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Basic science
Original research
Preclinical model of anterior circulation intracranial stenting
  1. Vania Anagnostakou1,
  2. Robert M King1,
  3. Liza Gutierrez2,
  4. Johanna D Black1,
  5. Juliana Lee3,
  6. Renu Virmani4,
  7. Ajit S Puri1,
  8. Adnan H Siddiqui5,6,
  9. Matthew J Gounis1
  1. 1 Department of Radiology, New England Center for Stroke Research, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
  2. 2 Canon Stroke and Vascular Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
  3. 3 StageBio, Frederick, Maryland, USA
  4. 4 Department of Cardiology, CVPath, Gaithersburg, Maryland, USA
  5. 5 Department of Neurosurgery and Radiology and Canon Stroke and Vascular Research Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA
  6. 6 Department of Neurosurgery, Gates Vascular Institute, Buffalo, New York, USA
  1. Correspondence to Professor Matthew J Gounis, Department of Radiology, New England Center for Stroke Research, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA; matthew.gounis{at}umassmed.edu

Abstract

Background Preclinical testing of intracranial stents is currently performed in the peripheral circulation, and rarely in the basilar artery of the dog.

Objective To test the feasibility of intracranial stenting in the middle cerebral artery (MCA) of the dog and explore the use of MRI to detect thromboembolic complications.

Methods Six purpose-bred cross-hound dogs were used for proof-of-concept stenting of both MCAs in each animal. Immediately following the procedure, the animals were imaged with MRI. MRI was repeated weekly for 1 month. After the final angiography at 30 days, the animals were euthanized for pathological assessment of the stents and the brain.

Results We successfully deployed 12 stents in the MCAs of all animals. We deployed three techniques for microcatheterization of the MCA—namely, directly through the internal carotid artery (ICA), using anastomotic arteries from the external carotid artery, or via the contralateral ICA through the anterior communicating artery. Two iatrogenic perforations of the ICA with formation of an arteriovenous fistula occurred, without clinical sequelae, which spontaneously resolved on follow-up. All animals tolerated the procedure and completed the follow-up surveillance. MRI revealed procedural thromboembolic induced areas of restricted diffusion, and only one instance of a delayed thromboembolic lesion during surveillance. At follow-up angiography, the devices were all patent.

Conclusion We describe a new preclinical model of intracranial stenting in the MCA. Such a model may prove useful for evaluating new surface modifications.

  • aneurysm
  • atherosclerosis
  • device
  • intervention

Data availability statement

Data are available upon reasonable request. Data are available by contacting the corresponding author.

https://doi.org/10.1136/jnis-2022-019692

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    Data availability statement

    Data are available upon reasonable request. Data are available by contacting the corresponding author.

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    Footnotes

    • Twitter @AjitSPuri1

    • Contributors VA, MJG: planning, conception, and design of the study, acquisition of data, analysis, interpretation of data, and drafting the manuscript. They are guarantors of the report. RMK, LG, JL, JDB, RV: data acquisition, protocol development, and all technical aspects of animal modeling and pathology. Provided critical editing of the manuscript. ASP, AHS: major contributions to study design and model development. Provided critical editing of the manuscript. All authors approved the final version of this manuscript to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding This study was sponsored by Imperative Care.

