Acoustic angiography of tumor vascular perfusion following high intensity focused ultrasound ablation

Perfluorocarbon contrast agents, both microbubbles and nanodroplets, are known to enhance high intensity focused ultrasound (HIFU) ablation. While it is known that HIFU ablation reduces vascular perfusion in tissue these effects have not been mapped with high-resolution imaging, such as acoustic angiography. We aimed to determine the acute and chronic effects of HIFU on tumors in the presence and absence of both microbubbles and nanodroplets. Pulsed HIFU (2 MPa, 1 MHz, 10% duty cycle, 1 Hz PRF for 5 s) was delivered to flank fibrosarcoma tumors (n=9). During HIFU, 4.5×10⁸ microbubbles or nanodroplets were infused via tail vein catheter (n=3 per group). Tumor perfusion was assessed 15 minutes and 72 hours after HIFU delivery. Only microbubbles resulted in a significant reduction in vascular perfusion (66.2±15.2%, p<0.05). Both nanodroplets and microbubbles reduced the growth rates of tumors, although not significantly. Tumors treated with microbubbles and nanodroplets during HIFU resulted in only 121±41% and 106±47% volume increases respectively compared to 177±65% for HIFU-only treated controls. These results suggest that vascular perfusion can be drastically reduced, and tumor vasculature can be remodeled with sub-ablative HIFU. Low pressure HIFU when combined with microbubbles has the potential to enhance the safety of HIFU therapy. The acoustic angiography technique applied herein is especially applicable for determining sub-ablative effects of ultrasound and contrast agents on vascular perfusion.