Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery.

Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS. SIGNIFICANCE: Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision.

Multi-class classification of breast tissue using optical coherence tomography and attenuation imaging combined via deep learning.

We demonstrate a convolutional neural network (CNN) for multi-class breast tissue classification as adipose tissue, benign dense tissue, or malignant tissue, using multi-channel optical coherence tomography (OCT) and attenuation images, and a novel Matthews correlation coefficient (MCC)-based loss function that correlates more strongly with performance metrics than the commonly used cross-entropy loss. We hypothesized that using multi-channel images would increase tumor detection performance compared to using OCT alone. 5,804 images from 29 patients were used to fine-tune a pre-trained ResNet-18 network. Adding attenuation images to OCT images yields statistically significant improvements in several performance metrics, including benign dense tissue sensitivity (68.0% versus 59.6%), malignant tissue positive predictive value (PPV) (79.4% versus 75.5%), and total accuracy (85.4% versus 83.3%), indicating that the additional contrast from attenuation imaging is most beneficial for distinguishing between benign dense tissue and malignant tissue.

Coherence function-encoded optical palpation.

Optical palpation maps stress at the surface of biological tissue into 2D images. It relies on measuring surface deformation of a compliant layer, which to date has been performed with optical coherence tomography (OCT). OCT-based optical palpation holds promise for improved clinical diagnostics; however, the complexity and cost hinder broad adoption. In this Letter, we introduce coherence function-encoded optical palpation (CFE-OP) using a novel optical profilometry technique that exploits the envelope of the coherence function rather than its peak position, which is typically used to retrieve depth information. CFE-OP utilizes a Fabry-Perot laser diode (bandwidth, 2.2 nm) and a single photodiode in a Michelson interferometer to detect the position along the coherence envelope as a function of path length. This technique greatly reduces complexity and cost in comparison to the OCT-based approach. We perform CFE-OP on phantom and excised human breast tissue, demonstrating comparable mechanical contrast to OCT-based optical palpation and the capability to distinguish stiff tumor from soft benign tissue.

Diagnostic concordance among pathologists interpreting breast core biopsies on secondary review over a 1-year period at an Australian tertiary hospital.

This study provides data on the diagnostic concordance between initial and review diagnoses of all breast core biopsy cases at a single tertiary hospital in Western Australia over a 1-year period. A retrospective review of all breast core biopsy cases between January 1 and December 31, 2016, was carried out at PathWest, Fiona Stanley Hospital in Perth, Western Australia. Each biopsy is reported by a single pathologist and then reviewed within 1 week by a panel of intradepartmental subspecialist breast pathologists, who either agree with the original diagnosis, have a minor discordant diagnosis, or a major discordant diagnosis. Records for 2036 core biopsies were available between January 1 and December 31, 2016. Of these, 56.0% (n = 1141) were classified as benign, 34.3% (n = 699) as malignant, 7.2% (n = 147) as indeterminate, 2.3% (n = 46) as nondiagnostic, and 0.1% (n = 3) as suspicious for malignancy. In 99.1% (n = 2018) of cases, there was agreement between initial and review diagnoses. In total, 0.9% (n = 18) were disagreements: 0.49% (n = 10) were major discordant disagreements and 0.39% (n = 8) were minor discordant disagreements. All cases of major discordant disagreements would have resulted in significant changes to clinical management. This study demonstrates that an Australian institution is providing a high-quality pathology service with a low error rate between initial and review diagnoses of breast core biopsies. It reinforces the importance of secondary review of biopsies in a timely fashion for detecting potentially serious misdiagnoses that could lead to inappropriate management.

Optical palpation for tumor margin assessment in breast-conserving surgery.

Intraoperative margin assessment is needed to reduce the re-excision rate of breast-conserving surgery. One possibility is optical palpation, a tactile imaging technique that maps stress (force applied across the tissue surface) as an indicator of tissue stiffness. Images (optical palpograms) are generated by compressing a transparent silicone layer on the tissue and measuring the layer deformation using optical coherence tomography (OCT). This paper reports, for the first time, the diagnostic accuracy of optical palpation in identifying tumor within 1 mm of the excised specimen boundary using an automated classifier. Optical palpograms from 154 regions of interest (ROIs) from 71 excised tumor specimens were obtained. An automated classifier was constructed to predict the ROI margin status by first choosing a circle diameter, then searching for a location within the ROI where the circle was ≥ 75% filled with high stress (indicating a positive margin). A range of circle diameters and stress thresholds, as well as the impact of filtering out non-dense tissue regions, were tested. Sensitivity and specificity were calculated by comparing the automated classifier results with the true margin status, determined from co-registered histology. 83.3% sensitivity and 86.2% specificity were achieved, compared to 69.0% sensitivity and 79.0% specificity obtained with OCT alone on the same dataset using human readers. Representative optical palpograms show that positive margins containing a range of cancer types tend to exhibit higher stress compared to negative margins. These results demonstrate the potential of optical palpation for margin assessment.

Camera-based optical palpation.

Optical elastography is undergoing extensive development as an imaging tool to map mechanical contrast in tissue. Here, we present a new platform for optical elastography by generating sub-millimetre-scale mechanical contrast from a simple digital camera. This cost-effective, compact and easy-to-implement approach opens the possibility to greatly expand applications of optical elastography both within and beyond the field of medical imaging. Camera-based optical palpation (CBOP) utilises a digital camera to acquire photographs that quantify the light intensity transmitted through a silicone layer comprising a dense distribution of micro-pores (diameter, 30-100 µm). As the transmission of light through the micro-pores increases with compression, we deduce strain in the layer directly from intensity in the digital photograph. By pre-characterising the relationship between stress and strain of the layer, the measured strain map can be converted to an optical palpogram, a map of stress that visualises mechanical contrast in the sample. We demonstrate a spatial resolution as high as 290 µm in CBOP, comparable to that achieved using an optical coherence tomography-based implementation of optical palpation. In this paper, we describe the fabrication of the micro-porous layer and present experimental results from structured phantoms containing stiff inclusions as small as 0.5 × 0.5 × 1 mm. In each case, we demonstrate high contrast between the inclusion and the base material and validate both the contrast and spatial resolution achieved using finite element modelling. By performing CBOP on freshly excised human breast tissue, we demonstrate the capability to delineate tumour from surrounding benign tissue.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.

Three-dimensional mapping of the attenuation coefficient in optical coherence tomography to enhance breast tissue microarchitecture contrast.

Effective intraoperative tumor margin assessment is needed to reduce re-excision rates in breast-conserving surgery (BCS). Mapping the attenuation coefficient in optical coherence tomography (OCT) throughout a sample to create an image (attenuation imaging) is one promising approach. For the first time, three-dimensional OCT attenuation imaging of human breast tissue microarchitecture using a wide-field (up to ~45 × 45 × 3.5 mm) imaging system is demonstrated. Representative results from three mastectomy and one BCS specimen (from 31 specimens) are presented with co-registered postoperative histology. Attenuation imaging is shown to provide substantially improved contrast over OCT, delineating nuanced features within tumors (including necrosis and variations in tumor cell density and growth patterns) and benign features (such as sclerosing adenosis). Additionally, quantitative micro-elastography (QME) images presented alongside OCT and attenuation images show that these techniques provide complementary contrast, suggesting that multimodal imaging could increase tissue identification accuracy and potentially improve tumor margin assessment.

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.

Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis.

Metastasis is the major cause of death in patients with cancer; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here, we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted as an autocrine mediator to modulate a range of known metastasis-regulating genes, including Smad7, via activation of canonical BMP-SMAD signaling. Restored BMP4 expression or therapeutically administered BMP4 protein, blocked metastasis and increased survival by sensitizing cancer cells to anoikis, thereby reducing the number of circulating tumor cells. Gene silencing of Bmp4 or its downstream mediator Smad7, reversed this phenotype. Administration of recombinant BMP4 markedly reduced spontaneous metastasis to lung and bone. Elevated levels of BMP4 and SMAD7 were prognostic for improved recurrence-free survival and overall survival in patients with breast cancer, indicating the importance of canonical BMP4 signaling in the suppression of metastasis and highlighting new avenues for therapy against metastatic disease. SIGNIFICANCE: Targeting the BMP4-SMAD7 signaling axis presents a novel therapeutic strategy to combat metastatic breast cancer, a disease that has had no reduction in patient mortality over 20 years. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/6/1304/F1.large.jpg.

Handheld probe for quantitative micro-elastography.

Optical coherence elastography (OCE) has been proposed for a range of clinical applications. However, the majority of these studies have been performed using bulky, lab-based imaging systems. A compact, handheld imaging probe would accelerate clinical translation, however, to date, this had been inhibited by the slow scan rates of compact devices and the motion artifact induced by the user's hand. In this paper, we present a proof-of-concept, handheld quantitative micro-elastography (QME) probe capable of scanning a 6 × 6 × 1 mm volume of tissue in 3.4 seconds. This handheld probe is enabled by a novel QME acquisition protocol that incorporates a custom bidirectional scan pattern driving a microelectromechanical system (MEMS) scanner, synchronized with the sample deformation induced by an annular PZT actuator. The custom scan pattern reduces the total acquisition time and the time difference between B-scans used to generate displacement maps, minimizing the impact of motion artifact. We test the feasibility of the handheld QME probe on a tissue-mimicking silicone phantom, demonstrating comparable image quality to a bench-mounted setup. In addition, we present the first handheld QME scans performed on human breast tissue specimens. For each specimen, quantitative micro-elastograms are co-registered with, and validated by, histology, demonstrating the ability to distinguish stiff cancerous tissue from surrounding soft benign tissue.

