diffusional kurtosis detects cortical demyelination in the ... · united st e cuprizone mo ung...

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Edwa 1 Ra INTRO within sponta followe studies Diffusi additio memb micros kurtos develo grey a METH ground demye MR sy ms, sl gradie (MK), Natick region ventra measu RESU histolo confirm with p throug MK an consis treatm compa reduce early s these histolo K // , K reflect comple mice w abnorm ard S Hui 1 , Joseph adiology, Medical ODUCTION: Th weeks after yo aneous remyelin ed by demyelina s have demonst onal Kurtosis Im onal information branes, organelle structural comple is metrics provid opment 15 and in d and white matter HODS: A total of d mouse chow elination. The con ystem. A respirat lice thickness=1 ent direction (0.5 axial (K // ) and ra k, MA) called Diff s of interest (RO al (vHP)) were m urements betwee LTS & DISCUSS ogical stain (Solo m demyelination. previous reports, ghout the entire C nd K throughout stent with the d ment). The axial d ared to that of ed only in the bC stages of patholo axial diffusion ch ogical correlation showed signifi s cortical demye exity not only in with demyelinati malities in grey m Diffusiona h A Helpern, 1 , Dav University of Sout United St he cuprizone mo oung adult mice ation occurs 2,3 . ation associated trated the patho maging (DKI) is a beyond that pro es) and water co exity in the grey des better differe different disease during the demy f 22 (8–10 weeks containing cupr ntrol (NC) group tion-gated 4-shot mm, data matr , 1, 1.5, 2 and 2 adial (K ) kurtosi fusional Kurtosis OIs) at the level manually drawn en CPZ and NC m SION: Illustrated ochrome) for NC . Fig.2 shows the CPZ mice show CC. Also, the non t the entire CC in degree of demy diffusivity λ // was NC, and the K // CC. Since axona ogy (before 4 we hanges (at 10 we n. A striking resu icant changes ( elination and rea white matter, bu on induced by c matter. Fig.2. cuprizregion and c (dorsa are sta al Kurtosis Det vid Guilfoyle 2 , Sco th Carolina (MUSC tates, 3 Dementia R ouse model is a are fed with th In this model, d with a microglia logy of the CC i diffusion MRI tec ovided by DTI 12-1 ompartments (ex y matter in addit ntiation of brain es processes 6,18 . yelination process s old) C57BL/6 m izone (0.2%), (B (n=10) was main t SE-EPI sequen rix=128×128, im .5 ms/μm 2 ). Frac s were derived f s Estimator (DKE of corpus callos using ImageJ mice. P < 0.05 w in Fig.1 are rep C and CPZ mou e ROI measurem wed significantly n-Gaussian diffus n the CPZ mice. yelination seen s increased in th / showed a tren l damage in this eeks of cuprizon eeks of cuprizon ult was that only decrease) in the active glial cells ut also in grey ma cuprizone, demo ROI measuremone treated (CPZs: corpus callosum caudal (pCC)), cl (dHP) and ventra andard deviations. tects Cortical ott Gerum 2 , Caixia C), Charleston, SC Research, Nathan K well characteriz he copper chela demylination is p al response 3,4 . Re in cuprizone mo chnique that exte 4 . Since non-Ga xtracellular and in tion to white ma tissue type, and The main goal o s in the cuprizon mice were used Bis(cyclohexanon ntained on a nor nce was used fo mage resolution= ctional anisotrop from the DKI dat E)) 20 . All paramet um (rostral (aCC ((http://rsb.info.n was considered a presentative b0 im se brain. Soloch ment of different y reduced FA an sion metrics show These diffusion at this phase ( he bCC, but dec nd for decrease model is variabl ne treatment) 7 , th e treatment) can y the non-Gauss e cortex of the accumulation 5 , c atter. In summar onstrating the sig ents of diffusion ) and control (NCm (rostral (aCC), m ortex (CT) and al (vHP)); * p < 0.0 Demyelinatio a Hu 2 , John LaFran C, United States, 2 M Kline Institute, Ora zed animal mode tor cuprizone (b predominantly fo ecently, cortical ouse model 6-11 . H ends DTI and qu aussian diffusion ntracellular), the atter structures. are sensitive to of this study was e mouse model. in this study. In ne) oxaldihydraz mal diet for 10 w r DKI acquisition 234×234 μm 2 , 4 py (FA), mean (M ta set 14 using an