Single slice EPI to visualize brain pulsations

 

We talk a lot about head motion in fMRI. As much as head motion can be limiting, it’s also important to remember that there is real brain motion, too, distinct from whatever the head might be doing. And whereas printed head cases or bite bars might reduce head motion to a large extent, the real brain motion occurs inside the skull in a way that is inaccessible to anything we can do during data collection. (In principle, one could gate acquisitions to the cardiac cycle, but this would invoke its own set of complications.) Instead, we are forced to deal with real brain motion as best we can during post-processing. The problem here is that our image processing tools usually work at the voxel level, leaving any sub-voxel motion unaddressed. 

A few years ago I was involved with a project to assess vibrations measurable on the skull. To relate what could be measured outside with what was happening inside the head, we used a single slice EPI sequence collected at a TR of 40 ms; a frame rate of 25 images per second. At this speed, all the dynamics produced by the arterial blood pressure wave - the mechanical force which propels the blood from the aorta - are visible in quite spectacular fashion right across the brain. Here are a couple of example scans:

 

 

Apart from the very obvious fluctuations in the lateral ventricles, note how the CSF in sulci also fluctuates with each heart beat. If you look very closely you’ll be able to see the brain tissue deforming, too. Several vessels, mostly veins, are visible. Pulsation in the superior sagittal sinus is especially prominent in the sagittal scan. In the transverse scan there are also large changes in the overall image intensity every few heart beats, and this is almost certainly due to breathing (which we didn't track).

Note that this type of contrast isn’t replicated precisely in your fMRI scans. Use of a single slice with a relatively high excitation flip angle (30 degrees) relative to the short TR (40 ms) means that we have considerable within slice and inflow T1 weighting, in addition to the T2* changes you’re used to thinking about for BOLD. But some scaled down version of these apparent T1 changes are in your fMRI data, especially if you’re not in the habit of using a small flip angle. (See this post and Gonzales-Castillo et al. (2013) for more information on setting the flip angle to minimize motion effects via image contrast.)

Perhaps more importantly, think about what’s happening at the tissue level. Even if we somehow magic away all the CSF and large vessel fluctuations, we’re still left with considerable non-linear movement of the brain tissue itself. This motion is greatest at the base of the brain, but displacement and shearing of many cortical areas can be seen in the above cine loops with the naked eye. Maybe ponder real brain motion the next time you click the button to apply a motion-correction or physiological noise reduction step in your processing pipeline. How well do you think your “motion correction” steps are tackling these low-level perturbations? Don’t forget they’re also working simultaneously on the (usually larger) displacements and rotations from real head motion and pseudo-motion produced by respiration (i.e. chest movements perturbing the magnetic field across the head). 

PS If you want to see more dynamic images of brain motion, check out the motion-amplified scans developed by Samantha Holdsworth's group: 2D, 3D, quantitative 3D. Not fMRI but still powerful reminders that the entire brain is moving almost all the time.

Can we separate real and apparent motion in QC of fMRI data?

 

A few years ago, Jo Etzel and I got into a brief but useful investigation of the effects of apparent head motion in fMRI data collected with SMS-EPI. The shorter TR (and smaller voxels) afforded by SMS-EPI generated a spiky appearance in the six motion parameters (three translations, three rotations) produced by a rigid body realignment algorithm for motion correction, such as MCFLIRT in FSL. The apparent head motion is caused by magnetic susceptibility variations of the subject's chest as he/she breathes, leading to a change in the magnetic field across the head which, in turn, adds a varying phase to the phase-encoded axis of the EPI. This varying phase then manifests as a translation in the phase-encoded axis. It's not a real motion, it's pseudo-motion, but unfortunately it is a real image translation that adds to any real head motion. I should emphasize here that this additive apparent head motion arises in conventional multi-slice EPI, too, but it's generally only when the TR gets short, as is often the case with SMS-EPI, that the apparent head motion can be visualized easily (as a spiky, relatively high frequency fluctuation in the six motion parameter traces). In EPI sampled at a conventional TR of 2-3 sec, there are only a small handful of data points (volumes) per breath for an average breathing rate of 12-16 breaths/minute and this leads to aliasing of most of the apparent head motion frequency. It may still be possible to see the spiky respiration frequency riding on the six motion parameters, but it's not always there as it is for TR much less than 2 seconds.

Once we'd satisfied ourselves we'd understood the problem fully, I confess I let the matter drop. After all, we have tools like MCFLIRT that try to apply a correction to all sources of head motion simultaneously, whether real or apparent. But now I'm wondering if we might be able to evaluate the real and apparent motion contributions separately, with a view to devising improved QC measures that can emphasize real head motion over the apparent head motion when it comes to making decisions on things like data scrubbing. Jo has been dealing with the appropriate framewise displacement (FD) threshold to use when including or excluding individual volumes. (See also this paper.)

Let's review one of the motion traces from my second 2016 blog post on this issue:

These traces come from axial SMS-EPI with SMS factor (aka MB factor ) of 6. The x axes are in seconds, corresponding to TR = 1 sec. (The phase-encoded axis is anterior-posterior, which is the magnet Y direction.) On the left is a subject restrained with only foam, on the right the same subject's head is restrained with a printed head case. During each run the subject was asked to take a deep breath and sigh on exhale every 30 seconds or so. We clearly see the deep breath-then-sigh episodes in both traces, regardless of the type of head restraint used. Yet it is also clear the apparent head motion, which is the high frequency ripple, dominates the Y, Z and roll traces on the left plot. On the right plot, the dominant effect of apparent head motion manifests in the Y trace, with a much reduced effect in the roll axis. Already we are seeing a slight distinction between the translations and rotations for apparent head motion. It looks like apparent head motion contributes more to translations than rotations, which makes sense given the physical origin of the problem. In which case, can we assume that by extension real head motion will dominate the rotations?

For now, let's assume that the deep breath-then-exhale episodes are producing considerable real head motion, in addition to the large apparent head motion spike from exaggerated chest movement. The left plot above shows that pitch, yaw and roll all characterize the six deep breaths readily. They are also visible in Z and X, but with considerably reduced magnitude. There's no clear effect in the Y trace which is dominated by the aforementioned apparent head motion. So far so good! When the head can actually move in the foam restraint, we have clear biases towards rotations for real head motion and translations for apparent head motion. 

What about the right plots? Real head motion is far harder to achieve because of the printed head case restraint. But we assume the apparent head motion is basically the same magnitude because it's chest motion, not head motion. So we might think of this condition as being a low (or lowest) real motion condition. As with the foam restraint on the left, we again see Y translations dominated by apparent head motion. The roll axis also displays considerable apparent head motion. And as for the foam restraint, the roll and pitch axes display something that may be real or apparent head motion for each of the deep breath-then-exhale periods. We can't be sure if the head (or the entire head case, or even the entire RF coil!) was really moving during each breath, but let's assume it was. If so, then for good mechanical head restraint we have the same rough biases as for foam restraint in our motion traces: real motion dominates rotations, apparent motion manifests mostly as translations.

