Abstract: High-spatial-resolution mass spectrometry imaging (HSR-MSI) provides precise spatial information on thousands of biomolecules without labelling across a tissue section. Deep learning methods, trained on large numbers of images, can be used to further improve resolution. However, the limited amount of HSR-MSI data that are publicly available mean that super-resolution reconstruction of images obtained by MSI using deep learning is still a challenge. Here we develop a deep learning framework based on transfer learning called MSI from optical super-resolution (MOSR) that substantially reduces the requirement for sample size. Needing only ten HSR-MSI images, the method transfers knowledge learned from abundant optical images (~15,000) to MSI tasks. Compared with the deep learning model without transfer learning, the MOSR model obtains better image quality with higher peak signal-to-noise ratios and structural similarity index values. It also achieves higher training efficiency and a stronger generalization performance. The MOSR model predicts HSR-MSI images with very small sample size and could transform applications with super-resolution MSI. Mass spectrometry imaging (MSI) can provide important information, but long imaging times are needed to achieve a high spatial resolution, which is why the amount of publicly available high-resolution MSI data for deep learning applications is limited. Liao and colleagues use transfer learning from optical super-resolution images to reduce the amount of MSI data that is needed.
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