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Post by mrsonde on Feb 15, 2019 15:37:19 GMT 1
A question for you Alan, if I may be allowed to pick your brain a little. Every few months for the past few years I come across a new report about the brain's alleged production of endogenous DMT (in the pineal gland), always followed with a strong caveat that these suggestive findings have not been conclusively confirmed, given the difficulties of analysing its presence in a living subject (other than rats). What I'm puzzled by is: why can't functional MRI, or spectrum analysis NMR more generally, be used to detect its presence, or lack of it? I understand it would be very hard to get a decent image from this, of its neural network for example, given the fine frequency differences involved (determined by small molecular bond influences - between DMT and serotonin, melatonin, and other compounds it's the precursor or at least smaller analogue of - as far as my understanding stretches), but what we're looking for at this stage is merely a determination of its presence.
Given the enormous importance of this question - it would be the obvious mechanism for the production of dreams, for example; or quite possibly be implicated in illnesses such as schizophrenia; and plainly be essential for understanding the role of the pineal, and probably neurotransmitters/hormones generally - why hasn't sNMR been used to settle the question, after at least five years of bickering about it?
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Post by alancalverd on Feb 16, 2019 1:37:23 GMT 1
Spectral NMR may identify a molecular target species in a solvent, but it is strictly an in vitro process. fMRI tracks blood flow in the brain, so it can indicate the physiological effect of a psychoactive stimulus but won't locate the source.
In my days of R&D at the Department of Health I asked a number of doctors what gadget was top of their wish list. Unanimously, they wanted the kit that Dr McCoy uses in Star Trek: a wand that tells you what is wrong with the patient, and a box that fixes it. Sadly, we are still a few weeks away from production.
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Post by mrsonde on Feb 16, 2019 2:14:17 GMT 1
Thanks alan - why strictly in vitro? Other forms of MRI are in vivo - what's the hurdle?
I had no idea fMRI was still so limited - what atom is used, and why so restricted?
Are these combined limitations due to lack of precision in the transmission, or the reception and analysis?
Remember - the question is merely: is this particular compound present?
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Post by alancalverd on Feb 16, 2019 10:56:39 GMT 1
Spectrometry requires a high and precise magnetic field strength. It's very difficult to build a magnet with more than about 3 tesla that can accommodate any recognisable part of the human body, and the inhomogeneity of the body then upsets the homogeneity of the magnet. Even with the best 21T magnets (where the sample size is limited to about 10 mm or less) you have to rotate the sample to average out the inhomogeneities, so it's very much in vitro. Bruker make 8T laboratory MRI systems that can accommodate a rat but the spectral resolution probably isn't adequate to distinguish DMT.
fMRI contrast depends on the difference in relaxation times between oxygenated and deoxygenated blood, or the diffusion of water. The difference signal is pretty weak so you have to start with a molecule that contains plenty of hydrogen nuclei - nothing else approaches a bare proton for detectability.
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Post by mrsonde on Feb 16, 2019 18:07:08 GMT 1
Spectrometry requires a high and precise magnetic field strength. It's very difficult to build a magnet with more than about 3 tesla that can accommodate any recognisable part of the human body, and the inhomogeneity of the body then upsets the homogeneity of the magnet. Even with the best 21T magnets (where the sample size is limited to about 10 mm or less) you have to rotate the sample to average out the inhomogeneities, so it's very much in vitro. Bruker make 8T laboratory MRI systems that can accommodate a rat but the spectral resolution probably isn't adequate to distinguish DMT. So the limitations are on the reception side? Obviously, MRI - NMR to be predantic, though I gather earth's field MRI is making enormous strides - works with geomagnetic field strengths. It seems very odd that reception is the problem, given we can build interferometry devices that can now almost see back to the Big Bang or produce images of electon orbits inside an atom! (Generally, I wonder about this drive to greater and greater strength magnetic fields - it seems to me that may have been a blind alley, or at least an unrpoductive diversion: the reason developments in MRI have taken so long.) Bare protons? Loose hydrogen molecules, hydrated molecules, or molecules forming hydrogen bonds? The latter are in most organic compounds in the body - anything that works with water and crucially the NH bond, anyway - amino acids, proteins, hormones, neurotransmitters. I would have thought the difference in signal from a Nitrogen nucleus - that's an "odd" atom, isn't it, producing a NMR response? - in DMT compared to, say, serotonin was much more discernible? Even using hydrogen, surely the difference in frequencies (determined by the environmentally surrounding bonds) of the H in those two compounds - for example - must be greater than that discernible between oxygenated and deoxygenated water in blood? |
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Post by alancalverd on Feb 17, 2019 1:17:22 GMT 1
Low field MRI has better tissue contrast because the relaxation times are longer, so the difference in relaxation between fat- and water-bound protons is greater. But lower fields also mean fewer protons are aligned with the primary field so there is less signal and a lower signal/noise ratio. We are pretty good at recovering the MRI signal but if it ain't there, you can't see it! The clinical imaging imperative is to get rapid acquisition of contiguous slices (because the damn patients tend to breathe, and that heart thingy keeps wobbling about) so you need plenty of signal, hence a strong primary field. Sod's law intervenes around 3T where the "chemical shift" - a shift in proton resonance frequency due to its bonding - distorts the image so that coplanar fat and water appear in slightly different planes and the anatomical value of the image is degraded. I worked on mid-field (0.6T) "open" magnets which give the theoretical optimum contrast/noise ratio and a signal/noise ratio similar to a conventional 1T solenoidal magnet.
If you want to find the source of DMT, my preferred investigation would be to use a radiolabelled specific precursor and look for its uptake areas and stimulated clearance. But I'm sure an endocrinologist would explain why the chemistry is a bit more complicated than that - it always is!
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Post by mrsonde on Feb 25, 2019 19:24:44 GMT 1
Low field MRI has better tissue contrast because the relaxation times are longer, so the difference in relaxation between fat- and water-bound protons is greater. But lower fields also mean fewer protons are aligned with the primary field so there is less signal and a lower signal/noise ratio. We are pretty good at recovering the MRI signal but if it ain't there, you can't see it! The clinical imaging imperative is to get rapid acquisition of contiguous slices (because the damn patients tend to breathe, and that heart thingy keeps wobbling about) so you need plenty of signal, hence a strong primary field. Sod's law intervenes around 3T where the "chemical shift" - a shift in proton resonance frequency due to its bonding - distorts the image so that coplanar fat and water appear in slightly different planes and the anatomical value of the image is degraded. I worked on mid-field (0.6T) "open" magnets which give the theoretical optimum contrast/noise ratio and a signal/noise ratio similar to a conventional 1T solenoidal magnet. Thanks alan. I think I followed most of that, just. It would be the pineal, if anywhere, I'm sure. The question would be - or at least the one I'm interested is - why? I'm particularly interested in the mechanism by which our body clocks get set, of course - and the suggestion that there's a very large peak in DMT production at childbirth. Yees...could it distinguish it from serotonin, dopamine, melatonin? |
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