Compression Optical Coherence Elastography Research Articles

Real-Time Strain and Elasticity Imaging in Phase-Sensitive Optical Coherence Elastography Using a Computationally Efficient Realization of the Vector Method

We present a real-time realization of OCT-based elastographic mapping local strains and distribution of the Young’s modulus in biological tissues, which is in high demand for biomedical usage. The described variant exploits the principle of Compression Optical Coherence Elastography (C-OCE) and uses processing of phase-sensitive OCT signals. The strain is estimated by finding local axial gradients of interframe phase variations. Instead of the popular least-squares method for finding these gradients, we use the vector approach, one of its advantages being increased computational efficiency. Here, we present a modified, especially fast variant of this approach. In contrast to conventional correlation-based methods and previously used phase-resolved methods, the described method does not use any search operations or local calculations over a sliding window. Rather, it obtains local strain maps (and then elasticity maps) using several transformations represented as matrix operations applied to entire complex-valued OCT scans. We first elucidate the difference of the proposed method from the previously used correlational and phase-resolved methods and then describe the proposed method realization in a medical OCT device, in which for real-time processing, a “typical” central processor (e.g., Intel Core i7-8850H) is sufficient. Representative examples of on-flight obtained elastographic images are given. These results open prospects for broad use of affordable OCT devices for high-resolution elastographic vitalization in numerous biomedical applications, including the use in clinic.

Quantitative compressive optical coherence elastography using structural OCT imaging and optical palpation to measure soft contact lens mechanical properties.

In this study, the principle of 'optical palpation' was applied to a compression optical coherence elastography (OCE) method using spectral domain optical coherence tomography (OCT). Optical palpation utilizes a compliant transparent material of known mechanical properties, which acts as a stress sensor, in order to derive the mechanical properties of a sample material under examination. This technique was applied to determine the mechanical properties of soft contact lenses, with one lens being used as the compliant stress sensor and the other as the sample under investigation to extract the mechanical properties. This compliant stress sensor allowed for the stress of the compression to be measured without the use of a force sensor. The strain of the materials was measured through an automatic boundary segmentation that tracks the material thickness (of the sensor and the sample) during compression through sequential structural OCT images. A total of five contact lens combinations were tested, using three separate commercially available contact lenses with unique mechanical properties. Various combinations of contact lens materials were used to further validate the technique. The Young's modulus derived from this method was compared to nominal manufacturer's values. Both accuracy and repeatability were assessed, with highly accurate measurements obtained, with a percentage difference between the nominal and experimentally derived Young's modulus being less than 6% for all the tested combinations as well as providing a Young's modulus that was not statistically significant different (p > 0.01) to the nominal value. The results demonstrate the potential of optical palpation in OCE to accurately measure the mechanical properties of a material without the use of sophisticated electronics to capture the stress of the sample. These findings have potential to be translated into a method for tissue mechanical testing with ex vivo and in vivo clinical applications.

1131P Intraoperative assessment of negative resection margins in breast-conserving surgery using optical coherence elastography

Breast conserving surgery (BCS) has become increasingly accepted as the surgical management of breast cancer in clinical practice. The main goal of BCS is the complete removal of cancer with clear surgical margins. This study demonstrates the results of the diagnostic accuracy of compression optical coherence elastography (C-OCE) method in ex vivo determining of “positive” and “negative” surgery margins in BCS.

Development of a handheld compression optical coherence elastography probe with a disposable stress sensor.

Optical coherence elastography (OCE) is a functional extension of optical coherence tomography (OCT). OCE measures a sample's deformation under force stimuli. Compression is often used to generate the force stimuli in OCE. In this Letter, we report the development of a handheld quantitative compression OCE probe with a novel stress senor, dedicated to measuring the force. The stress sensor consists of a circular glass window and a metal ring which are connected with polyurethane spokes. This sensor is mounted on the tip of the OCT sample arm as an imaging window, so that the force applied to the sample through the window can be measured by detecting the window displacement from the OCT image. The force-displacement function was first developed through simulation on COMSOL Multiphysics and eventually calibrated experimentally. A phase-sensitive OCT technique was employed to measure both the window displacement and the sample deformation. The performance of an OCE probe with this stress sensor was evaluated on a two-layer phantom. The results show that it is extremely capable of measuring the sample Young's modulus. Finally, we successfully measured the elasticity of the human fingertip, indicating a good potential of this OCE probe for in vivo elastogram measurement on human skin.

