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

Area of Science:

• Neuroimaging
• Neurology
• Biomarker Development

Background:

• Amyotrophic lateral sclerosis (ALS) involves structural connectivity damage extending beyond motor pathways.
• Diffusion tensor imaging (DTI) can visualize these changes, but requires standardization for biomarker use.
• Multicenter studies are crucial for validating DTI metrics across diverse MRI scanners and patient cohorts.

Purpose of the Study:

• To assess structural connectivity in ALS using DTI across a large, multicenter sample.
• To overcome challenges in processing multiplatform, multicenter DTI data.
• To establish DTI-based anatomical fingerprint patterns reflecting ALS disease stages.

Main Methods:

• Retrospective analysis of 442 DTI datasets from 253 ALS patients and 189 controls across eight international sites.
• Utilized fractional anisotropy (FA) maps and developed correction matrices and algorithms to pool data from varied equipment and protocols.
• Employed whole-brain-based statistical analysis of corrected FA maps.

Main Results:

• Confirmed significant alterations in corticospinal tracts, consistent with previous findings.
• Identified additional white matter tract changes in frontal lobe, brainstem, and hippocampal regions in ALS patients.
• Observed changes correlated with postmortem neuropathological stages and disease severity (ALS Functional Rating Scale).

Conclusions:

• Successfully processed and analyzed multiplatform, multicenter DTI data, demonstrating robust findings.
• Established DTI-based anatomical fingerprint patterns that reflect distinct ALS disease stages.
• Paved the way for using DTI metrics in natural history studies, prognostic stratification, and multisite clinical trials for ALS.