Endolymphatic hydrops evaluation on MRI: Practical considerations

Journal Pre-proof Endolymphatic considerations

hydrops

evaluation

on

MRI:

Practical

Rafael Maffei Loureiro, Daniel Vaccaro Sumi, Hugo Luis de Vasconcelos Chambi Tames, Carolina Ribeiro Soares, Marcio Cavalcante Salmito, Regina Lucia Elia Gomes, Mauro Miguel Daniel PII:

S0196-0709(19)31025-7

DOI:

https://doi.org/10.1016/j.amjoto.2019.102361

Reference:

YAJOT 102361

To appear in:

American Journal of Otolaryngology--Head and Neck Medicine and Surgery

Received date:

18 November 2019

Please cite this article as: R.M. Loureiro, D.V. Sumi, H.L. de Vasconcelos Chambi Tames, et al., Endolymphatic hydrops evaluation on MRI: Practical considerations, American Journal of Otolaryngology--Head and Neck Medicine and Surgery(2018), https://doi.org/ 10.1016/j.amjoto.2019.102361

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© 2018 Published by Elsevier.

Journal Pre-proof Endolymphatic Hydrops Evaluation on MRI: Practical Considerations

Section: Clinical Radiology

Rafael Maffei Loureiro, MDa Daniel Vaccaro Sumi, MDa

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Hugo Luis de Vasconcelos Chambi Tames, MDa Carolina Ribeiro Soares, MDa

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Marcio Cavalcante Salmito, MDb

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Regina Lucia Elia Gomes, MD, PhDa

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a - Hospital Israelita Albert Einstein

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Mauro Miguel Daniel, MD, PhDa

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Department of Radiology and Diagnostic Imaging

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Av. Albert Einstein, 627/701, 05652-900 São Paulo, SP, Brazil.

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b - Universidade Federal de São Paulo Department of Otorhinolaryngology and Cervico-Facial Surgery Rua Pedro de Toledo, 947, 04039-002, São Paulo, SP, Brazil.

Corresponding author: Rafael Maffei Loureiro Hospital Israelita Albert Einstein Department of Radiology and Diagnostic Imaging Av. Albert Einstein, 627/701, 05652-900 São Paulo, SP, Brazil1 Telephone/fax: +55-11-21512452

Journal Pre-proof [email protected] Footnote: 1 - permanent address, where the authors did the work.

Authors’ e-mail addresses: Rafael Maffei Loureiro: [email protected] Daniel Vaccaro Sumi: [email protected]

Carolina Ribeiro Soares: [email protected]

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Regina Lucia Elia Gomes: [email protected]

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Marcio Cavalcante Salmito: [email protected]

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Hugo Luis de Vasconcelos Chambi Tames: [email protected]

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Declarations of interest: none.

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Mauro Miguel Daniel: [email protected]

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This research did not receive any specific grant from funding agencies in the public,

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Abstract:

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commercial, or not-for-profit sectors.

Four-hour delayed three-dimensional fluid-attenuated inversion recovery (3DFLAIR) sequence after intravenous gadolinium-based contrast agent administration is an optimal magnetic resonance imaging technique to evaluate endolymphatic hydrops in patients with known or suspected Ménière’s disease. Nonenhanced endolymphatic space surrounded by enhanced perilymphatic space is evaluated in the cochlea and vestibule separately. In cochlear hydrops, the scala media is enlarged, potentially obliterating the scala vestibuli. In vestibular hydrops, the size of the saccule becomes equal to or larger than that of the utricle; as hydrops progresses, the saccule and utricle become larger and confluent until complete obliteration of the vestibule’s perilymphatic space.

Journal Pre-proof In patients with a unilateral clinical presentation of Ménière's disease, it is possible to depict the asymmetries of perilymph enhancement, which may be increased on the affected side and reflect a permeability alteration of the blood-perilymph barrier. In addition, endolymphatic hydrops can be observed in the asymptomatic ear of these patients with a unilateral clinical presentation, showing that Ménière's disease tends to

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undergo bilateral evolution over time.

