P07.04.b Development of a Hand-Held Intraoperative Focused Ultrasound Device to Open the Blood-Brain Barrier (Bbb)

BACKGROUND The blood brain barrier remains a formidable obstacle for the delivery of most therapeutics to infiltrative disease of diffuse glioma. The design of a hand-held intraoperative focused ultrasound device to open the blood-brain barrier (BBB) can enable direct drug delivery at the margins of a tumor resection and facilitate real time analyses of tumor resected pre- and post-sonication. MATERIAL AND METHODS A single-element, 17 mm, 1.6 MHz, with a 160 mm handle angled at ~27° to the transducer axis, was designed. To test the ability of this device to open the BBB with microbubbles in an intraoperative procedure, an IACUC-approved proof-of-principle study was conducted on 11 male Sprague-Dawley rats with the transducer positioned directly on the exposed frontal lobe after a craniotomy. Sonication was performed for 3 minutes (pulse length: 10 ms, pulse repetition rate: 1 Hz). RESULTS The calibrated in situ acoustic pressures used ranged from 0.75 MPa to 1.2 MPa (-3dB). Immediately following sonication, 2% Evans Blue (3 mL/kg) was injected via a tail vein catheter. The animals were sacrificed immediately after Evans Blue injection. Depending on the pressure, the whole brain dorsal and ventral views show the EB dye where sonication was performed. H&E sectioning of the sonicated brain did not demonstrate any intraparenchymal hemorrhage. CONCLUSION This preclinical proof-of-principle study demonstrates that the BBB can be opened safely and effectively intraoperatively following a craniotomy in rodents. As this device is designed to be hand-held when operating on humans, it can form the foundation for an interventional neuro-oncology program aimed at improving drug delivery and facilitating studies to favorably modulate the tumor microenvironment for patients with glioblastoma.