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Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young’s elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies.

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

We propose a nonlinear stress–strain law to describe nonlinear elastic properties of biological tissues using an analogy with the derivation of nonlinear constitutive laws for cracked rocks. The derivation of such a constitutive equation has been stimulated by the recently developed experimental technique—quasistatic Compression Optical Coherence Elastography (C-OCE). C-OCE enables obtaining nonlinear stress–strain dependences relating the applied uniaxial compressive stress and the axial component of the resultant strain in the tissue. To adequately describe nonlinear stress–strain dependences obtained with C-OCE for various tissues, the central idea is that, by analogy with geophysics, nonlinear elastic response of tissues is mostly determined by the histologically confirmed presence of interstitial gaps/pores resembling cracks in rocks. For the latter, the nonlinear elastic response is mostly determined by elastic properties of narrow cracks that are highly compliant and can easily be closed by applied compressing stress. The smaller the aspect ratio of such a gap/crack, the smaller the stress required to close it. Upon reaching sufficiently high compressive stress, almost all such gaps become closed, so that with further increase in the compressive stress, the elastic response of the tissue becomes nearly linear and is determined by the Young's modulus of the host tissue. The form of such a nonlinear dependence is determined by the distribution of the cracks/gaps over closing pressures; for describing this process, an analogy with geophysics is also used. After presenting the derivation of the proposed nonlinear law, we demonstrate that it enables surprisingly good fitting of experimental stress–strain curves obtained with C-OCE for a broad range of various tissues. Unlike empirical fitting, each of the fitting parameters in the proposed law has a clear physical meaning. The linear and nonlinear elastic parameters extracted using this law have already demonstrated high diagnostic value, e.g., for differentiating various types of cancerous and noncancerous tissues. [ABSTRACT FROM AUTHOR]

Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young's elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies. [ABSTRACT FROM AUTHOR]

We report a new application of compression optical coherence elastography (C‐OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small‐intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C‐OCE successfully estimated stiffness for each intestine‐wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C‐OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE‐revealed damaging and absence of tissue damage for ~15% elongation. Thus, C‐OCE has demonstrated a high potential for determining the safety tissue‐stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures. [ABSTRACT FROM AUTHOR]

Abstract We present a non-invasive (albeit contact) method based on Optical Coherence Elastography (OCE) enabling the in vivo segmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. The method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young’s modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the "gold-standard" histological data and the OCE-based stiffness map for the corresponding tissue regions. After such pre-calibration, the results of morphological segmentation of OCE-images demonstrate a striking similarity with the histological results in terms of percentage of the segmented zones. To validate the sensitivity of the OCE-method and demonstrate its high correlation with conventional histological segmentation we present results obtained in vivo on a murine model of breast cancer in comparative experimental study of the efficacy of two antitumor chemotherapeutic drugs with different mechanisms of action. The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentation of histological images. Numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.

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 < 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 < 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.

Optical coherence elastography (OCE) demonstrated impressive abilities for diagnosing tissue types/states using differences in their biomechanics. Usually, OCE visualizes tissue deformation induced by some additional stimulus (e.g., contact compression or auxiliary elastic‐wave excitation). We propose a new variant of OCE with osmotically induced straining (OIS‐OCE) and demonstrate its application to assess various stages of proteoglycan content degradation in cartilage. The information‐bearing signatures in OIS‐OCE are the magnitude and rate of strains caused by the application of osmotically active solutions onto the sample surface. OCE examination of the induced strains does not require special tissue preparation, the osmotic stimulation is highly reproducible, and strains are observed in noncontact mode. Several minutes suffice to obtain a conclusion. These features are promising for intraoperative method usage when express assessment of tissue state is required during surgical operations. The "waterfall" images demonstrate the development of cumulative osmotic strains in control and degraded cartilage samples. [ABSTRACT FROM AUTHOR]

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.

The possibility to assess molecular-biological and morphological features of particular breast cancer types can improve the precision of resection margin detection and enable accurate determining of the tumor aggressiveness, which is important for treatment selection. To enable reliable differentiation of breast-cancer subtypes and evaluation of resection margin, without performing conventional histological procedures, here we apply cross-polarization optical coherence tomography (CP-OCT) and compare it with a novel variant of compressional optical coherence elastography (C-OCE) in terms of the diagnostic accuracy (Ac) with histological verification. The study used 70 excised breast cancer specimens with different morphological structure and molecular status (Luminal A, Luminal B, Her2/Neo+, non-luminal and triple-negative cancer). Our first aim was to formulate convenient criteria of visual assessment of CP-OCT and C-OCE images intended (i) to differentiate tumorous and non-tumorous tissues and (ii) to enable more precise differentiation among different malignant states. We identified such criteria based on the presence of heterogeneities and characteristics of signal attenuation in CP-OCT images, as well as the presence of inclusions/mosaic structures combined with visually feasible assessment of several stiffness grades in C-OCE images. Secondly, we performed a blinded reader study of the Ac of C-OCE versus CP-OCT, for delineation of tumorous versus non-tumorous tissues followed by identification of breast cancer subtypes. For tumor detection, C-OCE showed higher specificity than CP-OCT (97.5% versus 93.3%) and higher Ac (96.0 versus 92.4%). For the first time, the Ac of C-OCE and CP-OCT were evaluated for differentiation between non-invasive and invasive breast cancer (90.4% and 82.5%, respectively). Furthermore, for invasive cancers, the difference between invasive but low-aggressive and highly-aggressive subtypes can be detected. For differentiation between non-tumorous tissue and low-aggressive breast-cancer subtypes, Ac was 95.7% for C-OCE and 88.1% for CP-OCT. For differentiation between non-tumorous tissue and highly-aggressive breast cancers, Ac was found to be 98.3% for C-OCE and 97.2% for CP-OCT. In all cases C-OCE showed better diagnostic parameters independently of the tumor type. These findings confirm the high potential of OCT-based examinations for rapid and accurate diagnostics during breast conservation surgery.

In this paper, we point out some practical obstacles arising in realization of compressional optical coherence elastography (OCE) that have not attracted sufficient attention previously. Specifically, we discuss (i) complications in quantification of the Young modulus of tissues related to partial adhesion between the OCE probe and soft intervening reference layer sensor, (ii) distorting influence of tissue surface curvature/corrugation on the subsurface strain distribution mapping, (iii) ways of signal-to-noise ratio (SNR) enhancement in OCE strain mapping when periodic averaging is not realized, and (iv) potentially significant influence of tissue elastic nonlinearity on quantification of its stiffness. Potential practical approaches to mitigate the effects of these complications are also described.