Potential referees:

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Dr. Mariana Dalaqua Hôpital du Valais Sion, Switzerland [email protected]

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Dr. Eloisa Gebrim Hospital das Clínicas – Universidade de São Paulo São Paulo, Brazil [email protected]

Journal Pre-proof Endolymphatic Hydrops Evaluation on MRI: Practical Considerations

Section: Clinical Radiology

Abstract: Four-hour delayed three-dimensional fluid-attenuated inversion recovery (3D-

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FLAIR) sequence after intravenous gadolinium-based contrast agent administration is an optimal magnetic resonance imaging technique to evaluate endolymphatic hydrops in

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patients with known or suspected Ménière’s disease. Nonenhanced endolymphatic space

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surrounded by enhanced perilymphatic space is evaluated in the cochlea and vestibule

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separately. In cochlear hydrops, the scala media is enlarged, potentially obliterating the scala vestibuli. In vestibular hydrops, the size of the saccule becomes equal to or larger

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than that of the utricle; as hydrops progresses, the saccule and utricle become larger and

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confluent until complete obliteration of the vestibule’s perilymphatic space. In patients with a unilateral clinical presentation of Ménière's disease, it is possible

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to depict the asymmetries of perilymph enhancement, which may be increased on the

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affected side and reflect a permeability alteration of the blood-perilymph barrier. In addition, endolymphatic hydrops can be observed in the asymptomatic ear of these patients with a unilateral clinical presentation, showing that Ménière's disease tends to undergo bilateral evolution over time.

Keywords: Meniere disease, endolymphatic hydrops, magnetic resonance imaging, gadolinium, perilymph, endolymph.

Abbreviations: 3D-FLAIR: three-dimensional fluid-attenuated inversion recovery; EH: endolymphatic hydrops; MD: Ménière's disease

Journal Pre-proof Declarations of interest: none.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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No color is needed for the figures in print.

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Main text:

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Ménière's disease (MD) is a labyrinthine condition that causes attacks of vertigo,

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often associated with fluctuating sensorineural hearing loss, tinnitus, and aural fullness [1]. This condition is associated with distension of the endolymphatic space of the inner ears,

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called endolymphatic hydrops (EH). Although EH is considered the histologic marker of

[2].

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MD in postmortem studies, the relationship between them is not yet completely understood

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Since the first visualization of EH in living patients with MD on magnetic resonance

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imaging [3], many studies have demonstrated the feasibility of this method to assess EH using delayed image acquisition after intravenous or intratympanic administration of gadolinium-based contrast agent, translating this evaluation from research into clinical practice [2]. The majority of these studies used inversion recovery sequences, mainly three-dimensional fluid-attenuated inversion recovery (3D-FLAIR), performed 4 to 6 hours after intravenous administration of the contrast agent [1]. The intravenous route is more practical and less invasive, simultaneously evaluates both ears, results in more uniformly distributed gadolinium, and allows assessment of the blood-perilymph barrier compared to the intratympanic route. Conversely, the intratympanic route requires a puncture in the tympanic membrane, depends on the permeability of the round and oval windows, requires

Journal Pre-proof a longer time before imaging acquisition (24 hours), and is considered an off-label use of gadolinium [4]. A drawback of the intravenous route is the lower gadolinium concentration achieved in the perilymph when compared to that in the intratympanic route, although it can be minimized with optimized MRI sequences [2]. In both routes, the contrast agent reaches the perilymph and does not reach the endolymph, which allows for visualization of EH in patients with MD [4].

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First, a 3-Tesla scanner and a head coil with a high number of receiving channels are required to maximize the signal-to-noise ratio. A combination of a head coil and a

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surface (ear) coil can also be used [2]. The 3D-FLAIR sequence should be acquired 4

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hours after intravenous administration of the contrast agent. This delay is required

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because gadolinium needs to reach an optimal concentration in the perilymph [4]. In our institution, intravenous contrast agent is administered at a double dose (gadobutrol, 1.0

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mmol/mL at a dose of 0.2 mmol/kg) to increase the enhancement of the perilymph, as

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described in previous studies [5,6]. Patients are imaged on a 3-Tesla scanner (Magnetom Prisma, Siemens HealthCare, Erlangen, Germany) with a 64-channel array head coil. The

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following parameters are used: TR = 6000 ms; TE = 170 ms; TI = 2000 ms; turbo factor =

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35; flip angle = 180°; slice thickness = 0.8 mm; FOV = 160 mm; matrix = 384 x 384; voxel size = 0.4 x 0.4 x 0.8 mm; number of excitations = 1; bandwidth = 186 Hz/pixel; scan time = 15 minutes. In addition to the double dose of intravenous gadolinium-based contrast agent, a constant flip angle is another recommendation to increase the enhancement of the perilymph [1]. Since this sequence has a long acquisition time, patient collaboration is critical to image quality. Imaging acquisition should be performed on the axial plane because most EH classifications are based on axial images [5,6,7,8]. Therefore, isotropic datasets for reformatting are not required, which would otherwise result in a longer acquisition time, neither is postprocessing of the images.

