Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Although previous work has provided significant insight into the process of intrinsic threshold histotripsy, the majority of these studies have used highly focused (i.e. f-number<0.6) transducers. In this study, we investigate the effects of f-number on the histotripsy intrinsic threshold and cavitation bubble cloud behavior using a 500 kHz array transducer, with the effective f-number of the transducer varied from 0.51 to 0.89. The intrinsic threshold did not significantly change with f-number, with the threshold remaining ~27–30 MPa for all conditions. The predictability of intrinsic threshold histotripsy was further demonstrated by experiments comparing the predicted and experimentally measured bubble cloud dimensions, with results showing close agreement for all f-numbers. Finally, the effects of f-number on “bubble density” and tissue fractionation efficiency were investigated, with results supporting the hypothesis that the density of the bubbles within the bubble cloud significantly decreases at higher f-numbers, resulting in decreased fractionation efficiency. Overall, this study provides significant insight into the effects of f-number on intrinsic threshold histotripsy that will help to guide the development of intrinsic threshold histotripsy for specific clinical applications.
BACKGROUND
Intracerebral hemorrhage (ICH) is characterized by a 30-d mortality rate of 40% and significant disability for those who survive.
OBJECTIVE
To investigate the initial safety concerns of histotripsy mediated clot liquefaction and aspiration in a porcine ICH model. Histotripsy is a noninvasive, focused ultrasound technique that generates cavitation to mechanically fractionate tissue. Histotripsy has the potential to liquefy clot in the brain and facilitate minimally invasive aspiration.
METHODS
About 1.75-mL clots were formed in the frontal lobe of the brain (n = 18; n = 6/group). The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Pigs underwent magnetic resonance imaging (MRI) 7 to 8 d after clot formation and were subsequently euthanized. Neurological behavior was assessed throughout. Histological analysis was performed on harvested brains. A subset of pigs underwent acute analysis (≤6 h).
RESULTS
Histotripsy was able to liquefy the center of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups.
CONCLUSION
This study presents the first analysis of histotripsy-based liquefaction of ICH in vivo. Histotripsy safely liquefies clots without significant additional damage to the perihematomal region. The liquefied content of the clot can be easily evacuated, and the undrained clot has no effect on pig survival or neurological behavior.
This in-vitro study investigated the effects of ultrasound frequency and focal spacing on blood clot liquefaction via transcranial histotripsy. Histotripsy pulses were delivered using two 256-element hemispherical transducers of different frequency (250 and 500 kHz) with 30 cm aperture diameters. A 4 cm diameter spherical volume of in-vitro blood clot was treated through three excised human skullcaps by electronically steering the focus with frequency proportional focal spacing: λ/2, 2λ/3 and λ with 50 pulses per location. The pulse repetition frequency (PRF) across the volume was 200 Hz, corresponding to a duty cycle of 0.08% (250 kHz) and 0.04% (500 kHz) for each focal location. Skull heating during treatment was monitored. Liquefied clot was drained via catheter and syringe in range of 6–59 mL in 0.9–42.4 minutes. The fastest rate was 16.6 mL/min. The best parameter combination was λ spacing at 500 kHz which produced large liquefaction through three skullcaps (23.1 ± 4.0, 37.1 ± 16.9 and 25.4 ± 16.9 mL) with the fast rates (3.2 ± 0.6, 5.1 ± 2.3 and 3.5 ± 0.4 mL/min). The temperature rise through the 3 skullcaps remained below 4 °C.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.