Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis
Chaoyue Wang,
Sean Foxley,
Olaf Ansorge,
Sarah Bangerter-Christensen,
Mark Chiew,
Anna Leonte,
Ricarda AL Menke,
Jeroen Mollink,
Menuka Pallebage-Gamarallage,
Martin R Turner,
Karla L Miller,
Benjamin C. Tendler
Affiliations
Chaoyue Wang
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom; Corresponding author.
Sean Foxley
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom; Department of Radiology, University of Chicago, United States
Olaf Ansorge
Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
Sarah Bangerter-Christensen
Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom; Brigham Young University, Provo, United States
Mark Chiew
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom
Anna Leonte
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom; University of Groningen,the Netherlands
Ricarda AL Menke
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom
Jeroen Mollink
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom; Department of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, the Netherlands
Menuka Pallebage-Gamarallage
Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
Martin R Turner
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom; Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
Karla L Miller
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom
Benjamin C. Tendler
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom
Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology.Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices.Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex.Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.
