Multiple sclerosis (MS) is a chronic, demyelinating, degenerative

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1 Dign Intervent Riol 2005; 11: Turkish Soiety of Riology 2005?????????????????????? NEURORADIOLOGY ORIGINAL ARTICLE The effetiveness of mgnetiztion trnsfer tehnique in the evlution of ute plques in the entrl nervous system of multiple slerosis ptients n its orreltion with the linil finings Köksl Atly, Hlun Brış Diren, Serkn Gelmez, Lütfi İnesu, Murt Terzi PURPOSE To etermine the vlue of mgnetiztion trnsfer (MT) imging in the evlution of ute plques, whih use linil finings in the rin mgneti resonne (MR) imges of ptients with relpsing-remitting multiple slerosis, n its orreltion with the linil finings. MATERIALS AND METHODS Forty ptients with relpsing-remitting multiple slerosis were inlue in the stuy. They were eing followe-up for the ignosis of relpsing-remitting multiple slerosis se on MDonl s riteri. To evlute the ute plques of the ptients, their T1- weighte spin eho sequenes were ivie into 3 groups: preontrst n postontrst MT imges (group 1), postontrst MT imges only (group 2), n preontrst n postontrst non-mt imges (group 3). The sensitivity n positive preitive vlues were lulte to etermine the orreltion etween the ptients onsiere to hve h ttks n the ute plques etete uring MR imging exmintions with T1-weighte spin eho. RESULTS After linil exmintions, in 25 of 40 ptients (62.5%), there were neurologil finings suggesting ute ttks. Among the 3 imging groups, there ws signifint ifferene in the numer of ute plques. In group 1 there were totl 30 finings suggesting ute plques; in group 2 33; n in group 3 there were 20. When the orreltion etween the ptients who were onsiere to hve h ttks fter their linil exmintions n the ute plques etete with T1- weighte spin eho exmintions were evlute, the sensitivity n positive preitive vlues were 97% n 100% in group 1, 87% n 78% in group 2, n 65% n 100% in group 3, respetively. CONCLUSION In MS, T1-weighte MT exmintions yiel more relile results for following up the tretment n hnges in the evelopment of the isese. They lso offer more effetive evlution of the ute plques tht use linil finings. Key wors: multiple slerosis rin mgneti resonne imging mgnetiztion trnsfer From the Deprtments of Riology (K.A. H.B.D., S.G., L.İ.), n Neurology (M.T.) Onokuz Myıs University Shool of Meiine, Smsun, Turkey. Reeive 6 Jnury 2005; revision requeste 2 Mrh 2005; revision reeive 24 My 2005; epte 10 June Multiple slerosis (MS) is hroni, emyelinting, egenertive isese, whih generlly strts in young ulthoo in the entrl nervous system (CNS). It is use y geneti n environmentl ftors ting upon utoimmune mehnisms, n progresses with reurrent, funtionl neurologil isorers. Despite welth of stuies, no single metho for efinitive ignosis of MS hs een foun, n s suh, it remins iffiult isese to ignose. Two of the most importnt fetures of the isese re its progression with ttks n the pperne of CNS lesions tht pper t vrious times in vrying white mtter lotions. One of the most ojetive riteri for ignosis of MS, s in mny other iseses, is the riologil imging of CNS lesions. Among the meil imging methos of the CNS, mgneti resonne (MR) imging is the only metho for speifi imging of emyelinting plques (1). With the new MR imging tehniques evelope in reent yers, more etile t hve een quire out the pthologil seline of MS plques. Mgnetiztion trnsfer (MT), whih is one of these tehniques, provies enhne evlution of the ute plques tht use the linil finings of MS n importnt t out the pthologil seline of the isese with quntittive mesurements (2, 3). The purpose of this stuy ws to etermine the vlue of MT imging in the evlution of ute plques, whih use linil finings in the rin MR imges of ptients with relpsing-remitting MS n its orreltion with the linil finings. Mterils n methos Forty ptients (30 femles, 10 mles) who were followe up for the ignosis of relpsing-remitting MS se on M Donl s riteri (4) n were seen in the neurology eprtment etween Deemer 2003 n June 2004 were inlue in the stuy. All the ptients were exmine y neurologists. We reore eh ptient's ge, ge t isese onset, urtion of the isese, initil finings of the isese, neurologil exmintion finings, follow-up time, n numer of totl n per yer ttks. The ffete funtionl systems were etermine oring to the expne isility sttus sle (5). Neurologil efets lsting minimum of 24 hours were epte to represent n ute ttk, epening on either sujetive expressions or ojetive oservtion. Symptoms resulting from infetion, whih inreses oy temperture, were onsiere to e flse ttks (4). Ptients who were onsiere to hve h ute ttks (relpse) or to e reovering from n ute ttk (remission) fter linil exmintions unerwent routine rin MR exmintions. Brin MR imging exmintions were performe in 1.5 T superonutive mgnet MR evie (Mgnetom Symphony Clss Mestro, 137

