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Magnetic Resonance Imaging in a Guinea Pig Model of Inner Ear
Decompression Sickness and Barotrauma
Nathan E. Pierce, MD; G. Joseph Parell, MD; Reordan O. De Jesus, MD;
Carolyn P. Ojano-Dirain, PhD; Patrick J. Antonelli, MD
Objectives/Hypothesis: Scuba diving may cause severe hearing loss and vertigo due to inner ear barotrauma and
decompression sickness. These may be difficult to differentiate clinically. Decompression sickness requires costly and potentially dangerous hyperbaric therapy, whereas such treatment may worsen barotrauma. The objective of this study was to
assess the potential utility of magnetic resonance imaging to identify and distinguish blood from air in the inner ear, manifestations of barotrauma and decompression sickness, using a guinea pig model.
Study Design: Prospective animal trial.
Methods: Magnetic resonance of the head was performed at 3 Tesla, pre- and postinjection of 2, 4, or 10 lL of air or
blood through the round window into the perilymph. With this model, 2 lL has been shown to cause hearing loss. Images
were reviewed by a neuroradiologist blinded to the treatment.
Results: All 14 normal ears, five of seven blood- and five of seven air-injected ears, were correctly interpreted. Two
blood- and one air-injected ear were interpreted as indeterminate. One air-injected ear was incorrectly interpreted as blood.
Conclusions: Magnetic resonance reliably distinguishes small volumes of air and blood in the guinea pig inner ear. Magnetic resonance should be evaluated for its utility in the diagnosis of inner ear barotrauma and decompression sickness in
scuba divers.
Key Words: Magnetic resonance imaging, decompression sickness, barotrauma, inner ear.
Level of Evidence: NA
Laryngoscope, 126:2106–2109, 2016
INTRODUCTION
Scuba diving is a common commercial, recreational,
and military activity. High-pressure environments, such
as scuba diving and hyperbaric chambers can cause
unique disorders, including barotrauma, decompression
sickness, and arterial gas embolism. Otolaryngologic
complaints account for approximately 80% of all scuba
diving–related disorders.1 In a series of 306 scuba divers
presenting to an otolaryngology clinic, 18% had disorders involving the inner ear.2
Scuba diving–related disorders involving the inner
ear fall largely into two categories: inner ear barotrauma
(IEBT) and inner ear decompression sickness (IEDS).3
From the Department of Otolaryngology (N.E.P., G.J.P., C.P.O.-D.,
and the Department of Radiology (R.O.D.), University of Florida,
Gainesville, Florida, U.S.A.
Editor’s Note: This Manuscript was accepted for publication
November 6, 2015.
Presented at the Triological Society Combined Sections Meeting,
Coronado, California, U.S.A., January 22–24, 2015.
A portion of this work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory’s AMRIS Facility,
which is supported by National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida. Financial support for
this study was provided by the University of Florida, Gainesville,
Florida.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Send correspondence to Patrick J. Antonelli, MD, University of
Florida, Otolaryngology Head & Neck Surgery, PO Box 100264, Gainesville, FL 32610. E-mail: [email protected]
P.J.A.),
DOI: 10.1002/lary.25811
Laryngoscope 126: September 2016
2106
Dive profiles and history can help to distinguish these
two entities. However, there is evidence that overlap can
exist,4 and differentiation can prove difficult. IEBT usually occurs during descent with difficulty equalizing middle ear pressure by forceful autoinflation. This is
thought to cause rupture of Reissner’s membrane, bleeding into the inner ear, or perilymph fistula formation.5–7
IEBT may show signs of middle ear barotrauma.8 Treatment of IEBT is bed rest, head elevation, and precautions to decrease cerebrospinal fluid and middle ear
pressures.7,9 Exploratory tympanotomy for a possible
perilymph fistula may be considered if symptoms do not
improve with conservative treatment.6
IEDS develops as a result of nitrogen bubbles accumulating in the tissues. The risk of IEDS is directly
dependent on the amount of nitrogen dissolved in the tissues—a function of both the depth and the duration of the
dive—and the rate of ascent. Classically, decompression
sickness presents with skeletal pain, skin marbling, and
neurologic changes caused by gas bubbles forming out of
solution. Irreversible hearing loss and vestibular symptoms may be prevented with rapid recompression.8,10
Objective testing to help guide clinical decision making in scuba diving–related inner ear injuries is lacking.
Magnetic resonance imaging (MRI) holds tremendous
potential for the differentiation of IEDS from IEBT. MRI
can demonstrate gas—the hallmark of IEDS—in soft tissues and fluid filled spaces (e.g., the inner ear). It can
also demonstrate the presence of blood— found in both
Pierce et al.: MRI in a Guinea Pig Model of IEDS and IEBT
TABLE I.
Number of Guinea Pig Ears Interpreted Correctly, Incorrectly, and
Indeterminate for Each Blood Injection, Air Injection, and No
Injection.
