An alternative method of tissue fractionation--boiling histotripsy--has been developed in a unique collaboration between and the University of Washington (UW) in Seattle and Moscow State University (MSU) in Russia. Drs. Vera A. Khokhlova, Lawrence A. Crum, and the growing UW/MSU teams have developed the method that uses longer (millisecond instead of microsecond) duration focused ultrasound pulses to generate a millimeter-sized boiling bubble (instead of a cavitation cloud) through tissue heating by shocks. Two papers that detailed their groundbreaking work were published in Ultrasound in Medicine and Biology and the Journal of the Acoustical Society of America.
Last year, the team successfully collaborated with Dr. A. Partanen from Philips Healthcare to determine the feasibility of using the Sonalleve clinical MR-HIFU system for boiling histotripsy. Accurate characterization of the system was performed using acoustic holography and nonlinear modeling methods, showing its capability to generate high-amplitude shock wave fields in the focus. These results were published in the August 2013 issue of IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.
Experimental studies on how to use the effects of nonlinear acoustics and, in particular, shock waves, in novel focused ultrasound technologies have been supported by the NIBIB Institute of the NIH and NSBRI (National Space Biomedical Research Institute) for more than 6 years. The MSU team members are known as experts in nonlinear acoustic modeling, and the studies at MSU have been supported by the Russian Foundation for Basic Research for more than 15 yearsIn the 6-year development of boiling histotripsy technique, the teams proved that rapid jumps from low to high pressures in acoustic waveforms (i.e., shocks) can form at the HIFU beam focus in tissue. These shocks heat the tissue very rapidly and create focal temperatures greater than 100°C in milliseconds. The localized, explosive boiling of tissue generates a millimeter-sized vapor bubble at the focus. Ultrasound shocks further interact with the bubble and liquefy tissue by generating a miniature acoustic fountain of tissue into the bubble.
They have found that if the pulse is not much longer than the time-to-boil, the thermal injury in boiling histotripsy lesions is negligible compared to the mechanical injury, and they use real-time ultrasound guidance to visualize the bubbles that appear at the focus. Dr. Crum finds boiling histotripsy easier to initiate and control than cavitation-cloud histotripsy.
The ongoing ex-vivo and in-vivo projects at UW supported by the National Institutes of Health and the National Space Biomedical Research Institute explore the use of boiling histotripsy to:
· fractionate tissue volume
· produce holes in connective tissue
· induce immune response
· enhance the release of biomarkers for diagnostics
· develop ultrasound and MRI methods for guiding and monitoring the treatment
Future directions for the UW team include looking at ways that this technology may be able to treat the kidneys and liver as well as its use for diagnostic biomarkers for certain types of cancer.