Clinical Radiology xxx (2017) 1e10

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Clinical Radiology
journal homepage: www.clinicalradiologyonline.net

Review

MRI in otology: applications in cholesteatoma and

nie
Me re’s disease
R.K. Lingam a, S.E.J. Connor b, *, J.W. Casselman c, T. Beale d
a
London Northwest Healthcare NHS Trust, London, UK
b
King’s College Hospital NHS Foundation Trust, London, UK
c
AZ Sint-Jan AV Hospital, Bruges, Belgium
d
University College Hospital London Hospitals NHS Foundation Trust, London, UK

Imaging of middle-ear cholesteatoma with diffusion-weighted imaging (DWI) magnetic

resonance imaging (MRI), and inner-ear endolymphatic hydrops (in Me
niere’s disease) with
post-gadolinium high-resolution MRI, are reviewed. DWI MRI provides for a more specific
diagnosis of tympano-mastoid cholesteatoma. There is an established and increasing role of
DWI MRI in detecting both primary and postoperative cholesteatoma, localising disease, and
planning surgery. The contemporary diagnostic accuracy of DWI is reviewed, pitfalls in
interpretation are described, and potential future developments are highlighted. High-
resolution post-gadolinium MRI of the inner ear is being explored for diagnosing endolym-
phatic hydrops. There is now increasing data to validate the application of three-dimensional
(3D)-fluid attenuated inversion recovery (FLAIR) sequences, performed at 4 hours post-
intravenous gadolinium, in the setting of potential Me
nie
re’s disease. The clinical context
and the evolution of these MRI techniques are discussed. Current MRI-based grading schemes
for endolymphatic hydrops are described, together with the available data on their clinical
implications.
Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of
Radiologists. All rights reserved.

Introduction imaging technique. Secondly, we review the imaging of

Me
nie
re’s disease (MD), where delayed gadolinium
This article explores two different otological conditions enhanced imaging of the inner ear is evolving as a method
in which MRI has an increasing role in diagnosis and patient for diagnosing endolymphatic hydrops (EH); however, this
management. The first clinical scenario is that of choles- is yet to be widely practiced.
teatoma imaging, where diffusion-weighted (DWI) MRI of
the middle ear and mastoid is now a well-established Imaging middle-ear cholesteatoma with DWI

Since the initial application of non-echoplanar DWI to

* Guarantor and correspondent: S. Connor, Neuroradiology Department,
Kings College Hospital, Denmark Hill, London SE5 9RS, UK. Tel.: þ44 (0)20
32999000.
E-mail address: steve.connor@nhs.net (S.E.J. Connor).
the detection of cholesteatoma,1,2 there has been significant
development, progress, and understanding of its role in the
management of both primary and postoperative middle-ear
cholesteatoma.

http://dx.doi.org/10.1016/j.crad.2017.09.002
0009-9260/Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

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Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
2 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10

DWI inflammation, and fluid, return a lower signal on the high b-

DWI is an imaging method that uses the diffusion of
water molecules to generate contrast in MRI images.3e5 An
apparent diffusion coefficient (ADC) map can be calculated
from two or more DWI sequences acquired with different b-
values. The ADC map is integral to the interpretation of the
DWI images as it is free from any T2-weighted effects, and
provides a true quantitative display of water diffusivity.6
Employing more b-values can strengthen the ADC map,
but at the expense of a longer scan time, with the risk of
patient movement and consequent image position misreg-
istration.7 Two main types of DWI sequence have been
applied to the imaging of the ear and skull base: the echo-
planar and non-echoplanar DWI. Although echoplanar DWI
has a shorter acquisition time than its non-echoplanar
counterpart, it is affected by airebone susceptibility arte-
facts and distortion, which limit its diagnostic performance
at the skull base and temporal bones.8,9 Current non-
echoplanar techniques include single-shot turbo spin-
echo (SSTSE) sequences (such as half-Fourier-acquired sin-
gle-shot turbo spin echo [HASTE]) and multishot turbo
spin-echo (MSTSE) sequences (such as periodically rotated
overlapping parallel lines with enhanced reconstruction
[PROPELLER]). DWI is capable of achieving high-resolution
images with section thicknesses of <3 mm.3e5
By virtue of its keratin content, cholesteatoma charac-
teristically demonstrates restricted diffusion on DWI. Due to
a combination of this restricted diffusion and the T2 shine-
through effect, cholesteatoma returns high signal intensity
compared to brain tissue on the DWI images obtained both
at b-values of 0 s/mm2 and at higher values of 800 or 1000
s/mm2 3e5 (Fig 1). It returns low value on the ADC map due
to the restricted diffusion.10 In comparison, non-
cholesteatomatous substrates, such as granulation tissue,
value (800 or 1000 s/mm2) images compared to the b¼0 s/
mm2 images and high signal on the ADC map.
Middle-ear cholesteatoma and treatment
Middle-ear cholesteatoma is a non-neoplastic disease
characterised by desquamated debris, surrounded by layers
of keratinising squamous epithelium. If left untreated, it can
erode the surrounding bone and ossicles and lead to com-
plications such as hearing loss, vertigo, facial nerve paral-
ysis, and meningitis.11 Surgical removal is the treatment of
choice and can be broadly classified as canal-wall-up (CWU)
or canal-wall-down (CWD) surgery depending on whether
the posterior canal wall is preserved.3 The CWD technique is
associated with an open mastoid cavity, which requires
regular outpatient suction clearance to remove wax that can
accumulate in the cavity. The cavity is easy to inspect and
cholesteatoma can be detected easily on otoscopy and
removed in the clinic. Conversely, the CWU technique
leaves a closed cavity, obviates the potential requirement
for lifelong ear care, improves the fitting of hearing aids
when required, and is less likely to lead to otorrhoea asso-
ciated with swimming; however, it is associated with a
higher risk of residual (up to 36%) and recurrent (up to 18%)
disease than CWD cases.12,13 Detecting postoperative dis-
ease clinically can be challenging and a mandatory second-
look surgery at 9e12 months following surgery is required;
however, avoiding second-look surgery via imaging confers
financial benefits and reduces potential surgical morbidity.
DWI in detecting postoperative middle-ear
cholesteatoma
Various imaging techniques have been evaluated for
detecting residual and recurrent cholesteatoma. Non-

