MRI quantification in vivo of corticosteroid induced thymus involution in mice: correlation with ex vivo measurements.
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.
Brooks
Keith J
KJ
Respiratory and Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, The Frythe, Welwyn, Herts AL6 9AR, UK.
Bunce
Keith T
KT
Haase
Michael V
MV
White
Alan
A
Changani
K Kumar
KK
Bate
Simon T
ST
Reid
David G
DG
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*
D005938:Glucocorticoids; D003907:Dexamethasone