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j ou rn a l h o m epa g e :w w w . e l s e v i e r . c o m / l o c a t e / j n e u m e t h
Research
article
Flexible
head-casts
for
high
spatial
precision
MEG
Sofie
S.
Meyer
a,∗,
James
Bonaiuto
b,
Mark
Lim
c,
Holly
Rossiter
a,
Sheena
Waters
b,
David
Bradbury
a,
Sven
Bestmann
b,
Matthew
Brookes
d,
Martina
F.
Callaghan
a,
Nikolaus
Weiskopf
a,e,
Gareth
R.
Barnes
aaWellcomeTrustCentreforNeuroimaging,InstituteofNeurology,UniversityCollegeLondon,London,UK bSobellDepartmentforMotorNeuroscienceandMovementDisorders,UniversityCollegeLondon,London,UK cChalkStudiosLtd,14WindsorSt.,N18QG,London,UK
dSirPeterMansfieldMagneticResonanceCentre,SchoolofPhysicsandAstronomy,UniversityofNottingham,Nottingham,UK eDepartmentofNeurophysics,MaxPlanckInstituteforHumanCognitiveandBrainSciences,Stephanstrasse1a,04103Leipzig,Germany
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•Weproposeamethodforconstructingflexiblehead-caststostabilizetheheadduringMEGscanning.
•Co-registrationerrorisminimizedbyusingMRIimagestopre-definefiducialcoillocations.
•Within-andbetween-sessionmovementis<0.25and<1mmrespectively.
•Thisenableshighreproducibilityofsourcelevelresults.
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Articlehistory:
Received21September2016 Receivedinrevisedform 18November2016 Accepted20November2016 Availableonline22November2016 Keywords:
Magnetoencephalography Headlocalization Spatialresolution MRI-MEGCo-registration Headmovementminimization Head-cast
3Dprinting
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Background:Incombinationwithmagnetoencephalographic(MEG)data,accurateknowledgeofthe brain’sstructureandlocationprovideaprincipledwayofreconstructingneuralactivitywithhigh tem-poralresolution.However,measuringthebrain’slocationiscompromisedbyheadmovementduring scanning,andbyfiducial-basedco-registrationwithmagneticresonanceimaging(MRI)data.The uncer-taintyfromthesetwofactorsintroduceserrorsintotheforwardmodelandlimitthespatialresolution ofthedata.
Newmethod:Wepresentamethodforstabilizingandreliablyrepositioningtheheadduringscanning, andforco-registeringMRIandMEGdatawithlowerror.
Results:Usingthisnewflexibleandcomfortablesubject-specifichead-castprototype,wefind within-sessionmovementsof<0.25mmandbetween-sessionrepositioningerrorsaround1mm.
Comparisonwithexistingmethod(s):Thismethodisanimprovementoverexistingmethodsforstabilizing theheadorcorrectingforlocationshiftson-oroff-line,whichstillintroduceapproximately5mmof uncertaintyatbest(Adjamianetal.,2004;Stolketal.,2013;Whalenetal.,2008).Further,thehead-cast designpresentedhereismorecomfortable,safer,andeasiertousethantheearlier3Dprintedprototype, andgiveslightlylowerco-registrationerrors(Troebingeretal.,2014b).
Conclusions:Weprovideanempiricalexampleofhowthesehead-castsimpactonsourcelevel repro-ducibility.Employmentoftheindividualflexiblehead-castsforMEGrecordingsprovideareliablemethod ofsafelystabilizingtheheadduringMEGrecordings,andforco-registeringMRIanatomicalimagesto MEGfunctionaldata.
©2016TheAuthor(s).PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBYlicense (http://creativecommons.org/licenses/by/4.0/).
∗ Correspondingauthor.
E-mailaddress:sofi[email protected](S.S.Meyer).
1. Introduction
In theory,the spatial precision attainable with
magnetoen-cephalography (MEG) increases monotonically with increasing
signalstrength(Grossetal.,2003;HillebrandandBarnes,2005,
2003).Inpracticehowever,thisincreaseisdifficulttoachieve.Two
ofthemainlimitationsareerrorsinco-registrationbetween
func-http://dx.doi.org/10.1016/j.jneumeth.2016.11.009
tionalMEGdataandanatomicalmagneticresonanceimaging(MRI)
data,andheadmovementduringscanning.Bothintroduce,atbest,
∼5mmofuncertaintyaboutthelocationoftheheadrelativeto
thesensors(Adjamianetal.,2004;Grossetal.,2013;Rossetal.,
2011;Singhetal.,1997;Stolketal.,2013;Whalenetal.,2008).
Critically,bothsourcesoferrornon-linearlycompromisethe
for-wardmodellingaccuracy(HillebrandandBarnes,2011,2003),and
reducethesignal-to-noiseratio(SNR)throughtopographical
blur-ring(Medvedovskyetal.,2007;Uutelaetal.,2001).
