High-frequency ultrasonic measurement of vascularization in phantoms and Avastin-treated mice with breast tumors

Abstract

Tissue vascularization is an important aspect of tissue engineering and oncology. The objective of this study was to determine if direct ultrasonic measurements in the 10–100 MHz range could be used as an in vivo vascularization assay. To simulate vascularization of tissue, phantoms were fabricated from agarose gel inclusions embedded in a gelatin-soluble fiber mixture. Ultrasonic tests were performed using two broadband ultrasonic transducers centered at 50 MHz. Results showed the samples with multiple agarose vasculature structures decreased the ultrasound wavespeed. As the level of vasculature decreased, the wavespeed of the ultrasound increased. Further investigation of vascularization included the in vivo evaluation of grafted breast cancer tumors in mice. The experimental group was composed of mice treated with Avastin, an angiogenesis inhibitor. The heterogeneity of the vasculature in the control tissue resulted in the scattering of the ultrasound, decreasing the wavespeed. Because the treated group contained less vascularized, more homogeneous tissue, the wavespeed was significantly higher. Results from both the phantom and mouse tumor studies revealed that the ultrasound wavespeed was inversely proportional to the level of vasculature. The results indicate that direct ultrasound wavespeed measurements in the 10–100 MHz range can be used to identify vascularization in tissue.