a prospective pilot investigation of brain volume, white matter hype..

February2016 Article11 Originalresearch published: 12 February 2016 doi: 10.3389/neur.2016.00011 Frontiers www.rontiersin.orgEdited LiyingZhang, Wayne State University, USA Reviewed Koliatsos,Johns Hopkins University School Medicine,USA Steven Robicsek, University Florida,USA *Correspondence: Alexander Rauscher rauscher@physics.ubc.ca Specialty section: journalFrontiers NeurologyReceived: 15September2015 Accepted: 22January2016 Published: 12February2016 Citation: JarrettM, TamR, Hernndez- TorresE, MartinN, PereraW, ZhaoY, ShahinfardE, DadachanjiS, TauntonJ, LiDKB RauscherA(2016) ProspectivePilot Investigation BrainVolume, White Matter Hyperintensities, HemorrhagicLesions after Mild Traumatic Brain Injury. Front. Neurol. 7:11. doi: 10.3389/fneur.2016.00011 Mtthyptt, ijuyMichael Jarrett RogerTam 2,3 EnedinoHernndez-Torres NancyMartin 4,5,6 WarrenPerera YinshanZhao ElhamShahinfard ShiroyDadachanji JackTaunton Li1,2,3 AlexanderRauscher 1,10,11 UBCMRI Research Centre, University BritishColumbia, Vancouver, BC, Canada, Radiology,University BritishColumbia, Vancouver, BC, Canada, MS/MRIResearch Group, University BritishColumbia, Vancouver, BC, Canada, Radiology,Richmond Hospital, Richmond, BC, Canada, Radiology,Burnaby Hospital, Burnaby, BC, Canada, Radiology,Delta Hospital, Delta, BC, Canada, MedicalImaging Department, St Vincent’s Hospital, Melbourne, VIC, Australia, Neurology,Department Medicine,University BritishColumbia, Vancouver, BC, Canada, SportsMedicine, Faculty Medicine,University BritishColumbia, Vancouver, BC, Canada, 10 Djavad Mowafaghian Centre BrainHealth, University BritishColumbia, Vancouver, BC, Canada, 11 Division Neurology,Department Pediatrics,University BritishColumbia, Vancouver, BC, Canada Traumatic brain injury (TBI) mostcommon neurological disorders. Hemorrhagic lesions whitematter hyperintensities (WMH) radiologicaleatures associated severeTBI. Brain volume reductions have also been observed during monthsollowing injury. conventionalmag- netic resonance imaging (MRI), which may trueeature merelydue limitedsensitivity imagingtechniques used so ar. Moreover, knownwhether volume reductions trauma-relatededema truevolume loss. Forty-ve collegiate-level ice hockey players (20 emales) 15controls emales),40 players underwent 3-T MRI hemorrhages[multi-echo susceptibility-weighted imaging (SWI)], WMH (three-dimensional fuid-attenuated inversion recovery), brainvolume hockeyseason. Concussed athletes underwent additional imaging neuropsychologicaltesting 3days,2weeks, 2monthsater injury. hockeyseason, brain volume reducedcompared 0.32%(p<0.034) wholecohort 0.26%(p<0.09) concussedathletes. Two weeks 2monthsater concussion, brain volume 0.08%(p=0.027) 0.035),respectively. WMHwere signicantly closer interacebetween gray matter whitematter compared signicantchanges WMHover studywere ound microhemorrhageswere detected icehockey. We conclude mildTBI does transientincreases brainvolume newmicrobleeds detectableater concussion. Brain volume reductions appear 2weeksater concussion persistuntil least2months ater concussion. Brain volume reducedbetween icehockey season. Kywod: mTBi,Mri, voum,uptbty-wtd mttyptt February 2016 Article11 Jarrettet al. Prospective Imaging Study ConcussionFrontiers www.rontiersin.orginTrODUcTiOn raumatic brain injury (BI) mostcommon neuro- logical disorders, incidencerates >650/100,000/year changesseen magneticresonance imaging (MRI) hemorrhages,white matter hyperintensities (WMH), brainvolume reduction. Tese eatures severebrain injury mostrequent type acutechanges conventionalimaging Evenmodern MRI techniques highereld strengths, gradientecho MRI susceptibility-weightedimaging (SWI), have detectedhemorrhages concussedpatients. Te absence bleedsmay trueeature limitedsensitivity imagingmethods used so ar. Moreover, microbleeds have necessarilytrauma related Brainvolume reductions have been reported occurbetween acutephases aer BI ollow-upaer several months knownwhether volumechanges trauma-related edema (pseudoatrophy) truevolume reductions. Tese observations considerationsraise some questions related conventionalimaging studies mildBI: rst, moreadvanced imaging [multi-echo SWI optimizedimage reconstruction 3Duid-attenuated inversion recovery (FLAIR) detectmicrobleeds concus-sion? second,does concussion lead acuteincreases brainvolume subsequentdecreases maymimic atrophy evaluatepatients twotime points post injury? Tese questions can datarom beore canonly highrisk mildBI. Here, we worked twoice hockey teams whom we ollowed over one season. cohort,we perormed MRI pre- allplayers 3days,2weeks, 2monthsaer concussion. weused multi-echo SWI microbleeds,3D FLAIR 3D1-weighted scans volumetricMRI. MaTerials wentyemale 25male players (mean age=21.23.1years) rom two Canadian Interuniversity Sports ice hockey teams par- ticipated study.Players received baseline MRI SportConcussion Assessment ool (SCA2)tests Septemberbeore icehockey season Onephysician onenon-physician, both unaliated teams,observed each preseason, regular season, postseasongame, 31games women’steams, respectively. When suspectedconcussion observedrom sideline(signs poorbalance, conusion, physi-cian removed playerrom clinicalevaluation rink,ollowed dressingroom. Concussed players were reerred