For what it's worth, a few years ago I was backing up Ghost images to an NTFS USB hard disk using Ghost 2003 and getting single large GHO files without any issues with span errors. I was booting WinPE 2.x
Check your machine and use USB-2 devices with a USB-2 port on the PC, as this normally avoids any issues with USB drivers.
If you are booting WinPE 5 or Win PE 10, check that you can see the source drive correctly. If not, you will need to find a SATA chipset driver for your machine, and you can load it dynamically using DRVLOAD (path to driver INF file) from the WinPE command line.
If you are DOS booting the flash drive - forget it, it's never going to work with modern hardware.