Speckle-dependent accuracy in phase-sensitive optical coherence tomography.

Phase-sensitive optical coherence tomography (OCT) is used to measure motion in a range of techniques, such as Doppler OCT and optical coherence elastography (OCE). In phase-sensitive OCT, motion is typically estimated using a model of the OCT signal derived from a single reflector. However, this approach is not representative of turbid samples, such as tissue, which exhibit speckle. In this study, for the first time, we demonstrate, through theory and experiment that speckle significantly lowers the accuracy of phase-sensitive OCT in a manner not accounted for by the OCT signal-to-noise ratio (SNR). We describe how the inaccuracy in speckle reduces phase difference sensitivity and introduce a new metric, speckle brightness, to quantify the amount of constructive interference at a given location in an OCT image. Experimental measurements show an almost three-fold degradation in sensitivity between regions of high and low speckle brightness at a constant OCT SNR. Finally, we apply these new results in compression OCE to demonstrate a ten-fold improvement in strain sensitivity, and a five-fold improvement in contrast-to-noise by incorporating independent speckle realizations. Our results show that speckle introduces a limit to the accuracy of phase-sensitive OCT and that speckle brightness should be considered to avoid erroneous interpretation of experimental data.

Compressional Optical Coherence Elastography of the Cornea.

Assessing the biomechanical properties of the cornea is crucial for detecting the onset and progression of eye diseases. In this work, we demonstrate the application of compression-based optical coherence elastography (OCE) to measure the biomechanical properties of the cornea under various conditions, including validation in an in situ rabbit model and a demonstration of feasibility for in vivo measurements. Our results show a stark increase in the stiffness of the corneas as IOP was increased. Moreover, UV-A/riboflavin corneal collagen crosslinking (CXL) also dramatically increased the stiffness of the corneas. The results were consistent across 4 different scenarios (whole CXL in situ, partial CXL in situ, whole CXL in vivo, and partial CXL in vivo), emphasizing the reliability of compression OCE to measure corneal biomechanical properties and its potential for clinical applications.

Static compression optical coherence elastography to measure the mechanical properties of soft contact lenses.

In this study, a novel method was developed for estimating the elastic modulus (Young's modulus) of soft contact lens materials using static compression optical coherence elastography. Using a commercially available spectral domain optical coherence tomography instrument, an experimental setup was developed to image a soft contact lens sample before and during compression with a known applied force, from which the lens material's mechanical properties can be derived. A semi-automatic segmentation method using graph-search theory and dynamic processing was used to trace the lens boundaries and to determine key structural changes within the images. To validate the method, five soft contact lens materials with a range of known elastic moduli and water contents were tested. The proposed method was successful in estimating the Young's modulus in the five different soft contact lens materials. It was demonstrated that the method provides highly repeatable measurements, with an intraclass correlation coefficient of >95%. The Young's modulus results were compared to published manufacturer data with no significant difference for four out of the five materials (p > 0.05). These results demonstrate that a static compression optical coherence tomography method can reliably measure the elastic modulus of soft contact lenses. This provides a methodology that can be used to explore in vitro contact lens mechanical properties, but more importantly, may also be extended to study the mechanical characteristics of in vivo or ex vivo tissue, provided that they can be imaged using OCT.

Analysis of sensitivity in quantitative micro-elastography.

