Phase-shift perfluorocarbon agents enhance high intensity focused ultrasound thermal delivery with reduced near-field heating

Linsey C. Phillips, Connor Puett, Paul S. Sheeran, Paul A. Dayton, G. Wilson Miller, Terry O. Matsunaga

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

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 (100-300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is 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 0.1 × 106 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 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, 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.

Original languageEnglish (US)
Pages (from-to)1473-1482
Number of pages10
JournalJournal of the Acoustical Society of America
Volume134
Issue number2
DOIs
StatePublished - Aug 1 2013

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Acoustics and Ultrasonics

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