[…] I still wouldn’t get your hopes up. As far as I can see, it offers no way to discern the state of the neurons, and admits that while it might be possible to get the structure for a small slice of the brain, getting it in 5nm detail for the whole volume is currently impossible, with no known way to overcome the current technological limitations. Many of those limitations are imposed by the wavelength of the medium you’re scanning with, and there’s just no easy way round that. The speed of scanning (which is also currently a showstopper for the ~5nm technologies that might otherwise be attractive) might be able to be improved, but bear in mind that you’re working at levels where the energy of the electrons/photons that you’re using to scan risk damaging the sample, and using more of them in parallel may damage it more. The data transfer/storage problem probably is solvable, by contrast.This stands out from the field in that it is actually in reply to something that someone who believes in cryonics has actually said; it only doesn’t meet the criteria that I asked for in my open letter in that it is blog comment rather than an article, but knowing how busy David is it’s hard to imagine him finding the time to rewrite it in article form any time soon, so with his permission I’m posting it as is.
I find it a bit worrying that the most promising technologies in the table on page  — SOM and SEM, especially combined with array tomography — have relatively little discussion in the text that I can see. This makes me suspect that they’re only even superficially attractive because not enough is known about them to know they don’t work.
Also, given that the conclusion says ‘this sets a resolution requirement on the order of 5 nm at least in two directions,’ there’s far too much discussion of technologies that can only scan down to resolutions two orders of magnitude higher than this. So the text gives the optimistic prediction that ‘[KESM] enables the imaging of an entire macroscopic tissue volume such as a mouse brain in reasonable time’, but what good is that given that KSEM only scans down to 300nm x 500nm? It’s an obvious question, and I’d expect an honestly-written paper to answer it. Because this paper doesn’t, I smell a rat (or, more likely, someone clutching at straws).
The discussion starts ‘As this review shows, WBE on the neuronal/synaptic level requires relatively modest increases in microscopy resolution…’ which may be technically true but vastly understates the difficulty of increasing the resolution of the techniques discussed.
Again, though, I’ll defer to someone who’s done this stuff more recently than I have (and in a medical area — I was mostly looking at metal-matrix composites rather than anything organic).