Arterial-phase contrast-enhanced ultrasonography for evaluating anti-angiogenesis treatment: A pilot study

AIM:To verify whether arterial-phase contrast-enhanced ultrasonography(CEUS) of tumor parenchymal tissue is useful for evaluation of anti-angiogenesis agents.METHODS:Rabbits with liver tumor were subjected to CEUS,and images of the nodular maximal diameter in vascular phase were recorded.Image analysis was performed to plot the time intensity curve(TIC) at the tumor parenchyma,which set the diameter of the region of interest of intensity measurement.The TIC was calculated to obtain the time to peak intensity(TPI) and the magnitude of PI.Rabbits were randomly assigned to a treatment group with sorafenib and a control group.Two weeks later,the same ultrasound examination was repeated followed by pathological testing to assess the effect of sorafenib on the liver tumor.RESULTS:In four rabbits in the treatment group,the rate of change of tumor size was decreased comparedwith that of the control(the rate 2.3 vs 7.9,P = 0.02).The TPI of the treatment group elongated significantly(the rate 3.1 vs 1.1,P = 0.07 for SonoVue,2.0 vs 0.88,P = 0.09 for Sonazoid).The magnitude of PI showed no significant changes.In pathological examination,capillary diameters in the treatment group were significantly smaller than those in the control group(26.4 vs 42.8 μm,P = 0.013).CONCLUSION:Analysis of the TIC in the arterial phase of tumor tissue could evaluate the efficacy of antiangiogenesis drug treatment in liver tumor.

Image of tumor metastasis and inflammatory lymph node enlargement by contrast-enhanced ultrasonography

AIM:To compare the difference between tumorinduced lymph node enlargement and inflammation-induced lymph node enlargement by contrast-enhanced ultrasonography and pathological findings. METHODS:A model of tumor-induced lymph node metastasis was prepared by embedding a VX2 tumor into the hind paws of white rabbits.A model of inflammation-induced enlargement was prepared by injecting a suspension of Escherichia coli into separate hind paws of white rabbits.Then,a solution of SonazoidTM(GE Healthcare,Oslo,Norway)was injected subcutaneously in the proximity of the lesion followed by contrast-enhanced ultrasonography of the enlarged popliteal lymph nodes. RESULTS:In the contrast-enhanced ultrasonography of the tumor-induced metastasis model,the sentinel lymph node was imaged.An area of filling defect was observed in that enlarged lymph node.In the histology examination,the area of filling defect corresponded to the metastatic lesion of the tumor.Contrast-enhanced ultrasonography of the model on inflammation-induced lymph node enlargement,and that of the acute inflam-mation model performed 3-7 d later,revealed dense staining that was comparatively uniform.The pathological findings showed acute lymphadenitis mainly due to infiltration of inflammatory cells.Contrast-enhanced ultrasonography that was performed 28 d post-infection in the acute inflammation model showed speckled staining.Inflammation-induced cell infiltration and fiberization,which are findings of chronic lymphadenitis, were seen in the pathological findings. CONCLUSION:Sentinel lymph node imaging was made possible by subcutaneous injection of SonazoidTM.Contrast-enhanced ultrasonography was suggested to be useful in differentiating tumor-induced enlargement and inflammation-induced enlargement of lymph nodes.