| Objective:Portal hypertension is a common complication of cirrhosis,and portal pressure gradient is an effective indicator for disease staging,treatment effect evaluation,and prognosis.In this study,hepatic arterial embolization of lipiodol and ethanol mixture was used to establish a model of porcine cirrhosis and portal hypertension.Hepatic venous pressure gradient(HVPG)was measured at different time points before and after modeling,and pathology,serology,magnetic resonance elastography(MRE)and intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)scan were performed.The correlation between HVPG and serological,MRE and IVIM-DWI parameters was explored.Secondly,portal pressure gradient(PPG)was measured before and after surgery in patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt,MRE and IVIM-DWI scans,blood tests was performed simultaneously.The relationship between PPG and MRE,IVIM-DWI parameters was evaluated,and to define whether MRE,IVIM-DWI scan can be used in the prediction of PPG as a noninvasive method.Method:1.Fifteen healthy Bama miniature pigs were randomly divided into experimental group and control group.The twelve pigs in the experimental group were subjected to hepatic arterial perfusion with 10 m L of a 1:3 ratio mixture of iodized oil and 95%alcohol.HVPG was measured by inserting a 6Fr Fogarty double-lumen balloon catheter through the jugular into hepatic vein about 2 cm from the junction of the hepatic vein and the inferior vena cava.Ultrasound-guided biopsy of liver was performed used a 18G biopsy needle.Three tissues from different sites were taken for pathological examination in the specimen tube.HE staining,Masson trichrome staining and reticular fiber staining were performed on the liver specimens.The liver fibrosis was graded by F0-F4 using METAVIR criteria.Blood tests include blood routine test,liver function,blood coagulation,plasma ammonia,and liver fibrosis.Functional magnetic resonance examination included MRE and 9 b-value IVIM-DWI scans.Liver biopsy,HVPG measurement,blood test,MRE and IVIM-DWI scans were performed at baseline and 4W,8W,and 12W.Animals in the experimental group were subjected to liver biopsy,PPG measurement,blood test,MRE and IVIM-DWI scan and TIPS surgery at 16W.Immediately after surgery and 3 days after surgery,PPG measurement,blood test and MRE,IVIM-DWI scan were performed.Then the animal is sacrificed and the liver tissue specimen is taken.2.From January 1,2017 to December 31,2018,we selected 25 patients with portal hypertension who underwent TIPS surgery,including 14 males and 11 females.Blood test and MRE,9 b-value IVIM-DWI scans were performed before TIPS surgery.PPG was measured before and after portosystemic shunt,and blood test and MRE,9 b-value IVIM-DWI scans were peformed again 3 days after surgery.Liver stiffness(LS)and spleen stiffness value(SS)was measured by the MRE-LAB software.The diffusion coefficient(D),perfusion coefficient(D*)and perfusion score(f)and IVIM-DWI signal attenuation curve was measured by the matlab-2014a software.3.SPSS statistical software was used to perform multi-correlation analysis using Pearson or Spearman test.PPC prediction equation was established by multiple linear regression analysis.The receiver operating characteristic curve was used to evaluate the diagnostic performance of relevant parameters for PPG.Results:1.All the experimental animals completed baseline examination and percutaneous transhepatic angiography and embolization.Pathological examination confirmed that 9 of the experimental animals reached F3 stage liver fibrosis and 2 reached F4 stage cirrhosis at 4 weeks after operation.All of 9 survived cases reached F4 stage cirrhosis at 8 weeks after embolization.The main causes of death included anesthesia accident,puncture bleeding and contrast agent allergy,and the model rate was 75%(9/12).Four animals underwent TIPS surgery,and all stents in the portosystemic shunts were occluded 3 days after surgery.There was no statistical difference between the baseline HVPG in the experimental group and the HVPG at each time point in the control