Figure 1 Non-echoplanar DWI images of a 30-year-old woman who had bilateral CWU mastoidectomy for cholesteatoma. The coronal (a) T2W
image and (b) b¼0 image show high signal soft tissue within the anterior middle ear cavities bilaterally. The (c) b¼1000 s/mm2 image shows
persistent high signal from the right middle-ear soft tissue, which also demonstrates low signal/value on the (d) ADC map in keeping with
residual cholesteatoma. On the left, the abnormal middle-ear soft-tissue loses signal on the b¼1000 s/mm2 image and returns high signal/value
on the ADC map in keeping with granulation (non-cholesteatomatous) tissue.

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Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10
echoplanar DWI is now considered the most diagnostically
accurate imaging investigation for the detection of post-
operative cholesteatoma.5 Computed tomography (CT),11
delayed contrast MRI,14 and echoplanar DWI8,9 have been
evaluated previously. Most studies demonstrate non-
echoplanar DWI has a sensitivity and specificity between
80e100% in detecting middle-ear cholesteatoma8,9,15e17
(Table 1). The largest meta-analysis to date, which
included 26 studies and 1,152 patient episodes, reported a
sensitivity and specificity of 91% and 92%, respectively, in
detecting middle-ear cholesteatoma.17 Although DWI
diagnosis is predominantly a qualitative assessment, a
quantitative assessment with ADC values can also aid in the
diagnosis of cholesteatoma, once the ADC threshold is
established for the scanner and the particular scanning
protocol.10 In addition to detecting disease, non-echoplanar
DWI has also been shown to correlate well with surgery, in
terms of depicting size and location of postoperative cho-
lesteatoma.18 Supplementing non-echoplanar DWI with
post-gadolinium-enhanced contrast imaging, however,
does not improve the diagnostic performance of non-
echoplanar DWI.14
Despite its high diagnostic performance, non-echoplanar
DWI is associated with some pitfalls in image interpreta-
tion.5 Its main limitation is decreased sensitivity for cho-
lesteatoma which are <2e3mm in size. There is also no
additional improvement in the detection of these small
cholesteatomas when scanning is performed at 3 T.19,20 If
DWI is to replace second-look surgery, then serial follow-up
monitoring of negative DWI cases is essential.21 This allows
time for small residual cholesteatoma pearls to grow large
enough to return the necessary DWI signal. Other causes of
false-negative non-echoplanar DWI studies include larger
cholesteatoma up to 6 mm, which lack the necessary ker-
atin to return the high DWI signal, auto-atticotomy (where
the central keratin has discharged leaving only an epithelial
lined sac or matrix), aspiration of cholesteatoma on
microsuction and patient movement artefacts.3e5 Causes of
false-positive studies include ear wax, proteinaceous fluid/
non-specific inflammation, operative materials, such as
silastic sheet, bone dust/powder, (calcified) cartilage, dental
brace artefacts, tympanosclerosis, cholesterol granuloma,
Table 1
Meta-analyses and systemic reviews on the diagnostic performance of non-echoplanar diffusion-weighted imaging (DWI) in detecting cholesteatoma.
Paper Type No. of studies
(year (no. of patient
published) episodes)
Jindal Systemic review 8 (207)
20118
Li 201315 Meta-analysis 10 (342)
Van Egmond Systemic review 7 (223)
201616
Muzaffar Systemic review 16 (444)
20169 and meta-analysis
Lingam Meta-analysis 26 (1152)
201717
a
Compares non-echoplanar with echoplanar DWI.
b
Separate subset analysis also available for primary and postoperative cholesteatoma.
Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
3
and squamous cell carcinoma of the external auditory ca-
nal.5 To optimise diagnostic accuracy, it is recommended
that non-echoplanar DWI images are interpreted with
copy-referenced conventional T1W and T2W images and
with ADC values.4,5 Indeterminate DWI signal can also be
resolved with serial monitoring to assess for resolution or
progression, and through discussion at regular clinicor-
adiological meetings.5
Cholesteatoma in children is more aggressive than adult
disease with a higher rate of recurrent and residual disease
following primary surgery.22 The otologist may therefore be
inclined to opt for second-look surgery, rather than imaging
to detect postoperative disease. A recent large prospective
observational study showed that DWI is equally effective for
the detection of postoperative disease in children as in
adults.23 The authors also described that successful scan-
ning could be achieved without the need for sedation, as
long as the procedure was explained well to the parent and
child beforehand. DWI is also a particularly attractive
technique for imaging children as it does not require radi-
ation exposure or administration of intravenous contrast
medium; however, given the higher risk of postoperative
disease, children should be monitored with DWI more
frequently in the absence of second-look surgery.
DWI is not routinely indicated following CWD mastoid-
ectomy procedures, as accumulating keratin within the
mastoid cavity can often be detected, and cleared with
microsuction in the outpatient department.3,16,24 DWI can
also return false-positive signals from wax accumulation in
the open mastoid cavity.5 Hence, for DWI to be used in this
clinical setting, the rationale for its application needs to be
clearly communicated to and discussed with the radiolo-
gists. DWI is valuable when disease is not readily visible on
otomicroscopic examination; such as disease extension into
the petrous apex or mastoid tip, deep location in an oblit-
erated cavity, or when medial to an opaque tympanic
membrane reconstruction.24
DWI in detecting primary middle-ear cholesteatoma
The diagnosis of primary cholesteatoma (initial choles-
teatoma before surgery) is usually made clinically and with
Cholesteatoma Sensitivity (%) Specificity (%) PPV (%) NPV (%)
cases
Postoperativea 91 96 97 85
Primary and 94 (95% CI: 80e98) 94 (95% CI: 85e98) - -
postoperativeb
Primary and Range: 43e92 Range: 58e100 Range: Range:
Postoperativeb 96e100 64e85
Postoperativea 89.79 94.57 96.5 80.46
Primary and 91 (95% CI: 87e95) 92 (95% CI: 86e96) - -
Postoperativeb