tric maps were m C), middle (bCC) nih.gov/ij/). Two- s statistically sig mages, MK maps hrome was perfo brain regions. C nd increased MD wed significantly changes are qua (10 weeks of c reased in the pC , but it was sig le and more prom he exact interpre n only be done w ian diffusion me CPZ mice, wh confirming that ry we observed, gnificant advant metrics for ) mice. Brain middle (bCC), hippocampus 05. Error bars on in the Cupr ncois 3 , Xingju Nie Medical Physics, N angeburg, New Yo el of demyelinat bis-cyclohexanon ound in the corp demyelination h However, no cor uantifies the non- n is believed to a e measures of D Indeed, severa changes in brain s to quantitatively the cuprizone (C zone, Sigma-Ald weeks. All in vivo n. The sequence 4 averages, 30 MD), axial (λ // ) an n in-house softwa masked (MD> 1.5 ), and caudal (pC -tailed t-test wa gnificant. s and the ormed to onsistent D and λ y reduced alitatively cuprizone CC when gnificantly minent in etation of with future etrics MK, ich likely kurtosis metrics for the first time tage of microstru REFERENC Scand Sup 39(6):597-6 Pathol, 11 Neuroimmu Am J Path Neuroimage Reson Med Reson Ima NMR Biome Res, 1283: Exp Neurol Reson Med Biomed, 19 NMR Biom Neuroimage Proc Intl So (2009) Neu (2008) Pro DK, et al. Tabesh A, e ACKNOWL 5R03EB009 Fig.1 (Solo rizone Mouse e 1 , Jens Jensen 1 , Al Nathan Kline Insti ork, NY, United Sta tion 1 . Reproducib ne oxaldihydrazo pus callosum (CC has also been ob rtical diffusion M -Gaussian behav arise from the p DKI can be consi al animal studies n microstructura y characterize th CPZ) treated gro drich) for a peri MRI experiment e parameters we gradient directio nd radial (λ ) diff are programmed 5 μm2/ms) to re CC), cortex (CT as performed to s are sensitive in e, non-Gaussian uctural characte CES: 1. Torkild ppl, 188:72-6; 2. 612; 3. Matsushi (1):107-16; 4. unol, 130(1-2):32 hol,172(4):1053- e, 26(1):132-40; d, 55:302–308; aging, 27(3):446- ed, 18(6):395-40 127-38; 11. Xie , 69(7):704-16; 1 d, 53(6):1432-40 9(2):236-47; 14. med, 23(7):698-7 e, 42(1):122-34; oc Mag Reson M uroimage, 45(2): oc Intl Soc Mag (1999) Magn et al. (2011) Mag LEDGMENTS: T 9711-2 (MFF) an 1. b0 images, ochrome) of control Model li Tabesh 1 , and Ma itute, Orangeburg, ates ble CNS demye one). After remo C), with oligoden bserved 5 . Previo MRI changes hav vior of water diffu resence of diffus idered natural in s have shown th l complexity ass he diffusional kur up (n=12) mice w iod of 10 weeks ts were performe ere: TR/TE=3000 ons 19 and five b fusivity, as well a d in Matlab (The duce partial volu ), hippocampus o assess differe ndicators of cha diffusion change rization using D dsen O, et al. (2 . Ludwin SK. (1 ima GK & More McMahon EJ, 2-45; 5. Skripulet -61; 6. Song S 7. Sun SW, et 8. Wu QZ, et a -53; 9. Merkler 03; 10. Gudi V, e e M, et al. (201 12. Jensen JH, e 0; 13. Lu H, et Jensen JH & He 710;15. Hui ES 16. Falangola Med 15:310.;17. C :386-92; 18. Ch Reson Med, 16: Reson Med, 4 gn Reson Med, 6 This study was s nd 1S10RR02353 MK maps, and l and cuprizone tre aria F Falangola 1,2 , New York, NY, lination will resu oval of the toxin ndrocyte damag ous diffusion MR ve been reported usion, contributin sion barriers (ce ndicators of tissu hat the diffusiona ociated with brai rtosis changes fo were fed a diet o s to induce CN ed on a 7T Agilen 0/30 ms, δ/=5/1 b-values for eac as, mean kurtos MathWorks, Inc ume effects. Brai dorsal (dHP) an ences in the RO nges in structura es in the cortex o DKI, especially fo 008) Acta Neuro 1978) Lab Inves ll P. (2001) Brai et al. (2002) tz T, et al. (2008 SK, et al. (2005 t al. (2006) Mag al. (2008) J Mag D, et al. (2005 et al. (2009) Brai 0) J Neuropatho et al. (2005) Mag al. (2006). NM elpern JA. (2010 S, et al. (2008 MF, et al. (2007 Cheung MM, et a heung MM, et a :3328. 19. Jone 42(3):515-525.20 65(3):823-36. supported by NI 34-01. histological sta ated group. ult n, e RI d. g ell e al n or of S nt 7 ch is c., n d OI al of or ol st, n J 8) 5) n n 5) n ol n R 0) 8) 7) al. al. es 0. H in 3066 Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)

