ACTR-42. INITIAL EXPERIENCE OF BLOOD-BRAIN BARRIER OPENING FOR CHEMOTHERAPEUTIC-DRUG DELIVERY TO BRAIN TUMOURS BY MR-GUIDED FOCUSED ULTRASOUND
Bibliographic record
Abstract
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. 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. 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. 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".