title: Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis.
abstract: OBJECTIVE
  Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters.
  
  
  METHODS
  Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM).
  
  
  RESULTS
  Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p<0.0001) and of kfor (F7,166=105.2; p<0.0001), and by an increase of T1free (F7,166=57.3; p<0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course.
  
  
  CONCLUSIONS
  Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event
authors.affiliation: Department of Neurology, Karl-Franzens-University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. franz.fazekas@uni-graz.at
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.forename: C
authors.initials: C
authors.lastname: Enzinger
authors.forename: T
authors.initials: T
authors.lastname: Seifert
authors.forename: S
authors.initials: S
authors.lastname: Strasser-Fuchs
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D005260:Female; D005682:Gadolinium; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a