To be sure we are talking about the same thing, I didn't use the "save as project" and then change a the png of a sprite.
I used the "save as single file" during all the production of the game.
So I guess changing a png I imported, to reimport a modified version afterward shouldn't confuse C2.
As far as I understand how C2 works, once you load a png C2 isn't supposed to keep any link to the file... is it ?