Three-dimensional structured illumination microscopy (3D-SIM) doubles the resolution of fluorescence imaging in all directions and enables optical sectioning with increased image contrast. However, 3D-SIM has not been widely applied to imaging deep in thick tissues due to its sensitivity to sample-induced aberrations, making the method difficult to apply beyond 10 µm in depth. Furthermore, 3D-SIM has not been available in an upright configuration, limiting its use for live imaging while mani...