With the eventual goal to use focused ultrasound to dissolve chronic deep vein blood thrombi, Kenneth B. Bader, PhD, and his colleagues at the University of Cincinnati recently completed a study to develop standards to regulate microbubble cloud formation during histotripsy pulses.
The three-part project was successful in first assessing the area, location, and type of microbubble activity and ablation during histotripsy using passive cavitation imaging. The second portion of the project developed an analytic mathematical model to predict the extent of the microbubble cloud. Phase three evaluated the efficacy of using histotripsy in conjunction with thrombolytic agents to enhance blood clot lysis. Are they close to translating their data to a clinical setting?
This study, based out of Dr. Christy Holland’s Image-Guided Ultrasound Therapeutics Laboratory at the University of Cincinnati Cardiovascular Center, will profoundly impact the advancement of clinical use of histotripsy. The analytic model developed by Dr. Bader can be used to predict the size of the ablation zone for pre-treatment planning and could aid the FDA in the development of regulatory standards for histotripsy.
The mechanically ablative action of cavitation generated by histotripsy is isothermal, and therefore cannot take advantage of the capabilities of MR thermometry to track treatment progress. Acoustic emissions generated by cavitation can serve as a surrogate for the mechanical action of the bubbles. Dr. Bader and colleagues employed passive cavitation imaging to track the location of cavitation and the amplitudes of the resulting acoustic emissions generated by histotripsy.
Sonothrombolysis can be used to dissolve the blood clots that may cause both arterial and venous occlusions. But all blood clots are not the same–some are soft, and others are stiff. Bader’s group has discovered that histotripsy may work well to treat stiff clots. Their future work will focus on this application, and they will submit a follow-on funding application to the National Institutes of Health (NIH).
To assist in this project, Adam Maxwell, PhD (University of Washington) collaborated with the University of Cincinnati in the design and development of a histotripsy system. Dr. Maxwell custom designed and built an amplifier unit to use in combination with a commercially available transducer (Imasonic, Voray-sur-l’Ognon, France). This specialized system was used by the University of Cincinnati to generate the histotripsy pulses.
Follow-on Funding from the NIH
The group hopes to receive NIH funding for a project to use histotripsy as an adjuvant to the front line therapy of catheter-delivered thrombolytics. They plan to investigate whether histotripsy could be used to remove critical chronic obstructions that remain after thrombolytic administration. In addition to standard thrombolytic drugs, thrombolytic loaded echogenic liposomes will be used. These lipid vesicles can be activated with ultrasound for localized release of the thrombolytic.