Dynamic optical coherence elastography (OCE) tracks mechanical wave propagation in the subsurface region of tissue to map its shear modulus. For bulk shear waves, the lateral resolution of the reconstructed modulus map (i.e., elastographic resolution) can approach that for OCT, typically a few tens of microns. However, skin, cornea and many other tissues are layered or bounded leading to the formation of guided mechanical waves. We performed numerical simulations and acoustic micro-tapping experiments to show that in bounded media, the elastographic resolution cannot reach the OCT structural resolution and is mainly defined by the thickness of the bounded tissue layer.
A novel polarization state tracing algorithm has been proposed to visualize depth-resolved birefringent information by using the polarization sensitive optical coherence tomography (PSOCT) system. This algorithm is compatible to the widely adopted single input PSOCT system which uses only one circularly polarized incident light. We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts (ex vivo) and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer (in vivo).
AμT-OCE was used to quantify changes in both the in-plane Young’s (E) and out-of-plane shear (G) moduli in human cornea following riboflavin/UVA crosslinking in a non-contact, non-destructive manner. Since OCT methods are broadly accepted in Ophthalmology, it suggests fast translation of AμT-OCE into clinical practice if results are confirmed in vivo. In addition, AμT-OCE can change diagnostic criteria of ectatic corneal diseases, leading to early diagnosis, reduced complications, customized surgical treatment, and new opportunities to develop personalized biomechanical models of the eye.
Cornea, the window of the eye, is critical for vision. The precise understanding of corneal biomechanical properties remains an unmet clinical need in early diagnosis and customized treatments for corneal blindness.
Our research group has developed a novel non-contact, non-invasive AuT-OCE method to quantify corneal elasticity. Because of the anisotropic corneal property due to its collagen structure, a nearly incompressible transversely isotropic (NITI) model was developed to characterize its elasticity. It has been shown that in-plane tensile and out-of-plane shear properties are defined by different moduli, E and G, respectively.
Our research offers new opportunities to develop a personalized biomechanical model based on quantitative maps of corneal mechanical moduli to quantify both biomechanical properties and predict final corneal shape, leading to potential early diagnosis and more precise surgical planning.
Reconstructive skin surgeries drive the clinical need for non-contact objective measurements of skin elasticity. Here we demonstrate that all three of skin’s elastic constants (in-plane and out-of-plane shear moduli and an additional modulus defining skin’s tensile anisotropy) and the orientation of collagen fibers in dermis can be determined from Rayleigh wave anisotropy in-plane with acoustic micro-tapping (AuT) OCE. A nearly-incompressible transverse isotropic (NITI) model was used to reconstruct skin’s moduli from OCE measurements in human forearm in vivo for five healthy volunteers. Co-registered polarization-sensitive (PS-) OCT shows that optical and mechanical axes are co-aligned at measured sites.
Recent advances in dynamic OCE have resulted in tools that can generate/track sub-mm wavelength mechanical waves in tissue. However, reconstructing material elasticity from measured wavefields needs an appropriate model accounting for tissue anisotropy, structure and geometry. We assume that tissues consisting of collagen fibers can be locally described with a model of a nearly incompressible transverse isotropic (NITI) medium using three elastic parameters to describe shear and tensile behavior. Examples of NITI media are discussed and the problem of inversion of moduli from bulk shear, Rayleigh and guided waves is considered.
Using numerical and analytical models of wave propagation in mechanically anisotropic materials, we highlight the complications associated with quantitative estimates of mechanical moduli in human skin. To obtain reliable, quantitative measurements of moduli in human skin, multiple aspects of mechanical wave propagation in structures typical of skin must be considered. Using a nearly incompressible transverse isotropic (NITI) model, preliminary measurements of both shear moduli (G and μ) in healthy in vivo human skin are presented.
Accurate estimates of corneal mechanical properties may improve diagnosis and treatment of many ophthalmic conditions. Recently, we introduced a nearly incompressible transversely isotropic (NITI) model based on two independent shear moduli determining tensile and out-of-plane shear behavior. Here, we directly compare acoustic micro-tapping OCE (AμT-OCE) modulus estimates with those obtained from mechanical testing on ex-vivo porcine corneas. Both OCE and mechanical testing show tensile behavior governed by a Young’s modulus on the order of MPa and out-of-plane shear behavior by a modulus on the order of tens of kPa, suggesting strong anisotropy in the cornea.
In assuming an isotropic model for soft-tissue, dynamic OCE can produce order of magnitude errors in Young’s modulus estimates relative to static mechanical tests. Considering corneal fiber arrangement, we propose a simplified transverse isotropic (TI) model of the cornea, which depends on moduli λ and μ and the independent modulus G (which affects the propagation of vertically polarized surface waves, such as those measured in OCE). Early theoretical and experimental studies suggest that this TI model of the cornea may greatly improve quantitative estimates of corneal mechanics obtained using dynamic OCE.
