Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis.

Overview

1. School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
2. Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Diseases, Shandong Provincial Key Laboratory of Mitochondrial Medicine and Rare Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
3. Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China
4. Department of Clinical Laboratory, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China
5. Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China

Abstract

In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452–0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.

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Data availability

The anonymized data presented in this article are available at the request of a qualified investigator, after review by the corresponding author. Final approval will be granted by the Research Ethics Committee of the School of Medicine, Shandong University. No custom code was generated specifically for data analysis in this study. All analyses were conducted using established software packages and publicly available tools, as described in the Methods and Supplementary material.

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Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 3 keywords, 4 funders, 28 references.

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This paper

Ma, M., Zhao, B., Gao, N., Sun, X., Shao, K., Lin, P., Li, W., Zhao, Y., Yu, D., Yan, C., Liu, S., & Yun, Y. (2026). Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis. Brain communications, 8(3), fcag190. https://doi.org/10.1093/braincomms/fcag190

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