Jo sees a similar distinction between real and apparent head motion in the motion parameter plots of her 2023 blog post. In her top plot, which she suggests is a low real motion condition, the apparent motion dominates Y and Z translations and the roll traces, exactly as my example above. Her second plot exhibits considerable real head motion. The apparent head motion is still visible as ripples on the Y and Z translation traces, but now it's clear the biggest changes arise in the three rotations and these changes are probably real head motion. Again, we have real motion dominating rotations while apparent motion manifests more in the translations.

Finally, let's consider Frew et al., who looked at head motion in pediatrics. Here's Figure 3 from their paper:

Using framewise displacement (FD), they show a transition from FD dominated by translations to FD dominated by rotations when considering low, medium and high (real) head motion subjects. Rotations and translations are both affected significantly in the medium movement group. Still, the trend here suggests that we might consider rotations alone as an index of real head motion if, as suggested above, apparent head motion contributes mostly to translations.

So, what might we do to separately evaluate real and apparent head motion? This is where you come in. I only have one starting idea, and that's to shift to considering FD using only rotations, rather than rotations and translations, when setting thresholds for the purposes of QC and scrubbing. Based on what I've presented here, we might be able to set a threshold for FD(rotations only) that will capture most of the real head motion and have a much reduced dependency on apparent head motion. This measure could help avoid mischaracterizing large apparent head motions as events to reject when they are inherently fixable with MCFLIRT and similar. (Real head motion produces a big spin history effect and likely introduces non-linear distortions in the images.) Whether the reverse is true - that is, whether FD(translations only) captures most of the apparent head motion and a reduced contribution from real head motion - I leave as an exercise for another day, but my suspicion is that it is not. Put another way, I think the focus should be on using the rotations to capture and evaluate real head motion. Pooling translations and rotations in measures like FD may be complicating the picture for us.

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Restraining the 32-channel coil

There has been a move towards custom head restraint in recent years. These devices are tailored to fit the subject in such a way that any movement of the head can be transmitted to the coil. It is therefore imperative to make sure that the RF coil is also well restrained.

On Siemens Trio and Prisma scanners, the 32-channel head coil is a special case. It was designed independent of the standard head coils. Restraint on the bed is thus a bit of an afterthought. Sticky pads on the base of the coil are designed to prevent movement through friction, but there are gaps on all four sides and no specific mechanism - slots, grooves, etc. - to lock the coil into a particular position. On my Trio, I was in the habit of putting the 32-channel coil all the way back to the frame of the bed, assuming that the most likely direction of motion from a subject would be backwards. Problem solved, right? No. By putting the coil all the way back, when using custom head restraint I actually put stress on the front two coil cables and this led to intermittent receive RF artifacts. A more refined fix was necessary.

My engineer built a simple frame (see photos below) that fits snugly into the rear portion of the bed frame and forces the coil onto protrusions that hold the standard (12-channel) coils properly. It also shims out the left and right gaps so there is no chance of side to side motion, either. With this device in place, the coil can only go one way: up. 

There has been some debate in the literature about the utility of custom head restraint for motion mitigation, with one group finding benefits while another found it made things worse. I note that both groups were using 32-channel coils on a Prisma, so proper head coil restraint may be a reason for different outcomes. I am now working on a fix for Prisma scanners and will do a separate post on the solution once it's been tested. (ETA April-May.) Until then, if you use a 32-channel coil on any Siemens scanner, my advice is to use additional restraint and make sure your coil is in a reliable, stable position. 

 

The coil restraint shim is put into position before the 32-channel coil.

Coil restraint shim in position.

Fluctuations and biases in fMRI data

In my last post I summarized the main routes by which different forms of actual or apparent motion can influence fMRI data. In the next few posts, I want to dig a little deeper into non-neural causes of variation in fMRI data. I am particularly interested in capturing information on the state of the subject at the time of the fMRI experiment. What else can be measured, and why might we consider measuring it? Brains don't float in free space. They have these clever life support systems called bodies. While most neuroimagers reluctantly accept that these body things are useful for providing glucose and oxygen to the brain via the blood, bodies can also produce misleading signatures in fMRI data. My objective in this series of posts is to investigate the main mechanisms giving rise to fluctuations and biases in fMRI data, then consider ways other independent measurements might inform the fMRI results.

Many causes, much complexity

There are three broad categories of fluctuations or biases imprinted in the fMRI data. I've tried to depict them in Figure 1. At top-right, in a cartoon red blood vessel, is the cascade of physiological events leading to BOLD contrast. Next, on the left, there are perturbations arising from the subject's body. Some of these are direct effects, like head motion, and some are propagated via modulation of the same physiological parameters that give rise to BOLD. Breathing is a good example of the latter. A change in breathing depth or frequency can change the arterial concentration of CO2, leading to non-neural BOLD changes. Furthermore, the breathing rate is intricately tied to the heart rate, via the vagus nerve, and so we can also expect altered brain pulsation. In the final category, depicted in my figure as scanner-based mechanisms at the bottom, we have experimental imperfections. In the last group are things that could be reduced or eliminated in principle, such as thermal drift in the gradients, wobbly patient beds, and resonance frequency shifts across the head arising from changing magnetic susceptibility of the chest during breathing. The thin blue lines connecting the different parts of the figure are supposed to show the main influences, with arrowheads to illustrate the directionality.

(Click image to enlarge.)

Figure 1. Major routes of modulation in time series data in an fMRI experiment. The flow chart in the depiction of a blood vessel, in red, is based on a figure from Krainik et al. 2013 and shows the main events leading to BOLD via neurovascular coupling. Main body-based mechanisms originate on the left, and scanner-based experimental imperfections are depicted on the bottom. All mechanisms ultimately feed into the fMRI data, depicted at center. Yellow boxes contain some of the main modulators of mechanisms that can produce either fluctuations or systematic biases in fMRI data.

Abbreviations: ANS - autonomic nervous system, HR - heart rate, CBVa - arterial cerebral blood volume, CBVv - venous cerebral blood volume, CMRO2 - cerebral metabolic rate of oxygen utilization, CBF - cerebral blood flow, OEF - oxygen extraction fraction, deoxyHb - deoxyhemoglobin, AR - autoregulation, pO2 - partial pressure of oxygen (O2 tension), pCO2 - partial pressure of carbon dioxide (CO2 tension).

