Spinal stiffness assessment by shear wave imaging in a genetic zebrafish scoliosis model treated with anti-inflammatory medication
Notice bibliographique
Résumé
Background: Idiopathic scoliosis (IS) is a disease characterized by an abnormal lateral curvature of the spine that affects up to 4% of the population. Recent models in zebrafish have elucidated genetic variants which contribute to scoliotic curvature through mechanisms of neuroinflammation, and oxidative stress. Additionally, in-vivo clinical studies have demonstrated that spinal structures stiffen in patients with IS. Shear wave elastography (SWE) is novel, non-invasive imaging technique used to quantitatively estimate tissue stiffness. Objective: Here, we investigated spinal stiffness using SWE in genetically mutant zebrafish with a heterozygous scoliosis variant ( dmh4/+) treated with N-acetylcysteine ethyl ester (NACET), a potent anti-oxidant and anti-inflammatory medication which has been demonstrated to reduce scoliosis curvature formation in zebrafish by up to 70%. Hypothesis: Compared to wildtype, spinal stiffness will increase in dmh4/+ zebrafish and there will be no difference in stiffness for NACET treated zebrafish. Methods: Wildtype (WT; n=20) and mutant ( dmh4/+; n=20) zebrafish aged 10 days post fertilization (dpf) (n=10 & n=10 treated with 500 μM of NACET), 16 dpf (n=10), and 21 dpf (n=10) were sacrificed and submerged in a dish containing 2% low melt agarose gel. An 18.75 MHz linear ultrasound probe was clamped to the dish apparatus dorsal to the zebra fish. Spinal stiffness was assessed by SWE, where faster shear wave velocities (SWV) represent stiffer tissue. The SWV data was processed using a well-verified, custom SWE analysis program on MATLAB by a n operator blinded to the zebrafish genotypes. Results: The spinal curvature of dmh4/+ zebrafish aged 10 dpf were morphologically indistinguishable from WT zebrafish aged 10 dpf. SWV was significantly increased in dmh4/+ zebrafish aged 10 dpf compared to WT (p<0.05). There was no difference in SWV between NACET treated dmh4/+ and NACET treated WT zebrafish aged 10 dpf (p>0.05). Furthermore, NACET treated dmh4/+ and WT zebrafish aged 10 dpf exhibited no difference in SWV compared to untreated WT zebrafish aged 10 dpf (p>0.05). Additionally, SWV was significantly increased in dmh4/+ zebrafish aged 16 and 21 dpf compared to WT (p<0.05). Conclusion: Here we demonstrate that spinal stiffness increases in zebrafish with scoliosis before the curvature pheno type is present and this increase in stiffness is sustained throughout development in later ages. Additionally, spinal stiffness in scoliosis is reduced following treatment with NACET. Our results provide evidence to support clinical trials assessing stiffness as preclinical diagnostic criteria for IS in children. Biotalent Canada - public grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».