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Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial
S Allen Counter1, Sahar Nikkhou-Aski, Peter Damberg
1*Neurology Department, Harvard University Biological Laboratories, Cambridge, Massachusetts, USA †Karolinska Experimental Research and Imaging Center, Karolinska Universitetssjukhuset Solna ‡Department of Clinical Neuroscience §Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm ||Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Hypothesis:
Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla.
Background:
A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI.
Methods:
Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces.
Results:
ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear.
Conclusion:
Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.