This paper summarizes the latest results on acoustic micro-tapping (AμT) -based OCE and provides answers to several important questions related to dynamic elastography, including: what is the maximum spatial resolution that can be achieved in dynamic OCE? How should propagation speed be measured in soft tissue, especially in layered or bounded media? How can tissue elastic properties be properly reconstructed from experimental data? What is the potential for clinical translation, and what barriers remain?
Dynamic optical coherence elastography (OCE) tracks elastic wave propagation speed within tissue, enabling quantitative three-dimensional imaging of the elastic modulus. We show that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus. Depending on the details of a boundary’s geometry and elasticity contrast, highly complex propagating fields produced near the boundary can substantially affect both the spatial resolution and contrast of the elasticity image. We demonstrate boundary effects on Rayleigh waves incident on a vertical boundary between media of different shear moduli. Lateral resolution is defined by the width of the transition zone between two media and is the limit at which a physical inclusion can be detected with full contrast. We experimentally demonstrate results using a spectral-domain OCT system on tissue-mimicking phantoms, which are replicated using numerical simulations. It is shown that the spatial resolution in dynamic OCE is determined by the temporal and spatial characteristics (i.e., bandwidth and spatial pulse width) of the propagating mechanical wave. Thus, mechanical resolution in dynamic OCE inherently differs from the optical resolution of the OCT imaging system.
Dynamic elastography is an attractive method to evaluate tissue biomechanical properties. Recently, it was extended from US- and MR-based modalities to optical ones, such as optical coherence tomography for three-dimensional (3-D) imaging of propagating mechanical waves in subsurface regions of soft tissues, such as the eye. The measured group velocity is often used to convert wave speed maps into 3-D images of the elastic modulus distribution based on the assumption of bulk shear waves. However, the specific geometry of OCE measurements in bounded materials such as the cornea and skin calls into question elasticity reconstruction assuming a simple relationship between group velocity and shear modulus. We show that in layered media the bulk shear wave assumption results in highly underestimated shear modulus reconstructions and significant structural artifacts in modulus images. We urge the OCE community to be careful in using the group velocity to evaluate tissue elasticity and to focus on developing robust reconstruction methods to accurately reconstruct images of the shear elastic modulus in bounded media.
In corneal collagen cross-linking (CXL), a treatment often used to stall the progression of keratoconus, a degenerative eye disease, corneal stroma is exposed to UV-light to improve mechanical stiffness by inducing covalent bonding. In clinical practice, a photoreactive riboflavin-solution is applied to the cornea and exposed to 3mW/cm2 of 365nm light for 30 minutes to accelerate cross-link formation. While this technique was recently approved for clinical use, time-evolving changes in CXL are not well understood. If the cornea is over-exposed, UV light may penetrate and damage deeper tissues. If underexposed, insufficient cross-linking may occur. Acoustic Micro-Tapping (AuT) with phase-sensitive OCT can non-invasively probe biomechanical changes in porcine and human cornea at multiple time points during UV-illumination using an air-coupled ultrasound transducer to deliver sufficient displacement on the corneal surface to launch a mechanical wave propagating as a guided mode. Here, guided wave propagation was captured at 100 spatial X-locations over 100 Y-planes to generate a 6 x 6 mm map of wave velocity across the corneal surface. The swept-source OCT system operated in BM mode at a functional frame rate of 16 kHz. In this experiment, corneas were scanned every 2 minutes during 30-minute UV exposure to analyze temporal changes in mechanical wave speed, central corneal thickness, and focusing power. Preliminary results suggest that changes in corneal structure and wave speed over time may infer rates of corneal cross-linking to refine UV illumination protocols and improve clinical outcomes.
Optical coherence elastography (OCE) holds great promise for quantitative characterization of corneal elasticity including robust measurements of the intraocular pressure (IOP) independent of corneal mechanical properties. To translate this method into a viable clinical tool, however, requires wideband, highly accurate mechanical wave measurements using mechanical stimulation requiring no physical contact with the cornea. We have developed a method of non-contact mechanical stimulation of soft media with precise spatial and temporal shaping. We call it acoustic micro-tapping (AuT) because it employs focused, air-coupled ultrasound (US) to induce significant mechanical displacement at the boundary of a soft material using reflection-based radiation force. Combining it with high-speed, four-dimensional (three space dimensions plus time) phase-sensitive optical coherence tomography (PhS-OCT) creates a non-contact tool for high-resolution and quantitative dynamic elastography of soft tissue at near real-time imaging rates. To demonstrate this approach, we present OCE results on a porcine cornea using a homemade, focused 1 MHz air-coupled piezoelectric transducer with a matching layer to launch an US wave through air onto the sample surface. To provide an acoustic line source approximating a 1-D excitation, the transducer was made from a cylindrical segment of a piezoelectric tube. A high-speed (1.6 MHz A-Scan rate) PhS-OCT system was utilized to measure acoustic wave propagation in the cornea at different intraocular pressures (IOPs). Results from this OCE study demonstrate that an air-coupled US wave reflected from an air/tissue interface provides significant radiation force to generate displacement for elasticity imaging for full mechanical characterization of the cornea.
