ACTR-42. INITIAL EXPERIENCE OF BLOOD-BRAIN BARRIER OPENING FOR CHEMOTHERAPEUTIC-DRUG DELIVERY TO BRAIN TUMOURS BY MR-GUIDED FOCUSED ULTRASOUND

Abstract

INTRODUCTION

Magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly open the blood-brain barrier (BBB) for targeted drug delivery. Animal models have shown the feasibility of BBB opening for delivery of a broad range of compounds. We describe the first experience of focused ultrasound mediated BBB opening in malignant brain tumours.

METHODS

This phase-one clinical trial was approved by Health Canada and our Research Ethics Board. A modified clinical MRgFUS brain system was used with a 3T MR scanner. Prior to BBB opening patients received a single dose of IV liposomal doxorubicin (N=1) or temozolomide (N=2). Patients were positioned in the FUS array with a stereotactic frame. Two targets close to the posterior margin of the tumor were chosen based on T2 images. A bolus injection of Definity microbubbles was applied simultaneously with each sonication. Post sonication, Gd-enhanced images were acquired to verify BBB openings, and T2*-weighted GRE images were collected to detect hemorrhage.

RESULTS

All patients tolerated FUS procedures and BBB opening well, with no adverse events. T2* images demonstrated a small degree of RBC extravasation, with no overt hemorrhage on standard T1, no edema on T2 or DWI changes on treatment or follow-up scans. BBB was successfully opened in all patients at each targeted location, with clear Gd enhancement. All patients underwent safe maximal surgical resection at 24 hours post-sonication.

DISCUSSION

Our initial experience of FUS-mediated BBB opening in high-grade glioma demonstrates the safety and feasibility of this emerging adjuvant modality. We were able to open the BBB, as demonstrated with Gd enhancement, in several discrete brain regions surrounding the tumour, without adverse events. Patients tolerated the procedure well. Next steps will include sonication of larger tumour volumes, done in conjunction with standard of care prescriptions of chemotherapeutic agents, for which the BBB is a major challenge.