Compression Optical Coherence Elastography Research Articles

Tissue Elasticity as a Diagnostic Marker of Molecular Mutations in Morphologically Heterogeneous Colorectal Cancer.

The presence of molecular mutations in colorectal cancer (CRC) is a decisive factor in selecting the most effective first-line therapy. However, molecular analysis is routinely performed only in a limited number of patients with remote metastases. We propose to use tissue stiffness as a marker of the presence of molecular mutations in CRC samples. For this purpose, we applied compression optical coherence elastography (C-OCE) to calculate stiffness values in regions corresponding to specific CRC morphological patterns (n = 54). In parallel to estimating stiffness, molecular analysis from the same zones was performed to establish their relationships. As a result, a high correlation between the presence of KRAS/NRAS/BRAF driver mutations and high stiffness values was revealed regardless of CRC morphological pattern type. Further, we proposed threshold stiffness values for label-free targeted detection of molecular alterations in CRC tissues: for KRAS, NRAS, or BRAF driver mutation-above 803 kPa (sensitivity-91%; specificity-80%; diagnostic accuracy-85%), and only for KRAS driver mutation-above 850 kPa (sensitivity-90%; specificity-88%; diagnostic accuracy-89%). To conclude, C-OCE estimation of tissue stiffness can be used as a clinical diagnostic tool for preliminary screening of genetic burden in CRC tissues.

Optical coherence elastography measures the biomechanical properties of the ex vivo porcine cornea after LASIK.

The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact. To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas. Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the fellow eye underwent LASIK. Changes in stiffness as a function of intraocular pressure (IOP) before and after LASIK were measured using each technique. ACUS-OCE showed that corneal stiffness changed as a function of IOP for both the untreated and the treated groups. The elastic wave speed after LASIK was lower than before LASIK. Hb-OCE and compression OCE showed regional changes in corneal strain after LASIK, where the absolute strain difference between the cornea anterior and posterior increased after LASIK. The results of this study suggest that LASIK may soften the cornea and that these changes are largely localized to the region where the surgery was performed.

Compression Optical Coherence Elastography for Assessing Lymph Node Status in Early Breast Cancer

Введение. Оценка состояния лимфатических узлов является важным фактором для определения стадии заболевания и выбора оптимальной тактики лечения при раке молочной железы (РМЖ). В настоящее время, остается потребность в применении новых высокоразрешающих методов визуализации, позволяющих интраоперационно оценивать статус лимфатических узлов, удаление которых будет достоверно определять степень распространения опухолевого процесса в регионарных лимфатических коллекторах без лимфаденэктомии. Таким методом может стать компрессионная оптическая когерентная эластография (К-ОКЭ), способная оценивать упругие свойства биотканей, которые значительно изменяются при метастатическом поражении лимфатических узлов. Цель исследования – изучить с помощью метода К-ОКЭ линейные (жесткость) и нелинейные упругие свойства лимфатических узлов при наличии или отсутствии в них метастазов РМЖ. Материалы и методы. Всего было исследовано 27 послеоперационных сигнальных и аксиллярных лимфатических узлов у 24 пациентов с верифицированным РМЖ с клинической стадией T1-2N0M0. В исследовании использовался скоростной спектральный мультимодальный ОКТ прибор (Институт прикладной физики РАН, Россия), который обеспечивает выполнение К-ОКЭ с вычислением абсолютных значений жесткости (модуля Юнга в кПа) и параметра упругой нелинейности ткани. Верификацию полученных ОКТ данных проводили с помощью стандартного гистологического исследования и все лимфатические узлы были разделены на четыре группы: нормальные (неактивные) (n=6), реактивные с фолликулярной гиперплазией (n=7), реактивные с синусовым гистиоцитозом (n=8) и метастатические (n=6). Результаты. В результате было установлено, что нормальные лимфатические узлы на изображениях К-ОКЭ характеризуются самыми низкими значениями жесткости в области коры с сохраненными лимфоидными фолликулами (<200 кПа). Реактивные лимфатические узлы с фолликулярной гиперплазией демонстрируют умеренное повышение жесткости (200-300 кПа) в области коры и более выраженное увеличение жесткости (400-600 кПа) в областях синусового гистиоцитоза. Метастатические лимфатические узлы характеризуются самыми высокими значениями жесткости (> 600 кПа). Взаимодополняющая оценка линейных и нелинейных упругих параметров ткани позволило с высокой статистической значимостью (р<0.001) дифференцировать все четыре основные состояния лимфатических узлов. Выводы. К-ОКЭ позволяет дифференцировать нормальные, реактивные и метастатические лимфатические узлы. К-ОКЭ демонстрирует высокий потенциал для быстрой интраоперационной оценки статуса лимфатических узлов в реальном времени и сохранения непораженных узлов.

