TY - JOUR T1 - Mesoscopic oblique plane microscopy (Meso-OPM) with a diffractive light sheet- enabling large-scale 4D cellular resolution imaging JF - bioRxiv DO - 10.1101/2022.03.29.486239 SP - 2022.03.29.486239 AU - Wenjun Shao AU - Minzi Chang AU - Kevin Emmerich AU - Patrick O Kanold AU - Jeff S Mumm AU - Ji Yi Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/08/01/2022.03.29.486239.abstract N2 - Fundamental understanding of large-scale dynamic connectivity within a living organism requires volumetric imaging over a large field of view (FOV) at biologically relevant speed and resolution. However, most microscopy methods make trade-offs between FOV and depth resolution, making it challenging to observe highly dynamic processes at cellular resolution in 3D across mesoscopic scales (e.g., whole zebrafish larva). To overcome this limitation, we have developed mesoscopic oblique plane microscopy (Meso-OPM) with a diffractive light sheet. By augmenting the illumination angle of the light sheet with a transmission grating, the axial resolution was improved ~6-fold over existing methods and ~2-fold beyond the diffraction limitation of the primary objective lens. We demonstrated an unprecedented FOV up to 5.4 × 3.3 mm with resolution of 2.5× 3 × 6 μm, allowing volumetric imaging of 3D cellular structures with a single scan. Applying Meso-OPM for in vivo imaging of zebrafish larvae, we report here the first in toto whole body volumetric recordings of neuronal activity at 2 Hz volume rate and the first example of whole body volumetric recordings of blood flow dynamics at 5 Hz with 3D cellular resolution.Competing Interest StatementThe authors have declared no competing interest. ER -