Abstract
We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.
Highlights
VGMisimreapgreseanrtedgibvyena.liSgthatbgilrietyenocfoblorauirn; vvoolluummeere(edquuctiivoanlsen(vtotlouma evochluamngee cch0%an) gbey wca0s%e )debmyownsatrramtincgollaocukrso;f (v2o–lu6m) Fercohmangleef;t(3t)oErxiegmhtp:laMryRI-1), magnetic resonace imaging (MRI)-c2a)s,eanddemVoGnsMtra;t(in2g) Etwxeominpalactriyvecalesseiodnes,meoanchstrloactaintegd laclcokseoftovothleumpoestcehriaonrgheo; r(n3)oEf xtheemlpaltaerrayl case demovnesnttrraictlien.gTthweyo sinhoawctivloewlevsioolunms,eeaincchrelaosceatbeedlocwlostheetocutth-oeffpopsotienrtio(lrighhotrnyeollfowtheinlaVteGraMl)v; e(n4)tricle
Our analysis suggests that this is the case for all different subtypes of active lesions (NL, chronic enlarging lesions (CEL), chronic shrinking lesions (CSL)) and for one of the 3 subtypes
We focused our analysis on non-enhancing multiple sclerosis (MS) lesions, it is highly likely that resolution of edematous tissue changes have contributed to shrinkage in lesions and possibly in the surrounding tissue
Summary
VGMisimreapgreseanrtedgibvyena.liSgthatbgilrietyenocfoblorauirn; vvoolluummeere(edquuctiivoanlsen(vtotlouma evochluamngee cch0%an) gbey wca0s%e )debmyownsatrramtincgollaocukrso;f (v2o–lu6m) Fercohmangleef;t(3t)oErxiegmhtp:laMryRI-1), MRI-c2a)s,eanddemVoGnsMtra;t(in2g) Etwxeominpalactriyvecalesseiodnes,meoanchstrloactaintegd laclcokseoftovothleumpoestcehriaonrgheo; r(n3)oEf xtheemlpaltaerrayl case demovnesnttrraictlien.gTthweyo sinhoawctivloewlevsioolunms,eeaincchrelaosceatbeedlocwlostheetocutth-oeffpopsotienrtio(lrighhotrnyeollfowtheinlaVteGraMl)v; e(n4)tricle. TheyEsxheomwpllaorwy nveowlumleseioinnscr(eNasLe) b(reeldowinthVeGcMut-aonffdpnoeiwnt (inligMhtRyI-e2l)lolwocaitnedVGinMth);e(4r)igEhxt ecmenptlraurmy new semiovale; (5) Exemplary chronic enlarging lesions (CEL) (red in VGM and enlarged in MRI-2) lesiondsor(sNalLt)o(rpeodsteinrioVrGhMornaonfdthneewrigihnt MlatRerIa-l2v) elontcraicteled; (i6n) tEhxeemripglhatrycecnhrtorunimc ssherminikoinvgallee;si(o5n)sE(xCeSmL)plary chron(biclueenlinargViGnMg laensidonshsr(uCnEkLen) (irnedMiRnI-V2)G; (M7a–a7nbd) eEnxleamrgpeladryinNML RthI-a2t)indvoorlsvailngtofpiboesrsteorfiotrhehoorpnticof the rightrlaadteiartaiol nve(n7tar)i.clTeh; e(6)deEpxeenmdepnltaroycccihpriotanlicarseharisnhkoiwngs lseisginoanlss (oCf SvLo)lu(bmlueediencrVeGasMe (a7nbd); s(h8aru–8nbk)en in MRI-2E)x;e(m7ap–la7rby) CESxLemwpitlharliyghNtLbltuheathainlovoinlvdiicnagtifingbesrhsrionfktahgeeoepffteicctsraadloiantgiobney(7oan)d. TThheeodriegpineanldlyenvitsoibclceipital area slehsoiowns(8saig);nthailss iosfeveonluvmisiebldeeincraeanseeig(h7bbo)u; r(i8nag–s8lbic)eEthxaetmdipdlanroyt cCoSnLtaiwn itthhe loirgihgitnbaluleesihoanlo(8bin).dicating shrinkage effects along beyond the originally visible lesion (8a); this is even visible in a neighbouring slice that did not contain the original lesion (8b) TheyEsxheomwpllaorwy nveowlumleseioinnscr(eNasLe) b(reeldowinthVeGcMut-aonffdpnoeiwnt (inligMhtRyI-e2l)lolwocaitnedVGinMth);e(4r)igEhxt ecmenptlraurmy new semiovale; (5) Exemplary chronic enlarging lesions (CEL) (red in VGM and enlarged in MRI-2) lesiondsor(sNalLt)o(rpeodsteinrioVrGhMornaonfdthneewrigihnt MlatRerIa-l2v) elontcraicteled; (i6n) tEhxeemripglhatrycecnhrtorunimc ssherminikoinvgallee;si(o5n)sE(xCeSmL)plary chron(biclueenlinargViGnMg laensidonshsr(uCnEkLen) (irnedMiRnI-V2)G; (M7a–a7nbd) eEnxleamrgpeladryinNML RthI-a2t)indvoorlsvailngtofpiboesrsteorfiotrhehoorpnticof the rightrlaadteiartaiol nve(n7tar)i.clTeh; e(6)deEpxeenmdepnltaroycccihpriotanlicarseharisnhkoiwngs lseisginoanlss (oCf SvLo)lu(bmlueediencrVeGasMe (a7nbd); s(h8aru–8nbk)en in MRI-2E)x;e(m7ap–la7rby) CESxLemwpitlharliyghNtLbltuheathainlovoinlvdiicnagtifingbesrhsrionfktahgeeoepffteicctsraadloiantgiobney(7oan)d. tThheeodriegpineanldlyenvitsoibclceipital area slehsoiowns(8saig);nthailss iosfeveonluvmisiebldeeincraeanseeig(h7bbo)u; r(i8nag–s8lbic)eEthxaetmdipdlanroyt cCoSnLtaiwn itthhe loirgihgitnbaluleesihoanlo(8bin).dicating shrinkage effects along beyond the originally visible lesion (8a); this is even visible in a neighbouring slice that did not contain the original lesion (8b)
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