Although some progress has been made in minimizing
co-registrationerror(Hironagaetal.,2014;Koessleretal.,2011;Nunez
andSilberstein,2000;Whalenetal.,2008),forexampleby
sta-bilizingtheheadduringrecording(Adjamianetal.,2004;Singh
etal.,1997),orcompensatingformovementsbothduringandafter
recording(Medvedovskyetal.,2015,2007;Nenonenetal.,2012;
Stolketal.,2013;Uutelaetal.,2001),implementationproblems
haveremained.Thesourcesofresidualerrorincludemisalignment
ofsurfaces,amplificationofsmallplacementerrorsatthefrontof
theheadtolargeerrorsatthebackofthehead,and/orrelianceon
invarianceinfiducialplacementwithinandacrossexperimenters
andsubjects(Adjamianetal.,2004).
Using3Dprintingtocreatesolidhead-castswhicharemoulded
to the surface of the head internally and to the inside of the
MEG scanner externally, we recently showed reduction of
co-registration errors to<2mm (Troebinger et al., 2014a, 2014b).
Althoughthesefirstsolidhead-castsgaveaccesstomuchhigher
qualitydata byminimizingboth co-registrationerror andhead
movement,theycoveredtheeyesandtheirrigidityreduced
par-ticipantcomfort,particularlyforlongrecordingsessions.Here,we
presentanewhead-castprototypemadeofflexiblepolyurethane
foamwhichleavestheeyesuncovered,andiseasier,safer,andmore
comfortabletouse.Theimprovedusercomfortisprimarilybecause
oftheflexibilitywhichmakesiteasierandfastertogetintoandout
oftheMEGscannerhelmet(dewar).Furthermore,the3Dprinting
isnowbasedonanMRIimage(asopposedtoanopticalscanusedin
Troebingeretal.,2014a,2014b)whichbothmaximisestheaccuracy
withwhichthecastfitsthehead,andminimizesco-registration
errorbypredefiningtheMEGfiducialcoillocationsinMRIspace.
Wedescribetheconstructionpipeline,thewithin-and
between-sessionheadmovementforsubjectswearingtheseheadcasts,and
assesstheestimatedco-registrationerror.Wethenshowhowthese
improvementsgiverisetohighbetween-sessionreproducibilityat
sourcelevel.
2. Materialsandmethods
Thissectionis dividedintotwo parts.First, wedescribethe
methodsusedforbuildinghead-casts.Next,wedescribethe
scan-ningproceduresforevaluatingthehead-castswithrespecttohead
stabilization,co-registration,andspatialprecision.
2.1. Participants
Datawerecollectedfromfourhealthyadultsubjects(4men,
meanage32.3yearsold).Allsubjectswereright-handedandhad
nohistoryofneurologicalorpsychiatricdisease.One(fifth)
partic-ipantwasexcludedfromtheanalysisbecauseofrecordingerrors.
Informedwrittenconsentwasgivenbyallsubjectspriorto
scan-ningandtheexperimentswerecarriedoutafterobtainingethical
approvalfromtheUniversityCollegeLondonethicscommittee(ref.
number5833/001).
2.2. MRIdataacquisition
Inordertoconstructthehead-cast,anaccurateimageofthe
scalp surface is required. To getthis, we first scanned
partici-pantsin a magneticresonance imaging (MRI) system(Fig. 1a).
ImageswereacquiredusingaSiemensTimTrio3Tsystem
(Erlan-gen,Germany).Duringthescan,theparticipantlayinthesupine
positionwiththeirheadinsidea12-channelcoil.Acquisitiontime
was3min42s,plusa45slocalizersequence.Wewerevery
cau-tiousofskindistortionsasanysucherrorscouldpotentiallymake
thehead-castill-fittingandthereforeuncomfortable.Forthis
rea-son,participantswerenotgivenpaddingorearphones,asthese
coulddisplacetheskinontheface,headorneck.Tominimize
audi-blenoisetheywereinsteadgivenearplugs.Theshortacquisition
time minimizesmotionandpotentialconsequential distortions.
Weusedanradiofrequency(RF)andgradientspoiledT1weighted
3Dfastlowangleshot(FLASH)sequencewiththefollowing
acqui-sitionparameters:imageresolution1mm3(1mmslicethickness),
field-ofviewsetto256,256,and192mmalongthephase(A–P),
read(H–F),andpartition(R–L;second3Dphaseencoding
direc-tion)directionsrespectively.Susceptibilitydifferencesexistingat
air-tissueinterfacescanleadtomagneticfieldinhomogeneityand
subsequentdistortionsorsignallossintheacquiredimage.
There-fore,topreservebrainmorphologyweusedasingleshotapproach
withhighreadoutbandwidth(425Hz/pixel)andminimumecho
time(2.25ms).Consequentlynosignificantgeometricdistortions
wereexpectedorobservedintheimages.Ashortrepetitiontime
(7.96ms)wasusedtominimiseacquisitiontimewhilethe
excita-tionflipanglewassetto12◦toensuresufficientsignal-to-noise
ratiofortheresultinganatomicalimage.Toacceleratethe
acqui-sition,apartialFourier(factor6/8)acquisitionwasusedineach
phase-encodeddirection.