2 Two investigtors evlute ll of the imges prospetively, n onsensus ws rehe on the finings. In ptients who were onsiere to hve h ttks se on linil exmintions, sensitivity n positive preitive vlues were lulte in orer to evlute the orreltion of ute plques tht were etermine in T1W SE sequenes etween three stuy groups. Sttistil nlysis ws me with Wiloxon signe rnk test, using SPSS 13.0 for Winows n p<0.020 ws epte to e the level of sttistil signifine. Figure Millimetri MS plque jent to the left lterl ventrile trium whih is hyperintense in trnsverse FLAIR () n isointense in trnsverse preontrst non-mt MR imges in 40-yer-ol femle ptient (). There is no pthologil enhnement in the plque re in trnsverse postontrst T1W non-mt MR imge (), ut there is homogenous enhnement in this re in trnsverse postontrst T1W MT MR imge (). 138 Septemer 2005 Dignosti n Interventionl Riology Siemens, Erlngen, Germny), with 6-hnnel stnr he oil, fiel of view (FOV) 24 m, n mtrix 256x256. Aoring to our onventionl MR imging protool, sgittl n trnsverse T2-weighte (T2W) spin eho (SE) (TR: 5710 mse, TE: 103 mse, NEX: 2, slie thikness: 5 mm, slie interposition: 0.5 mm, exmintion urtion: 1.20 minutes), trnsverse proton ensity (PD) (TR: 3270 mse, TE: 14 mse, NEX: 2, slie thikness: 5 mm, slie interposition: 1.5 mm, exmintion urtion: 2.30 minutes), n flui ttenute inversion reovery (FLAIR) (TR: 9000 mse, TE: 114 mse, TI: 2500 msn, NEX: 2, slie thikness: 5 mm, slie interposition: 1 mm, exmintion urtion: 4.20 minutes) sequenes were pplie. T1W SE sequene (TR: 500 mse, TE: 7.7 mse, slie thikness: 5 mm, slie interposition: 1 mm, exmintion urtion: 4.20 minutes) in oronl n trnsverse plnes ws performe twie, efore n fter injetion of 0.1 mmol/kg prmgneti ontrst mteril (Golinium-DTPA, Mgnevist, Shering, Germny). Preontrst n postontrst T1W sequenes were performe with n without MT. In orer to prevent time effet on ontrst enhnement, 20 of the T1W exmintions were strte with MT n the other 20 without MT. Lesions were initilly oserve with preontrst exmintions in sgittl, oronl, n trnsverse plnes. Susequently, for evlution of plques, whih use linil finings, T1W SE sequenes were ivie into 3 groups: preontrst n postontrst MT imges (group 1), postontrst MT imges (group 2), n preontrst n postontrst non-mt imges (group 3). Results Ages of the stuy ptients were etween 20 n 47 yers (men, 33.2 yers), n urtion of isese ws etween 3 months n 15 yers (men, 6.5 yers). The expne isility sttus sle vlues of the ptients were etween 1 n 8 (men, 2.86). Following linil exmintions, in 25 of 40 (62.5%) ptients, there were neurologil finings suggesting n ute ttk h een experiene. Among the rin MR imging of the three groups, T1W SE sequenes revele signifint ifferene in the numer of ontrst enhning ute plques (p<0.020). The numer of imges onsistent with ute plques ws 30 in group 1, 33 in group 2, n 20 in group 3. Imges from one ptient in group 1 (who ws onsiere to hve h n ute ttk oring to linil exmintions) revele no finings onsistent with ute plques. Five hyperintense ppernes tht were evlute to e ute plques in group 2 were lter etermine to e rtifts seonry to flse enhnement ue to MT tehnique when exmine with preontrst MT imges. A totl of 10 ute plques, whih were not etete in group 3, showe homogenous enhnement in postontrst MT imges (Figure 1). Among the ute plques foun in group 1, 15 were in periventriulr white mtter, 10 were in the entrum semiovle, three were in the ereellr peile, n two were in the orpus llosum (Figure 2). Among the ute plques, whih were not etete in group 2, five were in periventriulr white mtter, two were in the entrum semiovle, two were in the orpus llosum, n one ws lote in the ereellr peile (Figure 3). Atly et l.

