Optical Coherence Elastography Measurements Research Articles

Anisotropic elasticity measurements of the retina using optical coherence elastography

Anisotropic elasticity measurements of the retina are essential for retinal disease diagnosis and function assessment. Optical coherence elastography (OCE) is a high-resolution imaging technique for mapping the elasticity distribution of tissues. However, previous OCE measurements quantified the tissue elasticity in a single direction, resulting in a biased estimation of the elastic properties. In this study, we propose an OCE method with acoustic radiation force (ARF) excitation to map the retinal anisotropic elasticity in the depth and lateral directions. The axial elasticity was analyzed using the natural frequency of free vibration, and the lateral elasticity was quantified using the elastic wave velocity. After evaluating the feasibility of the OCE method on the phantoms, the anisotropic elasticity of ex vivo porcine retinas was mapped. The results show that the OCE method with ARF excitation can assess the elasticity in orthogonal directions and provide a comprehensive understanding of the elasticity of the anisotropic tissues.

Chirp excitation for natural frequency optical coherence elastography.

Optical coherence elastography (OCE) has recently been used to characterize the natural frequencies of delicate tissues (e.g., the in vivo human cornea) with sub-micron tissue oscillation magnitudes. Here, we investigate broadband spectrum sample stimulation using a contact-based piezoelectric transducer (PZT) chirp excitation and compare its performance with a non-contact, air-pulse excitation for OCE measurements on 1.0-7.5% agar phantoms and an ex vivo porcine cornea under intraocular pressures (IOPs) of 5-40 mmHg. The 3-ms duration air-pulse generated a ∼0-840 Hz excitation spectrum, effectively quantifying the first-order natural frequencies in softer samples (e.g., 1.0%-4.0% agar: 239-782 Hz, 198 Hz/%; porcine cornea: 68-414 Hz, 18 Hz/mmHg, IOP: 5-25 mmHg), but displayed limitations in measuring natural frequencies for stiffer samples (e.g., 4.5%-7.5% agar, porcine cornea: IOP ≥ 30 mmHg) or higher order natural frequency components. In contrast, the chirp excitation produced a much wider spectrum (e.g., 0-5000 Hz), enabling the quantification of both first-order natural frequencies (1.0%-7.5% agar: 253-1429 Hz, 181 Hz/%; porcine cornea: 76-1240 Hz, 32 Hz/mmHg, IOP: 5-40 mmHg) and higher order natural frequencies. A modified Bland-Altman analysis (mean versus relative difference in natural frequency) showed a bias of 20.4%, attributed to the additional mass and frequency introduced by the contact nature of the PZT probe. These findings, especially the advantages and limitations of both excitation methods, can be utilized to validate the potential application of natural frequency OCE, paving the way for the ongoing development of biomechanical characterization methods utilizing sub-micron tissue oscillation features.

Dolutegravir induces FOLR1 expression during brain organoid development.

During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.

Quantifying Elastic Properties of Environmental Biofilms using Optical Coherence Elastography.

Biofilms are complex biomaterials comprising a well-organized network of microbial cells encased in self-produced extracellular polymeric substances (EPS). This paper presents a detailed account of the implementation of optical coherence elastography (OCE) measurements tailored for the elastic characterization of biofilms. OCE is a non-destructive optical technique that enables the local mapping of the microstructure, morphology, and viscoelastic properties of partially transparent soft materials with high spatial and temporal resolution. We provide a comprehensive guide detailing the essential procedures for the correct implementation of this technique, along with a methodology to estimate the bulk Young's modulus of granular biofilms from the collected measurements. These consist of the system setup, data acquisition, and postprocessing. In the discussion, we delve into the underlying physics of the sensors used in OCE and explore the fundamental limitations regarding the spatial and temporal scales of OCE measurements. We conclude with potential future directions for advancing the OCE technique to facilitate elastic measurements of environmental biofilms.

High-Frequency Optical Coherence Elastography for Gingival Tissue Characterization: Variability in Stiffness and Response to Physiological Conditions.

Accurate measurement of gingiva's biomechanical properties invivo has been an active field of research but remained an unmet challenge. Currently, there are no noninvasive tools that can accurately quantify tensile and shear moduli, which govern gingival health, with sufficiently high accuracy. This study presents the application of high-frequency optical coherence elastography (OCE) for characterizing gingival tissue in both porcine models and human subjects. Dynamic mechanical analysis, histology studies, and strain analysis are performed to support the OCE result. Our findings demonstrate substantial differences in tissue stiffness between supra-dental and inter-dental gingiva, validated by dynamic mechanical analysis and OCE. We confirmed the viscoelastic, nearly linear, and transverse-isotropic properties of gingiva insitu, establishing the reliability of OCE measurements. Further, we investigated the effects of tissue hydration, collagen degradation, and dehydration on gingival stiffness. These conditions showed a decrease and increase in stiffness, respectively. While preliminary, our study suggests OCE's potential in periodontal diagnosis and oral tissue engineering, offering real-time, millimeter-scale resolution assessments of tissue stiffness, crucial for clinical applications and biomaterial optimization in reconstructive surgeries.

In situ assessment of lens elasticity with noncontact optical coherence elastography.

Lens biomechanics has great potential for application in clinical diagnostics and treatment monitoring of presbyopia and cataracts. However, current approaches to lens elastography do not meet the desired safety or sensitivity for clinical application. In this regard, we propose a noncontact optical coherence elastography (OCE) method to facilitate quantitative in situ imaging of lens elasticity. Elastic waves induced by air-pulse stimulation on the limbus propagate to the lens and are then imaged using custom-built swept-source optical coherence tomography to obtain the elastic wave velocity and Young's modulus. The proposed OCE method was first validated by comparing the results of in situ and in vitro measurements of porcine lenses. The results demonstrate that the Young's modulus measured in situ was highly consistent with that measured in vitro and had an intraclass correlation coefficient of 0.988. We further investigated the elastic changes induced by cold storage and microwave heating. During 36-hour cold storage, the mean Young's modulus gradually increased (from 5.62 ± 1.24 kPa to 11.40 ± 2.68 kPa, P < 0.0001, n = 9) along with the formation of nuclear opacities. 15-second microwave heating caused a greater increase in the mean Young's modulus (from 6.86 ± 1.21 kPa to 25.96 ± 8.64 kPa, P < 0.0025, n = 6) without apparent cataract formation. Accordingly, this study reports the first air-pulse OCE measurements of in situ lenses, which quantified the loss of lens elasticity during simulated cataract development with good repeatability and sensitivity, thus enhancing the potential for adoption of lens biomechanics in the clinic.

Micron-scale hysteresis measurement using dynamic optical coherence elastography.

We present a novel optical coherence elastography (OCE) method to characterize mechanical hysteresis of soft tissues based on transient (milliseconds), low-pressure (<20 Pa) non-contact microliter air-pulse stimulation and micrometer-scale sample displacements. The energy dissipation rate (sample hysteresis) was quantified for soft-tissue phantoms (0.8% to 2.0% agar) and beef shank samples under different loading forces and displacement amplitudes. Sample hysteresis was defined as the loss ratio (hysteresis loop area divided by the total loading energy). The loss ratio was primarily driven by the sample unloading response which decreased as loading energy increased. Samples were distinguishable based on their loss ratio responses as a function loading energy or displacement amplitude. Finite element analysis and mechanical testing methods were used to validate these observations. We further performed the OCE measurements on a beef shank tissue sample to distinguish the muscle and connective tissue components based on the displacement and hysteresis features. This novel, noninvasive OCE approach has the potential to differentiate soft tissues by quantifying their viscoelasticity using micron-scale transient tissue displacement dynamics. Focal tissue hysteresis measurements could provide additional clinically useful metrics for guiding disease diagnosis and tissue treatment responses.

Introduction to optical coherence elastography: tutorial.

Optical coherence elastography (OCE) has seen rapid growth since its introduction in 1998. The past few decades have seen tremendous advancements in the development of OCE technology and a wide range of applications, including the first clinical applications. This tutorial introduces the basics of solid mechanics, which form the foundation of all elastography methods. We then describe how OCE measurements of tissue motion can be used to quantify tissue biomechanical parameters. We also detail various types of excitation methods, imaging systems, acquisition schemes, and data processing algorithms and how various parameters associated with each step of OCE imaging can affect the final quantitation of biomechanical properties. Finally, we discuss the future of OCE, its potential, and the next steps required for OCE to become an established medical imaging technology.

Repetitive optical coherence elastography measurements with blinking nanobombs.

