發(fā)布時(shí)間：2018-02-03 16:09

  本文關(guān)鍵詞： 小腸 體層攝影術(shù) x線計(jì)算機(jī) CT灌注成像 動(dòng)物模型 小腸 缺血再灌注損傷 體層攝影術(shù) X線計(jì)算機(jī) CT灌注成像 動(dòng)物模型 小腸 缺血再灌注損傷 腸系膜動(dòng)脈 體層攝影術(shù) X線計(jì)算機(jī) 組織病理學(xué) 動(dòng)物模型 小腸 缺血再灌注損傷　出處：《復(fù)旦大學(xué)》2014年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：第一部分小腸多層螺旋CT灌注成像的可行性研究目的評(píng)價(jià)多層螺旋CT (MSCT)灌注成像定量評(píng)價(jià)小腸血流動(dòng)力學(xué)的可行性。材料和方法15只巴馬豬肌注氯胺酮、阿托品麻醉后固定,腹帶加壓控制呼吸偽影,采用Somatom Definition AS 128層螺旋CT,選定中腹部小腸最大范圍層面作為灌注掃描層面,采用Abdomen VPCT Long灌注掃描模式,灌注采集覆蓋范圍16.8cm。高壓注射器經(jīng)耳緣靜脈自動(dòng)注射碘普羅胺(370mgI/ml) 50ml,注射速率為5mL/s,同等速率追加生理鹽水30ml。掃描時(shí)間54.08s。圖像后處理及測(cè)量由兩名醫(yī)師在影像診斷工作站獨(dú)立完成,將圖像放大2倍左右,在血流量(BF)或血容量(BV)圖像上選取腸壁的感興趣區(qū)(ROI),通過(guò)灌注后處理軟件獲得BF、BV、平均通過(guò)時(shí)間(MTT)、表面通透性(PS)灌注偽彩圖,測(cè)量空腸和回腸腸壁的各灌注參數(shù)值。比較空腸和回腸各灌注參數(shù)差異,應(yīng)用Bland-Altman一致性分析來(lái)評(píng)價(jià)兩位醫(yī)師測(cè)量結(jié)果可重復(fù)性。結(jié)果豬腸道解剖與人類(lèi)相似,各灌注圖顯示小腸血流灌注豐富、分布基本均勻。小腸時(shí)間密度曲線(TDC)呈前期整體上升、中后期整體平臺(tái)的趨勢(shì)�？漳c和回腸各灌注參數(shù)值如下：BF為(35.57±7.12)ml/100ml/min和(33.81±8.96)ml/100ml/min, BV為(10.56±1.40) ml/100ml和(9.83±1.58) ml/100ml, MTT為(19.54±3.77)s和(21.02±4.46)s,PS為(22.25±5.71)ml/100ml/min和(23.69±4.53)nl/100ml/min�？漳c的BF和BV值略高于回腸,PS和MTT值略低于回腸,但差異均無(wú)統(tǒng)計(jì)學(xué)意義(p=0.463、0.284、0.464和0.720)。兩位醫(yī)師測(cè)量結(jié)果具有很好的一致性(差值均數(shù)分別為0.7907、0.0068、-0.3139和0.745)。結(jié)論應(yīng)用MSCT灌注成像評(píng)價(jià)小腸血流動(dòng)力學(xué)是可行的,小腸血供豐富,空回腸灌注參數(shù)值無(wú)明顯差異。第二部分小腸缺血再灌注損傷的多層螺旋CT灌注成像研究目的探討MSCT灌注成像評(píng)價(jià)急性小腸缺血再灌注損傷(IRI)的價(jià)值。材料和方法巴馬豬48頭,隨機(jī)分為IRI 1h、2h、3h、4h四個(gè)實(shí)驗(yàn)組(每組n=6)及相應(yīng)時(shí)間點(diǎn)的假手術(shù)組(每組n=5)和單純?nèi)毖M(n=4)。實(shí)驗(yàn)組開(kāi)腹用血管夾夾閉腸系膜上動(dòng)脈(SMA)主干2h后松開(kāi),再灌注分別為1h、2h、3h和4h;單側(cè)缺血組夾閉SMA 2h不進(jìn)行再灌注；假手術(shù)組僅開(kāi)腹和分離SMA主干。造模結(jié)束后行MSCT灌注掃描,設(shè)備、掃描方案、圖像分析、測(cè)量和觀察指標(biāo)同第一部分。掃描結(jié)束后處死動(dòng)物,用玻片刮取回腸粘膜冷凍,留取新鮮組織標(biāo)本,測(cè)定丙二醛(MDA)含量以及超氧化物歧化酶(SOD)活性；取遠(yuǎn)端小腸組織HE染色后評(píng)價(jià)組織損傷程度。比較各組間灌注參數(shù)差異,評(píng)價(jià)血流動(dòng)力學(xué)參數(shù)與MDA和SOD的相關(guān)性。結(jié)果IRI 4h組BF值低于假手術(shù)組[(18.832±4.687)VS (31.014±7.039) ml/100ml/min, p=0.018]; IRI 2h、3h、4h組BV值低于假手術(shù)組(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];四組IRI的MTT值與假手術(shù)組相比均具有統(tǒng)計(jì)學(xué)差異(p值分別為0.000、0.000、0.011、0.008)；IRI 3h和IRI 4h組的PS值與假手術(shù)組相比有統(tǒng)計(jì)學(xué)差異(p值分別為0.001和0.000)。四組IRI間BF、BV、PS值差異均具有統(tǒng)計(jì)學(xué)意義(F=9.965、10.856和5.511,p=0.005、0.000和0.007),MTT值差異則無(wú)統(tǒng)計(jì)學(xué)意義(F=1.760, p=0.191)。BF和BV值與MDA值呈顯著負(fù)相關(guān)(r=-0.714, p=0.000; r=-0.713, p=0.000),與SOD值呈顯著正相關(guān)(r=0.641,p=0.001; r=0.677, p=0.000)。與缺血組相比,再灌注后腸粘膜損傷沒(méi)有明顯加重。結(jié)論MSCT灌注成像能夠準(zhǔn)確反映小腸IRI及其動(dòng)態(tài)演變過(guò)程,與生化標(biāo)志物具有良好的相關(guān)性,是評(píng)價(jià)急性小腸IRI的有效方法。第三部分小腸缺血再灌注損傷的多層螺旋CT表現(xiàn)與病理對(duì)照研究目的探討小腸缺血再灌注損傷(IRI)的MSCT表現(xiàn)及與腸粘膜損傷相關(guān)性。材料和方法巴馬豬20頭,隨機(jī)分為IRI1h、2h、3h和4h四組(每組n=5),IRI造模方法同第二部分。采用128層螺旋CT機(jī),術(shù)前3天及術(shù)后即刻行全腹平掃、動(dòng)脈期和門(mén)脈期雙期增強(qiáng)掃描。增強(qiáng)采用高壓注射器經(jīng)耳緣靜脈注射碘普羅胺(370mgI/ml),劑量2ml/kg,注射速率為3mL/s,延遲時(shí)間分別為38s及72s,觀察和比較手術(shù)前后腸系膜密度、腸壁強(qiáng)化、腸管擴(kuò)張及腸腔積液情況。掃描結(jié)束后處死動(dòng)物,取遠(yuǎn)端小腸組織HE染色后光鏡下觀察組織病理學(xué)改變。 結(jié)果腸系膜密度增高僅見(jiàn)于IRI 4h組。IRI 1h、2h和3h組動(dòng)脈期和靜脈期強(qiáng)化值均與術(shù)前相仿,差異均無(wú)明顯統(tǒng)計(jì)學(xué)意義(動(dòng)脈期p=0.340、0.810和0.169;靜脈期p=0.608、0.659和0.343)；IRI 4h組動(dòng)脈期和靜脈期強(qiáng)化值均較術(shù)前明顯下降,但動(dòng)脈期差異無(wú)明顯統(tǒng)計(jì)學(xué)意義(p=0.071)；靜脈期差異有統(tǒng)計(jì)學(xué)意義(p=0.013)。