TIME: Tractography-Informed myelin estimation

Affiliations

¹ University 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. Electronic address: sara.bosticardo@univr.it.
² University of Verona, Diffusion Imaging and Connectivity Estimation (DICE) Lab, Department of Computer Science, Italy.
³ 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.
⁴ 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; University of Genova, Department of Health Sciences, Italy.
⁵ 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; University of Basel, Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, Switzerland.
⁶ 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; University Hospital Basel, Division of Radiological Physics, Department of Radiology, Switzerland.
⁷ 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.

PMID: 40939274
DOI: 10.1016/j.nicl.2025.103878

Free article

TIME: Tractography-Informed myelin estimation

Sara Bosticardo et al. Neuroimage Clin. 2025.

Free article

. 2025 Sep 8:48:103878.

doi: 10.1016/j.nicl.2025.103878. Online ahead of print.

Affiliations

¹ University 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. Electronic address: sara.bosticardo@univr.it.
² University of Verona, Diffusion Imaging and Connectivity Estimation (DICE) Lab, Department of Computer Science, Italy.
³ 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.
⁴ 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; University of Genova, Department of Health Sciences, Italy.
⁵ 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; University of Basel, Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, Switzerland.
⁶ 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; University Hospital Basel, Division of Radiological Physics, Department of Radiology, Switzerland.
⁷ 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.

PMID: 40939274
DOI: 10.1016/j.nicl.2025.103878

Abstract

Investigating myelin integrity within multiple sclerosis (MS) lesions and in normal-appearing white matter is crucial for understanding demyelination and remyelination processes. While most approaches assess global myelin changes or compare lesions with homologous regions in healthy controls, they do not allow direct within-tract comparisons between lesional and non-lesional tissue. We introduce the tractography-informed myelin estimate (TIME), a novel map designed to quantify tract-specific myelin loss. TIME integrates tractography with myelin-sensitive imaging, such as myelin volume fraction, to compare lesional and non-lesional segments within the same white matter tract. By modeling local deviations from the expected myelin volume fraction signal along streamlines, TIME captures tract-specific myelin damage while accounting for within-tract variability. TIME is based on a microstructure-informed tractography framework, with an extra compartment to model signal loss caused by lesions. We evaluated TIME in 159 MS patients, assessing its association with neurological disability at baseline and longitudinally over a median follow-up of two years. At baseline, higher myelin loss captured by TIME was significantly associated with worse disability (β = 0.14, p = 0.015). Longitudinally, greater baseline disability predicted faster TIME-quantified myelin loss, which was in turn associated with a higher risk of disability worsening. In contrast, lesion-averaged myelin volume fraction showed no significant associations with either baseline disability or its progression. TIME provides a detailed, tract-specific assessment of myelin damage, providing greater sensitivity than conventional metrics, highlighting its potential as a biomarker in MS.

Keywords: Focal Lesions; Multiple Sclerosis; Myelin; Tractography.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest S. Bosticardo has nothing to disclose. M. Battocchio has nothing to disclose. M. Ocampo-Pineda has nothing to disclose. A. Cagol has received speaker honoraria from Novartis and Roche. P.-J. Lu has nothing to disclose. E. Ruberte has nothing to disclose. N. de Oliveira Siebenborn has nothing to disclose. X. Chen has nothing to disclose. L. Melie Garcia has nothing to disclose. M. Weigel has nothing to disclose. L. Kappos has received no personal compensation. His institutions (University Hospital Basel/Foundation Clinical Neuroimmunology and Neuroscience Basel) have received and used exclusively for research support: payments for steering committee and advisory board participation, consultancy services, and participation in educational activities from: Actelion, Bayer, BMS, df-mp Molnia & Pohlmann, Celgene, Eli Lilly, EMD Serono, Genentech, Glaxo Smith Kline, Janssen, Japan Tobacco, Merck, MH Consulting, Minoryx, Novartis, F. Hoffmann-La Roche Ltd, Senda Biosciences Inc., Sanofi, Santhera, Shionogi BV, TG Therapeutics, and Wellmera, and license fees for Neurostatus-UHB products; grants from Novartis, Innosuisse, and Roche. J. Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_189140/1), University of Basel, Progressive MS Alliance, Bayer, Biogen, Celgene, Merck, Novartis, Octave Bioscience, Roche, Sanofi. A. Daducci has nothing to disclose. C. Granziera The University Hospital Basel (USB), as the employer of C.G., has received the following fees which were used exclusively for research support: (i) advisory boards and consultancy fees from Actelion, Novartis, Genzyme-Sanofi, GeNeuro, Hoffmann La Roche and Siemens; (ii) speaker fees from Biogen, Hoffmann La Roche, Teva, Novartis, Merck, Jannsen Pharmaceuticals and Genzyme-Sanofi; (iii) research grants: Biogen, Genzyme Sanofi, Hoffmann La Roche.

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

TIME: Tractography-Informed myelin estimation

Affiliations

TIME: Tractography-Informed myelin estimation

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources