Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100-300nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1x106 per cm3 resulted in mean lesion volumes of 80.4±33.1 mm3 and 52.8±14.2 mm3 (mean ±S.E.) respectively after 20 seconds of continuous 1 MHz HIFU at a peak negative pressure of 4MPa, compared to a lesion volume of 1.0±0.8 mm3 in agent-free control phantoms.
Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site.
Schematic representation of the changing shape of the vaporization fields (microbubble clouds) with increasing PFC concentrations and acoustic energies. A) The desired shape is a cigar (prolate ellipsoid) centered at the acoustic focal point (white dot). B) Tadpole lesions (asymmetric ellipsoids) occur as vaporization begins to concentrate in prefocal regions. C) Eventually, the microbubble clouds flatten (oblate ellipsoids) and mass along the frontal phantom surface. These shape changes can be appreciated qualitatively and can also be assessed quantitatively by measuring the length of the lateral axis (horizontal white line) and its distance from the central acoustic focal point. Control is considered lost as the lateral axis moves away from the focal point and lengthens.