Abstract
Head motion is a significant barrier to functional MRI (fMRI) in patients who are unable to tolerate awake scanning, including young children or those with cognitive and behavioural impairments. General anaesthesia minimises motion and ensures patient comfort, however the optimal anaesthesia regimen for fMRI in the paediatric setting is unknown. In this study, we tested the feasibility of anaesthetised fMRI in 11 patients (mean age = 9.8 years) with Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy associated with intellectual disability. fMRI was acquired during clinically-indicated MRI sessions using a synergistic anaesthesia regimen we typically administer for epilepsy neurosurgery: combined low-dose isoflurane (≤ 0.8% end-tidal concentration) with remifentanil (≤ 0.1 mcg/kg/min). Using group-level independent component analysis, we assessed the presence of resting-state networks by spatially comparing results in the anaesthetised patients to resting-state network templates from the ‘Generation R’ study of 536 similarly-aged non-anaesthetised healthy children (Muetzel et al. in Hum Brain Mapp 37(12):4286–4300, 2016). Numerous resting-state networks commonly studied in non-anaesthetised healthy children were readily identifiable in the anaesthetised patients, including the default-mode, sensorimotor, and frontoparietal networks. Independent component time-courses associated with these networks showed spectral characteristics suggestive of a neuronal origin of fMRI signal fluctuations, including high dynamic range and temporal frequency power predominantly below 0.1 Hz. These results demonstrate the technical feasibility of anaesthetised fMRI in children, suggesting that combined isoflurane-remifentanil anaesthesia may be an effective strategy to extend the emerging clinical applications of resting-state fMRI (for example, neurosurgical planning) to the variety of patient groups who may otherwise be impractical to scan.
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Data Availability
Data are available upon reasonable request.
Code Availability
All software applications used to analyse the data are freely available for download from the relevant developer websites (see footnotes provided in the text).
Notes
Abbreviations
- BOLD:
-
Blood-oxygen-level dependent
- fMRI:
-
Functional MRI
- FSL:
-
fMRIB Software Library
- FWE:
-
Family-wise error
- GIFT:
-
Group ICA for fMRI toolbox
- ICA:
-
Independent component analysis
- LF:
-
Iow frequency
- LGS:
-
Lennox-Gastaut syndrome
- HF:
-
High frequency
- MAC:
-
Minimum alveolar concentration
- MNI:
-
Montreal Neurological Institute
- PALM:
-
Permutation Analysis of Linear Models
- PCA:
-
Principal component analysis
- SOCK:
-
Spatially Organized Component Klassifikator
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Acknowledgements
We thank the patients and their families for participating in this research. We also thank Michael Kean and the MRI technologists at The Royal Children’s Hospital for coordinating scanning. We acknowledge the facilities and the scientific and technical assistance of the National Imaging Facility at the Florey node, and the support of the Victorian Government through the Operational Infrastructure Support Grant.
Funding
This work was supported by the National Health and Medical Research Council of Australia (Grant Number 628725, 2010–2013). Aaron E.L. Warren was supported by an Australian Government Research Training Program Scholarship, and post-doctoral fellowship funding from the Lennox-Gastaut syndrome Foundation (www.lgsfoundation.org). David F. Abbott was supported by fellowship funding from the National Imaging Facility. Simon J. Vogrin was supported by the RCH 1000 Fund within the Developmental Imaging research group at the Murdoch Children’s Research Institute and the Children’s MRI Centre, The Royal Children’s Hospital.
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Warren, A.E.L., Davidson, A., Vogrin, S.J. et al. Combined Isoflurane-Remifentanil Anaesthesia Permits Resting-State fMRI in Children with Severe Epilepsy and Intellectual Disability. Brain Topogr 33, 618–635 (2020). https://doi.org/10.1007/s10548-020-00782-5
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DOI: https://doi.org/10.1007/s10548-020-00782-5