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Esther Ruberte

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3 papers

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YNICL Journal 2025 Journal Article

TIME: Tractography-Informed myelin estimation

Sara Bosticardo
Matteo Battocchio
Mario Ocampo-Pineda
Alessandro Cagol
Po- Jui Lu
Esther Ruberte
Nina De Oliveira S. Siebenborn
Xinjie Chen

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.

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YNICL Journal 2023 Journal Article

Personalized maps of T1 relaxometry abnormalities provide correlates of disability in multiple sclerosis patients

Xinjie Chen
Sabine Schädelin
Po-Jui Lu
Mario Ocampo-Pineda
Matthias Weigel
Muhamed Barakovic
Esther Ruberte
Alessandro Cagol

OBJECTIVES AND AIMS: Quantitative MRI (qMRI) has greatly improved the sensitivity and specificity of microstructural brain pathology in multiple sclerosis (MS) when compared to conventional MRI (cMRI). More than cMRI, qMRI also provides means to assess pathology within the normal-appearing and lesion tissue. In this work, we further developed a method providing personalized quantitative T1 (qT1) abnormality maps in individual MS patients by modeling the age dependence of qT1 alterations. In addition, we assessed the relationship between qT1 abnormality maps and patients' disability, in order to evaluate the potential value of this measurement in clinical practice. METHODS: We included 119 MS patients (64 relapsing-remitting MS (RRMS), 34 secondary progressive MS (SPMS), 21 primary progressive MS (PPMS)), and 98 Healthy Controls (HC). All individuals underwent 3T MRI examinations, including Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) for qT1 maps and High-Resolution 3D Fluid Attenuated Inversion Recovery (FLAIR) imaging. To calculate personalized qT1 abnormality maps, we compared qT1 in each brain voxel in MS patients to the average qT1 obtained in the same tissue (grey/white matter) and region of interest (ROI) in healthy controls, hereby providing individual voxel-based Z-score maps. The age dependence of qT1 in HC was modeled using linear polynomial regression. We computed the average qT1 Z-scores in white matter lesions (WMLs), normal-appearing white matter (NAWM), cortical grey matter lesions (GMcLs) and normal-appearing cortical grey matter (NAcGM). Lastly, a multiple linear regression (MLR) model with the backward selection including age, sex, disease duration, phenotype, lesion number, lesion volume and average Z-score (NAWM/NAcGM/WMLs/GMcLs) was used to assess the relationship between qT1 measures and clinical disability (evaluated with EDSS). RESULTS: = 0.099, β = 0.269, 97.5 % CI = 0.078 to 0.461, p = 0.007). CONCLUSIONS: We showed that personalized qT1 abnormality maps in MS patients provide measures related to clinical disability, supporting the use of those maps in clinical practice.

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YNICL Journal 2022 Journal Article

Brain atrophy measurement over a MRI scanner change in multiple sclerosis

Tim Sinnecker
Sabine Schädelin
Pascal Benkert
Esther Ruberte
Michael Amann
Johanna M. Lieb
Yvonne Naegelin
Jannis Müller

BACKGROUND: A change in MRI hardware impacts brain volume measurements. The aim of this study was to use MRI data from multiple sclerosis (MS) patients and healthy control subjects (HCs) to statistically model how to adjust brain atrophy measures in MS patients after a major scanner upgrade. METHODS: We scanned 20 MS patients and 26 HCs before and three months after a major scanner upgrade (1.5 T Siemens Healthineers Magnetom Avanto to 3 T Siemens Healthineers Skyra Fit). The patient group also underwent standardized serial MRIs before and after the scanner change. Percentage whole brain volume changes (PBVC) measured by Structural Image Evaluation using Normalization of Atrophy (SIENA) in the HCs was used to estimate a corrective term based on a linear model. The factor was internally validated in HCs, and then applied to the MS group. RESULTS: Mean PBVC during the scanner change was higher in MS than HCs (-4.1 ± 0.8 % versus -3.4 ± 0.6 %). A fixed corrective term of 3.4 (95% confidence interval: 3.13-3.67)% was estimated based on the observed average changes in HCs. Age and gender did not have a significant influence on this corrective term. After adjustment, a linear mixed effects model showed that the brain atrophy measures in MS during the scanner upgrade were not anymore associated with the scanner type (old vs new scanner; p = 0.29). CONCLUSION: A scanner change affects brain atrophy measures in longitudinal cohorts. The inclusion of a corrective term based on changes observed in HCs helps to adjust for the known and unknown factors associated with a scanner upgrade on a group level.

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