Introduction to DMI

January 21, 2020

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To CiteDCA Citation Guide

00:00Hello and welcome to an introduction video about the Deuterium Metabolic imaging or dmi.
00:07In this video we'll try to explain what the Deuterium Metabolic imaging is.
00:12And to answer that we should know what the theorem is and what metabolic imaging is.
00:20For more would like to explain why you want to use the Deuterium Metabolic imaging or dmi.
00:25What do you need to run DMI at your particular site and where can you find the methods and other materials at this website,
00:34so that you can actually run dmi agile at your side.
00:39First, what is dmi? Dmi is part of a large family of isotope labeling and tracing methods that include carbon 13 amorous hyperpolarized Emerson Emirates.
00:53I nitrogen 15. Amorous oxygen 17 amorous and as a few more as well.
00:59All of these methods, they are aimed at detecting dynamic better.
01:04Poly part ways by following the fate of the Isotope from a given substrate into a variety of metabolic products.
01:13Let's look at an example.
01:15Let's look at glucose, which is a very important substrate for for example,
01:20brain metabolism to glucose is being taken up by the brain and undergoes glycolysis and being converted among many other things into lactic.
01:31Update can enter the TVA cycle where ultimately it can be converted to glutamate.
01:37Now, what we can do,
01:38we can measure the glutamate and elected and glucose to lactate in the glutamate.
01:44If we mention them overtime.
01:45We get horizontal lines because.
01:48The glutamate concentration doesn't really change overtime.
01:52The lactate concentration doesn't really change.
01:55Overtime and that is because the system is in a metabolic steady state.
02:00The elected concentration doesn't change because the number of molecules of like their monitors are being formed.
02:07Is equal to the number of molecules that are being broken down so therefore the in minus out is 0?
02:13Show measuring just the total pool as she would do with Protel Emirates.
02:19For example, doesn't give you any information on how fast this part way is that where isotope labeling strategies come in.
02:28If we now use glucose but it has now been isotopically labeled in the one position year or in the 6 position or in both positions at the same time
02:38that she 13 labeled glucose still undergoes the same metabolism.
02:43Where these are converted to lactate in which now the sea turtle labels in the 3 position like that can enter the Tissier cycle and ultimately that carbon 30 label
02:54is ending up in the four position of roommate now the appearance.
02:59Of the carbon Tutti label can be followed overtime for example,
03:03with carbon 13 NMR and then you can see the build up of the elected here in the build up of the glutamate.
03:11Now the system is still in metabolic.
03:13Steady state elected pool size.
03:15The total amount of lactate being present doesn't change.
03:19However, the system is not in a nicer topic.
03:22Steady state yet in the beginning of the curve,
03:26there is more seat urchin labeled like that being formed.
03:30Denary broken down and you can see the amount or she turtle level like that being built up.
03:36Now by measuring these kind of turnover curves.
03:39You can determine how fast is metabolic pathway is Furthermore simply the presence of C13 elected already proved that this part way is metabolically active.
03:51Now these curves can be measured as a concentration of the C 13.
03:58Fable metabolite overtime, but you can also convert it into a fractional enrichment,
04:03which is basically given by this equation.
04:06The amount of carbon 13 labeled Metabolite divided by the total pool size of the metabolite times 100%
04:13and then this curve is being converted into these kind of curves.
04:17Now you can see that from all the glucose that is present in a tissue about 80%
04:23is carbon 13 labeled from all the glutamate after about an hour and a half present in a tissue.
04:29About 40% is carbon 13 labeled.
04:32Now from these kind of curves you can measure these kind of curves two ways.
04:37One way is dynamically where you measure data point.
04:40Let's say every five or every 10 minutes and from then the turnover of these metabolites.
04:46You can get absolute metabolic fluxes in absolute units.
04:49Micromort program per minute. Sometimes is not necessary or practical in that case you can also do a steady state measurement where you only mention one data set.
05:00Let's say between these 2 lines about an hour and a half after you start the infusion that is circled steady state metabolic imaging experiment.
05:09And this proves the presence of metabolic pathway activity.
05:13If you see again see 30 lactate being formed.
05:16Then this part way must be present an must be active.
05:21Now these kind of experiments have been done for decades,
05:25carbon 13 NMR as being the classical example.
05:28Here is a typical C 13 volume in the occipital cortex of the human brain and it is a spectrum that you get from that volume with carbon 13 NMR
05:36and you can indeed see that the security level glucose has been converted to glutamate into glutamine and to lactate and that will provide you the information about this part
05:47ways. The downside of carbon to Tina Marie's it has a fairly low sensitivity that translate into large volumes and therefore the imaging is typically not really viable.
05:58It's typically see 30 metabolic spectroscopy.
06:02It is technically also very demanding.
06:04You need to have good spatial organization.
06:07You need to have polarization transfer to enhance the sensitivity need their broadband decoupling so technically this is not an easy experiment and therefore even though it is a very
06:17powerful research tool, it is not really a viable clinical tool.
06:21OK, so if we accept that carbon 13 is very powerful.
06:25But it's not clinically viable.
06:28What other options. Do we have well if you look at the glucose molecule the formulas basically C6H12O six so if the carbon 2 teen is not an option,
06:39then we only have the hydrogen or the oxygen to isotopically label.
06:44Now you could label. The oxygen ocean 17 has nuclear spin so that is possible.
06:51However, the label tends to rapidly exchange with water and you don't retain label long enough to map out entire metabolic pathways.
07:01So that leaves us with the hydrogen isotope.
07:04While hydrogen has 3 isotopes,
07:06it has the Protel Isotope,
07:08which we're all familiar with it has to deuterium isotope,
07:11which is basically an additional neutron and there is attrition,
07:15which has 2 additional neutral.
07:17The Proton and Ethereum are as stable.
07:20The tritium is not radioactive radioactive and therefore we will not talk about those.
07:26Protein is called highly abundant and deuterium makes up the rest.
07:31All three of them, actually have nuclear spin deuterium has a nucleus spin of one the frequency of deuterium is about 6,
07:391/2 times lower than that of Proton.
07:42And, of course, we are very familiar with proton with hydrogen Proton.
07:48Isotope becauses used for MRI and use for 90%
07:51of all NMR an amorous in vivo as well.
07:54The theorem is also being used quite a lot in NMR,
07:58but mostly for solvents and to provide a lock signal for high resolution NMR.
08:05But it actually turns out that deuterium Panama in vivo is actually also very promising,
08:11and that is the foundation of deuterium at the public image in so if we acquire deuterium spectrum from red brain in Vivo.
08:19We're getting a spectrum something like this.
08:22It has only one signal in it,
08:24which is the natural abundance voter signal at correspond to about 10 min imonar word of the theory AM.
08:32And they should of course,
08:34also be lipids in there,
08:35but lipids are in the signal to noise typically not high enough for lipids are very low.
08:40If you want to summarize the spectrum like this.
08:43It actually has really good signal to noise because the spectrum is acquired in one minute only and the secret noises high becaused deuterium has a large magnetic moment because
08:52of the spin. One it has short T1 relaxation times.
08:55It has a decent detour relaxation time so you have good sharp relatively sharp peaks and it is also a very robust method.
09:03You do have a nice water signal,
09:05which functions as an internal concentration reference?
09:09Which is really nice. But it is low enough so he don't need water suppression lipids are also low enough that sometimes you can detect a small little signal,
09:19but you don't need Liberty oppression,
09:22so overall. The acquisition methods can be very simple no water suppression.
09:26No liver suppression and finally be cause of the low larmore frequency,
09:31you are relatively insensitive to magnetic field and homogeneity.
09:35So this makes it very nice sensitive an robust method to acquire deuterium Spectra,
09:41an image is in Vivo.
09:43Now, if you now administer duty rated glucose,
09:46which is now has 2 deuterons at the 6 position and you wait.
09:50Let's say 60 minutes. Then,
09:52after 60 minutes. You can actually see the metabolic products of their glucose,
09:57which is shown here. It is basically broken down to lactate via glycolysis and that is an entry in TH cycle and it is ultimately ending up in the glutamate
10:07glutamine metabolic pool. Now. This again,
10:12the spectrum is is quite an only one minute,
10:15so if you have such a good signal to noise.
10:18You can use that signal to noise to either go really fast in time and acquire Spectra every second,
10:24few seconds or you can go in imaging mode and get spectrum.
10:28Small volumes and that's what dmi is all about so this is the setup deuterium coil in yellow Anna Proton Coil for anatomical imaging an shaming.
10:39And then basically the sequence is that you just acquire a 3 dimensional.
10:43Mr spectroscopic imaging of deuterium.
10:45You're going to get a TV and spectrum of all of these locations within the sensitive volume of the deuterium coil and you can see in anatomical image in the
10:54background that this is red brain.
