In general there is a limit to how much you can expect a plugin to understand. Although I did not know image format mattered, unless it features lossy compression like JPEG.. or compression at all.
The obvious solution is to keep these factors in mind when acquiring images. Use the same settings, bit depth, image size etc. But of course it is not always that easy. I ran into this bit depth sensitivty myself when a colleague wanted me to run his images that were sometimes 8bit, sometimes 16bit..
But there is a way around this issue. You can scale the image to a different bit depth. Divide the whole image by the highest value pixel, change image type and multiply to new range ie. 65536 for 16bit with 'scale when converting' disabled.
Or, if you have multichannel images like I do you can create composite rgbs and segment these rather than single channels. But in my case, all three channels feature fluorescent proteins that localize ubiquitously..
I am not sure what is the best practice for different sizes or zooms, maybe @iarganda has a clever solution.
edit, @cbe: At my office now. And I think this is an important question, these things are not so obvious to new users and maybe the main issues can be covered in the troubleshooting section of the wiki, along with some code structure that can adapt to, or handle errors from different inputs. (I can look into this myself in June if people agree, the simpler issues shouldn't be much work to cover).