Kelsey M. Kennedy

A Review of Optical Coherence Elastography: Fundamentals, Techniques and Prospects

In optical coherence elastography, images are formed by mapping a mechanical property of tissue. Such images, known as elastograms, are formed on the microscale, intermediate between that of cells and whole organs. Optical coherence elastography holds great promise for detecting and monitoring the altered mechanical properties that accompany many clinical conditions and pathologies, particularly in cancer, cardiovascular disease and eye disease. In this review, we first consider how the mechanical properties of tissue are linked with tissue function and pathology. We then describe currently prominent optical coherence elastography techniques, with emphasis on the methods of mechanical loading and displacement estimation. We highlight the sensitivity to microstrain deformations at tens of micrometer resolution. Throughout, optical coherence elastography is considered in the context of other elastography methods, mainly ultrasound elastography and magnetic resonance elastography. This context serves to highlight its advantages, early stage of development of applications, and strong prospects for future impact.

Review of tissue simulating phantoms with controllable optical, mechanical and structural properties for use in optical coherence tomography

We review the development of phantoms for optical coherence tomography (OCT) designed to replicate the optical, mechanical and structural properties of a range of tissues. Such phantoms are a key requirement for the continued development of OCT techniques and applications. We focus on phantoms based on silicone, fibrin and poly(vinyl alcohol) cryogels (PVA-C), as we believe these materials hold the most promise for durable and accurate replication of tissue properties.

Strain estimation in phase-sensitive optical coherence elastography

We present a theoretical framework for strain estimation in optical coherence elastography (OCE), based on a statistical analysis of displacement measurements obtained from a mechanically loaded sample. We define strain sensitivity, signal-to-noise ratio and dynamic range, and derive estimates of strain using three methods: finite difference, ordinary least squares and weighted least squares, the latter implemented for the first time in OCE. We compare theoretical predictions with experimental results and demonstrate a ~12 dB improvement in strain sensitivity using weighted least squares compared to finite difference strain estimation and a ~4 dB improvement over ordinary least squares strain estimation. We present strain images (i.e., elastograms) of tissue-mimicking phantoms and excised porcine airway, demonstrating in each case clear contrast based on the sample’s elasticity.

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.

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.

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

Abstract. 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.

Needle optical coherence elastography for tissue boundary detection

We incorporate, for the first time, optical coherence elastography (OCE) into a needle probe and demonstrate its ability to measure the microscopic deformation of soft tissues located well beyond the depth limit of reports to date. Needle OCE utilizes the force imparted by the needle tip as the loading mechanism and measures tissue deformation ahead of the needle during insertion. Measurements were performed in tissue-mimicking phantoms and ex vivo porcine trachea. Results demonstrate differentiation of tissues based on mechanical properties and highlight the potential of needle OCE for in vivo tissue boundary detection.

Analysis of mechanical contrast in optical coherence elastography

Abstract. Optical coherence elastography (OCE) maps the mechanical properties of tissue microstructure and has potential applications in both fundamental investigations of biomechanics and clinical medicine. We report the first analysis of contrast in OCE, including evaluation of the accuracy with which OCE images (elastograms) represent mechanical properties and the sensitivity of OCE to mechanical contrast within a sample. Using phase-sensitive compression OCE, we generate elastograms of tissue-mimicking phantoms with known mechanical properties and identify limitations on contrast imposed by sample mechanics and the imaging system, including signal-processing parameters. We also generate simulated elastograms using finite element models to perform mechanical analysis in the absence of imaging system noise. In both experiments and simulations, we illustrate artifacts that degrade elastogram accuracy, depending on sample geometry, elasticity contrast between features, and surface conditions. We experimentally demonstrate sensitivity to features with elasticity contrast as small as 1.1∶1 and calculate, based on our imaging system parameters, a theoretical maximum sensitivity to elasticity contrast of 1.002∶1. The results highlight the microstrain sensitivity of compression OCE, at a spatial resolution of tens of micrometers, suggesting its potential for the detection of minute changes in elasticity within heterogeneous tissue.

Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236-45. ©2015 AACR.

Improved measurement of vibration amplitude in dynamic optical coherence elastography

Abstract: Optical coherence elastography employs optical coherence tomography (OCT) to measure the displacement of tissues under load and, thus, maps the resulting strain into an image, known as an elastogram. We present a new improved method to measure vibration amplitude in dynamic optical coherence elastography. The tissue vibration amplitude caused by sinusoidal loading is measured from the spread of the Doppler spectrum, which is extracted using joint spectral and time domain signal processing. At low OCT signal-to-noise ratio (SNR), the method provides more accurate vibration amplitude measurements than the currently used phase-sensitive method. For measurements performed on a mirror at OCT SNR = 5 dB, our method introduces <3% error, compared to >20% using the phase-sensitive method. We present elastograms of a tissue-mimicking phantom and excised porcine tissue that demonstrate improvements, including a 50% increase in the depth range of reliable vibration amplitude measurement.