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An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis

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Abstract

Purpose

Intraventricular hemorrhage (IVH) affects approximately 50% of premature births where 50% further develop post-hemorrhagic ventricular dilation (PHVD). Patients face significant impact to long-term development if PHVD is not managed. Unfortunately, there is no accepted treatment to remove the thrombus caused by IVH. This paper describes an acute and chronic IVH model for use with magnetic resonance-guided focused ultrasound (MRgFUS) thrombolysis.

Methods

A total of 12 pigs (~ 1 month in age) were used in the model (eight acute and four chronic). A pre-operative brain MRI was obtained for ventricular targeting. 1.25 cm3/kg of autologous blood was injected through a burr hole lateral to the midline and anterior of the coronal suture at a rate of 0.6 cm3/min. A craniotomy was performed to simulate a “fontanelle”. Post-operative MRI was used to calculate the clot volume. Chronic piglets were recovered, monitored daily with a neurological scoring system (NSS), and MRI scanned for 21 days.

Results

The clot injection was well tolerated. The average clot size was 3987 mm3 (median = 4330 mm, standard deviation = 739 mm3). Postmortem examination validated the presence of the clot. In the chronic animals, there was an increase in ventricular volume of 30%. Transient neurological impairment immediately followed clot injection and with onset of hydrocephalus in the chronic animals.

Conclusions

This model establishes a measurable and targetable IVH clot in an MRI-based neonatal porcine model. The progressive post-hemorrhagic ventricular dilation in the chronic model is a potential alterable outcome from MRgFUS thrombolysis.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Anson Lam and Marvin Estrada at the Hospital for Sick Children for their animal support. This work was funded by Brain Canada and the Hospital for Sick Children.

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Authors and Affiliations

  1. University of Toronto, Toronto, Canada

    Thomas Looi, Adam Waspe, Kullervo Hynynen & James Drake

  2. Hospital for Sick Children, Toronto, Canada

    Thomas Looi, Karolina Piorkowska, Adam Waspe & James Drake

  3. University Medical Center Utrecht, Utrecht, Netherlands

    Charles Mougenot

  4. Sunnybrook Research Institute, Toronto, Canada

    Kullervo Hynynen

Authors
  1. Thomas Looi
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  2. Karolina Piorkowska
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  3. Charles Mougenot
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  4. Adam Waspe
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  5. Kullervo Hynynen
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  6. James Drake
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Correspondence to Thomas Looi.

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Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Looi, T., Piorkowska, K., Mougenot, C. et al. An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis. Childs Nerv Syst 34, 1643–1650 (2018). https://doi.org/10.1007/s00381-018-3816-8

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  • DOI: https://doi.org/10.1007/s00381-018-3816-8

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