Respiratory oscillations in EPI and SMS-EPI

tl;dr   When using SMS there is a tendency to acquire smaller voxels as well as use shorter TR. There are three mechanisms contributing to the visibility of respiratory motion with SMS-EPI compared to conventional EPI. Firstly, smaller voxels exhibit higher apparent motion sensitivity than larger voxels. What was intra-voxel motion becomes inter-voxel motion, and you see/detect it. Secondly, higher in-plane resolution means greater distortion via the extended EPI readout echo train, and therefore greater sensitivity to changes in B0. Finally, shorter TR tends to enhance the fine structure in motion parameters, often revealing oscillations that were smoothed at longer TR. Hence, it's not the SMS method itself but the voxel dimensions, in-plane EPI parameters and TR that are driving the apparent sensitivity to respiration. Similar respiration sensitivity is obtained with conventional single-shot EPI as for SMS-EPI when spatial and temporal parameters are matched.

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The effects of chest motion on the main magnetic field, B0, are well-known. Even so, I was somewhat surprised when I began receiving reports of likely respiratory oscillations in simultaneous multi-slice (SMS) EPI data acquired across a number of projects, centers and scanner manufacturers. (See Note 1.) Was it simply a case of a new method getting extra attention, revealing an issue that had been present but largely overlooked in regular EPI scans? Or was the SMS scheme exhibiting a new, or exacerbated, problem?

Upper section of Fig. 4 from Power, http://dx.doi.org/10.1016/j.neuroimage.2016.08.009, showing the relationship between apparent head motion (red trace) reported from a realignment algorithm and chest motion (blue trace) recorded by a respiratory belt. See the paper for an explanation of the bottom B&W panel.

Background

To follow the full chronology please begin by reviewing the series of blog posts by Jo Etzel at WashU. Her first post was on 12th August, 2016. Jo was quickly able to demonstrate the close relationship between chest motion measured by a belt and the head movement reported by realignment. (More detailed investigations here.) These findings matched the reports by Power in http://dx.doi.org/10.1016/j.neuroimage.2016.08.009. So far so good. We explored the possibility that the transmitter frequency feedback on her Skyra scanner - a wide body scanner with gradients prone to thermal drift - might be causing the problem, but that theory fell by the wayside when I was able to reproduce the same effects on my Trio, which doesn't have transmitter frequency feedback. What else changes when one uses SMS-EPI instead of single shot EPI? The most obvious concomitant change is TR. Indeed, many people use SMS specifically to obtain a TR well below 2000 ms. Might there be a different spin history effect, perhaps one with a flip angle dependence? Again, quick tests on my Trio suggested that flip angle, hence a short TR, wasn't the root cause. That said, I'll return to the short TR because it does affect the appearance of respiratory perturbations on motion parameters.

Thinking about concomitant parameter changes led us to the next candidate explanation. As with the tendency to use a lower TR for SMS-EPI than for regular EPI, there is also a tendency to drive the in-plane gradients harder. Here's the logical progression. We start with a change in the slice dimension whereby SMS permits, say, 2 mm slice thickness and full brain coverage in a TR below 2000 ms. Next, we are tempted to improve the in-plane resolution in order to get cubic voxels. The only way to get finer resolution in-plane is to make the frequency and phase encoding gradients work harder. The SMS scheme doesn't help (or hinder very much - see Note 2) the in-plane dimension, however, and there's only so much one can drive the gradients before the total gradient area must be increased through longer application times. (If you need a refresher on gradient areas and k-space in EPI, take a look at this post and its predecessors.) Thus, a further consequence of pushing up the in-plane resolution is to increase the echo spacing in the EPI readout echo train. This means we can expect higher distortion in the phase encoding axis. Again, let me emphasize that this isn't the fault of SMS but the way in which we seek to use it: for very high spatial resolution in all three dimensions, when only the slice dimension benefits directly from the SMS scheme.

With all these issues in mind, this week we ran some tests to try to isolate the B0 modulation from other possible mechanisms, especially direct mechanical motion.


Recent tests

We used two forms of head restraint in an attempt to separate real (mechanical) head movements from modulation of B0 via magnetic susceptibility of the chest. In the first set of measurements we used a custom 3D-printed head restraint which I will describe in detail in a later post. We then repeated the measurements using standard foam padding as the head restraint. The custom head holder doesn't totally eliminate head motion, but it's considerably better at restraining the head than foam pads! We used the 32-channel head coil on a Siemens Trio running VB17A. For SMS-EPI we used the MB-EPI sequence (R014) from CMRR.

The subject conducted the same self-paced breathing task for each run. He waited until about 30 seconds into the run (so that all single band reference images had been acquired and a T1 steady state was established) then inhaled deeply and exhaled immediately, as if sighing. The deep breath-and-sigh was repeated three more times, with gaps of approximately ten seconds in between. The idea was to maximize the chest expansion but without causing too much in the way of physiologic response (via hypercapnia), as one gets with a held breath.

For each type of head restraint we ran SMS-EPI with MB=6 acceleration for axial, sagittal and coronal slices, and then ran product EPI (ep2d_bold sequence) for the same three orientations. Other parameters: voxel dimensions 2mm x 2mm x 2mm, TE = 35-36 ms (coronal slices had slightly different gradient timing to get under the stimulus limit), TR = 1000 ms, flip angle = 30 deg, 66 interleaved slices with no gap for MB=6, 11 contiguous slices with 10% gap for ep2d_bold.

For convenience you may want to download the QuickTime videos (126 MB zip file) embedded below before reading further. (For full raw data, see Note 3.) It can be quite difficult to see subtle effects in YouTube videos, whereas with the QuickTime videos you can zoom and change the looping speed (initially set to 4 fps) easily. Here I show volumes 80-120 of 200-volume data sets, zoomed to give the best view of the pertinent features. In axial slices, for instance, motion is most easily visualized in superior slices, where small movements in the slice dimension produce large changes in the amount of brain tissue present. In a future post I hope to present the full motion traces for the tests, but for now I'm afraid you'll have to make do with these.

With only foam padding we can easily detect a lot of through-plane motion as well as some in-plane motion in the axial images acquired using MB=6:

This is the sort of motion that might be seen in some of the real data sets that have been reported. Now, noting again how difficult it is to see small effects in YouTube videos, contrast the above with what happens when the subject's head is held securely by a custom restraint:

There is now very little translation visible in-plane, while the through-plane motion has also been reduced considerably. There is some residual through-plane motion, however, suggesting that either the head case is unable to reduce head-to-foot (magnet Z axis) movements as well as it does X or Y axis movements, and/or the chest movement is perturbing the magnetic field along Z and producing apparent movement effects via B0 modulation. I'll come back to this distinction below.

Next, we would like know if what is observed for MB=6 is reproducible with conventional EPI. If so, it's unlikely that the problems reported for real data are due to the SMS scheme itself. Here is the product ep2d sequence with foam padding head restraint:

The in-plane and through-plane motions are very similar to those seen in the previous MB=6 data for foam head restraint. Similarly, using the custom restraint does a good job of prohibiting in-plane (X, Y axis) head movements but does leave small through-plane (Z axis) motion, just as was seen for the MB=6 data with custom head restraint:

At this point, then, there is good evidence that the SMS scheme is not responsible for a majority of respiratory motion sensitivity. The respiratory oscillations being reported are more likely due to some other feature(s) of the acquisition.

To get a better understanding of the motion sensitivity it's useful to separate the main field direction and the slice dimension. A sagittal acquisition has the twin benefits of slicing in what is usually the least motion-contaminated direction - the subject's left-to-right (magnet X) axis - as well as preserving the phase encoding direction anterior-posterior (A-P), as for the previous axial slices. We may thus assume that sensitivity to motion, or off-resonance effects, will be similar in the A-P direction (magnet Y axis) for axial and sagittal slices, but the slice dimensions will have different motion sensitivities.