Optical palpation for the visualization of tumor in human breast tissue.

Accurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity. Manual palpation, however, is subjective and has relatively low resolution. Here, we investigate a tactile imaging technique, optical palpation, for the visualization of tumor. Optical palpation generates maps of the stress at the surface of tissue under static preload compression. Stress is evaluated by measuring the deformation of a contacting thin compliant layer with known mechanical properties using optical coherence tomography. In this study, optical palpation is performed on 34 freshly excised human breast specimens. Wide field-of-view (up to ~46 × 46 mm) stress images, optical palpograms, are presented from four representative specimens, demonstrating the capability of optical palpation to visualize tumor. Median stress reported for adipose tissue, 4 kPa, and benign dense tissue, 8 kPa, is significantly lower than for invasive tumor, 60 kPa. In addition, we demonstrate that optical palpation provides contrast consistent with a related optical technique, quantitative micro-elastography. This study demonstrates that optical palpation holds promise for visualization of tumor in breast-conserving surgery.

Review of diagnostic error in anatomical pathology and the role and value of second opinions in error prevention.

AIMS: Diagnostic/interpretative accuracy can be challenging in anatomical pathology due to the subjective element of the diagnostic process. This can lead to false-negative or false-positive diagnoses of malignancy, variations in grading and diagnostic misclassification of a condition.It is imperative that an accurate diagnosis is achieved so that an appropriate and timely treatment is administered to the patient, for example, the success of targeted molecular therapeutic options for treatment of cancer is dependent on accurate anatomical pathology diagnoses being issued. METHODS: A literature review of diagnostic accuracy in selected specimen categories was undertaken and was compared with data on metropolitan and regional pathologist diagnostic proficiency performance in an external quality assurance programme from surveys provided 2015-2017. For each specimen category, cases having attracted a diagnostic inaccuracy (ie, major discordance) of ≥20% and cases attracting a combined error rate (ie, major and minor discordance) of ≥30% are reviewed and discussed. RESULTS: The rate of inaccurate diagnoses (assessed as a major discordance) ranged from 3% to 9% among the different specimen groups, with highest mean percentage of inaccurate diagnoses in gynaecology, dermatopathology and gastrointestinal specimens. CONCLUSIONS: It was possible to ascertain that gynaecology, dermatopathology and gastrointestinal specimens had presented the greatest diagnostic challenge to the participant pathologists, determined as highest rate of diagnostic inaccuracy, that is, major discordance with respective case target diagnoses.Through a combination of routine second opinions, directed retrospective peer review and participation in appropriate external quality assurance schemes, the risk associated with these diagnoses can be minimised.

Wide-field quantitative micro-elastography of human breast tissue.

Currently, 20-30% of patients undergoing breast-conserving surgery require a second surgery due to insufficient surgical margins in the initial procedure. We have developed a wide-field quantitative micro-elastography system for the assessment of tumor margins. In this technique, we map tissue elasticity over a field-of-view of ~46 × 46 mm. We performed wide-field quantitative micro-elastography on thirteen specimens of freshly excised tissue acquired from patients undergoing a mastectomy. We present wide-field optical coherence tomography (OCT) images, qualitative (strain) micro-elastograms and quantitative (elasticity) micro-elastograms, acquired in 10 minutes. We demonstrate that wide-field quantitative micro-elastography can extend the range of tumors visible using OCT-based elastography by providing contrast not present in either OCT or qualitative micro-elastography and, in addition, can reduce imaging artifacts caused by a lack of contact between tissue and the imaging window. Also, we describe how the combined evaluation of OCT, qualitative micro-elastograms and quantitative micro-elastograms can improve the visualization of tumor.

InForm software: a semi-automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance.

Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists' reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer's "InForm" software package to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist's assessment. We examined a cohort of eleven acute hepatitis samples and three non-alcoholic fatty liver disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm was configured to identify presumptive HPCs, CD45+ve inflammatory cells, areas of necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinflammation as evaluated by a pathologist, correlated with InForm outputs (r2 = 0.8192, p < 0.05). This study demonstrates that the InForm software package provides a useful tool for liver disease research, allowing rapid, and objective quantification of the presumptive HPCs and identifies histological features that assist with assessing liver disease severity, and potentially can facilitate diagnosis.

Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.

