Effects of FOLFOX Chemotherapy on Tumor Oxygenation and Perfused Vasculature: An In Vivo Study by Optical Techniques.

The effects of cytotoxic chemotherapy on tumor vasculature and oxygenation are in the focus of modern investigations because vascular structure and distribution of oxygen influence tumor behavior and treatment response. The aim of our study was to monitor changes in the vascular component of colorectal tumor xenografts induced by a clinical combination of chemotherapy drugs FOLFOX in vivo using two complementary techniques: diffuse reflectance spectroscopy (DRS) and optical coherence tomography-based microangiography (OCT-MA). These techniques revealed a slower decrease in tumor blood oxygenation in treated tumors as compared to untreated ones, faster suppression of tumor vasculature perfusion and increase in water content as a result of treatment, and decrease in total hemoglobin in untreated tumors.

Quantitative Assessment of Polarization and Elastic Properties of Endometrial Tissue for Precancer/Cancer Diagnostics Using Multimodal Optical Coherence Tomography.

: 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. : In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection.

The Effect of Cryotherapy on Buccal Blood Vessels Evaluated by Optical Coherence Tomography Angiography: A Pilot Study.

While cryotherapy is one of the traditional ways to reduce postoperative complications in maxillofacial surgery, the cooling degree is not regulated in most cases and the achieved effect is not properly controlled. Therefore, to develop optimal cooling modes, we propose to study the buccal vascular response to cooling, which has not been previously shown. To evaluate the effect of cooling, we analyzed vessel networks using optical coherence tomography angiography (OCT-A).

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.

Effects of Photodynamic Therapy on Tumor Metabolism and Oxygenation Revealed by Fluorescence and Phosphorescence Lifetime Imaging.

This work was aimed at the complex analysis of the metabolic and oxygen statuses of tumors in vivo after photodynamic therapy (PDT). Studies were conducted on mouse tumor model using two types of photosensitizers-chlorin e6-based drug Photoditazine predominantly targeted to the vasculature and genetically encoded photosensitizer KillerRed targeted to the chromatin. Metabolism of tumor cells was assessed by the fluorescence lifetime of the metabolic redox-cofactor NAD(P)H, using fluorescence lifetime imaging.

Oxygen Assessment in Tumors In Vivo Using Phosphorescence Lifetime Imaging Microscopy.

The oxygen level in a tumor is a crucial factor for its development and response to therapies. Phosphorescence lifetime imaging (PLIM) with the use of phosphorescent oxygen probes is a highly sensitive, noninvasive optical technique for the assessment of molecular oxygen in living cells and tissues. Here, we present a protocol for microscopic mapping of oxygen distribution in a mouse tumor model in vivo.

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.

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.

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.

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.

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.

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).

Simultaneous Probing of Metabolism and Oxygenation of Tumors In Vivo Using FLIM of NAD(P)H and PLIM of a New Polymeric Ir(III) Oxygen Sensor.

Tumor cells are well adapted to grow in conditions of variable oxygen supply and hypoxia by switching between different metabolic pathways. However, the regulatory effect of oxygen on metabolism and its contribution to the metabolic heterogeneity of tumors have not been fully explored. In this study, we develop a methodology for the simultaneous analysis of cellular metabolic status, using the fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactor NAD(P)H, and oxygen level, using the phosphorescence lifetime imaging (PLIM) of a new polymeric Ir(III)-based sensor (PIr3) in tumors in vivo.

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 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.

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.

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.

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.

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.

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).

Histological validation of in vivo assessment of cancer tissue inhomogeneity and automated morphological segmentation enabled by Optical Coherence Elastography.

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.

assessment of functional and morphological alterations in tumors under treatment using OCT-angiography combined with OCT-elastography.

Emerging methods of anti-tumor therapies require new approaches to tumor response evaluation, especially enabling label-free diagnostics and utilization. Here, to assess the tumor early reaction and predict its long-term response, for the first time we apply in combination the recently developed OCT extensions - optical coherence angiography (OCA) and compressional optical coherence elastography (OCE), thus enabling complementary functional/microstructural tumor characterization. We study two vascular-targeted therapies of different types, (1) anti-angiogenic chemotherapy (ChT) and (2) photodynamic therapy (PDT), aimed to indirectly kill tumor cells through blood supply injury.

OCT-elastography-based optical biopsy for breast cancer delineation and express assessment of morphological/molecular subtypes.

Application of compressional optical coherence elastography (OCE) for delineation of tumor and peri-tumoral tissue with simultaneous assessment of morphological/molecular subtypes of breast cancer is reported. The approach is based on the ability of OCE to quantitatively visualize stiffness of studied samples and then to perform a kind of OCE-based biopsy by analyzing elastographic B-scans that have sizes ~several millimeters similarly to bioptates used for "gold-standard" histological examinations. The method relies on identification of several main tissue constituents differing in their stiffness in the OCE scans.

Raster-scan optoacoustic angiography of blood vessel development in colon cancer models.

Raster-scan optoacoustic angiography at 532 nm wavelength with 50 μm lateral resolution at 2 mm diagnostic depth was used for quantitative characterization of neoangiogenesis in colon cancer models. Two tumor models of human colon adenocarcinoma (HT-29) and murine colon carcinoma (CT26) different in their histology and vascularization were compared. Tumors of both origins showed an inhomogeneous distribution of areas with high and low vascularization.

Can "Indirect" Contact Laser Surgery be Used for Fluorescence-Image Guided Tumor Resections? Preliminary Results.

Ensuring the complete removal of tumor tissue is the main challenge during resection operations. Recently, a technique of "indirect" contact laser surgery has been developed. In this study we assess the possibility of using such surgery for fluorescence image-guided tumor resection.