Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: Feasibility when considering the human skull

Focused ultrasound (FUS) exposure with the presence of microbubbles has shown its promise in temporally and targeted open the blood-brain barrier (BBB), and brings potential in delivering therapeutic agents into the brain for CNS disease treatment. Feasibility in using neuronavigation system to guide the FUS-BBB procedure in large animals has been demonstrated successfully, and the guidance precision has been measured to be acceptably low. However, it is still unknown whether same precision and power compensation strategy is valid when FUS beam is intend to penetrate the human skull. The purpose of this study is to verify that using neuronavigation system combined with a prior treatment plan can successfully guide FUS-BBB opening with the consideration of involvement of human skull. A human cadaver was employed to perform CT scan, and a treatment planning software was developed to simulate focal beam redistribution and pressure decay when transcranial FUS exposure were performed. During experiment, 4 groups were conducted to verify the success of BBB-opening when incorporating with the in-prior treatment plan. Our results suggest that under the guidance of neuronavigation and prior treatment planning is feasible to precisely guide the FUS-BBB opening procedure, and may have potential to be applied for future clinical brain drug delivery interventions.