CNSC-39. USE OF MAGNETIC RESONANCE-GUIDED FOCUSED ULTRASOUND IN THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA
Bibliographic record
Abstract
Abstract Diffuse intrinsic pontine glioma (DIPG) is the leading cause of brain tumour-related deaths in childhood. Current treatment is radiation with or without chemotherapy, as surgical resection is impossible due to its location within the brainstem. A major obstacle to treatment is impaired drug delivery across an intact blood-brain barrier (BBB). However, magnetic resonance-guided focused ultrasound (MRgFUS) can transiently open the BBB and enhance the delivery of BBB-impermeable drugs. Interestingly, MRgFUS has also been shown to modulate the immune response in treated regions, although this has not been characterized in DIPG models. We hypothesize that MRgFUS can be utilized to improve treatment effects of targeted drugs and immune-based therapies for patients with DIPG, specifically through enhanced delivery of therapeutics to increase drug efficacy and immunomodulation to boost anti-tumour immune responses. We used an MRgFUS system in a controller mode where acoustic pressure is adjusted based on the acoustic feedback received, and a fixed mode where pressure remains constant. Initial experiments focused on optimization using non-tumour bearing mice. Brain tissue was collected at 24-hours (n=8), 72-hours (n=10), and 1-week (n=10) post-MRgFUS. Immunohistochemistry was conducted for immune characterization of sonicated and non-sonicated regions in MRgFUS-treated and non-treated animals. Optimization results indicate that safe and effective opening is feasible when sonicating at an acoustic pressure of 300 kPa using the fixed pressure mode, and for a sonication period of 90 seconds using the controller mode. Preliminary immunohistochemistry results show increased macrophage infiltration in sonicated regions. Altogether, our results demonstrate that BBB opening can be replicated using different MRgFUS systems and parameters. Future studies include modulating these parameters to optimize immune cell infiltration within the brainstem, which may help extend treatment efficacies when combined with radiotherapy and chemotherapy. The use of MRgFUS is an exciting new tool for broadening therapeutic options for patients with DIPG.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".