Stiffness Mediated-Mechanosensation of Airway Smooth Muscle Cells on Linear Stiffness Gradient Hydrogels.

In obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), the extracellular matrix (ECM) protein amount and composition of the airway smooth muscle (ASM) is often remodelled, likely altering tissue stiffness. The underlying mechanism of how human ASM cell (hASMC) mechanosenses the aberrant microenvironment is not well understood. Physiological stiffnesses of the ASM were measured by uniaxial compression tester using porcine ASM layers under 0, 5 and 10% longitudinal stretch above in situ length. Linear stiffness gradient hydrogels (230 kPa range) were fabricated and functionalized with ECM proteins, collagen I (ColI), fibronectin (Fn) and laminin (Ln), to recapitulate the above-measured range of stiffnesses. Overall, hASMC mechanosensation exhibited a clear correlation with the underlying hydrogel stiffness. Cell size, nuclear size and contractile marker alpha-smooth muscle actin (αSMA) expression showed a strong correlation to substrate stiffness. Mechanosensation, assessed by Lamin-A intensity and nuc/cyto YAP, exhibited stiffness-mediated behaviour only on ColI and Fn-coated hydrogels. Inhibition studies using blebbistatin or Y27632 attenuated most mechanotransduction-derived cell morphological responses, αSMA and Lamin-A expression and nuc/cyto YAP (blebbistatin only). This study highlights the interplay and complexities between stiffness and ECM protein type on hASMC mechanosensation, relevant to airway remodelling in obstructive airway diseases.

Mechanical overload-induced release of extracellular mitochondrial particles from tendon cells leads to inflammation in tendinopathy.

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.

In vivo characterisation of field pea stem wall thickness using optical coherence tomography.

BACKGROUND: Modern field pea breeding faces a significant challenge in selecting lines with strong stems that resist lodging. Traditional methods of assessing stem strength involve destructive mechanical tests on mature stems after natural senescence, such as measuring stem flexion, stem buckling or the thickness of dry stems when compressed, but these measurements may not correspond to the strength of stems in the living plant. Optical coherence tomography (OCT) can be used as a noncontact and nondestructive method to measure stem wall thickness in living plants by acquiring two- or three-dimensional images of living plant tissue. RESULTS: In this proof-of-principle study, we demonstrated in vivo characterisation of stem wall thickness using OCT, with the measurement corrected for the refractive index of the stem tissue. This in vivo characterisation was achieved through real-time imaging of stems, with an acquisition rate of 13 milliseconds per two-dimensional, cross-sectional OCT image. We also acquired OCT images of excised stems and compared the accuracy of in vivo OCT measurements of stem wall thickness with ex vivo results for 10 plants each of two field pea cultivars, Dunwa and Kaspa. In vivo OCT measurements of stem wall thickness have an average percent error of - 3.1% when compared with ex vivo measurements. Additionally, we performed in vivo measurements of both stem wall thickness and stem width at various internode positions on the two cultivars. The results revealed that Dunwa had a uniform stem wall thickness across different internode positions, while Kaspa had a significantly negative slope of [Formula: see text]0.0198 mm/node. Both cultivars exhibited an increase in stem width along the internode positions; however, Dunwa had a rate of increase of 0.1844 mm/node, which is three times higher than that of Kaspa. CONCLUSIONS: Our study has demonstrated the efficacy of OCT for accurate measurement of the stem wall thickness of live field pea. Moreover, OCT shows that the trends of stem wall thickness and stem width along the internode positions are different for the two cultivars, Dunwa and Kaspa, potentially hinting at differences in their stem strength. This rapid, in vivo imaging method provides a useful tool for characterising physical traits critical in breeding cultivars that are resistant to lodging.

Analysis of friction in quantitative micro-elastography.

Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique capable of measuring the mechanical properties of tissue on the micro-scale. As QME requires contact between the imaging window and the sample, the presence of friction affects the accuracy of the estimated elasticity. In previous implementations, a lubricant was applied at the contact surfaces, which was assumed to result in negligible friction. However, recently, errors in the estimation of elasticity caused by friction have been reported. This effect has yet to be characterized and is, therefore, not well understood. In this work, we present a systematic analysis of friction in QME using silicone phantoms. We demonstrate that friction, and, therefore, the elasticity accuracy, is influenced by several experimental factors, including the viscosity of the lubricant, the mechanical contrast between the compliant layer and the sample, and the time after the application of a compressive strain. Elasticity errors over an order of magnitude were observed in the absence of appropriate lubrication when compared to uniaxial compression testing. Using an optimized lubrication protocol, we demonstrate accurate elasticity estimation (<10% error) for nonlinear elastic samples with Young's moduli ranging from 3 kPa to 130 kPa. Finally, using a structured phantom, we demonstrate that friction can significantly reduce mechanical contrast in QME. We believe that the framework established in this study will facilitate more robust elasticity estimations in QME, as well as being readily adapted to understand the effects of friction in other contact elastography techniques.

