The Experimental Study On Functional MR Imaging In The Evaluation Of Interventional Therapy Response Of Rabbit Extremity Soft Tissue Sarcoma

PART1The Application of Single Voxel Proton Magnetic Resonance Spectroscopy(SV-¹ HMRS) in Evaluating the Intervational Therapy Response of VX2 Soft Tissue Sarcoma in the Forelimb of RabbitObjective:To evaluate the primary application of conventional MRI and Single Voxel proton magnetic resonance spectroscopy(¹H MRS) in evaluating the intervational therapy response of VX2 soft tissue sarcoma in the proximal forelimb of experimental rabbit by comparing the ratio of the peak of Choline/Lipids called ratio_amp and the ratio of the area under the curve of Choline/Lipids named ratio_area measured on the spots of pre-interventional therapy and six and twenty four hours after interventional therapy respectively.Materials and Methods:Forty healthy New Zealand white rabbits,1.5-2.5kg weighted and 2-3 months old,were included in this study.0.15-0.2ml tumor tissue suspensions were injected into the proximate of rabbit forelimb(unilateral in the left side for 25 rabbits of male or female and bilateral for 15 males).All the rabbits underwent conventional MRI and MRS(PRESS sequence with VOI of 1.5-2.25cm³,FWHM of 8-14HZ and the suppression of water＞95%) examinations at the second to third week after implantation of the tumor tissues.Then interventional therapy was performed in the fifteen rabbits implanted bilaterally, among which ten rabbits survived exceed one day.And conventional MR imaging and single voxel proton MRS were carried out at the sixth and twenty-forth hour after interventional therapy.Post-processing was done at the ADW4.3 workstation,using the SAGE software.The data were analyzed with ANOVA by SPSS 15.0 statistical software(α=0.05).Results:Except for one,the others of fifty-five rabbits succeeded in tumor transplantation with the tumor diameters of 2,4.5 and 5 cm at the time of the forteenth,twenty-first and twenty-eighth day.The tumors were small and hard with little necrosis during two weeks.As to MRI signal intensity,the tumor showed iso-intense for parenchyma without heamorrage on T1W images and heterogeneous hyperintense on T₂WI with still high signal intensity for inner necrosis and surrounding edema areas,and showed apparent enhancement even more conspicuous in the tumor periphery after adminstration of Gd-DTPA.49 animal models had obvious Choline peak(higher than Creatine peak) at 3.2ppm distinguished from the normal muscle tissues,with the ratio_ampand ratio(area)(Mean±SD) were 0.38±0.17 and 0.22±0.16 respectively.On the spots of pre-interventional therapy and six and twenty four hours after interventional therapy,the ratioamp and ratioarea were 0.37±0.14, 0.28±0.13,0.24±0.11 and 0.25±0.18,0.17±0.22,0.10±0.14 respectively without any statistical difference.Histologically,tumors were composed of large,uniform,oval /round cells arranged in solid nests which was intensive in the periphery of tumors, with abundant nucleus rare cytoplasm.Necrosis was apparent in the interventional therapy group.Conclusions:It is possible to apply single voxel ¹H MRS to evaluate the intervational therapy response of VX2 soft tissue sarcoma in the forelimb of rabbit. Tumor parenchyma has a higher peak of Choline than that of Creatine,which is distinctive from the normal muscle tissue.Although the ratioamp and ratio(area) are decreasing after interventional therapy,there is no statistical difference.It seems to be inaccurate to make the Lipid peak as an internal standard. Objective:To investigate the primary application of T2*-weighted echo-planar perfusion MR imaging in rabbit VX2 soft tissue sarcoma model by comparing the values of NI(Negative enhancement intergral represented to rBV) and MSD (Maximum slope of decrease represented to rBF) between VX2 tumor parenchyma and normal muscle tissue and by analyzing the correlation between ratio^MI(tumor parenchyma/muscle),ratioMSD(tumor parenchyma/muscle) and ration_MVD(tumor parenchyma/muscle).Materials and Methods:Twenty-five adult New Zealand white rabbits(1.5-2.5kg,2-3months old) were implanted VX2 tumor tissue suspension into the intramuscular proximal deep of the left forelimb.Conventional MR and T2* first pass perfusion- weighted imaging(T2*-PWI) were performed 2-3 weeks later after the implantation of VX2 tumor.Twenty-three cases succeeded in performing the T2*-perfusion-weighted MR imaging,and 10 of 23 animals were randomly executed for HE and IHC(Immunohistochemisty) stained(CD34).Post