Pulsed-high intensity focused ultrasound (HIFU) exposures for enhanced delivery of therapeutics: Mechanisms and applications

Victor Frenkel, Cheri Deng, Brian E. O'Neill, Jade Quijano, Michael J. Stone, Sergio Dromi, Finie Hunter, Jianwu Xie, Timothy P. Quinn, Bradford J. Wood, King C.P. Li

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed.

Original languageEnglish (US)
Title of host publicationTHERAPEUTIC ULTRASOUND
Subtitle of host publication5th International Symposium on Therapeutic Ultrasound
Pages528-532
Number of pages5
DOIs
StatePublished - May 8 2006
Externally publishedYes
EventTHERAPEUTIC ULTRASOUND: 5th International Symposium on Therapeutic Ultrasound - Boston, MA, United States
Duration: Oct 27 2005Oct 29 2005

Publication series

NameAIP Conference Proceedings
Volume829
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

OtherTHERAPEUTIC ULTRASOUND: 5th International Symposium on Therapeutic Ultrasound
CountryUnited States
CityBoston, MA
Period10/27/0510/29/05

Keywords

  • Enhanced delivery
  • Pulsed-HTFU
  • Radiation forces
  • Tissue displacement

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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