neuropsycho-logical testing monthsaer concussion. Athletes were imaged aer hockeyseason March.Four non-concussed players completed only one time point wereexcluded. Fieen subjects (six males, nine emales, age 2.3years) rom sameuniversity were enrolled werescanned once. Inclusion criteria controlswere university students matchingage, contactsports, neurologicalcondition. Five additional subjects who did contactsports were scanned our times over 6months healthycontrols volumemeasurements. phantomdesigned qualitycontrol volu-metric measurements Alzheimer’sDisease Neuroimaging Initiative (ADNI) study scannedonce month(10). All sub- jects gave written inormed consent prior study,according BritishColumbia research ethics board HelsinkiDeclaration. im Magnetic resonance imaging data were acquired PhilipsAchieva scannerequipped eight-channelSENSE head coil, including ollowingscans: sagittalthree-dimensional 1-weighted scan 8.1ms, 3.7ms, ip angle acquisitionmatrix=256256160, eld view=256mm256mm160mm, voxel size=1mm1mm1mm, SENSEactor le–rightdirection); sagittalthree- dimensional FLAIR (R=8000ms, I=2400ms, E=337ms, ip angle acquisitionmatrix 160,eld 256mm 256mm 160mm, voxel size=1mm1mm1mm, SENSEactor le–rightdirection 2.5along anterior–posteriordirec- tion); multi-echoSWI using axial3D gradient echo scan (R=36ms, E=6/12/18/24/30ms, ip angle=17, acqui- sition matrix=44022264, eld view=220mm166mm128mm, acquired voxel size=0.5mm0.5mm2mm, reconstructed voxel size=0.5mm0.5mm1mm, SENSEactor 1.2along le–rightdirection) Susceptibility-weightedimaging data were reconstructed oine, individualechoes were averaged optimizecontrast between hemorrhages surroundingtis- sue, assuming R2* relaxation rates whitematter hemorrhage,which leads weightingcoecients 0.12,0.19, 0.22, 0.24, Allother images were recon- structed scannersoware. Te FLAIR images eachcon- cussed subject were registered correspondingSWI scans. Te FLAIR non-concussedplayers were registered baselineSWI scan. All image registration perormedhal-way avoidblurring oneimage more than other.Te SWI FLAIRimages were reviewed tworadiologists (Nancy Martin WarrenPerera) using custom viewing soware. Te radiologists yearsexperience), who were blinded control/playerstatus, concussion status, scans,reviewed scanstogether. Lesions identied con-sensus were digitally marked counted.Possible lesions (ques- tionable bothobservers) were marked subsequentlyreviewed together thirdradiologist (David distancerom corticalgray matter sulcaldepths, one author measured shorteststraight-line distance 3Drom eachTaBle Dmopfomto mofoud (+1bleed) (+1bleed) 1019 1123 Alllesions were WMH, onehemorrhage alreadypresent preseasonscan. missedfollow-up. TaBle outfo potoMri subjtcoud MWhiPoto MWhi 2010 11 16 2232 29 28 2014 13 29 February2016 Article11 Jarrettet al. Prospective Imaging Study ConcussionFrontiers www.rontiersin.orgWMH closestcortical gray matter nearestsul- cal depth, respectively. Lesions were also mapped alairachspace aneregistration electronicalairach atlas (11). Voumwo time point global brain volume changes were estimated based three-dimensional1-weighted scans, using FSL’s SIENA (12–14). SIENA extracts brain skullimages rom twotime point whole-head input data measurespercent brain volume change (PBVC) (15). All PBVC measurements were made against each subject’s baseline scan. sttt Statistical tests ullseason data were perormed using MALAB (2011a, Te MathWorks, Inc., Natick, MA, USA). Volume changes compared baselinewere evaluated ol-lowing groups: concussedplayers allpost-concussion time points, allconcussed players postseason, allnon-concussed players postseason, allsubjects postseason moreWMH (observed allsubjects postseason oneWMH baseline.Comparison controlWMH count baselinewere perormed using Wilcoxonrank-sum test. Repeated measures brainvolume change concussedsubjects were analyzed using mixedefect model StatisticalComputing, Vienna, Austria) (16, 17). Gender, age, SCA2 score, WMHcount eachtime point were included xedefects. resUlTs Over season,11 players were diagnosed concussion.Teir age, gender, brainlesions scores ullcohort 168MRI sessions were perormed during punctuateWMH non-concussedice hockey player Figure1.Te number hemor-rhages eachconcussed subject eachavailable time point Temedian number allhockey players 5.5(median Tenumber WMHexhibited some variability over time signicantassociation concussion.Te non-concussed players similarly showed WMHbetween pre- postseasonscans. Te distance (meanSD) corticalgray matter sulcaldepths Top:T2-weighted FLAIR 20-year-oldnon-concussed male ice hockey player showing punctuate WMH (red arrow heads). Bottom: composite image allWMH players(red, rom 41 players) controls(blue, rom 15 controls) registered standardbrain. February 2016 Article11 Jarrettet al. Prospective Imaging Study ConcussionFrontiers www.rontiersin.org4.33.4mm, respectively. WMH were principally ound rontlobe (75.2%). Te only hemorrhage detected wholecohort had already been present preseasonbaseline scan (subject signicantchanges lesionnum- ber over icehockey season, comparisons lesionnumber

a prospective pilot investigation of brain volume, white matter hyperintensities, and hemorrhagic lesions after mild traumatic brain injury(轻度创伤性脑损伤后脑容量、白质高信号和出血灶的前瞻性研究)

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