3 Figure 2 -. Millimetri MS plque jent to the right lterl ventrile frontl horn whih is hyperintense in trnsverse FLAIR () n milly hypointense in trnsverse preontrst non-mt MR imges in 42-yer-ol mle ptient (). There is no pthologil enhnement in the plque re in trnsverse postontrst T1W non-mt MR imge (), ut there is homogenous enhnement in this re in trnsverse postontrst T1W MT MR imge (). In two of 15 ptients who were onsiere to e remitting fter linil exmintions, three suspete hyperintense ppernes were oserve in white mtter jent to the lterl ventrile in postontrst MT imges, ut when preontrst MT imges were evlute, the hyperintense ppernes were unerstoo to e rtifts seonry to the MT tehnique. In 15 ptients postontrst MT imges, there were not ny pthologilly enhning lesions. When the orreltion etween the ptients who were onsiere to hve h ttks fter their linil exmintions n the ute plques etete with T1W SE exmintions of ll three groups ws evlute, the sensitivity n positive preition vlues were 97% n 100% in group 1, 87% n 78% in group 2, n 65% n 100% in group 3, respetively. In routine rin MR exmintions of ll of ptients, exept for ute plque res, there were multiple, hyperintense (some of them with teneny to olesene), emyelinting foi in the white mtter res. These were etermine to e intive, hroni glioti res. Disussion MS is importnt euse of its notle prevlene mong neurologil iseses, hroni progress, n the ft tht it ffets young ults. The high moriity rte of MS ontriutes to its importne mong neurologil isorers in young ults in vne ountries (6). Twenty perent of ptients eome erien n nother 20% epen on wheel hirs 15 yers fter isese onset. Despite tehnologil vnes in ignostis, no single metho for efinitive ignosis exists. Therefore, ignosis of MS through the orreltion of linil, lortory, n imging finings is still the most wiely epte pproh. The most effetive molity for riologil imging of lesions is MR imging, whih is one of the most ojetive tools for the ignosis (1). The lesions in MS re suivie into two types: ute n hroni plques, oring to the stge of the isese. As the tretment pln hnges long with the stge of the isese, isrimintion of plques with MR exmintion is very importnt. Bse on the results of long-term stuies n linil experiene, the existene of just one ontrst-enhning lesion is onsiere to e enough to strt tretment (7). Contrst enhne T1W exmintions re known to e superior to oth linil n non-ontrst (PD n T2W) exmintions in etermining MS tivity (8). There re severl methos use to improve oservtion of ontrst enhne ute plques in T1W exmintions. One of these methos is to inrese the ose of ontrst mteril ( mmol/kg), ut this is n expensive metho (9). Another metho is to inrese the time etween injetion n imge quisition (i.e., min. fter ontrst mteril injetion) in orer to inrese the ontrst mteril s effet in the extrellulr region. This is just s effetive s inresing the ontrst mteril ose, ut it lso inreses exmintion urtion (10, 11). Other methos inlue exmintion with 3 mm slie thikness, without interposition (12), n to otin ontrst enhne T1W sequenes with MT tehnique (3, 13). Mgnetiztion trnsfer tehnique hs een use s n importnt ritil MR tehnique to etermine potentil hnges in myelin sine In this tehnique, rel mgneti properties of tissues re ffete n ontrst/noise rtio is inrese inste of ontrst mteril kinetis (3). The proper riofrequeny prepulse t the eginning of the exmintion seletively sturtes protons in tissue proteins, ell memrnes, n protons oun to other mromoleules in the wter proton pool. Beuse the min riofrequeny pulse n not stimulte the sturte Volume 11 Issue 3 Mgnetiztion trnsfer in multiple slerosis 139

