Hello Cboley and Welcome to the Forum:
HVAC contractors use a duct calculator to size their jobs. It is like a little slide rule that gives instant answers. I worked for a National Distributor of HVAC-R for 3 years in the early 90's but, somehow, I have lost my calculator.
The best I remember a 3 X 12 duct will not carry over 100 cfm; same as a 6" round duct.
Unico, Inc. makes a system that is well suited for older homes.
They start with a high velocity/ high pressure unit and use an 8" square duct for a trunk line, a hose that looks like vacum cleaner hose, silencer adapters at the terimnis and use a register that is no larger than a porcelain bulb fixture. They are very convenient to snake through walls, ceilings and floors. I have talked to customers who had them and they were very well satisfied.