Optimization of Detection of Gadodiamide Brain Retention in Rats Using Quantitative T-2 Mapping and Intraperitoneal Administration

Background Currently, the gadolinium retention in the brain after the use of contrast agents is studied by T-1-weighted magnetic resonance imaging (MRI) (T(1)w) and T-1 mapping. The former does not provide easily quantifiable data and the latter requires prolonged scanning and is sensitive to motion. T-2 mapping may provide an alternative approach. Animal studies of gadolinium retention are complicated by repeated intravenous (IV) dosing, whereas intraperitoneal (IP) injections might be sufficient. Hypothesis T-2 mapping will detect the changes in the rat brain due to gadolinium retention, and IP administration is equivalent to IV for long-term studies. Study Type Prospective longitudinal. Animal Model A total of 31 Sprague-Dawley rats administered gadodiamide IV (N = 8) or IP (N = 8), or saline IV (N = 6) or IP (N = 9) 4 days per week for 5 weeks. Field strength/sequences A 7 T, T(1)w, and T-2 mapping. Assessment T-2 relaxation and image intensities in the deep cerebellar nuclei were measured pre-treatment and weekly for 5 weeks. Then brains were assessed for neuropathology (N = 4) or gadolinium content using inductively coupled plasma mass spectrometry (ICP-MS, N = 12). Statistical tests Repeated measures analysis of variance with post hoc Student-Newman-Keuls tests and Hedges' effect size. Results Gadolinium was detected by both approaches; however, T-2 mapping was more sensitive (effect size 2.32 for T-2 vs. 0.95 for T(1)w), and earlier detection (week 3 for T-2 vs. week 4 for T(1)w). ICP-MS confirmed the presence of gadolinium (3.076 +/- 0.909 nmol/g in the IV group and 3.948 +/- 0.806 nmol/g in the IP group). There was no significant difference between IP and IV groups (ICP-MS, P = 0.109; MRI, P = 0.696). No histopathological abnormalities were detected in any studied animal. Conclusion T-2 relaxometry detects gadolinium retention in the rat brain after multiple doses of gadodiamide irrespective of the route of administration. Evidence Level 1 Technical Efficacy Stage 1