Sunday, December 16, 2012

Will we ever be able to measure cortisol in real time?

In my Copious Free Time (CFT), I sometimes like to try to figure out how close we are to implementing some of the crazy technology I’d love to use in research. I want to learn more about the canid stress response, as a way of learning about canid domestication (domesticated animals have blunted stress responses, and this may be part of why they are so accepting of novelty and so easy to socialize). The hormone that most people use to study the stress response is cortisol.

I have written in the past about some of the many problems with studying cortisol. Two of those problems are
  • Getting hold of cortisol (from blood or even saliva) without increasing the animal’s stress and therefore invalidating your study, and
  • Measuring cortisol frequently enough to actually be able to track its very rapid changes in the bloodstream (changes on the order of minutes, continuing to occur and be important over the course of hours).
What we really need, obviously, is a Star Trek-style tricorder that we can point at an animal and ask “what is this animal’s blood cortisol level just now? And how about now?” So recently I was wondering how close we were to this technology.

I asked a friend who works in research imaging. She obligingly sent me a review paper to read, about studying dopamine levels in humans using PET. The problem this paper addresses is getting at the dopamine levels in the brain without having to slice open the skull (something we definitely don’t like to do in humans — and although we might be willing to do it in rats or mice, it is going to be hard to retest the same animal later to see how its dopamine levels have changed, seeing as how a common side effect of skull sliceage is death). This is a pretty cool technology. It goes something like this:
  • Inject the individual with a radiotracer which is attached to dopamine agonist or antagonist. The agonist or antagonist will attach to dopamine receptors, and the radiotracer will allow us to use PET to monitor how much of it is attached in the part of the brain that we care about.
  • Monitor the changes in the radiotracer in the region of interest. As dopamine levels in that region increase, the unlabelled dopamine will bump more and more labelled agonist or antagonist off of the receptors, which will mean there will be less radiotracer in the region. Less tracer implies more actual dopamine. Do math.

Egerton A., Mehta M.A., Montgomery A.J., Lappin J.M., Howes O.D., Reeves S.J., Cunningham V.J. & Grasby P.M. (2009). The dopaminergic basis of human behaviors: A review of molecular imaging studies, Neuroscience & Biobehavioral Reviews, 33 (7) 1109-1132. DOI:

You could use something similar to monitor cortisol binding in the brains of dogs. That would be very interesting, actually, but the studies I tend to envision are more concerned with cortisol amounts that are released from the adrenals. We are actually in a better position here with cortisol, compared to the suckers studying dopamine in the brain: dopamine is released in the brain and stays in the brain, so you never get a chance to see it in the bloodstream. The bloodstream is actually easier to get at than the brain, obviously.

Conversely, cortisol comes from the adrenal glands (way down near the kidneys, far from the brain). The brain sends a signal to the adrenals via very long nerves, and then the adrenals release more or less cortisol, for a longer or shorter period of time. It’s the “more” or “less”, “longer” or “shorter” that are interesting. I actually don’t know enough about where cortisol binds to say if using a radiotracer-labelled cortisol agonist or antagonist, to sit on binding sites, would be interesting, but I suspect this is not the right direction for this technology. Cortisol binds in organs all over the body and affects a lot of processes. Unlike with dopamine, where researchers are interested in very specific (hence small) brain areas, we would want to scan the whole body for cortisol binding.

The radiotracer idea is interesting, though. Maybe we could attach a radiotracer to one of the precursors of cortisol, like cholesterol? We would inject labelled cholesterol. The adrenals would take it up and convert it to cortisol. Then when they released cortisol, we could see the label spreading across the body. No need to measure binding. We could in fact just scan one part of the body where there is a lot of blood — a vein coming out of the adrenals? — to watch cortisol levels rise and fall. The downside: the use of PET to monitor the changes in the radiotracer label. PET is expensive and it requires the subject to hold... perfectly... still. Something dogs are not very good at doing.

What I really wanted, I decided, was something that works sort of the way a pulse oximeter works. Pulse oxes are little devices that you hook up to an animal while it is under anesthesia to monitor their blood oxygenation (you know, to tell if they are dying or not, something which ironically is often easier to tell just by looking at the animal, but we use the things anyways). These devices work by shining a light through an area of non-pigmented skin (such as the tongue, an unpigmented paw pad, or if all else fails, a vulva) and measuring how much hemoglobin (hence oxygen) is in the blood based on color. Could some such device measure amounts of tracer label?

I was letting these ideas percolate and considering how I might write them up for you, dear readers, when I completely by chance came across the following announcement: Sano Intelligence is working on a wearable patch which will continuously monitor blood chemistry.

A wearable patch! That’s actually a much better solution to this problem. It operates wirelessly, so you slap it on (at a cost of $1-2 per patch for materials, though much more in the end to the company to pay for development costs, I imagine) and then remotely monitor changes in blood sugar, electrolytes, and — cortisol? Of course the company does not mention cortisol as one of the substances the patch would monitor. I wonder if there is any reason it couldn’t be included, though. It would help if I had any idea how this patch worked. The company asserts that it’s non-invasive and does not hurt to apply. So how does it get at the substances in the bloodstream? Apparently the company isn’t saying until the patch is released.

So now I wait. If any of you out there in internet land know more, or have thoughts on how this might work, let me know!

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