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4 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10
otoscopy. CT is the established technique of choice for im-
aging primary cholesteatoma as it can accurately depict any
associated bony and ossicular chain erosion, and provide
necessary anatomical information for surgical planning.11
Nevertheless, DWI does have good diagnostic perfor-
mance in detecting primary cholesteatoma.5 It can aid in
diagnosing primary cholesteatoma in clinical situations,
such as high-risk tympanic retraction pockets, and when
otoscopic examination is hindered by an opaque tympanic
membrane or by a stenosed ear canal.5 DWI can also be
particularly useful in defining the true extent of choles-
teatoma and planning surgery,25,26 notably in cases where
the preoperative CT shows complete soft-tissue opacifica-
tion of the middle-ear cleft. More recently, DWI has been
described in monitoring disease progression in patients
who did not have surgical removal for various reasons.27
Future directions
Although DWI is a feasible replacement for relook sur-
gery, the optimal frequency and length of follow-up with
DWI is still subject to discussion and research. A recent
study has shown that initial negative postoperative DWI
can turn positive for cholesteatoma 2 years later on sur-
veillance. Currently, many institutions adopt annual sur-
veillance for 3e5 years and decisions for individual cases
are tailored to the clinical risk of disease recurrence. The
main drawback to this imaging strategy is the loss of the
patient to follow-up.3,5 This may be due to administrative
mishap, loss of patient contact, patient non-compliance,
and lack of awareness of the limitations of DWI by clini-
cians and patients. There is a real concern that the patient
lost to follow-up may present eventually with extensive
disease recurrence and associated morbidity and costs. To
comprehensively evaluate the cost-effectiveness of sur-
veillance with DWI, a large prospective multicentre rand-
omised controlled study is required to compare it with that
of second-look surgery.
As DWI is of value in depicting size, location, and extent
of cholesteatoma, it can provide useful information for both
operative planning and patient counselling; however, when
fused with CT, the disease can be also depicted against a
background of high-resolution bony anatomical detail
contributed by CT. This provides a navigational map for the
surgeon who is more acquainted with CT for planning sur-
gery. The fused map allows the surgeon to decide on and
plan the optimal approach and technique to clear the dis-
ease. Several small studies have shown that fused CT and
DWI images enable accurate localisation of disease in the
various middle-ear cleft subsites and aid surgical
planning28e31 (Fig 2). The technique has the potential for
providing essential guidance for less invasive surgery, such
as transcanal endocopic surgery.32 A 3D fusion map has also
been proposed.29 Registration of image sets for fusion is
currently performed automatically with manual fine-
tuning, but more advanced imaging fusion technology
may promote quicker, seamless, and accurate fusion with
multiplanar fusion capability. For postoperative cases,
acquisition of additional CT for fusion will incur radiation
Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
exposure; however, this may be overcome by using the
relevant anatomical landmarks from the initial preoperative
CT instead31
Imaging endolymphatic hydrops in
Meniere’s disease
MD is a disorder of the inner ear that is characterised by
episodic attacks of vertigo, tinnitus, fluctuating hearing loss,
sensation of fullness in the ear, and progressive loss of
audiovestibular function. MD usually only affects one ear,
although over time both ears may become involved.33,34
The disease usually presents between the ages of 40e60
years and females are more commonly affected than
males.35 There is an unpredictable clinical course with the
symptoms varying in severity from a minor nuisance to
being severely debilitating. Diagnosis is entrusted to clinical
presentation and pure tone audiometry, with additional
diagnostic investigations being non-standardised and
controversial36; however, the clinical diagnosis of MD may
be a challenge, particularly in the setting of atypical
symptoms, such as isolated fluctuating hearing loss
(cochlear MD), so there is considerable interest in the
development of a reliable imaging investigation for MD.
Background
MD was first identified as arising in the inner ear by
Prosper Me
niere37,38 over 150 years ago. A dilated endo-
lymphatic system or EH, has been determined by post-
mortem studies to be the pathological cause and the
morphological correlate33,39; however, the relationship
between EH and MD is not fully understood and is complex.
For instance, EH may result from a number of processes,
such as viral infection, trauma, autoimmune disorders, and
electrolyte imbalance; moreover, EH does not necessarily
result in symptoms of MD and EH is not present in all pa-
tients diagnosed with MD.40
The endolymphatic compartment is normally the
smaller central component of the inner-ear fluid, and it is
surrounded by a larger peripheral perilymphatic compart-
ment (Fig 3). Within the cochlea, the smaller endolymph
channel (or scala media) occupies 8e26% of the cochlea
fluid space on MRI, and is surrounded by the perilymphatic
fluid (within the scala tympani and vestibuli). Within the
vestibule, the endolymphatic saccule and utricle comprise
20e41% of the fluid space on MRI, and is also surrounded by
a larger perilymphatic compartment.41 The perilymph is
similar in composition to extracellular fluid, but the endo-
lymph is unique in that it has a higher concentration of
potassium than sodium. The formation and homeostasis of
the membranous labyrinth is not fully understood, but the
endolymphatic sac appears to play a role in reabsorbing the
endolymph.
Due to the varying and fluctuating symptoms, as well as
the difficulty confirming the diagnosis of MD in the absence
of post-mortem histology, several clinical classification
systems have been proposed.42 The currently used AAO-
HNS Committee on Hearing and Equilibrium classification