10:56And it has an implant at humor in the white area here.
11:01So if you look at Spectra for the normal brain tissue.
11:05You have again. The glucose the glue made an elected is very,
11:09very low if you now look.
11:11A spectrum in the tumor.
11:12You can see that the glucose has been reduced a little bit.
11:16The glutamate is essentially gone and the lactate is a high and elevated so this gives us a really nice image contrast based on Mataba Lism.
11:27Now you can also make Maps out of out of that day that you can get a glucose map glutamate mapping elected map like that.
11:35Being high glutamate being low can also make a ratio map gives you really high.
11:41Your contrast to noise based on metabolism,
11:43so that's very different from MRI,
11:46which is always water based image contrast.
11:49This is now metabolism. Based image contrast.
11:52This can also be done on humans and ultimately it will be our hope that if there's a patient and patients coming in getting the standard battery of Clinical.
12:02Mr images T2 weighted flat.
12:04Even with a contrast and hands susceptibility weighted imaging and diffusion weighted imaging and and.
12:11In the same session, the shop vac will also get a deuterium metabolic image.
12:16And you can for example,
12:17generates lactate over glutamate Maps and showing you very high contrast and will provide you a different dimension.
12:26Metabolic dimension that has been lacking Indiana in so many studies where that I've only used MRI.
12:35OK so assuming that you want to use dmi?
12:38What do you need well you need a sequel?
12:42You need an RF coil and shave a squirrel or for humans.
12:45It might be more volume coil.
12:47You need in substrate administration protocol,
12:50which in humans could potentially just be a simple drinking of the substrate now on the next few slides will go over these items that can all be downloaded from
13:00the website if you know where to look.
13:03So the sequence.
13:06It suppose acquire sequence with a phase encoding blip on all 3 axis.
13:10There's 2 modes in which you can sample all of K space or you can sample a spherical portion of K space.
13:17Now this sequence can be downloaded if you go through the resources tab and then Emma methods at the moment you can download the broker 3D D.
13:27My method an protocol in the future will hope to extend it to a variant,
13:32Siemens and all the other clinical platforms as well.
13:37We also hope to over an advice and drawings and a treaty.
13:43Like print files for RF coil of preclinical RF coils.
13:48We hope to provide you with layout something like this,
13:52where you get a file that you can't really print to print the Holder that can be like populated with the RF coil elements.
14:02Will also provide with Phantoms the Phantom holders at the moment.
14:07We're still working on making this as smooth as possible.
14:10After this is under construction.
14:13But once it is ready,
14:14you can also find it under the resources steps and then on the RF coils.
14:20Of course, you need to administer the substrates on animals.
14:24They will typically be an intervenous infusion.
14:28So on the website. You can find protocols for the infusion protocol for glucose an for acetate that will give you a nice and stable fractional enrichment in the blood
14:39plasma. You can also be found under resources steps and then under protocols.
14:45Finally, when you acquire dmi data you will need to process it.
14:49We are offering a processing platform refer to Sdmi Wizard.
14:54It allows you to load in dmi data from all the major vendors.
14:59Ultimately, you can then walk through the data look at individual.
15:05Spectra you can also look at Spectra in a 2 dimensional grids or even make metabolic images as shown here that can an overlay within anatomical.
15:16MRI this software can be found again under resources and you can also find some data set as well that you can.
15:25Used to practice the software with.
15:29We ask you if you want to get this warfare or any of the other components to fill in a quick full form and basically said some basic information about
15:38your institution about your email and where you can use indicate which items you want for download.
15:45We will certainly not use this information to share with 3rd parties.
15:49It is we simply want to use this to build up an email list,
15:53so that we can contact people who are interested in dmi if there is a new release of the software,
15:59or if there's a workshop that is dmi.
16:01A related basically just interesting things I don't anticipate this email to go out more than once a year so that would certainly be in very limited capacity.
16:12Finally, the website also provides some education,
16:15they will be showing their frequency frequently asked questions.
16:19There will be some videos at the moment?
16:22Is there's one other video,
16:24but that will definitely be built up overtime will also keep an active list of ALDI my related references both from Yuan from other institutions so that you have a
16:35nice one place to go to download everything dmi related.
16:39OK, This Is This is all we wanted to say.
16:41In this introduction video. Of course,
16:43please contact. A contact us.
16:45If you have any questions or if you need any help.
16:48And we wish you the best of luck with EMI.