Excitation of dye-loaded perfluorocarbon nanoparticles (nanobombs) can generate highly localized axially propagating longitudinal shear waves (LSW) that can be used to quantify tissue mechanical properties without transversal scanning of the imaging beam. In this study, we used repetitive excitations of dodecafluoropentane (C5) and tetradecafluorohexane (C6) nanobombs by a nanosecond-pulsed laser to produce multiple LSWs from a single spot in a phantom. A 1.5 MHz Fourier-domain mode-locked laser in combination with a phase correction algorithm was used to perform elastography. Multiple nanobomb activations were also monitored by detecting photoacoustic signals. Our results demonstrate that C6 nanobombs can be used for repetitive generation of LSW from a single spot for the purpose of material elasticity assessment. This study opens new avenues for continuous quantification of tissue mechanical properties using single delivery of the nanoparticles.

Clinical Corneal Optical Coherence Elastography Measurement Precision: Effect of Heartbeat and Respiration.

PurposeNormal physiological movements (e.g., respiration and heartbeat) induce eye motions during clinical measurements of human corneal biomechanical properties using optical coherence elastography (OCE). We quantified the effects of respiratory and cardiac-induced eye motions on clinical corneal OCE measurement precision and repeatability.MethodsCorneal OCE was performed using low-force, micro-air-pulse tissue stimulation and high-resolution phase-sensitive optical coherence tomography (OCT) imaging. Axial surface displacements of the corneal apex were measured (M-mode) at a 70-kHz sampling rate and three different stimulation pressures (20–60 Pa). Simultaneously, the axial corneal position was tracked with structural OCT imaging, while the heartrate and respiration were monitored over a 90 second period.ResultsRespiratory- and cardiac-induced eye motions have distinctly lower frequency (0.1–1 Hz) and much greater amplitude (up to ± 50 µm movements) than air-pulse-induced corneal tissue deformations (∼250 Hz, <1 µm). The corneal displacements induced during OCE measurements in vivo were –0.41 ± 0.06 µm (n = 22 measurements, coefficient of variation [CV]: 14.6%) and –0.44 ± 0.07 µm (n = 50 measurements, CV: 15.9%), respectively, from two human subjects at 40 Pa stimulation pressure. Observed variation in corneal tissue displacements were not associated with tissue stimulation magnitude, or the amplitude of physiologically induced axial eye motion.ConclusionsThe microsecond timescale and submicron tissue displacements observed during corneal OCE measurements are separable from normal involuntary physiological movements, such as the oculocardiac pulse and respiratory movements.Translational RelevanceThis work advances innovations in biomedical imaging and engineering for clinical diagnostic applications for soft-tissue biomechanical testing.

Multimodal quantitative optical elastography of the crystalline lens with optical coherence elastography and Brillouin microscopy.

Assessing the biomechanical properties of the crystalline lens can provide crucial information for diagnosing disease and guiding precision therapeutic interventions. Existing noninvasive methods have been limited to global measurements. Here, we demonstrate the quantitative assessment of the elasticity of crystalline lens with a multimodal optical elastography technique, which combines dynamic wave-based optical coherence elastography (OCE) and Brillouin microscopy to overcome the drawbacks of individual modalities. OCE can provide direct measurements of tissue elasticity rapidly and quantitatively, but it is a challenge to image transparent samples such as the lens because this technique relies on backscattered light. On the other hand, Brillouin microscopy can map the longitudinal modulus with micro-scale resolution in transparent samples. However, the relationship between Brillouin-deduced modulus and Young's modulus is not straightforward and sample dependent. By combining these two techniques, we can calibrate Brillouin measurements with OCE, based on the same sample, allowing us to completely map the Young's modulus of the crystalline lens. The combined system was first validated with tissue-mimicking gelatin phantoms of varying elasticities (N = 9). The OCE data was used to calibrate the Brillouin shift measurements and subsequently map the Young's modulus of the phantoms. After validation, OCE and Brillouin measurements were performed on ex-vivo porcine lenses (N = 6), and the Young's modulus of the lenses was spatially mapped. The results show a strong correlation between Young's moduli measured by OCE and longitudinal moduli measured by Brillouin microscopy. The correlation coefficient R was 0.98 for the phantoms and 0.94 for the lenses, respectively. The mean Young's modulus of the anterior and posterior lens was 1.98 ± 0.74 kPa and 2.93 ± 1.13 kPa, respectively, and the Young's modulus of the lens nucleus was 11.90 ± 2.94 kPa. The results presented in this manuscript open a new way for truly quantitative biomechanical mapping of optically transparent (or low scattering) tissues in 3D.