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 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10 5

Figure 2 A 50-year-old woman presented with left chronic ear discharge. Coronal high-resolution CT images of the temporal bone show
abnormal soft tissue in the (a) epitympanum and (b) mastoid. Coronal fused CT/DWI b¼1000 s/mm2 images show extent and bony relations of
primary acquired cholesteatoma depicted by restricted diffusion (red) in the (c) epitympanum and (d) superior mastoid. It does not involve the
posterior mastoid (e).

divides the disease into certain (post-mortem histological

confirmation of EH), definite, probable, and possible
categories.43

Early imaging in MD

The fluid-containing structures of the inner ears and the

Figure 3 Diagrammatic representation of the endolymphatic (dark
grey) and perilymphatic (light grey) compartments within the inner-
ear structures.
internal septa (e.g., the spiral lamina dividing the scala
tympani and vestibuli of the perilymph) have been clearly
visualised for over 20 years using high-resolution 3D
Fourier transform (FT) MRI sequences, such as CISS
(constructive interference in steady state)44,45; however,
conventional MRI was unable to distinguish the endolym-
phatic from the perilymphatic compartments within the
inner ear, and hence, could not directly depict EH. There was
some early interest in imaging the calibre of the endolym-
phatic sac, as it was proposed that narrowing of the sac
resulted in EH by obstructing the longitudinal flow of
endolymph. Some authors found the endolymphatic sac

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Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
6 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10
and duct to be less visible on MRI during episodes of MD
and even during remission in advanced cases46; however,
this approach was not widely accepted and this pathological
mechanism has now been challenged.47
A potential technique for directly imaging EH was first
discovered accidentally in animals with noise-induced
hearing loss, when trying to assess leakage of gadolinium
into the scala media on a high-field 4.7 T system.48,49 It was
shown that gadolinium accumulated in the perilymphatic
compartment but the endolymphatic compartment
remained impermeable due to the presence of tight junc-
tions. As the gadolinium resulted in T1 shortening within
the perilymphatic compartment, it became possible to
distinguish the two compartments. Now the endolymphatic
compartment could be separated from the remaining inner
fluid, so it was possible to demonstrate the morphological
changes of EH in animal studies.50
Translating this research into clinical practice was
problematic due to the relatively poor accumulation and
concentration of gadolinium in the perilymph. In order to
overcome the risk of systemic toxicity from high-dose
intravenous administration, an initial approach was to
instill intra-tympanic diluted gadolinium, which allowed
contrast medium to enter the perilymph via both the round
and oval windows. This was first tested successfully in
guinea pigs and then applied to human subjects on a 1.5 T
MRI system.51 The first clear demonstration of EH in MD
patients was in 2007, using diluted intratympanic injection
of gadolinium, a 3 T machine, and a 3D-FLAIR sequence52;
however, the use of an intratympanic method of adminis-
tration required a 24-hour delay before imaging, remained
off-label and was less clinically practical than intravenous
administration.
Evolution of MRI techniques in MD
Researchers then focused on developing techniques us-
ing intravenous gadolinium administration, and on opti-
mising MRI sequences, which demonstrated the individual
endolymphatic and perilymphatic compartments.
Compared with the intratympanic route of gadolinium
administration, intravenous administration also had the
advantage of allowing assessment and comparison of both
ears, being independent of round window permeability and
allowing an assessment of the bloodeperilymphatic barrier.
A clinically applicable high-resolution MRI sequence was
required, which could demonstrate the lower concentration
of gadolinium in the perilymph following intravenous in-
jection as compared with intratympanic injection. This
initially comprised an optimisation of the 3D-FLAIR se-
quences53 with inversion-recovery turbo spin echo (IR TSE)
sequences54 and heavily T2W 3D-FLAIR sequences55 also
being utilised. A 3 T magnet and a combination of a head
coil and a surface (ear) coil was required to optimise image
quality. A varying number of receive channels of the head
coil have been assessed in different studies. Such sequences
could be applied to distinguish the differing signals of
perilymph, endolymph, and bone. “Positive perilymph “or
“positive endolymph” images could be acquired by varying
Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
the inversion time of the 3D-FLAIR sequence. These se-
quences could then be visually compared with high-
resolution heavily T2W cisternographic sequences, which
demonstrated the total labyrinthine volume (both peri-
lymph and endolymph).56 Naganawa et al. developed a se-
ries of sequences and post-processing techniques for the
MRI of MD.57,58 For instance, a subtraction of a positive
endolymph image from a positive perilymph image was
termed HYDROPS (a HYbriD of Reversed image Of Positive
endolymph signal and native image of positive perilymph
Signal)57 and demonstrated anatomical information and the
inner-ear compartments in one image series; however, such
post-processing to decrease temporal bone signal is not
necessarily required, and less time-consuming or software-
intensive 3D-FLAIR-based techniques have also proven
successful.56
Investigators have also evaluated the impact of different
gadolinium administration regimes. The time interval be-
tween the intravenous gadolinium administration and im-
aging has been shown to influence the degree of
perilymphatic enhancement, with a 4-hour delay resulting
in greater contrast enhancement within the perilymph, in
both symptomatic and asymptomatic ears.59e61 The
contrast enhancement of the perilymph has also been
evaluated with differing gadolinium dosage, with standard
single (0.2 ml/kg body weight Gd-DTPA), double-dose and
triple-dose techniques all demonstrating EH in the cochlea
and vestibule with MD.62
MRI grading criteria for EH and correlation with MD
Various semi-quantitative grading criteria have been
reported in order to describe and investigate the appear-
ances of the dilated endolymphatic compartment. These
have been used to help validate the relationship between
the MRI appearances, and the presence or severity of clin-
ical features. Such semi-quantitative analysis has been
shown to correlate well with quantitative/volumetric
measures of the degree of EH.63 An early grading system
differentiated mild from significant EH on MRI.64 The ratio
of the endolymphatic space was compared to the whole
vestibular fluid space (both endolymph and perilymph);
with mild vestibular hydrops being defined as a ratio of
34e50% and severe vestibular hydrops being >50% of the
vestibule. Cochlear hydrops was observed as a dilated scala
media; with mild cochlear hydrops being reported when
the scala media remained smaller in volume than the
compressed scala vestibuli, and significant cochlear hydrops
being reported when the scala media was larger than the
scala vestibuli (Figs 4 and 5).
Other semi-quantitative grading systems have been
described, which have used differing cut-off values and
methods of evaluation (e.g., single versus multiple sec-
tions); however, there is currently no consensus on their
usage. There are few data on the grading of EH in patients
without MD and on the reproducibility of these observa-
tions.41,56,65,66 In a more recent study, the results of the
above semi-quantitative methods of grading were ques-
tioned. The authors noted that EH changes in saccular