As if that wasn't already a lot of complexity, I'm afraid there's more. In the yellow boxes of Figure 1 are some of the main modulators of the underlying mechanisms responsible for perturbing fMRI data. These modulators are usually considered to be confounds to the main experimental objective. I posted a list of them a few years ago. Caffeine is probably the best known. It modulates both the arterial cerebral blood volume (CBVa) as well as the heart rate (HR). We already saw that HR and breathing are coupled, so this produces a third possible mechanism for caffeine to affect fMRI data. There's also an obvious missing mechanism: its neural effects. Some direct neural modulators are summarized in Figure 2, placed in their own figure simply to make this a tractable project. I'll be going back to reconsider any direct neural effects at the end of the series, to make sure I've not skipped anything useful, but my main emphasis is the contents of Figure 1.

Figure 2. Potential modulators of neural activity during an fMRI experiment.

Measuring the modulators

There are about a dozen mechanisms leading to fluctuations in fMRI data. Note that some paths depicted in Figure 1 may contain multiple discrete mechanisms. The figure would be far too cluttered if every mechanism was depicted. Take head motion. It could be foam compressing through no fault of the subject, or it could be the subject fidgeting, or apparent head motion arising from the sensitivity of the EPI acquisition to off-resonance effects (for which there are at least two main contributions: thermal drift in the scanner and chest motion in the subject). I tried to estimate how many combinations are represented in Figure 1 but quickly gave up. It's several dozen. I'm not sure that knowing the number helps us. Clearly, it's an omelette.

So, what can we do about it? Well, there are only so many things one can measure before, during or after an MRI scan, so we should probably start there. In the first set of posts in this series I'll look at non-MRI measures that can be performed during fMRI data acquisition, to track moment to moment changes in some of the parameters of Figure 1. These will include:

• Heart rate
• Blood pressure
• Vascular low frequency oscillations in the periphery
• Respiration rate
• Expired CO2
• Electrodermal activity
• Eye tracking
• Head motion

Then, in the next set of posts I'll shift to assessing ancillary MRI measurements that can inform an fMRI experiment, such as:

• Anatomical scans
• Baseline CBF
• Blood oxygenation
• Cerebrovascular reactivity
• Calibrated fMRI (which is actually a slightly different way of doing the fMRI experiment, but requires some ancillary steps)

Finally, I'll consider informative, non-MRI data you could capture from questionnaires or relatively simple non-invasive testing. With better understanding, I am hoping that more researchers begin to consider physiology as earnestly as they do the domains involving psychology and statistics.

Major sources of apparent head motion in fMRI data

As I mentioned yesterday, there is a tendency when reviewing the output of a volume registration ("motion correction") algorithm to attribute all variations to real head motion. But, as was demonstrated last October, the magnetic susceptibility of the chest during breathing produces shifts in the magnetic field that vary spatially across the head, producing translations and shearing in EPI data that the volume registration algorithm can't distinguish from real head motion. Here I want to quickly review other major mechanisms by which we can get apparent head motion.

Let's start with contributions to real head motion. These include slow compression of foam designed to restrain the head, relaxation or tension of neck muscles, swallowing, fidgeting and the like. Printed head cases, bite bars and other restraint systems are of use here. Then there are body motions, including the extremities, that produce movement of the head via the neck. This is why you should instruct your subjects not to move at all during the scan. Telling a subject he shouldn't move his head is tantamount to saying that moving his feet is okay, and it's not. Subjects should move, e.g. to scratch or stretch, only when the scanner is silent.

Also included in the mechanical motion category is respiratory chest motion that couples unavoidably to the head because of that pesky neck thing. Pulsations of the brain with the cardiac cycle are another source of unavoidable direct motion in the organ of interest. The latter is real brain motion, of course.

Next, body motions (including from respiration) can produce head movement in the magnetic field via instability of the patient bed. Back in the early 2000s we had a Varian 4 T scanner. We had to construct rollers to catch and support the bed sled in the magnet bore because we had a cantilevered bed that deflected like a springboard otherwise. Every tiny movement of the subject caused the bed sled to bounce. For stability we want a strongly coupled system - subject to bed, bed to gradients/magnet - and we need to avoid any relative movement between them. I was reminded of this mechanism again recently. It's something to keep in mind as we work on respiratory instabilities because I note that my Trio has a bed cantilevered on the magnet face whereas Prisma scanners have a bed supported on the floor in front of the magnet. The latter should be a lot more stable, provided the bed has a solid foundation underneath it.

So far all the mechanisms I've considered have had a direct mechanical connection between the source of the motion and the brain. Chest motion can also affect the magnetic field via changing magnetic susceptibility from the air-filled lungs, as previously demonstrated. This is a through-space mechanism. In principle, movement of the extremities or any other part of the body (or other equipment in the bore) might also produce perturbation of the magnetic field across the head via magnetic susceptibility, but my intuition is that this would be a minor contributor to overall instability compared to the effects from the chest.

A well-known motion-like effect arises from thermal drift in the magnet. The gradients get warm with use and over time this causes drift in the magnetic field, e.g. via passive shimming iron that doesn't have the water cooling of the gradient set. Re-shimming can offset some of the effects of this mechanism between runs, but not within a run. When viewed from the perspective of your agnostic volume realignment algorithm, thermal drifts appear a lot like slow (real) head movements, e.g. as foam compresses or neck muscles relax. Re-shimming between runs helps with both, but I'm afraid it doesn't do anything within a run. De-trending is usually used to good effect here.

There are doubtless other sources of instability that can manifest as apparent head motion - anything that causes shifts in the on-resonance frequency during an EPI time series will do it - but here I've covered the main mechanisms of concern. Given robust head restraint to mitigate most of the direct head motion mechanisms (except brain pulsations), it seems that the next largest instabilities to tackle are the respiratory motion mechanisms. We have three to work on: residual direct motion through the neck, magnetic susceptibility of the chest, and the possible deflection of the patient bed.

"Power plots" of respiratory effects in EPI

This will be brief, a simple demonstration of the sort of features visible in a "Power plot" of an EPI time series. The goal is to emphasize that chest motion produces apparent head motion effects in typical analyses. Here the subject's head was held very firmly in the 32ch coil of my Siemens Trio using a custom printed head case. See the posts from October last year for more details. In this test the subject inhaled to near maximum and exhaled immediately, repeating the procedure every 30 seconds or so in a self-paced manner. The subject breathed normally otherwise. Critically, note that no breaths were held.

