Article Text
Abstract
Introduction Ischemic stroke is a leading cause of death and significant long-term disability worldwide. Mechanical thrombectomy is emerging as a standard treatment for eligible patients with large vessel occlusion (LVO) stroke over stent retrievers and drug therapy (tissue plasminogen activator – tPA). As clinical implementation of stent retrieval and aspiration thrombectomy increases, a need exists for physiologically relevant in vitro device efficacy testing. Critical to this testing is the development of standardized ‘soft’ and ‘hard’ synthetic blood clots that mimic the properties of human thrombi and are compatible with imaging technologies. Synthetic clots allow researchers to extract information regarding clot integration, model hemodynamic conditions, and quantify the physics of thrombectomy.
Methods This work develops polyacrylamide and alginate-based synthetic clots that are compatible with particle image velocity (PIV) and radiographic imaging techniques while maintaining mechanical properties of ‘soft’ and ‘hard’ human clots. These synthetic clots have standardized, repeatable mechanical properties that mimic two general human thrombi classifications: soft clot and hard clot, which together represent 80% of the human clots removed via mechanical thrombectomy each year. Dynamic mechanical analysis (DMA) testing using an HR2-Rheometer demonstrates comparable mechanical properties to human clots previously tested by this research group and provided in existing literature.
Results The synthetic clots are formulated with either 0.5%w/v polyethylene microspheres for PIV visualization or 20%w/v barium sulfate for angiographic visualization, enabling real-time imaging of clot behavior during thrombectomy simulations. To standardize a physiologically similar ‘hard’ and ‘soft’ clots, adjustments were made to the polymer solvent while keeping the polymer components, polyacrylamide (PAAM) and alginate (Alg) constant for both clots. Final clot formulation range was identified as 80 – 89vol% solvent for all PIV clots and 87 – 93vol% solvent for barium sulfate clots. The soft formulation shows compressive and shear properties of 8–9KPa and 2–3KPa, respectively. The hard clots are 4–6x stiffer, with compressive and shear properties of 41–42KPa and ~12KPa, respectively (table 1).
Conclusion Standardized synthetic clots offer a platform for reproducible device testing. Future research directions involve refining clot formulations for other clot types (i.e calcified, fibrin rich, etc.), exploring additional imaging technologies, and further enhancing the relevance of synthetic clots for device testing. This work provides a greater understanding of mechanical thrombectomy device efficacy, which may lead to quantifiable advances in device development and eventual improved clinical outcomes.
Disclosures K. Lewis: None. S. Robertson: None. H. Berns: None. J. Wells: None. W. Clark: None. T. Becker: 1; C; National Institute of Health.