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 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10 7

Figure 4 Normal appearances of the endolymphatic structures. (a) Inferior and (b) superior 3D FLAIR axial sections through the labyrinthine
structures (0.450.451.1 mm voxels) 4 hours following double-dose gadolinium. Note the normal-sized saccule (anterior arrow) and utricle
(posterior arrow).

Figure 5 EH. 3D FLAIR axial sections (0.450.451.1 mm voxels) through the labyrinthine structures in three different patients performed at 4
hours following double-dose gadolinium. (aeb) Cochlear and vestibular hydrops is shown with dilated scala media (white open arrows) as well
as enlargement with confluence of the saccule and utricle (black open arrows). The changes are more marked in (b) with further effacement of
the vestibular fluid space (black open arrows) and the scala vestibuli (white open arrows) by the dilated endolymphatic structures. (c) Isolated
cochlear hydrops grade demonstrating mild enlargement of the scala media within the basal, middle, and apical turns of the cochlea (arrows
indicating the scala media in basal and middle turns).

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Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
8 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10

morphology are more frequent than those of the utricle on
temporal bone sections, and hence, they evaluated the
inversion of the saccule to utricle ratio (SURI) on an oblique
sagittal section, as a marker of EH. SURI was only found in
patients with MD (50%) and was felt to be a more reliable
approach than conventional semi quantitative methods for
distinguishing subjects with MD from healthy subjects66
(Fig 6).
The MRI finding and grading of ED has also been corre-
lated with the clinical diagnosis of MD.67 It has been shown
that 90% of patients with clinical MD had EH on MRI,62,68
which is a similar frequency to that demonstrated in his-
topathological series. The frequency of EH on MRI also
correlates with the American Academy of Otolar-
yngologyeHead and Neck Surgery clinical diagnostic scale;
it is present in 73% of ears with clinically possible, 100% with
clinically probable and 95% with clinically definite MD.68 It
is of interest that MD more frequently features vestibular
symptoms than hearing loss in its early course, and this
correlates with the MRI findings which show more frequent
vestibular than cochlear hydrops. As is found on post-
mortem examinations, patients with MD also demonstrate
EH in clinically silent ears, and on MRI this is also shown
(although is noted to be less marked) in 22e65% of
cases.68,69 The severity of EH on MRI does not correlate with
the tinnitus and aural fullness of MD67; however, there is a
relationship with duration of disease. There have been
variable results when correlating MRI findings of ED with
hearing thresholds at differing frequencies and vestibular
function testing.67,70 It is of interest that EH has been
demonstrated in patients with “atypical” cochlear MD and
recurrent vestibulopathy, suggesting that there are similar
pathophysiological mechanisms as in MD.71,72 There is a
paucity of data on the application of these MRI grading
scales to endolymphatic structures in healthy subjects, but
some caseecontrol studies are now available.66
Current status
Due to the varying and fluctuating symptoms MD, it may
be difficult to diagnose clinically. There are increasing data
to validate the application of 3 T MRI performed at 4 hours
post-intravenous gadolinium with 3D-FLAIR sequences for
the diagnosis and grading of the associated EH. Although
the MRI demonstration and grading of EH does not feature
in current diagnostic criteria, it is likely that further tech-
nological developments and validation of these techniques
will result in it being a useful diagnostic tool, which in-
fluences therapeutic decisions and the evaluation of ther-
apeutic success in MD.

Figure 6 Saccule and utricle area assessment. 3D FLAIR 4 hours following double-dose gadolinium. Normal endolymphatic structures with
0.70.70.7 mm voxels. (a) Inferior section through vestibule, (b) superior section through vestibule, and (c) sagittal reformat through the
vestibule demonstrating the antero-inferior saccule (black open arrow) and the postero-superior utricle (white open arrow). (d) Inversion of the
saccule to utricle ratio in a patient with EH on an axial section with 0.450.451.1 mm voxels. There is only minor enlargement of the saccule
and utricle but note that the saccule (black open arrow) is larger than the utricle (white open arrow).