What we see are two striking features. First, there is banding with a period of approx 30 seconds, and the bright bands correspond with apparent head movement reported as framewise displacement (FD) in the top red trace. (TR is 1700 ms.) Some of this may be real head movement, but a lot arises from chest displacements modulating the magnetic field. This is the feature I want to emphasize. We need to be aware that not all sources of frame-to-frame variation reported by a volume registration (aka motion correction) algorithm are necessarily actual head motion. Last October I showed in a series of simple demonstrations how chest motion produces shearing and translations of EPI signals in a manner consistent with perturbation of magnetic field, rather than head motion per se. It's important for you to distinguish these two phenomena because the volume registration algorithm cannot differentiate them. It does its best to match volumes no matter the source of differences.

The second feature in the plots above I'm not going to get deep into here. It's for another day. But it's pretty hard to miss the dark bands that follow tens of seconds after each bright band. Notice that the dark bands don't tend to coincide with increased FD. That is, the origin of the dark bands isn't actual or apparent head motion but something else. They come from changes in BOLD signal as the arterial CO2 changes. This is the part of the "physiologic noise" that people try to model with things like RETROICOR and RVT, or from end-tidal CO2 measurements. Here, the perturbation in BOLD signal is driven by the strange breathing task, but it's not motion or motion-like. It's real physiology in the brain.

That's all for now! More posts on this stuff in the coming weeks.

Motion traces for the respiratory oscillations in EPI and SMS-EPI

This is a follow-up post to Respiratory oscillations in EPI and SMS-EPI. Thanks to Jo Etzel at WashU, you may view here the apparent head motion reported by the realignment algorithm in SPM12 for the experiments described in the previous post. Each time series is 200 volumes long, TR=1000 ms per volume. The realignment algorithm uses the first volume in each series as the template. The motion is plotted in the laboratory frame, where Z is the magnet bore axis (head-to-foot for a supine subject), X is left-right and Y is anterior-posterior for a supine subject.

In the last post I said that there were five total episodes of a deep breath followed by sigh-like exhale, but actually the subject produced a breath-exhale on average every 30 seconds throughout the runs. (This was a self-paced exercise.) Thus, what you see below (and in the prior post) has a rather large degree of behavioral variability. Still, the main points I made previously are confirmed in the motion traces. I'll begin with the axial scan comparison. Here are the motion parameters for the MB=6 axial acquisition with standard foam head restraint (left) versus the custom printed restraint (right):

MB=6, axial slices. Left: foam restraint. Right: custom 3D printed headcase restraint

The effect of the custom restraint is quite clear. The deep breath-then-sigh episodes are especially apparent when using only foam restraint. Note the rather similar appearance of the high frequency oscillations, particularly apparent in the blue (Y axis) traces between the two restraint systems, suggesting that the origin of these fluctuations is B0 modulation from chest motion rather than direct mechanical motion of the head. We cannot yet be sure of this explanation, however, and I am keeping an open mind just in case there are small movements that the custom head restraint doesn't fix.

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.

i-fMRI: A virtual whiteboard discussion on multi-echo, simultaneous multi-slice EPI

Disclaimer: This isn't an April Fool!

I'd like to use the collective wisdom of the Internet to discuss the pros and cons of a general approach to simultaneous multislice (SMS) EPI that I've been thinking about recently, before anyone wastes time doing any actual programming or data acquisition.

Multi-echo EPI for de-noising fMRI data

There has been quite a lot of interest in using multi-echo EPI to characterize and de-noise time series data, e.g.

http://www.ncbi.nlm.nih.gov/pubmed/22209809

These methods rest on one critical aspect: they use in-plane parallel imaging (GRAPPA or SENSE, usually depending on the scanner vendor) to render the per slice acquisition time reasonable. For example, with R=2 acceleration it's possible to get three echo planar images per slice at TEs of around 15, 40 and 60 ms. The multiple echoes can then be used to characterize BOLD from non-BOLD signal variations, etc.

The immediate problem with this scheme is that the per slice acquisition time is still a lot longer than for normal EPI, meaning less brain coverage. The suggestion has been to use MB/SMS to regain speed in the slice dimension. This results in the combination of MB/SMS in the slice dimension and GRAPPA/SENSE in-plane, thereby complicating the reconstruction, possibly (probably) amplifying artifacts, enhancing motion sensitivity, etc. If we could eliminate the in-plane parallel imaging and do all the acceleration through MB/SMS then that would possibly reduce some of the artifact amplification, might simplify (slightly) the necessary reference data, etc.

A different approach? 

12-channel versus 32-channel head coils for fMRI

At last month's Human Brain Mapping conference in Seattle, a poster by Harvard scientists Stephanie McMains and Ross Mair (poster 3412) showed yet more evidence that the benefits of a 32-channel coil for fMRI at 3 T aren't immediately obvious. Previous work by Kaza, Klose and Lotze in 2011 (doi: 10.1002/jmri.22614) had suggested that the benefits were regional, with cortical areas benefiting from the additional signal-to-noise ratio (SNR) whereas the standard 12-channel coil was superior for fMRI of deeper structures such as thalamus and cerebellum. The latest work by McMains and Mair confirms an earlier report from Li, Wang and Wang (ISMRM 17th Annual Meeting, 2009. Abstract #1614) that showed spatial resolution also affects the benefit, if any. In a nutshell, if a typical voxel resolution of 3 mm is used then the 32-channel coil provides no benefit over a 12-channel coil. The 32-channel coil was best only when resolution was pushed to 2 mm, thereby pushing the SNR down towards the thermal noise limit, or when using high acceleration, e.g. GRAPPA with acceleration, R > 2.

What's going on? In the first instance we need to think about the regimes that limit fMRI at different spatial resolutions. In the absence of subject motion and physiologic noise, the SNR of an EPI voxel will tend towards a thermal noise-limiting regime as it gets smaller. Let's assume a fairly typical SNR of 60 for a voxel that has dimensions 3.5x3.5x3.5 mm^3, as detected by a 12-channel head coil at 3 T. If we shrink the voxel to 3x3x3 mm^3 the SNR will decrease by ~27/43, to about 38, while if we shrink to 2x2x2 mm^3 the SNR will decrease to about 11. (Here I am assuming that all factors affecting N are invariant to resolution while S scales with voxel volume, which is sufficient for this discussion.) If we decrease the voxels to 1.5x1.5x1.5 mm^3 the SNR decreases to below five. The SNR is barely above one if we push all the way to 1x1x1 mm^3 resolution, which is why you don't often see fMRI resolution better than 2 mm at 3 T. Thus, if high spatial resolution is the goal then one needs to boost the SNR well beyond what we started of with to achieve a reasonable image. Hence the move to larger phased-array receive coils.

