Using a PHP IDE with integrated debugger allows realtime debugging, step thru, watch, etc. in PHP. However, some things can be tricky to set breakpoints: the Drupal module imagecache is one of them.

The trick to setting a breakpoint in imagecache is to understand that it's not really the same "debug session call" as when you actually hit the page containing imagecache references. It's really the respective img src="" that calls the imagecache module that needs to invoke the debug session, so rather than trying to debug the page, try opening the url that shows in src="" and debug that.