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(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10
References
1. De Foer B, Vercruysse J-P, Pilet B, et al. Single-shot, turbo spin-echo,
diffusion-weighted imaging versus spin-echo-planar, diffusion-
weighted imaging in the detection of acquired middle-ear choles-
teatoma. AJNR Am J Neuroradiol 2006;27:1480e2.
2. Dubrulle F, Souillard R, Chechin D, et al. Diffusion-weighted MR imaging
sequence in the detection of postoperative recurrent cholesteatoma.
Radiology 2006;238:604e10.
3. Khemani S, Singh A, Lingam RK, et al. Imaging of postoperative middle
ear cholesteatoma. Clin Radiol 2011;66:760e7.
4. M

s F, Mateos-Ferna
as-Estelle
ndez M, Carrascosa-Bisquert B, et al.
Contemporary non-echo-planar diffusion-weighted imaging of middle-
ear cholesteatomas. RadioGraphics 2012;32:1197e213.
5. Lingam RK, Nash R, Majithia A, et al. Non-echoplanar diffusion weighted
imaging in the detection of postoperative middle-ear cholesteatoma:
navigating beyond the pitfalls to find the pearl. Insights Imaging
2016;75:669e78.
6. Le Bihan D, Breton E, Lallemand D, et al. Separation of diffusion and
perfusion in intravoxel incoherent motion MR imaging. Radiology
1988;168:497e505.
7. Padhani AR, Liu G, Koh DM, et al. Diffusion-weighted magnetic reso-
nance imaging as a cancer biomarker: consensus and recommendations.
Neoplasia 2009;11:102e25.
8. Jindal M, Riskalla A, Jiang D, et al. A systematic review of diffusion-
weighted magnetic resonance imaging in the assessment of post-
operative cholesteatoma. Otol Neurotol 2011;32:1243e9.
9. Muzaffar J, Metcalfe C, Colley S, et al. Diffusion-weighted magnetic
resonance imaging for residual and recurrent cholesteatoma: a sys-
tematic review and meta-analysis. Clin Otolaryngol 2016;42(3).
10. Lingam RK, Khatri P, Hughes J, et al. Apparent diffusion coefficients for
detection of postoperative middle-ear cholesteatoma on non-echo-
planar diffusion-weighted images. Radiology 2013;269:504e10.
11. Khemani SC, Singh A, Lingam RK, et al. Radiological imaging of choles-
teatoma. Otorhinolaryngol 2010;3:69e78.
12. Tomlin J, Chang D, McCutcheon B, et al. Surgical technique and recurrence
in cholesteatoma: a meta- analysis. Audiol Neurotol 2013;18:135e42.
13. Kim JH, Choi SH, Chung JW. Clinical results of attico-antrotomy with
attic reconstruction or attic obliteration for patients with an attic cho-
lesteatoma. Clin Exper Otorhinolaryngol 2009;2:39e43.
14. De Foer B, Vercruysse JP, Bernaerts A, et al. Middle-ear cholesteatoma:
non-echo-planar diffusion-weighted MR imaging versus delayed
gadolinium-enhanced T1-weighted MR imagingdvalue in detection.
Radiology 2010;255:866e72.
15. Li PM, Linos E, Gurgel RK, et al. Evaluating the utility of non-echo-planar
diffusion-weighted imaging in the preoperative evaluation of choles-
teatoma: a meta-analysis. Laryngoscope 2013;123:1247e50.
16. van Egmond SL, Stegeman I, Grolman W, et al. A systematic review of
non-echo planar diffusion-weighted magnetic resonance imaging for
detection of primary and postoperative cholesteatoma. Otolaryngol Head
Neck Surg 2016;154:233e40.
17. Lingam RK, Bassett P. A Meta-analysis on the diagnostic performance of
non-echo-planar diffusion-weighted imaging in detecting middle-ear
cholesteatoma: 10 years on. Otol Neurotol 2017;31:521e8.
18. Khemani S, Lingam RK, Kalan A, et al. The value of non-echo planar
HASTE diffusion-weighted MR imaging in the detection, localisation and
prediction of extent of postoperative cholesteatoma. Clin Otolaryngol
2011;36:306e12.
19. Pizzini FB, Barbieri F, Beltramello A, et al. HASTE diffusion-weighted 3-
Tesla magnetic resonance imaging in the diagnosis of primary and re-
lapsing cholesteatoma. Otol Neurotol 2010;31:596e602.
20. Yamashita K, Yoshiura T, Hiwatashi A, et al. High-resolution three-
dimensional diffusion-weighted imaging of middle-ear cholesteatoma
at 3.0 T MRI: usefulness of 3D turbo field-echo with diffusion-sensitized
driven-equilibrium preparation (TFE-DSDE) compared to single-shot
echo-planar imaging. Eur J Radiol 2013;82(9):e471e5.
21. Steens S, Venderink W, Kunst D, et al. Repeated postoperative follow-up
diffusion-weighted magnetic resonance imaging to detect residual or
recurrent cholesteatoma. Otol Neurotol 2016;37:356e61.
22. Nevoux J, Lenoir M, Roger G, et al. Childhood cholesteatoma. Eur Ann
