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High-Resolution Imaging of the Middle Ear With Optical Coherence Tomography
A Feasibility Study
Costas Pitris, PhD;
Kathleen T. Saunders, BS;
James G. Fujimoto, PhD;
Mark E. Brezinski, MD, PhD
Arch Otolaryngol Head Neck Surg. 2001;127:637-642.
ABSTRACT
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Background Optical coherence tomography (OCT) is a new medical imaging technology
that generates cross-sectional images of tissue microstructure with micron-scale
resolution. Optical coherence tomography is analogous to ultrasound, measuring
the intensity of infrared light rather than acoustical waves.
Objective To demonstrate the feasibility of using OCT for ultra–high-resolution
imaging of the middle ear via ex vivo imaging studies of human tissue.
Design Images of the tympanic membrane and middle ear were acquired ex vivo,
through the ear canal, without perforating the tympanic membrane.
Materials Four excised intact temporal bones and the auditory apparatus were harvested
from cadavers and imaged fresh, without previous fixation.
Results The resulting images were compared with the gross sample and verified
the ability of OCT to delineate relevant structures, such as the tympanic
membrane and its sublayers, and the middle ear ossicles, nerves, and tendons
at higher resolutions than possible with standard clinical imaging technologies.
Conclusion The ability of OCT to produce high-resolution images of tissue structure,
without contact and in real time, as well as its ability to be integrated
with endoscopes, suggests that this technology could become a useful modality
for the diagnosis and management of a range of clinical middle ear abnormalities.
INTRODUCTION
MIDDLE EAR surgery is now performed routinely for conditions varying
from congenital abnormalities to trauma and tumors.1
Significant anatomical variation between patients sometimes necessitates presurgical
evaluation of the site of intervention.2 Several
imaging techniques are used to make middle ear surgery safer and more effective.
Computed tomography and magnetic resonance imaging, despite their increased
acceptance in neurosurgery and their valuable contribution to preoperative
assessment, are not suitable for real-time guidance of surgical interventions
in the head and neck.3 Endoscopy, either transmeatic
or transtubal, has also been applied in middle ear surgery; however, endoscopes
are restricted to imaging the surfaces of tissues.4, 5, 6
A technique that could perform real-time cross-sectional imaging to delineate
tissue disease with micron-scale resolution would be a powerful tool in the
diagnosis of disease. Optical coherence tomography (OCT) is an emerging imaging
technology currently under development that enables noncontact, noninvasive,
real-time, cross-sectional imaging of microstructure.7
Optical coherence tomography was first applied to image optically transparent
structures such as the anterior eye and retina.8, 9
Results of preliminary clinical investigations suggest that OCT is a promising
technology for the detection and management of a variety of retinal diseases,
including glaucoma and macular edema.10 Recent
advances have enabled the application of OCT to nontransparent tissue.11, 12, 13 Although the imaging
depth of OCT is limited by the light scattering and attenuation properties
of tissue, image penetrations of 2 to 3 mm can be achieved in most tissues.
The resolution of OCT is 1 to 15 µm, up to 2 orders of magnitude higher
than conventional ultrasound. Because imaging is being performed near the
resolution of histology, over the distance scales of a conventional biopsy,
OCT can function as a type of "optical biopsy." Previous studies13, 14, 15, 16, 17, 18
with OCT have included identification of abnormalities in the cardiovascular
system and the gastrointestinal, urinary, and reproductive tracts, in addition
to studies of neural tissue and cartilage. A small catheter-endoscope system
also has been developed that allowed high-resolution imaging to be performed
internally in a rabbit model.19, 20
This study demonstrates the feasibility of using OCT for ultra–high-resolution
imaging of the middle ear in ex vivo studies of human tissue. Images were
obtained that demonstrated the ability of OCT to image microstructural features
and demarcate tissue layers and bony structures. Microstructure was compared
with gross appearance to confirm the image interpretation and verified the
ability of OCT to delineate features that could be used in the diagnosis of
disease or as anatomical markers. The ability of OCT to generate 3-dimensional
images with resolution in the range close to that of histopathological examination
in real time supports the hypothesis that this optical technology will become
a powerful modality for the diagnosis and monitoring of conditions of the
middle ear.