15頭實(shí)驗(yàn)動(dòng)物出現(xiàn)腸腔擴(kuò)張及積液,以IRI 4h最為明顯,但無(wú)統(tǒng)計(jì)學(xué)差異。IRI 1h、2h、3h、4h組腸壁損傷主要局限于粘膜層,有不同程度的脫落和中性粒細(xì)胞浸潤(rùn),間質(zhì)水腫,毛細(xì)血管充血擴(kuò)張,但各組間腸粘膜損傷病理評(píng)分無(wú)統(tǒng)計(jì)學(xué)差異(p=0.797)。結(jié)論MSCT能顯示IRI的動(dòng)態(tài)演變過(guò)程,IRI 1h至3h僅見(jiàn)腸腔擴(kuò)張和積液,IRI 4h可見(jiàn)腸壁強(qiáng)化值下降和腸系膜水腫。在此過(guò)程中腸壁組織病理學(xué)損傷改變并無(wú)明顯進(jìn)展。第四部分小腸缺血再灌注繼發(fā)性肺損傷的多層螺旋CT表現(xiàn)及其病理對(duì)照研究目的 探討小腸缺血再灌注(IR)繼發(fā)性肺損傷的MSCT表現(xiàn)及其病理基礎(chǔ)。材料和方法 巴馬豬16頭,隨機(jī)分為IR實(shí)驗(yàn)組和假手術(shù)組(各8只)。IR實(shí)驗(yàn)組用動(dòng)脈夾夾閉SMA2小時(shí)后開(kāi)放動(dòng)脈進(jìn)行再灌注4小時(shí)。假手術(shù)組僅暴露并分離但不夾閉SMA。兩組于術(shù)后4h均行全胸部MSCT掃描,掃描準(zhǔn)直：0.6mm,重建層厚：1mm；層間距：0.7mmm,視野：294mm；管電壓：122kV；管電流：99mAS。在橫斷位圖像觀察肺部改變。所有動(dòng)物于掃描結(jié)束后處死,收集支氣管肺泡灌洗液(BALF)測(cè)定蛋白含量,檢測(cè)肺通透性指數(shù),計(jì)算肺組織濕干重比(W/D)。取肺組織HE染色后光鏡下觀察組織病理學(xué)改變。結(jié)果IR實(shí)驗(yàn)組有5頭豬MSCT見(jiàn)肺部異常,表現(xiàn)為肺野透亮度減低,肺內(nèi)散在斑片狀淡薄磨玻璃密度影,小葉間隔增厚,支氣管血管束增粗,肺內(nèi)網(wǎng)格狀高密度影。另3頭豬MSCT未見(jiàn)明顯異常。光鏡下IRI實(shí)驗(yàn)組所有5頭豬見(jiàn)不同程度的損傷改變,包括肺泡間隔增厚,間質(zhì)水腫,肺內(nèi)小血管擴(kuò)張,其中2例可見(jiàn)肺泡壁破壞、融合、肺泡腔,肺泡壁見(jiàn)及小葉間隔充填炎癥細(xì)胞、紅細(xì)胞及滲出液。其他3頭動(dòng)物僅見(jiàn)毛細(xì)血管充血和肺間隔水腫。假手術(shù)組MSCT未見(jiàn)明顯胸部異常征象,光鏡下肺組織結(jié)構(gòu)均正常。與假手術(shù)組相比,IR實(shí)驗(yàn)組肺濕干重比及肺通透性指數(shù)明顯升高。CT明確診斷肺損傷的敏感度為62.5%,特異度為100%。結(jié)論MSCT能夠較為準(zhǔn)確的顯示小腸缺血再灌注繼發(fā)性肺損傷,可作為臨床一站式檢查的有效工具。
[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.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R816.5;R574

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