There's real overhead. For instance, one spec that comes to mind the vendor starts the 0,0 pixel in the lower right. The spec calls for 0,0 to be the lower left

There's real overhead. For instance, one spec that comes to mind the vendor starts the 0,0 pixel in the lower right. The spec calls for 0,0 to be the lower left. That leads to an inverted handedness for all images. Not a problem in projection, but as soon as you start in 3D, it creates a real mess. Some software packages try to detect when the camera was this vendor, and correct for it (silently). Other software packages refuse to correct for it, because they don't have a reliable way to detect it. A pipeline might have 3-4 of these software packages involved, eventually you have no idea if you handedness is correct and no real way to tell without being at a high enough resolution that you can use biological landmarks of known handedness. Don't get me started on Euler angles. Caveat being I'm more used to electron microscopy, maybe these things aren't as important with light microscopy because the resolutions are lower?