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Supplemental material, sj-docx-1-ine-10.1177_15910199231157926 for A novel histological occlusion classification for coiled aneurysms based on multiphoton microscopy by Szatmary Zoltan, Cortese Jonathan, Mounier Jeremy and Perrin Marie-Laure, Janot Kevin, Couquet Claude, Aurélien Le Flahec, Leger-Bretou Claire, Mounayer Charbel, Rouchaud Aymeric, Sylvia M Bardet in Interventional Neuroradiology

Background and purpose In this study we tested the effect of antiangiogenics on a swine angiogenesis model that shares some brain AVM histological characteristics. The objective was to determine bevacizumab effects on retia volumes and on vessels’ wall. Materials and methods Fifteen pigs were divided into 3 groups: Five animals served as controls (group A), 5 animals underwent endovascular left external and common carotid artery occlusion (group B) and 5 animals underwent the same procedure and had an intra-arterial in-situ injection of bevacizumab (group C) 2 months after the occlusion. A DSA associated with 3D-rotational angiography was performed at day 0 and at 3 months in all groups in order to measure rete mirabile volumes. The animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. Results All VEGF-A receptors were blocked at the site of injection and there was a local enhanced endothelial proliferation and apoptosis. The volume of the retia remained unchanged after the bevacizumab injection. Retia vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection. Conclusion A single in-situ injection of bevacizumab in this swine angiogenesis model showed no change in retia volume and an extensive blockage of VEGF receptors at the site of injection one month later. Rete mirabile vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection, suggesting that bevacizumab antiangiogenic effect does not fragilize vessel wall. More studies are needed to confirm these preliminary insights of in-situ antiangiogenic effect on vascular malformations.

BackgroundWEB Shape Modification (WSM) over time is frequent after aneurysm treatment. In this study, we explored the relationship between histopathological changes and angiographic evolution over time in experimental aneurysms in rabbits treated with the Woven EndoBridge (WEB) procedure.MethodsQuantitative WSM was assessed using flat-panel computed tomography (FPCT) during follow-up by calculating height and width ratio (HR, WR), defined as the ratio between either measurement at an index time point and the measurement immediately after WEB implantation. The index time point varied from 1 day to 6 months. HR and WR were evaluated with angiographic and histopathological assessments of aneurysm healing.ResultsFinal HR of devices varied from 0.30 to 1.02 and final WR varied from 0.62 to 1.59. Altogether, at least 5% of HR and WR variations were observed in 37/40 (92.5%) and 28/40 (70%) WEB devices, respectively, at the time of final assessment. There was no significant correlation between complete or incomplete occlusion groups and HR or WR (p=0.15 and p=0.43). Histopathological analysis revealed a significant association between WR and aneurysm healing and fibrosis 1 month following aneurysm treatment (both pConclusionUsing longitudinal FPCT assessment, we observed that WSM affects both the height and width of the WEB device. No significant association was found between WSM and aneurysm occlusion status. Although presumably a multifactorial phenomenon, the histopathological analysis highlighted a significant association between width variations, aneurysm healing and fibrosis in the first month following aneurysm treatment.

RESUME L’objectif de notre etude etait d’evaluer la tolerance de l’uterus a une ischemie froide (IF) prolongee apres auto-transplantation (ATU) chez la brebis. Quatorze ATUetaient realisees au Laboratoire d’Analyses et de Recherches de Limoges entre Novembre 2015 et juin 2016 : 7 brebis transplantees apres 3 heures d’IF et 7 brebis apres 24 heures d’IF. Le transplant etait evalue macroscopiquement a JJ8. Une analyse histologique de l’uterus et du signal apoptotique (technique TUNEL et immunohistochimie de la caspase 3) etait effectuee avant le prelevement uterin (temoin), apres 90 minutes de reperfusion et a JJ8. Douze ATU etaient realisees avec succes (12114). Apres 90 minutes de reperfusion, l’analyse histologique revelait une inflammation moderee de l’endometre et de la sereuse uterine dans le groupe 3h d’IF, et une reaction inflammatoire importante dans le groupe 24 heures d’IF. Aucun signal apoptotique significatif n’etait observe dans les 2 groupes. Sept brebis etaient vivantes a J8. Deux uterus etaient macroscopiquement et histologiquement viables avec contractions uterines apres 3h d’IFet 3 apres 24h d’IF. Un uterus etait necrose dans chaque groupe. L’uterus semble tolerer une IF prolongee avant sa transplantation. D’autres recherches sur le gros animal sont necessaires pour confirmer ces premieres donnees.