4 Figure 3 -. Millimetri MS plque jent to the right lterl ventrile whih is hyperintense in trnsverse FLAIR () n isointense in trnsverse preontrst non-mt MR imges in 40-yer-ol, femle ptient (). There is inistint enhnement in the plque re in trnsverse postontrst T1W non-mt MR imge (), ut homogenous enhnement in this re in trnsverse postontrst T1W MT MR imge (). Also, there is liner signl inreses jent to oth lterl ventriles in pre- n postontrst MT imges seonry to rtifts ue to the exmintion tehnique. protons, equte eho n not e ollete from norml tissues n these res re seen s hypointense (2, 3). Beuse of the high onentrtion of mromoleules in myelin, this ffet is quite prominent in white mtter in the rin. Also, with this tehnique T1 relxtion time reution effet of ontrst mteril in pthologilly enhning tissues eomes more prominent n these res pper to e more hyperintense thn in exmintions without MT. Owing to these properties of the tehnique, in ontrst enhne T1W exmintions, the ontrst/noise rtio etween pthologil n norml tissues tht show signl erese s well s the enhnement of the lesions eomes more prominent (2, 10, 13). Finelli et l. showe tht signl intensity of enhning pthologil lesions 140 Septemer 2005 Dignosti n Interventionl Riology inreses 10% n ontrst/noise rtio inreses 108% with MT tehnique (13). In stuy of 31 ptients, Gur et l. showe tht the numer of pthologilly enhning ute plques ws totl of 65 in T1W MT n totl of 52 in T1W non-mt imges. In T1W non-mt imges, totl of 13 ute plques in 7 ptients were not etete, n those ptients were onsiere to e remitting (2). The mjor prolem in exmintions with MT tehnique is tht signl inreses in T1W imges, whih re similr to pthologil enhnement, n e seen. For this reson, in evlution of tive lesions seen in mny iseses, inluing MS, flse positive results re high n positive preitive vlue is low with MT tehnique (3, 10). However, these signl inreses lmost lwys n e seen in preontrst MT exmintions, n this mkes isrimintion esier (3). For this reson, either pre- or postontrst MT imges shoul e evlute together (3), or sutrte new imges shoul e forme (2). Srnelli et l. showe in stuy inluing 10 relpsing-remitting MS ptients tht in the group in whih pre- n postontrst MT imges were evlute together, totl of 52 ute plques were foun, the exmintion sensitivity ws 96%, n the positive preitive vlue ws 100% (3). However, in the group in whih only postontrst MT imges were evlute, totl of 50 ute plques were foun, n the exmintion sensitivity ws 93%, with positive preitive vlue of 73% (3). Gur et l. oserve totl of 52 ute plques in the evlution of postontrst T1W non-mt imges n totl of 62 signl inreses onsistent with ute plques in imges forme y sutrtion of pre- n postontrst T1W non-mt imges (2). In group 1 of our stuy, pre- n postontrst MT imges evlute together revele totl of 30 ppernes onsistent with ute plques, while in group 2 only postontrst MT imges were evlute reveling totl of 33, n in group 3 only postontrst non-mt imges were evlute, n totl of 20 were etete. When the orreltion etween the ptients who were onsiere to hve h ttks fter linil exmintions n the ute plques etete with T1W spin eho exmintions were evlute, the sensitivity n positive preitive vlues were 97% n 100% in group 1, 87% n 78% in group 2, n 65% n 100% in group 3, respetively. Eight hyperintensities tht were thought to e ute plques in evlution of only postontrst MT imges (group 2) were etermine to e seonry to rtifts ue to exmintion tehnique when pre- n postontrst MT imges (group 3) were evlute together. In previous stuies, sutrtion tehnique ws proven to e more useful in non-mt imges thn MT imges, n tht in orer to sutrt without rtifts, ptients nee to e solutely motionless n slies shoul pss extly from the sme level, whih turns out to e restriting ftor for the use of this tehnique (2, 3). With this knowlege in hn, we trie to etet flse enhnement y evluting pre- Atly et l.

