Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study.

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.

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.

Detection of acute and early-delayed radiation-induced changes in the white matter of the rat brain based on numerical processing of optical coherence tomography data.

Detection of radiation-induced changes of the brain white matter is important for brain neoplasms repeated surgery. We investigated the influence of irradiation on the scattering properties of the white matter using optical coherence tomography (OCT). Healthy Wistar rats undergone the irradiation of the brain right hemisphere. At seven time points from the irradiation procedure (2-14 weeks), an ex vivo OCT study was performed with subsequent calculation of attenuation coefficient values in the corpus callosum followed by immunohistochemical analysis. As a result, we discovered acute and early-delayed changes characterized by the edema of different severity, accompanied by a statistically significant decrease in attenuation coefficient values. In particular, these changes were found at 2 weeks after irradiation in the irradiated hemisphere, while at 6- and 12-week time points they affected both irradiated and contralateral hemisphere. Thus, radiation-induced changes occurring in white matter during the first 3 months after irradiation can be detected by OCT.

Depth-Resolved Attenuation Mapping of the Vaginal Wall under Prolapse and after Laser Treatment Using Cross-Polarization Optical Coherence Tomography: A Pilot Study.

Vaginal wall prolapse is the most common type of pelvic organ prolapse and is mainly associated with collagen bundle changes in the lamina propria. Neodymium (Nd:YAG) laser treatment was used as an innovative, minimally invasive and non-ablative procedure for the treatment of early-stage vaginal wall prolapse. The purpose of this pilot study was to assess connective tissue changes in the vaginal wall under prolapse without treatment and after Nd:YAG laser treatment using cross-polarization optical coherence tomography (CP OCT) with depth-resolved attenuation mapping. A total of 26 freshly excised samples of vaginal wall from 26 patients with age norm (n = 8), stage I-II prolapses without treatment (n = 8) and stage I-II prolapse 1-2 months after Nd:YAG laser treatment (n = 10) were assessed. As a result, for the first time, depth-resolved attenuation maps of the vaginal wall in the B-scan projection in the co- and cross-polarization channels were constructed. Two parameters within the lamina propria were target calculated: the median value and the percentages of high (≥4 mm-1) and low (<4 mm-1) attenuation coefficient values. A significant (p < 0.0001) decrease in the parameters in the case of vaginal wall prolapse compared to the age norm was identified. After laser treatment, a significant (p < 0.0001) increase in the parameters compared to the normal level was also observed. Notably, in the cross-channel, both parameters showed a greater difference between the groups than in the co-channel. Therefore, using the cross-channel achieved more reliable differentiation between the groups. To conclude, attenuation coefficient maps allow visualization and quantification of changes in the condition of the connective tissue of the vaginal wall. In the future, CP OCT could be used for in vivo detection of early-stage vaginal wall prolapse and for monitoring the effectiveness of treatment.

Multimodal OCT Control for Early Histological Signs of Vulvar Lichen Sclerosus Recurrence after Systemic PDT: Pilot Study.

Photodynamic therapy (PDT) is a modern treatment for severe or treatment-resistant vulvar lichen sclerosus (VLS). The chronic and recurrent nature of VLS requires control of recurrences at an early stage. In this paper, a non-invasive multimodal optical coherence tomography (OCT) method was used to control for early histological signs of VLS recurrence after systemic PDT using Photodithazine®. To interpret the OCT data, a histological examination was performed before PDT and 3 months after PDT. Two groups of patients were identified: with early histological signs of VLS recurrence (Group I, n = 5) and without histological signs of VLS recurrence (Group II, n = 6). We use structural OCT, OCT angiography, and OCT lymphangiography throughout 6 months after PDT to visually assess the skin components and to quantitatively assess the dermis by calculating the depth-resolved attenuation coefficient and the density of blood and lymphatic vessels. The OCT data assessment showed a statistically significant difference between the patient groups 3 months after PDT. In Group II, all the studied OCT parameters reached maximum values by the 3rd month after PDT, which indicated recovery of the skin structure. At the same time, in Group I, the values of OCT parameters did not approach the values those in Group II even after 6 months. The obtained results of multimodal OCT can be used for non-invasive control of early histological recurrence of VLS after systemic PDT and for adjusting treatment tactics in advance, without waiting for new clinical manifestations of the disease.

