OPTICAL COHERENCE ELASTOGRAPHY (OCE)

 

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.