Histotripsy, a technique that uses focused ultrasound for mechanical rather than thermal destruction of tissue, may be advantageous for the treatment of brain tissue. The aim of this project is to complete the proof-of-concept evaluation of histotripsy in brain tissue. First, phantom experiments will be performed using histotripsy through ex-vivo human skulls to demonstrate that histotripsy can be used to treat locations close to the skullcap and base of the skull without significantly heating the skull. Next, a full pathology report will be generated based on the initial acute histotripsy pig brain experiments to evaluate the treatment safety, particularly hemorrhage and edema at the lesion periphery. Finally, a chronic pig study will be performed to examine the safety issues within 48 to 72 hours after histotripsy brain treatment, with imaging and a full pathology report to describe the necrosis, apoptosis, hemorrhage, and edema.