2.3. Head-castconstruction
First,weextractedthescalpsurfacesfromtheMRIdatausing
SPM12(http://www.fil.ion.ucl.ac.uk/spm/)(Fig.1a).Thisconsistsof
registeringtheMRIimagewithatissueprobabilitymap(Ashburner
andFriston,1997)andclassifyingtissuesintodifferentclasses(such
asgreymatter,skull,skin,etc)onavoxel-by-voxelbasis.Thisis
donebyconstructingagenerativemodelwhichtakesintoaccount
boththevoxel-specificpriorprobabilityofbelongingtoagiven
tissueclass,anditsintensityintheMRIimage.Thismodelalso
esti-matesandcorrectsforthebiasfield(AshburnerandFriston,2005).
Weusedtheskintissueprobabilitymapandconvertedthisintoa
surfaceusingtheMATLABfunction‘isosurface’.Wethenconverted
thistessellatedsurfaceintostandardtemplatelibrary(STL)format
(Fig.1b)commonlyusedfor3Dprinting.Tospecifytheshapeofthe
fiducialcoils,weusedopticalwhitelightscanningtoobtaina3D
representationofasinglecoil.Thiswasdigitallydrawnin3Dand
thencheckedforitsaccuracybothagainstthedigitalwhitelight
scanaswellasthephysicalcoil,usingdigitalmeasuringcallipers.
Nextthreecopiesofthisvirtualcoilwereplaced,asper
conven-tion,atthenasion,leftperi-auricular(LPA),andrightperi-auricular
(RPA)sites.Note thatthis wasnotstrictlynecessary asanyset
ofdistantscalplocationswouldhaveenabledtheco-registration
procedure.Thisapproachthereforedoesnotsufferfrom
inaccura-ciesindetermininganatomicallandmarks,asiscommonlythecase
whenplacingfiducialcoilsontheheadduringMEGdata
acquisi-tion.Oneconstraintontheplacementofthecoilswasensuring
thatthecoil-bodyandextrudingwirewereflatagainstthescalp,in
ordertoremoveunnecessarystressormovementofthecoilwhen
thehead-castwasputonortakenoff.
Theoriginaldesign(Troebingeretal.,2014b)wasalteredsoas
tonowincludeeye-holeextensions,earflapswhichextenddown
belowtheears,andatopspacing-cylindertoaccuratelypositionthe
positiveheadmodelinthedewar-helmet(Fig.1c–f).Theearflaps
facilitategettingintoandoutofthescannermoreeasilyandsafely
(seeSafetyProceduresformoredetails)andalsoprovideanexternal
Fig.1. Overviewofhead-castconstructionsteps.a)HeadsurfaceisextractedfromananatomicalMRIimageusingthestandardSPM12segmentationprocedure.b)Head surfaceextractionisconvertedtoasurfacefileandfiducialcoilsareadded.ThecoillocationsaredefinedinMRIcoordinates.c)Apositioningcylinderatthetopoftheheadis addedtothevirtualmodeltodefinethepositionoftheheadinsidethehead-cast.Eyeextensionsareaddedtoenablevisionduringuse.d)Usingandadjustingthepositioning cylinder,eyeextensionsandearextensions,thevirtualheadmodelispositionedappropriatelyinsideavirtualcopyoftheMEGdewar.e)Thepositiveheadmodelis3D printed.f)The3Dprintisplacedinsidethemanufacturer-provideddewarcopy(asind)andfoamresinispouredintofillthegapbetweentheprintedpositiveheadmodel andthedewar.Thefiducialcoilprotrusionsonthe3Dprintedheadresultincoil-shapedandcoil-sizedindentationsinthehead-cast(thenasioncoilprotrusionisvisible betweentheeyesine).g)Thesubjectcannowweartheflexiblefoamhead-castandenterintothe(real)MEGdewarforscanning.
Thevirtual3Dmodelwasthusplacedinsideavirtualversionofthe
scannerdewar-helmet(Fig.1d)suchthatthedistancetothe
sen-sorswasminimized(byplacingtheheadasfarupinsidethedewar
aspossible)whileensuringthatvisionwasnotobstructed.Next,the
positivehead-model(plusspacingelementsandcoilprotrusions)
wasprintedusingaZcorp3Dprinterwith600×540dotsperinch
resolution(Fig.1e).The3Dprintedheadmodelwasthenplaced
insidethemanufacturer-providedreplicaofthedewar-helmetand
liquidresinwaspouredinbetweenthesurfacestofillthenegative
space.Theresinexpandsandsetswithin∼30s,andtheresulting
flexiblefoamconstitutes thesubject-specific head-cast(Fig.1f).
Notethatthecoilprotrusionsonthe3Dprintnowbecome
inden-tationsinthefoamhead-cast.Thefiducialcoilscanthusbeplaced
insidetheresultingindentationsandthehead-castcanbeworn
forscanning(Fig.1g).Thisremovesinaccuraciesindetermining
anatomicallandmarksforfiducialplacement,andalsoensuresthat
thesamelocationisusedforrepeatedscans.