processing was done at the ADW4.3 workstation.The ratio_NI(tumor parenchyma/ muscle),ratio(MSD)(tumor parenchyma/muscle) and ration(MVD)(tumor parenchyma/ muscle) were calculated and their correlations were analyzed.The data were analyzed with Wilcoxon signed-rank test,paired t-test and Pearson analysis by SPSS15.0 statistical software(α=0.05).Result:The NI values of tumor and normal muscle had obvious statistical difference(t＝-3.285,P＝0.003＜0.05),which exhibited a higher value of NI_tumor than that of NI_muscle(234.32±175.46,114.61±94.40).And the value of MSDtumor(393.73±227.30) was much more higher than that of MSD_muslce(154.44±69.20),which also showed a significant statistical difference(z＝-4.167,P＝0.000＜0.05) of the MSD values between the tumor and normal muscle tissues.The Ratio_NI and ration_MVD values had significant positive correlation(r＝0.779,P＝0.008＜0.05). However,there is no apparent correlation between ratio_MSD and ration_MVD values. Conclusions:T2* perfusion-weighted MR imaging describes the fist pass of blood through capillaries,which reflects the blood perfusion atraumaticly.It seems to be different significantly in the haemodynamics parameters between the tumor parenchyma and normal muscle tissues,which indicates the value of PWI in evaluating the intervational therapy response of VX2 soft tissue sarcoma in the PART3The Value of Diffusion-Weighted MR Imaging(DWI) in Evaluating the Intervational Therapy Response of VX2 Soft Tissue Sarcoma in the Forelimb of RabbitObjective:To evaluate the possibility of the primary application of diffusion-weighted MR imaging(DWI) in evaluating the intervational therapy response ofVX2 soft tissue sarcoma in the forelimb of rabbit by comparing the ADC value selected an optimal b value of tumor parenchyma,normal muscle and necrosis;and by comparing the ADC values pre-and post-interventional therapy between the study and control groups.Materials and Methods:Forty healthy New Zealand white rabbits,1.5-2.5kg weighted and 2-3 months old,were included in this study.0.15-0.2 ml tumor tissue suspensions were injected into the proximate of rabbit forelimb(unilateral in the left side for 25 rabbits of male or female and bilateral for 15 males).All the rabbits underwent conventional MRI and DWI examinations after 2-3 weeks,with b values at 200,400,600,800 and 1000 s/mm².Post processing was done at the ADW4.3 workstation.The data were analyzed by SPSS15.0 statistical software(α＝0.05). Results:54 of all the 55 rabbits were successfully transplanted VX2 tumor. Diffusion-weighted MR imaging was affected by T₂ shine through effect with a low b value(200 s/mm²),and the signal-to-noise ratio would decrease with a large b value (1000 s/mm²).ADC values(Mean±SD) of the tumor parenchyma were 1.56±0.11, 1.32±0.12,1.25±0.10,1.19±0.08 and 1.14±0.07 while b values were 200,400,600, 800 and 1000 s/mm² respectively.Along with the increased b values,the ADC values decreased.We presumed that the ideal DWI parameters might be gotten with b values at 600 or 800 s/mm².There was significant difference between the ADC values of the tumor parenchyma,necrosis and muscle tissues.The ADC value of tumor parenchyma was smaller than those of the necrosis and muscle tissues.In the experimental group the ADC values with b values at 600 or 800 s/mm² had significant statistical differences between pre-interventional therapy and post-interventional therapy on the spots of three,six and twenty-four hours.And the ADC values changed markedly at the prophase after interventional therapy.But it did not show any difference in the control group.Conclusions:It is possible to apply diffusion-weighted MR imaging to evaluate the intervational therapy response of in VX2 soft tissue sarcoma of rabbit extremity.Satisfied DWI can be obtained with moderate b values at 600 or 800 s/mm².Due to disparate ADC values of different tissues,DWI is useful in the discrimination of different tissues.The ADC values change markedly at the prophase after interventional therapy which may be used to monitor the interventional therapy response.Although DWI is more difficult to implement diagnosis ability in the musculoskeletal system than that in the brain,it is likely that DWI may provide some valuable information for differential diagnosis and investigation of the prognosis of soft tissue sarcoma.Furthermore,DWI might be useful in the differentiation between post-therapeutic changes and tumor recurrences of soft tissue tumors due to its distinctive ability between necrosis and viable tumor.