Finally, here is the third part of a three-part series of posts that have sought to determine a general protocol for resting state fMRI (rs-fMRI). In the first post I reviewed a paper by van Dijk et al. that showed that spatial and temporal resolution didn't make a huge difference to the way resting state networks could be detected using current methods (i.e. seed cross correlation or ICA).
In the second post I presented the results of some simple tests that aimed to determine what sort of spatial coverage could be attained with parameters in accordance with the conclusions of the van Dijk paper. Temporal SNR (TSNR) was used as a simple proxy for data quality. It was found that TSNR for 3.5 mm in-plane resolution was fairly consistent across a range of axial and axial-oblique slice orientations, as well as for sagittal slices.
One question remained, however: given the tolerance to a longish TR (compared to event-related fMRI) for detecting resting networks, would it be beneficial to acquire many thinner slices in a longer TR, or fewer thicker slices in a shorter TR? Following van Dijk et al. we wouldn't expect any huge penalty from extending the TR a bit, but there might be a gain of signal in regions suffering extensive dropout which would suggest that thinner slices might be useful.
The final experiment
Which brings us to today's post. The final comparison is between as many slices as we can get in a TR of 2500 ms, versus as many thinner slices as we can get in a TR of 3000 ms. Obviously, if one is going to increase the TR by a factor of 1.2 it follows that the slice thickness can be reduced by a similar factor to produce the same 3D volume coverage, ignoring a small discrepancy in inter-slice gap. Thus, the specific comparison was between:
(a) TR=2500 ms, slice thickness = 3 mm, gap = 0.3 mm, 43 interleaved slices, number of volumes = 144.
(b) TR=3000 ms, slice thickness = 2.5 mm, gap = 0.25 mm, 52 interleaved slices, number of volumes = 120.
The overall acquisition duration was 6 minutes for each test. Other acquisition parameters were:
Siemens 3 T Trio/TIM running VB15, 12-channel HEAD MATRIX coil, ep2d_bold pulse sequence, matrix=64x64, FOV=224x224 mm, TE=25 ms, bandwidth=2056 Hz/pixel, echo spacing=0.55 ms, fatsat=ON, MoCo=ON, no spatial filters.
A single slice orientation was tested: an axial-oblique prescription tilted approximately 15 degrees towards coronal, for efficient brain coverage. The flip angle was left at 78 degrees for the two experiments even though the TR was altered. (Indeed, the chances are a 90 degree flip angle could have been used for both TRs, so the 78 degree flip was considered to be valid for a direct comparison.) The subject - me again - lay in the magnet staring at the blue stripe on the magnet bore and tried (valiantly) not to fall asleep. (Is it too late to patent MRI scanners as a cure for insomnia...?)
TSNR images were produced for each image series (raw and rigid body motion-corrected), and regions of interest were compared. Interestingly, the 3 mm slices produced TSNR only 6% higher than the 2.5 mm slices. Neglecting physiologic noise and all that good stuff for a moment, based on voxel volume alone one would expect 20% higher (static) image SNR. And with an additional 24 frames (144 vs 120) a further 9.5% benefit to (static) image SNR should arise. The near 30% gain in (static) SNR didn't translate into such large gains in TSNR.
Though no attempt was made to quantify the reduced dropout, there didn't appear to be any significant effect of the thinner slices in the temporal and frontal lobes. Importantly there were no obvious artifacts in either series; the thinner slices didn't introduce any negative consequences visible on the TSNR images. Indeed, the general features of the 2.5 and 3 mm slice TSNR were remarkably consistent, although the edges of the brain in the thinner slices were marginally 'sharper' than for the 3 mm slices.
Conclusions and recommendations
Using 20% thinner slices, a proportionally longer TR and a fixed scan duration of 6 minutes produced only a 6% hit to TSNR, yet with a small (unquantified) improvement in the signal at the edges of the brain and possibly a minor benefit to high susceptibility regions.
So what does all this mean to you? In a nutshell, most of these parameters are a wash. Using a TR between 2500 and 3000 ms to cover the entire brain as efficiently as possible (i.e. thinnest slices, largest matrix in the time allotted) seems to be quite robust to small changes in any spatial parameter as measured by TSNR.
What, then, should we consider to be "standard," if anything? Assuming processing methods such as seeded cross correlations or ICA, and the aim to characterize what are presently considered to be the "typical" resting networks (DMN, etc.), then the following rough parameters appear to be suitable:
- TR in the range 2500-3000 ms.
- FOV in the range 192-224 mm.
- TE in the range 23-30 ms.
- Axial oblique slices in the range 10-30 degrees towards the coronal plane (though sagittal could be a viable option if brain stem is of interest).
It all looks quite generic, doesn't it? And I suppose that's the point. If there is no major advantage from a TR of 2500 ms versus 3000 ms, or an in-plane resolution of 3 mm versus 2.5 mm, then we might as well pick a set of numbers and stick with them. That way, if lots of people are using the same set of numbers it might make for easier comparisons between studies as well as opportunities for meta-analysis of pooled data. (Hey, we can all dream!)
Note, of course, that the tests presented in this series of posts are disposable: I was simply looking for show-stopping parameters, not an exhaustive hunt for the perfect protocol. But it does seem that there is robustness to the actual parameter set. Thus, making small changes to the above parameters is not expected to have large consequences (positive or negative).
Going out on a limb
Here goes nothing. I'm going to pick a set of numbers and await your opinions. I'm going with the small benefit to TSNR of the 3 mm slices, and the possibility that respiration effects might just be properly sampled (Nyquist criterion) with a TR of 2500 ms. And although I'm going to recommend an axial-oblique slice prescription for easy coverage of the entire cortex and cerebellum, I'd be interested to see what people get with sagittal slices. Thus, the final list of parameters:
TR=2500 ms, TE=25 ms, FOV=224x224 mm, matrix=64x64, forty-three 3 mm axial-oblique slices (10% gap) aligned approx 15 degrees towards coronal, flip angle=90 deg, 144 volumes (for a 6 minute run).
Physiological monitoring - heart rate and respiration - are also strongly advised, athough the benefit of these measures is still under debate. The way I see it, if you acquire the physio data you will have reserved the option to use them should a subsequent study find significant benefits. If you don't, well, you can figure out what you can't do!
Want the data from this post?
You can download a zip file containing all the raw DICOM images as well as DICOM versions of the mean, stdev and TSNR images here:
If you don’t already have a DICOM viewer, check out Osirix for Mac OSX (available via a link in the side bar). ImageJ from NIH also has some nice features for ROI analysis. I’ll post introductions to using these two programs in future posts.