Depth-resolved method for attenuation coefficient calculation from optical coherence tomography data for improved biological structure visualization.

Optical coherence tomography (OCT) is a promising tool for intraoperative tissue morphology determination. Several studies suggest that attenuation coefficient derived from the OCT images, can differentiate between tissues of different morphology, such as normal and pathological structures of the brain, skin, and other tissues. In the present study, the depth-resolved method for attenuation coefficient calculation was adopted for the real-world situation of the depth-dependent OCT sensitivity and additive imaging noise with nonzero mean. It was shown that in the case of sharp focusing (~10 µm spot full width at half maximum [FWHM] or smaller at 1.3 µm central wavelength) only the proposed method for depth-dependent sensitivity compensation does not introduce misleading artifacts into the calculated attenuation coefficient distribution. At the same time, the scanning beam focus spot with FWHM greater than 10 µm at 1.3 µm central wavelength allows one to use multiple approaches to the attenuation coefficient calculation without introducing noticeable bias. This feature may hinder the need for robust corrections for the depth-resolved attenuation coefficient estimations from the community.

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.

Intraoperative Assessment of Breast Cancer Tissues after Breast-Conserving Surgery Based on Mapping the Attenuation Coefficients in 3D Cross-Polarization Optical Coherence Tomography.

Intraoperative differentiation of tumorous from non-tumorous tissue can help in the assessment of resection margins in breast cancer and its response to therapy and, potentially, reduce the incidence of tumor recurrence. In this study, the calculation of the attenuation coefficient and its color-coded 2D distribution was performed for different breast cancer subtypes using spectral-domain CP OCT. A total of 68 freshly excised human breast specimens containing tumorous and surrounding non-tumorous tissues after BCS was studied. Immediately after obtaining structural 3D CP OCT images, en face color-coded attenuation coefficient maps were built in co-(Att(co)) and cross-(Att(cross)) polarization channels using a depth-resolved approach to calculating the values in each A-scan. We determined spatially localized signal attenuation in both channels and reported ranges of attenuation coefficients to five selected breast tissue regions (adipose tissue, non-tumorous fibrous connective tissue, hyalinized tumor stroma, low-density tumor cells in the fibrotic tumor stroma and high-density clusters of tumor cells). The Att(cross) coefficient exhibited a stronger gain contrast of studied tissues compared to the Att(co) coefficient (i.e., conventional attenuation coefficient) and, therefore, allowed improved differentiation of all breast tissue types. It has been shown that color-coded attenuation coefficient maps may be used to detect inter- and intra-tumor heterogeneity of various breast cancer subtypes as well as to assess the effectiveness of therapy. For the first time, the optimal threshold values of the attenuation coefficients to differentiate tumorous from non-tumorous breast tissues were determined. Diagnostic testing values for Att(cross) coefficient were higher for differentiation of tumor cell areas and tumor stroma from non-tumorous fibrous connective tissue: diagnostic accuracy was 91-99%, sensitivity-96-98%, and specificity-87-99%. Att(co) coefficient is more suitable for the differentiation of tumor cell areas from adipose tissue: diagnostic accuracy was 83%, sensitivity-84%, and specificity-84%. Therefore, the present study provides a new diagnostic approach to the differentiation of breast cancer tissue types based on the assessment of the attenuation coefficient from real-time CP OCT data and has the potential to be used for further rapid and accurate intraoperative assessment of the resection margins during BCS.

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.

Nondestructive label-free detection of peritumoral white matter damage using cross-polarization optical coherence tomography.