So that's the situation when the thermal noise is limiting. This is generally the case for anatomical MRI, but does it apply to fMRI? If something else is limiting - either physiologic noise or subject motion - then increasing the raw SNR may not help as expected. In fMRI we are generally less concerned with true (white) thermal noise than we are with erroneous modulation of our signal. It's not noise so much as it is signal changes of no interest. For this reason, Gonzalez-Castillo et al. (doi: 10.1016/j.neuroimage.2010.11.020) recently proposed using a very low flip angle in order to minimize physiologic noise while leaving functional signal changes unchanged.

From ISMRM e-poster 3352, available as a PDF via this link.

What if we can't even attain the physiologic noise-limiting regime? It's quite possible to be in a subject motion-limiting regime, as anyone who has run an fMRI experiment can attest. In that case, the use of a high dimensional array coil (of 32 channels, say) could actually impose a higher motion sensitivity on the time series than it would have had were it detected by a smaller array coil (of 12 channels, say), due to the greater receive field heterogeneity of the 32-channel coil. This was something a colleague and I considered last year, in an arXiv paper (http://arxiv.org/abs/1210.3633) and accompanying blog post. In an e-poster at this year's ISMRM Annual Meeting (abstract #3352; a PDF of the slides is available via this Dropbox link) we simulated the effects of motion on temporal SNR (tSNR), as well as the potential for spurious correlations in resting-state fMRI, when using a 32-channel coil. In doing these simulations we assumed perfect motion correction yet there were still drastic effects, as the above figure illustrates.

Whether the equivocal benefits of a 32-channel coil for routine fMRI (that is, using 3-ish mm voxels) are due to enhanced motion sensitivity, higher physiologic noise or some other factor I'm not in a position to say with any certainty. My colleagues and I, and others, are investigating ways that we might reduce the effects of receive field contrast on motion correction. The use of a prescan normalization is one idea that might help, at least a bit. The process has many assumptions and potential flaws, but it may offer the prospect of getting back some of what might be lost courtesy of the enhanced motion sensitivity. We simply don't know yet. The bigger problem, however, seems to be that a heterogeneous receive field contrast will impart motion sensitivity on a time series even if motion correction were perfect. Strong receive field heterogeneity, of the sort exhibited by a 32-channel head coil, is a killer if the subject moves.

Unless you are attempting to use highly accelerated parallel imaging (in particular the multiband sequences) and/or pushing your voxel size towards 2 mm, then, you're almost certainly better off sticking with the 12-channel coil as far as fMRI performance is concerned. Other scans, in particular anatomical scans and perhaps some diffusion-weighted scans, may benefit from larger array coils (because these scans may be in the thermal noise-limiting regime), but each application will need to be verified independently.

Resting state fMRI confounds

(Thanks to Dave J. Hayes for tweeting the publication of these papers.)

Two new papers provide comprehensive reviews of some of the confounds to the acquisition, processing and interpretation of resting state fMRI data. In the paper, "Resting-state fMRI confounds and cleanup," Murphy, Birn and Bandettini consider in some detail many of the noise sources in rs-fMRI, especially those having a physiologic origin.

In "Overview of potential procedural and participant-related confounds for neuroimaging of the resting state," Duncan and Northoff review the effects that other circumstantial factors, such as the scanner's acoustic noise, subject instructions, subjects' emotional state, and caffeine might have on rs-fMRI studies. Without due consideration, some or all of these factors may inadvertently become experimental variables; the implications for inter-individual differences are considerable. (I've reviewed some of the issues concerning what we can permit subjects to do before and during rs-fMRI in this post.)

While we're on the subject of confounds in rs-fMRI - especially those with a motion component - another confound that motion introduces is a sensitivity to the receive field heterogeneity of the head coil. This problem gets worse the more channels the coil has, because the coil elements get smaller as the number of channels goes up. For an introduction to the issue see this arXiv paper; there will also be simulations of the effect for a 32-channel coil at the ISMRM conference in a couple of weeks' time. (See e-poster, abstract #3352.) The result is that spurious correlations and anti-correlations can result, necessitating some sort of clever sorting or de-noising scheme to distinguish them from "true" brain correlations. I mention it here because there is a common misconception in the field that applying a retrospective motion correction step fixes all motion-related artifacts. It doesn't. Nor does including all of the motion parameters as regressors in a model. Motion has some insidious ways in which it can modulate the MRI signal level, and it is high time that we, as a field, reconsider very carefully what we are doing for motion correction, and why.

Finally, I'll note in passing that slice timing correction may not be a good idea for rs-fMRI. It's been known since the correction was first proposed that it should interact a with a motion correction step. (The two corrections should be applied simultaneously, as one 4D space-time correction rather than a separate 3D space then time correction, or vice versa.) I don't have data to share just yet, but if anyone is wondering whether they should include STC in their rs-fMRI analysis, as they would do for event-related fMRI, then my advice is to skip it until someone can prove to you that it has no unintended consequences. (Demonstration of unintended consequences to follow eventually....)


References:

Resting state fMRI confounds and cleanup. K Murphy, RM Birn and PA Bandettini, NeuroImage Epub.
DOI: 10.1016/j.neuroimage.2013.04.001

Overview of potential procedural and participant-related confounds for neuroimaging of the resting state. NW Duncan and G Northoff, J. Psychiatry Neurosci. 2013, 38(2), 84-96.
PMID: 22964258
DOI: 10.1503/jpn.120059

Review: Using a bias field map to improve motion correction of EPI time series

In a new paper entitled "Effects of image contrast on functional MRI image registration," Gonzalez-Castillo et al. evaluate the performance of motion correction (a.k.a. registration) following a pre-processing step that aims to remove the contrast imparted across images due to receive (and/or transmit) field heterogeneity. A bias field map is estimated from a target EPI, and this reference image is then used to normalize the other images in the time series. There are other aims in the paper, too: specifically, to evaluate the performance of image registration (EPI to EPI, or EPI to MP-RAGE anatomical) when the T1 contrast of time series EPIs is altered via the excitation RF flip angle. But in this post I am going to focus on the normalization part because it involves the RF receive field heterogeneity, and this instrumentally-induced contrast is of particular concern for exacerbating motion sensitivity in fMRI (as explained here).

Although others have compared prescan normalization between different array coils (see the references in this paper), this is the first paper I've seen that compares motion correction performance for EPI time series acquired with an array coil (a 16-channel array) to a single channel birdcage coil. Now, this isn't quite the straightforward comparison I might like - with the receive fields being the only difference - because in this instance the birdcage is also used to transmit the excitation RF pulses, making the transmission (Tx) field for the birdcage experiment more spatially heterogeneous than will be produced from the body RF coil that's used when acquiring with a receive-only array coil. Following? In other words, for the 16-channel array the receive (Rx) field heterogeneity is likely to dominate whereas for the birdcage coil the heterogeneities of both the transmit and receive fields are salient. Still, it's worth a look since the coil comparison highlights the issue of the scanner hardware's influence on EPI contrast, and on subsequent motion correction.