Otorhinolaryngol Head Neck Dis 2010;127:143e50.
Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
9
23. Nash R, Wong PY, Kalan A, et al. Comparing diffusion weighted MRI in
the detection of postoperative middle-ear cholesteatoma in children
and adults. Int J Pediatr Otorhinolaryngol 2015;79:2281e5.
24. Nash R, Kalan A, Lingam RK, et al. The role of diffusion-weighted magnetic
resonance imaging in assessing residual/recurrent cholesteatoma after
canal wall down mastoidectomy. Clin Otolaryngol 2016;41:307e9.
25. Majithia A, Lingam RK, Nash R, et al. Staging primary middle-ear cho-
lesteatoma with non-echoplanar (half-Fourier-acquisition single-shot
turbo spin- echo) diffusion-weighted magnetic resonance imaging
helps plan surgery in 22 patients: our experience. Clin Otolaryngol
2012;37:325e30.
26. Migirov L, Wolf M, Greenberg G, et al. Non-EPI DW MRI in planning the
surgical approach to primary and recurrent cholesteatoma. Otol Neurotol
2014;35:121e5.
27. Wong PY, Lingam RK, Pal S, et al. Monitoring progression of 12 cases of
non-operated middle-ear cholesteatoma with non-echoplanar diffusion
weighted magnetic resonance imaging: our experience. Otol Neurotol
2016;37(10):1573e6.
28. Plouin-Gaudon I, Bossard D, Ayari-Khalfallah S, et al. Fusion of MRIs and
CT scans for surgical treatment of cholesteatoma of the middle ear in
children. Arch Otolaryngol Head Neck Surg 2010;136:878e83.
29. Yamashita K, Hiwatashi A, Togao O, et al. High-resolution three-
dimensional diffusion-weighted MRI/CT image data fusion for choles-
teatoma surgical planning: a feasibility study. Eur Arch Otorhinolaryngol
2015;272:3821e4.
30. Locketz GD, Li PM, Fischbein NJ, et al. Fusion of computed tomography
and PROPELLER diffusion-weighted magnetic resonance imaging for the
detection and localization of middle-ear cholesteatoma. JAMA Otolar-
yngol Head Neck Surg 2016;142:947e53.
31. Alzahrani M, Alhazmi R, Be
lair M, et al. Postoperative diffusion weighted
MRI and preoperative CT scan fusion for residual cholesteatoma locali-
zation. Int J Pediatr Otorhinolaryngol 2016;90:259e63.
32. Watanabe T, Ito T, Furukawa T, et al. The efficacy of color mapped fusion
images in the diagnosis and treatment of cholesteatoma using trans-
canal endoscopic ear surgery. Otol Neurotol 2015;36:763e8.
33. Gurkov R, Pyyko I, Zou JK. Me
niere’s disease? A contemporary re-
evaluation of endolymphatic hydrops. J Neurol 2016;263:71e81.
34. Committee on hearing and equilibrium. Menieres disease: criteria for
diagnosis and evaluation of therapy for reporting. AAO-HNS Bulletin
1985;5:6e7.
35. Lopez-Escameza JA, Careyb J, Chungc W-H, et al. Diagnostic criteria for
Meniere’s disease List of acronyms. J Vestib Res 2015;25:1e7.
36. Muzzi E, Rinaldo A, Ferlito A. Me
niere disease: diagnostic instrumental
support. Am J Otolaryngol 2008;29:188e94.
37. Harcourt J, Barraclough K, Bronstein AM. Me
nie
re’s disease. BMJ
2014;349.
38. Atkinson M. Meniere’s original papers reprinted with an English
translation with commentaries and biographical sketch. Acta Otolar-
yngol 1961;162:1e78.
39. Hallpike CS, Cairns H. Observations on the pathology of Me
nie
re’s
syndrome. Proc R Soc Med 1938;31:1317e36.
40. Fraysse BG, Alonso AHW. Me
niere’s disease and endolymphatic
hydrops: clinical-histopathological correlations. Rhinol Laryngol Suppl
1980;89:2e22.
41. Liu F, Huang W, Meng X, et al. Comparison of noninvasive evaluation of
endolymphatic hydrops in Me
nie
re’s disease and endolymphatic space
in healthy volunteers using magnetic resonance imaging. Acta Otolar-
yngol 2012;132:234e40.
42. Van de HPH, Wuyts FL, Claes J, et al. Definition, classification and
reporting of Me
niere’s disease and its symptoms. Acta Otolaryngol Suppl
1997;526:5e9.
43. Lopez-Escamez JA, Carey J, Chung WH, et al. Diagnostic criteria for
Menie re’s disease. J Vestib Res Equilib Orientat 2015;25:1e7.
44. Brogan M, Chakeres DW, Schmalbrock P. High-resolution 3D FT MR
imaging of the endolymphatic duct and soft tissues of the otic capsule.
AJNR Am J Neuroradiol 1991;12:1e11.
45. Casselman JW, Kuhweide R, Deimling M, et al. Constructive interference
in steady state 3D FT MR imaging of the inner ear and cerebellopontine
angle. AJNR Am J Neuroradiol 1993;14:47e57.
46. Tanioka H, Kaga H, Zusho H, et al. MR of the endolymphatic duct and
sac: findings in meniere disease. AJNR Am J Neuroradiol 1997;18:45e51.