Let's go in the same order as before, starting with foam padding and MB=6 acquisition:

The through-plane motion that dominated axial slices has now largely vanished. There are two types of motion to distinguish here: translations in-plane, and changes in the amount of distortion. Motion effects on distortion are apparent as occasional stretches in the A-P (phase encoding) direction, as well as shearing in the cerebellum and spinal cord. When a custom head restraint is used to secure the head we see a big reduction in the translations in-plane, but the stretches and shearing in the A-P direction remain:

This pattern of apparent movement is consistent with modulation of the on-resonance frequency, i.e. by the expected magnetic susceptibility effects of chest motion. Changing the resonance frequency is equivalent to a phase shift in the phase encoding direction, and phase shifts produce translations in the phase encoding direction. Degradation of the shim also increases the amount of distortion, producing stretches and the appearance of shearing that is most easily discerned where the magnetic field homogeneity is already lowest, i.e. the inferior portions of the brain and the upper spinal cord.

As before, the next task is to verify that the effects seen for MB=6 are reproduced in conventional EPI, and they are. Here are the foam restraint images for sagittal slices acquired with the conventional ep2d sequence:

Using the custom head restraint again largely eliminates the head-to-foot translations while the stretches and shearing in the A-P direction remain:

Le's take a moment to reconsider the translations in the head-to-foot axis, which is the magnet Z axis. As I mentioned above, when using axial slices one cannot distinguish real movement in Z from modulation of the magnetic field along Z. The sagittal acquisitions - whether MB=6 or ep2d - reveal that the custom head restraint does a pretty good job of ameliorating real motion along Z. But there was still a rather pronounced "apparent motion" in the axial slices when using the same head restraint. Thus, it seems more likely that the residual through-plane motion effects in the axial data were due to magnetic susceptibility modulation of B0 than direct, mechanical movement. We can't be entirely sure - these data don't permit a categorical distinction of the two effects - but this explanation fits the data so far.

Shifting to a coronal prescription may provide more evidence for true mechanical motion effects in the head-to-foot direction when using a custom head restraint, if such movement exists. In the default setting provided by Siemens, the H-F axis will be the frequency encode dimension while L-R will be the phase encoding dimension. (See the post on stimulus limits for an explanation of the default gradient directions used by Siemens.) Modulation of B0 will produce only very tiny shifts in the frequency-encoded direction; the phase encoding dimension is the one most sensitive to resonance frequency shifts. So we can also predict that chest motion will produce stretches and shearing in the L-R direction in coronal EPI.

With simple foam padding there is a large amount of translation visible, here mostly in the H-F axis, that suggests direct mechanical motion is dominating the instability of MB=6 coronal images:

By using the custom head restraint we can eliminate the H-F translation to reveal more clearly the shearing effects that are most easily identified in the cerebellum, where the magnetic field homogeneity is low:

As for the sagittal data, then, holding the head securely leaves residual "apparent motion." Magnetic susceptibility effects dominate to produce distortions and shearing from modulation of B0 by chest movement.

All that remains is to verify the same behavior for conventional EPI as for SMS-accelerated EPI. Here are the product ep2d coronal images with only foam padding:

Plenty of translation as well as shearing on offer! But the custom head restraint eliminates the former to leave the latter:

We again have consistent behavior between SMS-EPI and conventional EPI. The head restraint system is the primary determinant of the motion effects seen in the time series. Residual or "apparent motion" effects left over in images acquired with good head restraint can be explained by the well-known properties of EPI. That is, by the sensitivity of the phase encoding axis (mainly) to off-resonance effects.


Summary

The first conclusion is trivial: good head restraint matters! We have always known this, but the ability of movement to dominate an EPI time series becomes more obvious the higher the resolution we try to use. Again, a moment's thought tells us this is also a trivial point. An image with voxels 1 cm on a side is already so lacking in detail that a few mm movement in any direction is unlikely to be easily detected by eye. Or, we might invert this thought and state that sub-voxel motion is hard to detect by inspection. This is an important point for those of you concerned about insidious motion contamination in resting-state fMRI in particular. Just because your motion parameters from realignment are "good" does not imply that your data are uncontaminated by motion!

But I'm getting ahead of myself. Here we are specifically concerned with SMS and any potential for greater motion sensitivity than for regular EPI. And my conclusion is that to a first approximation the motion sensitivity of SMS-EPI is not radically different to regular EPI, for matched spatial and temporal parameters.

Why, then, did people suddenly become concerned about motion in SMS-EPI? I think it's to do with the tendency to match the in-plane resolution to the slice thickness. In other words, it's the way SMS-EPI is being used rather than a problem with the SMS scheme per se. It is rare for someone to do 2 mm isotropic voxels with conventional EPI, but high spatial resolution is common once one gets a hold of an SMS sequence. Smaller voxels exhibit higher apparent motion sensitivity than larger voxels. What was intra-voxel motion becomes inter-voxel motion, and you see/detect it. Furthermore, higher in-plane resolution means greater distortion - shorter echo spacing in the EPI readout echo train - and concomitant greater sensitivity to changes in B0.

Higher spatial resolution is usually coupled with a tendency to use faster sampling (TR < 2000 ms) with SMS-EPI, and this also increases the visibility of oscillations at respiratory frequencies. Most respiration is sampled above the Nyquist frequency for TR=2000 ms, but this doesn't mean that respiratory oscillations can be readily identified in the motion parameters generated by realignment. Put another way, respiratory modulation is certainly present in your conventional EPI sampled at TR=2000 ms, whether or not you can identify it by inspection! Furthermore, the tests here with a custom head restraint indicate that you can't eliminate chest motion effects no matter what you do. They are "baked in" to your data. This is a big subject for another day.

What about additional motion sensitivity in the SMS scheme? The tests here suggest that a large fraction of the motion sensitivity in SMS is very similar to that for conventional EPI, which is not to say that SMS doesn't have additional sensitivities we should try to understand. For example, there is a possible mismatch between the single band reference data acquired at the start of the run and the accelerated time series data. For small motions - a few mm - the mismatch may not matter too much, since the spatial heterogeneity in the RF coil's receive field tends to vary quite slowly over short distances. This is something that needs to be investigated on its own. Likewise, the particular SMS reconstruction method, which may vary with the (vendor-specific) implementation and perhaps with options therein (see, for example, the Leak Block option in the CMRR sequence and literature on split-slice GRAPPA) may produce subtle motion effects in the data, some of which may be projected well beyond a slice and its neighbors.

There may be additional motion sensitivities that SMS might introduce as a further consequence of the way its used, rather than as an intrinsic property of SMS methodology. I'm thinking specifically of a potential T2 dependence, in addition to the well-known T1-dependent spin history mechanism, that may arise in species with long T2 (CSF is the prime concern) whenever the TR approaches the T2 of some signal component. This "steady state free precession" (SSFP) effect was demonstrated for serial single-shot EPI whenever coherent magnetization managed to survive the readout echo train and persists into the subsequent slice acquisition. (It is a consequence of insufficient crusher gradients at the end of a slice acquisition.) Some degree of robustness to SSFP effects may be provided by using a flip angle well below the Ernst angle. But optimal flip angle, and the possibility of SSFP effects, are both subjects for a later date. I will try to run some tests and make more detailed recommendations on flip angle selection for SMS-EPI (that is, for short TR fMRI) in the near future.

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Notes:

1.  The initial report came from Jo Etzel at WashU. She emailed me the same day that I happened to be reading Jonathan Power's latest preprint: http://dx.doi.org/10.1016/j.neuroimage.2016.08.009. In that paper, Power mentions that he observed relationships between apparent head motion, as reported by realignment parameters, and chest movement detected with a belt in several sets of SMS-EPI data he inspected. Annika Linke at SDSU then reported seeing similar oscillations in SMS data acquired on a GE Discovery MR750 scanner, indicating a problem independent of the scanner manufacturer. I subsequently received reports from sites with different Siemens platforms, including Prisma, Verio and Skyra. Thanks to all who offered data and experiences!

2.  As explained in my intro to SMS post, there is generally a need to use a longer excitation RF pulse width for SMS than for regular EPI, mostly because one is trying to define thinner slices. So the minimum TE tends to be a tad longer for SMS-EPI than regular EPI. This difference essentially disappears if one tries to define the same thin slices for regular EPI, except that this is rarely done in practice because the total brain coverage is so small.

3.  Each run comprised 200 volumes; the videos show only volumes 80-120. Data with the printed head restraint were acquired first, then the foam restraint was used. 1.4 GB zip file: https://dl.dropboxusercontent.com/u/26987499/patient.zip