Analysis of surface roughness in optical coherence elastography using a novel phantom

Compression optical coherence elastography (OCE) has shown promise in detecting diseases, such as breast cancer, based on changes in the elasticity of tissue. While the mechanical models used in OCE assume a flat surface, tissue typically exhibits surface topography that can lead to inaccurate estimation of elasticity in OCE images (elastograms). The coupling of surface topography and heterogeneous mechanical properties in tissue make it challenging to study the relative impact of surface roughness on image formation. To address this, we developed mechanically homogeneous phantoms that accurately replicate the surface topography of human breast tissue. Surface topography of breast tissue specimens was captured in three-dimensional (3-D) optical coherence tomography (OCT) scans. Molds replicating the surface roughness of tissue were generated using 3-D modelling and 3-D printing. The phantoms were then fabricated in the molds using polydimethylsiloxane. OCT was used to validate the accuracy of the phantom surface topography and the phantoms were then used to determine the impact of surface roughness in compression OCE elastograms. Surface roughness phantoms were shown to accurately reflect the surface topography of six breast tissue specimens with a correlation of 0.96 ± 0.03. When imaged with a variant of compression OCE called quantitative micro-elastography, surface roughness resulted in a slight decrease in elasticity accuracy with a mean percentage error of 8.2 % for a flat phantom compared to 11.7 % for the roughness phantom, and a larger decrease in elasticity precision, or sensitivity, with a mean relative standard deviation of 9.4 % for the flat phantom compared to 21.2 %, for the roughness phantom. Our results show that contrast in elastograms moderately correlated with the phantom surface profile (r = 0.59, p < 0.001) and that surface roughness introduces spatially-varying elasticity that should be considered in the analysis of elastograms in compression OCE.

Assessment of resection margins during breast-conserving surgery using multimodal optical coherence tomography

Background. Breast cancer (BC) has been ranked first in morbidity and mortality among the female population in Russian Federation for several years. Rapid and accurate intraoperative examination of the cleanliness of resection margins is the main condition for breast-conserving surgery (BCS) to reduce the risks of local recurrence.Aim. To examine the tumor margins and assess the cleanliness of the resection margins in BCS in patients diagnosed with BC using multimodal optical coherence tomography (MM OCT) with comparative planned histological and additional molecular genetic analysis.Materials and methods. The study was carried out on postoperative samples of tumor and non-tumor breast tissue obtained from 115 patients with BC T1–2N0M0G2–3 stage IA–IIA, after BCS in the volume of radical resection or lumpectomy with histological control of the resection margins. A spectral domain MM OCT device (OCT 1300-E, BioMedTech LLC, Russia) was used, which provides structural OCT images to study the backscattering properties of tissue and allows performing a quantitative assessment of the elastic properties of the tissue by compression optical coherence elastography (OCE).Results. The MM OCT method was able to determine the exact margins between the tumor and non-tumor breast tissue. The main signs of the tumor were a decrease in the level and depth of penetration of the OCT signal in the structural OCT images, as well as an increase in the stiffness values (&gt;200 kPa) in the OCE images with the highest stiffness values (&gt;600 kPa) in the area of tumor cell accumulations. The use of compression OCE made it possible to detect clusters of tumor cells in the margins of resection at a distance of 5 mm from the visible border of the tumor. Among the 132 studied resection margins in 6 cases, the positive resection margin was determined by the OCE method, which was subsequently confirmed histologically. The negative resection margins were characterized by the lowest stiffness values (&lt;200 kPa) in the OCE images and were confirmed by both histological analysis and molecular genetic analysis. ROC-analysis established a threshold stiffness value of 159.8 kPa, which indicates the presence of tumor tissue at the resection margins in the presence of a high stiffness area larger than 500 µm. The high diagnostic accuracy of the OCE method (98.5 %) was determined to distinguish between the negative and positive resection margins during BCS.Conclusion. The use of MM OCT with OCE modality makes it possible to clearly distinguish different types of breast tissue in BC (adipose tissue, connective tissue, accumulation of tumor cells). MM OCT can be used as an additional intraoperative tool for visualizing tumor cells boundaries and assessing the cleanliness of resection margins in real time during BCS.

Compression OCT-elastography combined with speckle-contrast analysis as an approach to the morphological assessment of breast cancer tissue.

Currently, optical biopsy technologies are being developed for rapid and label-free visualization of biological tissue with micrometer-level resolution. They can play an important role in breast-conserving surgery guidance, detection of residual cancer cells, and targeted histological analysis. For solving these problems, compression optical coherence elastography (C-OCE) demonstrated impressive results based on differences in the elasticity of different tissue constituents. However, sometimes straightforward C-OCE-based differentiation is insufficient because of the similar stiffness of certain tissue components. We present a new automated approach to the rapid morphological assessment of human breast cancer based on the combined usage of C-OCE and speckle-contrast (SC) analysis. Using the SC analysis of structural OCT images, the threshold value of the SC coefficient was established to enable the separation of areas of adipose cells from necrotic cancer cells, even if they are highly similar in elastic properties. Consequently, the boundaries of the tumor bed can be reliably identified. The joint analysis of structural and elastographic images enables automated morphological segmentation based on the characteristic ranges of stiffness (Young's modulus) and SC coefficient established for four morphological structures of breast-cancer samples from patients post neoadjuvant chemotherapy (residual cancer cells, cancer stroma, necrotic cancer cells, and mammary adipose cells). This enabled precise automated detection of residual cancer-cell zones within the tumor bed for grading cancer response to chemotherapy. The results of C-OCE/SC morphometry highly correlated with the histology-based results (r =0.96-0.98). The combined C-OCE/SC approach has the potential to be used intraoperatively for achieving clean resection margins in breast cancer surgery and for performing targeted histological analysis of samples, including the evaluation of the efficacy of cancer chemotherapy.

Quantification of linear and nonlinear elasticity by compression optical coherence elastography for determining lymph node status in breast cancer

We report the first application of compression optical coherence elastography (C-OCE) to evaluate both linear and nonlinear elastic properties of lymph nodes (LNs) for assessing their status, which is an important factor for detecting metastasis and staging breast cancer. The reported study involved 27 excised sentinel and axillary LNs from 24 patients with breast cancer, including normal LNs (n = 6), reactive LNs with follicular hyperplasia (n = 7) and sinus histiocytosis (n = 8), and metastatic LNs (n = 6). C-OCE data were compared with co-registered gold-standard histopathology and demonstrated a significantly higher contrast in differentiation of LNs as compared to structural optical coherence tomography imaging. Normal LNs are characterized by low stiffness values in the areas of LN cortex (<200 kPa). C-OCE revealed that abnormal reactive LNs with follicular hyperplasia exhibit moderately increased stiffness (200–300 kPa) in the cortex areas and more pronounced stiffness increase (400–600 kPa) in the areas of sinus histiocytosis. LNs with total metastasis exhibit fairly uniformly distributed highest stiffness values (>600 kPa). Since in terms of the tangent Young’s modulus there remained an appreciable overlap among these types of LNs, we also evaluated their elastic nonlinearity parameters. Complementary usage of both linear and nonlinear elastic parameters enabled very clear differentiation of all four main states of LNs. Thus, C-OCE imaging demonstrates high potential for future intraoperative usage to rapidly determine the LN status during breast-conserving surgery and to assess the extent of the cancer cells propagation in regional lymphatic collectors for preserving benign LNs. This is important for reducing the associated risks and complications (such as lymphedema) from excessive surgical removal of lymphoid structures.

Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography.

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young's modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer - low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors.

Compression Optical Coherence Elastography for Assessing Elasticity of the Vaginal Wall under Prolapse after Neodymium Laser Treatment

Early stages of pelvic organ prolapses are mainly associated with the pelvic floor disfunction as a result of elasticity changes in the connective tissues including the vaginal wall. In this study, for the first time we used a compression optical coherence elastography (C-OCE) method for assessing elasticity of the vaginal wall under prolapse conditions after intravaginal neodymium (Nd:YAG) laser treatment. C-OCE was used for a comparative ex vivo study of vaginal wall average values of stiffness (elastic Young’s modulus) in patients with age norm (n = 6), stage I–II prolapse (n = 5) without treatment and stage I–II prolapse post 1–2 months Nd:YAG laser treatment (n = 10). To verify the C-OCE data, the structural features of the submucosal connective tissue were identified morphometrically by Van Gieson staining using quantitative textural analysis of the state of collagen bundles. The results of a comparative evaluation of C-OCE and histological images demonstrate a statistically significant tissue stiffness decrease in vaginal wall prolapse compared to the age norm (73.5 ± 18.9 kPa vs. 233.5 ± 48.3 kPa; p &lt; 0.05). This agrees with the histologically revealed increase in the space between the bundles of collagen fibers, which leads to a decrease in the uniformity of their arrangement. After Nd:YAG laser treatment, we observed statistically significant connective tissue stiffness increase compared to vaginal wall prolapse without treatment (152.1 ± 19.2 kPa vs. 73.5 ± 18.9 kPa; p &lt; 0.05), which was associated with an increase in the local thickness of the collagen bundles, a change in their orientation, and an increase in the uniformity of their arrangement. The obtained results indicate that the C-OCE can be a robust method for detecting the early stages of vaginal wall prolapse and assessing the elastic modulus increase in the vaginal wall after laser treatment.

Application of compression optical coherence elastography for characterization of human pericardium: A pilot study.

The recent impressive progress in Compression Optical Coherence Elastography (C-OCE) demonstrated diverse biomedical applications, comprising ophthalmology, oncology, etc. High resolution of C-OCE enables spatially resolved characterization of elasticity of rather thin (thickness < 1 mm) samples, which previously was impossible. Besides Young's modulus, C-OCE enables obtaining of nonlinear stress-strain dependences for various tissues. Here, we report the first application of C-OCE to nondestructively characterize biomechanics of human pericardium, for which data of conventional tensile tests are very limited and controversial. C-OCE revealed pronounced differences among differently prepared pericardium samples. Ample understanding of the influence of chemo-mechanical treatment on pericardium biomechanics is very important because of rapidly growing usage of own patients' pericardium for replacement of aortic valve leaflets in cardio-surgery. The figure demonstrates differences in the tangent Young's modulus after glutaraldehyde-induced cross-linking for two pericardium samples. One sample was over-stretched during the preparation, which caused some damage to the tissue.