Motion problems in fMRI: Receive field contrast effects

Motion has been identified as a pernicious artifact in resting-state connectivity studies in particular. What part might the scanner hardware play in exacerbating the effects of subject motion?

My colleague over at MathematiCal Neuroimaging has been busy doing simulations of the interaction between the image contrast imposed by the receiver coil (the so-called "head coil") and motion of a sample (the head) inside that coil. The effects are striking. Typical amounts of motion create signal amplitude changes that easily rival the BOLD signal changes, and spurious spatial correlations can be introduced in a time series of simulated data.

The issue of receive field contrast was recognized in a recent review article by Larry Wald:

"Highly parallel array coils and accelerated imaging cause some problems as well as the benefits discussed above. The most problematic issue is the increased sensitivity to motion. Part of the problem arises from the use of reference data or coil sensitivity maps taken at the beginning of the scan. Movement then leads to changing levels of residual aliasing in the time-series. A second issue derives from the spatially varying signal levels present in an array coil image. Even after perfect rigid-body alignment (motion correction), the signal time-course in a given brain structure will be modulated by the motion of that structure through the steep sensitivity gradient. Motion correction (prospective or retrospective) brings brain structures into alignment across the time-series but does not alter their intensity changes incurred from moving through the coil profiles of the fixed-position coils. This effect can be partially removed by regression of the residuals of the motion parameters; a step that has been shown to be very successful in removing nuisance variance in ultra-high field array coil data (Hutton et al., 2011). An improved strategy might be to model and remove the expected nuisance intensity changes using the motion parameters and the coil sensitivity map."

In our recent work we take a first step towards understanding the rank importance of the receive field contrast as it may introduce spurious correlations in fMRI data. It's early days, there are more simulations ongoing, and at this point we don't have much of anything to offer by way of solutions. But, as a first step we are able to show that receive field contrast is ignored at our peril. With luck, improved definition of the problem will lead to clever ways to separate instrumental effects from truly biological ones.

Anyway, if you're doing connectivity analysis or otherwise have an interest in resting-state fMRI in general, take a read of MathematiCal Neuroimaging's latest blog post and then peruse the paper submitted to arXiv, abstract below.

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A Simulation of the Effects of Receive Field Contrast on Motion-Corrected EPI Time Series

D. Sheltraw, B. Inglis

(Submitted on 12 Oct 2012)

The receive field of MRI imparts an image contrast which is spatially fixed relative to the receive coil. If motion correction is used to correct subject motion occurring during an EPI time series then the receiver contrast will effectively move relative to the subject and produce temporal modulations in the image amplitude. This effect, which we will call the RFC-MoCo effect, may have consequences in the analysis and interpretation of fMRI results. There are many potential causes of motion-related noise and systematic error in EPI time series and isolating the RFC-MoCo effect would be difficult. Therefore, we have undertaken a simulation of this effect to better understand its severity. The simulations examine this effect for a receive-only single-channel 16-leg birdcage coil and a receive-only 12-channel phased array. In particular we study: (1) The effect size; (2) Its consequences to the temporal correlations between signals arising at different spatial locations (spatial-temporal correlations) as is often calculated in resting state fMRI analyses; and (3) Its impact on the temporal signal-to-noise ratio of an EPI time series. We find that signal changes arising from the RFC-MoCo effect are likely to compete with BOLD (blood-oxygen-level-dependent) signal changes in the presence of significant motion, even under the assumption of perfect motion correction. Consequently, we find that the RFC-MoCo effect may lead to spurious temporal correlations across the image space, and that temporal SNR may be degraded with increasing motion.

We're arXiving! (Another post on GRAPPA.)

In another move to accelerate the development of methods for neuroimaging applications, some colleagues and I recently decided to abandon a second attempt to publish a paper in traditional journals and opted for the immediacy of arXiv instead. (Damn, it feels good to be free of reviewers claiming "What problem? I don't see why a solution is even needed?" Whatever.) We've got another paper coming out on arXiv in a few days, too, although in this case we are exploring the possibility of a simultaneous submission to IEEE Trans Med Physics since it allows such tactics, and my colleagues in "real" physics do this all the time. Whether or not the IEEE submission happens the material will be out there in the world, naked, for all to view and poke at. Isn't this how science is supposed to work? I love it!

Anyway, for today, here's the skinny on the arXiv submission from August (which I inadvertently forgot to hawk on this blog even after tweeting it):

http://arxiv.org/abs/1208.0972

(Get a PDF fo' free via the link.)

Simultaneous Reduction of Two Common Autocalibration Errors in GRAPPA EPI Time Series Data

 

D. Sheltraw, B. Inglis, V. Deshpande, M. Trumpis *

(Submitted on 5 Aug 2012)

The GRAPPA (GeneRalized Autocalibrating Partially Parallel Acquisitions) method of parallel MRI makes use of an autocalibration scan (ACS) to determine a set of synthesis coefficients to be used in the image reconstruction. For EPI time series the ACS data is usually acquired once prior to the time series. In this case the interleaved R-shot EPI trajectory, where R is the GRAPPA reduction factor, offers advantages which we justify from a theoretical and experimental perspective. Unfortunately, interleaved R-shot ACS can be corrupted due to perturbations to the signal (such as direct and indirect motion effects) occurring between the shots, and these perturbations may lead to artifacts in GRAPPA-reconstructed images. Consequently we also present a method of acquiring interleaved ACS data in a manner which can reduce the effects of inter-shot signal perturbations. This method makes use of the phase correction data, conveniently a part of many standard EPI sequences, to assess the signal perturbations between the segments of R-shot EPI ACS scans. The phase correction scans serve as navigator echoes, or more accurately a perturbation-sensitive signal, to which a root-mean-square deviation perturbation metric is applied for the determination of the best available complete ACS data set among multiple complete sets of ACS data acquired prior to the EPI time series. This best set (assumed to be that with the smallest valued perturbation metric) is used in the GRAPPA autocalibration algorithm, thereby permitting considerable improvement in both image quality and temporal signal-to-noise ratio of the subsequent EPI time series at the expense of a small increase in overall acquisition time.

* For some strange arXiv technical reason the author list is reordered from that which appears (correctly) on the PDF. C'est la vie.

i-fMRI: Prospective motion correction for fMRI?

An ideal fMRI scanner might have the ability to update some scan parameters on-the-fly, in order to reduce or eliminate the effects of subject motion. Today, this approach is commonly referred to as "prospective motion correction" because the idea is to adapt the acquisition so that (some of) the effects of motion aren't recorded in the data, in contrast to the routinely employed retrospective motion correction schemes, such as an affine registration algorithm applied during post-processing; that is, in between the acquisition and the stats/modeling, which can lead some people to refer to such steps as "pre-processing" if you have a stats/modeling-centric view of the fMRI pipeline.

