Clinical Imaging Study Of Pancreatic Duct Stones And Preliminary Study On Fibrotic Molecular Imaging In Chronic Pancreatitis

Part 1 Quantitative factors of unenhanced CT for predictingfragmenting efficacy of extracorporeal shock wave lithotripsy onpancreatic duct stonesObjective: To find potential predictors at unenhanced computed tomography(CT)to evaluate the stone clearance rate(SCR)of pancreatic duct stones(PDS)by extracorporeal shock wave lithotripsy(ESWL).Methods: Including 106 patients with multiple pancreatic duct stones who were treated in our hospital from 2014 to 2016,the stones were all located in the head of the pancreas.All patients receive ESWL treatment.The number of shock waves per treatment was not more than 6,000.Stop ESWL treatment when the diameter of the stone is less than 3mm by X-ray fluoroscopy.Toshiba 320-slice spiral CT was used for upper abdominal scan before and after ESWL treatment.The Philip workstation was used to perform three-dimensional reconstruction of the image and measure the quantitative indicators.Calculate SCR based on changes in stone volume before and after treatment,we define the volume of stones before and after treatment as V0 and V1.SCR=[(V0)-(V1)]/(V0)×100%,and patients divided into three groups with threshold values of >90%,50-90% and <50% of SCR.The clinical characteristics of the patient's gender and age were recorded and number of ESWL treatment.The following indicators were measured on the CT image before treatment: the maximum transverse length(MTL)of the stone,the mean stone density(MSD)of the stone,and the standard deviation of the stone density(SDSD),variation coefficient of stone density(VCSD),pancreatic duct diameter(PDD),skin-stone distance(SSD),HU density(HD),where HD = MSD/MTL.Measurement data were expressed as ±S,and count data were expressed as N(%).First,univariate ordered logistic regression was used to analyze the differences between groups of clinical features and imaging features among groups A,B and C,and single-variant screening was performed.Then,the statistically significant variables(P<0.20)in the univariate analysis were included in the multivariate ordered logistic regression,and the independent predictors of SCR were screened.P<0.05(test level)was considered statistically significant.Statistical analysis was performed using IBM SPSS statistical software(version 21.0,Chicago,III).Results: This study included 106 cases,including 71 males and 35 females.The average age was 45.2 ± 13.3 years(minimum-maxima: 12-75 years).The size of the pre-calculus stone MTL ranged from 3.1 to 36 mm,the average volume of the stone was 5647.8±6487.0 mm3,and the average postoperative volume was 1918.8±2944.0 mm3.All patients received number of ESWL treatment ranging from 1-8 times,with an average of 2.5 ± 1.3 times,with an average SCR =(65.0 ± 25.9)%.VCSD is an independent predictor of predicting ESWL SCR(P=0.025).Conclusions: VCSD is an independent predictor of the efficacy of ESWL in the treatment of patients with pancreatic duct stones.The smaller the VCSD,the better the removal effect of pancreatic duct stones.Part 2 Quantification and Differentiation of Composition of MixedPancreatic duct stones Using Single-source Dual-Energy CT: An ExVivo StudyObjective: To evaluate the feasibility of using Single-source dual-energy CT(DECT)to quantify and differentiate calcium carbonate(CA)and non-calcium carbonate(NCA)components of pancreatic duct stones(PDS)with mixed composition.Methods: A total of 12 PDS harvested from general surgery department in our hospital were analyzed with micro-CT as a reference standard for CA and NCA composition.These stones were placed in a TOS water phantom of 35 cm diameter to simulate standard adult body size.High and low energy image sets were acquired from SS DECT scans with high/low tube potential pairs of 80 k Vp/140 k Vp.All the image sets were imported into an in-house software for further post-processing.CT number ratio(CTR),defined as the ratio of the CT number at 80 k Vp to 140 k Vp,was calculated for each pixel of the images.Threshold was preset between 1.00 and 1.25 to classify CA and NCA components.Pixels in PDS with CTR higher than the threshold were classified as CA,and those with CTR lower than the threshold were classified as NCA.The percentages of CA and NCA for each stone were determined by calculating the number of CA and NCA pixels.Finally,the minimal,maximal and root-mean-square errors(RMSE)of composition measured by SS DECT under each threshold were calculated by referring to the composition data from micro-CT.The optimal threshold was determined with the minimal RMSE.A paired t-test was used to compare the stone composition determined by DECT with micro-CT.Results: The optimal CTR threshold was 1.16,with RMSE of 6.0%.The minimum and maximum absolute errors were 0.22% and 11.35%,respectively.Paired t-test showed no statistically significant difference between DECT and micro-CT for characterizing CA and NCA composition(p=0.414).Conclusions: SS DECT is a potential approach for quantifying and differentiating CA and NCA components in PDS with mixed composition.Part 3 Molecular MRI of Collagen to Diagnose and Stage PancreasFibrosisObjective: To establish mouse models with different degrees of pancreatic fibrosis and prepare for fibrosis molecular MRI.To