Comparing Parameters Of Muscle VX₂ Tumor Vascularization In Rabbits Assessed By Contrast-Enhanced Ultrasonography And Dynamic Enhanced MRI

Background: Angiogenesis is not only morphological foundation for growth and spread of malignant tumors but also correlative with invasion and prognosis. In recent years, the study of angiogenesis has been gaining more consideration in medical field. Currently microvessel density is acknowledged as the gold standard to evaluate tumor angiogenesis. However, it can't become a perfect method because of its deficiency such as invasion, the dependence on sampling and so on. In our study, we designed an muscle VX2 tumor model to investigate and compare the application value of contrast enhanced ultrasonography(CEUS) and dynamic enhanced MRI in evaluating tumor vascularization of soft tissue. The perfusion of muscle VX2 carcinoma in rabbits was assessed by low mechanical-index real-time CEUS and dynamic enhanced MRI, meanwhile dynamic parameters were compared and correlated with microvessel density(MVD) /vascular endothelial growth factor(VEGF).Objective To investigate and compare the application value of contrast enhanced ultrasonography and dynamic enhanced MRI in evaluating tumor vascularization of soft tissue.Methods VX2 tumor suspension was injected in bilateral thighs of 10 New Zealand white rabbits to establish the model of muscle VX2 tumor in rabbit thighs. After 14-21 days, the rabbits were examined with CEUS after a bolus of SonoVue, then examined with dynamic enhanced MRI using Gd-DTPA. Their time-intensity curve of tumor was drawn and the dynamic parameters were calculated. These parameters include time to peak, peak intensity, ascending slope, area under curve, peak height and steepest slope. Then tumor specimens were stained with an endothelial cell marker named CD34. MVD was counted and VEGF was analyzed quantitatively.Results In the 10 rabbits, 18 tumors were established successfully in bilateral thigh muscle of nine rabbits, besides one rabbit died of anesthesia. Positive correlation was found between VEGF Score and MVD of tumor. Time-intensity curves of tumor were different from that of surrounding muscle tissue. The peak intensity(PI) and ascending slope(AS) and area under curve(AUC) of tumor were 0.45±0.13,0.041±0.022 and 21.61±8.42 respectively, which were higher than normal muscle. The time to peak was 13.81±4.15, which was lower than normal muscle.There was a correlation between MVD and the dynamic parameters(such as TTP, PI, AS, AUC, PH and Smax assessed by CEUS and dynamic enhanced MRI. The correlation coefficients were -0.478, 0.516, 0.585, 0.646, 0.554 and 0.574. The enhancement extent of tumor with different expressing VEGF is different.Conclusion 1. The model of muscle VX2 tumor in rabbit thigh was established successfully in our experiment. It is proved that the model is a practical and reliable tool that could be used for researching the tumor of soft tissue. 2. CUES can show better the small vessel and low speed blood flow. So it can be used to observe the perfusion of tumor and provide a non-invasive method to evaluate the antitumor effect. 3. There is a positive correlation between MVD and the dynamic parameters such as PI, AS, AUC, PH and Smax. Among these parameters, AUC is the best when correlated with MVD. CEUS can provide more valuable information in evaluating angiogenesis, guiding the clinic diagnosis, estimating prognosis of tumor in soft tissue.