2.4. MEGscanning
MEGrecordingsweremadeusinga275-channelCanadianThin
Films(CTF) MEG system withsuperconducting quantum
inter-ferencedevice(SQUID)-basedaxialgradiometers(VSMMedTech,
Vancouver,Canada)inamagneticallyshieldedroom.Thedata
col-lectedweredigitizedcontinuouslyatasamplingrateof600Hz.We
refertoSafetyProceduresforadescriptionofthegeneraloperating
andsafetyprocedures.
2.5. Experiment1:between-sessionvariability
Wefirsttestedhowconsistentlysubjectscouldberepositioned
withintheMEGscannerbyaskingthemtorepositionthemselves
inthescanner10times.Inadditiontomeasuringabsolutelocation
ofthehead-castusingthefiducialcoils,wealsoplaceda
refer-encecoilononesideofthenosetomeasurerelativedisplacements
betweenthehead-castandhead.Eachsubjectperformed10
sepa-rate10strials.Foreachrun,thesubjectfirstpositionedthemselves
insidethescannerwiththehead-caston,satstillfor10s,beforeand
afterwhichthefiducialcoilswerelocalized,andthesubjectthen
exitedthescannerandremovedthehead-cast.Thisremovaland
replacementwasrepeated10times.
Inadditiontothehealthysubjects,wealsoperformeda
simi-larexperimentusingthemanufacturerprovidedsphericalcurrent
dipole phantom. Thisexperiment wasdone in order toget an
approximationtothesystem-basednoiseinherentinlocalizationof
didnothaveahead-castforthephantombutkeptthefourfiducials
fixedonthesurfaceofitusingtape.Tomimicthere-positioning,
wephysicallyshifteditslocationbetweenthe10strials.
2.6. Experiment2:within-sessionvariabilityandbuttonpresses
Toassesstheeffectofreducedheadmotion(increasingSNR)and
improvedheadrepositioning (improvingrepeatability),we
ana-lyseddata froma singlesubject(subject3 fromExperiment1)
performingbuttonpressesacrosstwelve15-minsessionswith180
trialseach.Thesesessionswerespreadoverfourdays(whichwere
separatedbyseveralweeks)withthreerunsperday.Oneachtrial,
wepresentedasetofdotsmovingeitherleftorright,servingas
aninstructioncueforthesubjecttoindicatethemovement
direc-tionwithabuttonpressuponasubsequentGosignal.Allresponses
wereobtainedfromtherighthand.MEGdatawereacquiredata
samplingrateof1200Hz.
Datawereepochedaroundthebuttonpressonset(time0),and
abeamformer covariancematrix constructedbasedonthedata
fromthebetaband(15–30Hz)from−2000to2000ms.Toextract
thesourcelocations,beamformer-basedvolume-of-interest(VOI)
analysis was then carried out, comparing two time windows
([−1500–−1000]versus[500–1000]ms)togenerateastatistical
chisquarevolumecentredontheaverageleftprimarymotor
cor-texpeak(−34,−30,52mminMNIspace)witha20mmradius
and 1×1×1mm3 grid resolution. The data were subsequently
smoothedwithafull-widthhalf-maximumkernelof8mm.
3. Results
3.1. Between-sessionmovement
Tofirstestablishhowreproducibletheabsoluteheadposition
waswhenusinghead-casts,wemeasuredthefiducialcoillocations
across10repositioningtrials(Experiment1).Wefoundthatitwas
possibletorepositionthefiducialcoilsrelativetotheMEGsystem
within0.6mmstandarddeviationinanyonedimension(Fig.2a).
Nextwewereinterestedinwhetherthereisariskofthecoils
movingwithrespecttoeachotherwhenthehead-castistakenon
andoff.Weexaminedthisbycalculatingthestandarddeviationof
thedistancesbetweenfiducialcoilsacrossrepositioningtrials.We
foundnosuchmeasureableeffectasthestandarddeviationsofthe
distancesweresimilartothestandarddeviationoftheabsolute
locations(Fig.2b).Wefoundthatwhenwerepeatedthe
experi-mentusingaphantom(withthecoilsfixedonthesurfacehereof),
weobservedasimilarlevelofvariability,suggestingthatthiserror
isduetouncertaintyinthe(MEGsystem’s)localizationofthecoils
themselvesandnottocoilmovement.
