Turby

Have you come across the Teensy MicroMod ? https://www.sparkfun.com/products/16402 Not quite as many IO as you propose but is already commercially available off the shelf

The answer must be yes, but by how much I don't know. What about adding some SPI FRAM which can be written very fast many many times?

If you have a Teensy with Ethernet and a TFT screen that you update with buffers of 16 bit RGB565 pixel data you should be able to use this code, along with the supplied Mac or Windows client, to also display (and control) the screen remotely on...

Going back to the OP, I guess the solution depends on what level of accuracy and precsision is required.

FWIW trying to establish the distance moved by a train based its wheel rotation you quickly loose accuracy, which quickly accumlates over time and distance. When I worked on an ETCS project a few years back we had to resync actual train location...

How would it perform on the much faster T4.x?

Do you really need to generate a VR signal for the ECU under test? A VR signal ranges from very low voltatges to 10s of volts possibly 100's! Are you developing a VR Conditioner yourself or does the ECU already use one such as the MAX9926 or...

I've always kept the ISR handler to an absolute minimum, ie set flag / store data and the main loop checks for said flag and process the stored data. I never call Serial.printf within an ISR, even other "library" functions if at all possible.