Journal Pre-proof The examination can be performed in two steps: first, conventional sequences for inner ear evaluation are acquired, and whole-brain sequences may be included; then, 4 hours later, the patient returns and the 3D-FLAIR sequence is acquired. Alternatively, the examination can be performed in a single stage, whereby conventional sequences and 3D-FLAIR are performed together 4 hours after contrast administration. In this single-stage protocol, it is not possible to acquire the nonenhanced sequences; thus, this method

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should be reserved for specific situations, such as for patients who undergo examination under anesthesia.

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On imaging, nonenhanced endolymphatic space surrounded by gadolinium-

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enhanced perilymphatic space is evaluated in the cochlea and vestibule separately, both

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on the axial plane [6,8]. In the normal cochlea, the scala media (also called cochlear duct) containing endolymph is minimally visible in the central region of the cochlear turns, which

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are largely filled by enhanced perilymph (Fig. 1). In the normal vestibule, it is possible to

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visualize the saccule and utricle in the lower region, both containing endolymph and surrounded by a large enhanced perilymphatic space (Fig. 1) [6]. The saccule is smaller

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and more anterior, medial, and inferior compared to the utricle [8]. In patients with MD,

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distension of the endolymphatic space may be cochlear and/or vestibular to varying degrees (Fig. 2,3,4A). In cochlear hydrops, the scala media becomes enlarged, but without obliteration of the scala vestibuli in the early stages (Fig. 2); as hydrops progresses, a complete obliteration of the scala vestibuli can be observed (Fig. 3) [6]. In vestibular hydrops, the size of the saccule becomes equal to or larger than that of the utricle (Fig. 2,3) [7,8]; as hydrops progresses, the saccule and utricle become larger and confluent until complete obliteration of the vestibule’s perilymphatic space (Fig. 4A) [6,8]. Indeed, a recent meta-analysis showed an orderly progression of EH in the labyrinth instead of a random effect, beginning in the cochlea and then involving the saccule, utricle, ampullae,

Journal Pre-proof and semicircular canals [9]. Therefore, acknowledgment of this sequential distribution can be of great value when evaluating EH on magnetic resonance images. In patients with a unilateral clinical presentation of MD, it is possible to depict the asymmetries of perilymph enhancement, which may be increased on the affected side and reflect a permeability alteration of the blood-perilymph barrier (Fig. 2) [10,11,12]. Bernaerts et al. [8] showed that an increased cochlear perilymphatic enhancement has a very high

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specificity for definite unilateral MD, and this asymmetry should be evaluated in all patients with unilaterally symptomatic ears. In addition, EH can be observed in the asymptomatic

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ear of patients with a unilateral clinical presentation, showing that MD tends to undergo

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bilateral evolution over time [13].

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The similarity between the low signal from a nonenhanced endolymph and that from the surrounding bone may be challenging when interpreting the first examinations.

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One way to make this distinction easier is to analyze the 3D-FLAIR sequence together

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with a heavily T2-weighted sequence (Fig. 4A,B) [14]. Moreover, it is important to be aware of the expected regions that accumulate the contrast agent after 4 hours of

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administration: the anterior portion of the eyes, subarachnoid space surrounding the optic

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nerves, Meckel’s caves, and fundus of the internal auditory canals [4]. Recently, a few studies have shown the feasibility of using heavily T2-weighted sequences to diagnose saccule enlargement in MD patients without contrast agent administration [1,15]. However, the saccule measurement is potentially affected by band artifacts and has low reproducibility owing to the minuscule dimensions of the saccule. Moreover, these sequences do not identify the remaining endolymphatic space, limiting its clinical use [16]. EH is not exclusive to typical MD, but it can be observed in its monosymptomatic variants and other diseases, such as in inner ear malformations, schwannoma, and endolymphatic sac tumors [17]. Therefore, Gürkov et al. [18] proposed the term “hydropic

Journal Pre-proof ear disease” to encompass the full range of symptomatic inner ears with EH in a single classification based on clinical and imaging characteristics, including clinical variants as well the primary and secondary forms of MD. This concept highlights that there are patients with symptomatic EH who do not fulfill the current diagnostic criteria of MD because these criteria are purely clinical and do not consider the objective visualization of EH, the pathological hallmark of MD [17, 18].

