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Abstract Details

Quantitative Magnetisation Transfer Brain Imaging Reveals Altered Biological Integrity of Motor Regions in Amyotrophic Lateral Sclerosis
General Neurology
P14 - Poster Session 14 (8:00 AM-9:00 AM)
6-005
To undertake tract-based spatial statistics (TBSS) of quantitative magnetisation transfer imaging (qMTi) parameters in amyotrophic lateral sclerosis (ALS), in order to investigate the molecular mechanisms underlying disease pathogenesis.
ALS is a devastating disease characterised by loss motor neurons, but the biological mechanisms underlying the dynamics of the degenerative process remain unclear. Quantitative MRI techniques allow us to probe microstructural changes in the central nervous system. qMTi detects changes to semisolid macromolecular components (principally myelin) by observing transfer of magnetisation from the visible “free” water pool to the nearby semisolid pool.  qMTi parameters include the macromolecular fraction [f; representing myelin content], rate of magnetisation transfer [kf; reflecting macromolecular integrity], and free pool transverse relaxation time [T2f reflecting water content].

A Siemens Avanto 1.5T imager acquired qMTi and diffusion MRI brain scans of 23 ALS patients and 23 age-matched controls.  Patients’ disease duration, progression rate, ALS functional rating scale (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) scores were recorded.  Non-parametric permutation-based statistical analyses were performed applying threshold-free cluster enhancement using parameter voxels ‘skeletonised’ to within the main white matter tracts, and corrected for multiple comparisons at cluster level.

Skeletonised kf was reduced throughout the corticospinal tracts (CSTs), precentral gyri, corpus callosum (CC), corona radiata and frontal white matter bilaterally, whereas skeletonised T2f was increased within the CSTs, CC, corona radiata, cingulate gyrus and frontal white matter bilaterally.  f was unchanged.  Skeletonised kf in the CC showed a positive association with ECAS. 

In line with animal models of ALS demonstrating early breakdown of neuron-oligodendrocyte relationships, these findings suggest that although myelin content is not significantly reduced there is altered molecular integrity and/or composition within the cerebral white matter within motor areas.  This is associated with an augmented proportion of free water, a proxy measure of atrophy, supporting neurodegeneration within these regions.
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
Peter N. Leigh, BSc, MB, FÂ鶹´«Ã½Ó³»­ No disclosure on file
No disclosure on file