Document Detail

Quantitative MRI-pathology correlations of brain white matter lesions developing in a non-human primate model of multiple sclerosis.
MedLine Citation:
PMID:  16948176     Owner:  NLM     Status:  MEDLINE    
Experimental autoimmune encephalomyelitis (EAE) induced with recombinant human myelin/oligodendrocyte glycoprotein in the common marmoset is a useful preclinical model of multiple sclerosis in which white matter lesions can be well visualized with MRI. In this study we characterized lesion progression with quantitative in vivo MRI (4.7 T; T(1) relaxation time +/- Gd-DTPA; T(2) relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains; T(1) and T(2) relaxation times; MTR) and histology. The histopathological characterization included axonal density measurements and the numeric quantification of infiltrated macrophages expressing markers for early active [luxol fast blue (LFB) or migration inhibition factor-related protein-14 positive] or late active/inactive [periodic acid Schiff (PAS) positive] demyelinating lesion. MRI experiments were done every two weeks until the monkeys were sacrificed with severe EAE-related motor deficits. Compared with the normal appearing white matter, lesions showed an initial increase in T(1) relaxation times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement of lesions was associated with stabilized T(1) values, while T(2) initially increased and stabilized thereafter and MTR remained decreased. Gd-DTPA leakage was highly variable throughout the experiment. MRI characteristics of the cortex and (normal appearing) white matter did not change during the experiment. We observed that in vivo MTR values correlated positively with the number of early active (LFB+) and negatively with late active (PAS+) macrophages. Ex vivo MTR and relaxation times correlated positively with the number of PAS-positive macrophages. None of the investigated MRI parameters correlated with axonal density.
Erwin L A Blezer; Jan Bauer; Herbert P M Brok; Klaas Nicolay; Bert A 't Hart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  NMR in biomedicine     Volume:  20     ISSN:  0952-3480     ISO Abbreviation:  NMR Biomed     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-15     Completed Date:  2007-04-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8915233     Medline TA:  NMR Biomed     Country:  England    
Other Details:
Languages:  eng     Pagination:  90-103     Citation Subset:  IM    
Copyright Information:
c 2006 John Wiley & Sons, Ltd.
Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
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MeSH Terms
Brain / pathology*
Disease Models, Animal
Gadolinium DTPA
Magnetic Resonance Imaging / methods*
Multiple Sclerosis / pathology*
Reg. No./Substance:
80529-93-7/Gadolinium DTPA

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