Multiple-mouse magnetic resonance imaging with cryogenic radiofrequency probes for evaluation of brain development
A. Arbabi,
L. Spencer Noakes,
D. Vousden,
J. Dazai,
S. Spring,
O. Botelho,
T. Keshavarzian,
M. Mattingly,
J.E. Ellegood,
L.M.J. Nutter,
R. Wissmann,
J.G. Sled,
J.P. Lerch,
R.M. Henkelman,
B.J. Nieman
Affiliations
A. Arbabi
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands
L. Spencer Noakes
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Pre-Therapeutic Target Discovery, Regeneron Pharmaceuticals, Tarrytown, NY, United States
D. Vousden
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; DataKind UK, London, UK
J. Dazai
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada
S. Spring
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada
O. Botelho
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada
T. Keshavarzian
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
M. Mattingly
Bruker BioSpin Corporation, Billerica, MA, United States
J.E. Ellegood
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada
L.M.J. Nutter
The Centre for Phenogenomics, Hospital for Sick Children, Toronto, ON, Canada
R. Wissmann
Bruker BioSpin Corporation, Ettlingen, Germany
J.G. Sled
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
J.P. Lerch
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
R.M. Henkelman
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
B.J. Nieman
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Corresponding author. Brian J. Nieman, Hospital for Sick Children, Mouse Imaging Centre, The Centre for Phenogenomics, 25 Orde St, Toronto, ON, Canada, M5T 3H7.
Multiple-mouse magnetic resonance imaging (MRI) increases scan throughput by imaging several mice simultaneously in the same magnet bore, enabling multiple images to be obtained in the same time as a single scan. This increase in throughput enables larger studies than otherwise feasible and is particularly advantageous in longitudinal study designs where frequent imaging time points result in high demand for MRI resources. Cryogenically-cooled radiofrequency probes (CryoProbes) have been demonstrated to have significant signal-to-noise ratio benefits over comparable room temperature coils for in vivo mouse imaging. In this work, we demonstrate implementation of a multiple-mouse MRI system using CryoProbes, achieved by mounting four such coils in a 30-cm, 7-Tesla magnet bore. The approach is demonstrated for longitudinal quantification of brain structure from infancy to early adulthood in a mouse model of Sanfilippo syndrome (mucopolysaccharidosis type III), generated by knockout of the Hgsnat gene. We find that Hgsnat−/− mice have regionally increased growth rates compared to Hgsnat+/+ mice in a number of brain regions, notably including the ventricles, amygdala and superior colliculus. A strong sex dependence was also noted, with the lateral ventricle volume growing at an accelerated rate in males, but several structures in the brain parenchyma growing faster in females. This approach is broadly applicable to other mouse models of human disease and the increased throughput may be particularly beneficial in studying mouse models of neurodevelopmental disorders.