Introduction: To improve the quality of brain tumor resections, it is important to differentiate zones with myelinated fibers destruction from tumor tissue and normal white matter. Optical coherence tomography (OCT) is a promising tool for brain tissue visualization and in the present study, we demonstrate the ability of cross-polarization (CP) OCT to detect damaged white matter and differentiate it from normal and tumor tissues. Materials and methods: The study was performed on 215 samples of brain tissue obtained from 57 patients with brain tumors. The analysis of the obtained OCT data included three stages: 1) visual analysis of structural OCT images; 2) quantitative assessment based on attenuation coefficients estimation in co- and cross-polarizations; 3) building of color-coded maps with subsequent visual analysis. The defining characteristics of structural CP OCT images and color-coded maps were determined for each studied tissue type, and then two classification tests were passed by 8 blinded respondents after a training. Results: Visual assessment of structural CP OCT images allows detecting white matter areas with damaged myelinated fibers and differentiate them from normal white matter and tumor tissue. Attenuation coefficients also allow distinguishing all studied brain tissue types, while it was found that damage to myelinated fibers leads to a statistically significant decrease in the values of attenuation coefficients compared to normal white matter. Nevertheless, the use of color-coded optical maps looks more promising as it combines the objectivity of optical coefficient and clarity of the visual assessment, which leads to the increase of the diagnostic accuracy of the method compared to visual analysis of structural OCT images. Conclusions: Alteration of myelinated fibers causes changes in the scattering properties of the white matter, which gets reflected in the nature of the received CP OCT signal. Visual assessment of structural CP OCT images and color-coded maps allows differentiating studied tissue types from each other, while usage of color-coded maps demonstrates higher diagnostic accuracy values in comparison with structural images (F-score = 0.85-0.86 and 0.81, respectively). Thus, the results of the study confirm the potential of using OCT as a neuronavigation tool during resections of brain tumors.

Optical Coherence Tomography Angiography of the Intestine: How to Prevent Motion Artifacts in Open and Laparoscopic Surgery?

(1) Introduction. The problem that limits the intraoperative use of OCTA for the intestinal circulation diagnostics is the low informative value of OCTA images containing too many motion artifacts. The aim of this study is to evaluate the efficiency and safety of the developed unit for the prevention of the appearance of motion artifacts in the OCTA images of the intestine in both open and laparoscopic surgery in the experiment; (2) Methods. A high-speed spectral-domain multimodal optical coherence tomograph (IAP RAS, Russia) operating at a wavelength of 1310 nm with a spectral width of 100 µm and a power of 2 mW was used. The developed unit was tested in two groups of experimental animals-on minipigs (group I, n = 10, open abdomen) and on rabbits (group II, n = 10, laparoscopy). Acute mesenteric ischemia was modeled and then 1 h later the small intestine underwent OCTA evaluation. A total of 400 OCTA images of the intact and ischemic small intestine were obtained and analyzed. The quality of the obtained OCTA images was evaluated based on the score proposed in 2020 by the group of Magnin M. (3) Results. Without stabilization, OCTA images of the intestine tissues were informative only in 32-44% of cases in open surgery and in 14-22% of cases in laparoscopic surgery. A vacuum bowel stabilizer with a pressure deficit of 22-25 mm Hg significantly reduced the number of motion artifacts. As a result, the proportion of informative OCTA images in open surgery increased up to 86.5% (Χ2 = 200.2, p = 0.001), and in laparoscopy up to 60% (Χ2 = 148.3, p = 0.001). (4) Conclusions. The used vacuum tissue stabilizer enabled a significant increase in the proportion of informative OCTA images by significantly reducing the motion artifacts.

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.

Multiphoton microscopy assessment of the structure and variability changes of dermal connective tissue in vulvar lichen sclerosus: A pilot study.

In this article, we offer a novel classification of progressive changes in the connective tissue of dermis in vulvar lichen sclerosus (VLS) relying on quantitative assessment of the second harmonic generation (SHG) signal received from formalin fixed and deparaffinized tissue sections. We formulate criteria for distinguishing four degrees of VLS development: Initial-Mild-Moderate-Severe. Five quantitative characteristics (length and thickness type I Collagen fibers, Mean SHG signal intensity, Skewness and Coherence SHG signal) are used to describe the sequential degradation of connective tissue (changes in the structure, orientation, shape and density of collagen fibers) up to the formation of specific homogeneous masses. Each of the degrees has a characteristic set of quantitatively expressed features. We focus on the identification and description of early, initial changes of the dermis as the least specific. The results obtained by us and the proposed classification of the degrees of the disease can be used to objectify the dynamics of tissue changes during treatment.

Brain white matter morphological structure correlation with its optical properties estimated from optical coherence tomography (OCT) data.

