title: Unraveling the relationship between regional gray matter atrophy and pathology in connected white matter tracts in long-standing multiple sclerosis.
abstract: BACKGROUND
  Gray matter (GM) atrophy is common in multiple sclerosis (MS), but the relationship with white matter (WM) pathology is largely unknown. Some studies found a co-occurrence in specific systems, but a regional analysis across the brain in different clinical phenotypes is necessary to further understand the disease mechanism underlying GM atrophy in MS. Therefore, we investigated the association between regional GM atrophy and pathology in anatomically connected WM tracts.
  
  
  METHODS
  Conventional and diffusion tensor imaging was performed at 3T in 208 patients with long-standing MS and 60 healthy controls. Deep and cortical GM regions were segmented and quantified, and both lesion volumes and average normal appearing WM fractional anisotropy of their associated tracts were derived using an atlas obtained by probabilistic tractography in the controls. Linear regression was then performed to quantify the amount of regional GM atrophy that can be explained by WM pathology in the connected tract.
  
  
  RESULTS
  MS patients showed extensive deep and cortical GM atrophy. Cortical atrophy was particularly present in frontal and temporal regions. Pathology in connected WM tracts statistically explained both regional deep and cortical GM atrophy in relapsing-remitting (RR) patients, but only deep GM atrophy in secondary-progressive (SP) patients.
  
  
  CONCLUSIONS
  In RRMS patients, both deep and cortical GM atrophy were associated with pathology in connected WM tracts. In SPMS patients, only regional deep GM atrophy could be explained by pathology in connected WM tracts. This suggests that in SPMS patients cortical GM atrophy and WM damage are (at least partly) independent disease processes.
authors: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, The Netherlands.
authors: Martijn D
authors: MD
authors: Steenwijk
authors: Marita
authors: M
authors: Daams
authors: Petra J W
authors: PJ
authors: Pouwels
authors: Lisanne
authors: L
authors: J Balk
authors: Prejaas K
authors: PK
authors: Tewarie
authors: Jeroen J G
authors: JJ
authors: Geurts
authors: Frederik
authors: F
authors: Barkhof
authors: Hugo
authors: H
authors: Vrenken
mesh_terms: D016880:Anisotropy; D001271:Atlases as Topic; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009929:Organ Size; D066127:White Matter / Q000473:pathology*
keywords: diffusion tensor imaging; gray matter atrophy; magnetic resonance imaging; multiple sclerosis; volumetric magnetic resonance imaging
references: Lancet Neurol. 2008 Sep;7(9):841-51
references: 18703006
references: Brain Connect. 2013;3(3):255-64
references: 23573900
references: Radiology. 2014 Sep;272(3):832-42
references: 24761837
references: Neuroimage. 2006 Jul 1;31(3):968-80
references: 16530430
references: Neurology. 2006 Sep 26;67(6):960-7
references: 17000961
references: Mult Scler. 2013 Oct;19(11):1485-92
references: 23462349
references: Lancet. 2007 Aug 4;370(9585):389-97
references: 17679016
references: AJNR Am J Neuroradiol. 2005 Feb;26(2):341-6
references: 15709132
references: Neuroimage. 2011 Jun 1;56(3):907-22
references: 21352927
references: J Neurol Sci. 2009 Oct 15;285(1-2):268-9; author reply 269
references: 19500803
references: Mult Scler. 2009 Jun;15(6):687-94
references: 19435748
references: AJNR Am J Neuroradiol. 2012 Sep;33(8):1573-8
references: 22499842
references: Lancet Neurol. 2008 Oct;7(10):903-14
references: 18789766
references: Mult Scler. 2015 Sep;21(10):1280-90
references: 25583833
references: Mult Scler. 2014 Feb;20(2):227-33
references: 23858017
references: Neuroimage. 2007 Jan 15;34(2):509-17
references: 17112743
references: J Magn Reson Imaging. 2006 May;23(5):628-36
references: 16565955
references: Mult Scler. 2009 Jan;15(1):36-41
references: 18755823
references: Neurology. 2005 Jul 26;65(2):280-5
references: 16043800
references: J Neurol. 2007 Sep;254(9):1212-20
references: 17361339
references: Neurology. 2003 Apr 8;60(7):1157-62
references: 12682324
references: Arch Neurol. 2009 Feb;66(2):173-9
references: 19204153
references: J Neurol Sci. 2009 Jul 15;282(1-2):47-54
references: 19201003
references: Neurology. 2012 Oct 23;79(17):1754-61
references: 23019265
references: J Neurol Sci. 2009 Jul 15;282(1-2):55-60
references: 19286193
references: Neuroimage Clin. 2013 Oct 14;3:462-9
references: 24273728
references: Mult Scler. 2011 Sep;17(9):1098-106
references: 21586487
references: Neuroimage. 2004 Nov;23(3):1168-75
references: 15528116
references: Brain. 2003 Aug;126(Pt 8):1734-44
references: 12805100
references: Ann Neurol. 2011 Feb;69(2):292-302
references: 21387374
references: Hum Brain Mapp. 2009 Sep;30(9):2852-61
references: 19172648
references: Neuroimage. 2004 May;22(1):353-9
references: 15110026
references: Neuroimage. 2012 Mar;60(1):400-8
references: 22245259
references: Neurology. 1983 Nov;33(11):1444-52
references: 6685237
references: Neurology. 2012 Aug 7;79(6):523-30
references: 22764258
references: Neuroimage. 2009 Mar 1;45(1):60-7
references: 19013533
references: Neuroimage. 1999 Feb;9(2):179-94
references: 9931268
references: N Engl J Med. 2006 Mar 2;354(9):899-910
references: 16510744
references: J Neurol Sci. 2009 Jul 15;282(1-2):61-6
references: 19394969
references: BMC Neurol. 2011 Dec 12;11:153
references: 22152037
references: Curr Opin Neurol. 2013 Aug;26(4):345-52
references: 23812306
references: Ann Neurol. 2008 Sep;64(3):247-54
references: 18570297
references: Neuroimage Clin. 2012 Nov 30;2:120-31
references: 24179765
references: Brain. 2005 Nov;128(Pt 11):2705-12
references: 16230320
references: J Magn Reson Imaging. 2010 Jul;32(1):223-8
references: 20575080
references: Ann Neurol. 2008 Sep;64(3):255-65
references: 18661561
references: Mult Scler. 2013 Jun;19(7):904-11
references: 23069877
references: J Neurol Neurosurg Psychiatry. 2008 Nov;79(11):1236-44
references: 18469033
references: Neuroimage. 1999 Feb;9(2):195-207
references: 9931269