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Serum Neurofilament Light Chain Levels are Associated with Lower Thalamic Perfusion in Multiple Sclerosis
Dejan Jakimovski1, Niels Bergsland1,2, Michael G Dwyer1
1Buffalo Neuroimaging Analysis Center (BNAC), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14203, USA.
Abstract:
Both perfusion-weighted imaging (PWI) measures and serum neurofilament light (sNfL) chain levels have been independently associated with disability in multiple sclerosis (MS) patients. This study aimed to determine whether these measures are correlated to each other or independently describe different MS processes. For this purpose, 3T MRI dynamic susceptibility contrast (DSC)-PWI and single-molecule assay (Simoa)-based sNfL methods were utilized when investigating 86 MS patients. The perfusion measures of mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were derived for the normal-appearing whole brain (NAWB), the normal-appearing white matter (NAWM), the gray matter (GM), the deep GM (DGM), and the thalamus. The normalized CBV and CBF (nCBV and nCBV) were calculated by dividing by the corresponding NAWM measure. Age- and sex-adjusted linear regression models were used to determine associations between the DSC-PWI and sNfL results. False discovery rate (FDR)-adjusted p-values < 0.05 were considered statistically significant. A greater age and thalamic MTT were independently associated with higher sNfL levels (p < 0.001 and p = 0.011) and explained 36.9% of sNfL level variance. NAWM MTT association with sNfL levels did not survive the FDR correction. In similar models, a lower thalamic nCBF and nCBV were both associated with greater sNfL levels (p < 0.001 and p = 0.022), explaining 37.8% and 44.7% of the variance, respectively. In conclusion, higher sNfL levels were associated with lower thalamic perfusion.
Insights
Higher serum neurofilament light (sNfL) chain levels in multiple sclerosis (MS) patients correlate with reduced thalamic perfusion, indicating potential links between MS disease processes and brain blood flow.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Perfusion-weighted imaging (PWI) and serum neurofilament light (sNfL) chain levels are independently linked to disability in multiple sclerosis (MS).
- The relationship between these two MS biomarkers requires further investigation to understand distinct disease processes.
Purpose of the Study:
- To investigate the correlation between dynamic susceptibility contrast (DSC)-PWI measures and serum neurofilament light (sNfL) chain levels in MS patients.
- To determine if PWI and sNfL independently describe different aspects of MS pathology.
Main Methods:
- 86 MS patients underwent 3T MRI DSC-PWI and sNfL measurement using Simoa.
- Perfusion parameters (MTT, CBV, CBF) were analyzed in various brain regions, including the thalamus.
- Normalized CBV and CBF (nCBV, nCBF) were calculated relative to normal-appearing white matter (NAWM).
- Age- and sex-adjusted linear regression models with FDR correction were used to assess associations.
Main Results:
- Higher sNfL levels were independently associated with greater age and increased thalamic mean transit time (MTT).
- Lower thalamic normalized cerebral blood flow (nCBF) and normalized cerebral blood volume (nCBV) were significantly associated with higher sNfL levels.
- Thalamic MTT, nCBF, and nCBV collectively explained a substantial portion of the variance in sNfL levels (36.9%–44.7%).
Conclusions:
- Elevated sNfL levels in MS patients are associated with reduced perfusion in the thalamus.
- These findings suggest a link between neuroaxonal damage markers and altered brain hemodynamics in MS.