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Page 1: Diffusional Kurtosis Detects Cortical Demyelination in the ... · United St e cuprizone mo ung adult mice ation occurs2,3. tion associated rated the patho aging (DKI) is a beyond

Edwa1Ra

INTROwithin spontafollowestudiesDiffusiadditiomembmicroskurtosdevelogrey aMETHgrounddemyeMR syms, slgradie(MK), NatickregionventrameasuRESUhistoloconfirmwith pthrougMK anconsistreatmcompareduceearly sthese histoloK//, K┴reflectcomplemice wabnorm

ard S Hui1, Josephadiology, Medical

ODUCTION: Thweeks after yo

aneous remyelined by demyelinas have demonstonal Kurtosis Im

onal information branes, organellestructural compleis metrics provid

opment15 and in dand white matter HODS: A total ofd mouse chow elination. The conystem. A respiratlice thickness=1

ent direction (0.5axial (K//) and ra

k, MA) called Diffs of interest (RO

al (vHP)) were murements betweeLTS & DISCUSS

ogical stain (Solom demyelination.previous reports, ghout the entire Cnd K┴ throughoutstent with the d

ment). The axial dared to that of ed only in the bCstages of patholoaxial diffusion ch

ogical correlation┴ showed signifis cortical demyeexity not only in with demyelinatimalities in grey m

Diffusionah A Helpern, 1, DavUniversity of Sout

United St

he cuprizone mooung adult mice ation occurs2,3.

ation associated trated the patho

maging (DKI) is a beyond that pro

es) and water coexity in the greydes better differedifferent diseaseduring the demyf 22 (8–10 weekscontaining cuprntrol (NC) group tion-gated 4-shot mm, data matr, 1, 1.5, 2 and 2adial (K┴) kurtosifusional KurtosisOIs) at the level manually drawnen CPZ and NC mSION: Illustratedochrome) for NC. Fig.2 shows theCPZ mice show

CC. Also, the nont the entire CC indegree of demydiffusivity λ// wasNC, and the K//

CC. Since axonaogy (before 4 wehanges (at 10 wen. A striking resuicant changes (elination and reawhite matter, buon induced by c

matter.

Fig.2. cuprizoregionand c(dorsaare sta

al Kurtosis Detvid Guilfoyle2, Scoth Carolina (MUSCtates, 3Dementia R

ouse model is a are fed with th

In this model, dwith a microglialogy of the CC idiffusion MRI tec

ovided by DTI12-1

ompartments (exy matter in additntiation of brain

es processes6,18. yelination processs old) C57BL/6 mizone (0.2%), (B(n=10) was maint SE-EPI sequenrix=128×128, im.5 ms/μm2). Fracs were derived f

s Estimator (DKEof corpus callos using ImageJ mice. P < 0.05 w in Fig.1 are rep

C and CPZ moue ROI measuremwed significantlyn-Gaussian diffusn the CPZ mice. yelination seen s increased in th/ showed a trenl damage in this eeks of cuprizoneeks of cuprizonult was that onlydecrease) in the

active glial cells ut also in grey macuprizone, demo

ROI measuremeone treated (CPZ)s: corpus callosum

caudal (pCC)), col (dHP) and ventra

andard deviations.

tects Cortical ott Gerum2, CaixiaC), Charleston, SC

Research, Nathan K

well characterizhe copper chelademylination is pal response3,4. Rein cuprizone mochnique that exte4. Since non-Ga

xtracellular and intion to white matissue type, and The main goal o

s in the cuprizonmice were used Bis(cyclohexanonntained on a nornce was used fo

mage resolution=ctional anisotropfrom the DKI dat

E))20. All parametum (rostral (aCC((http://rsb.info.n

was considered apresentative b0 im

se brain. Solochment of different y reduced FA ansion metrics showThese diffusion at this phase (

he bCC, but decnd for decrease

model is variablne treatment)7, the treatment) can

y the non-Gausse cortex of the accumulation5, catter. In summaronstrating the sig

ents of diffusion ) and control (NC)m (rostral (aCC), mortex (CT) and al (vHP)); * p < 0.0

Demyelinatioa Hu2, John LaFranC, United States, 2MKline Institute, Ora

zed animal modetor cuprizone (b

predominantly foecently, cortical

ouse model6-11. Hends DTI and quaussian diffusionntracellular), the

atter structures. are sensitive to

of this study wase mouse model.in this study. In ne) oxaldihydrazmal diet for 10 wr DKI acquisition234×234 μm2, 4

py (FA), mean (Mta set14 using antric maps were mC), middle (bCC)nih.gov/ij/). Two-s statistically sig

mages, MK mapshrome was perfobrain regions. Cnd increased MDwed significantlychanges are qua(10 weeks of creased in the pC, but it was sigle and more promhe exact interpre

n only be done wian diffusion meCPZ mice, wh

confirming that ry we observed, gnificant advant

metrics for ) mice. Brain

middle (bCC), hippocampus

05. Error bars

on in the Cuprncois3, Xingju NieMedical Physics, Nangeburg, New Yo

el of demyelinatbis-cyclohexanonound in the corp

demyelination hHowever, no coruantifies the non-n is believed to ae measures of D

