There needs to be registry entries on the OS Boot Drive for programs to work.
Lets say you installed Microsoft Windows on your SSD and it has the drive letter C:\.
Then you make an Image of this install call it Image1 and you save it to your external Hard Drive E:\.
Then you install Microsoft Office on the D:\. This will create registry entries and program shortcuts on the C:\ Drives.
Then you make an Image of this install call it Image2 and you save it to your external Hard Drive E:\.
If you restore Image1 to C:\ the program shortcuts for Microsoft Office won't be present on D:\. You can go into D:\Program Files\... and launch the .exe but it will fail to launch as there are no registry entries for Microsoft Office on D:\ (and Product Activation issues).
If you restore Image2 to C:\ Microsoft Office will continue to work.