A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening
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Bibliographic record
Abstract
Blood-spinal cord barrier opening, using focused ultrasound and microbubbles, has the potential to improve drug delivery for the treatment of spinal cord pathologies.Delivering and detecting ultrasound through the spine is a challenge for clinical translation.We have previously developed short burst, phase keying exposures, which can be used in a dual-aperture configuration to address clinical scale targeting challenges.Here we demonstrate the use of these pulses for blood-spinal cord barrier opening, in vivo in pigs. Methods:The spinal cords of Yorkshire pigs (n=8) were targeted through the vertebral laminae, in the lower thoracic to upper lumbar region using focused ultrasound (486 kHz) and microbubbles.Four animals were treated with a combination of pulsed sinusoidal exposures (1.0-4.0MPa, non-derated) and pulsed short burst, phase keying exposures (1.0-2.0MPa, non-derated).Four animals were treated using ramped short burst, phase keying exposures (1.8-2.1 MPa, non-derated).A 250 kHz narrowband receiver was used to detect acoustic emissions from microbubbles.Blood-spinal cord barrier opening was assessed by the extravasation of Evans blue dye.Histological analysis of the spinal cords was used to assess tissue damage and excised vertebral samples were used in benchtop experiments.Results: Ramped short burst, phase keying exposures successfully modified the blood-spinal cord barrier at 16/24 targeted locations, as assessed by the extravasation of Evans blue dye.At 4 of these locations, opening was confirmed with minimal adverse effects observed through histology.Transmission measurements through excised vertebrae indicated a mean transmission of (47.0 7.0 %) to the target.Conclusions: This study presents the first evidence of focused ultrasound-induced blood-spinal cord barrier opening in a large animal model, through the intact spine.This represents an important step towards clinical translation.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it