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Published on: February 19, 2021
Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic
Chaoyue Wang1, Sean Foxley2, Olaf Ansorge3
1Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, United Kingdom.
Abstract:
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.
Insights
Quantitative susceptibility mapping (QSM) and R2* mapping reveal increased iron and myelin in the motor cortex of amyotrophic lateral sclerosis (ALS) brains. This MRI technique aids in understanding neurodegenerative disease mechanisms.
Area of Science:
- Neuroimaging
- Neurodegenerative Diseases
- Biophysics
Background:
- Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to iron and myelin concentrations.
- Quantitative susceptibility mapping (QSM) and R2* mapping provide insights into tissue composition.
Purpose of the Study:
- To develop and validate a processing pipeline for QSM and R2* mapping in fixed post-mortem whole brains.
- To compare QSM and R2* maps between amyotrophic lateral sclerosis (ALS) and control brains.
- To correlate MRI findings with histological measures of iron and myelin.
Main Methods:
- A multi-echo gradient echo sequence at 7T was used to scan twelve fixed post-mortem brains.
- Quantitative susceptibility mapping (QSM) and R2* maps were generated.
- Histological analysis of ferritin and myelin proteolipid protein was performed in specific cortical regions.
Main Results:
- Higher magnetic susceptibility and R2* values were observed in the primary motor cortex of ALS brains compared to controls.
- Positive correlations were found between magnetic susceptibility, R2* values, and histological estimates of myelin and ferritin.
- Four out of nine ALS brains showed hyperintense susceptibility and R2* signals in the primary motor cortex.
Conclusions:
- The developed MRI pipeline is robust for quantitative analysis of fixed post-mortem brains.
- Elevated iron and myelin in the motor cortex may be a feature of ALS.
- MRI-histology studies in post-mortem brains can elucidate the sources of susceptibility weighted MRI signals in neurodegeneration.
