Systems and methods for predicting images with enhanced spatial resolution using a neural network are provided herein. According to an aspect of the invention, a method includes accessing an input image of a biological sample, wherein the input image includes a first spatial resolution and a plurality of spectral images, and wherein each spectral image of the plurality of spectral images includes data from a different wavelength band at a different spectral channel; applying a trained artificial neural network to the input image; generating an output image at a second spatial resolution, wherein the second spatial resolution is higher than the first spatial resolution, and wherein the output image includes a fewer number of spectral channels than the plurality of spectral images included in the input image; and outputting the output image.