| PrefaceChina is a high incidence area of viral hepatitis,especially hepatitis B virus(HBV)infection?Taking hepatitis B as an example,WHO reported that there were about 257 million chronic HBV infections worldwide.About 887 thousand people worldwide died of HBV infection each year,including 30%of cirrhosis and 45%of primary hepatocellular carcinoma.In 2014,Chinese Center For Disease Control And Prevention(CDC)carried out serological epidemiological survey of hepatitis B among 1 to 29 years of age in the country.The prevalence of HBsAg among people aged 1 to 4,5 to 14 years and 15 to 29 years old were 0.32%,0.94%and 4.38%respectively.It is estimated that the prevalence of HBsAg is 5%to 6%in the general population of China.There are about 70 million cases of chronic HBV infection,of which about 20 to 30 million cases are chronic hepatitis B patient.Clinically,most patients with viral hepatitis are chronically infected and can develop into cirrhosis,severe hepatitis(liver failure)or hepatocellular carcinoma,which seriously threaten the health of the patients.For patients with chronic liver disease(CLD)or liver cirrhosis(LC),liver function assessment always plays an important role regardless of the presence of hepatocellular carcinoma(HCC).The pre-treatment of various acute and chronic liver diseases is to fully evaluate the liver function,and the evaluation of liver function has always been throughout the treatment process of various liver diseases,especially for patients with CLD or LC in the choice of treatment methods,efficacy evaluation and prognosis evaluation plays a key role.At present,there are many methods for the evaluation of liver function,including Child-Pugh classification,indole cyanogen green(ICG)clearance test,D sorbitol method,MELD score,imaging evaluation such as ultrasound elastography,etc..However,different methods have different emphasis and application conditions,which make it difficult to fully reflect the pathology and prognosis of the disease.In addition,the current liver function evaluation method focuses mainly on the evaluation of the overall liver function.With the promotion of the healthy China 2030 plan and the requirement of precision medical treatment,the requirement of regional liver function evaluation is increasing in clinical practice.Current research and clinical work do not pay much attention to the quantitative assessment of regional liver function and the impact of chronic hepatitis-related liver function heterogeneity on regional liver function assessment in different regions of interest.Some more accurate methods,such as indole green clearance test,are rare y used to specific clinical practice.In this study,multimode MR I was used to quantitatively evaluate liver function in patients with chronic viral hepatitis.PurposeTo investigate the feasibility and clinical value of intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)and Gd-EOB-DTPA enhanced magnetic resonance imaging in evaluating regional liver function in patients with chronic viral hepatitis.Materials and methodsCases of chronic viral Liver disease(CLD)We retrospectively analyzed the patients admitted to the Jinan Infectious Diseases Hospital from January 2015 to December 2016 and performed MRI tests at the same time.82 cases of chronic viral liver disease(ages 24?77)were included in this study(51 males and 31 females,average age of 52.7±11.9 years),and all patients were performed IVIM-DWI,of which 73(46 males and 37 females,average age of 53.2±11.8 years)were performed Gd-EOB-DTPA enhanced MRI.Healthy control groupTwenty(12 males and 8 females,average age of 37.1±13.4 years)performed abdominal MRI due for diagnosis of other benign diseases,such as suspicious cysts or hemangiomas(diameter?3cm,less than 3).Laboratory examination and clinical evaluation of liver functionAll patients performed serological examinations in the same laboratory within 1 week before/after MRI examination and assessed with liver disease through the Child-Pugh scoring system(CTP).MRI examination and related parametersAll patients and the health control group MRI were performed on Siemens 3.0 T MRI scanner.(1)Half-Fourier equation single-shot Turbo spin-echo time(HASTE),repeat time(TR)/echo time(TE):14000/86 ms,flip angle(FA):10,Matrix:512×512,FOV:400×400 mm,Slice thickness:5 mm,gap:20%,slices:24?30.(2)Dialytic navigation fast spin echo T2WI TR/TE:4251/105ms,FOV:400X400mm,Slice thickness:5mm,gap:20%,slices:30.(3)The in-opp phase T1WI use a fast gradient echo sequence or a Dixon sequence,TR/TE:4.0/2.5,1.2ms,FA:10,Matrix:512 X 512,FOV:450 X 390 mm,Slices thickness:3 mm,slices:72.(4)Free Breathing IVIM-DWI uses a single excitation plane echo sequence(SE-shot spin-echo),TR/TE:6500/67ms,echo spacing:0.52ms,FOV:400×262,seven diffusion gradients B-values(0,50,100,150,200,400 and 800 s/mm2)were used.(5)Contrast enhanced MRI(CE-MRI)uses three-dimensional volume interpolated body examination(3D-Vibe),TR/TE:4.1/2.1ms,FA:9,FOV:309X380,Slice thickness:3.0 mm.Gd-EOB-DTPA(injection dose:0.025 mmol/kg)+saline 20?30 ml injection,injection flow rate 1?1.5 ml/s.Dynamic enhancement scanning,and 10 min,20 min hepatobiliary phase(HBP)after contrast agent injection were performed.Image analysisPost-processing of the IVIM-DWI data were performed by using the MITK diffusion software(developed by the German Cancer Research Center,Division of Medical and Biological Informatics,Heidelberg,Germany)to acquire IVIM parameters of perfusion fractions(f),pure molecular diffusivity(D),and pseudo diffusivity(D*).For the liver parenchyma,four irregular ROIs(designed to carefully preserve at least 5 mm to the edge of liver,including whole segments as large as possible,and excluding visible vessels,focal hepatic lesions such as cyst and hemangioma,or imaging