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Original research
Development of an in vitro model of calcified cerebral emboli in acute ischemic stroke for mechanical thrombectomy evaluation
  1. Sarah Johnson1,
  2. Ray McCarthy2,
  3. Brian Fahy2,
  4. Oana Madalina Mereuta3,
  5. Seán Fitzgerald3,
  6. Julien Gaudirc4,
  7. Jean-Paul Remadi5,
  8. Eimad Shotar6,
  9. Nader-Antoine Sourour6,
  10. Karen Doyle3,
  11. Michael Gilvarry2,
  12. Patrick McGarry1,
  13. Peter E McHugh1,
  14. Frédéric Clarençon6,7
  1. 1 Biomedical Engineering, National University of Ireland Galway, Galway, Ireland
  2. 2 Cerenovus, Galway Neuro Technology Centre, Galway, Ireland
  3. 3 Department of Physiology, National University of Ireland Galway, Galway, Ireland
  4. 4 Department of Vascular Surgery, Pitié-Salpêtrière Hospital, Paris, France
  5. 5 Department of Cardiac Surgery, Amiens University Hospital, Amiens, France
  6. 6 Department of Neuroradiology, Pitie-Salpetriere Hospital, Paris, France
  7. 7 Sorbonne University, Paris, France
  1. Correspondence to Dr Frédéric Clarençon, Department of Interventional Neuroradiology, Groupe hospitalier Pitié Salêtrière, Paris 75013, France; fredclare5{at}


Background Calcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low.

Objective To recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA).

Methods An in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques.

Results CCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter.

Conclusion Characterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.

  • embolic
  • device
  • stroke
  • thrombectomy

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  • PEM and FC are joint senior authors.

  • Twitter @FitzSeanT

  • Contributors SJ was involved in study design, clot preparation, mechanical testing, micro-CT analysis, data analysis and interpretation, and manuscript writing and editing. RM was involved in study design, clot preparation, data analysis and interpretation, and manuscript writing and editing. BF was involved in in vitro model development, retrieval procedures, and associated data analysis and manuscript editing. OMM, SF, and KD performed histological staining and quantification and associated data analysis. JG, J-PR, ES, N-AS, and FC extracted and collected the calcified carotid plaque and cardiac valve samples. MG was involved in the initial concept of forming clot analogs and manuscript editing. PM and PEM contributed to the interpretation of the results and manuscript editing. FC was involved in the concept and study design, data analysis and interpretation, and manuscript writing and editing and performed the retrieval procedures. All authors reviewed, edited, and approved the final manuscript.

  • Funding This work was supported by Cerenovus, the Irish Research Council (grant No EPSPG/2015/92) and the NUI Galway Hardiman Research Scholarship.

  • Competing interests SJ reports grants from the Irish Research Council and the NUI Galway Hardiman Research Scholarship during the conduct of the study, and reports financial support from Cerenovus, outside the submitted work. RM and MG report a financial relationship with Cerenovus outside the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval The institutional review board and research ethics committee (National University of Ireland Galway REC 16-Sep-08) gave approval for this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Please contact the corresponding author with data sharing requests.