Label-free analysis of inflammatory tissue remodeling in murine lung tissue based on multiphoton microscopy, Raman spectroscopy and machine learning

基于多光子显微镜、拉曼光谱和机器学习的小鼠肺组织炎症组织重塑的无标记分析

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作者:Lucas Kreiss, Ingo Ganzleben, Alexander Mühlberg, Paul Ritter, Dominik Schneidereit, Christoph Becker, Markus F Neurath, Oliver Friedrich, Sebastian Schürmann, Maximilian Waldner

Abstract

Inflammatory fibrotic tissue remodeling can lead to severe morbidity. Histopathology grading requires extraction of biopsies and elaborate tissue processing. Label-free optical technologies can provide diagnostic readout without preparation and artificial stainings and show potential for in vivo applications. Here, we present an integration of Raman spectroscopy (RS) and multiphoton microscopy for joint investigation of the bio-chemical composition and morphological features related to cellular components and connective tissue. Both modalities show that collagen signatures were significantly increased in a murine fibrosis model. Furthermore, autofluorescence signatures assigned to immune cells show high correlation with disease severity. RS indicates increased levels of elastin and lipids. Further, we investigated the effect of joint data sets on prediction performance in machine learning models. Although binary classification did not benefit from adding more features, multi-class classification was improved by integrated data sets.

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