Agreed, emphatically, that we need more funding to go for empirical validation of cryonics premises and procedures. However, Aschwin de Wolf has pointed out one reason it is difficult to compare vitrified brains to fixed-embedded, namely dehydration. So I'm somewhat suspicious of the usefulness of the prize at this point in time.

A specific concern for Brain Preservation Technology Prize competitors using cryopreservation is that cryopreserved brains are currently very dehydrated. Due to this dehydration, which typically persists even after cryoprotectant removal, it is not yet clear that cryopreserved brains can be effectively evaluated by the Prize organizers. To be specific, the criterion for success is preservation of the connectome, which requires two things: preservation of synapses and preservation of enough information to infer the pattern of connections between them. Neural cryobiology researchers believe that they can achieve good ultrastructural preservation of the brain but dehydration compactifies the neuropil, reduces space between structures, and makes the tissue so dark in the electron microscope that it is hard to actually observe the synapses. So if a quick scanning method doesn’t discern all synapses that are actually there, it will fail. There are techniques for doing electron microscopy at cryogenic temperatures in the vitrified state, but these depend on the tissue being sliced before vitrification. Making slices out of a whole vitrified brain while vitrified is a tough problem. It is easier to make thin slices out of a whole brain that’s been turned into solid plastic because the resin used is designed for being cut into thin slices for microscopy. So plastination has a natural advantage in this competition — in terms of processing for the tests rather than in actual results.

A non-dehydrated brain is not only more likely to survive by information-theoretic criteria, and to e.g. benefit from ice-blockers, it is easier to scan for evidence of survival. So a high priority should be to achieve reduction in dehydration. An earlier discussion with Mike Darwin had me thinking it was a problem with myelination, but currently I am given to understand (per Aschwin de Wolf and Greg Fahy) that it is primarily a matter of the blood-brain barrier. Aschwin also mentioned that there should be evidence in the literature of what ideas to try next, since this is a problem in conventional drug delivery. Yuri Pichigu has developed an approach to opening the BBB, however 21CM found that it did not increase viability in rabbit brain slices. I'm not sure whether that failure is limited to viability or also extends to the morphological characteristics we are interested in here.

Anyway, dehydration and the blood-brain barrier is high in the search order for the next thing to solve. Without it, vitrification is a bit of a shot in the dark. We can speculate that dehydration is okay as long as it is relatively uniform, but it may not be (and of course isn't, in more poorly perfused patients).