用於增強空間分析和分子定位的三維質譜影像重建流程：以思覺失調小鼠大腦為例

Abstract

質譜成像是一種具有空間解析能力的分析技術，能提供不同分子的空間分佈情況，以便識別出空間模式、梯度或局部分子變化。質譜影像可以與其他的成像模式結合，如顯微鏡、螢光成像或磁共振成像，以獲取互補的信息，使研究人員能夠對樣本有更全面、完整的觀察。然而，傳統的二維質譜成像無法提供樣本在z軸上的詳細訊息，這使得分析和解釋複雜的三維結構變得具有挑戰性。三維質譜成像具有提升深度剖析能力並實現對給定樣本特定分子體積的定量分析潛力。它能夠評估組織內代謝物濃度的空間變化。三維質譜影像的研究持續增加，表明對探索質譜影像三維特性的興趣正在上升。 思覺失調症是一種影響人們思維、情感和行為的精神疾病。其中一個思覺失調症的假說是NMDA（N-甲基-D-天冬氨酸）受體的功能不足，這導致思覺失調症的臨床症狀。越來越多的新證據表明脂質代謝與思覺失調症之間可能存在著關聯。我們提供一個以思覺失調症鼠腦為例的三維質譜成像重建流程。透過該流程，可以將實驗所得不同深度的二維質譜影像重組成三維質譜影像，從而了解分子在三維空間中的分佈。透過比較思覺失調和正常小鼠海馬迴、紋狀體和內側前額葉皮層中的脂質強度，我們發現這三個腦區中的特定脂質在兩組樣本間存在顯著差異。

Mass spectrometry imaging (MSI) is a spatially resolved analytical technique that provides spatial distributions of different molecules, allowing for the identification of spatial patterns, gradients, or localized molecular changes. MSI can be combined with various imaging modalities, including microscopy, fluorescence imaging, and magnetic resonance imaging (MRI), to obtain complementary information, which enables researchers to have a more comprehensive and intact view of the sample. However, traditional 2D MSI does not provide detailed information along the z-axis of the sample. This makes it challenging to analyze and interpret complex 3D structures. Three-dimensional (3D) MSI has the potential to enhance depth profiling capabilities and allow for quantitative analysis of the volume. It enables the assessment of spatial variations in metabolite concentrations throughout a tissue volume. Research on 3D MSI is increasing, indicating a rising interest in exploring the 3D aspects of MSI. Schizophrenia is a psychiatric disorder characterized by cognitive, emotional, and behavioral disturbances. One of the hypotheses of schizophrenia is the hypofunction of NMDA (N-methyl-D-aspartate) receptors, which leads to the clinical symptoms of schizophrenia. An increasing body of emerging evidence indicates a potential association between lipid metabolism and schizophrenia. We provided a three-dimensional mass spectrometry imaging reconstruction protocol using schizophrenic mouse brains as an example. With this protocol, the 2D MSI data acquired at different depths can be reconstructed into a 3D MSI, allowing us to understand the spatial distribution of molecules in a 3D space. By comparing the lipid intensities in the hippocampus, striatum, and medial prefrontal cortex (mPFC) between schizophrenia and wild-type mice, we identified specific lipids in these three brain regions that showed significant differences between the two groups.