Differential passage of gadolinium through the mouse inner ear barriers evaluated with 4.7T MRI

Magnetic resonance imaging (MRI), supplemented by contrast agents, is a powerful tool that can be used to visualise the structures of the inner ear in vivo and assess some aspects of physiology, such as the permeability of agents through membranes. The mouse is an excellent animal species for investigating human diseases, including hearing loss but detailed MRI studies with contrast have not been reported. In this work, we aimed to demonstrate the limits of MR imaging resolution of the fine inner ear structures in the mouse and to explore the permeability of the intracochlear barriers to gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) administered by intravenous injection (IV) or intratympanic (IT) routes. Twenty-three female FVB mice were imaged with a 4.7-T MR scanner using both 2D and high resolution 3D sequences. Inner ear region of interest (ROI) signal intensities and perilymph volumes were evaluated. Finer structures were studied using 3D acquisition and reconstruction techniques and comparisons were made to similarly oriented histological sections that were examined by light microscopy. Gd-DOTA enhancement occurred in the perilymphatic compartment and highlighted the contiguous inner ear structures, but enhancement did not appear within the endolymph. The dynamic uptake of Gd-DOTA in the perilymphatic compartments reached an initial plateau 80min after IV administration and continued to slightly increase to a maximum level by 100min. The perilymph volume demonstrated by Gd-DOTA uptake was statistically significantly larger in the IV group (1.72mm(3)) than in the IT group (1.28mm(3)) (p<0.05).