Towards mechanical characterization of granular biofilms by optical coherence elastography measurements of circumferential elastic waves.

Microbial granular biofilms are spherical, multi-layered aggregates composed of communities of bacterial cells encased in a complex matrix of hydrated extracellular polymeric substances (EPS). While granular aggregates are increasingly used for applications in industrial and municipal wastewater treatment, their underlying mechanical properties are poorly understood. The challenges of viscoelastic characterization for these structures are due to their spherical geometry, spatially heterogeneous properties, and their delicate nature. In this study, we report a model-based approach for nondestructive characterization of viscoelastic properties (shear modulus and shear viscosity) of alginate spheres with different concentrations, which was motivated by our measurements in granular biofilms. The characterization technique relies on experimental measurements of circumferential elastic wave speeds as a function of frequency in the samples using the Optical Coherence Elastography (OCE) technique. A theoretical model was developed to estimate the viscoelastic properties of the samples from OCE data through inverse analysis. This work represents the first attempt to explore elastic waves for mechanical characterization of granular biofilms. The combination of the OCE technique and the theoretical model presented in this paper provides a framework that can facilitate quantitative viscoelastic characterization of samples with curved geometries and the study of the relationships between morphology and mechanical properties in granular biofilms.

Quantifying the effects of hydration on corneal stiffness with noncontact optical coherence elastography

To quantify the effects of the hydration state on the Young's modulus of the cornea. Biomedical Optics Laboratory, University of Houston, Houston, Texas, USA. Experimental study. Noncontact, dynamic optical coherence elastography (OCE) measurements were taken of insitu rabbit corneas in the whole eye-globe configuration (n=10) and at an artificially controlled intraocular pressure of 15mm Hg. Baseline OCE measurements were taken by topically hydrating the corneas with saline for 1hour. The corneas were then dehydrated topically with a 20% dextran solution for another hour, and the OCE measurements were repeated. A finite element method was used to quantify the Young's modulus of the corneas based on the OCE measurements. The thickness of the corneas shrank considerably after topical addition of the 20% dextran solution (∼680 μm to ∼370 μm), and the OCE-measured elastic-wave speed correspondingly decreased (∼3.2m/s to ∼2.6m/s). The finite element method results showed an increase in Young's modulus (500kPa to 800kPa) resulting from dehydration and subsequent thinning. Young's modulus increased significantly as the corneas dehydrated and thinned, showing that corneal geometry and hydration state are critical factors for accurately quantifying corneal biomechanical properties.

Stiffness Comparison of Tissue Phantoms using Optical Coherence Elastography without a Load Cell

Mechanical property of tissue is closely related to diseases such as breast cancer, prostate cancer, cirrhosis of the liver, and atherosclerosis. Therefore measurement of tissue mechanical property is important for a better diagnosis. Ultrasound elastography has been developed as a diagnostic modality for a number of diseases that maps mechanical property of tissue. Optical coherence elastography (OCE) has a higher spatial resolution than ultrasound elastography. OCE, therefore, could be a great help for early diagnosis. In this study, we made tissue phantoms and measured their compressive moduli with a rheometer measuring the response to applied force. Uniaxial strain of the tissue phantom was also measured with OCE by using cross-correlation of speckles and compared with the results from the rheometer. In order to compare stiffness of tissue phantoms by OCE, the applied force should be measured in addition to the strain. We, however, did not use a load cell that directly measures the applied force for each sample. Instead, we utilized one silicone film (called as reference phantom) for all OCE measurements that indirectly indicated the amount of the applied force by deformation. Therefore, all measurements were based on displacement, which was natural and effective for image-based elastography such as OCE.

Optical coherence elastography for evaluating customized riboflavin/UV-A corneal collagen crosslinking.

UV-induced collagen cross-linking is a promising treatment for keratoconus that stiffens corneal tissue and prevents further degeneration. Since keratoconus is generally localized, the efficacy of collagen cross-linking (CXL) treatments could be improved by stiffening only the weakened parts of the cornea. Here, we demonstrate that optical coherence elastography (OCE) can spatially resolve transverse variations in corneal stiffness. A short duration ( ? 1 ?? ms ) focused air-pulse induced low amplitude ( ? 10 ?? ? m ) deformations in the samples that were detected using a phase-stabilized optical coherence tomography system. A two-dimensional map of material stiffness was generated by measuring the damped natural frequency (DNF) of the air-pulse induced response at various transverse locations of a heterogeneous phantom mimicking a customized CXL treatment. After validation on the phantoms, similar OCE measurements were made on spatially selective CXL-treated in situ rabbit corneas. The results showed that this technique was able to clearly distinguish the untreated and CXL-treated regions of the cornea, where CXL increased the DNF of the cornea by ? 51 % . Due to the noncontact nature and minimal excitation force, this technique may be valuable for in vivo assessments of corneal biomechanical properties.