Objective To assess how the uterus tolerates extended cold ischemic storage before auto-transplantation in ewes. Study design Fourteen uterine auto-transplantations were performed in ewes from November 2014 to June 2015 at the Analysis and Research Laboratory of Limoges, France. The animals were divided into 2 groups: 7 after 3 h of cold ischemia timeand 7 after 24 h. Transplant was assessed ≥8 days after transplantation. Histology and apoptosis analyses (TUNEL method and indirect immunohistochemistry of cleaved Caspase 3) were performed before uterus retrieval (control), after 90 min following reperfusion and ≥8 days after transplantation. Results Twelve uterine auto-transplantations were successfully performed. The histological analysis at 90 min following reperfusion revealed a moderate inflammation of the endometrium and serosa in the 3-h group and severe inflammation in the 24-h group, but no significant apoptotic signal was found in either group. Seven ewes were alive at ≥8 days after transplantation: the macroscopic and histological analyses revealed two viable uteri in the 3-h group and three in the 24-h group. In each group one uterus was necrotic. Conclusion These first results in ewes suggest that the uterus is an organ with a good tolerance to extended cold ischemic storage before transplantation.

Aim Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. Material and Methods Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. Results No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. Conclusion MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.

BACKGROUND Even though flow-diverting stents are being increasingly used to treat intracranial aneurysms, the fate of jailed side branches remains controversial, with recent clinical data contradicting finding of earlier animal studies that reported patency. OBJECTIVE To quantify the surface area of the ostia after 3 months of jailing by flow-diverting stents as a more accurate means of patency evaluation. METHODS Ten large white swine were stented by flow-diverting stents placed at common carotid-ascending pharyngeal arterial bifurcation sites. A dual antiplatelet regimen was initiated 72 hours before stenting and maintained during follow-up. Optical coherence tomography was used to search for per-procedural thrombus formation. Selective control digital subtraction angiography was performed 12 weeks post-stenting. Subsequently, the stented arterial segments were harvested en bloc and observed under scanning electron microscopy, photographed, and quantified. RESULTS The absence of per-procedural thrombus formation was confirmed. All ostia were patent at 12 weeks (or 3 months) post stenting, with no angiographic or scanning electron microscopy-evident thrombus formation. The mean initial ostium surface was 2 048 617 ± 731 625 μm. At 3 months, the mean nonendothelialized ostium surface was 229 218 ± 140 172 μm, and mean endothelialized ostium surface was 1 819 399 ± 672 632 μm. A statistically significant difference (reduction) was observed between the initial and 12-week ostium surfaces (P < .001), with an significant statistical power (1.000). CONCLUSION Jailed side branches remained patent after stenting, but the surface quantifications showed significant endothelial coverage, with a significant reduction of patent ostium surfaces at 12 weeks post-stenting. ABBREVIATIONS APhA, ascending pharyngeal arteryCI, confidence interval3DRA, 3-dimensional rotational angiographyDSA, digital subtraction angiographyFDS, flow-diverting stentOCT, optical coherence tomographyOS, ostium surfaceSEM, scanning electron microscopy.

