Using Functional Magnetic Resonance Imaging To Study The Relationship Between Changes Of Liver Blood Supply And Regeneration After Partial Hepatectomy

【Purpose】At present,the initiation mechanism of residual liver regeneration after partial hepatectomy（PHx）is not clear.While,the main change that occurs immediately after PHx is the liver hemodynamics.It speculated that hemodynamic change might have close relationship with liver regeneration.Functional magnetic resonance imaging（f MRI）can quantify blood supply characteristics of liver parenchyma noninvasively.Intravoxel incoherent motion imaging（IVIM）can reflect blood flow and blood volume,and T2^*mapping can reflect blood oxygen content of the liver parenchyma.In this study,the most studied rat who had rapid liver regeneration ability was selected as the research object.PHx models with different proportional hepatectomy and same proportional hepatectomy with different liver status were constructed,and normal patients with left lateral sectionectomy（LLS）of the liver were collected.To explore the changes of liver blood supply and liver regeneration activity after PHx,and the impact of the extent of hepatectomy and liver status on liver blood supply and regeneration.【Subjects and Methods】This study was divided into three parts:the first and the second part were animal experiments,using male SD rats weighing 250～300g;the third part was clinical study,collecting normal people who have received LLS of the liver.In the first part,102 normal rats were randomly assigned to three groups,each group underwent different liver lobes resection to construct 30%,50%and 70%PHx models（N30%group,N50%group and N70%group）.Ten of 34 rats in each group were randomly selected for f MRI scanning.Liver IVIM and T2^*mapping were performed before operation,within 2 hours,on the 1th,2th,3th,5th,7th,14th and21th day after operation.The other 24 rats were used for pathological and blood biochemical examination（3 animals were randomly selected at each time point before operation,on the 1th,2th,3th,5th,7th,14th and 21th day after operation）.The D^*,PF,D and T2^*values of the liver parenchyma and liver volume at each time point were measured on MR images.Pathological indicators that reflects liver regeneration activity included hepatocyte Ki-67 index and hepatocyte diameter.Biochemical tests of liver function included alanine aminotransferase（ALT）,aspartate aminotransferase（AST）and total bilirubin（TBIL）.The changes of f MRI indexes,liver volume,liver pathological and biochemical results were observed dynamically in each group.The intra-and inter-group differences of liver f MRI indexes and liver volume were compared at each time point.The relationship between liver f MRI indexes,liver volume and pathological results were analyzed.In the second part,34 rats were injected with carbon tetrachloride（CCl₄）subcutaneously on the back of the neck to construct a liver fibrosis model for 8 weeks,followed by 30%PHx（F30%group,the same operation method as N30%group）.Ten rats were randomly selected for f MRI scanning,and liver IVIM and T2^*mapping were performed before operation,on the 1th,2th,3th,5th,7th,14th and 21th day after operation.The other 24 rats were used for liver pathological and blood biochemical examination（3 rats were randomly selected at each time point corresponding to f MRI scanning）.f MRI and blood biochemical indexes were as same as the first part.Pathological indicators included liver fibrosis grade,hepatocyte Ki-67 index and hepatocyte diameter.The changes of f MRI indexes,liver volume,pathological and biochemical results were observed dynamically.The differences of f MRI indexes and liver volume were compared at each time point.The correlation between liver f MRI indexes,liver volume and pathological results were analyzed.In addition,the differences of f MRI indexes and pathological results between F30%group and N30%group were compared.In the third part,99 consecutive subjects with LLS of the liver（parent living liver donors）were collected prospectively.Twenty-one,18,20,20,and 20 subjects received liver f MRI（IVIM and T2^*mapping）before operation,2 weeks,3 weeks,4weeks,and 8 weeks after operation,separately.The other 11 cases completed f MRI examination at all time points.D^*,PF,D,T2^*values of liver parenchyma and liver volume were measured at each time point.The changes of f MRI indexes and liver volume were observed dynamically and compared at each time point,and the relationship between f MRI indexes and liver volume were analyzed.【Results】1.The comparative analysis of different PHx groups in normal rats found that f MRI,pathological and biochemical indexes in each group all showed regular changes,and the trend of changing was similar.D^*value linked to blood flow of liver parenchyma decreased significantly after operation（compared with preoperative value,p<0.05）,and then gradually recovered.With the increase of hepatectomy amount,the degree of changing did not change,but the time required to return to normal increased.PF value linked to blood volume of liver parenchyma dropped to the lowest at 3 days after operation（compared with preoperative value,p<0.05）,and then gradually recovered.The degree of decline and the time required for recovery were proportional to the amount of hepatectomy.T2^*value linked to blood oxygen content of liver parenchyma dropped immediately and significantly after operation（compared with preoperative value,p<0.05）,and then gradually increased.The degree and speed of rising were affected by the amount of hepatectomy.Liver regeneration activity was proportional to the amount of hepatectomy.f MRI indexes linked to liver blood supply correlated to liver regeneration activity.2.The comparative analysis between F30%and N30%group showed that both D^*value linked to blood flow of liver parenchyma and PF value linked to blood volume of liver parenchyma showed an upward trend in F30%group.And,T2^*value linked to blood oxygen content of liver parenchyma increased gradually in the early period after operation.PF value and T2^*value in F30%group were significantly different with that in N30%group（p<0.05）.Compared with normal liver,regeneration activity of fibrotic liver was slightly lower,and hepatocyte hypertrophy lasted longer.PF value linked to blood volume of liver parenchyma correlated to liver regeneration activity（r=-0.756,p=0.04）.3.The dynamic monitoring of residual liver after LLS in normal subjects revealed that both D^*value linked to blood flow of liver parenchyma and PF value linked to blood volume of liver parenchyma had no obvious changes from 2 weeks to8 weeks after operation（p>0.05）.T2^*value linked to oxygen content of the liver parenchyma changed significantly after surgery（p<0.001）.The changes of liver T2^*values after LLS correlated to that of liver volume（r=-0.415,p=0.005）.【Conclusion】IVIM and T2^*mapping could monitor blood supply changes of liver parenchyma noninvasively after PHx.In rats with normal liver,the trend of changing in liver blood supply was similar among groups with different proportional hepatectomy.While,the degree of changing,and the speed of changing and recovering depended on the amount of hepatectomy.The blood supply of liver parenchyma correlated well with regeneration activity.In rats with fibrotic liver,regeneration activity was lower and the duration of hepatocyte hypertrophy was longer than normal rats after 30%hepatectomy.And liver PF values linked to blood volume correlated to liver regeneration activity.In normal subjects with liver LLS,f MRI indexes linked to blood flow and blood volume of liver parenchyma from 2 to 8 weeks after operation were similar with that in baseline.While,liver T2^*values linked to blood oxygen level of liver parenchyma increased significantly after operation,and correlated to the changes of liver volume.