What do we really know about fracturing?

The goal of any credible cryonics organization is to develop reversible cryopreservation to avoid passing on problems with the cryopreservation process itself to the next generation. While there is a lot of recognition for the need to eliminate cryoprotectant toxicity, it is rather obvious that it will not be possible to restore integrated function in a fractured brain.

The 2011 3rd Quarter issue of Cryonics magazine features a comprehensive update on intermediate temperature storage (ITS) by Dr. Brian Wowk. This article contains an important observation:

“Acoustic events consistent with fracturing were found to be universal during cooling through the cryogenic temperature range. They occurred whether patients were frozen or vitrified. If cryoprotection is good, they typically begin below the glass transition temperature (-123°C for M22 vitrification solution). If cryoprotective perfusion does not go well, then fracturing events begin at temperatures as warm as -90°C. Higher fracturing temperatures are believed to occur when tissue freezes instead of vitrifies because freezing increases the glass transition temperature of solution between ice crystals. The temperature at which fractures begin is therefore believed to be a surrogate measure of goodness of cryoprotection, with lower temperatures being better.”

This is an important observation because one of the arguments that is still being made against intermediate temperature storage is that Alcor routinely records fracturing events above the nominal glass transition temperature (Tg) of the vitrification solution. But if we recognize that such events can be (partly) attributed to ice formation due to ischemia-induced perfusion impairment it should be obvious that the recording of fracturing events above Tg as such cannot be an argument against ITS. After all, we also do not argue against the use of vitrification solutions because ice formation will still occur in ischemic patients that are perfused with vitrification solutions. Because cryonics patients almost invariably suffer some degree of ischemia prior to cryoprotective perfusion and cryopreservation, our knowledge about fracturing events in “ideal” human cases remains incomplete.

Hugh Hixon has developed a “crackphone” to detect acoustic events that are presumed to reflect fracturing events. A preliminary survey of the data reveals, roughly, that the first temperature at which cracking events are recorded is lower for the newer generation of vitrification solutions than for the older glycerol solutions. Does this mean that fracturing occurs at lower temperatures in “vitrified” patients? “The lowest first fracturing event recorded at Alcor was at a temperature of -134°C for M22.”

Is this what we can expect for M22 for all patients, or was this an “ideal” case, too? Would -130°C be a safe storage temperature? Does molecular-scale ice nucleation, as distinct from ice growth, constitute damage? Despite all the articles and discussions that have been devoted to the topic of intermediate temperature storage, we do not seem to know much yet about fracturing in (large) tissues that are well equilibrated with a vitrification solution and subjected to a responsible cooling protocol. While the crackphone data seem to support the use of the newer vitrification solutions for reducing fracturing, controlled studies of fracturing in vitrified tissues will need to be conducted in a lab to really understand what we can expect under ideal (non-ischemic) circumstances.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine July 2013