SincethefiducialcoillocationsarerecordedbytheMEGsystem,
changesinhead-positionrelativetothedewarduringrecording,
although undesirable, canbe accounted for.A more pernicious
sourceoferrorisrelativemovementoftheheadwithrespectto
thehead-cast.Toaddressthisdirectly,weplacedareferencecoilon
thenoseofthesubjectinordertomeasurethedistancesbetween
thisreferenceandthestandardfiducialcoils(Fig.2c).Unlikewith
thepreviousanalysiswheretherewasnodifferencebetween
mea-surementsmadewiththephantomandnormalsubjects,wenow
observedaneffectbeyondmeasurementerror.Wefoundthatthe
Fig.2.Between-sessionheadmovementresultsfromExperiment1(re-positioningtrialswhereeachofthefoursubjectscameoutofthescanner,removedthehead-cast,put itbackonandre-entered10times).a)Variabilityofabsolutecoillocations.Dotsshowthestandarddeviationoftheabsolutecoillocationoverthecourseoftheexperiment. Repositioningisprecisetowithin<0.6mmstandarddeviationforanycoilinanydimension.b)Coil-coildistancevariability.Thestandarddeviationsarecalculatedfromthe distancesbetweenthefiducialcoilsmeasuredinExperiment1.Thedistancesvary<0.5mmwhichiswithintherangeofmeasurementerror,asillustratedbythephantom measurements(blacksquares).c)Referencecoil-standardcoildistancevariability.Sameformatasb,butbasedonthedistancesbetweeneachofthethreestandardfiducial coilsandareferencecoilplacedonthenose.Thereismorevariabilitywithnormalsubjectsthanthephantom.d)Scatterplotshowingabsolutelocationsofreferencecoil inhead-centred(standardcoil-defined)space.Thisplotillustratesdimensionsalongwhichthereferencecoillocationvariesrelativetothestandardcoils:mostlyinthe Zdimension(up-down).e)Locationofthereferencecoilinhead-centredspace.Barsencodestandarddeviationofabsolutepositionofthereferencecoilinhead-centred spacemeasuredacross10repositioningtrials.Thelocationofthereferencecoildeviates<1.2mmfromthefiducialcoilsintheworstcase.NotethatvariabilityalongtheZ dimensionisalsorelativelyhighwiththephantom.Thestandarddeviationoverallsubjectswas0.50,0.57,and0.80mmfortheX,YandZdimensionsrespectively.
Fig.3. Within-sessionheadmovement.DatafromExperiment2.a)Absolute loca-tionoftheleftcoilintheX,YandZdimensionsoverthecourseof12(colourcoded) 15-mintrials.Thelocationismean-correctedindividuallyforeachtrial.Wefind thatthevariabilityacrosstimeisnegligible.Thelargestmovementsaredownwards (frompositivetonegative)inlinewiththesubjectslidingdowninthechair.b) Cir-clesshowthestandarddeviationsoftheabsolutecoillocationsforall12trialsinall dimensionsandforallcoils.Thestandarddeviationofthelocationsrecordedwas 0.22mmatmaximum.Z(vertical)isconsistentlythemostvariabledimension.
variabilityinthelocationofthehead-castrelativetotheheadwas
predominantlyduetouncertaintyintheZdimensionof1.2mm
standarddeviation.
Nextwewereinterestedinwhetherthesedifferencesin
dis-tancestothereferencecoilcouldbeattributedtodifferencesin
locationalongsomespatialdimensionsmorethanothers.Fig.2d
showsthatthemostvariabledimensionistheZ(up-down)
dimen-sion.Fig.2eshowsthestandarddeviationofthereferencecoilwith
respectto‘head-centred’space,meaningthatthecoordinateframe
isdefinedbythethreestandardfiducialcoils.Thesevaluesreflect
howmuchthereferencecoilmovedaroundrelativetothestandard
fiducialcoilsinsidethehead-castinX(front-back),Y(left-right),
andZ(up-down)dimensions.Wethusfoundthatthemainaxis
alongwhich additionalvariance occursis theZ(up-down)axis
(Fig.2d,e).Surprisingly,wefoundthishighestvariationintheZ
dimensiontobetrueforbothphantomandhumanmeasurements.
Thissuggestsincreasedmeasurementuncertainty in thisplane,
whichmaybeunrelatedtothehead-castbutperhapsduetothe
MEGsensorsandalgorithmsusedtolocalisethecoils,orsimply
theverticalmovementofthescanningchair(onwhichthephantom
rested)overtime.
3.2. Within-sessionmovement
Toevaluatetheheadlocationstabilityovertime,asinglesubject
wasscanned on 12 separate trials lasting 15min each
(Exper-iment 2). We found that results were almost identical across
fiducialcoils.Foranycoil,relativemovementsovertwelve15-min
runsweresub-millimetre(<0.75mm)andthemovement
predom-inantlyoccurredasdriftintheverticaldirection(leftcoilshownas
anexample,Fig.3a).Notethatthesetracesweremean-corrected
(suchthattheaverageheadpositionovereach15minperiodwas
settozero)butthatthestandarddeviationsofthesemeanswere
0.25,0.25and0.26mmfortheX,YandZdimensionsrespectively.
Acrossallcoils,wefoundthestandarddeviationsoflocationsover
timetobebelow0.22mmforanycoilsinanydimensions(Fig.3b).
