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Transcranial focused ultrasound has been studied for non-invasive and localized treatment of many brain diseases. The biggest challenge for focusing ultrasound onto the brain is the skull, which attenuates ultrasound and changes its propagation direction, leading to pressure drop, focus shift, and defocusing. We presented an optimization algorithm which automatically found the optimal location for placing a single-element focused transducer. At this optimal location, the focus shift was in an acceptable range and the ultrasound was tightly focused. The algorithm simulated the beam profiles of placing the transducer at different locations and compared the results. Locations with a normalized peak-negative pressure (PNP) above threshold were first found. Then, the optimal location was identified as the location with the smallest focal volume. The optimal location found in this study had a normalized PNP of 0.966 and a focal volume of 6.8% smaller than without the skull. A Zeta navigation system was used to automatically place the transducer and track the error caused by movement. These results demonstrated that the algorithm could find the optimal transducer location to avoid large focus shift and defocusing. With the Zeta navigation system, our algorithm can help to make transcranial focused ultrasound treatment safer and more successful.

For the past three decades, neurosurgeons have utilized cranial neuro-navigation systems, bringing millimetric accuracy to operating rooms worldwide. These systems require an operating room team, anesthesia, and, most critically, cranial fixation. As a result, treatments for acute neurosurgical conditions, performed urgently in emergency rooms or intensive care units on awake and non-immobilized patients, have not benefited from traditional neuro-navigation. These emergent procedures are performed freehand, guided only by anatomical landmarks with no navigation, resulting in inaccurate catheter placement and neurological deficits. A rapidly deployable image-guidance technology that offers highly accurate, real-time registration and is capable of tracking awake, moving patients is needed to improve patient safety. The Zeta Cranial Navigation System is currently the only non-fiducial-based, FDA-approved neuro-navigation device that performs real-time registration and continuous patient tracking. To assess this system’s performance, we performed registration and tracking of phantoms and human cadaver heads during controlled motions and various adverse surgical test conditions. As a result, we obtained millimetric or sub-millimetric target and surface registration accuracy. This rapid and accurate frameless neuro-navigation system for mobile subjects can enhance bedside procedure safety and expand the range of interventions performed with high levels of accuracy outside of an operating room.