I know this is an old thread, but I recently stumbled upon it whilst looking for a fix, and although I didn't find a solution here.. I thought I'd stop by and post my fix for a similar issue.
The iso I had been trying to load was an .ecm file, in other words, it's still compressed. In order to decompress it, you must first download Neill Corlett's Command-Line Pack.
(I can't post an external link, so just google it. Note: Click on the link that corresponds with your OS, NOT the source code)
Once you've unzipped the file, run the .ecm through the unecm application. Once the process is complete, run the newly decompressed image file as an iso in epsxe, and you should be good to go.
Hope that solves it for you ^^
P.S. I do not come here often, so if you have any questions, it may take quite a long time for me to see them.