TRAMFIX: TRavelling Across Melbourne for FIXel-based analysis (a reproducibility and reliability study)

Area of Science:

• Neuroimaging
• Diffusion MRI
• White Matter Analysis

Background:

• Fixel-based analysis (FBA) is a powerful tool for examining white matter microstructure using diffusion-weighted imaging (DWI).
• Assessing the reproducibility and reliability of FBA metrics across different MRI scanners is crucial for multi-site studies but remains largely unexplored.

Purpose of the Study:

• To evaluate the reproducibility and reliability of fixel-based measures (fibre density, fibre cross-section, fibre density and cross-section) across multiple 3T MRI scanners.
• To compare the reliability of FBA metrics with traditional diffusion tensor imaging (DTI) metrics.
• To introduce the TRAMFIX dataset for future research on multi-site FBA.

Main Methods:

• A multisite dataset (TRAMFIX) was created with 10 healthy adults scanned on four 3T MRI scanners using a harmonized multi-shell DWI protocol.
• Fixel-based measures (FD, FC, FDC) and DTI metrics (FA, MD) were extracted using site-specific and pooled processing pipelines.
• Reproducibility and reliability were assessed using within-subject coefficients of variation (CVws) and intraclass correlation coefficients (ICC) at whole-brain, tract, and fixel/voxel levels.

Main Results:

• Fixel-based metrics demonstrated high reproducibility (CVws: 0.51%-1.57%) and reliability (ICC: 0.782-0.994) at the whole-brain level.
• Tract-averaged FBA measures showed high reliability, particularly FC and FDC, though some FD measures had lower ICC (<0.8).
• Fixel-level analysis revealed spatial patterns of reliability, with lower ICC in subcortical/cerebellar regions and higher CVws at cortical boundaries, comparable or better than DTI metrics.

Conclusions:

• Fixel-based analysis metrics exhibit robust reproducibility and reliability, making them suitable for multi-site neuroimaging studies.
• The TRAMFIX dataset provides a valuable resource for investigating scanner and protocol effects on FBA measures.
• Further research into harmonization strategies is recommended for optimal data pooling across sites and scanners.