MATERIALS AND METHODS
Optical coherence tomography is analogous to ultrasound imaging but
is based on the detection of infrared light waves that are backscattered or
reflected from different layers and structures within the tissue. Unlike sound
waves, the speed of light is very high, rendering direct electronic measurement
of the echo delay of the reflected light (time for the signal to return) impossible.
Measurements can be performed using an interferometric correlation technique
known as low-coherence interferometry. In an interferometer, a light beam
from an optical light source is split into 2 parts, a reference beam and a
sample beam. The reference beam is reflected off a mirror at a known distance
and returns to the detector. The sample beam reflects off different layers
within the tissue, and light returning from the sample and reference arms
recombines. If the 2 light beams travel the same distances (optical path length)
to within the coherence length of the light, the 2 beams will interfere. If
the path lengths are mismatched, there is no interference. Optical coherence
tomography measures the intensity of interference of light backscattered or
reflected from different points within the tissue by moving the mirror in
the reference arm, which changes the distance that light travels in the reference
arm. In Figure 1B-C, light from
a coherent vs a low-coherent light source are shown, illustrating how low-coherence
light can be used to localize back-reflection sites and provide the desired
high resolution. Two- or 3-dimensional images are produced by scanning the
optical beam across the sample and recording the optical backscattering vs
depth at different transverse positions. The resulting image is a 2- or 3-dimensional
representation of the optical backscattering of the sample on a micron scale.
The logarithm of the backscattering signal is represented as a false color
or gray-scale image. A schematic of the complete OCT system is shown in Figure 2.
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Figure 1. Low-coherence interferometry principles.
Basic Michelson interferometer (A) and interference patterns, resulting from
the reference arm mirror movement, using a coherent (B) and low-coherent (C)
source. This technique measures the echo delay (time for a reflected light
beam to return) to yield the optical backscattering in the specimen vs depth.
z indicates location of the reference mirror; dz, depth resolution.
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Figure 2. Schematic of the fiber optic implementation
of the optical coherence tomography system. Optical coherence tomographic
images are generated by performing successive measurements of optical backscattering
vs depth at different transverse positions on the specimen. A/D indicates
analog-to-digital conversion circuitry.
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The depth resolution in OCT is defined by the property referred to as
the coherence length of the light source. A mathematical description yields:
(1)
where  z is the resolution,  is the wavelength, and
is the bandwidth, ie, the wavelength range, of the light source.21
Image depth resolution is inversely proportional to the bandwidth of the light
source. The experiments reported herein were performed using a superluminescent
source operating at a wavelength of 1310 nm, with a bandwidth, ,
of 50 nm. The 1310-nm wavelength in the near infrared has reduced optical
scattering and tissue absorption and thus allows deeper imaging in scattering
tissues. The bandwidth of the light source yields a 15-µm depth resolution.
Transverse resolution, perpendicular to the depth dimension, is defined
by the smallest focused spot size that the optics can produce on the specimen,
similar to microscopy. Transverse resolution trades off with the confocal
variable, ie, depth of focus. Transverse resolution is determined by the following
relationship:
(2)
where b is the confocal variable and is the wavelength
of the source.22The combination of optics and
focusing conditions used for the experiments reported herein resulted in a
10- to 20-µm transverse resolution. The penetration is approximately
2 to 3 mm in scattering tissue and is limited by light scattering and attenuation.23
In addition to its high resolution, several features of OCT suggest
it will be a powerful imaging technology for the diagnosis of a wide range
of pathological conditions. First, unlike ultrasound, OCT does not require
a transducing medium, and imaging can be performed directly through air. Second,
unlike computed tomography or magnetic resonance imaging, OCT can be performed
in or near real time, allowing information on tissue microstructure to be
obtained within the dynamic environment of an endoscopy or surgical suite.
Third, OCT is compact and portable, an important consideration for a clinically
viable device. Finally, OCT is fiber optic based, allowing relatively easy
integration with bronchoscopes and endoscopes without significant changes
in device diameter.
