Sonographic depiction of changes of tumor vascularity in response to various therapies.
OBJECTIVE
To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens.


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.


CONCLUSIONS
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.
Niermann
Kenneth J
KJ
Cancer Imaging Research Fellow, Vanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, Tennessee 37232, USA. ken.niermann@vanderbilt.edu
Fleischer
Arthur C
AC
Donnelly
Edwin F
EF
Schueneman
Aaron J
AJ
Geng
Ling
L
Hallahan
Dennis E
DE
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D003131:Combined Modality Therapy; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000517:prevention & control; D011758:Pyrroles / Q000494:pharmacology; D000077210:Sunitinib; D018615:Ultrasonography, Doppler, Color; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib