Experimental Study On Acute Hypatocyte Necrosis And Apoptosis With MRI, DWI And MRS

Partâ… Establishment of an experimental model of acute hepatocyte necrosis and apoptosisObjective: To establish an experimental model of acute hepatocyte necrosis and apoptosis by ligating both right hepatic artery and portal vein or only right portal vein in rat, and to evaluate the feasibility of TUNEL in examining hepatocyte apoptosis.Materials and methods: Thirty-six S-D rats were randomly divided into three groups, i. e., a control group with 4 rats for sham operation, a group for hepatic necrosis after both right hepatic artery and right portal vein ligated (HA+PV group), and a group for apoptosis after only right portal vein ligated (PV group). There were 4 sub-groups (4 for each) in necrosis or apoptosis group with 16 rats in each group. The rats in each group were examined by MRI, then sacrificed and sampled at 3h, 12h, 24h and 72h after operation. The apoptosis or necrosis in the right lobe and the proliferation in the left lobe were observed by HE staining, electron microscopy, and TUNEL staining with a quantitative analysis.Results: There were normal appearances of the morphology, volume and microscopic demonstration of both right and left hepatic lobes in sham-operating control group. In HA+PV group, hepatic right lobes were coagulatively necrosed. There was necrosis of liver cells in each sub-groups, accompanying with a few apoptic cells in the 3h sub-group. Along with the time extending, necrotic cells were increasing, and apoptic cells were decreasing. Necrosis in right lobes was at the most at 72h group. In PV group, hepatic right lobes were atrophied. Apoptosis was found at 3h, with its maximum at 24h and declined thereafter. The left lobes in two groups became hypertrophied, and proliferative cells reached the maximum in PV 72h sub-group. Conclutions: It is practical to establish experimental models of acute hepatocyte apoptosis and necrosis by the ligation of only right portal vein or the ligation of both right hepatic artery and portal vein in rats. Apoptosis is prominent at 24h after the ligation of right portal vein branch. At present, TUNEL is a practical way to precisely examine apoptosis in hepatic tissue with a very parallel result to the electronic microscopy. Partâ…¡Experimental Study on Acute Hypatocyte Necrosis and Apoptosis with MRI, DWI and MRSObjective: To demonstrate the ability and value of MR imaging (MRI), diffusion-weighted imaging (DWI), and MR spectroscopy (MRS) in detecting and characterizing necrosis and apoptosis in vivo with a comparison to the pathology after establishment of hepatic necrosis and apoptosis animal model by different surgical ligations of hepatic blood supply vessels.Materials and methods: Fifty-four S-D rats were randomly divided into three groups, i. e., a sham operating control group with 6 rats, a necrosis group (24 rats) after both right hepatic artery and right portal vein ligated (HA+PV group), and a apoptosis group (24 rats) where only right portal vein ligated (PV group). There were 4 sub-groups (6 rats each) in the HA+PV group or PV group. The rats in each group were examined by MRI, DWI, and MRS at 3h, 12h, 24h and 72h after the ligating operation. Signal intensity on T1WI, T2WI and ADC value of the right and left lobes were measured and the ratios of rT1WI,rT2WI,rADC were calculated. Single voxel PRESS 35 sequence were applied for spectroscopy analysis. The peak and area of metabolites were measured and the ratios between right and left lobes were calculated. After the examination, the animals were sacrificed and sampled immediately for HE and TUNEL staining. We compared the results of pathological examination and the results of MRI, DWI and MRS.Results: In HA+PV groups, there were an increase of signal intensity on T2WI and a decrease of ADC value on right hepatic lobes at 3h after operation. Along with time going, hyper-intensity on T2WI were obvious because of more and more necrotic cells. On T1WI, right lobes always appeared iso-intensity. At 24h after only right portal vein ligated, when right lobe atrophy and apoptic cells reached maximum, right hepatic lobes had typical appearances: hyper-intensity on T1WI, hypo-intensity on T2WI, and low value on ADC mapping. The right lobes appeared hyper-intensity on T2WI and the ADC value decreased at 72h, when both necrosis and apoptosis existed in the right lobes. At 3h in both HA+PV group and PV group, compared with left lobe, the Lip-Lac peak of hepatic right lobe increased obviously with few necrotic and apoptic cells. Along with necrotic and apoptic cells increased, the Lip-Lac peak of right hepatic lobe increased further. Similarly, Cho of the right hepatic lobe decreased at 12h after operation and more obviously thereafter. The ratios of Lip-Lac/Cho of right lobe increased in both HA+PV and PV group at 3h after operation, and more obviously in the PV 3h sub-group.Conclutions: At the early time of necrotic process, the hepatic tissue exhibited hyper-intensity on T2WI and DWI, iso-intensity on T1WI, decreased value of ADC. Tissue with a great number of apoptic cells showed slightly hyper-intensity on T1WI, slightly hypo-intensity on T2WI, and increased value of ADC. Hepatic lobes with apparent apoptosis will have typical manifestations on T1WI, T2WI, DWI and ADC mapping. There were an increase of Lip-Lac peak and a decrease of Cho in either necrotic or apoptic tissue. The ratio of Lip-Lac/Cho increase more obviously in apoptic tissue than in necrotic tissue in very early stage and make significance in differentiating acute necrosis and apoptosis. In practical setting, combined increases of Lip peak and Lip-Lac/Cho ratio in ~1H MRS with findings on T1WI, T2WI and DWI, we can detect apoptosis at a very early stage, and differentiate apoptosis with necrosis furthermore.