Quantitative micro-elastography (QME), a variant of compression optical coherence elastography (OCE), is a technique to image tissue elasticity on the microscale. QME has been proposed for a range of applications, most notably tumor margin assessment in breast-conserving surgery. However, QME sensitivity, a key imaging metric, has yet to be systematically analyzed. Consequently, it is difficult to optimize imaging performance and to assess the potential of QME in new application areas. To address this, we present a framework for analyzing sensitivity that incorporates the three main steps in QME image formation: mechanical deformation, its detection using optical coherence tomography (OCT), and signal processing used to estimate elasticity. Firstly, we present an analytical model of QME sensitivity, validated by experimental data, and demonstrate that sub-kPa elasticity sensitivity can be achieved in QME. Using silicone phantoms, we demonstrate that sensitivity is dependent on friction, OCT focus depth, and averaging methods in signal processing. For the first time, we show that whilst lubrication of layer improves accuracy by reducing surface friction, it reduces sensitivity due to the time-dependent effect of lubricant exudation from the layer boundaries resulting in increased friction. Furthermore, we demonstrate how signal processing in QME provides a trade-off between sensitivity and resolution that can be used to optimize imaging performance. We believe that our framework to analyze sensitivity can help to sustain the development of QME and, also, that it can be readily adapted to other OCE techniques.

Strain and elasticity imaging in compression optical coherence elastography: The two-decade perspective and recent advances.

Quantitative mapping of deformation and elasticity in optical coherence tomography has attracted much attention of researchers during the last two decades. However, despite intense effort it took ~15 years to demonstrate optical coherence elastography (OCE) as a practically useful technique. Similarly to medical ultrasound, where elastography was first realized using the quasi-static compression principle and later shear-wave-based systems were developed, in OCE these two approaches also developed in parallel. However, although the compression OCE (C-OCE) was proposed historically earlier in the seminal paper by J. Schmitt in 1998, breakthroughs in quantitative mapping of genuine local strains and the Young's modulus in C-OCE have been reported only recently and have not yet obtained sufficient attention in reviews. In this overview, we focus on underlying principles of C-OCE; discuss various practical challenges in its realization and present examples of biomedical applications of C-OCE. The figure demonstrates OCE-visualization of complex transient strains in a corneal sample heated by an infrared laser beam.

Handheld volumetric manual compression‐based quantitative microelastography

Compression optical coherence elastography (OCE) typically requires a mechanical actuator to impart a controlled uniform strain to the sample. However, for handheld scanning, this adds complexity to the design of the probe and the actuator stroke limits the amount of strain that can be applied. In this work, we present a new volumetric imaging approach that utilizes bidirectional manual compression via the natural motion of the user's hand to induce strain to the sample, realizing compact, actuator-free, handheld compression OCE. In this way, we are able to demonstrate rapid acquisition of three-dimensional quantitative microelastography (QME) datasets of a tissue volume (6 × 6 × 1 mm3 ) in 3.4 seconds. We characterize the elasticity sensitivity of this freehand manual compression approach using a homogeneous silicone phantom and demonstrate comparable performance to a benchtop mounted, actuator-based approach. In addition, we demonstrate handheld volumetric manual compression-based QME on a tissue-mimicking phantom with an embedded stiff inclusion and on freshly excised human breast specimens from both mastectomy and wide local excision (WLE) surgeries. Tissue results are coregistered with postoperative histology, verifying the capability of our approach to measure the elasticity of tissue and to distinguish stiff tumor from surrounding soft benign tissue.

Ultra-sensitive optical coherence elastography using a high-dynamic-range force loading scheme for cervical rigidity assessment

An ultra-sensitive, wide-range force loading scheme is proposed for compression optical coherence elastography (OCE) that allows for the quantitative analysis of cervical tissue elasticity ex vivo. We designed a force loading apparatus featuring a water sink for minuscule incremental loading through a volume-controlled water droplet, from which the Young's modulus can be calculated by fitting the stress-strain curve. We validated the performance of the proposed OCE system on homogenous agar phantoms, showing the Young's modulus can be accurately estimated using this scheme. We then measured the Young's modulus of rodent cervical tissues acquired at different gestational ages, showing that the cervical rigidity of rodents was significantly dropped when entering the third trimester of pregnancy.

