MR Assessment Of The Effect Of Sorafenib In The Treatment Of Liver Cancer In Rats

Part ⅠPreliminary study of magnetic resonance imaging of rat hepatomamodelObjective:Build rat hepatoma model，perform MRI imaging, whichinclude DWI and dynamic contrast-enhanced scans. Select the best b-value ofDWI sequence and compare the strengthening effect of the two contrastagents.Materials and Methods: Wistar rats, male, were made liver cancermodel by planting method.The rats were divided into Gadoxetate Disodiumgroup （A group）and Gadoleric Acid Meglumine Salt Injection group （Bgroup） randomly.Then,all rats underwent MRI scans,which includingT1W1-SE,T2W1-SE,DWI and dynamic contrast-enhanced scans. We chooseb values of50,100,150,400,600,800,1000s/mm~2.The enhanced scan includeddynamic enhancement after injection of contrast medium and hepatobiliaryphase (20min).Three rats which were selected randomly after scanning weresacrificed.Tumor tissue performed pathological staining including HEstaining.Measured the signal value of the liver parenchyma and tumor tissueunder each b value and ADC value, and then calculated the the tumor and liverparenchymal contrast to noise ratio (CNR) and ADC ratio. In dynamiccontrast-enhanced image, designated regions of interest in the liverparenchyma and tumor. Calculate and compare relative enhancement ratio andcontrast to noise ratio(CNR) of the two contrast agents before strengtheningand on the time of reaching peak and hepatobiliary phase.Result:①43of45rats made model successfully.Each rats had an roundliver tumor with the average of the maximum diameter of1.04cm±0.32cm.The mass displayed high signal intensity in the sequence of T2W1andlow signal intensity in the sequence of T1W1.The border of these masses were clear without necrosis and bleeding.②Masses were relatively high signal inthe DWI sequences. As the b value increases, the signals of the tumor andliver parenchyma reduced gradually. The tumor’s CNR were significantlydifferent in each b value(F=2.990, P=0.01).When b value was100s/mm~2,CNR was the best.When b=50,100,150,400s/mm~2,it has no significantdifference among groups,and when b=600,800,1000s/mm~2,it has no significantdifference among groups.As the b value increased, the ADC value reducedgradually. There were significant differences in the ADC ratio of liverparenchyma and tumor in each b value(F value=25.391, P <0.05). When theb value was100s/mm~2, ADC ratios were the best.It was statistically differentcompared with other b values. when b=600,800,1000s/mm~2,it has nosignificant difference among groups.③The A group and B group’s CNR weredifferent before strengthening and on the time of reaching peak andhepatobiliary phase (F=9.630, P=0.002<0.05). The CNR of tumor of thetwo contrast agents were different(F=0.324, P=.003<0.05). Theenhancement ratio of liver parenchyma between two contrast agents weredifferent on time of reaching peak and hepatobiliary phase (F=140.556, P<0.05);Two contrast agents’s enhancement ratio of liver parenchyma weredifferent(F=11.726, P=0.01). The A is higher than B in the peak time andHepatobiliary phase.④The CNR and enhancement rate of hepaticparenchymal between two contrast agents are different in T1W1-SE sequence.The A is better than B. The enhancement ratio of the turmor between the twocontrast agents was not statistically significant.⑤HE staining confirmed ashepatocellular carcinoma;CD34staining showed high vascular density;VEGFstaining was highly expresssd.Conclusion: The CNR and ADC ratio were the best when b was100s/mm~2. The Gadoxetate Disodium is better than Gadoleric Acid MeglumineSalt Injection.PartⅡAssessment of the efficacy of sorafenib treatment in rats with livercancer with magnetic resonance imagingObjective:To assess the efficacy of sorafenib in treatment of rats with liver cancer with MRI.Materials and Methods:40male Wistar rats were selected for model,and they were divided into experimental group (30) and the control group (10).Experimental group rats were gavaged with sorafenib(20mg/kg) for21days,the control group were gavaged with equal doses saline daily. MRI wasperformed before and after treatment, The check sequence includeT1W1-SE,T2W1-SE,DWI,and the dynamic contrast-enhanced T1W1-SE bygadolinium plug disodium. The b Value was set at50,100,150,400,600,800,1000s/mm~2in the DWI sequence. After theinspection, the rats were killed, and tumor tissue isolated from the liver forpathological examination, including HE staining and immunohistochemicalstaining including CD34（MVD）and VEGF. Changes in tumor size,ADCvalues, peak time of Dynamic contrast-enhanced scan,maximum rising slopeand percentage maximum signal strengthening were observed before and aftertreatment in the two groups. The value of MVD and the percentage ofVEGF-positive cells were calculated, and the correlation analysis of thesedatas and MRI images measures.Results:①In the experimental group, size of tumor was1.04±0.067cmand0.64±0.084cm before and after treatment. The size became smaller aftertreatment,with P=0.013,and showed significant differences.②In theexperimental group, when the b value was set at50,100,400,600,800,1000s/mm~2, the ADC value showed significantdifferences with P<0.05before and after treatment. Under the different b value,the ADC value showed significant differences with P<0.05before and aftertreatment.When b value was set at50s/mm~2, the ADC value showed the mostdifference before and after treatment. However, in the control group, the ADCvalue had no significant differences with P>0.05. Under the different b value,the ADC value showed significant differences with P<0.05betweenexperimental and control group,and the most difference was at b value50s/mm~2.③Tumor tissue appeared relatively high signal before injection ofcontrast agent,and heterogeneous enhancement after injection of contrast agent, then reduced gradually.Treated by Sorafenib, TTP were48.78±25.09s and54.50±22.91s before and after treatment,which had no significant differences;MSI were18.61±4.69and9.93±3.33,which showed significant differences;SIRmax were0.87±0.17and0.56±0.18which showed significant differences.In the the placebo,the three indices had no significant differences.④HEstaining showed focal necrosis of the tumor after treatment;MVD wasdecreased significantly after treatment; Before treatment, VEGF was highlyexpressed,but showed low expression after treatment. In control group,MVDwas high denity of blood vessels and VEGF was expressed highly.It showedCorrelation between MVD﹑VEGF and the ADC value﹑MSI﹑SIRmax.Conclusion: It’s effective that Sorafenib treat of liver cancer in rats,andthe efficacy can be assessed by MRI.