Regional Lipid Expression Abnormalities Identified Using MALDI IMS Correspond to MRI-Defined White Matter Hyperintensities within Post-mortem Human Brain Tissues

单同位素质量 化学 质谱成像 白质 高强度 马尔迪成像 磁共振成像 基质辅助激光解吸/电离 质谱法 髓鞘 病理 生物化学 中枢神经系统 神经科学 生物 色谱法 医学 放射科 吸附 解吸 有机化学
作者
William W. Pinsky,Aaron J. Harris,Austyn D. Roseborough,Wenxuan Wang,Ali R. Khan,Kristina Jurčić,Ken K.‐C. Yeung,Stephen Pasternak,Shawn N. Whitehead
出处
期刊:Analytical Chemistry [American Chemical Society]
卷期号:93 (4): 2652-2659 被引量:10
标识
DOI:10.1021/acs.analchem.0c05017
摘要

Periventricular white matter hyperintensities (pvWMHs) are a neurological feature detected with magnetic resonance imaging that are clinically associated with an increased risk of stroke and dementia. pvWMHs represent white matter lesions characterized by regions of myelin and axon rarefaction and as such likely involve changes in lipid composition; however, these alterations remain unknown. Lipids are critical in determining cell function and survival. Perturbations in lipid expression have previously been associated with neurological disorders. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an emerging technique for untargeted, high-throughput investigation of lipid expression and spatial distribution in situ; however, the use of MALDI IMS has been previously been limited by the need for non-embedded, non-fixed, fresh-frozen samples. In the current study, we demonstrate the novel use of MALDI IMS to distinguish regional lipid abnormalities that correlate with magnetic resonance imaging (MRI) defined pvWMHs within ammonium formate washed, formalin-fixed human archival samples. MALDI IMS scans were conducted in positive or negative ion detection mode on tissues sublimated with 2,5-dihydroxybenzoic acid or 1,5-diaminonaphthalene matrices, respectively. Using a broad, untargeted approach to lipid analysis, we consistently detected 116 lipid ion species in 21 tissue blocks from 11 different post-mortem formalin-fixed human brains. Comparing the monoisotopic mass peaks of these lipid ions elucidated significant differences in lipid expression between pvWMHs and NAWM for 31 lipid ion species. Expanding our understanding of alterations in lipid composition will provide greater knowledge of molecular mechanisms underpinning ischemic white matter lesions and provides the potential for novel therapeutic interventions targeting lipid composition abnormalities.
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