Analysis of spatial resolution in phase-sensitive compression optical coherence elastography.

Optical coherence elastography (OCE) is emerging as a method to image the mechanical properties of tissue on the microscale. However, the spatial resolution, a main advantage of OCE, has not been investigated and is not trivial to evaluate. To address this, we present a framework to analyze resolution in phase-sensitive compression OCE that incorporates the three main determinants of resolution: mechanical deformation of the sample, detection of this deformation using optical coherence tomography (OCT), and signal processing to estimate local axial strain. We demonstrate for the first time, through close correspondence between experiment and simulation of structured phantoms, that resolution in compression OCE is both spatially varying and sample dependent, which we link to the discrepancies between the model of elasticity and the mechanical deformation of the sample. We demonstrate that resolution is dependent on factors such as feature size and mechanical contrast. We believe that the analysis of image formation provided by our framework can expedite the development of compression OCE.

Compression optical coherence elastography with two-dimensional displacement measurement and local deformation visualization.

Current compression-based optical coherence elastography (OCE) only measures the axial displacement of a tissue, although the tissue also undergoes lateral displacement and microstructural alteration by the compression. In this Letter, we demonstrate a new compression-based OCE method that visualizes not only axial displacement, but also lateral displacement and microstructural decorrelation (MSD). This method employs complex correlation-based displacement and MSD measurements. It is implemented in a swept-source optical coherence tomography system with an active submicrometer compression. The performance of the method was demonstrated by measuring the porcine carotid artery and esophagus. The results showed significant axial and lateral displacements in the tissues by compression. An MSD map demonstrates high-contrast mechanical-property imaging.

Volumetric quantitative optical coherence elastography with an iterative inversion method.

It is widely accepted that accurate mechanical properties of three-dimensional soft tissues and cellular samples are not available on the microscale. Current methods based on optical coherence elastography can measure displacements at the necessary resolution, and over the volumes required for this task. However, in converting this data to maps of elastic properties, they often impose assumptions regarding homogeneity in stress or elastic properties that are violated in most realistic scenarios. Here, we introduce novel, rigorous, and computationally efficient inverse problem techniques that do not make these assumptions, to realize quantitative volumetric elasticity imaging on the microscale. Specifically, we iteratively solve the three-dimensional elasticity inverse problem using displacement maps obtained from compression optical coherence elastography. This is made computationally feasible with adaptive mesh refinement and domain decomposition methods. By employing a transparent, compliant surface layer with known shear modulus as a reference for the measurement, absolute shear modulus values are produced within a millimeter-scale sample volume. We demonstrate the method on phantoms, on a breast cancer sample ex vivo, and on human skin in vivo. Quantitative elastography on this length scale will find wide application in cell biology, tissue engineering and medicine.

Strain Tensor Imaging in Compression Optical Coherence Elastography

Compression optical coherence elastography forms images based on the mechanical properties of tissue by mapping the local strain in response to a compressive load. Strain is described by a second-order tensor, comprising six independent components. The majority of compression elastography methods, however, measure and form their analyses from a single axial component, which relies on the assumption that the stress in tissue is uniform and uniaxial. However, in general, tissues are complex and heterogeneous, and rarely comply with this assumption. This can lead to inaccuracies and misinterpretation of image contrast in compression optical coherence elastography. Here, we image the full strain tensor and demonstrate its utility in unambiguously characterizing deformation in structured phantoms and ex vivo tissues. We derive additional parameters from the strain tensor, and map the local compressibility, anisotropy of deformation, and total equivalent strain. Such analysis is enabled by an efficient non-iterative approach to measuring the three-dimensional displacement field via a closed-form solution to a collection of the amplitude of complex correlation coefficients across multiple digitally shifted images. Strain tensor imaging is likely to lead to more accurate estimation of tissue mechanical properties, improving the utility of compression optical coherence elastography in clinical and biological applications.

