Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10848137 | Steroids | 2005 | 6 Pages |
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 μl 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
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Keith J. Brooks, Keith T. Bunce, Michael V. Haase, Alan White, K. Kumar Changani, Simon T. Bate, David G. Reid,