Correct
No injection
Blood
Air
Incorrect
Indeterminate
14
0
0
5
5
0
1
2
1
IEDS and IEBT—from other fluids (e.g., normal spinal
fluid or perilymph). MRI at 3 Tesla (T) is a relatively safe
diagnostic procedure in individuals without ferromagnetic
implants or foreign bodies.11,12 Though transient sensory
symptoms (e.g., vertigo, nausea, and dysgeusia) are not
uncommon, no serious health effects have been reported
below 8 T.11 To date, no studies have assessed the sensitivity of clinically available MRI for detecting signs of
IEBT and IEDS. The goal of this study was to explore the
feasibility of 3 T MRI for detecting air and blood in the
inner ear using a guinea pig model.
MATERIALS AND METHODS
Experimental Design
This study was approved by the University of Florida
Institutional Animal Care and Use Committee (IACUC). Seven
mixed gender, Cavia albino, 350-g Hartley guinea pigs (Charles
River, Wilmington, MA) underwent surgery as previously
described,13–16 with injection of blood or air into the scala tympani to serve as a model for IEBT and IEDS. MRI scans were
obtained before and after inner ear injections. Therefore, each
animal ear served as its own control. Animals were sacrificed
under deep anesthesia after conclusion of the final scan.
The entire volume of the inner ear space in a guinea pig is
20.9 lL and the perilymph is 15.94 lL.17 It has also been shown
that injection of 1.5-2 lL of air into the inner ear space of
guinea pigs causes measurable changes in otoacoustic emissions.18 The IEDS model was established by injecting air into
the inner ear space through the round window, and the IEBT
model was established by injecting blood into the inner ear
space through the round window.
MRI
Anesthetized animals underwent pre- and postinjection MRI
scans of the head with attention given to the inner ear. Scans
were obtained on a Philips Achieva 3.0 Tesla clinical scanner
(3.2.1 software; Philips Healthcare, Amsterdam, the Netherlands).
T1 fluid-attenuated inversion recovery (FLAIR) and T2 driven
equilibrium pulse (DRIVE) images were obtained. T1 and FLAIR
imaging techniques were chosen due to the ability to adequately
visualize blood. T2 DRIVE, which demonstrates a high fluid signal of the perilymph, was hypothesized to visualize air well, due
to the signal void it would produce. Imaging protocols were developed by a neuroradiologist and an imaging scientist by modifying
existing human protocols. Acquired images were stored for later
blinded review by the neuroradiologist. The radiologist’s interpretation on the presence or absence of blood or air in the inner ear
was recorded and compared to the known exposure condition.
Given the small sample sizes involved, only qualitative comparisons were performed.
RESULTS
All seven guinea pigs completed the surgery and
imaging protocol. Four animals were injected with 4 lL,
two animals were injected with 2 lL, and one was
injected with 10 lLl as a positive control. The blinded
radiologist correctly interpreted all 14 negative control
(no injection) ears. Five of seven blood and five of seven
air-injected ears were correctly interpreted. One airinjected (4 lL) ear was incorrectly interpreted. Two the
blood-injected (2, 4 lL) ears were interpreted as indeterminate. One of the air-injected (2 lL) ears was interpreted as indeterminate (Table I). T1 imaging showed
blood well, but air was poorly visualized. Similarly,
FLAIR images identified blood, but air was not well
seen. T2 DRIVE easily identified air. Injected blood was
also discernible but not as well visualized as in the T1
and FLAIR imaging (Figs. (1 and 2), and (1 and 3)).
DISCUSSION
Anesthesia was induced with xylazine (5 mg/kg subcutaneous [SC]) and ketamine (40 mg/kg SC). After a 5-minute period
of quiet, the hair was clipped, and lidocaine was injected SC
over the mastoid bullae and skull dorsum for local anesthesia.
Thermal support was provided preoperatively, intraoperatively,
and postoperatively. After betadine skin preparation, oblique
skin incisions were made over the nuchal crest and extended
posteriorly and laterally. A third incision was carried anteriorly
along the midline. The temporalis muscle was elevated anterolaterally. The mastoid bulla was entered with a cutting bur. The
round window was fully exposed. At that point, the incision was
lightly closed with suture and the preinjection MRI was performed. After imaging, the wound was opened and each round
window was injected with either blood or air using a Hamilton
syringe and a 32-gauge needle. The volumes of injections were
2, 4, or 10 lL. The incision was again lightly closed. Postinjection scans were obtained. Thereafter, the animal was sacrificed
under deep anesthesia.
Scuba diving–related inner ear diving injuries are
known to result from failure to equilibrate, with bleeding
into the tissues and spaces (i.e., IEBT), or accumulation
of nitrogen bubbles in the tissues due to overly rapid
ascent (i.e., IEDS).3–8 To date, differentiation of these disorders has relied on dive parameters and clinical history.