In vision correction surgeries, the corneal stroma is subject to limbal-relaxing incisions which change the focusing power of the cornea, but can damage tissue and put the patient at risk of complication. A non-invasive method to launch a mechanical wave in tissue, referred to as Acoustic Micro-Tapping (AuT), is demonstrated with phase-sensitive spectral domain OCT (SD-OCT) to probe for biomechanical changes in porcine and human cornea samples following arcuate keratotomy (AK). This method uses an air-coupled ultrasound transducer to deliver sufficient displacement on the corneal surface to launch a mechanical wave propagating as a guided mode. Rayleigh-Lamb wave propagation is captured at 100 spatial locations 6 mm across the corneal surface, resulting in a high resolution elastogram. The SD-OCT system operates in the MB mode at a functional frame rate of 47 kHz to detect local wave behavior for analysis of the group velocity, group displacement amplitude, displacement attenuation, phase velocity over the bandwidth of the excitation, mean frequency, and bandwidth. An analysis of mechanical wave behavior shows reduced wave speed up to 20% following an incision through 3/4th of the cornea in porcine tissue samples, indicating a potential reduction in elastic modulus. This technique was performed on porcine and human corneas following PRK incision to demonstrate progress toward clinical translation.
Recently we used ultrasound from an air-coupled transducer for non-contact excitation of broadband mechanical waves in soft tissue such as cornea. The transient displacement, generated by “Acoustic Micro-Tapping” (AuT), was then measured using phase-sensitive spectral domain OCT (SD-OCT). In addition traditional surface wave speed measurement, we investigated complementary methods to characterize the mechanical properties of the target material. We note that the maximum frequency, as well as the group velocity, of the surface wave is related to both the phase velocity of the material and the spatial width of the acoustic pulse. If the spatial and temporal profile of the excitation is well defined, it may be possible to infer elastic modulus from the frequency profile of a propagating mechanical wave. To assess the effect of the spatial profiles of the AuT excitation on frequency profiles of resulting mechanical waves, acoustic pulses with different spatial width (from 0.1 to 1 mm) were applied to agar phantoms with different shear modulus (from 1 to 100 kPa) to generate mechanical waves, and a SD-OCT system with a functional frame rate of 47 kHz was used to track wave propagation. For validation, simulations with the same acoustic and mechanical properties were performed using a finite element method (FEM) to analyze induced wave propagation. The phantom experiment and simulation exhibited similar increase in the maximum frequency with decreasing excitation width. Both estimates also agreed well with previous theoretical results.
With the onset of clinically available spectral domain (SD-OCT) and swept source (SS-OCT) systems, clinicians are now easily able to recognize sub retinal microstructure and vascularization in the choroidal and scleral regions. As the bloodrich choroid supplies nutrients to the upper retinal layers, the ability to monitor choroid function accurately is of vital importance for clinical assessment of retinal health. However, the physical appearance of the choroid blood vessels (darker under a healthy Retinal Pigmented Epithelium (RPE) compared to regions displaying an RPE atrophic lesion) has led to confusion within the OCT ophthalmic community. The differences in appearance between each region in the OCT image may be interpreted as different vascular patterns when the vascular networks are in fact very similar. To explain this circumstance, we simulate light scattering phenomena in the RPE and Choroid complexes using the finite difference time domain (FDTD) method. The simulation results are then used to describe and validate imaging features in a controlled multi-layered tissue phantom designed to replicate human RPE, choroid, and whole blood microstructure. Essentially, the results indicate that the strength of the OCT signal from choroidal vasculature is dependent on the health and function of the RPE, and may not necessarily directly reflect the health and function of the choroidal vasculature.
