QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions
| Autor: | Mayyan Mubarak, Steven Toro, Alexey Dimov, Calvin Park, Mireia Guerau-de-Arellano, Thanh D. Nguyen, Weiyuan Huang, Ulrike W. Kaunzner, Shun Zhang, Maya Levine-Ritterman, Yi Wang, Susan A. Gauthier, David Pitt, Stephanie A. Amici, Kelly M. Gillen, Gerald Ponath |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Myeloid Multiple Sclerosis Imaging biomarker Iron Induced Pluripotent Stem Cells Neurosciences. Biological psychiatry. Neuropsychiatry Lesion White matter 03 medical and health sciences 0302 clinical medicine medicine Humans RC346-429 Research Articles Cells Cultured Microglia business.industry General Neuroscience Multiple sclerosis Quantitative susceptibility mapping Middle Aged medicine.disease Magnetic Resonance Imaging White Matter Hyperintensity 030104 developmental biology medicine.anatomical_structure Neuroinflammatory Diseases Female Neurology. Diseases of the nervous system Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Biomarkers RC321-571 Research Article |
| Zdroj: | Annals of Clinical and Translational Neurology Annals of Clinical and Translational Neurology, Vol 8, Iss 4, Pp 877-886 (2021) |
| ISSN: | 2328-9503 |
| Popis: | Background Inflammation in chronic active lesions occurs behind a closed blood–brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron. Objective To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions. Methods MS brain slabs were imaged with MRI and QSM, and processed for histology. Immunolabeled cells were quantified in the lesion rim, center, and adjacent normal‐appearing white matter (NAWM). Iron+ myeloid cell densities at the rims were correlated with susceptibilities. Human‐induced pluripotent stem cell (iPSC)‐derived microglia were used to determine the effect of iron on the production of reactive oxygen species (ROS) and pro‐inflammatory cytokines. Results QSM hyperintensity at the lesion perimeter correlated with activated iron+ myeloid cells in the rim and NAWM. Lesions with high punctate or homogenous QSM signal contained no or minimally activated iron− myeloid cells. In vitro, iron accumulation was highest in M1‐polarized human iPSC‐derived microglia, but it did not enhance ROS or cytokine production. Conclusion A high QSM signal outlining the lesion rim but not punctate signal in the center is a biomarker for chronic inflammation in white matter lesions. |
| Databáze: | OpenAIRE |
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