    • Competing interests MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; 2. Research support from the NIH, the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 3. Associate editor of basic science on the JNIS editorial board. RV: grants from the NIH, Leducq Foundation, 4C Medical, 4Tech, Abbott Vascular, Ablative Solutions, Absorption Systems, Advanced NanoTherapies, Aerwave Medical Inc, Alivas, Amgen Inc, Asahi Medical, Aurios Medical, Avantec Vascular, BD Bioscences, Biosensors, Biotronik, Biotyx Medical, Bolt Medical Inc, Boston Scientific, Canon Inc, Cardiac Implants LLC, Cardiawave, CardioMech, Cardionomic, CeloNova BioSciences Inc, Cerus Endovascular Inc, Chansu Vascular Technologies LLC, Children’s National Medical Center, Concept Medical, Cook Medical, Cooper Health, Cormaze Technologies GmbH, CRL/AccelLab, CroíValve, CSI, DexCom Inc, Edwards Lifesciences, Elucid Bioimaging, eLum Technologies Inc, Emboline Inc, Endotronix, Envision, Filterlex, Imperative Care Inc, Innovative Cardiovascular Solutions LLC, Intact Vascular Inc, Interface Biolgics, InterShunt Technologies Inc, Invatin Technologies, Lahav CRO, LimFlow, L & J Biosciences, Lutonix, Lyra Therapeutics Inc, Mayo Clinic, Maywell, MD Start, MedAlliance, Medanex Clinic, Medtronic plc, Mercator Limited, MicroPort, MicroVention, Neovasc Inc, Nephronyx Ltd, Nova Vascular, Nyra Medical, Occultech, Olympus Therapeutics, OhioHealth, OrbusNeich, Ossio, phenox Inc, Pi-Cardia, Polares Medical, PolyVascular, Profusa Inc, ProKidney LLC, Protembis, Pulse Biosciences Inc, Qool Therapeutics, Recombinetics, ReCor Medical Inc, Regencor Inc, Renata Medical, Restore Medical Ltd, Ripple Therapeutics, Rush University, Sanofi SA, Shockwave Medical, Sahajanand Medical Technologies Limited, SoundPipe, Spartan Micro, SpectraWAVE Inc, Surmodics Inc, Terumo Corporation, Jacobs Institute, Transmural Systems LLC, Transverse Medical Inc, TruLeaf Medical, University of California, San Francisco, University of Pennsylvania Medical Center, Vascudyne Inc, Vesper, Vetex Medical, WhiteSwell, WL Gore and Associates Inc, and Xeltis and personal fees from Abbott Vascular, Boston Scientific, CeloNova BioSciences Inc, OrbusNeich, Terumo Corporation, W. L. Gore and Associates Inc, Edwards Lifesciences, Cook Medical, CSI, ReCor Medical, Sino Medical Sciences Technology Inc, Surmodics Inc, Bard BD, Medtronic plc, and Xeltis outside the submitted work. ASP: 1. Consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical; 2. Research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular; 3. Stockholder: InNeuroCo, Agile, Perfuze, Galaxy, and NTI. AHS: consulting fees: Amnis Therapeutics, Apellis Pharmaceuticals, Inc., Boston Scientific, Canon Medical Systems USA, Inc., Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc., Cerenovus, Cerevatech Medical, Inc., Cordis, Corindus, Inc., Endostream Medical, Ltd, Imperative Care, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc., Penumbra, Q’Apel Medical, Inc., Rapid Medical, Serenity Medical, Inc., Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc., VasSol, Viz.ai, Inc., W.L. Gore and Associates. Leadership or fiduciary role in other board, society, committee or advocacy group: Past secretary of the board of the Society of NeuroInterventional Surgery (2020-2021), chair of the Cerebrovascular Section of the AANS/CNS. Stock or stock options: Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc., Cognition Medical, CVAID Ltd., E8, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., International Medical Distribution Partners, Launch NY, Inc., NeuroRadial Technologies, Inc., Neurotechnology Investors, Neurovascular Diagnostics, Inc., PerFlow Medical, Ltd., Q’Apel Medical, Inc., QAS.ai, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc. (purchased 2020 by Medtronic), Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc., Cognition Medical, CVAID Ltd., E8, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., International Medical Distribution Partners, Launch NY, Inc., NeuroRadial Technologies, Inc., Neurotechnology Investors, Neurovascular Diagnostics, Inc., PerFlow Medical, Ltd., Q’Apel Medical, Inc., QAS.ai, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc. (Purchased 2020 by Medtronic), Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, SongBird Therapy, Spinnaker Medical, Inc., StimMed, LLC, Synchron, Inc., Three Rivers Medical, Inc., Truvic Medical, Inc., Tulavi Therapeutics, Inc., Vastrax, LLC, VICIS, Inc., Viseon, Inc. Other financial or non-financial interests: National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.