Sonographic depiction of changes of tumor vascularity in response to various therapies

Purpose: To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens. Materials and Methods: Tumor cells were implanted subcutaneously in thirty-two mice and assigned to four treatment groups: control, radiation therapy, antiangiogenesis therapy (VEGF [vascular endothelial growth factor] receptor antagonist, SU11248), or combined antiangiogenesis and radiation therapy. Twenty of these mice were scanned with power Doppler sonography at two time points over the course of treatment, and power-weighted pixel densities were assessed. The other twelve mice each underwent subcutaneous placement of a dorsal skin-fold window over the tumor site, allowing for daily angiogenesis assessment of vascular length density. All tumor specimens had correlative histologic analyses performed, including immunohistochemical stains for microvasculature. Results: Sonographic measurements revealed significant longitudinal differences in tumor vascularity among the four treatment groups: control mice receiving no treatment demonstrated a doubling in intra-tumor color pixel density (P < 0.02); those receiving radiation alone increased by 68% (P < 0.04); those receiving oral therapy alone increased by 44% (P = 0.016); and those receiving combination therapy decreased by 38% (P < 0.02). Tumor vascularity independently measured in the twelve mice with the skin-fold windows revealed a similar response to each type of treatment. Post-mortem tumor histology was consistent with both sonographic and skin-fold window measurements. Conclusion: Power Doppler sonography was accurate and reliable in measuring tumor vascularity changes in this model. These results were independently confirmed by a quantitative method relying on direct visualization of the microvasculature. Because it is rapid and non-invasive, sonographic quantification is beneficial in assessing the anti-angiogenic effects of various treatment strategies for cancer.