Multiscale imaging of colitis in mice using confocal laser endomicroscopy, light-sheet fluorescence microscopy, and magnetic resonance imaging

The objective of our study is to develop a multimodality approach by combining magnetic resonance imaging (MRI) and optical imaging methods to assess acute murine colitis at the macro- and microscopic level. In vivo MRI is used to measure the cross-sectional areas of colons at the macroscopic level. Dual-color confocal laser endomicroscopy (CLE) allows in vivo examination of the fluorescently labeled epithelial cells and microvessels in the mucosa with a spatial resolution of ∼1.4 μm during ongoing endoscopy. To further validate the structural changes of the colons in three-dimensions, ex vivo light-sheet fluorescence microscopy (LSFM) is applied for in-toto imaging of cleared colon sections. MRI, LSFM, and CLE findings are significantly correlated with histological scoring (p < 0.01) and the inflammation-associated activity index (p < 0.01). Our multimodality imaging technique permits visualization of mucosa in colitis at different scales, which can enhance our understanding of the pathogenesis of inflammatory bowel diseases.