MRI quantification in vivo of corticosteroid induced thymus involution in mice: correlation with ex vivo measurements |
| |
Authors: | Brooks Keith J Bunce Keith T Haase Michael V White Alan Changani K Kumar Bate Simon T Reid David G |
| |
Affiliation: | Respiratory and Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, The Frythe, Welwyn, Herts AL6 9AR, UK. |
| |
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. |
| |
Keywords: | MRI Thymus Involution Corticosteroid Dexamethasone Mouse |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|