Correlative Chemical Imaging and Spatial Chemometrics Delineate Alzheimer Plaque Heterogeneity at High Spatial Resolution.
Correlative Chemical Imaging and Spatial Chemometrics Delineate Alzheimer Plaque Heterogeneity at High Spatial Resolution.
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DOI：
10.1021/jacsau.2c00492
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发表时间：
2023-03-27
期刊：
影响因子：
8
通讯作者：
Hanrieder, Jorg
中科院分区：
文献类型：
--
作者：
Wehrli, Patrick M;Ge, Junyue;Michno, Wojciech;Koutarapu, Srinivas;Dreos, Ambra;Jha, Durga;Zetterberg, Henrik;Blennow, Kaj;Hanrieder, Jorg
我们提出了一种新的，相关的化学成像策略的基础上多模式基质辅助激光解吸/电离（MALDI）质谱成像（MSI），高光谱显微镜，和空间化学计量学。我们的工作流程通过实施1 + 1-进化图像配准来实现多模态成像数据的精确几何对齐，并将其整合到一个通用的、真正的多模态成像数据矩阵中，并保持MSI分辨率（10 μm），从而克服了与相关MSI数据采集和对齐相关的挑战。这使得多模态成像数据的多元统计建模，使用一种新的多块正交分量分析方法，以确定MSI像素分辨率的成像模式之间和内部的生化签名的协变。我们证明了该方法的潜力，通过其对描绘阿尔茨海默氏病（AD）病理学的化学特征的应用。在这里，转基因AD小鼠大脑的三峰MALDI MSI描绘了β-淀粉样蛋白（Aβ）斑块相关的脂质和Aβ肽的共定位。最后，我们建立了一个改进的图像融合方法相关MSI和功能荧光显微镜。这允许高空间分辨率（300 nm）预测相关的多模式MSI特征，这些特征朝向与Aβ致病性密切相关的单个斑块特征内的不同淀粉样蛋白结构。
We present a novel, correlative chemical imaging strategy based on multimodal matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), hyperspectral microscopy, and spatial chemometrics. Our workflow overcomes challenges associated with correlative MSI data acquisition and alignment by implementing 1 + 1-evolutionary image registration for precise geometric alignment of multimodal imaging data and their integration in a common, truly multimodal imaging data matrix with maintained MSI resolution (10 μm). This enabled multivariate statistical modeling of multimodal imaging data using a novel multiblock orthogonal component analysis approach to identify covariations of biochemical signatures between and within imaging modalities at MSI pixel resolution. We demonstrate the method’s potential through its application toward delineating chemical traits of Alzheimer’s disease (AD) pathology. Here, trimodal MALDI MSI of transgenic AD mouse brain delineates beta-amyloid (Aβ) plaque-associated co-localization of lipids and Aβ peptides. Finally, we establish an improved image fusion approach for correlative MSI and functional fluorescence microscopy. This allowed for high spatial resolution (300 nm) prediction of correlative, multimodal MSI signatures toward distinct amyloid structures within single plaque features critically implicated in Aβ pathogenicity.