We hypothesize that the integrity of the blood brain barrier (BBB) limits the penetration of the checkpoint inhibitor targeted therapy, anti-
PD-1 antibody, thereby restricting the immune response and the abscopal effect for intracranial metastatic melanoma. Mechanical
disruption of the BBB with focused ultrasound (FUS) with microbubbles can allow for great drug penetration and enhance the immune
response. The addition of stereotactic radiosurgery (SRS) and immunotherapy with FUS will result in in situ tumor vaccination effects
resulting in intracranial protection from new intracranial metastatic seeding.