3D Volumetric Mechanosensation of MCF7 Breast Cancer Spheroids in a Linear Stiffness Gradient GelAGE.

The tumor microenvironment presents spatiotemporal shifts in biomechanical properties with cancer progression. Hydrogel biomaterials like GelAGE offer the stiffness tuneability to recapitulate dynamic changes in tumor tissues by altering photo-energy exposures. Here, a tuneable hydrogel with spatiotemporal control of stiffness and mesh-network is developed. The volume of MCF7 spheroids encapsulated in a linear stiffness gradient demonstrates an inverse relationship with stiffness (p < 0.0001). As spheroids are exposed to increased crosslinking (stiffer) and greater mechanical confinement, spheroid stiffness increases. Protein expression (TRPV4, ß1 integrin, E-cadherin, and F-actin) decreases with increasing stiffness while showing strong correlations to spheroid volume (r2  > 0.9). To further investigate the role of volume, MCF7 spheroids are grown in a soft matrix for 5 days prior to a second polymerisation which presents a stiffness gradient to equally expanded spheroids. Despite being exposed to variable stiffness, these spheroids show even protein expression, confirming volume as a key regulator. Overall, this work showcases the versatility of GelAGE and demonstrates volume expansion as a key regulator of 3D mechanosensation in MCF7 breast cancer spheroids. This platform has the potential to further investigation into the role of stiffness and dimensionality in 3D spheroid culture for other types of cancers and diseases.

A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence.

Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects. Here, we develop a surgically optimized biodegradable hyaluronic acid-based hydrogel for sustained intraoperative delivery of Toll-like receptor 3 agonist poly(I:C) and demonstrate that it significantly reduces tumor recurrence after surgery in multiple mouse models. Mechanistically, poly(I:C) induces a transient interferon alpha (IFNα) response, reshaping the tumor/wound microenvironment by attracting inflammatory monocytes and depleting regulatory T cells. We demonstrate that a pre-existing IFN signature predicts response to the poly(I:C) hydrogel, which sensitizes tumors to immune checkpoint therapy. The safety, immunogenicity, and surgical feasibility are confirmed in a veterinary trial in canine soft tissue tumors. The surgically optimized poly(I:C)-loaded hydrogel provides a safe and effective approach to prevent cancer recurrence.

Evaluating Distribution of Foveal Avascular Zone Parameters Corrected by Lateral Magnification and Their Associations with Retinal Thickness.

Purpose: To examine the distribution of foveal avascular zone (FAZ) parameters, with and without correction for lateral magnification, in a large cohort of healthy young adults. Design: Cross-sectional, observational cohort study. Participants: A total of 504 healthy adults, 27 to 30 years of age. Methods: Participants underwent a comprehensive ophthalmic examination including axial length measurement and OCT angiography (OCTA) imaging of the macula. OCT angiography images of combined superficial and deep retinal vessel plexuses were processed via a custom software to extract foveal avascular zone area (FAZA) and foveal density-300 (FD-300), the vessel density in a 300-µm wide annulus surrounding the FAZ, with and without correction for lateral magnification. Bland-Altman analyses were performed to examine the effect of lateral magnification on FAZA and FD-300, as well as to evaluate the interocular agreement in both parameters. Linear mixed-effects models were used to examine the relationship between retinal thicknesses and OCTA parameters. Main Outcome Measures: The FAZA and FD-300, corrected for lateral magnification. Results: The mean (standard deviation [SD]) of laterally corrected FAZA and FD-300 was 0.22 mm2 (0.10 mm2) and 51.9% (3.2%), respectively. Relative to uncorrected data, 55.6% of corrected FAZA showed a relative change > 5%, whereas all FD-300 changes were within 5%. There was good interocular symmetry (mean right eye-left eye difference, 95% limits of agreement [LoA]) in both FAZA (0.006 mm2, -0.05 mm2, to 0.07 mm2) and FD-300 (-0.05%, -5.39%, to 5.30%). There were significant negative associations between central retinal thickness and FAZA (ß = -0.0029), as well as between central retinal thickness and FD-300 (ß = -0.044), with the relationships driven by inner, not outer, retina. Conclusions: We reported lateral magnification adjusted normative values for FAZA and FD-300 in a large cohort of young, healthy eyes. Clinicians should strongly consider accounting for lateral magnification when evaluating FAZA. Good interocular agreement in FAZA and FD-300 suggests the contralateral eye can be used as control data.

