7-Tesla sodium magnetic resonance imaging of the inner ears in unilateral Ménière’s Disease and endolymphatic hydrops: An exploratory study

7-Tesla sodium magnetic resonance imaging of the inner ears in unilateral Ménière’s Disease and endolymphatic hydrops: An exploratory study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 7-Tesla sodium magnetic resonance imaging of the inner ears in unilateral Ménière’s Disease and endolymphatic hydrops: An exploratory study Steve Connor FRCR, Peter Lally, Irumee Pai, Haneefah Brnwari, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7420941/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Nov, 2025 Read the published version in BMC Medical Imaging → Version 1 posted 10 You are reading this latest preprint version Abstract Background 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 ( 23 Na) concentration in the endolymph relative to the surrounding perilymph would result in a differential reduction in 23 Na-MRI signal in inner ears with endolymphatic hydrops (EH). This proof of principle study explored the feasibility of 7-Tesla (7T) 23 Na-MRI to lateralise EH ears in unilateral MD. Methods In this prospective study, 7T 23 Na-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 23 Na 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. Results 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. Conclusion 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. Trial registration NCT04370366; registered 29/4/20 magnetic resonance imaging Meniere’s Disease ultra-high-field MRI endolymphatic hydrops sodium Figures Figure 1 Figure 2 Figure 3 Figure 4 Background The inner ear fluid comprises a central endolymphatic compartment which is separated by membranes from the surrounding larger perilymphatic compartment. The principle endolymphatic structures are the saccule and utricle of the vestibule, and the scala media of the cochlea. Ménière’s disease (MD) is an inner ear condition with a typical clinical presentation of episodic vertigo, low- to mid-frequency hearing loss and fluctuating aural symptoms and has a prevalence of up to 513/100,000 [ 1 ]. The pathological hallmark of MD is endolymphatic hydrops (EH) which represents an expansion of the endolymphatic space (ES) into the surrounding perilymphatic space (PS) [ 2 ]. Temporal bone studies demonstrate EH in 98.8% of patients with clinically suspected MD [ 3 ]. Differential permeability of the endolymph and perilymph to gadolinium-based contrast agents (GBCA) allows the enhancing PS to be distinguished from the non-enhancing ES on delayed post-GBCA MRI three-dimensional inversion recovery (3D-IR) sequences. Three-dimensional inversion recovery (3D-IR) sequences enable the detection of low concentrations of gadolinium in the perilymph with high resolution depiction of the inner ear compartments on delayed post-GBCA MRI. Following its initial description in 2007 [ 4 ], MRI has been progressively utilised worldwide for the demonstration of EH. Meta-analysis has indicated a high sensitivity (87%) and specificity (91%) for the diagnosis of MD with optimal combinations of MRI descriptors [ 5 ]. The increasing role of MRI in hydropic ear disease, has led to proposals for imaging-based rather than clinical terminology [ 6 ] and the emergence of MRI features in diagnostic guidelines for MD [ 7 ]. Intravenous GBCAs have an excellent safety record but they are not exempt from safety considerations. A causative relationship between less stable linear chelate GBCAs and nephrogenic systemic fibrosis is described in patients with severe renal insufficiency. In addition, there is evidence of gadolinium deposition in the human brain after multiple administrations, although this is reduced with macrocyclic agents [ 8 , 9 ]. Therefore, it would be beneficial to develop a non-contrast enhanced MRI technique to detect and monitor MD [ 10 ]. Whilst there are some reports of EH being demonstrated with non-contrast high resolution T2 weighted (T2w) [ 10 ] and 3D Fluid Attenuated Inversion Recovery (3D-FLAIR) sequences [ 11 ], these have not been widely reproduced. The ES and PS have distinctive ionic compositions which are maintained by ion channels and transport mechanisms [ 12 , 13 ]. The maintenance of ion haemostasis is required for hair cell function with endolymph surrounding the stereocilia and perilymph bathing the hair cell bodies. Hair cells depolarize with motion, so allowing the transduction of sound and head acceleration into the nerve impulses necessary for normal hearing and balance. One notable feature of the ionic environment is that the sodium ( 23 Na) concentration in the ES (1.3 mM) is considerably lower than that of the PS (141–148 mM) [ 14 ]. It may be hypothesised that this differential biodistribution of 23 Na concentration could be probed with 23 Na MRI, and that the expanded ES in patients with MD would result in lower 23 Na MRI signal relative to the normal ear. 23 Na MRI signal is limited by the low natural abundance, rapid quadrupolar relaxation and lower gyromagnetic ratio of 23 Na [ 15 ], although this may be partly mitigated by imaging at ultra-high field strength. Validation of 23 Na MRI outside the brain, kidney and cartilage is limited, and imaging of the inner ears is particularly challenging due to magnetic susceptibility gradients at bone and air interfaces, small anatomical structures and suboptimal coil sensitivity for deep skull base structures. We aimed to explore whether a ²³Na 7 Tesla (7T) MRI sequence could distinguish pathological ears by detecting asymmetrically reduced ²³Na signal in patients with unilateral MD and EH. Method Participants All methods in this prospective study were carried out in accordance with relevant guidelines and regulations and the experimental protocol was approved by the institutional ethical committee (Health Research Authority. Southwest Frenchay Research Ethics Committee. Initial approval 16/6/20. Amendment approval 15/11/22. IRAS ID: 259867, Rec Reference: 20/SW/0085). Informed consent was obtained from all subjects. The Picture Archiving and Communication System (Sectra AB, Sweden) was interrogated for consecutive patients undergoing clinical delayed post-GBCA inversion recovery (IR) MRI between December 2017 and October 2022. These patients had presented with symptoms of EH including episodic vertigo, sudden-onset or fluctuating SNHL, aural fullness and tinnitus. The contemporary clinical and audiometric data was reviewed by two observers (SC, IP) who were blinded to imaging findings, and patients were classified according to the current 2015 Barany Society criteria [ 19 ]. Clinical data was recorded in the six months and audiometry in the twelve months prior to the MRI study. The delayed post-GBCA IR sequences were independently analysed by two radiologists (PT, SC), with 7- and 25-years of subspecialty head and neck radiology experience. The radiologists rated the images according to the Nakashima criteria [ 20 ] whilst blinded to clinical diagnosis. Participants were eligible for the study when both observers recorded unilateral “definite MD” on clinical review and both radiologists recorded unilateral severe (Grade 2 Nakashima) vestibular and cochlear EH on imaging analysis. A priori exclusion criteria were inadequate contemporary clinical details for diagnostic classification, clinical or radiological suspicion of secondary hydrops, previous inner ear operations, and technically inadequate MR imaging. The first four eligible participants, determined by the date of their initial diagnostic MRI scan, were invited to take part in the research 7 tesla (7T) 23 Na MRI study 7-tesla (^23Na) MRI study in accordance with the study protocol. 23 Na MRI sequence and reconstruction development 23 Na MRI of the inner ears was refined on a 7T Magnetom® Terra scanner, (Siemens Healthineers, Erlangen) using a 1Tx/ 32Rx 23 Na head coil (Rapid Biomedical, Rimpar) through iterative phantom and healthy volunteer (HV) imaging. Initial HV sequences were performed with acquisition times of 40–55 minutes to evaluate parameter changes, which were applied to an approximately 30 minutes sequence that could be tolerated by participants. A 3D Cones k -space trajectory was utilised which allowed for very short echo times and repeat time (TR) of 23 Na MRI, whilst providing increased signal to noise (SNR) efficiency and good motion properties [ 16 ]. A balanced steady-state free precession (bSSFP) sequence was employed [ 17 ] since it demonstrated greater SNR on phantom and HV studies compared to a fast low angle shot (FLASH) sequence. A disadvantage of the bSSFP sequence is its sensitivity to static field (B 0 ) inhomogeneity in the region of the inner ears due to local air, bone and fluid interfaces, and this resulted in banding artefact which was exacerbated by the ultra-high field strength. Therefore, phase cycling was used to enable systematic displacement of band locations and reduction in band conspicuity through image summation [ 18 ]. A 3 mm voxel size provided suboptimal delineation of the inner ears, and a 2 mm voxel size was considered to provide an appropriate balance of SNR and spatial resolution. Blurring of the images was reduced with a 2 ms readout compared to 4 ms and 10 ms readouts. The TR remained as required for the longer readout of 10 ms. A further reduction in TR would have precluded the application of a high enough flip angle for efficient fluid imaging whilst remaining within specific absorption rate (SAR) limits. The final research 7T 23 Na MRI study comprised a bSSFP phased cycled sequence and a 3D cones trajectory: 1ms radiofrequency pulse width, 2x2x2 mm resolution, 240 mm 3 field of view, flip angle 25 0 , TR 14.26/TE 1.06ms, 2ms readout and 5 phase cycles with time per phase cycle 6.24 min. A complex summation of the five phased cycled datasets, each adjusted by its own linear phase cycling increment, resulted in three signal components (F 0 , F 1 , and F − 1 ) [ 21 ]. Each data set was reconstructed via nonuniform-FFT (conjugate-gradient SENSE) [ 22 ], and a composite image combined all three F-state components via root sum of squares. The images were reconstructed with a frequency offset sweep set at 20Hz steps from − 100 to 200 Hz to correct for local susceptibility effects and were saved as 4 D stacks [X Y Z Hz offset] in NIfTI format. Clinical delayed post-gadolinium 3D-IR MRI sequences Delayed post-gadolinium 3D-IR MRI sequences and three dimensional (3D) T2w structural imaging of the inner ears and been previously acquired according to routine clinical scanning protocols. The delayed post-gadolinium 3D-IR MRI sequences were used to assess participant eligibility whilst 3D T2w structural imaging were used for subsequent image fusion with 23 Na MRI. Clinical MRI was performed on a 3T Magnetom® Skyra (Siemens Healthineers, Erlangen) scanner with a 64-channel head coil. 3D-IR sequences with phase corrected real reconstruction (3D real-IR) were acquired 4 hours after intravenous administration of gadoterate meglumine (0.2 mmol/kg) according to the institutional clinical protocol. 3D T2w imaging to delineate the inner ear anatomy was performed with a T2w sampling perfection with application optimised contrasts using different flip angle evolution (T2w SPACE). Siemens product sequences were used with parameters tabulated in Table 1 . Table 1 MRI parameters for clinical imaging of the inner ears 3D real-IR 3D real-IR T2-SPACE Repetition time 6000 ms 15130 ms 1000 ms Echo time 180 ms 550 ms 125 ms Inversion time 2000 ms 2700 ms NA Number of excitations 1 1 2 Refocusing flip angle 180° (constant) 130° (constant) 100° Pixel band width 220 435 255 Echo train length 27 267 52 Pixel spacing 0.7 mm 0.66 mm 0.31 mm Slice thickness 0.7 mm 0.6 mm 0.3 mm Matrix size 256 x 240 320 x 270 262 x 512 Field of view 190 x 178 mm 210 X177 mm 80 x 160 mm Acquisition time 13.38 min 11.21 min 6.38 min Registration and qualitative analysis The reconstructed combined F state 23 Na MR images were viewed across the range of off-resonance frequencies using ImageJ [ 23 ]. The 23 Na MR image quality and artefact (distortion, susceptibility and ghosting) was evaluated according to a Likert scale (Table 2 ) [ 24 ]. The optimal frequency offset for the depiction of each inner ear with minimal blurring was then selected. All 23 Na MRI images grey scale imaging may be accessed in the supplementary data. Two observers (SC, IP) independently registered the 23 Na MR images to the 3T T2w SPACE sequence for each ear using 3D-Slicer 5.6.2 [ 25 ] landmark-based registration, using 9–16 control points (Fig. 1 ). The T2w SPACE sequence was chosen as the fixed volume and the 23 Na MRI as the moving volume in thin-plate spline mode. Table 2 Grading scales for image quality, artefact, signal visibility and anatomical compatibility Image quality Artefact Visibility Anatomical compatibility 0 Non-diagnostic 0 Severe effect 0 Not visible 0 Structure not visible 1 Suboptimal 1 Moderate effect 1 Decreased signal relative to adjacent structure* 1 Major concern/minority ( 50%) overlap ** 3 Excellent 3 No artefact 3 Increased signal relative to adjacent structure* 3 Entirely concordant * Adjacent structure is the cerebello-pontine angle cistern for internal auditory meatus signal and the internal auditory meatus for inner ear (cochlea and vestibule) signal **This may be because signal extends outside of the anatomical structure or only overlaps part of the anatomical structure The two observers independently analysed the 23 Na MR images in isolation and then with the 23 Na MR images registered and fused to the T2w SPACE sequence (Fig. 2 , 3 ), whilst blinded to clinical and delayed post-GBCA 3D-IR data. The visibility and anatomical compatibility of 23 Na MRI signal in each IAM, cochlea and vestibule were qualitatively graded with Likert scales (Table 2 ). The visibility grades were based on the qualitative evaluation of 23 Na MR signal intensity (NaSI) when compared to that returned by adjacent structures (Table 2 ). The grading of anatomic compatibility was based on prior anatomical knowledge for the 23 Na MR images in isolation and depended on overlap with the corresponding anatomy on the T2w SPACE sequence for the registered and fused images (Table 2 ). The certainty of laterality was classified by comparing the difference between cochlea or vestibule visibility grade and the adjacent fundus of the IAM between the two sides. If either cochlea or vestibule visibility grade (relative to the fundus of the IAM) was 1 point greater than the contralateral ear and it had least grade 2 anatomic compatibility on both sides, then it was classified as possible laterality. If either cochlea or vestibule visibility grade was 2 points greater (relative to the fundus of the IAM) than the contralateral ear and it had at least grade 2 anatomic compatibility on both sides, then it was classified as definite laterality. Segmentation and quantitative analysis The observers subsequently manually segmented each cochlea, vestibule and lateral half of IAM on the T2w SPACE images, facilitated by comparable intensity-based thresholding (Fig. 4 ). The manually segmented masks were visualized by 3D maximum intensity projections to ease quality assessment. The segmentations were then transferred to the transformed 23 Na MRI, and the SI statistics were extracted for each of the segmented volumes. Statistical analysis The mean, standard deviation and median of the NaSI for each cochlea and vestibule was documented, and the ratio of the median cochlea and vestibule NaSI to that of the adjacent IAM was calculated. Intraclass correlation coefficients (ICC) evaluated the absolute agreement of inner ear (cochlea and vestibule) median NaSI between the two observers. The small sample size precluded reliability statistics for the qualitative analysis [ 26 ]. Results Participant characteristics There were 4 eligible participants imaged (age mean 60.3 years, range 33–78 years; 2f, 2m) with a mean duration of symptoms of 16 years (range 3–40 years). The laterality of MD, audio-vestibular symptoms, audiogram and vestibular function tests are presented in Table 3 . The laterality of the MD, audio vestibular symptoms, audiogram and vestibular function tests are presented in Table 3 . Complete replacement of the vestibular perilymph by the dilated endolymphatic structures was evident on delayed post-GBCA MRI in 3/4 participants. Table 3 Demographic, clinical and delayed post-gadolinium MRI data for the four participants Participant Age/sex Ménière’s Disease laterality Symptoms Vestibular function tests Duration of symptoms Audiogram Time interval between clinical MRI and research 23 Na MRI Nakashima hydrops MRI grade (19) ipsilateral cochlea/ vestibule Nakashima hydrops MRI grade (19) contralateral cochlea/vestibule A 78/M left Ipsilateral tinnitus, HL, vertigo (3–5 hours) Ipsilateral calorics/VNG abnormal Contralateral normal 17 years Ipsilateral pan-frequency Contralateral panfrequency 60 months 2/2 Complete replacement of the vestibule by endolymph 0/0 B 62/F right Ipsilateral tinnitus, HL, vertigo (2min-1 hour) Ipsilateral calorics/ VHIT/VNG abnormal Contralateral normal 3 years Ipsilateral pan-frequency Contralateral HFSNHL > 3K 31 months 2/2 Complete replacement of the vestibule by endolymph 0/0 C 68/M left Ipsilateral tinnitus, HL, aural fullness, vertigo (30 min-12 hours) Ipsilateral VHIT/VNG normal 40 years Ipsilateral pan-frequency Contralateral HFSNHL > 6K 7 months 2/2 Complete replacement of the vestibule by endolymph 0/0 D 33/F left Ipsilateral tinnitus, HL, aural fullness, vertigo (3–4 hours) None performed 4 years Ipsilateral pan-frequency Contralateral normal 9 months 2/2 > 50% replacement of the vestibule by endolymph 0/0 HL Hearing loss; HFSNHL High frequency sensorineural hearing loss; VHIT Video head impulse test; VNG Videonystagmograph Qualitative analysis The outcomes of the qualitative analysis for image quality, IAM and inner ear visibility, anatomic compatibility and laterality are tabulated (Table 4 ) and illustrated in Figs. 2 and 3 (normal right ears and hydropic left ears). Eight ears in four participants were analysed by two observers (total of 16 observations). 23 Na MRI image quality was suboptimal with at least a moderate effect of artefact in 2/4 studies, largely due to distortion, blurring and ghosting resulting from movement artefact. The optimal frequency offsets selected for the depiction of each inner ear were (right/left) + 200Hz /+200Hz, + 40Hz /-60Hz, -60Hz /-160Hz and + 60Hz / -100Hz for participants A, B, C and D respectively. The IAMs were at least partially visible in all 23 Na MRI studies prior to registration and fusion, with anatomical compatibility grades of 2 or 3 indicating that the majority of the IAM was depicted in 10/16 observations. When considering the cochlea and vestibule separately, following registration and fusion of 23 Na MRI, anatomical compatibility grades increased in 6/32 observations, decreased grades in 4/32, and remained the same in 22/32. Grade 2 or 3 anatomical compatibility grades were achieved in 12/16 normal inner ear observations following registration and fusion. Table 4 Qualitative analysis of 23 Na MRI studies for the four participants: Image quality, artefact, signal visibility, anatomical compatibility and lateralisation Participant Image quality Artefact Observer Signal visibility/Anatomical compatibility *Certainty of hydrops laterality and side Side of laterality correct/incorrect Right IAM Right cochlea Right vestibule Left IAM Left cochlea Left vestibule A 1 1 Pre-registration 1 1/1 3/1 3/1 1/2 0/0 1/1 None NA 2 1/2 3/2 3/2 1/2 0/0 0/0 Definite/left Correct Post-registration 1 1/1 3/2 3/2 1/2 0/0 1/1 Definite /left Correct 2 1/2 3/2 3/2 1/2 0/0 0/0 Definite/left Correct B 2 2 Pre-registration 1 2/2 2/1 2/1 2/3 1/1 1/1 None NA 2 1/1 1/1 1/1 2/2 1/1 1/1 None NA Post-registration 1 1/2 2/1 2/1 2/2 1/1 1/1 None NA 2 1/1 1/1 0/0 2/3 1/2 1/2 None NA C 2 2 Pre-registration 1 1/3 1/3 1/3 1/3 1/1 0/0 Possible/left Correct 2 1/3 1/2 1/2 1/3 0/0 1/1 Possible/left Correct Post-registration 1 1/3 1/3 1/3 1/3 0/0 0/0 Possible/left Correct 2 1/3 1/2 1/2 1/3 0/0 0/0 Possible/left Correct D 1 0 Pre-registration 1 1/1 1/1 1/1 1/1 0/0 0/0 None NA 2 1/1 2/1 2/1 1/1 1/1 1/1 None NA Post-registration 1 I/2 2/2 1/1 1/1 0/0 0/0 Definite/left Correct 2 1/1 2/1 2/2 1/1 0/0 1/1 Possible/left Correct IAM; internal auditory meatus Inner ear grades in the inner ear with EH are in bold *The certainty of laterality was based on the relative difference in visibility of either the cochlea or vestibule to the IAM fundus when comparing the two sides. If either cochlea or vestibule visibility grade (relative to the fundus of the IAM) was 1 point greater than the contralateral ear and it had least grade 2 anatomic compatibility on both sides, then it was classified as possible laterality. If either cochlea or vestibule visibility grade was 2 points greater (relative to the fundus of the IAM) than the contralateral ear and it had at least grade 2 anatomic compatibility on both sides, then it was classified as definite laterality. Prior to registration and fusion, the anatomical compatibility and visibility grades indicated EH lateralisation in only 1/4 participants (participant C) for both observers. However, following registration and fusion with structural T2w SPACE imaging, there were 3/4 participants with lateralisation correctly independently predicted by both observers. Quantitative analysis The mean, standard deviation and median inner ear NaSI are shown for the cochlea (Table 5 ) and the vestibule (Table 6 ). The mean (range) of cochlea volume was 83 (63–110) mm 3 for observer 1 and 80 (59–115) mm 3 for observer 2, whilst the mean (range) of vestibular volume was 47 (31–59) mm 3 for observer 1 and 41 (33–50) mm 3 for observer 2. Table 5 Quantitative analysis of the cochlea on 23 Na MRI studies for the four participants Participant Endolymphatic hydrops cochlea signal intensity (x10 − 5 ) Normal cochlea signal intensity (x10 − 5 ) *Ratio of normal cochlea median signal: hydropic cochlea median signal *Ratio of normal cochlea/IAM median signal: hydropic cochlea /IAM median signal Mean SD Median Median cochlea/ Median IAM signal Mean SD Median Median cochlea/ Median IAM signal A Observer 1 6.4 2.7 6.2 0.7 8.4 3.8 7.9 1.7 1.5:1 2.0:1 Observer 2 5.4 2.1 6.0 0.6 10.1 4.5 10.1 1.4 B Observer 1 7.0 1.3 7.7 0.9 5.5 2.9 6.4 0.8 0.8:1 0.8:1 Observer 2 6.0 3.2 7.1 1.1 5.7 2.6 5.9 0.7 C Observer 1 5.5 2.5 4.7 0.4 4.9 1.1 5.1 0.5 1.2:1 1.2:1 Observer 2 4.8 2.8 3.6 0.4 3.9 1.9 4.5 0.5 D Observer 1 6.3 3.0 5.2 0.6 5.9 3.9 8.2 1.7 1.3:1 2.8:1 Observer 2 3.5 1.5 3.5 0.3 4.3 3.1 2.9 0.5 *Calculated from the mean of the two Table 6 Quantitative analysis of the vestibule on 23 Na MRI studies for the four participants Participant Endolymphatic hydrops vestibule signal intensity (x10 − 5 ) Normal vestibule signal intensity (x10 − 5 ) *Ratio of Normal vestibule median signal: hydropic vestibule median signal *Ratio of normal vestibule/IAM median signal: hydropic vestibule /IAM median signal Mean SD Median Median vestibule/ Median IAM signal Mean SD Median Median vestibule/ Median IAM signal A Observer 1 6.3 3.3 5.7 0.6 9.1 4.8 10.3 1.3 2.1:1 2.9:1 Observer 2 4.6 1.1 4.6 0.4 9.5 5.0 11.7 1.6 B Observer 1 6.3 2.4 7.1 0.8 5.6 2.7 5.9 0.8 0.8:1 0.7:1 Observer 2 9.5 5.0 9.7 1.3 6.0 2.3 7.0 0.8 C Observer 1 4.4 2.3 3.2 0.3 6.0 3.3 7.9 0.7 1.9:1 1.9:1 Observer 2 4.1 1.7 3.3 0.4 5.2 2.4 4.3 0.5 D Observer 1 6.5 4.4 6.9 0.8 5.6 3.0 5.1 1.1 1.1:1 2.2:1 Observer 2 4.6 3.0 4.3 0.4 5.8 3.7 7.7 1.4 *Calculated from the mean of the two observers Based on the average ratings from the two observers, the normal: EH median NaSI ratios for the cochlea were 1.4:1, 0.8:1, 1.2:1, and 1.3:1 in the four participants. For the vestibule, the normal: EH median NaSI ratios were 2.1:1, 0.8:1, 1.9:1, and 1.1:1. The median NaSI was decreased in both the cochlea and vestibule of the EH ears in the 3/4 participants (participants A, C and D) who had the correct lateralisation on qualitative analysis following registration and fusion. When the median inner ear NaSI was scaled to the adjacent IAM NaSI, the corresponding ratios were 2.0:1, 0.8:1, 1.2: 1 and 2.8: 1 (mean 1.7:1) for the cochlea and 2.9:1, 0.7:1, 1.9:1 and 2.2: 1 (mean 1.9:1) for the vestibule. The ICC for the inner ear median NaSI was 0.70 (95% CI; 0.15–0.89). Discussion A 23 Na MRI bSSFP sequence was developed for the demonstration of the inner ears on a 7T MRI system. In four participants with unilateral MD, both observers correctly lateralised the ear with severe vestibulo-cochlear endolymphatic hydrops in only 1/4 participants with a signature of reduced inner ear signal on qualitative assessment of 23 Na MRI data alone. However, when 23 Na MRI was registered and fused to a T2 SPACE sequence, there was successful endolymphatic hydrops lateralisation by both observers in 3/4 participants. There was no incorrect lateralisation of EH by either observer either before or after registration and fusion. It was not possible to lateralise in participant B, and the potential reasons for this are discussed below. On quantitative analysis of segmented inner ear structures, the same 3/4 participants demonstrated increased 23 Na MRI median signal intensity in both the cochlea (1.2–1.5 times) and vestibule (1.1–2.1 times) in the normal ear relative to the symptomatic MD ear. The ratio between the median signal intensity of the normal and the pathological inner ears increased when it was scaled to the signal intensity of the adjacent IAM, with a 1.2–2.8:1 ratio for the cochlea and a 1.9–2.9:1 ratio for the vestibule. There are no previous reports of 23 Na MRI being applied to inner ear imaging, with considerable challenges resulting from the small volume anatomical structures and the variation in static magnetic field (B 0 ) due to juxtaposition of bone, air and fluid. Our 23 Na MRI research sequence and post-processing was adapted to maximise SNR efficiency at adequate spatial resolution and to address artefacts due to off-resonance frequencies. Acquisition with a fast (non-Cartesian) 3D-Cones trajectory was employed to reduce the duration of signal readout, as required by the rapid T2* decay of 23 Na, and to improve SNR [ 16 ]. A bSSFP sequence was also utilised to boost SNR [ 17 ], with the banding artefact minimised by utilising a short TR and employing phase-cycling [ 18 ] with signal averaging across cycles. It was decided a priori that a 30-minute sequence would be reasonable from the patient perspective, but 2/4 of the MRI studies demonstrated suboptimal image quality due to participant movement. More targeted array coils with parallel imaging strategies [ 27 ] and methods to reconstruct high-quality MRI data from limited k-space data [ 28 ] may optimise 7T 23 Na MRI inner ear imaging in the future. The findings of this study indicate that 23 Na MRI can detect changes in MD, inviting exploration of other potential applications to inner ear pathologies. Firstly, 23 Na MRI may have a role in evaluating interval changes in size of the endolymphatic compartment and monitoring the evolution of EH, since structural imaging has been proven to be limited in its ability to demonstrate treatment response and explain fluctuations in symptoms [ 29 , 30 ]. Secondly, there may be a wider role for 23 Na MRI in probing the ionic milieu of the inner ear as an insight to disease processes. It is recognised that increases or variations in endolymph sodium concentrations result in cellular dysfunction, and clinical audio-vestibular disorders [ 31 , 32 ]. However, there are logistical and technical difficulties in obtaining fluid samples in vivo, since it is both invasive and the composition may be disturbed during surgical procedures [ 33 ]. 23 Na MRI could offer a non-invasive bio-marker to evaluate the sodium concentration of the pathological inner ear in the presence of normal structural MRI appearances. For instance, abnormalities of sodium haemostasis have been linked with other inner ear conditions including sudden onset hearing loss due to ischaemic anoxia [ 34 – 36 ] and genetic conditions such as non-syndromic autosomal recessive deafness (DFNA8/10) [ 37 ]. Thirdly, there may also be a role in assessing the impact of systemic alterations of sodium concentration on inner ear metabolism [ 38 ]. In this regard, it has long been observed that otologic symptoms are aggravated after high salt intake [ 39 , 40 ] whilst low sodium intake is beneficial in MD [ 41 ]. Finally, it should be considered whether targeting the evaluation to individual inner ear structures may be beneficial. Since EH is able to replace a greater proportion of the vestibular PS than is possible in the cochlea, this may be the focus of future studies in MD, and our data did confirm a greater degree of vestibular than cochlear NaSI asymmetry. In participant B, there was no qualitative lateralisation of EH or increased 23 Na MRI median signal intensity in the normal ear relative to the MD ear, despite good image quality. This leads us to re-examine the assumption in our hypothesis, which was that the hydropic ES would always demonstrate low 23 Na concentrations like the normal ES. There is some data to suggest that there may be paradoxical increases in the 23 Na concentrations in the presence of EH [ 42 – 45 ], which would diminish NaSI asymmetry and may explain the findings in this participant. Potential mechanisms include the reduced extraction of 23 Na from the endolymph in the extra-osseous endolymphatic sac [ 13 , 43 , 44 ] or direct communications between the ES and PS [ 45 ]. Changes in endolymphatic 23 Na concentrations have also been implicated in premenstrual exacerbation [ 46 ] and genetic forms [ 47 ] of MD, whilst animal studies of EH have also shown 2-3x increases in ES 23 Na concentration [ 48 ]. There are study limitations which should be documented. Firstly, the exploratory nature of the study should be emphasised, with the sample size being limited in its ability to allow statistical analysis and firm conclusions. Assessing the clinical validity of ²³Na MRI will require a larger cohort of patients with MD and a normal control population. Secondly, the aforementioned technical challenges in obtaining adequate inner ear SNR limited the spatial resolution, with a minimum achievable 2mm 3 voxel size. The inner ear segmentation volumes were concordant with previous estimates [ 49 ] such that the vestibule corresponded to a maximum of 5 voxels and the cochlea to a maximum of 10 voxels on 23 Na MRI. This limited the confidence of registration and accurate quantification of inner ear signal. Thirdly, methodological aspects should be addressed. The landmark-based registration process was user dependent and potentially impacted on the reliability of quantitative measures. An alternative approach would be to acquire spatially aligned proton MRI structural imaging concurrently with 23 Na MRI to aid registration, but this was precluded in our study by the lack of a receiver array for proton in the dual tuned coil, which precludes acquisition of inner ear images of the required resolution. It should also be considered that 7–60 months had elapsed between the clinical and the research MRI studies with the potential for interval changes, although previous longitudinal studies have indicated that fluctuations in the endolymphatic volume are unlikely [ 50 ]. Whilst the contralateral MD ear may be considered a suboptimal control in view of the potential to develop bilateral MD, this was mitigated by the selection of patients without any evidence of EH in the contralateral ear on delayed post-gadolinium 3D-IR MRI. Finally, we should be guarded about the wider applicability of these methods and results. Only patients with unilateral severe EH were examined, so the results may not be generalised to milder forms. In addition, the evaluation of asymmetry would not be pertinent to bilateral MD. Whilst the potential to apply absolute inner ear NaSI in this setting would warrant further investigation, the overlap between the NaSI values of pathological EH and normal ears in this study would argue against this approach. Moreover, the relevance to routine clinical scanning is limited since 23 Na coils and ultra-high-field MRI are not currently in widespread use. In this regard, translation to lower field strength using iterative denoising reconstruction algorithms should be investigated. Conclusion This exploratory study demonstrates the potential for qualitative analysis of 7T ²³Na MRI to lateralise severely hydropic ears in patients with unilateral definite MD, although there remain technical challenges to acquisition and post-processing. Optimal evaluation required registration and fusion with structural imaging and was supported by the results of quantitative analysis. The absence of qualitative and quantitative NaSI asymmetry in one participant, should lead to caution in accepting the clinical validity of this technique and may challenge the underlying assumption that there are low sodium concentrations in the hydropic ES. Despite the limitations, this study provides a proof of principle for the potential role of ²³Na MRI in the evaluation of MD without the requirement for gadolinium-based contrast agents and supports a theoretical basis for its wider evaluation in MD and other inner ear pathologies. Abbreviations bSSFP balanced steady-state free precession 3D-FLAIR 3D Fluid Attenuated Inversion Recovery 3D-IR Three-dimensional inversion recovery EH endolymphatic hydrops ES endolymphatic space FLASH fast low angle shot GBCA gadolinium-based contrast agents IR inversion recovery MD Ménière’s disease MRI magnetic resonance imaging (MRI) PS perilymphatic space 23 Na sodium NaSI 23 Na sodium MRI signal intensity SAR specific absorption rate SI signal intensity SNR signal to noise ratio SPACE sampling perfection with application optimised contrasts using different flip angle evolution T Tesla T2w T2 weighted TR repeat time Declarations Ethics approval and consent to participate Health Research Authority. Southwest Frenchay Research Ethics Committee. Ref 20/SW/0085. Initial approval 16/6/20. Amendment approval 15/11/22. We certify that the research was conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. • Consent for publication Consent was obtained from all participants and indicates ‘I allow the use of any information or results arising from this study for healthcare and/or medical research purposes.’ • Availability of data and material The data supporting this article has been deposited in the King’s College London research data repository, KORDS, at https://doi.org/10.18742/28368968. It is not openly available due to conditions of participant consent and may be shared with researchers on request. • Competing interests The authors declare that they have no competing interests • Funding The study was funded by the Royal College of Radiology Kodak Radiology Fund Scholarship. The funder did not have any specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Authors also acknowledge funding support from Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z); National Institute for Health Research Biomedical Research Centre at Guy’s & St Thomas’ Hospitals and King’s College London; Cancer Research UK National Cancer Imaging Translational Accelerator (A27066); the UK Research & Innovation London Medical Imaging and Artificial Intelligence Centre • Authors' contributions SC conceived the study, designed the study, acquired, analyzed and interpreted the patient data and drafted a manuscript. PL acquired, analysed and interpreted data. IP acquired and analysed data. HB acquired data. PT acquired data. SO designed the work, JH designed the work, interpreted data and substantially revised the draft manuscript All authors read and approved the final manuscript and have agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work Acknowledgements The study was funded by the Royal College of Radiology Kodak Radiology Fund Scholarship. The funder did not have any specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Authors also acknowledge funding support from Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z); National Institute for Health Research Biomedical Research Centre at Guy’s & St Thomas’ Hospitals and King’s College London; Cancer Research UK National Cancer Imaging Translational Accelerator (A27066); the UK Research & Innovation London Medical Imaging and Artificial Intelligence Centre References Havia M, Kentala E, PyykkÖ I. Prevalence of Menière’s Disease in General Population of Southern Finland. Otolaryngology–Head and Neck Surgery. 2005; 133:762–8. Hallpike CS, Cairns H.Observations on the pathology of Ménière’s Syndrome. JLO.1938; 53:625–55. Foster CA, Breeze RE. Endolymphatic hydrops in Ménière's disease: cause, consequence, or epiphenomenon? Otol Neurotol.2013; 234:1210-4. doi: 10.1097/MAO.0b013e31829e83df. PMID: 23921917 Nakashima T, Naganawa S, Sugiura M et al. Visualization of endolymphatic hydrops in patients with Meniere’s disease. Laryngoscope.2007; 117(3):415–20. Connor S, Grzeda MT, Jamshidi B, Ourselin S, Hajnal JV, Pai I. Delayed post gadolinium MRI descriptors for Ménière’s disease: a systematic review and meta-analysis. Eur Radiol.2023; 12: 7113-7135. doi: 10.1007/s00330-023-09651-8 Gürkov R, Jerin C, Flatz W, Maxwell R. Clinical manifestations of hydropic ear disease (Menière's). Eur Arch Otorhinolaryngol.2018; 276:27-40. doi: 10.1007/s00405-018-5157-3 Iwasaki S, Shojaku H, Murofushi T et al. Committee for Clinical Practice Guidelines of Japan Society for Equilibrium Research. Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research. Auris Nasus Larynx2020; 48:15-22. doi: 10.1016/j.anl.2020.10.009 Marckmann P, Skov L, Rossen K et al.Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol.2006; 17: 2359–2362. Ramalho J, Semelka RC, Ramalho M, Nunes RH, Al Obaidy M, Castillo M. Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update. American Journal of Neuroradiology.2016; 37:1192-1198. Venkatasamy A, Veillon F, Fleury A et al. Imaging of the saccule for the diagnosis of endolymphatic hydrops in Meniere disease, using a three-dimensional T2-weighted steady state free precession sequence: accurate, fast, and without contrast material intravenous injection. Eur Radiol.2017; Exp 1:14. doi: 10.1186/s41747-017-0020-7 Ishii M, Tanaka H, Asai R et al. New non-contrast MRI of endolymphatic hydrops in Ménière's disease considering inversion time. Laryngoscope Investig Otolaryngol.2024; 9: e1314. doi: 10.1002/lio2.1314. PMID: 39130211 Couloigner V, Sterkers O, Ferrary E. What's new in ion transports in the cochlea? Pflugers Arch.2012; 453:11-22. doi: 10.1007/s00424-006-0103-4 Trune DR. Ion homeostasis in the ear: mechanisms, maladies, and management. Curr Opin Otolaryngol Head Neck Surg.2010; 18: 413-9. doi: 10.1097/MOO.0b013e32833d9597 Wangemann P, Schacht J. Homeostatic mechanisms in the cochlea. In Springer Handbook of Auditory Research: The Cochlea, ed. Dallos P, Popper AN, Fay R. Springer, New York: 1996.p130-185. https://doi.org/10.1007/978-1-4612-0757-3_3 Madelin G, Regatte RR. Biomedical applications of sodium MRI in vivo. Journal of Magnetic Resonance Imaging.2013; 38: 511–529. Gurney PT, Hargreaves BA, Nishimura DG. Design and analysis of a practical 3D cones trajectory. Magn Reson Med. 2006; 55:575-82. doi: 10.1002/mrm.20796 Brnawi HA, Balaji K, Kukran S, Connor SEJ, Hajnal JV, Bangerter NK et al. Boosting SNR for sodium BSSFP imaging . Proc Intl Soc Mag Reson Med. 2024; 32:3035. Bangerter NK, Hargreaves BA, Vasanawala SS, Pauly JM, Gold GE, Nishimura DG. Analysis of multiple-acquisition SSFP. Magn Reson Med.2004; 51:1038-47. doi: 10.1002/mrm.20052. PMID: 15122688. Nakashima T, Naganawa S, Pyykkö I et al. Grading of endolymphatic hydrops using magnetic resonance imaging. Acta Otolaryngol Suppl.2009; 560:5-8. doi: 10.1080/00016480902729827 Lopez-Escamez JA, Carey J, Chung WH et al. Diagnostic criteria for Ménière’s disease. J Vestib Res.2015; 25:1–7. doi: 10.1007/s00106-017-0387-z Knoll F, Schwarzl A, Diwoky C, Sodickson DK. gpuNUFFT - An open-source GPU library for 3D regridding with direct Matlab interface. In: ISMRM-ESMRMB; 10-16 May 2014; Milan, Italy. https://archive.ismrm.org/2014/4297.html Scheffler K. A pictorial description of steady-states in rapid magnetic resonance imaging. Concepts Magn. Reson.1999; 11: 291-304. https://doi.org/10.1002/(SICI)1099-0534(1999)11:53.0.CO;2-J Schindelin J, Arganda-Carreras I, Frise E et al. Fiji: an open-source platform for biological-image analysis. Nat Methods.2012; 9: 676–682. https://doi.org/10.1038/nmeth.2019 Keaveney S, Dragan A, Rata M et al. Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study. Insights Imaging.2023; 14: 170. https://doi.org/10.1186/s13244-023-01498-3 Fedorov A, Beichel R, Kalpathy-Cramer J et al. 3D Slicer as an image computing platform for quantitative imaging network. Magn Reson Imag. 2012; 30:1323-41. doi: 10.1016/j.mri.2012.05.001. Bujang M A, Baharum N. Guidelines of the minimum sample size requirements for Cohen’s Kappa. Epidemiology Biostatistics and Public Health.2017; 14: e12267-1-e12267-10. https://doi.org/10.2427/12267 Wilcox M, Wright SM, McDougall M. A review of non-1H RF receive arrays in magnetic resonance imaging and spectroscopy. IEEE Open J Eng Med Biol. 2020; 1:290–300. Zhao Y, Guo R, Li Y, Thulborn KR, Liang Z-P. High-resolution sodium imaging using anatomical and sparsity constraints for denoising and recovery of novel features. Magn Reson Med. 2021; 86: 625–636. https://doi.org/10.1002/mrm.28767 Jerin C, Floerke S, Maxwell R, Gürkov R. Relationship between the extent of endolymphatic hydrops and the severity and fluctuation of audiovestibular symptoms in patients with Menière's Disease and MRI evidence of hydrops. Otol Neurotol.2018; 39: e123-e130. doi: 10.1097/MAO.0000000000001681. Zhang Y, Cui Y, Hu Y et al. Changes in endolymphatic hydrops visualized by magnetic resonance imaging after sac surgery. J. Huazhong Univ. Sci. Technol. [Med. Sci.].2016; 36, 736–740. https://doi.org/10.1007/s11596-016-1654-z Kim SH, Marcus DC. Regulation of sodium transport in the inner ear. Hear Res.2011; 280: 21-9. doi: 10.1016/j.heares.2011.05.003 Shi X, Gillespie PG, Nuttall AL. Na+ influx triggers bleb formation on inner hair cells. Am J Physiol Cell Physiol.2005; 288:C1332-41. doi: 10.1152/ajpcell.00522.2004 Mirza S, Gokhale S. Pathophysiology of Meniere’s Disease. Up to Date on Meniere’s Disease. InTech. 2017: Available at: http://dx.doi.org/10.5772/66388.InTech. doi: 10.5772/66388 Konishi T. Some observations on negative endocochlear potential during anoxia. Acta Otolaryngol. 1979; 87:506-516. https://doi.org/10.3109/00016487909126459 Lazarini PR, Camargo AC. Idiopathic sudden sensorineural hearing loss: etiopathogenic aspects. Braz J Otorhinolaryngol.2006; 72:554-61. doi: 10.1016/s1808-8694(15)31004-1 Sellick PM, Johnstone BM. Changes in cochlear endolymph Na + concentration measured with Na + specific microelectrodes. Pflugers Arch.1972; 336: 11–20. https://doi.org/10.1007/BF00589137 Guipponi M, Vuagniaux G, Wattenhofer M et al. The transmembrane serine protease (TMPRSS3mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaCin vitro. Hum Mol Genet. 2002; 11:2829-36. doi: 10.1093/hmg/11.23.2829 Cate WJ, Curtis LM, Rarey KE. Effects of low-sodium, high-potassium dietary intake on cochlear lateral wall Na+,K(+)-ATPase. Eur Arch Otorhinolaryngol.1994; 251:6-1. Choi HS, Chang JH, Kim JH, Kang JW. Is high sodium intake associated with hearing impairment? The association between spot urine sodium concentration and hearing threshold in Korean adolescents. Asia Pac J Clin Nutr.2018; 27:646-648. doi: 10.6133/apjcn.042017.09 Furstenberg AC, Lashmet FH, Lathrop F. Menière's symptom complex: medical treatment. 1934. Ann Otol Rhinol Laryngol.1992; 101:20-31. doi: 10.1177/000348949210100109 Perlman HB, Goldinger JM, Cales JO. Electrolyte studies in Meniere's disease. Laryngoscope.1953; 63:640-651. Rizk HG, Mehta NK, Qureshi U et al. Pathogenesis and Etiology of Ménière Disease: A Scoping Review of a Century of Evidence. JAMA Otolaryngol Head Neck Surg.2022; 148:360–368. doi:10.1001/jamaoto.2021.4282 Eckhard AH, Zhu M, O'Malley JT et al. Inner ear pathologies impair sodium-regulated ion transport in Meniere's disease. Acta Neuropathol.2019;137:343-357. doi: 10.1007/s00401-018-1927-7. Kim SH, Park HY, Choi HS et al. Functional and molecular expression of epithelial sodium channels in cultured human endolymphatic sac epithelial cells. Otol Neurotol.2009;30:529–534. doi:10.1097/MAO.0b013e31819a8e0e. Schuknecht HF, Rüther A. Blockage of longitudinal flow in endolymphatic hydrops. Eur Arch Otorhinolaryngol. 1991; 248:209-17. doi: 10.1007/BF00173659. Andrews JC, Honrubia V. Premenstrual exacerbation of Meniere's disease revisited. Otolaryngologic Clinics of North America. 2010;43: 1029-1040. doi: 10.1016/j.otc.2010.05.012. Teggi R, Zagato L, Delli Carpini S et al. Genetics of ion homeostasis in Ménière’s Disease. Eur Arch Otorhinolaryngol.2017; 274, 757–763. https://doi.org/10.1007/s00405-016-4375-9 Silverstein H, Takeda T. Endolymphatic Sac Obstruction Biochemical Studies. Annals of Otology, Rhinology & Laryngology.1977; 86:493-499. doi:10.1177/000348947708600408. Buckingham RA, Valvassori GE. Inner Ear Fluid Volumes and the Resolving Power of Magnetic Resonance Imaging: Can it Differentiate Endolymphatic Structures? Annals of Otology, Rhinology & Laryngology.2001; 110:113-117. doi:10.1177/000348940111000204 Li J, Wang L, Hu N et al. Longitudinal variation of endolymphatic hydrops in patients with Ménière's disease. Ann Transl Med.2023; 11:44. doi: 10.21037/atm-22-6313 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7420941","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508164747,"identity":"8dd20075-5677-4f8b-8faa-b018aeb54c49","order_by":0,"name":"Steve Connor FRCR","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie2RMQrCQBBFJwTWZiBtREmusLKFCpK7yEKqHMA+YJUDCAa8gkdYCWyVA2yZIFilCKRJYWFCCKRx1c5iX/WLecwfBsBg+HtqAcshCc0UmWTrJAB/U2z8RvEvsXRrCLz1IpbNLg8QZllhY/5eoZKE8xNwtk0lP0eKI2BIbVQahSBjCGJ/VRGzo1p0xaKuYa0pdnQa9hyVTa84lV4BidYdRgVUp7j9Fl0xGa7KhHJGVcitJOdI3Ae9pZrz/TgrRHsIPKp4Bq0MPMfhZVFJTbFh1yT3jxKfBIPBYDDoeQFFAEsRGdfyVwAAAABJRU5ErkJggg==","orcid":"","institution":"King’s College London","correspondingAuthor":true,"prefix":"","firstName":"Steve","middleName":"Connor","lastName":"FRCR","suffix":""},{"id":508164748,"identity":"deb9831d-4718-44aa-885a-9da3d2ab7fd2","order_by":1,"name":"Peter Lally","email":"","orcid":"","institution":"Imperial College London","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Lally","suffix":""},{"id":508164749,"identity":"44668762-819e-41ab-8812-c876b1b3b65a","order_by":2,"name":"Irumee Pai","email":"","orcid":"","institution":"King’s College London","correspondingAuthor":false,"prefix":"","firstName":"Irumee","middleName":"","lastName":"Pai","suffix":""},{"id":508164750,"identity":"65940f84-16e2-4fbd-8d0d-8382de3d647a","order_by":3,"name":"Haneefah Brnwari","email":"","orcid":"","institution":"Imperial College London","correspondingAuthor":false,"prefix":"","firstName":"Haneefah","middleName":"","lastName":"Brnwari","suffix":""},{"id":508164751,"identity":"1a270f00-ae42-4011-908d-5182af26c5ce","order_by":4,"name":"Philip Touska","email":"","orcid":"","institution":"Guy’s Hospital and St Thomas’ Hospital","correspondingAuthor":false,"prefix":"","firstName":"Philip","middleName":"","lastName":"Touska","suffix":""},{"id":508164752,"identity":"65ed6c5e-d47d-42e5-bfc4-d3ea1dcfc264","order_by":5,"name":"Sebastien Ourselin","email":"","orcid":"","institution":"King’s College London","correspondingAuthor":false,"prefix":"","firstName":"Sebastien","middleName":"","lastName":"Ourselin","suffix":""},{"id":508164753,"identity":"4adc057e-a088-40d9-8afc-1e9e30ef668f","order_by":6,"name":"Joseph V Hajnal","email":"","orcid":"","institution":"King’s College London","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"V","lastName":"Hajnal","suffix":""}],"badges":[],"createdAt":"2025-08-20 23:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7420941/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7420941/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12880-025-01986-6","type":"published","date":"2025-11-11T15:57:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90465159,"identity":"baf26b57-1d12-48fb-99a6-525d23b2dcf4","added_by":"auto","created_at":"2025-09-03 05:13:49","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":145573,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e23\u003c/sup\u003eNa MRI axial images demonstrating landmark placement for registration. These are placed in the a) fourth ventricle (L-4, L-12), medial cerebello-pontine angle cistern (L-3, L-15) and internal auditory meatus (L-16) and b) lateral cerebello-pontine angle cistern (L-7) and Meckel’s caves (L-4, L-5). Selected corresponding points are shown in c) and d) on the structural T2-SPACE sequences.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7420941/v1/1cd43ab6811d143b897978ad.jpeg"},{"id":90463708,"identity":"49ee5601-f1d4-426e-a74c-766b498cfb7a","added_by":"auto","created_at":"2025-09-03 05:05:49","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":79354,"visible":true,"origin":"","legend":"\u003cp\u003eDelayed post-gadolinium 3D inversion-recovery (a,b), unfused \u003csup\u003e23\u003c/sup\u003eNa MRI images (c,d) and \u003csup\u003e23\u003c/sup\u003eNa MRI images registered/fused to \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images (e,f). Participant C with left sided severe vestibulo-cochlear endolymphatic hydrops and good quality \u003csup\u003e23\u003c/sup\u003eNa MRI images. The endolymphatic hydrops was correctly lateralised by observer 1 on \u003csup\u003e23\u003c/sup\u003eNa MRI images both before and after registration/fusion to structural imaging. The cochlea (vertical filled arrow) and vestibule (horizontal filled arrow) are indicated. Delayed post gadolinium 3D inversion-recovery sequence demonstrates the enhancing perilymphatic space with small non-enhancing endolymphatic structures in the normal right ear (a) whilst there are dilated endolymphatic structures in the pathological left ear with endolymphatic hydrops (b). The enhancing left vestibular perilymph is completely replaced by the enlarged endolymphatic structures.\u0026nbsp; Axial \u003csup\u003e23\u003c/sup\u003eNa MRI images and registered/fused \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images of the right ear (c and e) and left ear (d and f). The cochlea and vestibule are indicated on the registered/fused \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images (e, f) and their expected locations are indicated on \u003csup\u003e23\u003c/sup\u003eNa MRI images (c, d). The normal right ear (a and c) demonstrates \u003csup\u003e23\u003c/sup\u003eNa MRI grade 1 signal relative to the adjacent internal auditory meatus (vertical open arrow), but with anatomical compatibility scored as grade 3 (entirely concordant). The pathological left ear with endolymphatic hydrops (b and d) did not demonstrate any visible \u003csup\u003e23\u003c/sup\u003eNa MRI signal (grade 0) in the line of the inner ear structures on the registered/fused \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images (d) despite clear visibility of signal within the internal auditory meatus (vertical open arrow). The \u003csup\u003e23\u003c/sup\u003eNa MRI images grey scale imaging may be accessed in the supplementary data.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7420941/v1/b4a2a139445d47e46c2adb53.jpeg"},{"id":90463709,"identity":"8c2f7005-df42-47b8-b5a1-2f680c0670c4","added_by":"auto","created_at":"2025-09-03 05:05:49","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":80897,"visible":true,"origin":"","legend":"\u003cp\u003eDelayed post-gadolinium 3D inversion-recovery (a,b), unfused \u003csup\u003e23\u003c/sup\u003eNa MRI images (c,d) and \u003csup\u003e23\u003c/sup\u003eNa MRI images registered/fused to \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images (e,f). Participant A with left sided severe vestibulo-cochlear endolymphatic hydrops and suboptimal quality \u003csup\u003e23\u003c/sup\u003eNa MRI images. The endolymphatic hydrops was only correctly lateralised by observer 1 on \u003csup\u003e23\u003c/sup\u003eNa MRI images after it was registered and fused to structural imaging. The cochlea (vertical filled arrow) and vestibule (horizontal filled arrow) are indicated. Delayed post gadolinium 3D inversion-recovery sequence demonstrates the enhancing perilymphatic space with small non-enhancing endolymphatic structures in the normal right ear (a) whilst there are dilated endolymphatic structures in the pathological left ear with endolymphatic hydrops (b). Axial \u003csup\u003e23\u003c/sup\u003eNa MRI images and registered/fused \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images through the right ear (c and e) and left ear (d and f). The cochlea (vertical filled arrow) and vestibule (horizontal filled arrow) are indicated on the registered/fused \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images (e, f) and their expected locations are indicated on \u003csup\u003e23\u003c/sup\u003eNa MRI images (c, d). The normal right ear (c) demonstrated \u003csup\u003e23\u003c/sup\u003eNa MRI grade 3 signal lateral to the internal auditory meatus (vertical open arrow) but the anatomical compatibility of this signal was uncertain and scored as grade 1 (minor overlap). However, following registration and fusion (c) there was noted to be major overlap with the inner ear structures. The pathological EH left ear (b and d) did not demonstrate any visible \u003csup\u003e23\u003c/sup\u003eNa MRI inner ear signal (grade 0) lateral to the internal auditory meatus (vertical open arrow). Note the \u003csup\u003e23\u003c/sup\u003eNa MRI signal from the inferior temporal lobes which lies anterior to the cochlea on each side. The \u003csup\u003e23\u003c/sup\u003eNa MRI images grey scale imaging may be accessed in the supplementary data.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7420941/v1/ee574b9c3ac80731e6cd086a.jpeg"},{"id":90463713,"identity":"7c929f34-4d35-4a24-866e-ba614a679854","added_by":"auto","created_at":"2025-09-03 05:05:49","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":144028,"visible":true,"origin":"","legend":"\u003cp\u003eScreenshots from 3D-Slicer 5.6.2 illustrate the segmentation of the inner ear structures and the internal auditory meatus. Segmentations of the a) vestibule, b) cochlea and c) lateral internal auditory meatus are shown with multiplanar reformatted images and 3D-rendering (top right in each pane). The corresponding segmentations of the d) vestibule, e) cochlea and f) lateral internal auditory meatus are overlaid on axial fused registered \u003csup\u003e23\u003c/sup\u003eNa MRI- T2-SPACE images.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7420941/v1/d2d7529e4428a03ec165bb9f.jpeg"},{"id":96105017,"identity":"751513bc-64b2-43ff-a28f-2d35daf782c8","added_by":"auto","created_at":"2025-11-17 16:07:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1883147,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7420941/v1/a1b06c5b-9316-4f7f-b829-6919ade75d48.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"7-Tesla sodium magnetic resonance imaging of the inner ears in unilateral Ménière’s Disease and endolymphatic hydrops: An exploratory study","fulltext":[{"header":"Background","content":"\u003cp\u003eThe inner ear fluid comprises a central endolymphatic compartment which is separated by membranes from the surrounding larger perilymphatic compartment. The principle endolymphatic structures are the saccule and utricle of the vestibule, and the scala media of the cochlea. M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s disease (MD) is an inner ear condition with a typical clinical presentation of episodic vertigo, low- to mid-frequency hearing loss and fluctuating aural symptoms and has a prevalence of up to 513/100,000 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The pathological hallmark of MD is endolymphatic hydrops (EH) which represents an expansion of the endolymphatic space (ES) into the surrounding perilymphatic space (PS) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Temporal bone studies demonstrate EH in 98.8% of patients with clinically suspected MD [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDifferential permeability of the endolymph and perilymph to gadolinium-based contrast agents (GBCA) allows the enhancing PS to be distinguished from the non-enhancing ES on delayed post-GBCA MRI three-dimensional inversion recovery (3D-IR) sequences. Three-dimensional inversion recovery (3D-IR) sequences enable the detection of low concentrations of gadolinium in the perilymph with high resolution depiction of the inner ear compartments on delayed post-GBCA MRI. Following its initial description in 2007 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], MRI has been progressively utilised worldwide for the demonstration of EH. Meta-analysis has indicated a high sensitivity (87%) and specificity (91%) for the diagnosis of MD with optimal combinations of MRI descriptors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The increasing role of MRI in hydropic ear disease, has led to proposals for imaging-based rather than clinical terminology [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and the emergence of MRI features in diagnostic guidelines for MD [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIntravenous GBCAs have an excellent safety record but they are not exempt from safety considerations. A causative relationship between less stable linear chelate GBCAs and nephrogenic systemic fibrosis is described in patients with severe renal insufficiency. In addition, there is evidence of gadolinium deposition in the human brain after multiple administrations, although this is reduced with macrocyclic agents [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, it would be beneficial to develop a non-contrast enhanced MRI technique to detect and monitor MD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Whilst there are some reports of EH being demonstrated with non-contrast high resolution T2 weighted (T2w) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and 3D Fluid Attenuated Inversion Recovery (3D-FLAIR) sequences [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], these have not been widely reproduced.\u003c/p\u003e\u003cp\u003eThe ES and PS have distinctive ionic compositions which are maintained by ion channels and transport mechanisms [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The maintenance of ion haemostasis is required for hair cell function with endolymph surrounding the stereocilia and perilymph bathing the hair cell bodies. Hair cells depolarize with motion, so allowing the transduction of sound and head acceleration into the nerve impulses necessary for normal hearing and balance. One notable feature of the ionic environment is that the sodium (\u003csup\u003e23\u003c/sup\u003eNa) concentration in the ES (1.3 mM) is considerably lower than that of the PS (141\u0026ndash;148 mM) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It may be hypothesised that this differential biodistribution of \u003csup\u003e23\u003c/sup\u003eNa concentration could be probed with \u003csup\u003e23\u003c/sup\u003eNa MRI, and that the expanded ES in patients with MD would result in lower \u003csup\u003e23\u003c/sup\u003eNa MRI signal relative to the normal ear. \u003csup\u003e23\u003c/sup\u003eNa MRI signal is limited by the low natural abundance, rapid quadrupolar relaxation and lower gyromagnetic ratio of \u003csup\u003e23\u003c/sup\u003eNa [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], although this may be partly mitigated by imaging at ultra-high field strength. Validation of \u003csup\u003e23\u003c/sup\u003eNa MRI outside the brain, kidney and cartilage is limited, and imaging of the inner ears is particularly challenging due to magnetic susceptibility gradients at bone and air interfaces, small anatomical structures and suboptimal coil sensitivity for deep skull base structures.\u003c/p\u003e\u003cp\u003eWe aimed to explore whether a \u0026sup2;\u0026sup3;Na 7 Tesla (7T) MRI sequence could distinguish pathological ears by detecting asymmetrically reduced \u0026sup2;\u0026sup3;Na signal in patients with unilateral MD and EH.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eParticipants\u003c/p\u003e\u003cp\u003e All methods in this prospective study were carried out in accordance with relevant guidelines and regulations and the experimental protocol was approved by the institutional ethical committee (Health Research Authority. Southwest Frenchay Research Ethics Committee. Initial approval 16/6/20. Amendment approval 15/11/22. IRAS ID: 259867, Rec Reference: 20/SW/0085). Informed consent was obtained from all subjects.\u003c/p\u003e\u003cp\u003eThe Picture Archiving and Communication System (Sectra AB, Sweden) was interrogated for consecutive patients undergoing clinical delayed post-GBCA inversion recovery (IR) MRI between December 2017 and October 2022. These patients had presented with symptoms of EH including episodic vertigo, sudden-onset or fluctuating SNHL, aural fullness and tinnitus. The contemporary clinical and audiometric data was reviewed by two observers (SC, IP) who were blinded to imaging findings, and patients were classified according to the current 2015 Barany Society criteria [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Clinical data was recorded in the six months and audiometry in the twelve months prior to the MRI study.\u003c/p\u003e\u003cp\u003eThe delayed post-GBCA IR sequences were independently analysed by two radiologists (PT, SC), with 7- and 25-years of subspecialty head and neck radiology experience. The radiologists rated the images according to the Nakashima criteria [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] whilst blinded to clinical diagnosis. Participants were eligible for the study when both observers recorded unilateral \u0026ldquo;definite MD\u0026rdquo; on clinical review and both radiologists recorded unilateral severe (Grade 2 Nakashima) vestibular and cochlear EH on imaging analysis. A priori exclusion criteria were inadequate contemporary clinical details for diagnostic classification, clinical or radiological suspicion of secondary hydrops, previous inner ear operations, and technically inadequate MR imaging. The first four eligible participants, determined by the date of their initial diagnostic MRI scan, were invited to take part in the research 7 tesla (7T) \u003csup\u003e23\u003c/sup\u003eNa MRI study 7-tesla (^23Na) MRI study in accordance with the study protocol.\u003c/p\u003e\u003cp\u003e\u003csup\u003e23\u003c/sup\u003eNa MRI sequence and reconstruction development\u003c/p\u003e\u003cp\u003e\u003csup\u003e23\u003c/sup\u003eNa MRI of the inner ears was refined on a 7T Magnetom\u0026reg; Terra scanner, (Siemens Healthineers, Erlangen) using a 1Tx/ 32Rx \u003csup\u003e23\u003c/sup\u003eNa head coil (Rapid Biomedical, Rimpar) through iterative phantom and healthy volunteer (HV) imaging. Initial HV sequences were performed with acquisition times of 40\u0026ndash;55 minutes to evaluate parameter changes, which were applied to an approximately 30 minutes sequence that could be tolerated by participants. A 3D Cones \u003cem\u003ek\u003c/em\u003e-space trajectory was utilised which allowed for very short echo times and repeat time (TR) of \u003csup\u003e23\u003c/sup\u003eNa MRI, whilst providing increased signal to noise (SNR) efficiency and good motion properties [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A balanced steady-state free precession (bSSFP) sequence was employed [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] since it demonstrated greater SNR on phantom and HV studies compared to a fast low angle shot (FLASH) sequence. A disadvantage of the bSSFP sequence is its sensitivity to static field (B\u003csub\u003e0\u003c/sub\u003e) inhomogeneity in the region of the inner ears due to local air, bone and fluid interfaces, and this resulted in banding artefact which was exacerbated by the ultra-high field strength. Therefore, phase cycling was used to enable systematic displacement of band locations and reduction in band conspicuity through image summation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A 3 mm voxel size provided suboptimal delineation of the inner ears, and a 2 mm voxel size was considered to provide an appropriate balance of SNR and spatial resolution. Blurring of the images was reduced with a 2 ms readout compared to 4 ms and 10 ms readouts. The TR remained as required for the longer readout of 10 ms. A further reduction in TR would have precluded the application of a high enough flip angle for efficient fluid imaging whilst remaining within specific absorption rate (SAR) limits.\u003c/p\u003e\u003cp\u003eThe final research 7T \u003csup\u003e23\u003c/sup\u003eNa MRI study comprised a bSSFP phased cycled sequence and a 3D cones trajectory: 1ms radiofrequency pulse width, 2x2x2 mm resolution, 240 mm\u003csup\u003e3\u003c/sup\u003e field of view, flip angle 25\u003csup\u003e0\u003c/sup\u003e, TR 14.26/TE 1.06ms, 2ms readout and 5 phase cycles with time per phase cycle 6.24 min. A complex summation of the five phased cycled datasets, each adjusted by its own linear phase cycling increment, resulted in three signal components (F\u003csub\u003e0\u003c/sub\u003e, F\u003csub\u003e1\u003c/sub\u003e, and F\u003csub\u003e\u0026minus;\u0026thinsp;1\u003c/sub\u003e) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Each data set was reconstructed via nonuniform-FFT (conjugate-gradient SENSE) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and a composite image combined all three F-state components via root sum of squares. The images were reconstructed with a frequency offset sweep set at 20Hz steps from \u0026minus;\u0026thinsp;100 to 200 Hz to correct for local susceptibility effects and were saved as 4 D stacks [X Y Z Hz offset] in NIfTI format.\u003c/p\u003e\u003cp\u003eClinical delayed post-gadolinium 3D-IR MRI sequences\u003c/p\u003e\u003cp\u003eDelayed post-gadolinium 3D-IR MRI sequences and three dimensional (3D) T2w structural imaging of the inner ears and been previously acquired according to routine clinical scanning protocols. The delayed post-gadolinium 3D-IR MRI sequences were used to assess participant eligibility whilst 3D T2w structural imaging were used for subsequent image fusion with \u003csup\u003e23\u003c/sup\u003eNa MRI. Clinical MRI was performed on a 3T Magnetom\u0026reg; Skyra (Siemens Healthineers, Erlangen) scanner with a 64-channel head coil. 3D-IR sequences with phase corrected real reconstruction (3D real-IR) were acquired 4 hours after intravenous administration of gadoterate meglumine (0.2 mmol/kg) according to the institutional clinical protocol. 3D T2w imaging to delineate the inner ear anatomy was performed with a T2w sampling perfection with application optimised contrasts using different flip angle evolution (T2w SPACE). Siemens product sequences were used with parameters tabulated in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMRI parameters for clinical imaging of the inner ears\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3D real-IR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3D real-IR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT2-SPACE\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRepetition time\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6000 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15130 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1000 ms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEcho time\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e180 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e550 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e125 ms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInversion time\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2000 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2700 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of excitations\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRefocusing flip angle\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e180\u0026deg; (constant)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130\u0026deg; (constant)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100\u0026deg;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePixel band width\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e220\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e435\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e255\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEcho train length\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e267\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePixel spacing\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.66 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.31 mm\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSlice thickness\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3 mm\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMatrix size\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e256 x 240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e320 x 270\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e262 x 512\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eField of view\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e190 x 178 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e210 X177 mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80 x 160 mm\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAcquisition time\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.38 min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.21 min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.38 min\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRegistration and qualitative analysis\u003c/p\u003e\u003cp\u003eThe reconstructed combined F state \u003csup\u003e23\u003c/sup\u003eNa MR images were viewed across the range of off-resonance frequencies using ImageJ [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The \u003csup\u003e23\u003c/sup\u003eNa MR image quality and artefact (distortion, susceptibility and ghosting) was evaluated according to a Likert scale (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The optimal frequency offset for the depiction of each inner ear with minimal blurring was then selected. All \u003csup\u003e23\u003c/sup\u003eNa MRI images grey scale imaging may be accessed in the supplementary data. Two observers (SC, IP) independently registered the \u003csup\u003e23\u003c/sup\u003eNa MR images to the 3T T2w SPACE sequence for each ear using 3D-Slicer 5.6.2 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] landmark-based registration, using 9\u0026ndash;16 control points (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The T2w SPACE sequence was chosen as the fixed volume and the \u003csup\u003e23\u003c/sup\u003eNa MRI as the moving volume in thin-plate spline mode.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGrading scales for image quality, artefact, signal visibility and anatomical compatibility\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eImage quality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eArtefact\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eVisibility\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAnatomical compatibility\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon-diagnostic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSevere effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNot visible\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eStructure not visible\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSuboptimal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eModerate effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDecreased signal relative to adjacent structure*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMajor concern/minority (\u0026lt;\u0026thinsp;50%) overlap\u003cb\u003e**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMinimal effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSimilar signal to adjacent structure*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMinor concern/major (\u0026gt;\u0026thinsp;50%) overlap\u003cb\u003e**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExcellent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo artefact\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIncreased signal relative to adjacent structure*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEntirely concordant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e*\u003cem\u003eAdjacent structure\u003c/em\u003e is the cerebello-pontine angle cistern for internal auditory meatus signal and the internal auditory meatus for inner ear (cochlea and vestibule) signal\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e**This may be because signal extends outside of the anatomical structure or only overlaps part of the anatomical structure\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe two observers independently analysed the \u003csup\u003e23\u003c/sup\u003eNa MR images in isolation and then with the \u003csup\u003e23\u003c/sup\u003eNa MR images registered and fused to the T2w SPACE sequence (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), whilst blinded to clinical and delayed post-GBCA 3D-IR data. The visibility and anatomical compatibility of \u003csup\u003e23\u003c/sup\u003eNa MRI signal in each IAM, cochlea and vestibule were qualitatively graded with Likert scales (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The visibility grades were based on the qualitative evaluation of \u003csup\u003e23\u003c/sup\u003eNa MR signal intensity (NaSI) when compared to that returned by adjacent structures (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The grading of anatomic compatibility was based on prior anatomical knowledge for the \u003csup\u003e23\u003c/sup\u003eNa MR images in isolation and depended on overlap with the corresponding anatomy on the T2w SPACE sequence for the registered and fused images (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The certainty of laterality was classified by comparing the difference between cochlea or vestibule visibility grade and the adjacent fundus of the IAM between the two sides. If either cochlea or vestibule visibility grade (relative to the fundus of the IAM) was 1 point greater than the contralateral ear and it had least grade 2 anatomic compatibility on both sides, then it was classified as possible laterality. If either cochlea or vestibule visibility grade was 2 points greater (relative to the fundus of the IAM) than the contralateral ear and it had at least grade 2 anatomic compatibility on both sides, then it was classified as definite laterality.\u003c/p\u003e\u003cp\u003eSegmentation and quantitative analysis\u003c/p\u003e\u003cp\u003eThe observers subsequently manually segmented each cochlea, vestibule and lateral half of IAM on the T2w SPACE images, facilitated by comparable intensity-based thresholding (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The manually segmented masks were visualized by 3D maximum intensity projections to ease quality assessment. The segmentations were then transferred to the transformed \u003csup\u003e23\u003c/sup\u003eNa MRI, and the SI statistics were extracted for each of the segmented volumes.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe mean, standard deviation and median of the NaSI for each cochlea and vestibule was documented, and the ratio of the median cochlea and vestibule NaSI to that of the adjacent IAM was calculated. Intraclass correlation coefficients (ICC) evaluated the absolute agreement of inner ear (cochlea and vestibule) median NaSI between the two observers. The small sample size precluded reliability statistics for the qualitative analysis [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eParticipant characteristics\u003c/p\u003e\u003cp\u003eThere were 4 eligible participants imaged (age mean 60.3 years, range 33\u0026ndash;78 years; 2f, 2m) with a mean duration of symptoms of 16 years (range 3\u0026ndash;40 years). The laterality of MD, audio-vestibular symptoms, audiogram and vestibular function tests are presented in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The laterality of the MD, audio vestibular symptoms, audiogram and vestibular function tests are presented in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Complete replacement of the vestibular perilymph by the dilated endolymphatic structures was evident on delayed post-GBCA MRI in 3/4 participants.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic, clinical and delayed post-gadolinium MRI data for the four participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge/sex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eM\u0026eacute;ni\u0026egrave;re\u0026rsquo;s Disease laterality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSymptoms\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eVestibular function tests\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDuration of symptoms\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAudiogram\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTime interval between clinical MRI and research \u003csup\u003e23\u003c/sup\u003eNa MRI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNakashima hydrops MRI grade (19)\u003c/p\u003e\u003cp\u003eipsilateral\u003c/p\u003e\u003cp\u003ecochlea/ vestibule\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNakashima hydrops MRI grade (19) contralateral\u003c/p\u003e\u003cp\u003ecochlea/vestibule\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78/M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIpsilateral tinnitus, HL, vertigo\u003c/p\u003e\u003cp\u003e(3\u0026ndash;5 hours)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIpsilateral calorics/VNG abnormal\u003c/p\u003e\u003cp\u003eContralateral normal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIpsilateral\u003c/p\u003e\u003cp\u003epan-frequency\u003c/p\u003e\u003cp\u003eContralateral panfrequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e60 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003cp\u003eComplete replacement of the vestibule by endolymph\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0/0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eright\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIpsilateral tinnitus, HL, vertigo\u003c/p\u003e\u003cp\u003e(2min-1 hour)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIpsilateral calorics/\u003c/p\u003e\u003cp\u003eVHIT/VNG abnormal\u003c/p\u003e\u003cp\u003eContralateral normal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIpsilateral\u003c/p\u003e\u003cp\u003epan-frequency\u003c/p\u003e\u003cp\u003eContralateral HFSNHL\u0026thinsp;\u0026gt;\u0026thinsp;3K\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e31 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003cp\u003eComplete replacement of the vestibule by endolymph\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0/0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68/M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIpsilateral tinnitus, HL, aural fullness, vertigo (30 min-12 hours)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIpsilateral\u003c/p\u003e\u003cp\u003eVHIT/VNG\u003c/p\u003e\u003cp\u003enormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIpsilateral\u003c/p\u003e\u003cp\u003epan-frequency\u003c/p\u003e\u003cp\u003eContralateral HFSNHL\u0026thinsp;\u0026gt;\u0026thinsp;6K\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003cp\u003eComplete replacement of the vestibule by endolymph\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0/0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIpsilateral tinnitus, HL, aural fullness, vertigo (3\u0026ndash;4 hours)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNone performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIpsilateral\u003c/p\u003e\u003cp\u003epan-frequency\u003c/p\u003e\u003cp\u003eContralateral normal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;50%\u003c/p\u003e\u003cp\u003ereplacement of the vestibule by endolymph\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0/0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003cb\u003eHL\u003c/b\u003e Hearing loss; \u003cb\u003eHFSNHL\u003c/b\u003e High frequency sensorineural hearing loss; \u003cb\u003eVHIT\u003c/b\u003e Video head impulse test; \u003cb\u003eVNG\u003c/b\u003e Videonystagmograph\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eQualitative analysis\u003c/p\u003e\u003cp\u003eThe outcomes of the qualitative analysis for image quality, IAM and inner ear visibility, anatomic compatibility and laterality are tabulated (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) and illustrated in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e (normal right ears and hydropic left ears). Eight ears in four participants were analysed by two observers (total of 16 observations). \u003csup\u003e23\u003c/sup\u003eNa MRI image quality was suboptimal with at least a moderate effect of artefact in 2/4 studies, largely due to distortion, blurring and ghosting resulting from movement artefact. The optimal frequency offsets selected for the depiction of each inner ear were (right/left)\u0026thinsp;+\u0026thinsp;200Hz /+200Hz, +\u0026thinsp;40Hz /-60Hz, -60Hz /-160Hz and +\u0026thinsp;60Hz / -100Hz for participants A, B, C and D respectively. The IAMs were at least partially visible in all \u003csup\u003e23\u003c/sup\u003eNa MRI studies prior to registration and fusion, with anatomical compatibility grades of 2 or 3 indicating that the majority of the IAM was depicted in 10/16 observations. When considering the cochlea and vestibule separately, following registration and fusion of \u003csup\u003e23\u003c/sup\u003eNa MRI, anatomical compatibility grades increased in 6/32 observations, decreased grades in 4/32, and remained the same in 22/32. Grade 2 or 3 anatomical compatibility grades were achieved in 12/16 normal inner ear observations following registration and fusion.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eQualitative analysis of \u003csup\u003e23\u003c/sup\u003eNa MRI studies for the four participants: Image quality, artefact, signal visibility, anatomical compatibility and lateralisation\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eImage quality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eArtefact\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eObserver\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c11\" namest=\"c6\"\u003e\u003cp\u003eSignal visibility/Anatomical compatibility\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e*Certainty of hydrops laterality and side\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSide of laterality correct/incorrect\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRight IAM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRight cochlea\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRight vestibule\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLeft IAM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLeft cochlea\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eLeft vestibule\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePre-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDefinite/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePost-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDefinite /left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDefinite/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePre-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e2/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e2/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePost-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e2/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e2/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePre-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePossible/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePossible/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePost-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePossible/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePossible/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePre-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePost-registration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eI/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDefinite/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e0/0\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e1/1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePossible/left\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eCorrect\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003eIAM; internal auditory meatus\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003eInner ear grades in the inner ear with EH are in \u003cb\u003ebold\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003e*The certainty of laterality was based on the relative difference in visibility of either the cochlea or vestibule to the IAM fundus when comparing the two sides. If either cochlea or vestibule visibility grade (relative to the fundus of the IAM) was 1 point greater than the contralateral ear and it had least grade 2 anatomic compatibility on both sides, then it was classified as possible laterality. If either cochlea or vestibule visibility grade was 2 points greater (relative to the fundus of the IAM) than the contralateral ear and it had at least grade 2 anatomic compatibility on both sides, then it was classified as definite laterality.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e Prior to registration and fusion, the anatomical compatibility and visibility grades indicated EH lateralisation in only 1/4 participants (participant C) for both observers. However, following registration and fusion with structural T2w SPACE imaging, there were 3/4 participants with lateralisation correctly independently predicted by both observers.\u003c/p\u003e\u003cp\u003eQuantitative analysis\u003c/p\u003e\u003cp\u003eThe mean, standard deviation and median inner ear NaSI are shown for the cochlea (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) and the vestibule (Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The mean (range) of cochlea volume was 83 (63\u0026ndash;110) mm\u003csup\u003e3\u003c/sup\u003e for observer 1 and 80 (59\u0026ndash;115) mm\u003csup\u003e3\u003c/sup\u003e for observer 2, whilst the mean (range) of vestibular volume was 47 (31\u0026ndash;59) mm\u003csup\u003e3\u003c/sup\u003e for observer 1 and 41 (33\u0026ndash;50) mm\u003csup\u003e3\u003c/sup\u003e for observer 2.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eQuantitative analysis of the cochlea on \u003csup\u003e23\u003c/sup\u003eNa MRI studies for the four participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u003cp\u003eEndolymphatic hydrops\u003c/p\u003e\u003cp\u003ecochlea signal intensity (x10\u003csup\u003e\u0026minus;\u0026thinsp;5\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003ecochlea signal intensity (x10\u003csup\u003e\u0026minus;\u0026thinsp;5\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e*Ratio of\u003c/p\u003e\u003cp\u003enormal cochlea median signal: hydropic cochlea median signal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e*Ratio of\u003c/p\u003e\u003cp\u003enormal cochlea/IAM median signal:\u003c/p\u003e\u003cp\u003ehydropic cochlea /IAM median signal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMedian cochlea/ Median IAM signal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eMedian cochlea/\u003c/p\u003e\u003cp\u003eMedian IAM signal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.5:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2.0:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.8:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.8:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.2:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.2:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.3:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2.8:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"12\"\u003e*Calculated from the mean of the two\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eQuantitative analysis of the vestibule on \u003csup\u003e23\u003c/sup\u003eNa MRI studies for the four participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u003cp\u003eEndolymphatic hydrops\u003c/p\u003e\u003cp\u003evestibule signal intensity (x10\u003csup\u003e\u0026minus;\u0026thinsp;5\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003evestibule signal intensity (x10\u003csup\u003e\u0026minus;\u0026thinsp;5\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e*Ratio of\u003c/p\u003e\u003cp\u003eNormal vestibule median signal:\u003c/p\u003e\u003cp\u003ehydropic vestibule median signal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e*Ratio of\u003c/p\u003e\u003cp\u003enormal vestibule/IAM median signal:\u003c/p\u003e\u003cp\u003ehydropic vestibule /IAM median signal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMedian vestibule/ Median IAM signal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eMedian vestibule/\u003c/p\u003e\u003cp\u003eMedian IAM signal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2.1:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2.9:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.8:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.7:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.9:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.9:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.1:1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2.2:1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObserver 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"12\"\u003e*Calculated from the mean of the two observers\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBased on the average ratings from the two observers, the normal: EH median NaSI ratios for the cochlea were 1.4:1, 0.8:1, 1.2:1, and 1.3:1 in the four participants. For the vestibule, the normal: EH median NaSI ratios were 2.1:1, 0.8:1, 1.9:1, and 1.1:1. The median NaSI was decreased in both the cochlea and vestibule of the EH ears in the 3/4 participants (participants A, C and D) who had the correct lateralisation on qualitative analysis following registration and fusion. When the median inner ear NaSI was scaled to the adjacent IAM NaSI, the corresponding ratios were 2.0:1, 0.8:1, 1.2: 1 and 2.8: 1 (mean 1.7:1) for the cochlea and 2.9:1, 0.7:1, 1.9:1 and 2.2: 1 (mean 1.9:1) for the vestibule. The ICC for the inner ear median NaSI was 0.70 (95% CI; 0.15\u0026ndash;0.89).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA \u003csup\u003e23\u003c/sup\u003eNa MRI bSSFP sequence was developed for the demonstration of the inner ears on a 7T MRI system. In four participants with unilateral MD, both observers correctly lateralised the ear with severe vestibulo-cochlear endolymphatic hydrops in only 1/4 participants with a signature of reduced inner ear signal on qualitative assessment of \u003csup\u003e23\u003c/sup\u003eNa MRI data alone. However, when \u003csup\u003e23\u003c/sup\u003eNa MRI was registered and fused to a T2 SPACE sequence, there was successful endolymphatic hydrops lateralisation by both observers in 3/4 participants. There was no incorrect lateralisation of EH by either observer either before or after registration and fusion. It was not possible to lateralise in participant B, and the potential reasons for this are discussed below. On quantitative analysis of segmented inner ear structures, the same 3/4 participants demonstrated increased \u003csup\u003e23\u003c/sup\u003eNa MRI median signal intensity in both the cochlea (1.2\u0026ndash;1.5 times) and vestibule (1.1\u0026ndash;2.1 times) in the normal ear relative to the symptomatic MD ear. The ratio between the median signal intensity of the normal and the pathological inner ears increased when it was scaled to the signal intensity of the adjacent IAM, with a 1.2\u0026ndash;2.8:1 ratio for the cochlea and a 1.9\u0026ndash;2.9:1 ratio for the vestibule.\u003c/p\u003e\u003cp\u003eThere are no previous reports of \u003csup\u003e23\u003c/sup\u003eNa MRI being applied to inner ear imaging, with considerable challenges resulting from the small volume anatomical structures and the variation in static magnetic field (B\u003csub\u003e0\u003c/sub\u003e) due to juxtaposition of bone, air and fluid. Our \u003csup\u003e23\u003c/sup\u003eNa MRI research sequence and post-processing was adapted to maximise SNR efficiency at adequate spatial resolution and to address artefacts due to off-resonance frequencies. Acquisition with a fast (non-Cartesian) 3D-Cones trajectory was employed to reduce the duration of signal readout, as required by the rapid T2* decay of \u003csup\u003e23\u003c/sup\u003eNa, and to improve SNR [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A bSSFP sequence was also utilised to boost SNR [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], with the banding artefact minimised by utilising a short TR and employing phase-cycling [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] with signal averaging across cycles. It was decided a priori that a 30-minute sequence would be reasonable from the patient perspective, but 2/4 of the MRI studies demonstrated suboptimal image quality due to participant movement. More targeted array coils with parallel imaging strategies [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and methods to reconstruct high-quality MRI data from limited k-space data [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] may optimise 7T \u003csup\u003e23\u003c/sup\u003eNa MRI inner ear imaging in the future.\u003c/p\u003e\u003cp\u003eThe findings of this study indicate that \u003csup\u003e23\u003c/sup\u003eNa MRI can detect changes in MD, inviting exploration of other potential applications to inner ear pathologies. Firstly, \u003csup\u003e23\u003c/sup\u003eNa MRI may have a role in evaluating interval changes in size of the endolymphatic compartment and monitoring the evolution of EH, since structural imaging has been proven to be limited in its ability to demonstrate treatment response and explain fluctuations in symptoms [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Secondly, there may be a wider role for \u003csup\u003e23\u003c/sup\u003eNa MRI in probing the ionic milieu of the inner ear as an insight to disease processes. It is recognised that increases or variations in endolymph sodium concentrations result in cellular dysfunction, and clinical audio-vestibular disorders [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, there are logistical and technical difficulties in obtaining fluid samples in vivo, since it is both invasive and the composition may be disturbed during surgical procedures [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. \u003csup\u003e23\u003c/sup\u003eNa MRI could offer a non-invasive bio-marker to evaluate the sodium concentration of the pathological inner ear in the presence of normal structural MRI appearances. For instance, abnormalities of sodium haemostasis have been linked with other inner ear conditions including sudden onset hearing loss due to ischaemic anoxia [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] and genetic conditions such as non-syndromic autosomal recessive deafness (DFNA8/10) [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Thirdly, there may also be a role in assessing the impact of systemic alterations of sodium concentration on inner ear metabolism [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. In this regard, it has long been observed that otologic symptoms are aggravated after high salt intake [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] whilst low sodium intake is beneficial in MD [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Finally, it should be considered whether targeting the evaluation to individual inner ear structures may be beneficial. Since EH is able to replace a greater proportion of the vestibular PS than is possible in the cochlea, this may be the focus of future studies in MD, and our data did confirm a greater degree of vestibular than cochlear NaSI asymmetry.\u003c/p\u003e\u003cp\u003eIn participant B, there was no qualitative lateralisation of EH or increased \u003csup\u003e23\u003c/sup\u003eNa MRI median signal intensity in the normal ear relative to the MD ear, despite good image quality. This leads us to re-examine the assumption in our hypothesis, which was that the hydropic ES would always demonstrate low \u003csup\u003e23\u003c/sup\u003eNa concentrations like the normal ES. There is some data to suggest that there may be paradoxical increases in the \u003csup\u003e23\u003c/sup\u003eNa concentrations in the presence of EH [\u003cspan additionalcitationids=\"CR43 CR44\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], which would diminish NaSI asymmetry and may explain the findings in this participant. Potential mechanisms include the reduced extraction of \u003csup\u003e23\u003c/sup\u003eNa from the endolymph in the extra-osseous endolymphatic sac [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] or direct communications between the ES and PS [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Changes in endolymphatic \u003csup\u003e23\u003c/sup\u003eNa concentrations have also been implicated in premenstrual exacerbation [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] and genetic forms [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] of MD, whilst animal studies of EH have also shown 2-3x increases in ES \u003csup\u003e23\u003c/sup\u003eNa concentration [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThere are study limitations which should be documented. Firstly, the exploratory nature of the study should be emphasised, with the sample size being limited in its ability to allow statistical analysis and firm conclusions. Assessing the clinical validity of \u0026sup2;\u0026sup3;Na MRI will require a larger cohort of patients with MD and a normal control population. Secondly, the aforementioned technical challenges in obtaining adequate inner ear SNR limited the spatial resolution, with a minimum achievable 2mm\u003csup\u003e3\u003c/sup\u003e voxel size. The inner ear segmentation volumes were concordant with previous estimates [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] such that the vestibule corresponded to a maximum of 5 voxels and the cochlea to a maximum of 10 voxels on \u003csup\u003e23\u003c/sup\u003eNa MRI. This limited the confidence of registration and accurate quantification of inner ear signal. Thirdly, methodological aspects should be addressed. The landmark-based registration process was user dependent and potentially impacted on the reliability of quantitative measures. An alternative approach would be to acquire spatially aligned proton MRI structural imaging concurrently with \u003csup\u003e23\u003c/sup\u003eNa MRI to aid registration, but this was precluded in our study by the lack of a receiver array for proton in the dual tuned coil, which precludes acquisition of inner ear images of the required resolution. It should also be considered that 7\u0026ndash;60 months had elapsed between the clinical and the research MRI studies with the potential for interval changes, although previous longitudinal studies have indicated that fluctuations in the endolymphatic volume are unlikely [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Whilst the contralateral MD ear may be considered a suboptimal control in view of the potential to develop bilateral MD, this was mitigated by the selection of patients without any evidence of EH in the contralateral ear on delayed post-gadolinium 3D-IR MRI. Finally, we should be guarded about the wider applicability of these methods and results. Only patients with unilateral severe EH were examined, so the results may not be generalised to milder forms. In addition, the evaluation of asymmetry would not be pertinent to bilateral MD. Whilst the potential to apply absolute inner ear NaSI in this setting would warrant further investigation, the overlap between the NaSI values of pathological EH and normal ears in this study would argue against this approach. Moreover, the relevance to routine clinical scanning is limited since \u003csup\u003e23\u003c/sup\u003eNa coils and ultra-high-field MRI are not currently in widespread use. In this regard, translation to lower field strength using iterative denoising reconstruction algorithms should be investigated.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis exploratory study demonstrates the potential for qualitative analysis of 7T \u0026sup2;\u0026sup3;Na MRI to lateralise severely hydropic ears in patients with unilateral definite MD, although there remain technical challenges to acquisition and post-processing. Optimal evaluation required registration and fusion with structural imaging and was supported by the results of quantitative analysis. The absence of qualitative and quantitative NaSI asymmetry in one participant, should lead to caution in accepting the clinical validity of this technique and may challenge the underlying assumption that there are low sodium concentrations in the hydropic ES. Despite the limitations, this study provides a proof of principle for the potential role of \u0026sup2;\u0026sup3;Na MRI in the evaluation of MD without the requirement for gadolinium-based contrast agents and supports a theoretical basis for its wider evaluation in MD and other inner ear pathologies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ebSSFP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ebalanced steady-state free precession\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e3D-FLAIR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003e3D Fluid Attenuated Inversion Recovery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e3D-IR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eThree-dimensional inversion recovery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eendolymphatic hydrops\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eES\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eendolymphatic space\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFLASH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003efast low angle shot\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGBCA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003egadolinium-based contrast agents\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003einversion recovery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eM\u0026eacute;ni\u0026egrave;re\u0026rsquo;s disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emagnetic resonance imaging (MRI)\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eperilymphatic space\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003csup\u003e23\u003c/sup\u003eNa\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esodium\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNaSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003e\u003csup\u003e23\u003c/sup\u003eNa sodium MRI signal intensity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSAR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003especific absorption rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esignal intensity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSNR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esignal to noise ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSPACE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esampling perfection with application optimised contrasts using different flip angle evolution\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTesla\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eT2w\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eT2 weighted\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erepeat time\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eHealth Research Authority. Southwest Frenchay Research Ethics Committee. Ref 20/SW/0085. Initial approval 16/6/20. Amendment approval 15/11/22. We certify that the research was conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.\u003c/p\u003e\n\n\u003cp\u003e• Consent for publication\u003c/p\u003e\n\u003cp\u003eConsent was obtained from all participants and indicates ‘I allow the use of any information or results arising from this study for healthcare and/or medical research purposes.’\u003c/p\u003e\n\n\u003cp\u003e• Availability of data and material\u003c/p\u003e\n\u003cp\u003eThe data supporting this article has been deposited in the King’s College London research data repository, KORDS, at https://doi.org/10.18742/28368968. It is not openly available due to conditions of participant consent and may be shared with researchers on request.\u003c/p\u003e\n\n\u003cp\u003e• Competing interests \u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\n\u003cp\u003e• Funding \u003c/p\u003e\n\u003cp\u003eThe study was funded by the Royal College of Radiology Kodak Radiology Fund Scholarship. The funder did not have any specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Authors also acknowledge funding support from Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z); National Institute for Health Research Biomedical Research Centre at Guy’s \u0026amp; St Thomas’ Hospitals and King’s College London; Cancer Research UK National Cancer Imaging Translational Accelerator (A27066); the UK Research \u0026amp; Innovation London Medical Imaging and Artificial Intelligence Centre\u003c/p\u003e\n\n\u003cp\u003e• Authors' contributions \u003c/p\u003e\n\u003cp\u003eSC conceived the study, designed the study, acquired, analyzed and interpreted the patient data and drafted a manuscript. PL acquired, analysed and interpreted data. IP acquired and analysed data. HB acquired data. PT acquired data. SO designed the work, JH designed the work, interpreted data and substantially revised the draft manuscript \u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript and have agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe study was funded by the Royal College of Radiology Kodak Radiology Fund Scholarship. The funder did not have any specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Authors also acknowledge funding support from Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z); National Institute for Health Research Biomedical Research Centre at Guy’s \u0026amp; St Thomas’ Hospitals and King’s College London; Cancer Research UK National Cancer Imaging Translational Accelerator (A27066); the UK Research \u0026amp; Innovation London Medical Imaging and Artificial Intelligence Centre\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHavia M, Kentala E, Pyykk\u0026Ouml; I. Prevalence of Meni\u0026egrave;re\u0026rsquo;s Disease in General Population of Southern Finland. Otolaryngology\u0026ndash;Head and Neck Surgery. 2005; 133:762\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eHallpike CS, Cairns H.Observations on the pathology of M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s Syndrome. JLO.1938; 53:625\u0026ndash;55.\u003c/li\u003e\n\u003cli\u003eFoster CA, Breeze RE. Endolymphatic hydrops in M\u0026eacute;ni\u0026egrave;re\u0026apos;s disease: cause, consequence, or epiphenomenon? Otol Neurotol.2013; 234:1210-4. doi: 10.1097/MAO.0b013e31829e83df. PMID: 23921917\u003c/li\u003e\n\u003cli\u003eNakashima T, Naganawa S, Sugiura M et al. Visualization of endolymphatic hydrops in patients with Meniere\u0026rsquo;s disease. Laryngoscope.2007; 117(3):415\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eConnor S, Grzeda MT, Jamshidi B, Ourselin S, Hajnal JV, Pai I. Delayed post gadolinium MRI descriptors for M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s disease: a systematic review and meta-analysis. Eur Radiol.2023; 12: 7113-7135. doi: 10.1007/s00330-023-09651-8\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;rkov R, Jerin C, Flatz W, Maxwell R. Clinical manifestations of hydropic ear disease (Meni\u0026egrave;re\u0026apos;s). Eur Arch Otorhinolaryngol.2018; 276:27-40. doi: 10.1007/s00405-018-5157-3\u003c/li\u003e\n\u003cli\u003eIwasaki S, Shojaku H, Murofushi T et al. Committee for Clinical Practice Guidelines of Japan Society for Equilibrium Research. Diagnostic and therapeutic strategies for Meniere\u0026apos;s disease of the Japan Society for Equilibrium Research. Auris Nasus Larynx2020; 48:15-22. doi: 10.1016/j.anl.2020.10.009\u003c/li\u003e\n\u003cli\u003eMarckmann P, Skov L, Rossen K et al.Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol.2006; 17: 2359\u0026ndash;2362.\u003c/li\u003e\n\u003cli\u003eRamalho J, Semelka RC, Ramalho M, Nunes RH, Al Obaidy M, Castillo M. Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update. American Journal of Neuroradiology.2016; 37:1192-1198.\u003c/li\u003e\n\u003cli\u003eVenkatasamy A, Veillon F, Fleury A et al. Imaging of the saccule for the diagnosis of endolymphatic hydrops in Meniere disease, using a three-dimensional T2-weighted steady state free precession sequence: accurate, fast, and without contrast material intravenous injection. Eur Radiol.2017; Exp 1:14. doi: 10.1186/s41747-017-0020-7\u003c/li\u003e\n\u003cli\u003eIshii M, Tanaka H, Asai R et al. New non-contrast MRI of endolymphatic hydrops in M\u0026eacute;ni\u0026egrave;re\u0026apos;s disease considering inversion time. Laryngoscope Investig Otolaryngol.2024; 9: e1314. doi: 10.1002/lio2.1314. PMID: 39130211\u003c/li\u003e\n\u003cli\u003eCouloigner V, Sterkers O, Ferrary E. What\u0026apos;s new in ion transports in the cochlea? Pflugers Arch.2012; 453:11-22. doi: 10.1007/s00424-006-0103-4\u003c/li\u003e\n\u003cli\u003eTrune DR. Ion homeostasis in the ear: mechanisms, maladies, and management. Curr Opin Otolaryngol Head Neck Surg.2010; 18: 413-9. doi: 10.1097/MOO.0b013e32833d9597\u003c/li\u003e\n\u003cli\u003eWangemann P, Schacht J. Homeostatic mechanisms in the cochlea. In Springer Handbook of Auditory Research: The Cochlea, ed. Dallos P, Popper AN, Fay R. Springer, New York: 1996.p130-185. https://doi.org/10.1007/978-1-4612-0757-3_3\u003c/li\u003e\n\u003cli\u003eMadelin G, Regatte RR. Biomedical applications of sodium MRI in vivo. Journal of Magnetic Resonance Imaging.2013; 38: 511\u0026ndash;529.\u003c/li\u003e\n\u003cli\u003eGurney PT, Hargreaves BA, Nishimura DG. Design and analysis of a practical 3D cones trajectory. Magn Reson Med. 2006; 55:575-82. doi: 10.1002/mrm.20796\u003c/li\u003e\n\u003cli\u003eBrnawi HA, Balaji K, Kukran S, Connor SEJ, Hajnal JV, Bangerter NK et al. Boosting SNR for sodium BSSFP imaging\u003cem\u003e. \u003cem\u003eProc Intl Soc Mag Reson Med.\u003c/em\u003e\u003c/em\u003e 2024; 32:3035.\u003c/li\u003e\n\u003cli\u003eBangerter NK, Hargreaves BA, Vasanawala SS, Pauly JM, Gold GE, Nishimura DG. Analysis of multiple-acquisition SSFP. Magn Reson Med.2004; 51:1038-47. doi: 10.1002/mrm.20052. PMID: 15122688.\u003c/li\u003e\n\u003cli\u003eNakashima T, Naganawa S, Pyykk\u0026ouml; I et al. Grading of endolymphatic hydrops using magnetic resonance imaging. Acta Otolaryngol Suppl.2009; 560:5-8. doi: 10.1080/00016480902729827\u003c/li\u003e\n\u003cli\u003eLopez-Escamez JA, Carey J, Chung WH et al. Diagnostic criteria for M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s disease. J Vestib Res.2015; 25:1\u0026ndash;7. doi: 10.1007/s00106-017-0387-z\u003c/li\u003e\n\u003cli\u003eKnoll F, Schwarzl A, Diwoky C, Sodickson DK. gpuNUFFT - An open-source GPU library for 3D regridding with direct Matlab interface. In: ISMRM-ESMRMB; 10-16 May 2014; Milan, Italy. https://archive.ismrm.org/2014/4297.html\u003c/li\u003e\n\u003cli\u003eScheffler K. A pictorial description of steady-states in rapid magnetic resonance imaging. Concepts Magn. Reson.1999; 11: 291-304. https://doi.org/10.1002/(SICI)1099-0534(1999)11:5\u0026lt;291::AID-CMR2\u0026gt;3.0.CO;2-J\u003c/li\u003e\n\u003cli\u003eSchindelin J, Arganda-Carreras I, Frise E et al. Fiji: an open-source platform for biological-image analysis. Nat Methods.2012; 9: 676\u0026ndash;682. https://doi.org/10.1038/nmeth.2019\u003c/li\u003e\n\u003cli\u003eKeaveney S, Dragan A, Rata M et al. Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study. Insights Imaging.2023; 14: 170. https://doi.org/10.1186/s13244-023-01498-3\u003c/li\u003e\n\u003cli\u003eFedorov A, Beichel R, Kalpathy-Cramer J et al. 3D Slicer as an image computing platform for quantitative imaging network. Magn Reson Imag. 2012; 30:1323-41. doi: 10.1016/j.mri.2012.05.001.\u003c/li\u003e\n\u003cli\u003eBujang M A, Baharum N. Guidelines of the minimum sample size requirements for Cohen\u0026rsquo;s Kappa. Epidemiology Biostatistics and Public Health.2017; 14: e12267-1-e12267-10. https://doi.org/10.2427/12267\u003c/li\u003e\n\u003cli\u003eWilcox M, Wright SM, McDougall M. A review of non-1H RF receive arrays in magnetic resonance imaging and spectroscopy. IEEE Open J Eng Med Biol. 2020; 1:290\u0026ndash;300. \u003c/li\u003e\n\u003cli\u003eZhao Y, Guo R, Li Y, Thulborn KR, Liang Z-P. High-resolution sodium imaging using anatomical and sparsity constraints for denoising and recovery of novel features. Magn Reson Med. 2021; 86: 625\u0026ndash;636. https://doi.org/10.1002/mrm.28767\u003c/li\u003e\n\u003cli\u003eJerin C, Floerke S, Maxwell R, G\u0026uuml;rkov R. Relationship between the extent of endolymphatic hydrops and the severity and fluctuation of audiovestibular symptoms in patients with Meni\u0026egrave;re\u0026apos;s Disease and MRI evidence of hydrops. Otol Neurotol.2018; 39: e123-e130. doi: 10.1097/MAO.0000000000001681. \u003c/li\u003e\n\u003cli\u003eZhang Y, Cui Y, Hu Y et al. Changes in endolymphatic hydrops visualized by magnetic resonance imaging after sac surgery. J. Huazhong Univ. Sci. Technol. [Med. Sci.].2016; 36, 736\u0026ndash;740. https://doi.org/10.1007/s11596-016-1654-z\u003c/li\u003e\n\u003cli\u003eKim SH, Marcus DC. Regulation of sodium transport in the inner ear. Hear Res.2011; 280: 21-9. doi: 10.1016/j.heares.2011.05.003\u003c/li\u003e\n\u003cli\u003eShi X, Gillespie PG, Nuttall AL. Na+ influx triggers bleb formation on inner hair cells. Am J Physiol Cell Physiol.2005; 288:C1332-41. doi: 10.1152/ajpcell.00522.2004\u003c/li\u003e\n\u003cli\u003eMirza S, Gokhale S. Pathophysiology of Meniere\u0026rsquo;s Disease. Up to Date on Meniere\u0026rsquo;s Disease. InTech. 2017: Available at: http://dx.doi.org/10.5772/66388.InTech. doi: 10.5772/66388\u003c/li\u003e\n\u003cli\u003eKonishi T. Some observations on negative endocochlear potential during anoxia. Acta Otolaryngol. 1979; 87:506-516. https://doi.org/10.3109/00016487909126459\u003c/li\u003e\n\u003cli\u003eLazarini PR, Camargo AC. Idiopathic sudden sensorineural hearing loss: etiopathogenic aspects. Braz J Otorhinolaryngol.2006; 72:554-61. doi: 10.1016/s1808-8694(15)31004-1\u003c/li\u003e\n\u003cli\u003eSellick PM, Johnstone BM. Changes in cochlear endolymph Na\u003csup\u003e+\u003c/sup\u003e concentration measured with Na\u003csup\u003e+\u003c/sup\u003e specific microelectrodes. Pflugers Arch.1972; 336: 11\u0026ndash;20. https://doi.org/10.1007/BF00589137 \u003c/li\u003e\n\u003cli\u003eGuipponi M, Vuagniaux G, Wattenhofer M et al. The transmembrane serine protease (TMPRSS3mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaCin vitro. Hum Mol Genet. 2002; 11:2829-36. doi: 10.1093/hmg/11.23.2829\u003c/li\u003e\n\u003cli\u003eCate WJ, Curtis LM, Rarey KE. Effects of low-sodium, high-potassium dietary intake on cochlear lateral wall Na+,K(+)-ATPase. Eur Arch Otorhinolaryngol.1994; 251:6-1.\u003c/li\u003e\n\u003cli\u003eChoi HS, Chang JH, Kim JH, Kang JW. Is high sodium intake associated with hearing impairment? The association between spot urine sodium concentration and hearing threshold in Korean adolescents. Asia Pac J Clin Nutr.2018; 27:646-648. doi: 10.6133/apjcn.042017.09\u003c/li\u003e\n\u003cli\u003eFurstenberg AC, Lashmet FH, Lathrop F. Meni\u0026egrave;re\u0026apos;s symptom complex: medical treatment. 1934. Ann Otol Rhinol Laryngol.1992; 101:20-31. doi: 10.1177/000348949210100109\u003c/li\u003e\n\u003cli\u003ePerlman HB, Goldinger JM, Cales JO. Electrolyte studies in Meniere\u0026apos;s disease. Laryngoscope.1953; 63:640-651.\u003c/li\u003e\n\u003cli\u003eRizk HG, Mehta NK, Qureshi U et al. Pathogenesis and Etiology of M\u0026eacute;ni\u0026egrave;re Disease: A Scoping Review of a Century of Evidence. \u003cem\u003eJAMA Otolaryngol Head Neck Surg.2022; \u003c/em\u003e148:360\u0026ndash;368. doi:10.1001/jamaoto.2021.4282\u003c/li\u003e\n\u003cli\u003eEckhard AH, Zhu M, O\u0026apos;Malley JT et al. Inner ear pathologies impair sodium-regulated ion transport in Meniere\u0026apos;s disease. Acta Neuropathol.2019;137:343-357. doi: 10.1007/s00401-018-1927-7.\u003c/li\u003e\n\u003cli\u003eKim SH, Park HY, Choi HS et al. Functional and molecular expression of epithelial sodium channels in cultured human endolymphatic sac epithelial cells. Otol Neurotol.2009;30:529\u0026ndash;534. doi:10.1097/MAO.0b013e31819a8e0e.\u003c/li\u003e\n\u003cli\u003eSchuknecht HF, R\u0026uuml;ther A. Blockage of longitudinal flow in endolymphatic hydrops. Eur Arch Otorhinolaryngol. 1991; 248:209-17. doi: 10.1007/BF00173659. \u003c/li\u003e\n\u003cli\u003eAndrews JC, Honrubia V. Premenstrual exacerbation of Meniere\u0026apos;s disease revisited. Otolaryngologic Clinics of North America. 2010;43: 1029-1040. doi: 10.1016/j.otc.2010.05.012. \u003c/li\u003e\n\u003cli\u003eTeggi R, Zagato L, Delli Carpini S et al. Genetics of ion homeostasis in M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s Disease. Eur Arch Otorhinolaryngol.2017; 274, 757\u0026ndash;763. https://doi.org/10.1007/s00405-016-4375-9\u003c/li\u003e\n\u003cli\u003eSilverstein H, Takeda T. Endolymphatic Sac Obstruction Biochemical Studies. Annals of Otology, Rhinology \u0026amp; Laryngology.1977; 86:493-499. doi:10.1177/000348947708600408.\u003c/li\u003e\n\u003cli\u003eBuckingham RA, Valvassori GE. Inner Ear Fluid Volumes and the Resolving Power of Magnetic Resonance Imaging: Can it Differentiate Endolymphatic Structures? Annals of Otology, Rhinology \u0026amp; Laryngology.2001; 110:113-117. doi:10.1177/000348940111000204\u003c/li\u003e\n\u003cli\u003eLi J, Wang L, Hu N et al. Longitudinal variation of endolymphatic hydrops in patients with M\u0026eacute;ni\u0026egrave;re\u0026apos;s disease. Ann Transl Med.2023; 11:44. doi: 10.21037/atm-22-6313\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"magnetic resonance imaging, Meniere’s Disease, ultra-high-field MRI, endolymphatic hydrops, sodium","lastPublishedDoi":"10.21203/rs.3.rs-7420941/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7420941/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWhilst 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 M\u0026eacute;ni\u0026egrave;re\u0026rsquo;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 (\u003csup\u003e23\u003c/sup\u003eNa) concentration in the endolymph relative to the surrounding perilymph would result in a differential reduction in \u003csup\u003e23\u003c/sup\u003eNa-MRI signal in inner ears with endolymphatic hydrops (EH). This proof of principle study explored the feasibility of 7-Tesla (7T) \u003csup\u003e23\u003c/sup\u003eNa-MRI to lateralise EH ears in unilateral MD.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn this prospective study, 7T \u003csup\u003e23\u003c/sup\u003eNa-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 \u003csup\u003e23\u003c/sup\u003eNa 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.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn 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\u0026ndash;2.8 times higher in the normal cochlea and 1.9\u0026ndash;2.9 times higher in the vestibule, compared to the EH ear. Intraclass correlation coefficient for inner ear median NaSI was 0.70.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis exploratory study revealed the potential for severe EH to be qualitatively and quantitatively lateralised with 7T \u0026sup2;\u0026sup3;Na MRI in patients with unilateral definite MD.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial registration\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNCT04370366; registered 29/4/20\u003c/p\u003e","manuscriptTitle":"7-Tesla sodium magnetic resonance imaging of the inner ears in unilateral Ménière’s Disease and endolymphatic hydrops: An exploratory study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 05:05:44","doi":"10.21203/rs.3.rs-7420941/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-16T14:13:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-15T10:05:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-15T07:34:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72058542941387915792167045289352624651","date":"2025-08-25T10:01:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156260275781841975885393559519005825223","date":"2025-08-25T03:00:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-25T02:58:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-22T20:25:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-22T09:32:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-22T09:32:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2025-08-20T23:25:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"645da97c-7b70-4f47-82fe-63eb19969c25","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:01:18+00:00","versionOfRecord":{"articleIdentity":"rs-7420941","link":"https://doi.org/10.1186/s12880-025-01986-6","journal":{"identity":"bmc-medical-imaging","isVorOnly":false,"title":"BMC Medical Imaging"},"publishedOn":"2025-11-11 15:57:47","publishedOnDateReadable":"November 11th, 2025"},"versionCreatedAt":"2025-09-03 05:05:44","video":"","vorDoi":"10.1186/s12880-025-01986-6","vorDoiUrl":"https://doi.org/10.1186/s12880-025-01986-6","workflowStages":[]},"version":"v1","identity":"rs-7420941","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7420941","identity":"rs-7420941","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}