Optical coherence elastography assessment of corneal viscoelasticity with a modified Rayleigh-Lamb wave model

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.

Investigating Elastic Anisotropy of the Porcine Cornea as a Function of Intraocular Pressure With Optical Coherence Elastography

To evaluate the elastic anisotropy of porcine corneas at different intraocular pressures (IOPs) using a noncontact optical coherence elastography (OCE) technique. A focused air-pulse induced low amplitude (≤ 10 µm) elastic waves in fresh porcine corneas (n = 7) in situ in the whole eye globe configuration. A home-built phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at different stepped radial directions. A closed-loop feedback system was used to artificially control the IOP and the OCE measurements were repeated as the IOP was incrementally increased from 15 to 30 mm Hg in 5-mm Hg increments. The OCE measurements demonstrated that the stiffness of the cornea increased as a function of IOP and elastic anisotropy of the cornea became more pronounced at higher IOPs. The standard deviation of the modified planar anisotropy coefficient increased from 0.72 ± 0.42 at an IOP of 15 mm Hg to 1.58 ± 0.40 at 30 mm Hg. The presented noncontact OCE method was capable of detecting and assessing the corneal elastic anisotropy as a function of IOP. Due to the noninvasive nature and small amplitude of the elastic wave, this method may be able to provide further information about corneal health and integrity in vivo. [J Refract Surg. 2016;32(8):562-567.].

Analysis of the effect of the fluid-structure interface on elastic wave velocity in cornea-like structures by OCE and FEM

Air-pulse optical coherence elastography (OCE) is a promising technique for quantifying biomechanical properties of the cornea. This technique typically involves imaging and analysis of the propagation of the air-pulse induced elastic waves to reconstruct corneal biomechanical properties using an analytical model. However, the effect of the fluid-structure interface (FSI) at the corneal posterior surface on the elastic wave velocity is not accounted for in many models. In this study, we examined the effect of the FSI with OCE experiments on contact lenses with and without fluid in the posterior gap. Finite element models (FEM), also with and without the FSI, were constructed to simulate the elastic wave propagation based on the OCE measurements. The FEM and OCE results were in good agreement demonstrating the feasibility of the method. To further investigate the effect of the FSI, OCE experiments and subsequent FEM simulations were conducted on in situ rabbit corneas before and after rose bengal/green light corneal collagen cross-linking (RGX). Both the OCE experiments and the FE simulations demonstrated that the FSI significantly reduced the group velocity of the elastic wave, and thus, should be considered when determining corneal biomechanical properties from an appropriate mechanical model. By matching the FEM-calculated velocity to the OCE-measured velocity, the corneal elasticity was quantified. The Young’s modulus of the rabbit cornea before RGX was E = 65 ± 10 kPa at a controlled intraocular pressure (IOP) of 15 mmHg. After RGX, the Young’s modulus increased to E = 102 ± 7 kPa at the same IOP.

Quantitative methods for reconstructing tissue biomechanical properties in optical coherence elastography: a comparison study

We present a systematic analysis of the accuracy of five different methods for extracting the biomechanical properties of soft samples using optical coherence elastography (OCE). OCE is an emerging noninvasive technique, which allows assessment of biomechanical properties of tissues with micrometer spatial resolution. However, in order to accurately extract biomechanical properties from OCE measurements, application of a proper mechanical model is required. In this study, we utilize tissue-mimicking phantoms with controlled elastic properties and investigate the feasibilities of four available methods for reconstructing elasticity (Young’s modulus) based on OCE measurements of an air-pulse induced elastic wave. The approaches are based on the shear wave equation (SWE), the surface wave equation (SuWE), Rayleigh-Lamb frequency equation (RLFE), and finite element method (FEM), Elasticity values were compared with uniaxial mechanical testing. The results show that the RLFE and the FEM are more robust in quantitatively assessing elasticity than the other simplified models. This study provides a foundation and reference for reconstructing the biomechanical properties of tissues from OCE data, which is important for the further development of noninvasive elastography methods.

Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.