Mapping Large Strains in Phase-Sensitive OCT: Key Role of Supra-Pixel Displacement Tracking in Incremental Strain Evaluation

Displacement tracking is an important step in realization of compression optical coherence elastography (C-OCE), especially in the context of obtaining nonlinear stress-strain dependences and subsequent evaluation of the tissue Young’s modulus. The rapidly progressing phase-sensitive C-OCE, however, enables direct measurements of only rather small interframe strains (below 1%), for which displacements are also small. Obtaining stress-strain curves for larger strains (~10% and greater) in phase-sensitive C-OCE can be made via cumulation of interframe strains and particle displacements. The resultant values of the so-found cumulative displacements may significantly exceed the pixel size, whereas measurements of the phase variations in C-OCE are usually performed by comparing the signals from the same pixel in a series of compared scans. When displacements of particles in a series of acquired scans reach supra-pixel values, simple pixel-to-pixel estimation of interframe phase variations may lead to significant errors in evaluating linear and nonlinear elastic properties of tissues. Thus, for large strains, adequate accounting for the resultant supra-pixel displacements of order of several pixels and greater is of key importance for undistorted mapping of elastic properties of heterogeneous materials, as well as for correct tracking of boundaries separating tissue regions with different elastic properties. In this paper we discuss the elastographic procedures of correct tracking of supra-pixel displacements in phase-sensitive C-OCE and give real examples demonstrating the importance of such displacement tracking for undistorted reconstruction of two-dimensional maps of linear and nonlinear elastic properties of real biological tissues .

Subcellular mechano-microscopy: high resolution three-dimensional elasticity mapping using optical coherence microscopy.

The importance of cellular-scale mechanical properties is well-established, yet it is challenging to map subcellular elasticity in three dimensions. We present subcellular mechano-microscopy, an optical coherence microscopy (OCM)-based variant of three-dimensional (3-D) compression optical coherence elastography (OCE) that provides an elasticity system resolution of 5 × 5 × 5 µm: a 7-fold improvement in system resolution over previous OCE studies of cells. The improved resolution is achieved through a ∼5-fold improvement in optical resolution, refinement of the strain estimation algorithm, and demonstration that mechanical deformation of subcellular features provides feature resolution far greater than that demonstrated previously on larger features with diameter >250 µm. We use mechano-microscopy to image adipose-derived stem cells encapsulated in gelatin methacryloyl. We compare our results with compression OCE and demonstrate that mechano-microscopy can provide contrast from subcellular features not visible using OCE.

Nonlinear Elasticity Assessment with Optical Coherence Elastography for High-Selectivity Differentiation of Breast Cancer Tissues.

Soft biological tissues, breast cancer tissues in particular, often manifest pronounced nonlinear elasticity, i.e., strong dependence of their Young’s modulus on the applied stress. We showed that compression optical coherence elastography (C-OCE) is a promising tool enabling the evaluation of nonlinear properties in addition to the conventionally discussed Young’s modulus in order to improve diagnostic accuracy of elastographic examination of tumorous tissues. The aim of this study was to reveal and quantify variations in stiffness for various breast tissue components depending on the applied pressure. We discussed nonlinear elastic properties of different breast cancer samples excised from 50 patients during breast-conserving surgery. Significant differences were found among various subtypes of tumorous and nontumorous breast tissues in terms of the initial Young’s modulus (estimated for stress < 1 kPa) and the nonlinearity parameter determining the rate of stiffness increase with increasing stress. However, Young’s modulus alone or the nonlinearity parameter alone may be insufficient to differentiate some malignant breast tissue subtypes from benign. For instance, benign fibrous stroma and fibrous stroma with isolated individual cancer cells or small agglomerates of cancer cells do not yet exhibit significant difference in the Young’s modulus. Nevertheless, they can be clearly singled out by their nonlinearity parameter, which is the main novelty of the proposed OCE-based discrimination of various breast tissue subtypes. This ability of OCE is very important for finding a clean resection boundary. Overall, morphological segmentation of OCE images accounting for both linear and nonlinear elastic parameters strongly enhances the correspondence with the histological slices and radically improves the diagnostic possibilities of C-OCE for a reliable clinical outcome.

