If you mean the graphics are all stored as 16-bit UYUV data then it will require custom drawing code rather than using tilemaps & drawgfx etc. (as MAME can only draw up to 8-bit source graphics anyway) I had to do custom for X2222 prototype for example as the actual gfx data there is raw 15-bit colour data.
If you mean just the palette is in that format, then it should just require decoding in the palette writes?