A pilot post-mortem study identifies a strong correlation between the attenuation coefficient estimated from the OCT data and some morphological features of the sample, namely the number of nuclei in the field of view of the histological image and the fiber structural parameter introduced in the study to quantify the difference in the myelinated fibers arrangements. The morphological features were identified from the histopathological images of the sample taken from the same locations as the OCT images and stained with the immunohistochemical (IHC) staining specific to the myelin. It was shown that the linear regression of the IHC quantitative characteristics allows adequate prediction of the attenuation coefficient of the sample. This discovery opens the opportunity for the usage of the OCT as a neuronavigation tool.

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.

OCT-Guided Surgery for Gliomas: Current Concept and Future Perspectives.

Optical coherence tomography (OCT) has been recently suggested as a promising method to obtain in vivo and real-time high-resolution images of tissue structure in brain tumor surgery. This review focuses on the basics of OCT imaging, types of OCT images and currently suggested OCT scanner devices and the results of their application in neurosurgery. OCT can assist in achieving intraoperative precision identification of tumor infiltration within surrounding brain parenchyma by using qualitative or quantitative OCT image analysis of scanned tissue. OCT is able to identify tumorous tissue and blood vessels detection during stereotactic biopsy procedures. The combination of OCT with traditional imaging such as MRI, ultrasound and 5-ALA fluorescence has the potential to increase the safety and accuracy of the resection. OCT can improve the extent of resection by offering the direct visualization of tumor with cellular resolution when using microscopic OCT contact probes. The theranostic implementation of OCT as a part of intelligent optical diagnosis and automated lesion localization and ablation could achieve high precision, automation and intelligence in brain tumor surgery. We present this review for the increase of knowledge and formation of critical opinion in the field of OCT implementation in brain tumor surgery.

Lymph vessels visualization from optical coherence tomography data using depth-resolved attenuation coefficient calculation.

Multimodal optical coherent tomography grows popularity with researchers and clinicians over the past decade. One of the modalities is lymphangiography, which allows visualization of the lymphatic vessel networks within optical coherence tomography (OCT) imaging volume. In the present study, it is shown that lymphatic vessel visualization obtained from the depth-resolved attenuation coefficient distributions, corrected for the noise, shows improved contrast and detail in comparison with previously proposed approaches. We also argue that the two most popular approaches for lymphatic vessel visualization, namely simple intensity thresholding and vesselness calculation based on local Hessian matrix eigenvalues, imply different definitions of the lymphatic vessel's appearance in the OCT volume and lead to the different networks.

Prospects of Intraoperative Multimodal OCT Application in Patients with Acute Mesenteric Ischemia.

INTRODUCTION: Despite the introduction of increasingly multifaceted diagnostic techniques and the general advances in emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). METHODS AND PARTICIPANTS: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), whereby the ischemic segments of the intestine were examined. Nine others were operated on for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. RESULTS: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT images of non-ischemic (control group), viable ischemic, and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations, and the type and density of the vasculature. CONCLUSION: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Multiphoton tomography in differentiation of morphological and molecular subtypes of breast cancer: A quantitative analysis.

In this study multiphoton tomography, based on second harmonic generation (SHG), and two-photon-excited fluorescence (TPEF) was used to visualize both the extracellular matrix and tumor cells in different morphological and molecular subtypes of human breast cancer. It was shown, that quantified assessment of the SHG based imaging data has great potential to reveal differences of collagen quantity, organization and uniformity in both low- and highly- aggressive invasive breast cancers. The values of quantity and uniformity of the collagen fibers distribution were significantly higher in low-aggressive breast cancer compared to the highly-aggressive subtypes, while the value representing collagen organization was lower in the former type. Additionally, it was shown, that TPEF detection of elastin fibers and amyloid protein may be used as a biomarker of detection the low-aggressive breast cancer subtype. Thus, TPEF/SHG imaging offers the possibility of becoming a useful tool for the rapid diagnosis of various subtypes of breast cancer during biopsy as well as for the intraoperative determinination of tumor-positive resection margins.

Diagnostic Accuracy of Cross-Polarization OCT and OCT-Elastography for Differentiation of Breast Cancer Subtypes: Comparative Study.

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.