Have you ever wondered whether it's appropriate to put a research subject into a dark, confined tube that makes an awful din, whereupon the subject may learn that his brain has some abnormality, and still expect the subject's brain to operate in a state representative of his normal cognition (and not that of a stressed out basket-case)? And what about the bioeffects of the high magnetic field itself, or of the rapidly switched gradients and their induced electric currents in body tissue? To date there has been scant evidence that the action of studying human cognition via an MRI scanner actually modifies that brain function in a manner that might be considered a significant issue for interpretation of fMRI results.
Putting aside the cognitive effects of a loud background noise and claustrophobia, the question remains whether the static and time-varying magnetic fields are modifying brain function in a substantial fashion. There are some well-known side effects of high magnetic fields: vertigo (see Note 1), and a metallic taste are the two phenomena tied directly to presence of, or movement through, a high magnetic field. (See Note 2.) But these effects tend to be mild and/or transitory, as a subject acclimatizes to the magnetic field, and can usually be rendered negligible by taking care not to make rapid head movements in or around the magnet.
A colleague forwarded to me yesterday a paper from a Dutch group (van Nierop et al., "Effects of magnetic stray fields from a 7 tesla MRI scanner on neurocognition: a double-blind randomized crossover study." Occup. Environ. Med. 2012 Epub) that investigates the effects of head movements in the intense stray field region of a 7 T magnet. So, first of all, some good news: if you're doing fMRI at 1.5 or 3 T and you're not in the habit of asking your subjects to thrash their heads around wildly at the mouth of the magnet or once inside the magnet bore, then so far as is known today you're in the clear. The effects reported in this paper pertain specifically to head movement in the really intense gradients that comprise the stray magnetic field around the outside of a passively shielded 7 T magnet. (The iron shield is outside the magnet, leaving considerable gradients in the vicinity of the magnet when compared to the actively shielded 1.5 and 3 T magnets most of us have nowadays.)
And with that preamble let's look at the summary of the paper:
OBJECTIVE: This study characterises neurocognitive domains that are affected by movement-induced time-varying magnetic fields (TVMF) within a static magnetic stray field (SMF) of a 7 Tesla (T) MRI scanner.
METHODS: Using a double-blind randomised crossover design, 31 healthy volunteers were tested in a sham (0 T), low (0.5 T) and high (1.0 T) SMF exposure condition. Standardised head movements were made before every neurocognitive task to induce TVMF.
RESULTS: Of the six tested neurocognitive domains, we demonstrated that attention and concentration were negatively affected when exposed to TVMF within an SMF (varying from 5.0% to 21.1% per Tesla exposure, p<0.05), particular in situations were high working memory performance was required. In addition, visuospatial orientation was affected after exposure (46.7% per Tesla exposure, p=0.05).
CONCLUSION: Neurocognitive functioning is modulated when exposed to movement-induced TVMF within an SMF of a 7 T MRI scanner. Domains that were affected include attention/concentration and visuospatial orientation. Further studies are needed to better understand the mechanisms and possible practical safety and health implications of these acute neurocognitive effects.
Okay, so let's make sure we're clear that although the test magnetic field strengths mentioned are 0.5 and 1.0 T, this refers to two heterogeneous regions of a stray magnetic field on the outside of a 7 T magnet:
These two locations are not equivalent to the homogeneous fields that you would find at the center of a 0.5 or a 1.0 T MRI magnet. What is important here is the strong gradient of magnetic field, with each location in space being designated by its point amplitude of either 0.5 or 1.0 T, as shown in the contours of the above figure. Fore and aft of these points the magnetic field varies very quickly with distance, whereas at the center of a 0.5 or a 1.0 T magnet there would be a homogeneous field region larger than the dimensions of a human head. Thus, it is important to recognize that in this study it's the head's movement through these intense gradients that is generating the bioeffects. The study says nothing whatsoever about head movements inside the homogeneous field region at the center of 0.5, 1.0, 3 or even 7 T magnets.
And so to the behavioral portion of the study. Subjects moved their head in prescribed ways in between a suite of behavioral tasks:
"The head movements consisted of 10 movements in vertical and 10 in horizontal direction (covering an angle of 180 degrees in 0.8 seconds), the start of each movement indicated by an auditory cue. The accompanying TVMF at head height in sitting position in the 0.5 (low) and 1.0 T (high) conditions were on average approximately 1200 and 2400 mT/s, respectively..."
Although the pulsed magnetic field gradients we use for spatial encoding may be driven as fast as 20 T/s, the time integral of our familiar gradients is small; a ramp up time is usually around 200 microseconds, after which the gradient is constant (and of low amplitude, maybe 35 mT/m, relative to the polarizing magnet strength of 1.5, 3 or 7 T) until it is switched off in a similarly short time. So 1.2 - 2.4 T/s for almost a second (800 ms) is quite a lot of time varying magnetic field; considerably more than arises from a scanner's pulsed gradients. And each movement was repeated ten times in a row (I think at the 800 ms rate, although I wasn't absolutely clear on that point from the methods section).
