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TIME: Tractography-Informed myelin estimation.

Sara Bosticardo1, Matteo Battocchio2, Mario Ocampo-Pineda3

  • 1University of Verona, Diffusion Imaging and Connectivity Estimation (DICE) Lab, Department of Computer Science, Italy; University Hospital Basel and University of Basel, Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Switzerland; University Hospital and University Basel, Multiple Sclerosis Centre, Departments of Neurology, Clinical Research and Biomedicine, Switzerland; University Hospital Basel and University of Basel, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Switzerland.

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|September 12, 2025
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Summary
This summary is machine-generated.

Tractography-Informed Myelin Estimate (TIME) quantifies tract-specific myelin loss in multiple sclerosis (MS). This novel method reveals significant associations between myelin damage and neurological disability, outperforming traditional metrics.

Keywords:
Focal LesionsMultiple SclerosisMyelinTractography

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Area of Science:

  • Neuroimaging
  • Neurology
  • Biomarker Development

Background:

  • Understanding myelin integrity in multiple sclerosis (MS) lesions and normal-appearing white matter is key to demyelination and remyelination research.
  • Current methods often assess global myelin changes or compare lesions to healthy controls, lacking direct within-tract comparisons.
  • There is a need for methods that can quantify tract-specific myelin loss within individual white matter tracts.

Purpose of the Study:

  • To introduce and validate the Tractography-Informed Myelin Estimate (TIME), a novel map for quantifying tract-specific myelin loss in MS.
  • To assess the association of TIME-quantified myelin loss with neurological disability at baseline and longitudinally.
  • To compare the sensitivity of TIME with conventional myelin metrics.

Main Methods:

  • Developed TIME by integrating tractography with myelin-sensitive imaging (myelin volume fraction) to compare lesional and non-lesional segments within the same white matter tract.
  • Modeled local deviations from expected myelin volume fraction along streamlines to capture tract-specific damage.
  • Evaluated TIME in 159 MS patients, assessing associations with neurological disability at baseline and over a two-year follow-up.

Main Results:

  • Higher myelin loss measured by TIME at baseline was significantly associated with worse neurological disability (β=0.14, p=0.015).
  • Greater baseline disability predicted faster TIME-quantified myelin loss longitudinally, which correlated with increased risk of disability worsening.
  • Lesion-averaged myelin volume fraction showed no significant associations with baseline disability or its progression.

Conclusions:

  • TIME provides a sensitive, tract-specific assessment of myelin damage in MS.
  • TIME demonstrates greater sensitivity than conventional metrics for evaluating myelin loss.
  • TIME shows potential as a valuable imaging biomarker for MS, correlating with disability and disease progression.