Characterization of tumor vasculature distributions in central and peripheral regions based on Doppler ultrasound

Tumor heterogeneity is a major obstacle to therapy, and thus, how to achieve the maximal therapeutic gain in tumor suppression is an important issue. To accomplish this goal, assessing changes in tumor behaviors before treatment is helpful for physicians to adjust treatment schedules. In this study, the authors longitudinally and spatially investigated tumor perfusion and vascular density by power Doppler imaging and immunohistochemical analysis, respectively. Moreover, the authors developed a method to describe quantitatively the spatial distribution of the vasculature within the central and peripheral regions of tumors.Tumor perfusion was estimated by power Doppler images at an operating frequency of 25 MHz. To avoid the attenuation effect of such high-frequency ultrasound, murine tumors were subcutaneously transplanted into the thighs of mice and then monitored for 11 days. The tumors were removed at various time intervals for immunohistochemical analysis of their vascular density using CD31 staining. The spatial characteristics of the tumor vasculature were quantified by a γ value, which characterizes the rate at which vascular signals increase with the fractional sizes of the peripheral area within the tumor.During tumor progression, the volume of tumor perfusion in the power Doppler images was strongly correlated with the vascular density determined by immunohistochemical analysis. In addition, the γ value significantly decreased with increased tumor size in the power Doppler images but not in the immunohistochemical analysis.Although the tumor perfusion and vascular density estimates showed good temporal correlations during tumor progression, they did not show good spatial correlations due to tumor perfusion patterns changing from homogeneous to heterogeneous. In contrast to the perfusion patterns, the vascular density of the tumor remained uniformly distributed. In the present study, no necrosis regions were found in the tumor experiments. Furthermore, the measurement of γ value is a simple method for assessing the vasculatures of spatial distribution within tumors.