Imaging of Endolymphatic Hydrops at 7T MRI

Meniere's Disease is an inner ear disease characterised by progressive, fluctuating hearing loss and dizziness. Pathologically, it is characterised by endolymphatic hydrops. The diagnosis of Meniere's Disease can be elusive since it relies on the subjective reporting of symptoms and there is no definitive diagnostic test. Non-specific symptoms can occur in the early stages of Meniere's Disease and the disease progression can also fluctuate unpredictably. The cochlear and vestibular compartments may be differentially involved so there maybe clinical variability characterised by solely audiological or vestibular symptoms (1).

The structural correlate of MD is endolymphatic hydrops, in which the central smaller endolymphatic compartment of the inner ear (including the cochlear duct, saccule and utricle) expands into the surrounding peri-lymphatic chambers. Pathological studies of temporal bones in subjects with MD have demonstrated EH in most cases of Meniere's Disease (2) and its presence is required for, the diagnosis of 'certain Meniere's Disease' according to 1995 American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) guidelines(3). An accepted in vivo biological marker for endolymphatic hydrops has yet to be established. Recent developments in MRI technology and techniques have however allowed the demonstration of EH and the clinical application of these imaging studies is now being explored.

High resolution T2-weighted sequences are widely used for the demonstration of labyrinthine anatomy and pathology however they are unable to distinguish the endolymphatic from perilymphatic compartments and hence are generally unable to depict endolymphatic hydrops. The potential role of gadolinium in discriminating the endolymphatic chamber alone first became apparent in animal studies, since gadolinium was seen to accumulate in the perilymph but was excluded from the endolymph by the impermeable tight junctions. Intra-tympanic administration of gadolinium was initially explored, whereby high concentrations could enter the labyrinth through round window diffusion, however the evolution of clinically applicable high resolution sequences at 3T has allowed for gadolinium to be administered by the less invasive intravenous route. Delayed (4 hours post administration) gadolinium enhanced high resolution imaging is now used at a number of centres worldwide for the evaluation of Meniere's Disease patients, although acquisition and analysis methods continue to evolve. This is most frequently performed with 3D Fluid Attenuated Inversion Recovery with variable flip angles turbo spin echo sequence (3D SPACE FLAIR) or 3D real inversion recovery sequence (3D real IR.

The identification of cochlear or vestibular hydrops by MRI in vivo may support the diagnosis of Meniere's disease in cases with incomplete phenotypes and where there are other diagnostic considerations such as vestibular migraine or autoimmune ear disease. It may also facilitate early identification, thus guiding future treatment options for patients who have traditionally been required to take a watchful waiting approach to see how their symptoms may evolve or "trial-and-error" approach to management. The identification of bilateral endolymphatic hydrops in a patient with unilateral fluctuating aural symptoms might predict future bilateral disease and potentially influence therapeutic approaches. Establishing imaging as a biomarker in Meniere's disease may allow a contribution to diagnostic criteria and to define homogenous cohorts for longitudinal studies of natural history and treatment response.

The degree of hydrops in each cochlea and vestibule is semi-quantitatively graded (4,5) and the saccule to utricle ratio index (SURI) is routinely recorded . SURI is a qualitative comparison of the volume of the saccule relative to the utricle for which a combination of oblique sagittal and axial reformats are used .MRI assessment of SURI has proved a reliable qualitative marker being 50% sensitive and 100% specific for MD and this is felt to be due to the preferential enlargement of the more compliant saccule in EH (6). Additional features recorded include any asymmetric cochlea enhancement and asymmetry in size of the endolymphatic structures.

However there are deficiencies with this MRI approach which we would like to address with an exploratory study of Meniere's disease patients on 7 Tesla MRI:

1. Gadolinium has an excellent safety record when used at low doses (0.1-0.3 mmol/kg) in patients with normal renal function. However a causative relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis is described in patients with renal insufficiency, and there is also increasing evidence that they deposit in the human brain after multiple administrations, although the clinical significance of this remains uncertain (7). Therefore the development of non-contrast enhanced MRI techniques using high resolution 3-dimensional (3D) Fourier transform MR imaging sequences such as constructive interference in steady state (CISS) is of considerable interest. In this regard, some groups have explored the utility of measuring saccular height on T2w sequences as a marker of endolymphatic hydrops, although the reliability and reproducibility of these techniques requires confirmation (8,9). We could speculate that high resolution T2w imaging at 7 Tesla provides increased SNR so may allow superior definition of these small endolymphatic structures of the inner ear, allowing increased confidence and reproducibility of the observations, and allowing better discrimination of endolymphatic hydrops from normal ears. Correlation with the location of endolymphatic structures on contemporary delayed post gadolinium inversion recovery sequences would add validation to the interpretation of the T2w imaging appearances.

2. Due to the small size of the inner ear structures being imaged and susceptibility effects arising from the adjacent aerated temporal bone, the SNR and resolution are currently limited on 3D delayed post gadolinium IR imaging at 3T, making accurate delineation of some of the structures (e.g. the cochlear duct) extremely difficult, and hence limiting diagnostic confidence. This is particularly relevant in the early phase of the disease when the structures are less dilated, which is unfortunate since the clinical diagnosis is also most challenging at this stage. The lack of clear delineation also impacts on the precision and inter-observer agreement of minor (semi-quantitative lower grade) hydrops diagnosis. There is potential for increased spatial resolution and SNR at 7T MRI with better depiction of the endolymphatic structures on the delayed post gadolinium 3D IR sequence. This may result in differing semi-quantitative scoring and quantitative measures of the internal inner ear structures and improved discrimination of symptomatic from asymptomatic ears compared with 3T MRI.

It is hypothesized that HR T2w imaging at 7T will allow the reliable and reproducible detection of internal inner ear structures, which correlate with the size of endolymphatic structures on 3D post gad IR imaging and which may be used to distinguish symptomatic from asymptomatic ears in patients with unilateral MD.

A cohort of 16 adult patients with unilateral Meniere's disease audio-vestibular symptoms which satisfy 2015 Barany criteria and which would be referred for delayed post gadolinium clinical MRI scanning as per the current standard clinical protocol at GSTT.

PRIMARY OBJECTIVE:

1. Assess the reproducibility and confidence in detecting a series of internal inner ear structures (which may reflect the location of endolymphatic structures) on high resolution (HR) T2w imaging at 7T.

2. Correlate the location and linear measurements of these internal inner ear structures on T2w sequences at 7T, with the position and size of endolymphatic structures as located and measured on the delayed post gadolinium 3D IR sequences.

3. Ability of the quantitative measurements on HR T2w at 7T to distinguish symptomatic from asymptomatic ears.

SECONDARY OBJECTIVES:

To compare 3T with 7T for the:

1. Definition and reproducibility of measurements of the internal inner ear structures on HR T2w sequences and the endolymphatic structures on the delayed post gadolinium 3D IR sequence.

2. Semi-quantitative scoring and quantitative measures of the internal inner ear structures on HR T2w sequences and the endolymphatic structures on the delayed post gadolinium 3D IR sequence.