5 n postontrst MT imges together in our stuy (Figure 3). Quntittive MT stuies (MT rtio, MT histogrm urve, n MT properties of norml white mtter) in reent yers hve ontriute to inresing the importne n usge of the tehnique, in prtiulr, y reveling importnt t out the heterogenous seline of MS. Disrimintion of eem n emyelinting res n e me y lulting MT rtios of the lesions in MS (10, 14). Petrell et l. showe in stuy tht MT rtios of homogenous enhning lesions re higher thn rim enhning or nonenhning plques (15). Low MT rtios of nonenhning or rim enhning plques proly hnge epening on the egree of myelin loss. In the sme stuy, MT rtios in the enter of rim enhning lesions were eresing ue to myelin loss n were higher in the periphery of the lesion ue to inflmmtion; this fining prove tht MT rtios re importnt in unerstning the pthologil seline of MS lesions (15). Postmortem stuies in MS plques etermine tht MT rtios in plque res erese ue to emyelintion n xonl loss, ut inrese ue to lte remyelintion (16). MT rtios etete in norml white mtter res of MS ptients provie importnt quntittive t out tissue mge, whih is useful in enlightening the omplex pthologil proess of the isese. In omprison with helthy ontrol groups, MT rtios in plque res n norml white mtter signifintly erese in MS (17). Rovris et l. lulte the reution of MT rtios in norml white mtter n their results were 4.9% in seonrily progressive MS ptients, 3% in overll relpsing-remitting MS ptients, 2.7% in erly relpsing-remitting MS ptients, n 2.5% in enign MS ptients, in omprison with helthy ontrol ptients. It hs een emonstrte tht in ll MS types, n espeilly in seonrily progressive MS ptients, there re wiespre normlities in not only plque res ut norml white mtter whih the isese ffets s well (14). In this sme stuy, orreltion etween the men reution of MT rtios in norml white mtter n T2 lesion lo, n the expne isility sttus sle vlue ws emonstrte (14). Guo et l. showe tht MT rtios in norml white mtter res jent to MS plques re higher thn other norml white mtter res, n re lower thn plque res (18). This is n importnt fining proving tht myelin hs een mge in MS plques n white mtter res jent to the plques. In onlusion, T1W MT exmintions in MS yiele more relile results in following up the tretment n the hnges in the evelopment of the isese. They lso offere more effetive evlution of the ute plques, whih use linil finings. For this reson, it woul e more pproprite to otin postontrst T1W SE exmintions with MT tehnique in imging of tive lesions in emyelinting iseses, espeilly MS, tht use pthologil finings in white mtter. Quntittive MT stuies in reent yers inrese the importne n usge of the tehnique, in prtiulr, y reveling importnt t out the heterogenous seline of MS. Referenes 1. 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Mgnetiztion trnsfer imging. J Neurol Si 2000; 172: Petrell J, Grossmn R, MGown J, Cmpell G, Cohen J. Multiple slerosis lesions: reltionship etween MR enhnement pttern n mgnetiztion trnsfer effet. AJNR Am J Neuroriol 1996; 17: Shmierer K, Srvilli F, Altmnn DR, Brker GJ, Miller DH. Mgnetiztion trnsfer rtio n myelin in postmortem multiple slerosis rin. Ann Neurol 2004; 56: Troulsee A, Dehmeshki J, Peters KR, et l. Disility in multiple slerosis is relte to norml ppering rin tissue MTR histogrm normlities. Mult Sler 2003; 9: Guo AC, Jewells VL, Provenzle JM. Anlysis of norml-ppering white mtter in multiple slerosis: omprison of iffusion tensor MR imging n mgnetiztion trnsfer imging. AJNR Am J Neuroriol 2001; 22: Volume 11 Issue 3 Mgnetiztion trnsfer in multiple slerosis 141