X-Message-Number: 5008
Date: Tue, 17 Oct 1995 09:36:58 -0700 (PDT)
From: Joseph Strout <>
Subject: tissue-degeneration model

In scuba diving, it is important to keep track of the amount of nitrogen 
which diffuses into your tissues, because this nitrogen will be released 
when the pressure decreases, and if released too fast, could cause 
bubbles in the blood (affectionately dubbed "the bends").  This used to 
be done with tables compiled empirically, but lately, they've developed 
"dive computers" which contain a relatively simple model of various 
tissues and track the nitrogen concentrations over time.  This allows 
a diver to have a more accurate picture of his or her body's state, 
diving longer and more safely.

It occurs to me that a similar model for brain tissue state would be very 
useful.  Every case is different; different conditions of ischemia, 
fixation, temperatures, etc.  Moreover, to extrapolate cryomicroscopy 
results from small tissue samples to entire brains, we need estimates of 
how each effect scales with tissue thickness and time.  (And, more 
importantly, we need to APPLY these estimates, so that we don't blindly 
suggest that what works for a 1-mm tissue slice will work for an entire 
brain).

Such a model would certainly not replace experience and good judgement, 
but it could serve as a valuable aid.  Each patient's condition and 
treatment would be entered into the model, giving a picture of the state 
of his/her brain tissue at varying depths from the outside or from the 
vasculature.  Alternative treatments could then be "tried" first on the 
model, to see the effect on a variety of measures.  As treatments are 
applied, the model would be updated at each step, and the suspension team 
leader would glance at it now and then to make sure they hadn't 
overlooked any side-effects or whatever.

As new treatments (e.g., microwave fixation) are developed in cryobiology 
or microscopy, these could be entered into the model.  We could then have 
much more productive discussion about alternatives.  The model would also 
make it painfully clear where more research is needed.

Difficult?  Certainly, but probably not impossible.  The "state" of the 
tissue (our real interest) could be measured along several independent 
dimensions, such as:
	- mobility or viscosity (how "hard" or "soft" is it?)
	- synapse/spine degeneration
	- cell membrane integrity
	- dislocation (i.e., how far has a "part" moved from its
	  proper position)

Inputs would all be functions of time, and would include:
	- perfusion solution (constituents)
	- application method (external, vascular, other?)
	- temperature

Even if such a model never proves good enough for clinical use, building 
it might serve to focus attention on important issues and effects.  What 
do you think?

,------------------------------------------------------------------.
|    Joseph J. Strout           Department of Neuroscience, UCSD   |
|               http://www-acs.ucsd.edu/~jstrout/  |
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