Hi Mags,
Daan gave a good response to this question in another thread. The original question there does not cover the prospect of having an adequate number of DWIs in multiple phase encoding directions independently, but the point regarding EPI distortions making the spatial distribution of noise not quite equivalent between phase encoding directions holds here. Personally I’ve historically just concatenated everything together then denoised, but I trust Daan’s judgement here moreso than my own. It’s also a common source of uncertainty, so might be worth turning into a Wiki page.
Cheers
Rob