Visualizing kinetics of diffusional penetration in tissues using OCT-based strain imaging.

We report a new application of the recently developed technique, Optical Coherence Elastography (OCE) to quantitatively visualize kinetics of osmotic strains due to diffusive penetration of various osmotically active solutions into biological tissues. The magnitude of osmotic strains may range from fractions of one per cent to tens per cent. The visualized spatio-tempotal dynamics of the strains reflect the rates of osmotic dehydration and diffusional penetration of the active solute, which can be controlled by concentration of the solution components.

Geophysics-Inspired Nonlinear Stress-Strain Law for Biological Tissues and Its Applications in Compression Optical Coherence Elastography.

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.

K-Space Approach in Optical Coherence Tomography: Rigorous Digital Transformation of Arbitrary-Shape Beams, Aberration Elimination and Super-Refocusing beyond Conventional Phase Correction Procedures.

For the most popular method of scan formation in Optical Coherence Tomography (OCT) based on plane-parallel scanning of the illuminating beam, we present a compact but rigorous K-space description in which the spectral representation is used to describe both the axial and lateral structure of the illuminating/received OCT signals. Along with the majority of descriptions of OCT-image formation, the discussed approach relies on the basic principle of OCT operation, in which ballistic backscattering of the illuminating light is assumed. This single-scattering assumption is the main limitation, whereas in other aspects, the presented approach is rather general.

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.

New Neutralizing Epitope Exposed on the Domain II of Tick-Borne Encephalitis Virus Envelope Glycoprotein E.

, formerly tick-borne encephalitis virus (TBEV), belongs to the genus. TBEV is transmitted by tick bites and infection with TBEV can lead to serious disorders of the central nervous system. In this study, a new protective monoclonal mouse antibody (mAb) FVN-32, with high binding activity to glycoprotein E of TBEV, was selected and examined in post exposure prophylaxis in a mouse model of TBEV infection.

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.

Application of compression optical coherence elastography for characterization of human pericardium: A pilot study.

The recent impressive progress in Compression Optical Coherence Elastography (C-OCE) demonstrated diverse biomedical applications, comprising ophthalmology, oncology, etc. High resolution of C-OCE enables spatially resolved characterization of elasticity of rather thin (thickness < 1 mm) samples, which previously was impossible. Besides Young's modulus, C-OCE enables obtaining of nonlinear stress-strain dependences for various tissues.

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.

Optical Coherence Elastography as a Tool for Studying Deformations in Biomaterials: Spatially-Resolved Osmotic Strain Dynamics in Cartilaginous Samples.

This paper presents a recently developed variant of phase-resolved Optical Coherence Elastography (OCE) enabling non-contact visualization of transient local strains of various origins in biological tissues and other materials. In this work, we demonstrate the possibilities of this new technique for studying dynamics of osmotically-induced strains in cartilaginous tissue impregnated with optical clearing agents (OCA). For poroelastic water-containing biological tissues, application of non-isotonic OCAs, various contrast additives, as well as drug solutions administration, may excite transient spatially-inhomogeneous strain fields of high magnitude in the tissue bulk, initiating mechanical and structural alterations.

Simulating scan formation in multimodal optical coherence tomography: angular-spectrum formulation based on ballistic scattering of arbitrary-form beams.

We present a computationally highly efficient full-wave spectral model of OCT-scan formation with the following features: allowance of arbitrary phase-amplitude profile of illuminating beams; absence of paraxial approximation; utilization of broadly used approximation of ballistic scattering by discrete scatterers without limitations on their density/location and scattering strength. The model can easily incorporate the wave decay, dispersion, measurement noises with given signal-to-noise ratios and arbitrary inter-scan displacements of scatterers. We illustrate several of such abilities, including comparative simulations of OCT-scans for Bessel versus Gaussian beams, presence of arbitrary aberrations at the tissue boundary and various scatterer motions.

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.

In vivo multimodal optical imaging of dermoscopic equivocal melanocytic skin lesions.

There is a wide range of equivocal melanocytic lesions that can be clinically and dermoscopically indistinguishable from early melanoma. In the present work, we assessed the possibilities of combined using of multiphoton microscopy (MPM) and optical coherence angiography (OCA) for differential diagnosis of the equivocal melanocytic lesions. Clinical and dermoscopic examinations of 60 melanocytic lesions revealed 10 benign lesions and 32 melanomas, while 18 lesions remained difficult to diagnose.

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).

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.

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.

Characterization of neutralizing monoclonal antibody against tick-borne encephalitis virus in vivo.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen in the family Flaviviridae and causes one of the most severe human neuroinfections. In this study, a neutralizing mouse mAb 14D5, which was previously shown to have cross-reactive binding to several flaviviruses belonging to the TBEV group, was examined for its prophylactic and therapeutic effects in BALB/c mice infected with TBEV. Before and after infection, mice were administrated mAb 14D5 at doses 100 μg and 10 μg per mouse.

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.

Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study.

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection.

Interplay of temperature, thermal-stresses and strains in laser-assisted modification of collagenous tissues: Speckle-contrast and OCT-based studies.

Moderate heating of collagenous tissues such as cartilage and cornea by infrared laser irradiation can produce biologically nondestructive structural rearrangements and relaxation of internal stresses resulting in the tissue reshaping. The reshaping results and eventual changes in optical and biological properties of the tissue strongly depend on the laser-irradiation regime. Here, a speckle-contrast technique based on monochromatic illumination of the tissue in combination with strain mapping by means of optical coherence elastography (OCE) is applied to reveal the interplay between the temperature and thermal stress fields producing tissue modifications.

Analysis of low-scattering regions in optical coherence tomography: applications to neurography and lymphangiography.

Analysis of semi-transparent low scattering biological structures in optical coherence tomography (OCT) has been actively pursued in the context of lymphatic imaging, with most approaches relying on the relative absence of signal as a means of detection. Here we present an alternate methodology based on spatial speckle statistics, utilizing the similarity of a distribution of given voxel intensities to the power distribution function of pure noise, to visualize the low-scattering biological structures of interest. In a human tumor xenograft murine model, we show that these correspond to lymphatic vessels and nerves; extensive histopathologic validation studies are reported to unequivocally establish this correspondence.

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.

Accurate early prediction of tumour response to PDT using optical coherence angiography.

Prediction of tumour treatment response may play a crucial role in therapy selection and optimization of its delivery parameters. Here we use optical coherence angiography (OCA) as a minimally-invasive, label-free, real-time bioimaging method to visualize normal and pathological perfused vessels and monitor treatment response following vascular-targeted photodynamic therapy (PDT). Preclinical results are reported in a convenient experimental model (CT-26 colon tumour inoculated in murine ear), enabling controlled PDT and post-treatment OCA monitoring.

Revealing structural modifications in thermomechanical reshaping of collagenous tissues using optical coherence elastography.

Moderate heating of such collagenous tissues as cornea and cartilages by infra-red laser (IR laser) irradiation is an emerging technology for nondestructive modification of the tissue shape and microstructure for a variety of applications in ophthalmology, otolaryngology and so on. Postirradiation high-resolution microscopic examination indicates the appearance of microscopic either spheroidal or crack-like narrow pores depending on the tissue type and irradiation regime. Such examinations usually require special tissue preparation (eg, staining, drying that affect microstructure themselves) and are mostly suitable for studying individual pores, whereas evaluation of their averaged parameters, especially in situ, is challenging.