Field Drift and fMRI

Some scanners suffer from rather large field drifts after fMRI acquisitions, due to heating of passive shims and other metal in the scanner.  We are working on the extent to which this impacts measurements. Dr Benjamin Glaubitz in Bochum acquired this data showing the dramatic field drift caused by a single 10-minute fMRI run. Gannet seems to do a reasonable job of correcting the drift (although whether it removes all the effects of the drift is not yet clear).

 Clearly there are some studies which require fMRI to be performed before GABA-MRS< but if you can avoid it, we'd suggest leaving fMRI (or DTI) until after the GABA scans.

A GABA paper review of 2012

Mainly to stop the promise of Gannet 2.0 from haunting me in the most recent post, I thought I'd do a quick look-back over 2012.  Some of this is shameless plugging, some is poorly focused musings...  either way, here is a quick review with links to some of our (and other people's) GABA MRS papers from 2012).

December 2012
For me, the highlight was the acceptance of our "Current Pracice in GABA MRS" review paper that came out of the 2011 Cardiff Symposium.  Paul Mullins did a great job of keeping it moving and it should be out in the new year in a special edition on GABA MRS.

November 2012

Dikoma Shungu's groups published a few GABA papers this year, this paper in OCD and also two AGP papers (!) earlier in the year in Schizophrenia and Depression.

September 2012
Charlie Stagg in Oxford has done some great work manipulating the GABA system with TMS and tDCS, and here she asks the million-dollar question "What are we measuring with GABA MRS?". A very interesting question and paper.

August 2012
Linking in great with the "What are we measuring?" question are a few genetic studies that relate brain, or in this case CSF, GABA to genetic variants.

July 2012
It was great to see a couple of long-term collaborations come to fruit in July, with James Stone publishing his Ketamine challenge study in Molecular Psychiatry, and my ADHD collaboration with Stewart Mostofsky in AGP.

June 2012
The role of GABA in sleep is an interesting area and a few groups have started to look at Insomnia.

May 2012
Speaking of collaborations baring fruit, Brad Foerster and the UMichigan group have published a pilot in ALS, with a follow-up of a larger cohort in press at JAMA Neurology.

Feb 2012
Graeme Mason's group showed that ethanol decreases brain GABA, maybe a counter-intuitive result, but one that fits with a 'more GABA, better performance' trend in individual difference studies.

Jan 2012
While doing reading for a grant submission in 2010, I let myself get waylaid by writing a review of the same material.  This kicked off a productive (in papers terms) 2012 for us, and a second paper for my postdoc Nick Puts.  The first paper also came out that applied GABA MRS to Parkinson's Disease - an area where the technique is very relevant, if only we can get things to work well subcortically.

If your paper isn't up here, I probably missed it - no slight intended!

Towards Gannet 2.0

Several things have come up that suggest the best way forward is to re-organise a lot of the code, and work toward Gannet 2.0. But for now, I am also working to maintain and improve the current Gannet version.  The most recent changes, in response to a major site visit hiccup, seem to be positive for Philips .sdat data but may potentially be negative for other data types.
One of the major changes in Gannet 2.0 will be that the workflow for different data types is integrated wherever possible.  This is likely to be challenging, jsut as the current edit, as changes for one datatype might adversely affect another. Things are likely to progress incrementally.

Gannet Glitch Report

If you are considering downloading Gannet today, please wait a week. We have a minor issue that needs fixing (and I am out of the office).

It concerns a longer-term issue of 'Is the Off or the On spectrum acquired first?'. My general advice is Off first, but sometime data gets acquired On-first, and that requires a couple of minus signs to be added in... these have unfortunately seeped into the Master thread online. A better way to handle it would be to auto-detect whether on or Off are first - a longer project than the quick fix, and one for the future. I will post immediately that things are returned to normal.

New Gannet Functionality: Siemens Water reference

Following up from a user request and bringing it into line with the other vendors, Siemens data can now be analysed with a water reference (in addition to the Creatine reference previously used).  The syntax for this is:

MRS_struct  = GannetLoad({'OFF.rda' 'ON.rda'},{'water.rda'});
MRS_struct=GannetFit(MRS_struct);

The new code version can be downloaded from the link above left.

80 ms > 68 ms

With a strong sense of the robustness and reproducibility of GABA-edited MRS, we need a new experiment like a hole in the head. But the main limitation of standard 68-ms-TE acquisitions (and the main barrier to clear and precise interpretation of results) is the co-editing of macromolecular signal.  It is also an easy (and fair) complaint of reviewers that observed effects may be driven by the MM signal. So maybe there is room for improvement.

There are two ways to address MM: acquire a metabolite-nulled scan (as done in the original Rothman and Mescher papers); or use Henry's symmetric editing scheme.  Metabolite nulling has two main issues, adding noise to the GABA signal and invovling the subtraction of two scans that cannot be acquired in an interleaved fashion. The elegant symmetric editing scheme is not widely applied at 3T because of constraints on the length,  and therefore selectivity, of editing pulses that can be shoe-horned into a 68 ms TE. 

The slice-selective PRESS scan on which MEGA-PRESS is based typically has a minimum TE of 30-35 ms, due to limited peak B1 (~ 14 uT), the need for shaped RF pulses with 'rectangular' spatial profile and the inclusion of gradient pulses. Based on such a sequence, it is typical to use editing pulses of duration 14 ms for GABA editing in a TE of 68 ms.  14 ms pulses are insufficiently selective for symmetric editing, and suppression of MM results in suppression of GABA signal as well.

However, simply by increasing the TE to 80 ms (and there is surprisingly little downside to doing so), 20 ms editing pulses can be accommodated which allow symmetric suppression of MM. Bob is, as they say, your mother's brother.  Unfortunately now we need to spend a couple of years establishing the reproducibility and robustness of the 80 ms sequence... harumph.

(For the record, I should say that some Siemens scanners can do PRESS at much shorter TEs, being capable of 20 uT body coil RF.  On these scanners there is more room for longer editing pulses in a 68 ms acquisition and all this is irrelevant.)

All this is explained better, and more fully, in our forthcoming MRM paper.  Watch this space

Simulations

Following an interesting chat at ISMRM, I was put onto NMRSCOPEB - a simulation package within jMRUI.  It is incredibly easy to install and start working with and after a half day of work, I have managed to modify their PRESS sequence to have editing pulses in it and produce the following...

Small steps, but a great new (to me) tool.

NMRSCOPEB outputs data in matlab format and works through simple code files and a great table-based GUI. It also has a bunch of spin-systems already saved (as per Govindaraju et al. for GABA). I am happy to share the sequence files with anyone interested.

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Less Glowing Update
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Following this up, I started trying to do simulations of spatial positions within the voxel (which is needed to get the right simulated spectrum.  There appears to be a bug in how NMRSCOPEB handles spatial information, so I would strongly recommend not using NMRSCOPEB for simulation of spectra for makeing basis sets etc, where spatial information is crucial. As a quick look-see is seems to be OK.