A grading scale for the degree of endolymphatic hydrops has been proposed for use in research settings that was validated using identical histologic criteria and has also been applied for clinical evaluations [61, 69, 70]. The normal limit of ratio of the endolymphatic area over the vestibular fluid space (sum of the endolymphatic and perilymphatic area) is 33% and any increase in the ratio would be indicative of endolymphatic hydrops [70, 71]. According to the criteria, mild endolymphatic hydrops in the vestibule cover the ratio of 34–50% and significant endolymphatic hydrops cover the ratio of more than 50% in the vestibule [70]. The respective evaluation of the ratio of the endolymphatic area over the total fluid space in the cochlea is correlated to the displacement of Reissner’s membrane. Normally, the Reissner’s membrane remains in situ and is shown as a straight border between the endolymph-containing scala media and the perilymph-containing scala vestibuli. Mild endolymphatic hydrops display an extrusion of the Reissner’s membrane towards the scala vestibuli and result in an enlargement of the scala media with an area of less than that of the scala vestibuli. Severe endolymphatic hydrops cause an increase of the scala media with an area larger than that of the scala vestibule [70]. A similar grading system on the ordinal level, with three degrees of severity for cochlear hydrops (mild, marked, extreme), has also been proposed [72]. In cadavers without symptom history, the ratio of the endolymphatic space to the total vestibular fluid space ranged from 26.5 to 39.4% [70, 73].
The perilymphatic space facing the vestibule is sealed by the annular stapedial ligament and the perilymphatic space of scala tympani is sealed by the round window membrane. Animal and human experiments indicate that on MRI the perilymphatic space in the vestibule is filled with GdC earlier and more intensively than the perilymphatic space of scala tympani [74, 75]. Thus, the cochlear perilymph space was often poorly filled with GdC than the vestibular part. Zou et al. [76–78] performed a series of experiments by sealing either the round or oval windows and demonstrated that the permeability of the round window was poorer than that of the oval window. This also explains why the treatment of severe MD with low dose gentamicin infrequently causes deafness (less than 5% with two gentamicin injections) [79, 80] but is effective in ablation of vestibular complaints. For the visualization of inner ear membranes, therefore, it is important to fill the upper posterior part of the middle ear cavity with GdC so that the contrast agent has the possibility to be transported also via the oval window as the annular ligament is quite porous. Intratympanic administration of GdC provided efficient loading of the contrast agent in the inner ear perilymph and reduced the risk of systemic toxicity but raised concerns of local toxicity, as it is off label and requires puncture of the tympanic membrane. Such local toxicity was not observed during short, medium or long-term follow-up [81–83]. In addition, image quality might be compromised owing to impaired GdC penetration of the round and oval window membranes [78, 84] and only the injected side of the inner ear can be evaluated [58]. To evaluate both ears simultaneously, it is necessary to inject GdC into both sides [68, 85, 86]. These drawbacks hinder the widespread use of this procedure [87]. The development of more sensitive MRI techniques facilitates endolymphatic hydrops imaging using a single dose of intravenous GdC [56, 88]; this method is intensively used as a clinical research method [89–91]. To establish the normal range of endolymph ratio, healthy volunteers were scanned after intratympanic [70, 73] and intravenous [92] GdC applications. Figure 4 demonstrates the visualization of endolymphatic hydrops with different MRI protocols. Figure 5 demonstrates a combined use of intratympanic GdC in right side and intravenous GdC in the a patient with Meniere’s disease with affected right side to allow comparison between both ears and contrasting of GdC in both inner ears.
Fig. 4. A 72-year-old man with the clinical suspection of left Meniere’s disease. Images are obtained 4 hours after IV-SD-GBCM. Conceptual diagram for the image generation of HYDROPS-Mi2 and HYDROPS2-Mi2. Upper row images indicate the generation of HYDROPS-Mi2. HYDROPS image, which is the subtraction of positive endolymphatic image (not shown) from positive perilymphatic image (heavily T2-weighted 3D-FLAIR, not shown) is multiplied by T2-weighed MR cisternography. Note that black areas (arrows) represent endolymphatic space in labyrinth and white areas represent perilymphatic space on HYDROPS-Mi2. Contrast between endo- and perilymphatic space is very strong, while the back ground signal is quite uniform on HYDROPS-Mi2. Lower row images indicate the generation of HYDROPS2-Mi2. HYDROPS2 image, which is the subtraction T2-weighed MR cisternography from positive perilymphatic image (heavily T2-weighted 3D-FLAIR, not shown) is multiplied by T2-weighed MR cisternography. Note that black areas (arrows) represent endolymphatic space in labyrinth and white areas represent perilymphatic space on HYDROPS2-Mi2 similar to HYDROPS-Mi2. Contrast between endo- and perilymphatic space is very strong, while the back ground signal is quite uniform on HYDROPS2-Mi2 similar to HYDROPS-Mi2. With permission of Jpn J Radiol [58].
The measurement of endolymph volume ratio following 3D-real inversion recovery images obtained 24 h after intratympanic GdC using machine learning and automated local thresholding segmentation algorithms has been reported with highly reproducible results and a highly significant correlation between hearing loss and cochlear endolymphatic hydrops