A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis

Abstract

ObjectiveDamage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size.Methods442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups.ResultsAnalysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings.InterpretationThis large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

“…1) [14,19]. Naturally, the duration and transition of each stage cannot be determined within the context of post-mortem cross-sectional studies; nevertheless, in vivo diffusion-tensor imaging (DTI) and diffusion-weighted imaging (DWI)-based results gained from ALS patients fit in well with the proposed hypothetical sequence of neuropathological staging [20][21][22][23][24]. stage 1: Abnormal changes develop not only in Betz pyramidal cells in the deep layer Vb of the primary motor cortex (Brodmann field 4) [25] but also in lower brainstem and spinal cord α-motor neurons (▶Fig.…”

New insights into the clinical neurophysiological assessment of ALS

“…The results provided by TST were shown to correlate to those provided by DTI [46], but the TST was found to be frankly more sensitive in the detection of UMN involvement in ALS patients [43]. However, a recent multicentre study showed that the reliability of DTI tractography might improve in terms of specificity and sensitivity in the diagnosis of ALS, but on condition of using complex processing and analysis methods [69]. Thus, the real value of this technique in the individual diagnosis of ALS remains to be determined in daily practice.…”

Revealing the microstructural brain damage in amyotrophic lateral sclerosis: the relentless pursuit to approach an imaging biomarker

“…Despite all this clinical and etiopathogenic complexity, some faces of ALS, including FTD-MND continnum, have been elucidated by magnetic resonance imaging (MRI) techniques, which have proved to be useful to reveal microstructural brain abnormalities associated with different rates of symptom progression 6,7 . A plausible biomarker for upper motor neuron degeneration in ALS is becoming tangible after recent advances in high-throughput MRI techniques, through which one can believe that we are going to the forefront of a breakthrough able to translate research findings into reliable clinical tests that will support the practice of personalized medicine 8,9,10 .…”