Biomechanical assessment of chronic liver injury using quantitative micro-elastography.

Hepatocellular carcinoma is one of the most lethal cancers worldwide, causing almost 700,000 deaths annually. It mainly arises from cirrhosis, which, in turn, results from chronic injury to liver cells and corresponding fibrotic changes. Although it is known that chronic liver injury increases the elasticity of liver tissue, the role of increased elasticity of the microenvironment as a possible hepatocarcinogen is yet to be investigated. One reason for this is the paucity of imaging techniques capable of mapping the micro-scale elasticity variation in liver and correlating that with cancerous mechanisms on the cellular scale. The clinical techniques of ultrasound elastography and magnetic resonance elastography typically do not provide micro-scale resolution, while atomic force microscopy can only assess the elasticity of a limited number of cells. We propose quantitative micro-elastography (QME) for mapping the micro-scale elasticity of liver tissue into images known as micro-elastograms, and therefore, as a technique capable of correlating the micro-environment elasticity of tissue with cellular scale cancerous mechanisms in liver. We performed QME on 13 freshly excised healthy and diseased mouse livers and present micro-elastograms, together with co-registered histology, in four representative cases. Our results indicate a significant increase in the mean (×6.3) and standard deviation (×6.0) of elasticity caused by chronic liver injury and demonstrate that the onset and progression of pathological features such as fibrosis, hepatocyte damage, and immune cell infiltration correlate with localized variations in micro-elastograms.

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.

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.

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.

Three-dimensional mechanical characterization of murine skeletal muscle using quantitative micro-elastography.

Skeletal muscle function is governed by both the mechanical and structural properties of its constituent tissues, which are both modified by disease. Characterizing the mechanical properties of skeletal muscle tissue at an intermediate scale, i.e., between that of cells and organs, can provide insight into diseases such as muscular dystrophies. In this study, we use quantitative micro-elastography (QME) to characterize the micro-scale elasticity of ex vivo murine skeletal muscle in three-dimensions in whole muscles. To address the challenge of achieving high QME image quality with samples featuring uneven surfaces and geometry, we encapsulate the muscles in transparent hydrogels with flat surfaces. Using this method, we study aging and disease in quadriceps tissue by comparing normal wild-type (C57BL/6J) mice with dysferlin-deficient BLAJ mice, a model for the muscular dystrophy dysferlinopathy, at 3, 10, and 24 months of age (sample size of three per group). We observe a 77% decrease in elasticity at 24 months in dysferlin-deficient quadriceps compared to wild-type quadriceps.

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.

Smartphone-based optical palpation: towards elastography of skin for telehealth applications.

Smartphones are now integral to many telehealth services that provide remote patients with an improved diagnostic standard of care. The ongoing management of burn wounds and scars is one area in which telehealth has been adopted, using video and photography to assess the repair process over time. However, a current limitation is the inability to evaluate scar stiffness objectively and repeatedly: an essential measurement for classifying the degree of inflammation and fibrosis. Optical elastography detects mechanical contrast on a micrometer- to millimeter-scale, however, typically requires expensive optics and bulky imaging systems, making it prohibitive for wide-spread adoption in telehealth. More recently, a new variant of optical elastography, camera-based optical palpation, has demonstrated the capability to perform elastography at low cost using a standard digital camera. In this paper, we propose smartphone-based optical palpation, adapting camera-based optical palpation by utilizing a commercially available smartphone camera to provide sub-millimeter resolution imaging of mechanical contrast in scar tissue in a form factor that is amenable to telehealth. We first validate this technique on a silicone phantom containing a 5 × 5 × 1 mm3 embedded inclusion, demonstrating comparative image quality between mounted and handheld implementations. We then demonstrate preliminary in vivo smartphone-based optical palpation by imaging a region of healthy skin and two scars on a burns patient, showing clear mechanical contrast between regions of scar tissue and healthy tissue. This study represents the first implementation of elastography on a smartphone device, extending the potential application of elastography to telehealth.

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.

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.

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.

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.