artifacts),were placed by choosing different levels of the liver(slices near the visceral and diaphragmatic surfaces were discarded to eliminate intestinal gas and respiratory motion artifacts).The ROIs were manually drawn in the extra segments of the left lobe(EL),medial segments of the left lobe(ML),anterior segments of the right lobe(AR),and posterior segments of the right lobe(PR)(Figure 1).All ROIs were positioned on DWI with b-values of 50 by two radiologists,one with 15 years and the other with 7 years of experience in abdominal MRI.For each liver segment,IVIM parameters(f,D,and D*)were calculated by the average of measured value at 6?15 different level of transverse liver sections.The average f,D,and D*values of the four liver segments were taken as the whole liver IVIM parameters.The RE value of Gd-EOB-DTPA enhanced MRI measurements were refer to the above methods at 10min and 20min HBP images.Statistical analysisAll statistical analyses were performed using SPSS 21.0 for Windows(IBM,Armonk,NY,USA).Two-sided P-values<0.05 were considered statistically significant.Continuous data were tested for normal distribution using the Kolmogorov-Smirnov test.The IVIM-DWI parameters and RE were expressed as mean ±standard deviations.One-way ANOVA with the LSD post hoc test was used to evaluate those parameters among different liver segments.Different parameters between the CTP class A group and the CTP class B+C group was compared using the Student t test.The receiver operator characteristic curve(ROC)was used to compare the ability of f,D,and D*values,and RE values in discriminating patients with CTP class A and CTP class B+C.Pearson correlation was used to evaluate the correlations between the IVIM,RE parameters and the CTP scores.ResultsBy IVIM-DWI and Gd-EOB-DTPA enhanced MRI,stable multi-modal quantitative/semi-quantitative parameters can be obtained in patients with chronic hepatitis.1.Evaluation of liver heterogeneity by IVIM-DWI and Gd-EOB-DTPA enhanced MRIThe differences of f,D,D*,and RE values between different hepatic segments are statistically significant(P<0.05),confirmed that there are heterogeneity differences in IVIM parameters between different hepatic segments.The difference of f between different hepatic segments in the control group was statistically significant(P=0.017),and there was no significant difference of D and D between the hepatic segments(P values were 0.176 and 0.388,respectively).f values of CTP Class A group are higher than those of CTP Class B+C group(P<0.01).D values of between CTP A and B+C group were significantly different in EL(extra left lobe),PR(posterior right lobe),and whole liver(P<0.05).D values of between CTP A and B+C group were significantly different in EL,IL(inner left lobe),PR,and whole liver(P<0.05).The differences between IVIM parameters and RE were statistically significant in chronic hepatitis group and control group.Compared with chronic hepatitis group,f and D were relatively high and D was relatively low.2.Relationship between IVIM-DWI parameters and CTP classification of liver functionOf the 82 patients in the IVIM-DWI group,there were 40 cases in the CTP A group.Due to the small number of CTP C cases,CTP B and C cases were merged into CTP B+C groups,a total of 42 cases(CTP B 40 cases,CTP C 2 cases).In patients with viral hepatitis,f(P=0.001),and D(P=0.038)were independently related to the CTP classification,while D was not significantly related to the CTP classification(P=0.451).Pearson correlation analysis showed that,in the IVIM parameters,f,D,D*of extra left lobe and averages of whole liver were all related to CTP score.There was a moderate correlation between the CTP sore,and the f of anterior right lobe and whole liver,the f of inner left lobe and posterior right lobe,and the D*of inner left lobe.There was no significant correlation between the CTP sore,and the D of inner left lobe and anterior right lobe,the D and D*of posterior right lobe.Furthermore,f,D,D*have a certain correlation with the main biochemical indicators of serum.The area under the ROC curve(AUC)of the whole liver f,D,and D*value was statistically significant,with AUC 0.88(95%CI:0.81?0.96,P=0.000)and 0.65(95%CI:0.52?0.77,respectively).P=0.024)and 0.73(95%CI:0.62?0.84,P=0.000).In the prediction of patients with CTP A and CTP B+C,when the average f value was 0.29,the AUC was 0.88(95%CI:0.81?0.96),the sensitivity was 86.8%,and the specificity was 81.8%.3.Relationship between RE value of Gd-EOB-DTPA enhancement and CTP classification of liver functionThe average RE10 and RE20 of liver were calculated according to RE values of Gd-EOB-DTPA in the first part.The RE-values of Gd-EOB-DTPA enhanced MR I were related to the main Serological markers.The differences between the control group and the different CTP grades were compared.According to CTP scores,73 patients in the hepatitis group were divided into CTP A group(35 cases)and CTP B+C group(38 cases,CTP B 37 cases,CTP C 1 case).The correlation between RE10,RE20 and CTP scores in different liver regions was calculated.The areas under the ROC curve of whole liver RE10 and RE20 are 0.88 and 0.89,respectively,which are statistically significant.According to the ROC curve analysis,when RE10 was 66,the sensitivity in prediction of patients with CTP A and CTP B+C was 86.5%and the specificity was 83.3%.when RE20 was 75,The sensitivity in prediction of patients of CTP A and CTP B+C was 86.5%,and the specificity was 88.9%.ConclusionLiver IVIM-DWI and Gd-EOB-DTPA enhanced MRI can provide safe,effective,repeatable quantitative imaging methods for assessing liver function in patients with chronic viral hepatitis.Which is expected to perform an evaluation of segmental liver function damage. |
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