Samples for this study were obtained from cadavers and were imaged fresh
without previous fixation. This avoided changes in optical properties associated
with fixation. The specimens were placed in a Petri dish and irrigated with
isotonic saline solution to prevent dehydration during imaging. The OCT probe
was 15 mm from the tympanic membrane (TM), a working distance that can be
adjusted according to the imaging optics used. The acquisition of each image
required between 10 and 30 seconds depending on the size (number of pixel
elements) of the image. Because the OCT beam is invisible, tissue registration
was performed with a visible light guiding beam. The samples were then dissected,
and the TM was removed to reveal the underlying structures. Microscopic examination
of the samples enabled verification of tissue identity and in most instances
allowed identification of sources of tissue contrast in the OCT images.
RESULTS
Multiple transverse OCT images were acquired through the intact TM over
a 5 x 5-mm area spaced 40 µm apart. Figure 3 shows a typical specimen with the TM dissected after OCT
imaging. Images were displayed on a logarithmic intensity scale, with the
least backscattered areas shown in white and the most backscattered areas
shown in black.
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Figure 3. Typical specimen with the tympanic
membrane dissected after optical coherence tomographic imaging to expose the
structures of the middle ear. M indicates manubrium of malleus; I, long process
of incus; CT, chorda tympani nerve; TT, tendon of tensor tympani muscle; and
solid lines A and B, imaging planes of the images in Figure 4.
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Ex vivo OCT images of the human middle ear taken through the auditory
canal as consecutive cross sections perpendicular to the malleus, from the
neck to the manubrium, are shown in Figure
4. The TM can be identified, and the layered nature of that tissue
is also evident. Also visible are the manubrium of malleus, the long process
of incus, the chorda tympani nerve, and the tendon of the tensor tympani muscle.
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Figure 4. Ex vivo optical coherence tomographic
images of the human middle ear taken through the auditory canal at successive
distances from the head of the malleus. The tympanic membrane (TM) can be
identified, and the layered nature of that tissue is also evident. Also visible
are the manubrium of the malleus (M), the long process of incus (I), the chorda
tympani nerve (CT), and the tendon of the tensor tympani muscle (TT) (image
size, 5 x 5 mm; resolution, 15 µm).
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Volume reconstruction of a data set of ex vivo OCT images of the human
middle ear is shown in Figure 5.
The set consisted of 142 images spanning a total volume of 5 x 5 x
5 mm. The data were then rendered using simple projection algorithms included
in an image processing package (NIH Image; National Institutes of Health,
Bethesda, Md). The 3-dimensional nature of the structures identified in Figure 4 is visible from different viewing
angles. False color was used to highlight different structures for clarity.
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Figure 5. Volume reconstruction of a data
set of ex vivo optical coherence tomographic images of the human middle ear.
The 3-dimensional nature of the structures identified in Figure 4 are visible
from different view angles: superior (A), coronal (B), lateral (C), and medial
(D). The tympanic membrane (TM), the manubrium of the malleus (M), the long
process of incus (I), the chorda tympani nerve (CT), and the tendon of the
tensor tympani muscle (TT) can be identified (volume size, 5 x 5 x
5 mm; 142 cross-sectional images; resolution, 15 µm).
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COMMENT
This work demonstrates the feasibility of OCT for cross-sectional and
3-dimensional imaging of middle ear structures without the need to perforate
the TM. Images correlated well with gross anatomy. The primary focus of this
study was to demonstrate the feasibility of OCT imaging of normal tissue.
Additional studies will be required to examine the ability to assess different
abnormalities and pathological conditions in vitro and in vivo.
The advantage of OCT is that cross-sectional imaging of structures in
the middle ear can be performed noninvasively through the intact TM. However,
because the TM is not optically transparent, the image quality is less than
if the structures were directly optically accessible by myringotomy. Transverse
resolution degrades when structures are imaged behind the TM because of optical
scattering and aberration effects. There is a decrease in signal for structures
imaged behind the TM because of optical scattering. Attenuation of the optical
signal limits the depth of penetration of imaging in most solid tissues to
1 to 2 mm. These effects are observed in the OCT images shown in Figure 4. Increased scattering in superficial
structures can also prevent light from reaching lower structures, resulting
in "shadowing," similar to that observed in ultrasound imaging. Shadowing
artifacts are observed in Figure 4
behind dense structures such as the malleus and incus. Finally, there are
also depth of field limitations for imaging structures outside the focal plane
of the image. Increased depth of field can be achieved by scanning the focus
of the lens similar to C-mode scanning in ultrasound.
