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In vivo transcranial and noninvasive cavitation detection with blood-brain barrier (BBB) opening in nonhuman primates is hereby reported. The BBB in monkeys was opened transcranically using focused ultrasound (FUS) in conjunction with microbubbles. A passive cavitation detector, confocal with the FUS transducer, was used to identify and monitor the bubble behavior. During sonication, the cavitation spectrum, which was found to be region-, pressure-, and bubble-dependent, provided real-time feedback regarding the opening occurrence and its properties. These findings demonstrate feasibility of transcranial, cavitation-guided BBB opening using FUS and microbubbles in noninvasive human applications.