No diagnostic testing has been validated for the distinction of these disorders. In this study, we sought to determine if small volumes of blood and air in the inner ear
could be visualized using MRI. Using a guinea pig model,
which has an inner ear volume much smaller than that
of a human, we found that small —but enough to induce
auditory dysfunction18,19—volumes of either blood or air
within the inner ear were easily visualized and differentiated with a clinical MRI scanner.
Diagnostic imaging is an established method of
diagnosing a range of scuba diving–related injuries,
including arterial gas embolism, pneumocephalus, pulmonary barotrauma, and is occasionally used forensically.20–22 Imaging is not routinely used in obvious cases
of systemic decompression sickness due to the urgency
of recompression.10 Cases of isolated IEDS (i.e., without
systemic signs of decompression sickness) should be
Laryngoscope 126: September 2016
Pierce et al.: MRI in a Guinea Pig Model of IEDS and IEBT
Surgical Technique
2107
Fig. 1. T1-weighted images. (A) Preinjection image. (B) Postinjection
image shows increased signal to
injected blood (solid arrow) and
absence of signal due to injected air
(dashed arrow).
Fig. 2. Fluid-attenuated inversion
recovery images. (A) Preinjection
image. (B) Postinjection image
shows increased signal due to
injected blood (solid arrow) and
absence of signal due to injected air
(dashed arrow).
rare, as decompression sickness is a systemic process.
Not surprisingly, little has been published on imaging in
IEDS. The sole article on imaging in IEDS reported the
cause to be cerebellar infarction.23 Similarly, very little
has been published on IEBT.24
Pneumolabyrinth, an expected finding in IEDS, has
ironically been reported related to barotrauma.25,26
Hemolabyrinth has been ascribed to a range of disorders
including idiopathic sudden sensorineural hearing loss27
and IEDS.4 Thus, it is possible that both blood and gas
may be found in the inner ear in both IEDS and IEBT.
Being able to radiographically visualize gas and blood in
the inner ear using MRI may allow for improved understanding of the pathophysiology of these scuba diving–
related inner ear injuries, as well as possibly being able
to guide treatment. The latter has been a point of
controversy.28,29
MRI has long been held as the imaging modality of
choice for nonosseous, acquired lesions of the inner ear,
particularly in cases of sudden sensorineural hearing loss
or acute onset of vertigo.27,30–33 Our findings suggest that
the 3 T MRI protocols we employed are far from 100%
accurate for the identification of blood and air in the
guinea pig inner ear. Computed tomography (CT) might
also be of value in distinguishing IEBT from IEDS, as it
has been shown to be capable of demonstrating small volumes of air in the labyrinth.34 Although CT has been
shown to be highly accurate in identifying blood in cerebrospinal fluid following subarachnoid hemorrhage,35
blood would not be resolved in the labyrinth in most
Fig. 3. T2 driven equilibrium pulse
images. (A) Preinjection image. (B)
Postinjection image shows diffuse
decrease in cochlear signal due to
injected blood (solid arrow) and loss
of signal in the basal turn of the
cochlea from the injected air
(dashed arrow).
Laryngoscope 126: September 2016
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Pierce et al.: MRI in a Guinea Pig Model of IEDS and IEBT
situations with standard techniques. MRI has been
reported to be more sensitive in the identification of
blood,36 especially in more chronic situations.37 MRI has
long been known to be superior to CT in the identification
of central nervous system manifestations of decompression sickness38 and retrolabyrinthine pathology,39 which
may help in the management of patients with scuba diving–related inner ear symptoms. Thus, though we would
expect MRI to be superior to CT for evaluating scuba diving–related inner ear injuries, CT may also prove helpful.
This study utilized modifications of existing human
MRI protocols for use in guinea pigs. We refined these
protocols by studying three animals in a pilot study. In
T1 and FLAIR techniques, blood was seen as diffuse
increase of signal within the cochlea. Neither imaging
modality showed injected air well. Air was better visualized as a loss of signal in the T2 DRIVE imaging, and
blood was seen as a diffusely decreased signal. Further
improvements are likely with additional refinements in
the imaging protocol.
Use of the guinea pig model may also introduce differences from what may be seen in humans. For example,
the guinea pig has a patent cochlear aqueduct, whereas
the human does not.40 Also, the guinea pig cochlea is more
uniformly surrounded by air than the human cochlea,
increasing susceptibility artifacts. Both would, however, be
expected to bias our findings toward lower sensitivity of
MRI to air and blood in the inner ear of the guinea pig. As
it is impossible to atraumatically introduce air into the
inner ear, further bias may have been introduced.
CONCLUSION
MRI reliably distinguishes small volumes of air and
blood in the guinea pig inner ear. MRI should be evaluated for its utility in the diagnosis of IEBT and IEDS
in scuba divers.
Acknowledgments
The authors extend thanks to Song Lai, PhD, and Tammy
Nicholson for assisting in acquiring the images.
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