GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury

Background Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia. Purpose To investigate whether GdDO3NI, a nitroimidazole-based T-1 MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI. Study Type Prospective. Animal Model TBI-induced mice (controlled cortical impact model) were intravenously injected with either conventional T-1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n = 5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized. Field Strength/Sequence 7 T/T-2-weighted spin echo and T-1-weighted gradient echo. Assessment Injured animals were imaged with T-2-weighted spin-echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T-1-weighted gradient-echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post-imaging for immunohistochemical analysis. Statistical Tests One-way analysis of variance and two-sample t-tests were performed with a P < 0.05 was considered statistically significant. Results GdDO3NI retention in the injury region at 2.5-3 hours post-injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% +/- 27.43% vs. 20.68% +/- 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement. Data Conclusion GdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T-1-weighted MRI at 2.5-3 hours postcontrast. Evidence Level 1 Technical Efficacy Stage 1