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Original research
Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept
  1. Jildaz Caroff1,
  2. Robert M King2,4,
  3. Jennifer E Mitchell3,
  4. Miklos Marosfoi2,
  5. Joseph R Licwinko3,
  6. Heather L Gray-Edwards2,
  7. Ajit S Puri2,
  8. Thomas L Merrill3,5,
  9. Matthew J Gounis2
  1. 1Interventional Neuroradiology, NEURI Center, Bicêtre Hospital, Le Kremlin- Bicêtre, France
  2. 2New England Center for Stroke Research, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  3. 3FocalCool, Mullica Hill, New Jersey, USA
  4. 4Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA
  5. 5Department of Mechanical Engineering, Rowan University, Glassboro, NJ, USA
  1. Correspondence to Dr Matthew J Gounis, Department of Radiology, University of Massachusetts, Worcester MA 1655, USA; matthew.gounis{at}umassmed.edu

Abstract

Introduction The neuroprotective benefit of therapeutic hypothermia (TH) has been demonstrated, but systemic side effects and time required to achieve effective TH in acute ischemic stroke (AIS) care limits clinical use. We investigate rapid and localized cooling using a novel insulated catheter in an ischemia-reperfusion model.

Methods In phase I (n=4), cold saline was delivered to the canine internal carotid artery via an insulated catheter. Temperature was measured using intracerebral thermocouples. The coolant flow rate was varied to meet a target temperature of 31–32°C in the hemisphere infused. In phase II (n=8), a temporary middle cerebral artery occlusion was created. Five dogs underwent localized TH at the optimal flow rate from phase I, and the remaining animals were untreated controls. Cooling was initiated 5 min before recanalization and continued for an additional 20 min following 45 min of occlusion duration. The outcome was infarct volume and neurological function.

Results Ipsilateral tissue cooling rates were 2.2±2.5°C/min at a flow rate of 20–40 mL/min with an observed minimum of 23.8°C. Tissue cooling was localized to the ipsilateral side of the infusion with little impact on temperatures of the core or contralateral hemisphere of the brain. In phase II, animals tolerated TH with minimal systemic impact. Infarct volume in treated animals was 0.2±0.2 cm3, which was smaller than in sham animals (3.8±1.0 cm3) as well as six untreated historical control animals (4.0±2.8 cm3) (p=0.013).

Conclusions Proof-of-concept data show that localised brain TH can be quickly and safely achieved through a novel insulated catheter. The small infarct volumes suggest potential benefit for this approach.

  • acute ischemic stroke
  • mechanical thrombectomy
  • animal model
  • hypothermia
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Footnotes

  • Contributors All authors: designed and performed the experiments, analysed the data, drafted the manuscript, and approved the final manuscript.

  • Funding This research was funded by NIH 1 R43 NS095573-01A1 (PI: TLM). JC was supported by research grants from the Fulbright Program, the Philippe Foundation, and the French Society of Radiology (SFR-CERF). The content is solely the responsibility of the authors and does not reflect the opinions of the sponsors.

  • Competing interests RMK declares no competing interest. JC: has received educational scholarships from Medtronic Neurovascular and Microvention/Terumo. MM: Fee-for-service consulting for Stryker Neurovascular and InNeuroCo. JEM, JRL. and TLM: are employees of FocalCool. ASP: consultant for Medtronic Neurovascular and Stryker Neurovascular; research grants from Medtronic Neurovascular and Stryker Neurovascular. MJG: has been a consultant on a fee-per-hour basis for Cerenovus, Imperative Care, Mivi Neurosciences, Phenox, Route 92 Medical, Stryker Neurovascular; holds stock in Imperative Care and Neurogami; and has received research support from the National Institutes of Health (NIH), USA–Israel Binational Science Foundation, Anaconda, Cerenovus, Cook Medical, Gentuity, Imperative Care, InNeuroCo, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Neuravi, Neurogami, Philips Healthcare, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, and the Wyss Institute.

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

  • Data sharing statement Data presented in the manuscript.

  • Patient consent for publication Not required.

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