Histotripsy pulses will be delivered transcranially to excised bovine brain samples mounted within excised human skullcaps using a transmit-receive capable, transcranial histotripsy array available in our lab. Lesions will be generated in the brain samples by applying between 1 and 1000 histotripsy pulses to single focal locations within them and the ACE signals emitted by each cavitation event will be acquired during therapy using the array elements. Histological analyses of the treated samples will be performed to quantify the damage outcomes as a function of cavitation exposure. Correlations between features of the ACE signals and the histological damage outcomes will then be investigated to identify associations between the ACE features and generated damage. Following this, these experiments will be repeated to generate large lesions (>1cm) to determine if/how lesion size impacts assessments of therapy-generated tissue damage based on the correlations established for the single focal-site lesions and modifications to the correlational model(s) will be made to account for lesion volume if/as necessary. Finally, real-time algorithms for processing the ACE signals to identify features correlated with damage outcomes will be developed and validated by repeating the above experiments and comparing algorithm-predicted damage outcomes with post-treatment histological observations.
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