QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions.
QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions.
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DOI：
10.1002/acn3.51338
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发表时间：
2021-04
影响因子：
5.3
通讯作者：
Pitt D
中科院分区：
文献类型：
--
作者：
Gillen KM;Mubarak M;Park C;Ponath G;Zhang S;Dimov A;Levine-Ritterman M;Toro S;Huang W;Amici S;Kaunzner UW;Gauthier SA;Guerau-de-Arellano M;Wang Y;Nguyen TD;Pitt D
慢性活动性病变的炎症发生在封闭的血脑屏障后面，无法用MRI检测到。激活的小胶质细胞高度富含铁，并可通过定量磁化率图(QSM)可视化，QSM是一种用于描绘铁的核磁共振技术。探讨MS病变不同QSM高信号模式的组织病理学相关性。对MS脑片进行MRI和QSM成像，并进行组织学检查。免疫标记细胞在病变边缘、中心和邻近正常外观的白质(NAWM)进行定量。边缘的铁+髓系细胞密度与易感性相关。采用人诱导多能干细胞(IPSC)来源的小胶质细胞，研究铁对ROS和促炎细胞因子产生的影响。病变周边的QSM高信号与边缘和NAWM中活化的铁+髓系细胞相关。高点状或均匀QSM信号的病灶不含或低激活的铁−髓系细胞。在体外，在M1极化的人IPSC来源的小胶质细胞中，铁的积累最高，但它不能促进ROS或细胞因子的产生。高QSM信号勾勒出病变边缘而不是中心点状信号，是白质病变慢性炎症的生物标志物。
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. To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions. 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. 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. 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.
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影响因子：
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作者：
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通讯作者：
Prinz, Marco
影响因子：
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Weiner, Howard L.
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通讯作者：
Fossati V
影响因子：
29
作者：
Absinta, Martina;Sati, Pascal;Reich, Daniel S.
通讯作者：
Reich, Daniel S.
影响因子：
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作者：
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通讯作者：
Schwingenschuh P