title: MRI quantification in vivo of corticosteroid induced thymus involution in mice: correlation with ex vivo measurements.
abstract: Thymus involution is a useful marker of transactivation-mediated side effects in preclinical therapeutic index testing of new anti-inflammatory glucocorticosteroids, and is usually measured post mortem. We have validated the use of MRI for non-invasive in vivo measurement of mouse thymus involution induced by dexamethasone (DEX). Tl-weighted spin echo 7 T images provided satisfactory contrast between thymus and surrounding connective tissue and fat. Increasing doses of DEX caused thymus involution, reflected in MRI volume (87+/-14, 33+/-10, 28+/-6, 16+/-7 microl in dosage groups of Cremophor vehicle, 1, 10 and 30 mg/kg subcutaneous respectively, n=6/group, mean+/-standard deviation) and post mortem wet weight (64+/-12, 33+/-6, 25+/-9, 23+/-8 mg). Correlation between MRI volumes and wet weights was very good (r=0.842). Measuring pre-dose MRI volumes and then assessing DEX effects as post-dose change from baseline produced no statistical advantage relative to considering post-dose MRI thymus volume alone, probably due to variability in pre-dose baseline values compounding post-dose variability. Smaller group sizes were sufficient to achieve a given statistical power using MRI post-dose volume than using wet weight, suggesting a role for MRI in differentiating the effects of compounds which produce similar effects, or in contexts where the use of large groups of animals is impractical or ethically unacceptable.
authors.affiliation: Respiratory and Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, The Frythe, Welwyn, Herts AL6 9AR, UK.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Brooks
authors.forename: Keith T
authors.initials: KT
authors.lastname: Bunce
authors.forename: Michael V
authors.initials: MV
authors.lastname: Haase
authors.forename: Alan
authors.initials: A
authors.lastname: White
authors.forename: K Kumar
authors.initials: KK
authors.lastname: Changani
authors.forename: Simon T
authors.initials: ST
authors.lastname: Bate
authors.forename: David G
authors.initials: DG
authors.lastname: Reid
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D013223:Statistics as Topic; D013950:Thymus Gland / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone