Optical
coherence elastography (OCE) is an emerging biomedical imaging technique used
to produce images of biological tissue in micron and submicron level and map
the biomechanical property of tissues. This technology is based on the
currently popular optical coherence tomography (OCT) technique. In theory, OCT
generates a structural image based on light scattering determined by minute
changes in the refractive index of different tissue and cell types, while OCE
utilizes local tissue motion as a function of an applied stress to infer tissue
stiffness (i.e., elasticity).
Many diseases
affect the structural organization and function of human cells, collagen
fibers, and extracellular matrix. Therefore, changes in local elastic moduli
may be used to diagnose and help manage treatment of diseased tissue within the
cornea, sclera, lens, and retina. Biomechanical testing can be comparatively
advantageous to probe structural characteristics in both diseased and healthy
tissues that are difficult to contrast using classical OCT methods.
The goal
of OCE is to produce images of tissue elastic and viscoelastic properties, and
ultimately quantitative maps of the static (i.e., low-frequency) Young’s
modulus from maps of tissue displacements and strains detected with OCT.
An OCE
system uses three steps to obtain information related to tissue elasticity: (1)
mechanical loading, (2) tissue response, and (3) motion detection.
Elasticity
imaging requires a physical stress to deform (displace) tissue. Resulting
displacements are measured with OCT to compute strains, detect vibrations, or
track the propagation of a mechanical wave. The stress–strain response of
tissue, local vibration behavior, or mechanical wave content, can each be
mapped spatially to solve for metrics such as the Young’s (or shear) modulus.
Mechanical
loading methods are static and dynamic using both contact and noncontact
approaches. For clinical applications in the anterior segment of the eye, it
appears that dynamic, noncontact methods are the most translatable. Current
noncontact methods include air-puff excitation, optical excitation, and acoustic
microtapping (AμT) using air-coupled ultrasound. For measurements in the cornea
(and sclera), optical excitation and AμT provide high bandwidth and spatially
precise excitation well-matched to mechanical wave analysis.
Soft
tissue responds to dynamic loading by launching mechanical waves. Broadband
excitations produce mechanical waves, which in bulk materials exhibit wave
speed and attenuation directly related to tissue viscoelastic parameters. Using
these methods, robust, quantitative elasticity maps of structures within the
anterior segment of the eye, especially the cornea, are possible.
Precise
knowledge of corneal biomechanics is critical for early diagnosis, optimal
management of diseased corneas (e.g., keratoconus) and predicting the risks of
surgical intervention of healthy corneas, such as post-LASIK ectasia. In
addition, traditional IOP measurements using direct contact are often con
founded by the elastic properties of the cornea. Instruments such as the ORA
and DSA attempt to account for these properties by monitoring the corneal
response to a dynamic mechanical stimulus as part of IOP measurement. Dynamic
tonometry is being considered as a potential screening tool for glaucoma and
myopia, where there is recent evidence that corneal elasticity is linked to
disease progress 70% of the population. However, it is clear that these measurements
are highly susceptible to experimental conditions and cannot be used to map
fundamental corneal viscoelastic parameters at high spatial resolution.
Therapeutic
interventions, such as UV cross linking, have been monitored with OCE to
measure the progression and retardation of collagen degradation.
Current
refractive surgery planning uses a population-based average of corneal
biomechanics rather than a customized treatment plan, which occasionally produces
unpredictable treatment outcomes even with the most conservative selection
criteria. The availability of an accurate, personalized corneal biomechanical
map of individual cornea from high-resolution OCE may enable a customized
treatment plan for each patient, with the biomechanical response adequately
predicted for the long term.
Current
clinical IOP measurements rely on indirect techniques with limited accuracy
because ocular biomechanics cannot be taken into account on a
patient-by-patient basis. Available systems used to measure IOP in vivo, such
as Goldmann applanation, ORA, and dynamic contour and non-contact tonometry,
may be improved by calibration methods that account for corneal mechanical
properties. Additionally, it is difficult for conventional (not OCE based)
tonometry systems to directly visualize the distribution of local corneal
mechanical properties in addition to providing robust estimates of quantitative
modulus values. As current clinical gold standards struggle to accurately
estimate the influence of corneal mechanical properties on IOP, approaches
utilizing available systems may lead to misinformed clinical decision making, a
niche where OCE may find great utility.
OCE has
also shown utility in lens analysis. With aging, the natural crystalline lens
becomes less pliable causing reduced accommodation. This can be directly
measurable using OCE methods, as demonstrated using acoustic radiation force (ARF-OCE)
to detect age-related stiffness in rabbit lens. It has, however, also been
reported that increased IOP affects the shear wave speed in the lens, implying
a less understood IOP dependence on lens mechanical moduli.
ARF-OCE
has also been demonstrated as a method to assess elasticity within the retina,
potentially providing additional information regarding cellular degradation
from measurements of retinal and choroidal stiffness, as well as providing
further insight into how IOP affects ocular function.
Once
reliable and robust measurements of elastic modulus become possible in a
noninvasive manner, the micro- and macrostructure of tissue may be used to
infer vast amounts of pathophysiological data.
