Preclinical modeling of mechanical thrombectomy

Abstract

Mechanical thrombectomy to treat large vessel occlusions (LVO) causing a stroke is one of the most effective treatments in medicine, with a number needed to treat to improve clinical outcomes as low as 2.6. As the name implies, it is a mechanical solution to a blocked artery and modeling these mechanics preclinically for device design, regulatory clearance and high-fidelity physician training made clinical applications possible. In vitro simulation of LVO is extensively used to characterize device performance in representative vascular anatomies with physiologically accurate hemodynamics. Embolus analogues, validated against clots extracted from patients, provide a realistic simulated use experience. In vitro experimentation produces quantitative results such as particle analysis of distal emboli generated during the procedure, as well as pressure and flow throughout the experiment. Animal modeling, used mostly for regulatory review, allows estimation of device safety. Other than one recent development, nearly all animal modeling does not incorporate the desired target organ, the brain, but rather is performed in the extracranial circulation. Computational modeling of the procedure remains at the earliest stages but represents an enormous opportunity to rapidly characterize and iterate new thrombectomy concepts as well as optimize procedure workflow. No preclinical model is a perfect surrogate; however, models available can answer important questions during device development and have to date been successful in delivering efficacious and safe devices producing excellent clinical outcomes. This review reflects on the developments of preclinical modeling of mechanical thrombectomy with particular focus on clinical translation, as well as articulate existing gaps requiring additional research.

Keywords: Acute ischemic stroke; Animal model; Clot; In-vitro model; Thrombectomy device.