Once each subject had shaken then nodded his head the requisite ten times apiece, it was time to assess the magnetic hangover effects. The behavioral tasks performed after a new block of head movements were as follows:
"Neurocognitive domains were selected based on brain functions that are most relevant for surgeons and other medical professionals operating near MRI, for example, visual perception, motor performance as well as more general functions concerning attention, concentration and (working) memory.
"...the test battery was composed of tasks that are relatively short (<4 min each), insensitive to ceiling effects and to influences of practice and level of intelligence."
And, of course, they took good care to ensure that participants weren't able to figure out whether they were in either experimental condition or in the sham condition (a mock scanner) while doing each of the three sessions.
You'll have to read the paper for the details of the tasks, it is all Swahili to me. I shall assume that the tasks were all sound, and report their findings:
 |
| (Click to enlarge.) |
"...we observed a significant exposure-response relationship, indicating a decrease in attention related to a reduced working memory and a decrease in visuospatial perception. Also in verbal memory functioning (story recall), a subtle decrease was seen, but this association did not reach statistical significance (p=0.07)."
Naturally, this study has some limitations and the authors point them out:
"The current study design does not allow us to disentangle any effect to be associated only with SMF or TVMF or with the combination of both."
In other words they're not sure whether it's the strong gradient or the strong magnetic field that is causing the electrical currents in the brain that lead to behavioral changes. This would leave open the possibility that similar head movements conducted inside the homogeneous magnetic field at the center of your 1.5 or 3 T scanner could have similar bioeffects. Not that subjects are encouraged to make such movements, but according to this study the possibility cannot be excluded. Interesting.
A further limitation concerns the duration of the bioeffects relative to the task durations:
"...the duration of any effect of motion-induced TVMF is unknown. Since it is not feasible to induce strong TVMF (by head movements) during the completion of a task, subjects performed head movements immediately before each single task. This implies that we would only pick up an effect of TVMF lasting longer than the duration of a single task (from 30 to 180 seconds). Our results show that effects due to TVMF would have to last for at least 90 s, that is the longest task for which we found a statistically significant effect (reaction time task). This is longer than most other tasks except for the Kappers, memory and letter/number sequencing tasks which took up to 180 s and did not show significant effects of exposure."
One would naively expect there to be some sort of temporal relationship between the time (and magnitude) of head movements and the length of the hangover from them. Still, the hangover seemed to affect only certain cognitive domains, at least as could be measured by these relatively long task blocks.
What about the other, better-known effects of magnetic field exposure?
"Based on the questionnaire after each session, in the sham, low and high exposure condition, 4, 10 and 19 subjects, respectively, reported sensory symptoms. For example, in the highest exposure condition, a metallic taste (12 subjects) was most commonly reported followed by dizziness (six subjects), headache (five subjects) and nausea (one subject)."
So, what does it all mean for fMRI? Are our subjects essentially "drunk on MRI" at the time of their scan? This study was focused on the safety of personnel working around high magnetic fields and not on the performance of fMRI subjects, so we need to read between the lines a little bit. For starters, unless you are exceedingly reckless in the way you manage your subjects as you install them in the scanner, you're not likely to encounter the sorts of head movements used in this study. Furthermore, I don't think you can extrapolate from these results and say anything meaningful about potential bioeffects in the homogeneous center of MRI magnets, even 7 T ones. Still, it would be interesting to know if rapid head movements once inside the scanner have effects on cognition. And it might be useful to know whether the movements considered in this paper would show (reduced?) bioeffects in the stray field of 3 T and lower magnets, if only to know precisely what bioeffects it is we are avoiding by having our subjects move slowly (and then not at all once they have been inserted into the magnet bore).
__________________
Notes
1. A 2011 paper from Johns Hopkins suggested the following mechanism for MR-induced vertigo or dizziness:
Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus.
From Roberts et al., "MRI Magnetic Field Stimulates Rotational Sensors of the Brain." Current Biology 21(19), 1635-40 (2011). PDF is here.
2. Peripheral nerve stimulation and the (rare) generation of magnetophosphenes is tied to the rapidly switched magnetic field gradients. PNS can be quite easily achieved on a modern 3 T scanner and can be distracting even if there isn't a direct modulation of the brain by the magnetic fields. It's important to ensure subjects don't form big loops by crossing their feet or clasping their hands together during a scan. But magnetophosphenes - flashes in the retina - are hard to generate in a typical clinical MRI. I would expect high-powered insert gradient sets to be capable of triggering them, but I've never experienced them myself in any standard body gradient set. I have, however, experienced them in an experimental MRI scanner that uses a pre-polarizing (pulsed) electromagnet.
No comments:
Post a Comment