Page 21 - Spring2019

Michael D. Gray
Address:
Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL) Institute of Biomedical Engineering University of Oxford Oxford OX3 7DQ United Kingdom
Email:
michael.gray@eng.ox.ac.uk
Eleanor P. Stride
Address:
Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL) Institute of Biomedical Engineering University of Oxford Oxford OX3 7DQ United Kingdom
Email:
eleanor.stride@eng.ox.ac.uk
Constantin-C. Coussios
Address:
Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL) Institute of Biomedical Engineering University of Oxford Oxford OX3 7DQ United Kingdom
Email:
constantin.coussios@eng.ox.ac.uk
https://doi.org/10.1121/AT.2019.15.1.21
Snap, Crackle, and Pop: Theracoustic Cavitation
Emerging techniques for making, mapping, and using acoustically driven bubbles within the body enable a broad range of innovative therapeutic applications.
Introduction
The screams from a football stadium full of people barely produce enough sound energy to boil an egg (Dowling and Ffowcs Williams, 1983). This benign view of acoustics changes dramatically in the realm of focused ultrasound where biological tissue can be brought to a boil in mere milliseconds (ter Haar and Coussios, 2007). Although the millimeter-length scales over which these effects can act may seem “surgical,” therapeutic ultrasound (0.5-3.0 MHz) is actually somewhat of a blunt instrument compared with drug molecules (<0.0002 mm) and the cells (<0.1 mm) that they are intended to treat.
Is therapeutic acoustics necessarily that limiting? Not quite. Another key phenom- enon, acoustic cavitation, has the potential to enable subwavelength therapy. De- fined as the linear or nonlinear oscillation of a gas or vapor cavity (or “bubble”) under the effect of an acoustic field, cavitation can enable preferential absorption of acoustic energy and highly efficient momentum transfer over length scales dictated not only by the ultrasound wavelength but also by the typically micron-sized di- ameter of therapeutic bubbles (Coussios and Roy, 2008). Under acoustic excitation, such bubbles act as “energy transformers,” facilitating conversion of the incident field’s longitudinal wave energy into locally enhanced heat and fluid motion. The broad range of thermal, mechanical, and biochemical effects (“theracoustics”) re- sulting from ultrasound-driven bubbles can enable successful drug delivery to the interior of cells, across the skin, or to otherwise inaccessible tumors; noninvasive surgery to destroy, remove, or debulk tissue without incision; and pharmacological or biophysical modulation of the brain and nervous system to treat diseases such as Parkinson’s or Alzheimer’s.
Where do these bubbles come from in the human body? Given that nucleating (forming) a bubble within a pure liquid requires prohibitively high and potentially unsafe acoustic pressures (10-100 atmospheres in the low-megahertz frequency range), cavitation has traditionally been facilitated by injection of micron-sized bubbles into the bloodstream. However, the currently evolving generation of thera- peutic applications requires the development of biocompatible submicron cavita- tion nucleation agents that are of comparable size to both the biological barriers they need to cross and the size of the drugs alongside which they frequently travel. Furthermore, the harnessing and safe application of the bioeffects brought about by ultrasonically driven bubbles requires the development of new techniques capable of localizing and tracking cavitation in real time at depth within the human body. And thus begins our journey on making, mapping, and using bubbles for “thera- coustic” cavitation.
©2019 Acoustical Society of America. All rights reserved.
volume 15, issue 1 | Spring 2019 | Acoustics Today | 19