Improvements in the delivery optics, acquisition rates, and resolution
are also necessary to transform the current OCT system into a viable clinical
apparatus. Although a bench-top OCT microscope system was used for this study,
a variety of other clinical imaging devices have been developed. Optical coherence
tomography also has been effectively integrated with an ophthalmologic slitlamp
for retinal imaging.8 Handheld imaging probes
have been developed and demonstrated in open-field surgical imaging.24 These devices are based on the necessary focusing
optical elements and galvanometers, which can scan the beam in any direction.
Optical coherence tomography delivery optics can be further miniaturized and
also integrated with standard otoscopes. An OCT otoscope would allow simultaneous
viewing of the ear canal and OCT imaging through the TM at any area within
the otoscope's field of view. With such devices, the OCT beam can be delivered
to the target tissues in a variety of settings and imaging can be performed
through the ear canal or via endoscopic access to the middle and inner ear.
The acquisition rate for images in this study ranged from 10 to 30 seconds
per image. This is too slow to prevent motion artifacts in clinical imaging.
Recently, OCT systems have been developed that can generate images of 500
to 250 transverse pixels at 4 to 8 frames per second.20
These high-speed systems have enabled in vivo imaging to be performed in animal
models. Image speeds up to video rates are possible; however, there is a signal-to-noise
trade-off because signal levels decrease in proportion to imaging speed. Signal
can be increased by increasing the incident optical power; however, permissible
light exposure levels will ultimately govern the maximum imaging speed and
image penetration.
The 15-µm resolution of images used in this study allows imaging
of tissue architecture but does not allow cellular-level imaging to be performed.
The ability to identify cellular structures would be useful in the assessment
of a wide range of disorders. Recently, ultra–high-resolution OCT has
been demonstrated using a solid-state laser light source that achieves resolutions
on the order of approximately 1 µm.25
Although these sources are relatively complex and not yet viable for a clinical
instrument, robust sources with similar performance characteristics will likely
be available in the near future. Therefore, higher-resolution in vivo imaging
should be possible in future clinical OCT systems.
The ability of OCT to perform noninvasive imaging of middle ear structures
suggests many applications in the diagnosis and presurgical evaluation of
middle ear abnormalities. Cross-sectional images and 3-dimensional reconstructures
of middle ear structure can be performed. This study focused on imaging through
the intact TM to demonstrate feasbility for noninvasive imaging. Imaging with
OCT can be performed in bone with depths of up to 2 to 3 mm.18
If direct optical access to middle ear structures is possible, imaging of
cochlear structures might be possible. Optical coherence tomography also has
been applied for imaging nerve fascicle structure,15
and it might be used for guiding surgical interventions involving the seventh
and eighth nerve bundles. The image resolution of OCT is higher than that
of other standard clinical imaging techniques. In addition, OCT imaging can
be performed noninvasively, without contact, and without the need for a transducing
medium as in ultrasound. These features, combined with its ease of integration
with optical instruments and low cost, suggest that OCT might be a useful
technology for diagnostic imaging and surgical guidance in the middle ear.
AUTHOR INFORMATION
Accepted for publication November 14, 2000.
This research was supported in part by grants R01 HL63953-01 (Dr Brezinski),
1RO1AR44812-01 (Dr Brezinski), NIH-9-RO1-EY11289-10 (Dr Fujimoto), and NIH-1-RO1-CA75289-01
(Dr Fujimoto) from the National Institutes of Health, Bethesda, Md, and Office
of Naval Research grant N00014-97-1-1066 from the Medical Free Electron Laser
Program (Drs Fujimoto and Brezinski).
We gratefully acknowledge the helpful suggestions and assistance of
Saumil N. Merchant, MD, Massachusetts Eye and Ear Infirmary, Boston.
From the Research Laboratory of Electronics and the Department of Electrical
Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge
(Drs Pitris and Fujimoto); Harvard Medical School, Boston, Mass (Drs Pitris
and Brezinski); and Department of Orthopedics, Brigham and Women's Hospital,
Boston (Ms Saunders and Dr Brezinski).
Corresponding author and reprints: James G. Fujimoto, PhD, Department
of Electrical Engineering and Computer Science, Massachusetts Institute of
Technology, 50 Vassar St, Room 36-345, Cambridge, MA 02139.
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