Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation

Abstract

A cost-effective method for serial in vivo imaging of tumor microvasculature has been developed.We evaluated acoustic angiography (AA) for visualizing and assessing non-small cell lung tumor (A549) microvasculature in mice prior to and following tumor vascular disruption by vasculartargeted gold nanoparticles (GNPs) and radiotherapy. Standard B-mode and microbubbleenhanced AA images were acquired at pre-and post-treatment time points. Using these modes, a new metric, 50% Vessel Penetration Depth (VPD 50 ) was developed to characterize the 3D spatial heterogeneity of microvascular networks. We observed an increase in tumor perfusion after radiation-induced vascular disruption, relative to control animals. This was also visualized in vessel morphology mode, which showed a loss in vessel integrity. We found that tumors with poorly perfused vasculature at day 0 exhibited a reduced growth rate over time. This suggested a new method for reducing in-group treatment response variability by using pre-treatment microvessel maps to objectively identify animals for study removal.

Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption

“…Here we have shown that although the underlying mechanism of treatment is still vascular disruption, overall tumor growth was still hindered compared to control treatment and long term hypoxia was prevented. This transient vascular disruption was further confirmed by Kwon et al demonstrating an increase in microbubble perfusion 24 hours post therapy followed by normalization to baseline levels, indicative of normalization of tumor vasculature flow [55].…”

B-Mode and Doppler Ultrasonography in a Murine Model of Ehrlich Solid Carcinoma With Different Growth Patterns

“…Vascular flow is important because the volume of the tumor is small, and it is essential for rapid growth; therefore, tumors that achieve more angiogenesis may grow faster (37). In a study quantifying tumor perfusion by acoustic angiography, was observed that an animal of the untreated control group had small tumor growth and exhibited poor perfusion within the tumor compared to the other animals of the same group (39). In contrast, when we analyze the evolution of VI over time, we observe that the FG group has a higher initial VI but tends to decrease over time.…”