Ultra-high-resolution mapping of myelin and g-ratio in a panel of Mbp enhancer-edited mouse strains using microstructural MRI
Vladimir Grouza,
Hooman Bagheri,
Hanwen Liu,
Marius Tuznik,
Zhe Wu,
Nicole Robinson,
Katherine A. Siminovitch,
Alan C. Peterson,
David A. Rudko
Affiliations
Vladimir Grouza
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Hooman Bagheri
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
Hanwen Liu
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Marius Tuznik
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Zhe Wu
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
Nicole Robinson
Histology Innovation Platform, Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada
Katherine A. Siminovitch
Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada; Mount Sinai Hospital, Lunenfeld-Tanenbaum and Toronto General Hospital Research Institutes, Toronto, Ontario, Canada
Alan C. Peterson
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada
David A. Rudko
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada; Corresponding author at: Montreal Neurological Institute and Hospital, Office WB314, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
Non-invasive myelin water fraction (MWF) and g-ratio mapping using microstructural MRI have the potential to offer critical insights into brain microstructure and our understanding of neuroplasticity and neuroinflammation. By leveraging a unique panel of variably hypomyelinating mouse strains, we validated a high-resolution, model-free image reconstruction method for whole-brain MWF mapping. Further, by employing a bipolar gradient echo MRI sequence, we achieved high spatial resolution and robust mapping of MWF and g-ratio across the whole mouse brain. Our regional white matter-tract specific analyses demonstrated a graded decrease in MWF in white matter tracts which correlated strongly with myelin basic protein gene (Mbp) mRNA levels. Using these measures, we derived the first sensitive calibrations between MWF and Mbp mRNA in the mouse. Minimal changes in axonal density supported our hypothesis that observed MWF alterations stem from hypomyelination. Overall, our work strongly emphasizes the potential of non-invasive, MRI-derived MWF and g-ratio modeling for both preclinical model validation and ultimately translation to humans.
