Blood‐Brain Barrier Closure Time After Controlled Ultrasound‐Induced Opening Is Independent of Opening Volume
Bibliographic record
Abstract
Objectives Microbubble‐mediated focused ultrasound (US) opening of the blood‐brain barrier (BBB) has shown promising results for the treatment of brain tumors and conditions such as Alzheimer disease. Practical clinical implementation of focused US treatments would aim to treat a substantial portion of the brain; thus, the safety of opening large volumes must be investigated. This study investigated whether the opened volume affects the time for the BBB to be restored after treatment. Methods Sprague Dawley rats (n = 5) received bilateral focused US treatments. One hemisphere received a single sonication, and the contralateral hemisphere was targeted with 4 overlapping foci. Contrast‐enhanced T1‐weighted magnetic resonance imaging was used to assess the integrity of the BBB at 0, 6, and 24 hours after focused US. Results At time 0, there was no significant difference in the mean enhancement between the single‐ and multi‐point sonications (mean ± SD, 29.7% ± 18.4% versus 29.7% ± 24.1%; P = .9975). The mean cross‐sectional area of the BBB opening resulting from the multi‐point sonication was approximately 3.5‐fold larger than that of the single‐point case (14.2 ± 4.7 versus 4.1 ± 3.3 mm2; P < .0001). The opened volumes in 9 of 10 hemispheres were closed by 6 hours after focused US. The remaining treatment location had substantially reduced enhancement at 6 hours and was closed by 24 hours. Histologic analysis revealed small morphologic changes associated with this location. T2‐weighted images at 6 and 24 hours showed no signs of edema. T2*‐weighted images obtained at 6 hours also showed no signs hemorrhage in any animal. Conclusions The time for the BBB to close after focused US was independent of the opening volume on the time scale investigated. No differences in treatment effects were observable by magnetic resonance imaging follow‐up between larger‐ and smaller‐volume sonications, suggesting that larger‐volume BBB opening can be performed safely.
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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 | 0.001 |
| 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) | 0.001 | 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".