Objective: Phase aberration correction is essential in transcranial histotripsy to compensate for focal distortion caused by the heterogeneity of the intact skull bone. This paper improves the 2-step aberration correction (AC) method that has been previously presented and develops an AC workflow that fits in the clinical environment, in which the computed tomography (CT)-based analytical approach was first implemented, followed by a cavitation-based approach using the shockwaves from the acoustic cavitation emission (ACE).Approach:A 700 kHz, 360-element hemispherical transducer array capable of transmit-and-receive on all channels was used to transcranially generate histotripsy-induced cavitation and acquire ACE shockwaves. For CT-AC, two ray-tracing models were investigated: a forward ray-tracing model (transducer-to-focus) in the open-source software Kranion, and an in-house backward ray-tracing model (focus-to-transducer) accounting for refraction and the sound speed variation in skulls. Co-registration was achieved by aligning the skull CT data to the skull surface map reconstructed using the acoustic pulse-echo method. For ACE-AC, the ACE signals from the collapses of generated bubbles were aligned by cross-correlation to estimate the corresponding time delays.Main results:The performance of the 2-step method was tested with 3 excised human calvariums placed at 2 different locations in the transducer array. Results showed that the 2-step AC achieved 90 ± 7% peak focal pressure compared to the gold standard hydrophone correction. It also reduced the focal shift from 0.84 to 0.30 mm and the focal volume from 10.6 to 2.0 mm³on average compared to the no AC cases.Significance:The 2-step AC yielded better refocusing compared to either CT-AC or ACE-AC alone and can be implemented in real-time for transcranial histotripsy brain therapy.

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