On the face of it, ameliorating motion effects by not permitting them to be recorded in the time series data is a wonderful idea. Indeed, as the subtitle to this blog attests, I am a huge fan of fixes applied during the acquisition rather than waiting until afterwards to try to post-process away unwanted effects. But this preference assumes that any method actually works, and works robustly, in everyday use. For sure there will be limitations and compromises, yet the central question is whether the benefits outweigh the costs. In the specific case of prospective motion correction, then, does a scheme (a) eliminate the need to use retrospective motion correction, and (b) does it reduce the effects of motion without bizarre failure modes that can't be predicted or circumvented easily?

A good place to begin evaluating prospective motion correction schemes - indeed, all motion correction schemes - is to first asses their vulnerabilities. It's no good if the act of fixing one part of the acquisition introduces an instability elsewhere. Failure modes should be benign. Below, I list the major hurdles for motion correction schemes to overcome, then I consider how elaborate any solutions might need to be. The goal is to decide whether - or when - prospective motion correction can be considered better than the alternative (default) approach of trying to limit all subject motion, and deal with the consequences in post-processing.


What do we mean by motion correction anyway?

As conducted today, motion correction applied during post-processing generally refers to an affine or sometimes a non-linear registration algorithm that seeks to maintain a constant anatomical content in a stack of slices throughout a time series acquisition. Prospective motion correction generally refers to the same goal: conserving the anatomical content over time. But, as is well known, there are concomitant changes in the imaging signal, and perhaps the noise, when a head moves inside the magnet. Other signal changes that are driven by motion may remain in the time series data after "correction." Indeed, depending on the cost function being used, the performance of the motion correction algorithm to maintain constant anatomy over time may be compromised by these concomitant modulations.

Now, we obviously want to try to maintain the anatomical content of a particular voxel constant through time or we have a big problem for analysis! But as a goal we should use a more restrictive definition for an ideal motion correction method: after correction we seek the elimination of all motion-driven signal (and noise) modulations. The only signal changes remaining should be neurally-driven BOLD changes (if we're using BOLD contrast, which I assume in this post) and "physiologic noise" that isn't strongly coupled to head (skull) motion. (Accounting for physiologic noise is usually treated separately. That's the assumption I'll use in this post, although at a very fine spatial scale it's clear that physiologic noise is another form of motion sensitivity.)


Motion sensitivities in fMRI experiments

A useful first task is to consider all the substantial signal changes in a time series acquisition that can be driven by subject motion. What signal changes are concomitant with changes of anatomical content as the brain moves relative to the imaging volume? How complicated is this motion sensitivity? What aspects of the signal changes will require hardware upgrades to the scanner, and/or pulse sequence modifications in order to negate them? And are these capabilities already designed into a modern scanner or will they require substantial re-design? These are the questions to keep in mind as we review the major motion sensitivities.

Common intermittent EPI artifacts: Subject movement

More fMRI experiments are ruined by subject motion than any other single cause. At least, that is my anecdotal conclusion from a dozen years' performing post-acquisition autopsies on "bad" data. The reasons for this vulnerability are manifold, starting with the type of subjects you're trying to scan. You may be interested in people for whom remaining still is difficult or impossible without sedation of some kind.

However, I think there is another reason why many (most?) fMRIers end up with more subject motion than is practicable: they haven't taken the time to think through the different ways that subjects can thwart your best efforts. In other words, what we are considering is largely experimental technique, or bedside manner as medical types refer to this stuff.

With the possible (and debatable) exception of bite bars, which aren't popular for myriad reasons, there is no panacea for motion. Why? As we shall see, it's not just movement of the head that's a concern. You need to consider a subject's comfort, arousal level, propensity to want to breathe, and many other things that might be peripheral to your task but are very much on the mind of your (often fMRI-naive) subjects.

Now, before we get any farther I need to outline what this post will cover, and what it won't. The focus of this post is on single-shot, unaccelerated gradient echo EPI - the sort of plain vanilla sequence that the majority of sites use for fMRI. I won't be covering the effects of motion on parallel imaging such as GRAPPA, for example. I will also restrict discussion here to the effects of motion on axial slices. Hopefully you can extrapolate to different slice prescriptions. But, rest assured that this isn't the last word in motion, not by a long chalk. Motion has come up before on this blog, e.g. in relation to GRAPPA for EPI, and the ubiquity of the problem implies that the issue will arise in many subsequent posts, too. Take today's post as an introduction to the general problem.

My final caveat on the utility of today's post. As this blog is focused on practical matters I will restrict the bulk of the discussion to things that you'll see and can control online, in real time. There are many tools that can be used to provide useful diagnostics post hoc, some of which I will mention. But this isn't a post aimed at showing you what went wrong. Rather, the intent of this post is to describe what is going wrong, such that you might be able to intercede and fix the situation. Some sites have useful real-time diagnostics that can tell you when (and perhaps how) a subject is moving, but they aren't widespread. Thus, for today's post we shall keep things simple and restrict the discussion to what can be seen in the EPIs themselves, as they are acquired.

WARNING: If you haven't run an fMRI experiment in a while then you might want to stop reading this post here and go and review the earlier post, Understanding fMRI artifacts: "Good" axial data. That post highlights our target: the low motion case.


Eye movements

Let's start simply. Here is a video of a subject intentionally moving his eyes to a target. Saccading is the technical term, I hear. (See Note 1 for experimental details. Parameters were fixed throughout for this post, unless mentioned to the contrary in any section below.) There are twenty volumes played back at a rate of 5 frames/sec:

GRAPPA and multi-band imaging. And motion. Again.

 

It's come to my attention that some of the latest accelerated (aka multiplexed) EPI sequences are now being made available to some sites with vendor/collaborative research agreements, a move that should catalyze their verification, testing and eventual application for neuroscience. The distribution of these pulse sequences to the wider world is great news! The potential is considerable! However, those wanting to conduct neuroscience experiments today with these zippy new tools should bear in mind the not inconsiderable risks. I want to warn you to think very carefully before taking the plunge.

Today's accelerated EPI sequences combine techniques such as multi-band (MB) acquisition with simultaneous echo refocusing (SER) and/or GRAPPA (1,2). In previous posts I've highlighted the increased motion sensitivity of parallel imaging methods such as GRAPPA. The MB family of methods also require "reference scan data" in order to reconstruct the time series images, and as such they are inherently more motion-sensitive than your plain vanilla single-shot EPI. Indeed, similar principles are used to reconstruct MB images as for GRAPPA, and the basic motion sensitivities are the same, i.e. motion during the reference data acquisitions will contaminate all images in a subsequent time series, while motion after the reference data but during the (accelerated) time series will lead to mismatches and spatial artifacts that will degrade temporal stability. In short, using these accelerated sequences is akin to sharpening the motion sensitivity profile of your experiment, and you will need to ensure a high degree of subject compliance to get good data.