nie
10 R.K. Lingam et al. / Clinical Radiology xxx (2017) 1e10
47. Merchant SN, Adams JC, Nadol JB. Pathophysiology of Meniere’s syn-
drome: are symptoms caused by endolymphatic hydrops? Otol Neurotol
2005;26:74e81.
48. Zou J, Pyykko€ I, Yoshida T, et al. Milestone research on Meniere’s disease by
visualizing endolymphatic hydrops using gadolinium-enhanced inner ear
MRI and the challenges in clinical applications. Austin J Radiol 2015;2:1035.
49. Zou J, Pyykko I, Bretlau P, et al. In vivo visualization of endolymphatic
hydrops in guinea pigs: magnetic resonance imaging evaluation at 4.7
tesla. Ann Otol Rhinol Laryngol 2003;112:1059e65.
50. Niyazov DM, Andrews JC, Strelioff D, et al. Diagnosis of endolymphatic
hydrops in vivo with magnetic resonance imaging. Otol Neurotol
2001;22:817e9.
51. Zou J, Pyykko € I, Bjelke B, et al. Communication between the peril-
ymphatic scalae and spiral ligament visualized by in vivo MRI. Audiol
Neurotol 2005;10:145e52.
52. Nakashima T, Naganawa S, Sugiura M, et al. Visualization of endolym-
phatic hydrops in patients with Me
niere’s disease. Laryngoscope
2007;117:415e20.
53. Naganawa S, Sugiura M, Kawamura M, et al. Imaging of endolymphatic
and perilymphatic fluid at 3T after intratympanic administration of
gadolinium-diethylene-triamine pentaacetic acid. AJNR Am J Neuroradiol
2008;29:724e6.
54. Naganawa S, Satake H, Kawamura M, et al. Separate visualization of
endolymphatic space, perilymphatic space and bone by a single pulse
sequence; 3D-inversion recovery imaging utilizing real reconstruction
after intratympanic Gd-DTPA administration at 3 Tesla. Eur Radiol
2008;18:920e4.
55. Naganawa S, Kawai H, Sone M, et al. Increased sensitivity to low con-
centration gadolinium contrast by optimized heavily T2-weighted 3D-
FLAIR to visualise endolymphatic space. Magn Reson Med Sci
2010;9:73e80.
56. Sepahdari AR, Ishiyama G, Vorasubin N, et al. Delayed intravenous
contrast-enhanced 3D FLAIR MRI in Me
nie
re’s disease: correlation of
quantitative measures of endolymphatic hydrops with hearing. Clin
Imaging 2015;39:26e31.
57. Naganawa S, Yamazaki M, Kawai H, et al. Imaging of Me
nie
re’s disease
after intravenous administration of single-dose gadodiamide: utility of
multiplication of MR cisternography and HYDROPS image. Magn Reson
Med Sci 2013;12:63e8.
58. Naganawa S, Yamazaki M, Kawai H, et al. MR imaging of Me
niere’s
disease after combined intratympanic and intravenous injection of
gadolinium using HYDROPS2. Magn Reson Med Sci 2014;13:133e7.
59. Kim TY, Park DW, Lee YJ, et al. Comparison of inner ear contrast
enhancement among patients with unilateral inner ear symptoms in
MR images obtained 10 minutes and 4 hours after gadolinium injection.
AJNR Am J Neuroradiol 2015;36:2637e42.
Please cite this article in press as: Lingam RK, et al., MRI in otology: applications in cholesteatoma and Me re’s disease, Clinical Radiology
(2017), http://dx.doi.org/10.1016/j.crad.2017.09.002
60. Sano R, Teranishi M, Yamazaki M, et al. Contrast enhancement of the
inner ear in magnetic resonance images taken at 10 minutes or 4 hours
after intravenous gadolinium injection. Acta Otolaryngol
2012;132:241e6.
61. Tagaya M, Teranishi M, Naganawa S, et al. 3 Tesla magnetic resonance
imaging obtained 4 hours after intravenous gadolinium injection in
patients with sudden deafness. Acta Otolaryngol 2010;130:665e9.
62. Suzuki H, Teranishi M, Sone M, et al. Contrast enhancement of the inner
ear after intravenous administration of a standard or double dose of
gadolinium contrast agents. Acta Otolaryngol 2011;131:1025e31.
63. Homann G, Vieth V, Weiss D, et al. Semi-quantitative vs. volumetric
determination of endolymphatic space in Menie re’s disease using
endolymphatic hydrops 3T-HR-MRI after intravenous gadolinium in-
jection. PLoS One 2015;10:e0120357. http://dx.doi.org/10.1371/journal
.pone.0120357.
64. Nakashima T, Naganawa S, Pyykko I, et al. Grading of endolymphatic
hydrops using magnetic resonance imaging. Acta Otolaryngol Suppl
2009;560:5e8.
65. Fang ZM, Chen X, Gu X, et al. A new magnetic resonance imaging scoring
system for perilymphatic space appearance after intratympanic gado-
linium injection, and its clinical application. J Laryngol Otol
2012;126:454e9.
66. Attye A, Eliezer M, Boudiaf N, et al. MRI of endolymphatic hydrops in
patients with Me
nie
re’s disease: a case-controlled study with simplified
classification based on saccular morphology. Eur Radiol 2016 Dec 20.
1007/s00330-016-4701-z.
67. Wu Q, Dai C, Zhao M, et al. The correlation between symptoms of def-
inite Meniere’s disease and endolymphatic hydrops visualized by
magnetic resonance imaging. Laryngoscope 2016;126:974e9.
68. Pyykko € I, Nakashima T, Yoshida T, et al. Me
nie
re’s disease: a reappraisal
supported by a variable latency of symptoms and the MRI visualisation
of endolymphatic hydrops. BMJ Open 2013;3:1e10.
69. Bara
th K, Schuknecht B, Monge Naldi A, et al. Detection and grading of
endolymphatic hydrops in Meniere disease using MR. AJNR Am J Neu-
roradiol 2014;59:62e7.
70. Seo YJ, Kim J, Choi JY, et al. Visualization of endolymphatic hydrops and
correlation with audio-vestibular functional testing in patients with
definite Meniere’s disease. Auris Nasus Larynx 2013;40:167e72.
71. Kato M, Sugiura M, Shimono M, et al. Endolymphatic hydrops revealed
by magnetic resonance imaging in patients with atypical Meniere’s
disease. Acta Otolaryngol 2013;133:123e9.
72. Attye
A, Dumas G, Tropre s I, et al. Recurrent peripheral vestibulopathy:
Is MRI useful for the diagnosis of endolymphatic hydrops in clinical
practice? Eur Radiol 2015;25:3043e9.

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