Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada.
Department of Medical Biophysics, University of Western Ontario, London, N6A 5C1 Ontario, Canada.
Anal Chem. 2021 Feb 2;93(4):2652-2659. doi: 10.1021/acs.analchem.0c05017. Epub 2021 Jan 19.
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 ; 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.
脑室周围白质高信号（PVWMHs）是一种通过磁共振成像检测到的神经学特征，与中风和痴呆的风险增加相关。PVWMHs 代表白质病变，其特征是髓鞘和轴突稀疏区域，因此可能涉及脂质组成的变化；然而，这些改变仍然未知。脂质在确定细胞功能和存活方面至关重要。脂质表达的扰动先前与神经障碍有关。基质辅助激光解吸/电离（MALDI）成像质谱（IMS）是一种用于非靶向、高通量研究脂质表达和空间分布的新兴技术；然而，MALDI IMS 的使用以前受到需要非嵌入、非固定、新鲜冷冻样本的限制。在当前的研究中，我们展示了 MALDI IMS 的新用途，以区分与磁共振成像（MRI）定义的 PVWMHs 相关的区域脂质异常，这些异常存在于用甲酸铵洗涤、福尔马林固定的人类存档样本中。MALDI IMS 扫描分别在 2,5-二羟基苯甲酸或 1,5-二氨基萘基质升华的组织中以正离子或负离子检测模式进行。使用广泛的非靶向脂质分析方法，我们在来自 11 个不同死后福尔马林固定人脑的 21 个组织块中一致检测到 116 种脂质离子物种。比较这些脂质离子的单同位素质量峰，阐明了 PVWMHs 和 NAWM 之间 31 种脂质离子物种的脂质表达存在显著差异。扩大对脂质组成变化的理解将为缺血性白质病变的分子机制提供更多的知识，并为针对脂质组成异常的新型治疗干预提供潜力。
