Lixin Chin

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.

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.

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.

Imaging of skin birefringence for human scar assessment using polarization-sensitive optical coherence tomography aided by vascular masking

Abstract. We demonstrate the in vivo assessment of human scars by parametric imaging of birefringence using polarization-sensitive optical coherence tomography (PS-OCT). Such in vivo assessment is subject to artifacts in the detected birefringence caused by scattering from blood vessels. To reduce these artifacts, we preprocessed the PS-OCT data using a vascular masking technique. The birefringence of the remaining tissue regions was then automatically quantified. Results from the scars and contralateral or adjacent normal skin of 13 patients show a correspondence of birefringence with scar type: the ratio of birefringence of hypertrophic scars to corresponding normal skin is 2.2±0.2 (mean±standard deviation), while the ratio of birefringence of normotrophic scars to normal skin is 1.1±0.4. This method represents a new clinically applicable means for objective, quantitative human scar assessment.

Wide-field optical coherence micro-elastography for intraoperative assessment of human breast cancer margins

Incomplete excision of malignant tissue is a major issue in breast-conserving surgery, with typically 20 - 30% of cases requiring a second surgical procedure arising from postoperative detection of an involved margin. We report advances in the development of a new intraoperative tool, optical coherence micro-elastography, for the assessment of tumor margins on the micro-scale. We demonstrate an important step by conducting whole specimen imaging in intraoperative time frames with a wide-field scanning system acquiring mosaicked elastograms with overall dimensions of ~50 × 50 mm, large enough to image an entire face of most lumpectomy specimens. This capability is enabled by a wide-aperture annular actuator with an internal diameter of 65 mm. We demonstrate feasibility by presenting elastograms recorded from freshly excised human breast tissue, including from a mastectomy, lumpectomies and a cavity shaving.

Three-dimensional optical coherence elastography by phase-sensitive comparison of C-scans

Abstract. We present an acquisition method for optical coherence elastography (OCE) that enables acquisition of three-dimensional elastograms in 5 s, an order of magnitude faster than previously reported. In this method, based on compression elastography, the mechanical load applied to the sample is altered between acquisitions of consecutive optical coherence tomography volume scans (C-scans). The voxel-by-voxel phase difference between the volumes is used to determine the axial displacement and determining the gradient of the axial displacement versus depth gives the local axial strain. We demonstrate sub-100-microstrain sensitivity and high contrast in elastograms, acquired in 5 s, of structured phantoms and freshly excised rat muscle tissue that are comparable in strain sensitivity and dynamic range to our previously reported B-scan-based method. The much higher acquisition speed may expedite the translation of OCE to clinical and in vivo applications.

Three-dimensional optical coherence micro-elastography of skeletal muscle tissue

In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle tissue including fibers, fascicles and tendon, and can also detect necrotic lesions in skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. In many instances, OCME provides better or additional contrast complementary to that provided by OCT. These results suggest that OCME could provide new understanding and opportunity for assessment of skeletal muscle pathologies.

Quantitative assessment of muscle damage in the mdx mouse model of Duchenne muscular dystrophy using polarization-sensitive optical coherence tomography

Minimally invasive, high-resolution imaging of muscle necrosis has the potential to aid in the assessment of diseases such as Duchenne muscular dystrophy. Undamaged muscle tissue possesses high levels of optical birefringence due to its anisotropic ultrastructure, and this birefringence decreases when the tissue undergoes necrosis. In this study, we present a novel technique to image muscle necrosis using polarization-sensitive optical coherence tomography (PS-OCT). From PS-OCT scans, our technique is able to quantify the birefringence in muscle tissue, generating an image indicative of the tissue ultrastructure, with areas of abnormally low birefringence indicating necrosis. The technique is demonstrated on excised skeletal muscles from exercised dystrophic mdx mice and control C57BL/10ScSn mice with the resulting images validated against colocated histological sections. The technique additionally gives a measure of the proportion (volume fraction) of necrotic tissue within the three-dimensional imaging field of view. The percentage necrosis assessed by this technique is compared against the percentage necrosis obtained from manual assessment of histological sections, and the difference between the two methods is found to be comparable to the interobserver variability of the histological assessment. This is the first published demonstration of PS-OCT to provide automated assessment of muscle necrosis.

En face parametric imaging of tissue birefringence using polarization-sensitive optical coherence tomography

Abstract. A technique for generating en face parametric images of tissue birefringence from scans acquired using a fiber-based polarization-sensitive optical coherence tomography (PS-OCT) system utilizing only a single-incident polarization state is presented. The value of birefringence is calculated for each A-scan in the PS-OCT volume using a quadrature demodulation and phase unwrapping algorithm. The algorithm additionally uses weighted spatial averaging and weighted least squares regression to account for the variation in phase accuracies due to varying OCT signal-to-noise-ratio. The utility of this technique is demonstrated using a model of thermally induced damage in porcine tendon and validated against histology. The resulting en face images of tissue birefringence are more useful than conventional PS-OCT B-scans in assessing the severity of tissue damage and in localizing the spatial extent of damage.