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We are excited that EDITINGSCHOOL and the GABA MRS symposium will be going ahead in November, in person. We have just finalized a block booking of 30 rooms for 42 registrants. Most people are coming to both events, so we will be able to arrange a degree of continuity across the programs.
Abstract submission is now underway for the symposium.
The day-to-day stability of GABA is an important assumption for many research projects, particularly those investigating neurochemical change/difference as a result of intervention or disorder. While reliability studies have typically found baseline MRS measures of GABA to be stable, some work has pointed to systematic changes linked to the menstrual cycle. Consequently, some researchers have since chosen to include only males within their samples, which can be deeply problematic for the generalisability of findings. Previous work exploring GABA change across the menstrual cycle has involved relatively small samples and been restricted to a small number of anatomical regions. Therefore, we are proposing to extend and expand upon this important work by running a large multisite project using a standardized methodological approach. Our proposal is for each site to collect data from 1-3 naturally cycling female participants before pooling the data. We are very keen to hear from research teams interested in getting involved in the project. Please contact – Katherine.dyke@nottingham.ac.uk for details.
The purpose of this post is to describe our standard process for scanning phantoms, and describe phantom-specific parameters that we use. Acquiring excellent-quality phantom spectra on clinical scanners is a real challenge, which requires a certain amount of witchcraft.
Excellent phantom spectra have narrow lines (~1-2 Hz), so the individual lines of multiplets are resolved, and flat undisturbed baselines to enable accurate phasing and integration.
The first step of acquiring excellent phantom spectra is preparing an excellent phantom (old instructions for a good GABA phantom).
Relatively high concentration (~10 mM) is a great start, since phantom experiments often involve parameter series of >10 individual experiments.
Sodium azide helps keep the bugs down (and build-up of gunk impacts shimming).
Store your phantom in a dark fridge to minimize breakdown, but also know your metabolites (GABA lasts ‘forever’, GSH less well, I think).
Use a bottle with friendly geometry that doesn’t result in violent field distortions (we used to use old peanut jars or milk cartons, and they were a lottery on this count). The 1 liter Nalgene bottle style 2125 is fine without being perfect. Spherical containers are better and more contentrated.
Avoid air bubbles. It’s better to fill the phantom up (and sacrifice exact concentration) that sacrifice shimmability.
The second step is placement. Try to locate your phantom centrally within the head coil and the main B0 field. A perfect spherical phantom at isocenter in a perfect magnet shouldn’t need shimming, so the closers you can get your ‘cylindrical’ phantom aligned with the central axis of the magnet, the better. If your phantom has an air bubble (most do), it is usually worth tilting the phantom to keep it up one end (ideally in the ‘cap’ region) rather than along the full light of the bottle. Placement judgment and luck in equal measure; sometimes I spend 20 minutes trying to optimize shim and WS on a phantom and just give up. After physically moving it within the bore, I start again.
Even with good shimming, phantoms are less homogeneous than we’d like. Voxel sizes of 2x2x2 cm^3 often yield (noiser) spectra with narrower lines than 3x3x3 cm^3 voxels.
On the Philips system, we use the pb-auto projection-based shimming routine, and it performs well (and quickly) both for phantoms and in vivo. However, you don’t have the option to tweak individual shim currents to optimize the line width manually, so excellent phantom shimming involves an iterative process of slightly moving and/or rotating the voxel, re-running the prep and checking the line width. The reported line width (in the log box) is an imprecise indication, but mostly we rely upon viewing the spectra to check linewidth.
The final piece of the puzzle is water suppression (WS). We tend to use the ‘exc’ option with WS optimization ON for phantom experiments. The automated optimization does a good job of keeping baseline disturbances from residual water signal to a minimum. The quality of WS achievable is dependent on shim quality, and we tend to optimize shim and WS at the same time. Again, sometimes you just can’t get things nice enough, even after moving the voxel around, so you have to reposition the phantom in the scanner. I tend to schedule 30 minutes to get great shim and WS, and then the time to acquire experiments, so 1 hour is never enough to get a full phantom dataset (even when it is technically ‘enough’). Take you time, and get everything just right. This also helps with not mis-entering a parameter series, another common failure mode of phantom experiments!
One final note on chemical shift: your phantom is likely to be at room-temperature and ‘close-to-physiological’ pH. Chemical shifts and coupling constants can depend on temperature (and pH) and for our commonest phantoms the water line tends to come at ~4.8 ppm. For frequency-selective experiments like edited MRS, you need to account for this in setting editing pulse frequencies. This is handled in our patch via the BASING parameter ‘water freq’. The scanner tends to assume the water line comes at 4.68 ppm, so we can infer the correct water shift from a processed spectrum by checking how far off-resonance the metabolite signals appear in teh SpectroView window.
One common artifact that we see in MR spectra are unwanted water echoes. The spectrum below shows this behavior around 4 ppm. It manifests as a region of the spectrum with ‘locally increased noise’, which is more accurately considered as a broad signal with a large first-order phase error.
This happens when the sequence accidentally refocuses water signals from outside of voxel OOV (or merely fails to fully suppress them with the gradient pulses), and can seriously interfere with quantification. For a given brain location and acquisition protocol, these artifacts are relatively consistent and so can be ‘optimized away ‘. This process is something we advise collaborators to do every time they set up a protocol for a new brain region.