It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery. As a result, it remains unclear if the mechanical contrast observed is maintained in WLE specimens. In this manuscript, we begin to address this issue by performing a feasibility study of OCME on 17 freshly excised, intact WLE specimens. In addition, we present two developments required to sustain the progression of OCME towards intraoperative deployment. First, to enable the rapid visualization of en face images required for intraoperative assessment, we describe an automated segmentation algorithm to fuse en face micro-elastograms with OCT images to provide dual contrast images. Secondly, to validate contrast in micro-elastograms, we present a method that enables co-registration of en face images with histology of WLE specimens, sectioned in the orthogonal plane, without any modification to the standard clinical workflow. We present a summary of the observations across the 17 specimens imaged in addition to representative micro-elastograms and OCT images demonstrating contrast in a number of tumor margins, including those involved by invasive ductal carcinoma, mucinous carcinoma, and solid-papillary carcinoma. The results presented here demonstrate the potential of OCME for imaging tumor margins.

False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.

A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position. On ultrasound (US), a corresponding 13×9×10 mm irregular hypoechoic mass with internal vascularity was noted and both breasts had a complex heterogeneous fibroglandular background pattern. US-guided core biopsy with marker clip insertion was performed with the diagnosis of a grade 2 invasive ductal carcinoma (IDC). In view of the parenchymal pattern on mammography and US, contrast-enhanced spectral mammography (CESM) was performed for local staging. Mild background enhancement was noted, but there was no enhancement at the lesion site. The patient elected to have bilateral mastectomies and sentinel node biopsies. Final histopathology showed a node negative 11 mm grade 2 oestrogen and progesterone receptor positive, IDC.

Simplifying the assessment of human breast cancer by mapping a micro-scale heterogeneity index in optical coherence elastography.

Surgical treatment of breast cancer aims to identify and remove all malignant tissue. Intraoperative assessment of tumor margins is, however, not exact; thus, re-excision is frequently needed, or excess normal tissue is removed. Imaging methods applicable intraoperatively could help to reduce re-excision rates whilst minimizing removal of excess healthy tissue. Optical coherence elastography (OCE) has been proposed for use in breast-conserving surgery; however, intraoperative interpretation of complex OCE images may prove challenging. Observations of breast cancer on multiple length scales, by OCE, ultrasound elastography, and atomic force microscopy, have shown an increase in the mechanical heterogeneity of malignant breast tumors compared to normal breast tissue. In this study, a micro-scale mechanical heterogeneity index is introduced and used to form heterogeneity maps from OCE scans of 10 ex vivo human breast tissue samples. Through comparison of OCE, optical coherence tomography images, and corresponding histology, malignant tissue is shown to possess a higher heterogeneity index than benign tissue. The heterogeneity map simplifies the contrast between tumor and normal stroma in breast tissue, facilitating the rapid identification of possible areas of malignancy, which is an important step towards intraoperative margin assessment using OCE.

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.

Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes.

BACKGROUND: Evaluation of lymph node involvement is an important factor in detecting metastasis and deciding whether to perform axillary lymph node dissection (ALND) in breast cancer surgery. As ALND is associated with potentially severe long term morbidity, the accuracy of lymph node assessment is imperative in avoiding unnecessary ALND. The mechanical properties of malignant lymph nodes are often distinct from those of normal nodes. A method to image the micro-scale mechanical properties of lymph nodes could, thus, provide diagnostic information to aid in the assessment of lymph node involvement in metastatic cancer. In this study, we scan axillary lymph nodes, freshly excised from breast cancer patients, with optical coherence micro-elastography (OCME), a method of imaging micro-scale mechanical strain, to assess its potential for the intraoperative assessment of lymph node involvement. METHODS: Twenty-six fresh, unstained lymph nodes were imaged from 15 patients undergoing mastectomy or breast-conserving surgery with axillary clearance. Lymph node specimens were bisected to allow imaging of the internal face of each node. Co-located OCME and optical coherence tomography (OCT) scans were taken of each sample, and the results compared to standard post-operative hematoxylin-and-eosin-stained histology. RESULTS: The optical backscattering signal provided by OCT alone may not provide reliable differentiation by inspection between benign and malignant lymphoid tissue. Alternatively, OCME highlights local changes in tissue strain that correspond to malignancy and are distinct from strain patterns in benign lymphoid tissue. The mechanical contrast provided by OCME complements the optical contrast provided by OCT and aids in the differentiation of malignant tumor from uninvolved lymphoid tissue. CONCLUSION: The combination of OCME and OCT images represents a promising method for the identification of malignant lymphoid tissue. This method shows potential to provide intraoperative assessment of lymph node involvement, thus, preventing unnecessary removal of uninvolved tissues and improving patient outcomes.