no significant difference (F=1.760, p=0.191).BF and BV value was negatively correlated with MDA value (r=-0.714, p=0.000; r=-0.713, p=0.000), and positively correlated with SOD values (r=0.641, p=0.001; r=0.677, p=0.000). With the ischemia group, reperfusion injury of intestinal mucosa did not increase significantly. Conclusion MSCT perfusion imaging can reflect the evolution process of intestinal IRI and dynamic, have good correlation with the biochemical markers, is the effective method for evaluation of acute intestinal IRI. The third part of intestinal ischemia reperfusion Multi slice spiral CT and pathological damage control of intestinal ischemia reperfusion injury (IRI) and intestinal mucosa injury and the correlation between MSCT findings. Materials and methods in 20 pigs were randomly divided into IRI1h, 2h, 3H and 4H in the four groups (n=5 each), IRI modeling method with using second parts. 128 slice CT, 3 days before and immediately after surgery for abdominal plain and dual phase enhanced arterial phase and portal venous phase enhancement scan. A high pressure syringe through ear vein injection iopromide (370mgI/ml), dose 2ml/kg, injection rate is 3mL/s, the delay time were 38S and 72s, were observed before and after and to compare the surgical mesenteric density, bowel wall enhancement, bowel dilatation and intestinal effusion. The animal were sacrificed after the scan, the distal small intestine tissue HE staining under light microscope observation of histopathological changes. The mesenteric density increased in IRI 4H group.IRI only 1H, 2h and 3H groups in arterial phase And the enhancement of venous phase values were similar with the preoperative, the differences were statistically significant (p=0.340,0.810 and 0.169 arterial venous phase; and 0.343 p=0.608,0.659); IRI group 4H arterial and venous phase enhancement value were significantly decreased, but the arterial phase difference was not statistically significant (p=0.071); there was statistical significance vein phase difference (p=0.013) luminal dilatation and effusion.15 head of experimental animal, IRI 4H was the most obvious, but no significant difference in the.IRI 1H, 2h, 3h, 4H group of intestinal injury was mainly confined to the mucosal layer, with different degrees of loss and neutrophil infiltration, interstitial edema, capillary congestion expansion. But among the groups intestinal mucosa injury score no significant difference (p=0.797). Conclusion MSCT can show the process of dynamic evolution of IRI, IRI 1h to 3H was observed in luminal dilatation and hydrops, IRI 4H showed the enhancement of intestinal wall decreased and mesenteric edema in this process. Injury change no significant progress in intestinal tissue pathology. The fourth part of intestinal ischemia reperfusion of multislice spiral CT and pathology secondary lung injury control study to investigate intestinal ischemia reperfusion (IR) MSCT manifestations and pathologic basis of secondary lung injury. Materials and Fa Bama I 16, were randomly divided into experimental group and IR the sham operation group (.IR = 8) in the experiment group was clamped for SMA2 hours after the open artery 4 hours after reperfusion. Sham operation group only exposed and separated but not clamped two SMA. after operation in group 4H underwent total thoracic MSCT scan, scan collimation 0.6mm, reconstruction thickness: 1mm layer; spacing: 0.7mmm, vision: 294mm; voltage: 122kV; tube current: 99mAS. in transverse images. The pulmonary changes were observed in all animal were sacrificed after the scan, collect the bronchoalveolar lavage fluid (BALF) for the determination of protein content, lung permeability refers to The number of calculated lung wet to dry weight ratio (W/D). Lung tissue HE staining under light microscope observation of histopathological changes. The results of IR experimental group 5 pigs showed abnormal lung MSCT, lung brightness reduction, lung weak scattered patchy ground glass opacity, interlobular septal thickening, bronchus bronchiolectasis, lung grid like high density shadow. The other 3 pigs MSCT had no obvious abnormalities. Under light microscope, IRI experimental group all 5 pigs see changes, including alveolar septal thickening, interstitial edema, small intrapulmonary vascular dilatation, 2 cases of alveolar wall damage, alveolar fusion. Cavity, alveolar wall and septa filled with inflammatory cells, red blood cells and exudate. The other 3 animal only capillary congestion and pulmonary edema. The MSCT interval in sham operation group had no obvious signs of abnormal chest, lung tissue under light microscope structure were normal. Compared with sham operation group, IR group lung wet The dry weight ratio and the pulmonary permeability index increased significantly. The sensitivity and the specificity of.CT in the diagnosis of lung injury were 62.5% and 100%. respectively. Conclusion MSCT can accurately display secondary lung injury after intestinal ischemia-reperfusion, and it can be used as an effective tool for clinical one-stop examination.

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R816.5;R574

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