Compression optical coherence elastography versus strain ultrasound elastography for breast cancer detection and differentiation: pilot study

The aims of this study are (i) to compare ultrasound strain elastography (US-SE) and compression optical coherence elastography (C-OCE) in characterization of elastically linear phantoms, (ii) to evaluate factors that can cause discrepancy between the results of the two elastographic techniques in application to real tissues, and (iii) to compare the results of US-SE and C-OCE in the differentiation of benign and malignant breast lesions. On 22 patients, we first used standard US-SE for in vivo assessment of breast cancer before and then after the lesion excision C-OCE was applied for intraoperative visualization of margins of the tumors and assessment of their type/grade using fresh lumpectomy specimens. For verification, the tumor grades and subtypes were determined histologically. We show that in comparison to US-SE, quantitative C-OCE has novel capabilities due to its ability to locally control stress applied to the tissue and obtain local stress-strain curves. For US-SE, we demonstrate examples of malignant tumors that were erroneously classified as benign and vice versa. For C-OCE, all lesions are correctly classified in agreement with the histology. The revealed discrepancies between the strain ratio given by US-SE and ratio of tangent Young's moduli obtained for the same samples by C-OCE are explained. Overall, C-OCE enables significantly improved specificity in breast lesion differentiation and ability to precisely visualize margins of malignant tumors compared. Such results confirm high potential of C-OCE as a high-speed and accurate method for intraoperative assessment of breast tumors and detection of their margins.

Multimodal Heartbeat and Compression Optical Coherence Elastography for Mapping Corneal Biomechanics.

The biomechanical properties of the cornea have a profound influence on the health, structural integrity, and function of the eye. Understanding these properties may be critical for diagnosis and identifying disease pathogenesis. This work demonstrates how two different elastography techniques can be combined for a multimodal approach to measuring corneal biomechanical properties. Heartbeat optical coherence elastography (Hb-OCE) and compression OCE were performed simultaneously to measure the stiffness of the cornea in an in vivo rabbit model. Measurements were further performed after collagen crosslinking to demonstrate how the combined technique can be used to measure changes in corneal stiffness and map mechanical contrast. The results of this work further suggest that measurements from Hb-OCE and compression OCE are comparable, meaning that Hb-OCE and compression OCE may be used interchangeably despite distinct differences in both techniques.

Analysis of strain estimation methods in phase-sensitive compression optical coherence elastography.

In compression optical coherence elastography (OCE), deformation is quantified as the local strain at each pixel in the OCT field-of-view. A range of strain estimation methods have been demonstrated, yet it is unclear which method provides the best performance. Here, we analyze the two most prevalent strain estimation methods used in phase-sensitive compression OCE, i.e., weighted least squares (WLS) and the vector method. We introduce a framework to compare strain imaging metrics, incorporating strain sensitivity, strain signal-to-noise ratio (SNR), strain resolution, and strain accuracy. In addition, we propose a new phase unwrapping algorithm in OCE, fast phase unwrapping (FPU), and combine it with WLS, termed WLSFPU. Using the framework, we compare this new strain estimation method with both a current implementation of WLS that incorporates weighted phase unwrapping (WPU), termed WLSWPU, and the vector method. Our analysis reveals that the three methods provide similar strain sensitivity, strain SNR, and strain resolution, but that WLSFPU extends the dynamic range of accurate, measurable local strain, e.g., measuring a strain of 2.5 mɛ with ∼4% error, that is ×11 and ×15 smaller than the error measured using WLSWPU and the vector method, respectively. We also demonstrate, for the first time, the capability to detect sub-resolution contrast in compression OCE, i.e., changes in strain occurring within the strain axial resolution, and how this contrast varies between the different strain estimation methods. Lastly, we compare the performance of the three strain estimation methods on mouse skeletal muscle and human breast tissue and demonstrate that WLSFPU avoids strain imaging artifacts resulting from phase unwrapping errors in WLSWPU and provides improved contrast over the other two methods.

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.