Histotripsy Liquefaction of Large Hematoma for Intracerebral Hemorrhage Using Millisecond-Length Ultrasound Pulse Groups Combined With Fundamental and Second Harmonic Superposition: A Preliminary Study

Abstract

Intracerebral hemorrhage is a life-threatening acute cerebrovascular disease characterized by a 30-d mortality rate of 40% and substantial disability for those who survive. The objective of this study is to investigate the feasibility of histotripsy-mediated efficient and fine liquefaction of large-volume hematoma by utilizing a protocol of millisecond-length ultrasound pulse groups combined with fundamental and second harmonic superposition. Experiments were initially performed in an in vitro hematoma phantom, using a two-element confocal-annular array. Results showed that a single ellipsoid shape, histotripsy lesion with major dimensions of 10.8 ± 1.2 mm axially and 4.8 ± 0.2 mm laterally was successfully generated. Controllability of the lesion shape and size could be realized by modulating treatment parameters in single-spot experiments. Large-volume hematomas were efficiently and finely liquefied through multisonications via a treatment strategy under the relatively optimized treatment parameters. Liquefied contents were evacuated and analyzed using a particle sizing system. The size of the lysates for the most part ranged from 4-8 μm, with more than 99% of them being smaller than 10 μm. Experiments were then conducted in an optically transparent tissue phantom to explore the liquefaction mechanisms. The phantom was composed of polyacrylamide hydrogel, embedded with bovine serum albumin (BSA), and a thin phantom layer consisted of red blood cells in the BSA polyacrylamide gel was inlayed in the BSA gel phantom. The related mechanisms, such as the frequent boiling that occurred at multiple positions and the enhanced cavitation, revealed the quick development of the lesion in the phantom and the efficient liquefaction of the clot. These results indicated that the proposed histotripsy approach is feasible for the efficient, precise and fine liquefaction of large-volume hematoma and may be developed as a useful tool for intracerebral hemorrhage treatment.

Keywords: Boiling; Enhanced cavitation; Fundamental and second harmonic superposition; Histotripsy; Liquefying large hematoma; Millisecond-length ultrasound pulse groups.