Indeed, severachanges in brain

s to quantitatively the cuprizone (Czone, Sigma-Ald

weeks. All in vivo n. The sequence4 averages, 30

MD), axial (λ//) ann in-house softwamasked (MD> 1.5), and caudal (pC-tailed t-test wa

gnificant. s and the ormed to onsistent D and λ┴ y reduced alitatively cuprizone CC when gnificantly minent in etation of

with future etrics MK, ich likely kurtosis metricsfor the first time

tage of microstru

REFERENCScand Sup39(6):597-6Pathol, 11NeuroimmuAm J PathNeuroimageReson MedReson ImaNMR BiomeRes, 1283:Exp NeurolReson MedBiomed, 19NMR BiomNeuroimageProc Intl So(2009) Neu(2008) ProDK, et al. Tabesh A, e ACKNOWL5R03EB009

Fig.1(Solo

rizone Mouse e1, Jens Jensen1, AlNathan Kline Instiork, NY, United Sta

tion1. Reproducibne oxaldihydrazo

pus callosum (CChas also been obrtical diffusion M-Gaussian behavarise from the p

DKI can be consial animal studiesn microstructuray characterize th

CPZ) treated grodrich) for a periMRI experiment

e parameters wegradient directio

nd radial (λ┴) diffare programmed5 µm2/ms) to reCC), cortex (CTas performed to

s are sensitive ine, non-Gaussian uctural characte

CES: 1. Torkildppl, 188:72-6; 2.612; 3. Matsushi(1):107-16; 4.

unol, 130(1-2):32hol,172(4):1053-e, 26(1):132-40;d, 55:302–308; aging, 27(3):446-ed, 18(6):395-40127-38; 11. Xie, 69(7):704-16; 1d, 53(6):1432-409(2):236-47; 14. med, 23(7):698-7e, 42(1):122-34; oc Mag Reson Muroimage, 45(2):oc Intl Soc Mag (1999) Magn et al. (2011) Mag

LEDGMENTS: T9711-2 (MFF) an

1. b0 images, ochrome) of control

Model li Tabesh1, and Maitute, Orangeburg,ates

ble CNS demyeone). After remoC), with oligodenbserved5. Previo

MRI changes havvior of water diffuresence of diffusidered natural ins have shown thl complexity ass

he diffusional kur

up (n=12) mice wiod of 10 weeksts were performe

ere: TR/TE=3000ons19 and five bfusivity, as well ad in Matlab (The duce partial volu), hippocampus

o assess differe

ndicators of chadiffusion changerization using D

dsen O, et al. (2. Ludwin SK. (1ima GK & MoreMcMahon EJ,

2-45; 5. Skripulet-61; 6. Song S 7. Sun SW, et8. Wu QZ, et a

-53; 9. Merkler 03; 10. Gudi V, ee M, et al. (20112. Jensen JH, e0; 13. Lu H, et Jensen JH & He710;15. Hui ES 16. Falangola

Med 15:310.;17. C:386-92; 18. ChReson Med, 16:Reson Med, 4

gn Reson Med, 6

This study was snd 1S10RR02353

MK maps, and l and cuprizone tre

aria F Falangola1,2

, New York, NY,

lination will resuoval of the toxinndrocyte damagous diffusion MRve been reportedusion, contributinsion barriers (ce

ndicators of tissuhat the diffusionaociated with brairtosis changes fo

were fed a diet os to induce CNed on a 7T Agilen0/30 ms, δ/∆=5/1b-values for eacas, mean kurtosMathWorks, Inc

ume effects. Braidorsal (dHP) an

ences in the RO

nges in structuraes in the cortex o

DKI, especially fo

008) Acta Neuro1978) Lab Invesll P. (2001) Braiet al. (2002)

tz T, et al. (2008SK, et al. (2005t al. (2006) Magal. (2008) J MagD, et al. (2005

et al. (2009) Brai0) J Neuropatho

et al. (2005) Magal. (2006). NM

elpern JA. (2010S, et al. (2008MF, et al. (2007

Cheung MM, et aheung MM, et a:3328. 19. Jone42(3):515-525.2065(3):823-36.

supported by NI34-01.

histological staated group.

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3066Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)