Transcranial Cavitation Mapping of Blood-Brain Barrier Opening Regions in Alzheimer's Disease Patients Using a Neuronavigation-Guided Focused Ultrasound System

We present real-time cavitation monitoring and mapping in a clinical trial for blood-brain barrier (BBB) opening in Alzheimer’s disease (AD) patients using a neuronavigation-guided focused ultrasound (FUS) system. Six AD patients (N = 6, age = 68.5 ± 9.5) were sonicated at the right prefrontal lobe with a single-element FUS transducer (PNP = 0.2 MPa, fc = 0.25 MHz, pulse length = 10 ms, PRF = 2 Hz, duration = 2 min) with the microbubble administration (Definity). We performed passive cavitation detection (PCD) using a single-element hydrophone (N = 4), and passive acoustic mapping (PAM) with a 64-element phased array transducer (N = 2). Five patients showed successful BBB opening (volume = 654 ± 394 mm3) on day0, and closure on day3, confirmed by contrast-enhanced T1-weighted MRI, while one patient served as a negative BBB opening case due to the insufficient microbubble administration. Ultra-harmonic cavitation dose (CD) correlated with the opening volume (R2 = 0.66, N = 4), but harmonic and broadband CDs showed a relatively poor correlation (R2 = 0.06 and 0.33). Cavitation maps (N = 2) showed a spatial distribution of acoustic energy that roughly coincided with the respective BBB opening location. We thus demonstrated the successful BBB opening and cavitation monitoring with the neuronavigation-guided system that allowed for a cost-effective procedure compared to the MR-guided approaches. The PCD and PAM showed promising results for potentially predicting the BBB opening volume and location found in MRI.