Abstract

Introduction Large animal models are utilized for preclinical neuroendovascular research, and aid in the characterization and de‐risking of novel therapeutic approaches. To date, only a single prior study has been published providing a detailed account of an ovine model (Corriedale sheep) for cerebral venous access. The generalizability of these experiments has not yet been validated externally. In an effort to replicate these findings and de‐risk a novel, non‐surgical trans‐dural venous sinus approach to the cerebrum, cerebral venous access was attempted in 3 sheep specimens using transcranial and endovascular approaches. We report our experience validating this large animal model for translational and preclinical research. Methods 3 animal experiments were performed at the UCLA TRIC laboratory between 02/2022 and 10/2022. The sheep were anesthesitized and handled under approval of the Animal Research Committee at UCLA (protocol ARC 2020‐19). The neck and groin areas were shaved and aseptically prepped. MRI Brain and MR Brain venogram imaging was performed on a 3T Siemens Magnetom MRI. Femoral artery and external jugular vein access were obtained using the Seldinger technique under ultrasound guidance and did not require a surgical cut down. Two Suffolk and one Rambouillet sheep were used (average weight 60 kg and 40 kg, respectively). The animals were transferred to the catheter laboratory and image guidance was performed with a monoplane Siemens Artis Zeego. A transcranial approach to the dorsal sagittal sinus was attempted in one Suffolk sheep specimen utilizing a Hubly Drill and a micro‐puncture kit. An endovascular approach to the dorsal sagittal sinus was attempted in second Suffolk sheep specimen using a 25 cm, 8 Fr Pinnacle Sheath via the external jugular vein followed by a 132 cm Catalyst 5 catheter, 0.027" Medtronic Marksman, Stryker SL‐10 and Offset microcatheters assembled over 0.014" Synchro Standard and exchange‐length Choice PT microguidewires. In a third experiment, an endovascular approach to the dorsal sagittal sinus was attempted in a Rambouillet sheep specimen using a 95 cm TracStar, 115 cm Catalyst 5 catheter, and 0.027" Medtronic Marksman microcatheter assembled over 0.014" Synchro Standard and exchange‐length Boston Scientific (BS) Choice PT microguidewires. The 0.027" Marksman microcatheter was subsequently exchanged for a 2.7 French BS Stingray LP coronary CTO re‐entry microcatheter in the Rambouillet sheep, which was tracked to the anterior third of the dorsal sagittal sinus over the exchange length wire. Results A transcranial approach to the dorsal sagittal sinus was complicated by misaligned needle trajectories resulting in brain parenchymal damage. The external jugular vein was the conduit for accessing the first and second emissary veins of the retroauricular foramen (figure 2). Access to the temporal and then transverse sinuses was possible from either of the aforementioned emissary veins. Interestingly, the morphology of the dorsal sagittal sinus was bifid and each vessel channel measured between 1.65 – 1.7 mm in diameter (figure 1). Access to the temporal sinus from an endovascular approach was possible with all microcatheters. However, access with a 0.027" microcatheter beyond the torcular herophili and into the dorsal sagittal sinus was only possible in the Rambouillet sheep despite its smaller body size. Intermediate catheters (>4 Fr) could not be advanced beyond the skull base in none of the sheep breeds. Lastly, microcatheter advancement into the cerebral hemispheric space across a transdural venous sinus puncture access point deliberately created by wire perforation was feasible from the Stingray re‐entry system after exchanging for a 0.017" microcatheter. A coil (Stryker Target) was deployed extravascularly from the 0.017" microcatheter for post‐mortem characterization (figure 3). Conclusion One of three experiments met criteria for success. Due to reliance on a monoplane projection, a transcranial approach failed as an access route to the dorsal sagittal sinus resulting in iatrogenic parenchymal damage. Despite the larger body size, the second Suffolk sheep dural venous sinus system could not be catheterized beyond the skull base, likely due to the small caliber or focal stenosis of the temporal or transverse sinuses. The Rambouillet sheep breed proved to be a more adequate specimen for cerebral venous—specifically dorsal sagittal sinus—access with larger bore microcatheters. Based on this experience, careful selection of an appropriate sheep breed is necessary for modeling endovascular cerebral venous access and assessing novel procedures.

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