Background <p>Whilst delayed post-gadolinium MRI has led to a shift in the diagnostic paradigm of Meniere’s Disease (MD), there remains a strong desire to develop a non-contrast enhanced MRI technique to detect and monitor MD. The endolymphatic space (ES) undergoes hydropic expansion in Ménière’s Disease (MD) and the concentration of sodium ions in the endolymph is at least 10 times lower than that in the perilymph. It was hypothesised that the lower sodium (²³Na) concentration in the endolymph relative to the surrounding perilymph would result in a differential reduction in ²³Na-MRI signal in inner ears with endolymphatic hydrops (EH). This proof of principle study explored the feasibility of 7-Tesla (7T) ²³Na-MRI to lateralise EH ears in unilateral MD.</p> Methods <p>In this prospective study, 7T ²³Na-MRI was performed in participants with both unilateral definite MD and severe vestibulo-cochlear EH on a delayed post-gadolinium real inversion recovery sequence. Two blinded independent observers qualitatively graded the visibility and anatomical compatibility of inner ear ²³Na MRI signal intensity (NaSI), before and after registering to 3D T2-weighted (T2w) MRI and determined the certainty of EH laterality. The internal auditory meatus (IAM), cochlea and vestibule were segmented using 3D Slicer and NaSI was quantified. Inner ear median NaSI were scaled to the adjacent IAM median NaSI and compared between the two ears.</p> Results <p>In 4 unilateral MD participants (mean age 60.3 years, 2 men), both observers correctly predicted EH laterality in 1/4 before and 3/4 participants after fusion to 3D T2w MRI. There was no incorrect lateralisation of EH by either observer, either before or after registration and fusion. In the 3 participants correctly lateralised, quantitative analysis revealed the median inner ear NaSI scaled to the ipsilateral IAM was 1.2–2.8 times higher in the normal cochlea and 1.9–2.9 times higher in the vestibule, compared to the EH ear. Intraclass correlation coefficient for inner ear median NaSI was 0.70.</p> Conclusion <p>This exploratory study revealed the potential for severe EH to be qualitatively and quantitatively lateralised with 7T ²³Na MRI in patients with unilateral definite MD.</p> Trial registration <p>NCT04370366; registered 29/4/20.</p>