| Part I Establishment of implanted rat model of liver cancer and histopathological findings.Objective:To study the feasibility of establishing a rat model of liver cancer by direct injection of Walker/LLC-WRC 256 ascites tumor cell suspension.Methods:24 healthy male SD rats were randomly divided into 2 groups,one group with 20 rats for establishing rat model,the other group with 4 rat for blank control group.Establishment of rat model:0.5ml Walker/LLC-WRC 256 tumor strains(about 0.5×107 cells)were injected into the abdominal cavity of weaning mice for seed preservation and passage,the above process was repeated after 7 days for two consecutive times.After passage,cancerous ascites were centrifuged and concentrated to obtain semi-liquid suspension of concentrated tumor cells,which were directly injected into the left lobe of rat liver at a dose of 0.05ml(about 5×106 cells).The incision was disinfected regularly after the operation to prevent infection.Control group:rats freely drank water,fed food,and no cancerous ascites were injected into the liver.The modeling group was divided into group for 5 day,group for 6 day,group for 7 day and group for 8 day according to the modeling period,5 rats in each group,those rats were examined by liver MRI.Rats in the modeling group and the control group were sacrificed immediately after the scanning,and the general liver condition,tumor morphology,size,whether there is metastasis in the abdominal cavity,and histopathological examination of the rats were observed.Results:16 rat models of liver cancer were established successfully,with a total of 18 lesions,and the positive rate of inoculation was 80%.The macroscopic appearance of tumor nodules were nodular or irregularly shaped yellow-white fish-like fleshy tissue with clear boundaries.Hemorrhage and necrosis could be seen in the center of some large tumors.HE staining showed that tumor cells arrange disorderly,with different sizes,shapes,deep-dyed big nucleolus,mitotic figures and marked pleomorphism.There was patchy necrosis without nuclei among some tumor cells.The rats in the control group had soft liver texture,smooth surface and luster.No tumor nodules were found on the surface and inside of the liver.HE staining showed normal structure of the hepatic lobule.The hepatocyte cords were arranged regularly and densely,and dispersed radially to the periphery.The cells were free of degeneration,necrosis,and the nucleus was rounded,and no mitotic figures were observed.Conclusion:The rat model of liver cancer can be established successfully by direct injection of Walker/LLC-WRC 256 tumor strains.Part ? The value of MRI diagnosis of situ implanted liver cancer in rats by nano contrast agent manganese hexacyanoferrate potassiumObjective:To explore the diagnostic value and pathological basis of enhanced MR imaging of implanted rat model of liver cancer established by Walker/LLC-WRC 256 tumor strains with manganese hexacyanoferrate potassium nanoparticles.Methods:20 modeling rats were subjected to serial plain scanning of TSE-T1WI and TSE-T2WI-SPAIR using a Achieva 1.5 T superconducting magnetic resonance imager(Philips,The Netherlands)and a Microscopy 4.7 cm microcoil(Philips,The Netherlands).then,the manganese hexacyanoferrate potassium nano contrast agent KMn[Fe(CN)6]was injected into the tail vein,with the concentration of 45mmol/L and the injection dose of 1ml/300g weight.MR enhanced scanning of the liver was performed at 5min,30min,1h and 2h after the injection respectively.After MR scanning,all rats were sacrificed immediately and these liver tissue was taken for histopathological examination.The ROI was delineated by ViewForum4.1 software and the normal liver tissue(SI Liver)and the tumor(SI lesion)and background noise signal intensity standard deviation(SD)were measured at each time point before and after enhancement,and calculated the signal-to-noise ratio(SNR)of normal Liver tissue and tumor tissue,and absolute value of contrast to noise ratio(|CNR|)respectively.Then,rendering the SNRLiver-time,SNRLesion-time and | CNR |-time curve.The SNRLiver,SNRLesion and |CNR| in T1WI and T2WI before and after enhancement were compared using anova of single-factor repeated measurement.Results:The SNRLiver values before and after T1WI enhancement were:71.61±3 3.26?96.21 ±46.08?105.08±44.54?94.74±44.19?90.15±40.17.The SNRLesion values before and after T1WI enhancement were:52.70±26.97?52.77±26.77?53.57±26.82?52.95±26.07?53.00±26.48.|CNR| values before and after T1WI enhancement were:18.91±12.44?43.44±24.51?51.51±22.39?41.79±22.66?37.15±19.16.The difference between SNRLesion values before and after T1WI enhancement was not statistically significant(P>0.05),while the statistical difference between the SNRLiver values and ICNRI values before and after T1WI enhancement were highly significant(P<0.01),and compared with the pre-enhancement,there was statistical difference in SNRLiver values and|CNR| values(P<0.05).The SNRLiver values before and after T2WI enhancement were:16.38±6.54?6.95± 1.68?5.54± 1.64?3.97± 1.44?5.60±1.96.The SNRLesion values before and after T2WI enhancement were:34.55± 15.77?34.45± 15.62?34.49± 15.58?34.55± 15.51?34.49± 15.73.|CNR| values before and after T2WI enhancement were:18.17±9.96?27.50±14.68?28.95± 14.97?30.58± 14.63?28.89±14.34.The difference between SNRLesion values before and after T2WI enhancement was not statistically significant(P>0.05),while the statistical difference between the SNRLiver values and ICNRI values before and after T2WI enhancement were highly significant(P<0.01),and compared with the pre-enhancement,there was statistical difference in SNRLiver values and |CNR|values(P<0.05).Prussian blue staining showed that the blue-stained KMn[Fe(CN)6]nanoparticles were clustered in the Kupffer cells of hepatic sinus region,while noblue-stained particles were observed in liver cancer lesions.Conclusion:nano contrast agent KMn[Fe(CN)6]has T1 positive enhancement effects and T2 negative enhancement effect for the normal liver tissue with T1-T2 dual modal contrast agent characteristics,and time window of imaging is wide.However,Kupffer cells are scarce in liver cancer,the image signal in T1WI and T2WI has no obvious change.Then,nano contrast agent KMn[Fe(CN)6]is helpful for the detection and qualitative diagnosis of liver cancer... |
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