The key parameters are the voxel orientation (transverse/coronal/sagittal) which changes the ordering of the slice-selective pulses within the PRESS sequence (or rotates the experiment 90 degrees about a cube-face) and the water-fat shifts (L/R etc) which flip the slice-selective gradients one-by-one (reflecting the experiment spatially a plane parallel to a cube-face).
Before you work on a challenging brain region, make sure your sequence works in PCC or some other ‘easy’ region with which you have experience. When you are sure the sequence is set up correctly, then you can move onto this geometric optimization.
Step 1: Run an in vivo scan in a new brain region. Use 320 averages and ~25ml volume so you know what to expect in terms of SNR. If the spectrum looks ‘clean’ with respect to these OOV echoes, then I would not continue with this process. Run a new subject and hopefully that’ll look fine too.
Step 2: If you see OOV echoes, run scans with all three options of the orientation parameter, and select the one that gives the smallest OOV echoes.
Step 3: With that orientation, start working on the water-fate shifts. One quick option is to flip all three and see if it solves your problem. Hopefully you can see the OOV echoes in the Spectroscopy tool on the scanner. For each water-fat axis, select the option that gives the smallest OOV echoes.
This process is not 100% reproducible across subjects, but it is enough to be useful.
One final note: The data above were acquired from this midline ACC voxel. The orange box corresponds to the 3 ppm signal and the white to the chemical-shift-displaced water signal. When setting up a new voxel location, I tend to recommend setting the water-fat shifts to put the white box ‘inside‘ the orange box. By ‘inside’, I mean away from scalp and other challenging areas.. towards the middle of the brain….
We are really excited to announce that we are holding the 6th International Symposium on Advanced MRS and GABA at the end of the year. It will be preceded by an in-person EDITINGSCHOOL course. We are hopeful that vaccinations will continue to have an effect and that we will be able to travel by then. Go here to get your tickets booked.
EDITINGSCHOOL
EDITINGSCHOOL is a 3-day course (Nov 15-18) exclusively dedicated to edited MRS. It will cover background MRS theory, theory of editing, editable metabolites, analysis software, quantification, and practical tips on acquisition and data review.
6th International Symposium on Advanced MRS and GABA
The GABA MRS symposium (Nov 18-21) is an opportunity to present your advanced MRS study of GABA (or other metabolites), to a broad audience with a common interest in the methodology. All accepted abstracts will be orally presented, so this is a great opportunity for junior scientists to present in that format.
The two events will happen back-to-back at the beautiful XCaret Occidental Resort in Playa Del Carmen, Mexico. All tickets include food and accommodation in addition to access to the EDITINGSCHOOL and/or symposium.
Nov 15: Arrival and opening reception
Nov 16: All-day EDITINGSCHOOL PROGRAM (program TBA, but likely to follow this format)
Nov 17: All-day EDITINGSCHOOL PROGRAM (program TBA, but likely to follow this format)
Nov 18: Morning EDITINSCHOOL break-outs; departure for EDITINGSCHOOL-only attendees
Afternoon arrival for Symposium-only attendees and evening mixer
Nov 19: All-day Symposium (sessions of oral abstracts)
Nov 20: All-day Symposium (sessions of oral abstracts and break-outs)
Nov 21: Discussions and Departure
We are excited to re-open early registration for these events until the end of March. Go to https://www.eventbee.com/v/editingschool-and-gaba-mrs-symposium-2021/event?eid=164490043 to get your tickets booked.
We will have options for solo rooms or shared accommodation (we can assign you a roommate, if you don't have one). If you have a non-attendee partner that would like to attend, buy a SOLO ticket for you and a non-attendee roommate ticket for them.
FAQ
Who is this aimed at?
EDITINGSCHOOL and the Symposium will be invaluable to students, whether just starting out or preparing to write up, and postdocs using or developing MRS. Faculty, particularly those from a neuroscience/clinical background, will also find something to chew on.
Where is this?
EDITINGSCHOOL will be at the beautiful X-Caret Occidental hotel in Playa Del Carmen, Mexico. Flights to Cancun are relatively easy from North America and Europe, and a shuttle will take you down to the resort.
What am I getting?
Registration will include hotel accommodation, all food, and the course itself. It is a bargain.
How much does this cost?
There will be several rates, based on single/shared room, early/standard/late, and EDITINGSCHOOL/Symposium/both registration. To register for BOTH, early registration, running from now until March 31st will cost: $900 (shared room) and $1200 (single room). Standard Registration, before Sep 15th will cost: $1200 (shared room) and $1600 (single room), and late registration will be $2400 (single room only). These rates for either the Symposium or EDITINGSCHOOL only are: $540 (shared room) and $700 (single room). Standard Registration, before Sep 15th will cost: $700 (shared room) and $900 (single room), and late registration will be $1400 (single room only).
We are looking to recruit two postdoctoral fellows to join our team developing new acquisition and analysis methods for MRS. Any prior experience with MRI or MRS is applicable, we are just looking to recruit someone curious and motivated to join our team. If you might be interested do reach out by email ( raee2 at jhu dot edu), as I am keen to talk to any interested candidates. Whatever your background, exspecially if it differs from ours, we want to hear from you.
We have active projects investigating oxidative stress in autism and are developing the tools for a large multi-site project imaging the neonatal brain. A postdoctoral fellowship in our lab is an excellent way to build up your skills for a successful independent research career. Don’t hesitate to drop us an email.