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; Benedicte Marechal; Tobias Kober; Jens Kuhle; Ludwig Kappos; Lester Melie-Garcia; Cristina Granziera

NeuroImage: Clinical (Jan 2023)

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,
Benedicte Marechal,
Tobias Kober,
Jens Kuhle,
Ludwig Kappos,
Lester Melie-Garcia,
Cristina Granziera

Affiliations

Xinjie Chen: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Sabine Schädelin: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Po-Jui Lu: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Mario Ocampo-Pineda: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Matthias Weigel: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland
Muhamed Barakovic: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Esther Ruberte: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Alessandro Cagol: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Benedicte Marechal: Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland
Tobias Kober: Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland
Jens Kuhle: Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Ludwig Kappos: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Lester Melie-Garcia: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Cristina Granziera: Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Corresponding author.

Journal volume & issue: Vol. 37
p. 103349

Abstract

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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: The average qT1 Z-score was higher in WMLs than in NAWM. (WMLs: 1.366 ± 0.409, NAWM: −0.133 ± 0.288, [mean ± SD], p < 0.001). The average Z-score in NAWM in RRMS patients was significantly lower than in PPMS patients (p = 0.010). The MLR model showed a strong association between average qT1 Z-scores in white matter lesions (WMLs) and EDSS (R2 = 0.549, β = 0.178, 97.5 % CI = 0.030 to 0.326, p = 0.019). Specifically, we measured a 26.9 % increase in EDSS per unit of qT1 Z-score in WMLs in RRMS patients (R2 = 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.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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