Themaximalabsolutechangesinthecoillocationswere0.69,0.5
and0.75mmfortheleft,nasion,andrightfiducialrespectively(the
correspondingminimalchangeswere0.06,0.11,and0.06mm).All
ofthemaximawereintheZ(up-down)dimension.Wereasonthat
theexplanationfortheslightlylargerabsolutechangesand
stan-darddeviationsinthisdimensionisthattheheightofthehead-cast
insidethedewarmaychangeslightlyoverthecourseofatrial,e.g.
becausethesubjectrelaxesandthereforeslouchesandloses
pos-turemore.Wealsosuspectthatthereisslightlylowersensitivity
intheZaxis(seephantomdatainFig.2e)whichcouldbedueto
thesensorconfiguration(seeDiscussion).
3.3. Datareproducibility
InFig.4weshowrecordingsfromasinglesubjectperforming
repeatedrighthandbuttonpressesover multiplesessions
con-ductedover severaldays(Experiment2).Thebeamformerpeak
from11/12sessions(consistingof180trialseach)fellonthesame
three 1mm3 grid locationswhile one fell more dorso-laterally
whenconstrainedtothesamecontralateralhemisphereasthe
oth-ers.
4. Discussion
Wehavedevelopedanovelmethodforbuildingflexibleand
subject-specific MEG head-casts to stabilise the head during
recording.Thismethodmakesuseofthesubject’sMRIimageboth
tobuildthehead-castby3Dprintinganimageoftheheadshape,
andtoco-registertheMEGandMRIdata.Wefindthatusingthis
technique for head-castdesign, thewithin-session head
move-mentmeasuredwithasinglesubjectrecordedoverseveralsessions
rangesfrom0.06 to0.75mmwhen measuredover an
approxi-mately15minperiod.We estimatethemaximalco-registration
errorduringthesemeasurementstobearound1.2mm.
Thehead-castsweredesignedtoimprovebothsubjectcomfort
andsafety.Bymakingthecastsflexibleandaddingearflaps,we
madeiteasiertoenter andexitthedewar,minimizingtherisk
ofgettingstuckor requiringassistance. Additionally,we added
eyeholeswhichenablesubjectstoseeandthereforeparticipate
inexperimentsusingvisualstimuliand/oreyetracking.Together,
thesefeaturesmakethehead-castslessintimidatingtowearand
openupthepossibilityofawiderrangeofexperiments.
Impor-tantlythehead-castsdonotobstructbreathing,vision,ortalking
althoughhearingmaybemildlycompromised.Wehavenotfound
thesehead-caststoinduceanxietyorclaustrophobia.However,we
screenedforthesebyaskingsubjectsaboutclaustrophobic
vulner-abilitypriortoanytesting.
Theothermajordifferencebetweenthisgenerationof
head-castsandtheprevious,isthatthe3Dprintisnowbaseddirectly
ontheMRIimageeliminatingtheneedforopticalscanning.We
optimisedanMRIacquisitionsequencetoeliminatedistortionson
thesurfaceofthehead.Themanufacturingprocessisnonetheless
notcompletelystraightforward.Whilstsomehead-castsfitvery
well,othersrequireremovalofsectionsthatconstitutepressure
pointsonthehead,typicallyneartheeyeholesandtemples.This
seemstobemorepronouncedinsubjectswithlongerhair.
WithrespecttotheMRIimagingsequenceused,our
require-mentsinselectingtheoptimalsequencewereasfollows:1)tohave
moderatelyhighresolution(1mmisotropic),withalargefieldof
viewinordertobeabletodistinguishthescalpwithsufficient
spa-tialspecificity;2)tomaximiseSNRefficiency,and3)tominimise
anyartefactthatmightappearoutsideofthebrain.Themost
com-monsourceofuncontrollableartefactinMRIisparticipantmotion.
Focalmotionduringdataacquisitionleadstodistributedartefact
outsideofthebrain,whichitwasessentialthatweavoidedby
keep-ingthesequenceasshortaspossible.However,accelerationoptions
werelimitedsincewedidnotwanttouseparallelimagingto
accel-eratetheacquisition,asthisapproachinherentlyleadstoaliasing
thatneedstobeunfolded.Therefore,wechosetofocussolelyon
Fig.4. Consistencyofdatafeaturesacrossfourseparatescanningdays.Colouredspheresrepresentbeta(15–30Hz)reboundpeaksfromExperiment2.Thepeaklocations reflectthemaximumchisquarestatisticwhencomparingpre-buttonpressdata(−1500–−1000ms)topost-buttonpressdata(500–1000ms)acrossa20mmradius, 1×1×1mm3resolutionspherecentredaroundtheaverageleftprimarymotorcortexpeak(−34,−30,52).Notethatthesolutionswerenotconstrainedbythemeshas reconstructionwasvolumetric.Datashownaresmoothedusingan8mmkernel.
hasnopreparationpulses(unlikeMPRAGE-likeacquisitions),itcan
continuouslyacquiredatawithveryshortTR(7.96mshere)giving
ithighSNRefficiencywithaminimalscantimeofjust3min42s.
Pilotingshowedthatthisapproachwasmorethanadequatefor
MEGhead-castdesign.