Contexte et objectif Les malformations arterioveineuses cerebrales (MAVc) sont des malformations vasculaires cerebrales rares. Le but de notre travail etait de tester l’effet de bexacizumab sur un modele animal d’angiogenese presentant des caracteristiques des MAVs cerebrales. Materiels et methodes Dix porcs ont ete divises en 2 groupes. Les animaux ont subi une occlusion endovasculaire de la carotide commune gauche selon le modele decrit et 5 animaux ont eu une injection intraarterielle bolus de 10 mg/kg de bevacizumab (BVZ) a M2. Une ASN, associee a l’angiographie 3D-RA a ete realisee au jour 0 et a 3 mois. Le volume du rete mirabile (mL) a ete calcule par un outil de segmentation adapte a partir d’un algorithme decrit precedemment. Des echantillons de sang arteriel ont ete preleves, pour les mesures de VEGF aux meme moments. Enfin, les animaux ont ete sacrifies a trois mois et le rete a ete preleve chirurgicalement pour l’examen histologique. Resultats A l’imagerie de suivi a 3 mois, le volume du rete a ete calcule et compare entre les animaux. Il y avait une tendance a des niveaux plus eleves de VEGF dans le serum entre J0 et M3 dans le groupe de l’injection de BVZ. Les resultats histologiques montrent que une seule injection d’anti-angiogenique in situ, a un effet important et durable sur l’angiogenese et modifie l’evolution des caracteristiques histologiques similaires aux MAV cerebrales. Conclusion L’angiogenese qui est un facteur important de formation et d’evolution des MAVs cerebrales peut etre modifiee par l’administration d’une seule dose d’anti-angiogeniques in situ.

BackgroundAngiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs.ObjectiveTo develop an animal model sharing the same pathological characteristics as human brain AVMs.Materials and methodsTen pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of the retia was calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations.ResultsAt 3 months, a significantly higher rete volume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6.ConclusionsUnilateral endovascular occlusion of the CCA–ECA results in angiogenesis triggering of the rete mirabile with both significant augmentation of the rete volume and histological evidence of pro-angiogenic stimulation.

Transmissible spongiform subacute encephalopathies (TSSE) occurring under natural conditions include mainly scrapie in sheep and goat, chronic wasting disease (CWD) in Cervidae, and bovine spongiform encephalopathy (BSE). The precautionary measures taken against BSE are now bearing fruit, as case numbers decrease every year, particuiarly in France. Moreover numerous studies have shown the interest of clinical examination of cattle to detect BSE in the field. In the other ruminants, chronic wasting disease (CWD) remains a matter of concern in North America, while new worries have appeared on scrapie in small ruminants : a BSE-like strain has been discovered in a case of goat scrapie in France, genetic selection to fight sheep scrapie is being questioned (emergence of “atypical cases” in “resistant” animals, especially the Nor98 strain of scrapie). These data demonstrate the interest of active monitoring of scrapie of small ruminants in Europe., Les encéphalopathies spongiformes subaiguës transmissibles (ESST) animales comprennent principalement, dans les conditions naturelles, la tremblante des petits ruminants, la maladie du dépérissement chronique des cervidés (MDCC) et l’encéphalopathie spongiforme bovine (ESB). On observe actuellement les résultats de l’efficacité des mesures de précaution concernant l’ESB avec une diminution du nombre des cas chaque année, en particulier en France. Par ailleurs, de nombreuses études démontrent l''intérêt de l''examen clinique des bovins pour la détection de l''ESB. Chez les autres ruminants, la maladie du dépérissement chronique des cervidés (MDCC) demeure une préoccupation en Amérique du Nord, alors que de nouvelles inquiétudes apparaissent dans le cas de la tremblante des petits ruminants : découverte d’une souche de type ESB dans un cas de tremblante caprine en France, remise en question de la sélection génétique dans la lutte contre la tremblante ovine (apparition de «cas atypiques» chez des animaux «résistants», en particulier avec la souche tremblante Nor 98). Ces données démontrent l’intérêt d’une surveillance active de la tremblante des petits ruminants en Europe., Couquet C., Allix S., Brugère-Picoux Jeanne, Adjou Karim Tarik, El Hachimi Hamid, Brugère Henri. Epidémiologie et aspects cliniques des encéphalopathies spongiformes subaiguës transmissibles (ESST) animales. In: Bulletin de l'Académie Vétérinaire de France tome 158 n°4, 2005. pp. 423-428.

International audience; AIM: Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. MATERIAL AND METHODS: Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. RESULTS: No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. CONCLUSION: MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.

Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80 mg/kg. After a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8 h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.