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In summary, recent advances in magnetic resonance imaging have allowed for the visualization of EH, the histological counterpart of MD. Delayed intravenous gadolinium-

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enhanced 3D-FLAIR is a reliable technique for evaluating endolymph-containing structures

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in clinical practice through a dedicated protocol. However, further longitudinal and

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multicenter studies are needed to validate this method and include it in the diagnostic

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criteria of MD.

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Figures:

Journal Pre-proof Figure 1. MRI of normal inner ears, axial plane, 3D-FLAIR 4 hours postcontrast. The cochlear turns are almost completely filled with contrast-enhanced perilymph; the scala media is minimally visible as a thin line (arrowheads) in the central region of the cochlear turns. Normal saccules (short arrows) and utricles (long arrows) are separated and surrounded by contrast-enhanced perilymph. The saccules are smaller than the utricles

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and they occupy the smallest part of the vestibular area.

Figure 2. Patient with definite right-sided Ménière’s disease. MRI of the inner ears, axial plane, 3D-FLAIR 4 hours postcontrast. Cochlear and vestibular hydrops on the right side: mild distension of the scala media (arrowheads), without obliteration of the scala vestibuli (dashed arrow); the saccule (short arrow) is larger than the utricle (long arrow) and they are not confluent. There is also asymmetrical perilymphatic enhancement, increased on the right side (dashed arrow) compared to the left side.

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Figure 3. Patient with definite bilateral Ménière’s disease. MRI of the inner ears, axial

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plane, 3D-FLAIR 4 hours postcontrast. Cochlear and vestibular hydrops: the scala media

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is enlarged (arrowheads), obliterating the scala vestibuli on both sides; the saccules (short arrows) and utricles (long arrows) are also enlarged and almost confluent, occupying most

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of the vestibular area. There is also mild protrusion of the utricles in the lateral and

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posterior semicircular canals.

Figure 4. Patient with definite right-sided Ménière’s disease. MRI of the right inner ear, axial plane. (A) 3D-FLAIR 4 hours postcontrast. There is a diffuse enlargement of the

Journal Pre-proof cochlear (arrowheads) and vestibular (long arrow) endolymphatic space. The saccule and utricle are enlarged and confluent, occupying all the vestibular area (long arrow). There is also enlargement of the endolymphatic space in part of the lateral and posterior semicircular canals (short arrows). (B) Heavily T2-weighted sequence, axial plane. This cisternographic sequence helps to differentiate the nonenhanced endolymph from the lowsignal surrounding bone in subfigure A.

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[4] Naganawa S, Nakashima T. Visualization of endolymphatic hydrops with MR imaging in patients with Ménière's disease and related pathologies: current status of its methods and clinical significance. Jpn J Radiol 2014;32(4):191-204. https://doi.org/10.1007/s11604-0140290-4. [5] Nakashima T, Naganawa S, Pyykko I, Gibson WP, Sone M, Nakata S, et al. Grading of endolymphatic hydrops using magnetic resonance imaging. Acta Otolaryngol Suppl 2009;(560):5-8. https://doi.org/10.1080/00016480902729827

Journal Pre-proof [6] Baráth K, Schuknecht B, Naldi AM, Schrepfer T, Bockisch CJ, Hegemann SC. Detection and grading of endolymphatic hydrops in Menière disease using MR imaging. AJNR Am J Neuroradiol 2014;35(7):1387-92. https://doi.org/10.3174/ajnr.A3856. [7] Attyé A, Eliezer M, Boudiaf N, Tropres I, Chechin D, Schmerber S, et al. MRI of endolymphatic hydrops in patients with Meniere’s disease: a case-controlled study with a simplified classification based on saccular morphology. Eur Radiol 2017;27(8):3138-46.

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