Abstract Details

Title Quantitative Magnetisation Transfer Brain Imaging Reveals Altered Biological Integrity of Motor Regions in Amyotrophic Lateral Sclerosis

Topic General Neurology

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-005

Objective 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.

Background 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 [k_f; reflecting macromolecular integrity], and free pool transverse relaxation time [T_2f reflecting water content].

Design/Methods

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.

Results

Skeletonised k_f was reduced throughout the corticospinal tracts (CSTs), precentral gyri, corpus callosum (CC), corona radiata and frontal white matter bilaterally, whereas skeletonised T_2f was increased within the CSTs, CC, corona radiata, cingulate gyrus and frontal white matter bilaterally. f was unchanged. Skeletonised k_f in the CC showed a positive association with ECAS.

Conclusions 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, FAAN	No disclosure on file
	No disclosure on file

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