Experimental Research Of Superparamagnetic Iron Oxide Nanoparticles Distribution Change In The Diethylnitrosamine SD Rats Induced Cirrhosis Liver Cancer Formation Process

Hepatocellular carcinoma is one of the most common malignant tumor in our country.Due to HCC early symptoms conceals, combining incidence of cirrhosis is extremely high, poor liver function reserve, patients are middle-late, resection rate is low, and high recurrence rate after resection.Therefore, early diagnosis and treatment of HCC is facing enormous challenges.This experiment established animal models like human cirrhosis liver cancer occurrence and development process,by giving SD rats for small doses of diethylnitrosamine free drinking.Dynamic analysised in the process of induced cancer in different periods Kupffer cells in diseased tissue after phagocytosing superparamagnetic iron oxide of MR imaging performance and pathology contrast.Studied of SPIO distribution changes in different pathological organization in the process of inducing cirrhosis liver cancer.Not only can assess the function of Kupffer cells, and early diagnosis of liver diffuse lesions, detection of malignant liver lesions and for molecular imaging research has important clinical value and significance.This study mainly includes three parts.The first part:Establishing SD rats cirrhosis liver cancer model and MR imaging performancesObjective:To establish rats cirrhosis liver cancer model,research liver cancer detection rate before and after SPIO enhanced under the background of cirrhosis liver cancer.Methods:30male SD rats were randomly divided into the experimental group(n=20) and the control group(n=10), the experimental group to0.1mg/ml of DENA solution free drinking, the control group to sterilization physiological saline. After the treatment20W respectively took rats and performed plain MR with T1WI、T2WI、T2*WI and SPIO enhanced MR.Calculated SIR、CNR and PSIL.Took greater than2mm focal nodules,counted the inspection number of before and after enhancing MRI the sequence and pathology. Analysised specimens with HE staining.Results:Experimental group of rats levels [(130.43±8.83) and (415.00±55.44) U/L respectively] were significantly higher than the control group [(39.57±7.25) and (132.93±39.03) U/L respectively](P<0.001). Liver cancer nodules showed slightly low, equal and slightly high signals in T1WI plain scan,the detection rate was46.88%,high and slightly high signal and mixed signals in T2WI plain scan, detection rate was84.38%,equal and slightly high signals in T2*WI plain scan,detection rate was53.13%.The total detection rate among them has statistically difference (P<0.001).Injected SPIO after1h then enhancing scanning, T1WI sequences liver cancer detection rate was71.88%, T2WI was94.79%, T2*WI was91.67%, there was statistical significance among them (P<0.05).However before and after the enhancement liver cancer detection rate difference on T2WI without statistical significance (P>0.05), T1WI and T2*WI was statistically significant (P<0.001).SIR on each sequence were lower than plain scan (P<0.001). Liver canoer tissue SIR had no obvious change before and after enhancement (P>0.05).The T2*WI sequence PSIL value was the largest, T2WI second,T1WI least,their difference had statistical significance (P<0.001). Liver cancer tissue PSIL values in each sequence comparison statistically significant differences was not found (P>0.05).On each sequence CNR was significantly improved than pre-enhancement,the difference was statistically significant (P<0.05).Conclusion:Diethylnitrosamine induced SD rats model of liver cirrhosis liver cancer was close to the human cirrhosis liver cancer occurrence and development process. Through SPIO enhance MR scanning can effectively enhance the liver tumor and normal liver tissue signal intensity ratio,and enhance detection rate of small hepatocellular carcinoma under the background of cirrhosis.The second part:Study on the phagocytic activity of Kupffer cells with SPIO-enhanced MR Imaging in SD rats with Cirrhosis liver cancerObjective:To research the relationship between SPIO enhanced MRI signal performances and Kupffer cells in different pathological organization in cirrhosis liver cancer formation process.Methods:30male SD rats, respectively established simple cirrhosis model10,cirrhosis liver cancer model10, and control group10.Respectively before and after SPIO enhanced scan.Calculated PSIL.Specimen were done HE and Perl’s blue staining.Analysised the relationship between enhanced signal change and the number of Kupffer cells of lesions.Results:After injected SPIO lh,normal liver tissue signals in each sequence uniform declined obviously, simple cirrhosis of the liver tissue mild homogeneous down, compared with normal liver tissue, cirrhosis of the liver tissue adjacent to carcinoma uneven declined, and hepatocellular carcinoma tissue signal had no obvious change.In the same sequence each different lesion tissues PSIL comparison difference had statistical significance (P<0.001), normal liver tissue PSIL value in each sequence was the largest,simple cirrhosis of the liver tissue and cirrhosis of the liver tissue adjacent to carcinoma were in turn, liver tissue PSIL was minimal-Perl’s blue staining showed the blue dye particles amount of the normal liver tissue was the most, simple cirrhosis tissue slightly reduce, but the difference between them was not statistically significant (P>0.05). Carcinoma side cirrhosis tissue blue dye particles was least than before two kinds of organization. Liver cancer tissue had a few or even no blue dye particles. The four different liver organizational blue dye particles number had statistical significance (P<0.001). There was a Linear correlation trend between PSIL and blue dye particles amount (P <0.001).Conclusion:Through SPIO enhance MR scanning not only can indirectly reflect different pathological changes organization Kupffer cell number and function change of state, but also for the early diagnosis of diffuse liver disease and malignant liver lesions detection had important clinical value and significance.The third part:perimental research on using MRI assessment superparamagnetic iron oxide nanoparticles distribution change in Cirrhosis liver cancer tissueObjective:To research superparamagnetic iron oxide nanoparticles (SPIO) as MRI contrast agent distribution changes in cirrhosis liver cancer organization, then to investigate the feasibility of using in molecular target imaging.Methods:Established cirrhosis liver cancer model25, and control group10.After the treatment20W performed plain MR and SPIO enhanced MR, after injection SPIO1h,24h,48h,72h and96h respectively scanning, every time5rats, control group take2, after scanning immediately executing. Analysising the MR images, and doing HE and Perl’s blue staining.Results:After injection SPIO1h, signals of the normal liver tissue and carcinoma side cirrhosis tissue declined obviously in each sequence, PSIL value achieved maximum in24h, then after48h,72h and96h successively decreased, their difference had statistical significance (P<0.001). The normal liver tissue signal decreased range was the most in24h. While liver cancer tissue signal no obvious change in each time, there was no statistical significance(P>0.05). Perl’ s blue staining showed the Kupffer cell amount of the normal liver tissue and carcinoma side cirrhosis tissue achieved the most in24h, then phasedown, the normal liver tissue reduction range maximum, there was statistical significance among them (P<0.001). Part of high differentiation of liver cancer tissue had a few scattered Kupffer cells, poorly differentiated liver cancer tissue without Kupffer cells.There was a Linear correlation trend between PSIL and Kupffer cells amount(P<0.001).Conclusion:Through SPIO enhance MR scanning can use to detection of malignant liver lesions, furthermore, become MRI contrast agent used for targeted molecular imaging potential.