An embodiment may involve obtaining an image composed of color channels, wherein each of the color channels represents colors therein with n bits per pixel; quantizing each of the color channels to be represented by m bits per pixel; using a space-filling curve to convert each of the color channels as quantized into respective vectors; generating, for each of the respective vectors, a respective set of m arrays, wherein the m arrays for a particular vector of the respective vectors contain indices of where a fixed value selected from a range of 0 to m−1 is found in the particular vector; applying, to each of the m arrays for each of the respective vectors, differential encoding and compression of the indices therein; mapping each of the m arrays for each of the respective vectors to blocks of nucleotides; synthesizing the blocks; and storing, in a DNA-based storage medium, the blocks.