group.The HVPG of the experimental groupwere 9.98±3.14 cm H2O(n=11),11.19±5.28 cm H2O(n=9),and 9.55±4.67 cm H2O(n=6)at 4W,8W and 12W after embolization,which was significantly higher than the baseline(P<0.05).The PPG of the 4 experimental animals after TIPS operation was significantly lower than that before surgery,but they all increased again 3 days after operation.There was no statistical difference between the baseline liver LS of the experimental group and the LS of the control group at each time point.In the experimental group,the LS at 4W,8W,and 12W after embolization were 3.51±1.06 k Pa(n=11),4.22±1.51 k Pa(n=9),and 4.86±2.37 k Pa(n=6),which was significantly higher than the baseline(P<0.05).The LS of the 4 experimental groups after TIPS surgery was significantly lower than that before,but they all rose again 3 days after surgery.There was no significant difference in D and D*between the experimental group and the control group at baseline(0W),4W,8W,12W.The f value of the experimental group was significantly lower than that before the embolization(P<0.01),but there was no significant change in the control group.The f value in the 4 experimental group animals of TIPS was significantly higher than that before surgery(P<0.01),but decreased again 3 days after surgery.There were no significant statistical differences in serum test results between the experimental group,the control group and the two groups at different time points.There was a significant correlation between AST,Bil T,LS,f and HVPG(P<0.05).The HVPG prediction equation was obtained by fitting the multi-factor model to lg HVPG=0.079×LS-0.01×f.2.Twenty-five patients successfully completed TIPS and PPG mesurement,and no complications occurred during the perioperative period.The average preoperative PPG was 34.12±8.22cm H2O,and the average postoperative time was 12.86±6.45cm H2O(P<0.001).The average postoperative PPG decreased by 21.25±9.44cm H2O,which was about 62.2%.The average LS of TIPS was 3.90±1.19k Pa and SS was 5.39±1.66k Pa.The average postoperative LS was 3.18±0.97 k Pa and SS was 3.55±1.10 k Pa,which was significantly lower than that before operation.The difference was statistically significant.(P<0.01).The average D value before TIPS was 0.58±0.18×10-3mm2/s,D*value was9.08±1.31×10-3mm2/s,f value was 40.38±5.13%,and the average postoperative D value was 0.98±1.85×10-3mm2/s,D*value was 10.40±1.45×10-3mm2/s and the f value was47.26±5.13%,which was significantly higher than that before operation.The difference was statistically significant(P<0.01).After the TIPS opration,the PLT of patients decreased from 81.68±45.32×109/L to 60.16±31.72×109/L,ALT increased from22.68±11.83U/L to 106.72±213.58U/L,and AST increased from 29.44±11.72U/L to105.24±165.65 U/L,Bil T increased from 20.61±12.47 umol/L to 25.87±13.54umol/L,C IV increased from 52.39±31.83ng/m L to 79.22±47.38ng/m L,and HA increased from204.15±188.70ng/m L to 463.71±609.49ng/m L,the postoperative changes were statistically significant(P<0.05).APRI index and KING index increased significantly after surgery(P<0.01),There were no significant differences in other blood tests before and after surgery.3.Through multiple correlation analysis,there was a correlation between PPG and D*,f,ALT,AST,Bil T,APRI index,FIB-4 index,LS and SS(P<0.05).Multiple linear regression analysis showed that SS and f were effective predictors(P<0.05),and had good sensitivity and specificity for judging whether PPG was greater than 16cm H2O.Conclusion:1.MRE and IVIM-DWI scan have certain diagnostic value for portal hypertension model of pig liver cirrhosis.There is a significant correlation between LS and f values and HVPG.HVPG can be effectively predicted by LS and f values.2.MRE and IVIM-DWI can reflect the change of PPG before and after TIPS surgery in patients with portal hypertension,and there is a significant correlation between SS and f values and PPG.MRE and IVIM-DWI magnetic resonance scans are expected to be an accurate method for non-invasive assessment of portal pressure gradients. |
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