Experimental And Clinical Application Of Hepatic CT Perfusion Imaging In The Study Of Hepatic Fibrosis

IntroductionHepatic fibrosis is a disease of excessive collagen deposition in liver due to disbalance of collagen generation and degradation during the progression of many chronic hepatic diseases. They often accompant with hepatocytic inflammation and easily develop into hepatic cirrhosis. About 9.75% of Chinese are infectors of hepatic virus and a population of more than 30 million suffer from hepatitis virus B. Currently, diagnosis and gradation of hepatic fibrosis mainly depend on liver biopsy, and an efficient noninvasive diagnostic method is desirable.After hepatic fibrosis or cirrhosis, hepatic blood flow is changed by the increase of circulation resistance which is caused by collagen deposition and reformation of hepatic lobules, and thus secondary hyperflow of visceral blood . CT perfusion imaging, as a kind of functional imaging, is brought out on the base of radioactive tracer dilute theory and center volume theory, through which organ hemodynamics can be evaluated from the microcirculation level and its changes can be detected before morphology appears different. It has been approved that hepatic CT perfusion value is related to disease severity, but this technology has not been applied to the research of hepatic fibrosis gradation.In update clinics, a noninvasive examine technology is needed not only for early diagnosis and further intime therapy of hepatic fibrosis or cirrhosis, but also for clinical follow-up and prognosis estimation. Our aim is to investigate whether CT perfusion imaging can reflect blood flow changes before and after hepatic fibrosis. Any regularity, if existed, would supply some evidence for clinical diagnosis and treatment follow-up of hepatic fibrosis.Materials and MethodsPartISeventy white rabbits, weighting from 2 to 2.5 kilograms, were randomly divided into experimental group (n=62) and control group (n=8). Intragastic administration of CCl₄ was performed in experimental group once a week after 14-day addition of Phenobarbital (50mg/day) to their forage. Meanwhile, control group received water only. The initial dose of CCl₄ was 60μg and subsequent doses were adjusted to keep AST and ALT within the range of 400 and 800 IU/L during the whole process. At the 8th, 12th, 16th, and 20th week respectively, 8 rabbits in the experimental group and 2 rabbits in the control group were selected for CT perfusion imaging with an injection of 1.5ml/kg Omnipaque at a rate of 1ml/s through the ear vein. Then after region of interest (ROI) was drawn, TDC and perfusion parameters including HAP, HPP, HTP and HPI were autogenerated. After perfusion imaging, the rabbits were sacrificed and liver was processed for HE staining, Masson's Trichrome method staining and reticular fiber staining. Hepatic fibrosis was graded according to the pathologic results.Part II1. 31 patients (28 cases were hepatitis B and 3 cases were hepatitis C), with an average age of 38.3 years (ranging from 15 to 57 years) were included in our research. The final diagnosis of all cases was confirmed by puncture biopsy and four groups were formed accordingly: hepatitis group: grade So, 5 cases; gentle fibrosis group: grade S₁ or S₂, 9 cases; moderate fibrosis group: grade S₃, 6 cases; severe fibrosis group: grade S₄, 11 cases. Hepatitis group, gentle fibrosis group and moderate fibrosis group were arbitrarily merged into hepatic disease group and severe fibrosis group were assigned as hepatic cirrhosis group. 6 outpatients with no hepatopathy history and negative findings in physical examination and imaging were chosen as control.2. dynamic CT scan was performed with the hepatic hilar lever at the center 6 seconds after pumping injection of contrast medium (Omnipaque) at a rate of 5 ml/sec (total dose 40ml) through a 20 gauge plastic cannula from the antecubital vein.3. Serologic indices included: thrombocyte count, GGT, cholesterol, AST, ALT, A/G. Forn index, APRI index, AST/ALT were calculated. Their correlation with the extent of hepatic fibrosis was analyzed. Hepatic fibrosis of above stage S₂ was considered positive. With specificity as abscissae and sensitivity as ordinate, ROC curve was drawn and AUC was automatically calculated out. AUC=1.0 stood for a perfect index of test results. AUC < 0.5 indicated no diagnostic value.Results Part I1. In experimental group, rabbits died gradually 4 weeks after CC14 administration with a peak at the 8th to 12th week. Finally there remained 3 rabbits in S₀ stage, 9 rabbits in S₁, 8 in S₂, 6 in either S₃ or S₄ respectively. The control group all survived.2. Hepatic portal vein perfusion increased and hepatic artery perfusion decreased with the aggravation of hepatic fibrosis. There were significant differences of HPP and HTP either between S₃ stage and control group or between S4 stage and control group. HPI of S₄ stage was significantly different from that of S₁ stage and that of control group.Part II1. Comparison among hepatic disease group, hepatic cirrhosis group and control group. There was no statistical difference of HAP among each group. HPP, HTP and HPI were notably different between each two of the hepatic cirrhosis group, hepatic disease group and control group. There was statistical difference of HPP and HTP between hepatic disease group and control group.2. Comparison among each fibrosis group and control group. Hepatic portal vein perfusion and total hepatic perfusion became decreased with the aggravation of hepatic fibrosis. There was no statistical difference of HAP between each experimental group and control group. Neither the hepatitis group nor the gentle fibrosis group showed statistical difference from the control group in any perfusion parameter. HPP and HTP of moderate fibrosis group and severe fibrosis group were statistically different from those of control group, but showed no difference between themselves. HPI of severe fibrosis group differed statistically from that of each other group.3. Comparison of serologic indices among each groupStatistical correlation of Forns index, APRL, PLT, PT and A/G was found with the extent of hepatic fibrosis. According to the analysis of ROC curve, Forns index ,PT and Apri index could indicate obvious hepatic fibrosis (S>2).Conclusions1. By CT perfusion imaging, hemodynamic conditions in certain hepatic fibrosis stage could be detected; and blood flow of hepatic portal vein and artery could be quantified.2. By CT perfusion imaging, the regularity of blood flow changes in hepatic vein and artery could be observed in different fibrosis stages. Hepatic portal vein perfusion and total hepatic perfusion took on a descending tendency from hepatitis to fibrosis and finally to cirrhosis.3. CT perfusion imaging, as a noninvasive and repeatable method, could provide -reliable evidence for the early detection of severe hepatic fibrosis, which is important in clinical practice.4. Forns index, Apri index and PT helped to discriminate stages of obvious hepatic fibrosis (S>2), which is meaningful in clinics.