Canine Model for Selective and Superselective Cerebral Intra-Arterial Therapy Testing

Abstract

Purpose: With advancing endovascular technology and increasing interest in minimally invasive intra-arterial therapies such as stem cell and chemotherapy for cerebral disease, the establishment of a translational model with cerebral circulation accessible to microcatheters is needed. We report our experience catheterizing canine cerebral circulation with microcatheters, present high-resolution angiographic images of the canine vascular anatomy, describe arterial branch flow patterns and provide measurements of canine arterial conduits.Materials and Methods: Angiograms were performed on 10 intact purpose-bred hounds. Angiography, measurements of arterial conduits and catheterization information for intracranial arterial branches were obtained.Results: Selective and superselective cerebral angiography was successful in all subjects. Relevant arterial mean diameters include the femoral (4.64 mm), aorta (9.38 mm), external carotid (3.65 mm), internal carotid arteries (1.6 mm), vertebrobasilar system and Circle of Willis branches. Catheterization of the Circle of Willis was achieved via the posterior circulation in all subjects tested (n=3) and the use of flow directed microcatheters resulted in reduced arterial tree deformation and improved superselection of intracranial vessels. Catheterization of the intracranial circulation was attempted but not achieved via the internal carotid artery (n=7) due to its tortuosity and subsequent catheter related vasospasm.Conclusion: The canine cerebral vasculature is posterior circulation dominant. Anterior circulation angiography is achievable via the internal carotid artery, but direct cerebral arterial access is best achieved via the posterior circulation using flow-directed microcatheters. It is feasible to deliver intra-arterial therapies to selective vascular territories within the canine cerebral circulation, thus making it a viable animal model for testing novel intra-arterial cerebral treatments.

Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

“…The IA route was shown to be safe and cell targeting efficiency was superior compared to the IV route in animal models 8 . Cannulation of MCA via ICA in dogs was successful using 1.2 F microcatheter in contrast to Camstra et al 28 who reported frequent vasospasms while transitioning through tortuosities of ICA. We have demonstrated an excellent safety profile for the GRP delivery procedure in all transplanted animals.…”

Intra-Arterial Transplantation of Stem Cells in Large Animals – A Minimally-Invasive Strategy for the Treatment of Disseminated Neurodegeneration

“…The IA route was shown to be safe and cell targeting e ciency was superior compared to the IV route in animal models 17 . Cannulation of MCA via ICA in dogs was successful using 1.2 F microcatheter in contrast to Camstra et al 18 who reported frequent vasospasms while transitioning through tortuosities of ICA. We have demonstrated an excellent safety pro le for the GRP delivery procedure in all transplanted animals.…”

Preclinical animal brain tumor models for interventional neuro-oncology

“…While dogs can potentially increase drug development speeds by bypassing the phases of testing needed for a human trial, recruitment of client dogs with naturally occurring brain tumors is slow and limited by similar issues as a human trial. Moreover, in preliminary studies with non-tumor bearing canines, although ESIA infusion can be safely performed,11 the canine model presents significant limitations imposed by internal carotid artery tortuosity, high cost, and ethical handling issues 12. To address these issues, we and others13 turned to rabbits with relatively straight internal carotid anatomy, and whose costs and handling are more conducive to large studies.…”