Akeypointisthatthehead-castscanbeusedtomaintainthe
headinanyposition–basedonthepositioningofthedigitalscalp
outlinewithinthedewar-evenwhenthatmeansthatoversmall
regionsthereisnofoambetweentheheadandthedewar(andthe
distancetothesensorsisminimized).Butthisofcoursealsomeans
thatthisparticularpositioningoftheheadwillnotbeoptimalfor
allexperiments.Itisworthpointingoutthatthedistancecylinder
lengthvariesasafunctionofheadsize;thesmallerthehead,the
moreoffsetfromthetopisneededtoensurevision.
Withrespecttothesubjectiveexperienceofwearingthe
head-cast,we findthatsubjectsexperiencethemasconstrainingand
unusualatfirst,butthattheyquicklygetaccustomedtothe
expe-rience(usuallyafterafewrecordings),andtheyimproveatentering
andexitingthedewarefficiently.Multiplesubjectshaveremarked
that itis obvioustothem when thehead-castisfit incorrectly
whenenteringthedewar,butnotnecessarilybefore.Wehavealso
observed thatsomeexperienced subjectsfindit easier torelax
whilebeingscannedwhenwearingahead-castastheydonothave
improve-ment,aspreviousmethodshavereliedonself-stabilization(e.g.
withbitebarstoholdtheheadinposition(Adjamianetal.,2004;
Muthukumaraswamy,2013;Singhetal.,1997))whichinducesa
riskofincreasedmuscleactivityandconcomitantartefacts(Kumar
etal.,2003;Muthukumaraswamy,2013;O’Donnelletal.,1974; Whithametal.,2007).
Themain advance of this head-cast approach is that unlike
otherco-registrationminimization approaches,thespecification
offiducialpoints,andextractionofscalpsurfacebasedonthesame
originalMRIscansimultaneouslyminimizesco-registrationerror
andheadmovement.Inturn,thisimprovesthereproducibilityof
data(Fig.4).Inpreviouswork(Troebingeretal.,2014b)wehave
shownthatthereductionofwithin-sessionmovementfrom5to
1mmgivesrisetoaneffective5foldincreaseinSNR.Notably,high
reproducibilityimplieshighprecisionbutnotnecessarilyaccuracy.
However,thehighSNRrecordingsmeanthatthisframeworkcan
beusedtodirectlytestbetweendifferentforwardmodels(e.g.the
headindifferentpositions,see(Lópezetal.,2012))deliveringan
accuracymeasurethatencompassesthecompletesource
recon-structionpathway.
Anumberof caveatsremain.First,weaddresstheincreased
uncertaintyofcoillocalisationintheZdimensionasobservedwith
increasederrorin phantom measurements(Fig.2e). Thiscould
eitherbeduetotheinternalalgorithmusedtolocatethefiducial
coilsbasedontheirmagneticsignatureorsimplythemovement
ofthescanner-chair.Second,theco-registrationestimatebased
onthereferencecoil (Fig.2c)mayhavebeenpessimisticasthe
tapeholdingthereferencecoil inplaceonthesideofthenose
extendedbeyondthecoilandwaseasilytuggedonbythe
head-cast.Additionally,thelocationofthereferencecoilwasbothbelow
andoutsideofthedewar,meaningthatitwouldprovideafurther
challengetotheinternalMEGcoillocalizationprocedure.
More-over,prospectivemotioncorrectionmethodswhereasmalloptical
markeristrackedwithsub-micronmovementandsub-degree
rota-tionprecisionhasshown thatplacingthemarkeronthebridge
ofthenoseisunstable,asuncorrelated movementbetweenthe
markerandthebraincanbeobserved,likelyduetomalleabilityof
theskin(Toddetal.,2015).
Asmentionedperhapsthemostpernicioussourceoferrordue
tothesedevicesismovementofthesubject’sheadrelativetothe
head-cast.Inthiscasethefiduciallocationswouldappearstable
overtimewhilst,forexample,thesubjectwasslowlyslippingout
ofthecast.BasedonourreproducibilitymeasurementsinFig.2c
therefittingofthecastovertimedoesnotseemtobeaproblem,
buttheremaybesomesubjects(duetotheshapeoftheirheads)
whocanslidedownwardswithintheheadcastwithouthead-cast
movement.Inthefuturewewillbeginusinga4thcoil(attachedto
thehead)formoreroutinemeasurementsinordertoquantifythis.
Giventhatthebrainissuspendedincorticospinalfluidinsidethe
skull,itmustbeacknowledgedthatitremainsambiguouswhether
thedifferencebetweenthebrainlocationwhilesupine(duringthe
MRIscan)andsitting(duringtheMEGscan)couldbeaffectingour
estimates.Thereisariskthatwhentheheadchangesorientation
withrespecttogravity,thebrainshiftswhenthedensityor
thick-nessoftheCSFlayerbetweenthebrainandtheskullchanges.Ithas
beenapproximatedthatthethischangeinthicknessis∼30%which
equatestoapproximately1mm(Hilletal.,1998;Riceetal.,2013).