Optical coherence elastography (OCE) can provide clinically valuable information based on local measurements of tissue stiffness. Improved light sources and scanning methods in optical coherence tomography (OCT) have led to rapid growth in systems for high-resolution, quantitative elastography using imaged displacements and strains within soft tissue to infer local mechanical properties. We describe in some detail the physical processes underlying tissue mechanical response based on static and dynamic displacement methods. Namely, the assumptions commonly used to interpret displacement and strain measurements in terms of tissue elasticity for static OCE and propagating wave modes in dynamic OCE are discussed with the ultimate focus on OCT system design for ophthalmic applications. Practical OCT motion-tracking methods used to map tissue elasticity are also presented to fully describe technical developments in OCE, particularly noting those focused on the anterior segment of the eye. Clinical issues and future directions are discussed in the hope that OCE techniques will rapidly move forward to translational studies and clinical applications.
In this work the effects of incident intensity and effective camera dynamic range on image acquisition of both frozen and time-averaged dynamic speckle patterns, and their effects on laser speckle contrast imaging are addressed. A nematic liquid crystal, phase-only, spatial light modulator (SLM) was employed to generate laser speckle in a controlled and repeatable fashion. By addressing the calculated spatial contrast of frozen and time-averaged dynamic speckle patterns imaged across a wide range of intensities, we present a description of optimum intensity characteristics that should be observed when using LSCI. The results indicate the importance of assessing the intensity of the signal quantized by the camera in LSCI. By analyzing intensity PDF’s during image acquisition of speckle patterns used in LSCI, an optimum incident intensity can be detected when a single, polarized speckle frame displays the first order statistics characteristic of fully developed speckle. Our results indicate that there is a range of laser power densities where the ensuing imaged speckle exhibit optimum sensitivity to flow as well as relatively constant calculated contrast values. It is clear that at high intensities, high frequency information is lost due to camera saturation, resulting in a decrease in contrast. When imaging speckle at low intensity, there is a risk for loss of data during the digital quantization process. The results are presented in a generalized fashion, so they should be applicable to any LSCI system, regardless of incident laser power or camera depth.
Before laser speckle contrast imaging (LSCI) can be used reliably and quantitatively in a clinical setting, there are several theoretical and practical issues that still must be addressed. In order to address some of these issues, an electro-optical system that utilizes a nematic liquid crystal spatial light modulator (SLM) to mimic LSCI experiments was assembled. The focus of this paper is to address the issue of how incident intensity affects LSCI results. Using the SLM-based system, we systematically adjusted incident intensity on the SLM and assessed the resulting first- and second-order statistics of the imaged speckle to explain the corresponding spatial contrast values in both frozen and time-integrated speckle patterns. The SLM-based system was used to generate speckle patterns with a controlled minimum speckle size, probability intensity distribution, and temporal decorrelation behavior. By eliminating many experimental parameters, this system is capable of serving as a useful intermediary tool between computer simulation and physical experimentation for further developing LSCI as a quantitative imaging modality.
In this study, we developed a dark-field illuminated reflectance fiber-optic microscope (DRFM) along with an algorithm for l1-norm minimization of fiber bundle image to provide intrinsic endoscopic imaging with cellular resolution. To suppress specular reflection from fiber bundle facets, we adopted a dark-field configuration. To remove the honeycomb pattern of fiber bundle while preserve image resolution and contrast, we chose to minimize the image l1 norm using iterative shrinkage thresholding (IST) algorithm.
Laser speckle contrast imaging (LSCI) is a non- or minimally- invasive modality for observing relative blood flow or perfusion. Recently, there has been an effort to use LSCI for truly quantitative blood flow measurements. However, this effort has been hampered not only by real theoretical issues, but also by challenges associated with numerous experimental parameters that can potentially impact the calculated contrast values. In this work, we present our efforts at using a nematic liquid crystal, phase-only, spatial light modulator (SLM) to mimic LSCI experiments with precisely controlled experimental parameters. This approach permits the rapid experimental investigation of numerous factors including: The effects of different flow models on LSCI contrast values; the effects of multiple decorrelation times in the same depth of field; the effects of ‘static’ scatterers; and the effects of camera settings relative to speckle decorrelation times, just to name a few. We have found that an SLM is a useful tool for the experimental investigation of LSCI that eliminates many of the experimental variables associated with typical flow model experiments or in vivo experimentation. LSCI experiments with SLMs are a useful intermediary between computer simulations and physical flow models.
In this work, we demonstrated that bulk motion could lead to increased background in OCT microangiography image.
Based on our motion analysis, we developed an adaptive thresholding method to reduce artifact in OCT
microangiography caused by transient bulk motion. Motion artifact reduced microangiography was demonstrated in a
1.3μm spectral domain OCT system using graphic processing unit (GPU) for real-time signal processing. We conducted
in vivo microvasculature imaging on human skin. Our results clearly show that the adaptive thresholding is highly
effective in motion artifact removal.
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