Quantitative Compression Optical Coherence Elastography as an Inverse Elasticity Problem

Quantitative elasticity imaging seeks to retrieve spatial maps of elastic moduli of tissue. Unlike strain, which is commonly imaged in compression elastography, elastic moduli are intrinsic properties of tissue, and therefore, this approach reconstructs images that are largely operator and system independent, enabling objective, longitudinal, and multisite diagnoses. Recently, novel quantitative elasticity imaging approaches to compression elastography have been developed. These methods use a calibration layer with known mechanical properties to sense the stress at the tissue surface, which combined with strain, is used to estimate the tissue's elastic moduli by assuming homogeneity in the stress field. However, this assumption is violated in mechanically heterogeneous samples. We present a more general approach to quantitative elasticity imaging that overcomes this limitation through an efficient iterative solution of the inverse elasticity problem using adjoint elasticity equations. We present solutions for linear elastic, isotropic, and incompressible solids; however, this method can be employed for more complex mechanical models. We retrieve the spatial distribution of shear modulus for a tissue-simulating phantom and a tissue sample. This is the first time, to our knowledge, that the iterative solution of the inverse elasticity problem has been implemented on experimentally acquired compression optical coherence elastography data.

Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography.

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties. To overcome this limitation, we present quantitative micro-elastography, which combines compression OCE with a compliant stress sensor to image tissue elasticity. The sensor consists of a layer of translucent silicone with well-characterized stress-strain behaviour. The measured strain in the sensor is used to estimate the two-dimensional stress distribution applied to the sample surface. Elasticity is determined by dividing the stress by the strain in the sample. We show that quantification of elasticity can improve the ability of compression OCE to distinguish between tissues, thereby extending the potential for inter-sample comparison and longitudinal studies of tissue elasticity. We validate the technique using tissue-mimicking phantoms and demonstrate the ability to map elasticity of freshly excised malignant and benign human breast tissues.

Near Video-Rate Optical Coherence Elastography by Acceleration With a Graphics Processing Unit

We present a graphics processing unit (GPU)-accelerated optical coherence elastography (OCE) system capable of generating strain images (elastograms) of soft tissue at near video-rates. The system implements phase-sensitive compression OCE using a pipeline of GPU kernel functions to enable a highly parallel implementation of OCE processing using the OpenCL framework. Developed on a commercial-grade GPU and desktop computer, the system achieves a processing rate of 21 elastograms per second at an image size of 960 × 400 pixels, enabling high-rate visualization during acquisition. The system is demonstrated on both tissue-simulating phantoms and fresh ex vivo mouse muscle. To the best of our knowledge, this is the first implementation of near video-rate OCE and the fastest reported OCE processing rate, enabling, for the first time, a system capable of computing and displaying OCE elastograms interactively during acquisition. This advance provides new opportunities for medical imaging of soft tissue stiffness using optical methods.

Analysis of image formation in optical coherence elastography using a multiphysics approach.

IMAGE FORMATION IN OPTICAL COHERENCE ELASTOGRAPHY (OCE) RESULTS FROM A COMBINATION OF TWO PROCESSES: the mechanical deformation imparted to the sample and the detection of the resulting displacement using optical coherence tomography (OCT). We present a multiphysics model of these processes, validated by simulating strain elastograms acquired using phase-sensitive compression OCE, and demonstrating close correspondence with experimental results. Using the model, we present evidence that the approximation commonly used to infer sample displacement in phase-sensitive OCE is invalidated for smaller deformations than has been previously considered, significantly affecting the measurement precision, as quantified by the displacement sensitivity and the elastogram signal-to-noise ratio. We show how the precision of OCE is affected not only by OCT shot-noise, as is usually considered, but additionally by phase decorrelation due to the sample deformation. This multiphysics model provides a general framework that could be used to compare and contrast different OCE techniques.

Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure.

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.