Plan, then scan.

Now, I'm not suggesting you dismiss out of hand these sequences for your research. I am suggesting that you apply a lot of forethought, taking the time to consider several important factors. I've written before about evaluating pulse sequences that are new (or new to you). Your first task is to determine whether you even need a fancy, partly validated, highly risky pulse sequence to answer your neuroscience question. If the answer isn't a resounding "yes," why take the risk? Next, you should ask yourself how the pulse sequence should be set up to provide the optimum data. For instance, do you know which slice direction is best for minimizing motion sensitivity and/or receive field bias (g-factor) for the multi-band sequence? And do you know which RF coil to use, and why? If you can't establish your experimental setup based on sound principles that's a suggestion you either don't have the expertise yourself or you aren't collaborating with someone with the requisite expertise. (Me? I could guess, but that's about it! Without doing a validation study of my own I'd be winging it. Which is kinda my point!)

Please don't just go download and use the latest and greatest technique because it's new and cool. I've seen this movie before, and ninety nine times out of a hundred it ends in tears. Please put some justification and logic into your choices before you go and spend hundreds of hours and thousands of dollars finding yet another way that motion can confound an fMRI experiment. Eyes wide open!

__________________

References:

1.  S Moeller, et al. "Multiband multislice GE-EPI at 7 tesla, with 16-fold acceleration using partial parallel imaging with application to high spatial and temporal whole-brain fMRI." Magn. Reson. Med. 63, 1144-53 (2009).

2.  DA Feinberg, et al. "Multiplexed echo planar imaging for sub-second whole brain fMRI and fast diffusion imaging." PLoS ONE 5(12), e15710 (2010).

GRAPPA: another warning about motion sensitivity

 
I wrote a post in May last year to highlight the enhanced motion sensitivity of GRAPPA-EPI compared to single-shot EPI for fMRI. Paul Mullins and I had also discussed the use of GRAPPA for resting-state fMRI in the Comments of an earlier post. The literature is still fairly quiet on the adverse effects of GRAPPA for fMRI although, as I noted in the May post, there are one or two reports of reduced fMRI sensitivity when using parallel imaging, some of which might be attributable to motion (whether it was diagnosed as motion or not in the published work).

In the May, 2011 post I explained the two types of motion sensitivity that plague GRAPPA in its usual incarnation for EPI time series acquisitions. The first type - motion contamination of the auto-calibration scans (ACS) - might be mitigated by vigilance and a suitably resilient task script, e.g. one that uses plenty of null events at the start of the acquisition, before the first real stimulus is presented, to give the operator sufficient time to evaluate the images being generated with the current ACS and decide whether or not to stop and start over. This approach is no guarantee that motion won't have contaminated the ACS, but simple tactics like this can help avoid the worst effects of motion during the start of the run.

The second type of motion is that which happens after the ACS and during the (under-sampled) time series itself. This problem is one of mismatch. Displacement of the head from its position during the ACS acquisition can lead to spatial errors in the current image volume. Thus, whilst attaining motion-free ACS might be considered essential for fMRI, maintaining proper matching of the ACS to the under-sampled time series is also important. The bigger the mismatch the more likely there will be a penalty in statistical power for the time series.

In this post I want to tackle the issue of non-head motion in the scanner, and its effects on GRAPPA-EPI images. This investigation was motivated by one of my users who reported seeing occasional "banding" in a study that had used GRAPPA-EPI. The traditional evaluation of head motion suggested that the subjects weren't moving very much, so I started looking into other possible instabilities. I was quite surprised just how sensitive GRAPPA-EPI can be to small perturbations, as you will shortly see.


A quick review of some brain data

Let's begin by looking at one of the problem GRAPPA-EPI data sets from a human subject. The acquisition specifics are as follows: 12-channel head RF coil on a Siemens Trio/TIM scanner, GRAPPA with R = 2, reconstructed matrix = 96x96, FOV = 224x224 mm, slice thickness = 3 mm, 10% gap, interleaved sagittal slices, flip angle = 90 deg, TR/TE=2000/26 ms, echo spacing = 0.8 ms, readout bandwidth = 1408 Hz/pixel.

Here is a cine-loop through the raw data:

Light relief (to buy me time).... This year's IgNobel in Medicine

Anyone who has ever experienced an fMRI scan knows two things about the effects of the method on a subject: (1) it's soporific, and (2) like a long car journey, you don't need to pee until five minutes after you've started. So this year's IgNobel Prize in Medicine, awarded jointly to two groups, caught my attention. Their work shows how the need to urinate can affect performance on some simple mental tests - just the sort of tests that we use in our fMRI experiments.

Implications for fMRI?

An enjoyable summary of the winning researchers' work is available on this Scientific American blog. According to this summary (Yeah, I haven't got around to reading the papers themselves yet. I'm training to be a mainstream science journalist ;-), needing to pee could have your subjects performing better (yes, better) on delayed gratification tasks, but worse on cognitive tasks. I take these results at face value - I have to, I've not read the papers - but I do want to think a little more about the implications for fMRI studies. It's hard enough keeping people awake, let alone motivated to do a task. And as for providing *additional* motivation for a task... The mind boggles!

"I feel the need, the need to pee!"

So, short of rejecting subjects who rush to the toilet the moment they get out of the scanner, what else could we do to control for the effects? Perhaps we could insist that subjects must be able to sit in a waiting room for 20 minutes post-scan - no pee - and only then opt to retain their scan data.

What else might produce a similar effects in subjects? General discomfort? You have to wonder, given the "need-to-pee" effect, whether a subject's general state of (un)happiness in the scanner might well be interfering with his mental performance. If so, having pressure points in a subject's lower back or whatever could have him significantly altering his task ability.

Alternatively, perhaps the need to pee and general discomfort merely increases a subject's propensity to move. We all know that this is one of the Stages of Having to Pee:

So perhaps this amusing research has some important ramifications for fMRI studies after all. As with so many other state factors - caffeine use, stress, menstrual cycle, etc. - it could just be another in a long litany of issues that contribute to our relatively poor inter-subject variability. You know my feeling on the matter: if you can control for it, control it. And if you can't control for it but you can measure it, MEASURE IT! Would it really be the end of the world if you were to ask your subject to rate her "need to pee" as she exits the scanner? How amusing would it be to see your effect disappear having  regressed out the "need to pee" score?



PS I really will have a last post on EPI k-space along very soon! I promise!