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Published on: July 28, 2013
Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple
Alessandro Cagol1, Mario Ocampo-Pineda1, Po-Jui Lu1
1From the Translational Imaging in Neurology (ThINk) Basel (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., L.K., C.G.), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel; Department of Neurology (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., J.K., L.K., C.G.), University Hospital Basel; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., J.K., L.K., C.G.), University Hospital Basel and University of Basel, Switzerland; Dipartimento di Scienze della Salute, (A.C., M.P.S.), Università degli Studi di Genova, Italy; Division of Radiological Physics (M.W.), Department of Radiology, University Hospital Basel; Laboratory for Research in Neuroimaging (A.L.), Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne; Neuropsychology and Behavioral Neurology Unit (P.C.), Division of Cognitive and Molecular Neuroscience, University of Basel, Switzerland; and IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy.
Background And Objectives:
In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI).
Methods:
Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity.
Results:
Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy.
Discussion:
These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.
Insights
Advanced MRI reveals significant thalamic damage in multiple sclerosis (MS) patients, linked to disease progression. Quantitative MRI biomarkers show potential for guiding future MS treatments.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Thalamic atrophy is common in multiple sclerosis (MS).
- Mechanisms of thalamic volume loss and its relation to disease progression are poorly understood.
- In vivo characterization of thalamic microstructure in MS is needed.
Purpose of the Study:
- To comprehensively characterize in vivo pathologic changes within thalamic microstructure in patients with MS (PwMS) using advanced multiparametric quantitative MRI (qMRI).
- To compare thalamic alterations between PwMS and healthy controls (HCs) and among MS disease phenotypes.
- To investigate the relationship between thalamic damage and clinical/MRI measures of disease severity.
Main Methods:
- Quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) were used to assess thalamic microstructural integrity.
- Cross-sectional and longitudinal data were collected from 183 PwMS and 105 HCs, with a 2-year follow-up for 127 PwMS and 73 HCs.
- PwMS included relapsing-remitting MS (RRMS) and progressive MS (PMS) phenotypes.
Main Results:
- PwMS showed significant thalamic alterations including demyelination and disrupted iron homeostasis, affecting normal-appearing tissue.
- Longitudinal analysis revealed accelerated myelin loss and neurodegeneration in PwMS.
- Progressive MS (PMS) demonstrated significantly accelerated thalamic degeneration compared to RRMS.
- Thalamic qMRI alterations correlated with clinical, cognitive, and conventional MRI measures of disease burden.
- Disability progression was associated with accelerated thalamic degeneration, with qMRI metrics predicting disability.
Conclusions:
- Thalamic damage in MS is extensive and clinically relevant, strongly linked to disease progression.
- Advanced qMRI biomarkers offer potential for monitoring and guiding interventions for thalamic neurodegeneration in MS.
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