investigate the feasibility and application value of molecular MRI with gadolinium type I collagen targeted probe(EP3533)in the diagnosis and grading of pancreatic fibrosis.Methods: We randomly divide 42 male C57 BL / 6 mice into control group,mild pancreatic fibrosis group and moderate-to-severe pancreatic fibrosis group.They were intraperitoneally injected with normal saline(control group)and cerulein(50 ?g/kg)or ethanol(3g/kg,33%)combined with cerulein independently,the entire modeling cycle lasts 6 weeks.After the models were established,four mice in each group were injected intravenously with Cy5.5-EP3533(500 g Cy5.5/ kg)which was synthesized in advance.One hour later,the mice were sacrificed and the pancreas was taken out and placed in a small animal optical imaging system for quantitative fluorescence observation.The remaining three groups of model mice were injected with EP3533(20 mol/ kg)via the tail vein,and T1 WI images were collected multiple times within 5 to 60 minutes after the enhancement.After the the scan,the mice were sacrificed and the pancreas was taken for pathological evaluation and fibrosis grading.To ensure complete metabolism of Gd-DTPA,mice in the moderate-to-severe pancreatic fibrosis group were injected with non-targeted contrast agent Gd-DTPA(100 mol/ kg)72 hours before injection of EP3533,and T1 WI images were collected multiple times within 5 to 60 minutes after enhancement.The ROI was delineated at the pancreas level of the T1 WI image,and the SNR value and ? SNR value at each time point before and after enhancement were measured.The degree of enhancement at different time points after EP3533 enhancement in different groups of mice was compared.The comparison between the two related samples was performed by paired sample t test or signed rank test;the repeated measurement data were analyzed by repeated measures analysis of variance for comparison between groups.Statistical analysis was performed using SPSS 21,and the test level ? was taken as 0.05 on both sides.Results: Pathologically confirmed pancreatic fibrosis changes in the mild pancreatic fibrosis group and moderate to severe pancreatic fibrosis group,which were confirmed by pathology and the fibrosis grade of the latter was higher than the former.Mice with moderate to severe pancreatic fibrosis received Gd-DTPA and EP-3533 enhanced scans,and the SNR of pancreas reached a peak of 46.02±9.5 after 5 minutes of Gd-DTPA injection.The pancreatic SNR decreased sharply during the 5-60 min period,and the pancreas SNR decreased to 60 min.It has been reduced to 33.82±7.08;after the metabolism of Gd-DTPA is complete,the SNR of pancreas in mice with severe pancreatic fibrosis in the same group reaches 41.42±8.91 5 min after EP3533 injection,and the pancreatic SNR continues to increase gradually in the period of 5-60 min.The pancreatic SNR peaked at 51.85±7.35 at 40 min,and the pancreatic ?SNR at 40 min in the EP3533 group was significantly higher than that in the Gd-DTPA group(p<0.001).The pancreatic ?SNR at 30 min,40 min,and 60 min after EP3533 injection showed moderate to severe fibrosis > mild fibrosis > control group.After repeated measures analysis of variance,it was found that there was interaction between time and group(p <0.01),so no main effect analysis was needed,and the individual effect analysis of the treatment group was directly performed.Inter-group effect analysis of variance showed that the differences between the three groups were statistically significant(p<0.001).Further,three groups of models at the above three time points were compared by LSD-t test.The ?SNR between the two mice showed that the difference in pancreatic ?SNR between the control group and the mild fibrosis group was statistically significant at 30 min(p=0.011);the difference in pancreatic ?SNR between the control group and the moderately severe fibrosis group statistically significant(p < 0.001);the difference in pancreatic ?SNR between the mild fibrosis group and the moderately severe fibrosis group was statistically significant(p = 0.001).At 40 min,the difference in pancreatic ?SNR between the control group and the mild fibrosis group was statistically significant(p<0.001);the difference in pancreatic ?SNR between the control group and the moderate-severe fibrosis group was statistically significant(p<0.001);The difference in pancreatic ?SNR between the fibrosis group and the moderately severe fibrosis group was statistically significant(p=0.005).At 60 min,the difference in pancreatic ?SNR between the control group and the mild fibrosis group was statistically significant(p<0.001);the difference in pancreatic ?SNR between the control group and the moderate-severe fibrosis group was statistically significant(p<0.001);The difference in pancreatic ?SNR between the fibrosis group and the moderately severe fibrosis group was statistically significant(p < 0.001).One hour after Cy5.5-EP3533 injection,the fluorescence intensity of normal pancreas,mildly fibrotic pancreas and moderately severe fibrotic pancreas increased in turn.Conclusion: We successfully established two mouse models of different degrees of pancreatic fibrosis,and the pathogenesis mimics human alcoholic chronic pancreatitis.The ?SNR of EP3533 at 30 min,40min,and 60 min can help identify mouse models of different degrees of fibrosis.