Weemphasizehoweverthatusinghead-castswhilesubjectsare
supineremovestheabilitytousegravitytoexitthedewar,causing
thesafetytobecompromised.Althoughitwouldbeinterestingto
directlyquantifytheseshiftsthoughsuchcomparisons,wedecided
nottoduetothesafetyissuesoutlinebelow.
Otherpotentialdataacquisitionproblemswhichwepositthat
thehead-castssolvetoadegreebutwhichwehavenotformally
testedaretomuscleartefacts(Muthukumaraswamy,2013),
par-ticularlywhenusingbite-bars (Adjamianetal.,2004),andslow
within-sessiondrifts(Stolketal.,2013).
Moreover,wehaveextendedtheprototypedesignsuchthatit
canaccommodatesubjectwithlongorthickhair(Supplementary
Fig.1).Thisextendstheusefulnessofthesedevicesandmeansthat
alargersegmentofthepopulationcanbescanned.Weareworking
ontestingwhetherthismodificationaffectsheadstabilization,
re-positioning,orinanywayintroducesunknownerrors.
Theresultsofthepresentstudysuggestthatemploymentof
theindividualflexiblehead-castsforMEGrecordingsprovidean
accurateandreliablemethodofsafelystabilizingthehead
loca-tionduringMEGrecordings,andforco-registeringMRIanatomical
imagestoMEG functionaldata.Thisdesign isideallysuited for
studieswhichrequiresensitivelongitudinalMEGmeasurements.
5. Safetyprocedures
Anyhead-castsposeasignificantsourceofriskofinjuryto
sub-jectsifusedincorrectly.Becausethehead-castsaredesignedtofit
thesubject’sheadinternallyandtheMEGdewarexternally,the
participant’sheadisfirmlyfixedinsidethedewarduringscanning.
ThismeansthatanyunexpectedmovementofthechairorMEG
systemhasthepotentialtocausesevereneckinjury.Ourprimary
safetymeasureisthereforetoensurethatneitherthechairnor
thedewarismovedwhilethesubjectiswearingahead-cast.This
meansthat theinitialpositioningof thesubject(aswellasany
subsequentadjustmentstotheheightorangleofthechair)only
takesplacewhenthesubjectisnotinsidethescannerwearinga
head-cast.Toenterorexitthedewar,thesubjectthereforeslides
inandoutoftheseatunassisted.Inourexperience,thistakessome
practicebutiseasilyandquicklymastered.However,thismeans
thatonlyhealthy,agilevolunteersubjectsaresuitableforhead-cast
scanning.Inordertoensuremaximalcomfortandsafetyof
partici-pants,wehavedevelopedasetofsafetyprocedurestobefollowed
byallresearcherscarryingoutMEGscansinvolvinghead-casts.We
alsoscreensubjectstoavoidscanningparticipantswith
claustro-phobia,andplaceapanicbuttoninsidethemagneticallyshielded
roomshouldthesubjectwish,atanytime,tostopscanning.
Weadvisethatonlyauthorisedpersonnelareallowedtoscan
volunteerswithahead-cast.
Forthesereasonswehavedecidednevertousethehead-cast
withasubjectinsupinepositionwheretheconsequencesof
unex-pectedrelativemovementbetweenthedewarandthebedcould
bemuchmoreserious.
We refertooursafety guidelines,standard operating
proce-dures,trainingguide,volunteerguide,andemergencyprocedures
availableontheMEGcommunitywebsite(http://megcommunity.
org/ under instrumentation>peripherals>subject stabilization)
whichalsocontainsalinktoaninstructionvideoforexperimenters.
Conflictofinterest
WehavereadtheSocietyforNeuroscience’spolicyonconflictof
interestanddeclarethefollowinginterests:MLholdsapositionina
company(ChalkStudiosLtd)thatproducesthehead-castsreported
inthiswork;hetookpartinthedesignandmanufactureofthe
head-castsbutplayednopartinthedataanalysis.Theotherauthors
declarenocompetingfinancialinterests.
Acknowledgements
TheauthorsgratefullyacknowledgefundingfromtheWellcome
Trust,theMedicalResearchCouncilandEngineeringandPhysical
SciencesResearchCouncilgrantMR/K6010/86010/1,theMedical
BBSRCresearchgrant BB/M009645/1.MJB isfunded by a
Med-icalResearch Council New InvestigatorGrant (MR/M006301/1).
The Wellcome Trust Centre for Neuroimaging is supported by
corefundingfromtheWellcomeTrust091593/Z/10/Z.Theresearch
leadingtotheseresultshasreceivedfundingfromtheEuropean
ResearchCouncilundertheEuropeanUnion’sSeventhFramework
Programme(FP7/2007-2013)/ERCgrantagreementno616905.
AppendixA. Supplementarydata
Supplementarydataassociatedwiththisarticlecanbefound,in
theonlineversion,athttp://dx.doi.org/10.1016/j.jneumeth.2016.
11.009.
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