Ekaterina A. Sergeeva

Novel algorithm of processing optical coherence tomography images for differentiation of biological tissue pathologies

A numerical algorithm based on a small-angle approximation of the radiative transfer equation (RTE) is developed to reconstruct scattering characteristics of biological tissues from optical coherence tomography (OCT) images. According to the algorithm, biological tissue is considered to be a layered random medium with a set of scattering parameters in each layer: total scattering coefficient, variance of a small-angle scattering phase function, and probability of backscattering, which fully describe the OCT signal behavior versus probing depth. The reconstruction of the scattering parameters is performed by their variation to fit the experimental OCT signal by the theoretical one using a time-saving genetic algorithm. The proposed reconstruction procedure is tested on model media with known scattering parameters. The possibility to estimate scattering parameters from OCT images is studied for various regimes of OCT signal decay. The developed algorithm is applied to reconstruct optical characteristics of epithelium and stroma for normal cervical tissue and its pathologies, and the potential to distinguish between the types of pathological changes in epithelial tissue by its OCT images is demonstrated.

Simulation of optical coherence tomography images by Monte Carlo modeling based on polarization vector approach.

Monte Carlo method is applied for simulation of 2D optical coherence tomography (OCT) images of skin-like model. Layer boundaries in skin model feature curved shape which agrees with physiological structure of human skin. The effect of coherence properties of probing radiation on OCT image formation and speckles in the detected OCT signal is considered. The developed model is employed for image simulation both for conventional and polarization dependent time-domain OCT modalities. Simulation of polarized OCT signal is performed using vector approach developed previously for modeling of electromagnetic field transfer in turbid media.

Perspectives of mid-infrared optical coherence tomography for inspection and micrometrology of industrial ceramics

Optical coherence tomography (OCT) is a promising tool for detecting micro channels, metal prints, defects and delaminations embedded in alumina and zirconia ceramic layers at hundreds of micrometers beneath surfaces. The effect of surface roughness and scattering of probing radiation within sample on OCT inspection is analyzed from the experimental and simulated OCT images of the ceramic samples with varying surface roughnesses and operating wavelengths. By Monte Carlo simulations of the OCT images in the mid-IR the optimal operating wavelength is found to be 4 µm for the alumina samples and 2 µm for the zirconia samples for achieving sufficient probing depth of about 1 mm. The effects of rough surfaces and dispersion on the detection of the embedded boundaries are discussed. Two types of image artefacts are found in OCT images due to multiple reflections between neighboring boundaries and inhomogeneity of refractive index.

Differential diagnosis of human bladder mucosa pathologies in vivo with cross-polarization optical coherence tomography

Quantitative image analysis and parameter extraction using a specific implementation of polarization-sensitive optical coherence tomography (OCT) provides differential diagnosis of mucosal pathologies in in-vivo human bladders. We introduce a cross-polarization (CP) OCT image metric called Integral Depolarization Factor (IDF) to enable automatic diagnosis of bladder conditions (assessment the functional state of collagen fibers). IDF-based diagnostic accuracy of identification of the severe fibrosis of normal bladder mucosa is 79%; recurrence of carcinoma on the post-operative scar is 97%; and differentiation between neoplasia and acute inflammation is 75%. The promising potential of CP OCT combined with image analysis in human urology is thus demonstrated in vivo.

Speckle statistics in OCT images: Monte Carlo simulations and experimental studies

The speckle pattern of an optical coherence tomography (OCT) image carries potentially useful sample information that may assist in tissue characterization. Recent biomedical results in vivo indicate that the distribution of signal intensities within an OCT tissue image is well described by a log-normal-like (Gamma) function. To fully understand and exploit this finding, an OCT Monte Carlo model that accounts for speckle effects was developed. The resultant Monte Carlo speckle statistics predictions agree well with experimental OCT results from a series of control phantoms with variable scattering properties; the Gamma distribution provides a good fit to the theoretical and experimental results. The ability to quantify subresolution tissue features via OCT speckle analysis may prove useful in diagnostic photomedicine.

Optical coherence tomography for quality assessment of embedded microchannels in alumina ceramic

Large-scale and cost-effective manufacturing of ceramic micro devices based on tape stacking requires the development of inspection systems to perform high-resolution in-process quality control of embedded manufactured cavities, metal structures and defects. With an optical coherence tomography (OCT) system operating at 1.3 μm and a dedicated automated line segmentation algorithm, layer thicknesses can be measured and laser-machined channels can be verified in alumina ceramics embedded at around 100 μm depth. Monte Carlo simulations are employed to analyze the abilities of OCT in imaging of the embedded channels. The light scattering parameters required as input data for simulations are evaluated from the integrating sphere measurements of collimated and diffuse transmittance spectra using a reconstruction algorithm based on refined diffusion approximation approach.

Light Propagation in NIR Spectroscopy of the Human Brain

In study of the brain, oxygenation changes in the cerebral cortex are of great interest, since the concentrations of oxyhaemoglobin and deoxyhaemoglobin change due to coupling of hemodynamics to cortical neural activity. In order to non-invasively monitor oxygenation in the cerebral cortex by near-infrared spectroscopy (NIRS), light should penetrate into brain tissue to a depth of approximately 1-2 cm. Many studies show that by increasing the source-detector distance, illuminating light penetrates deeper into brain tissue. Using tissue-mimicking phantom measurements, forehead in vivo measurements, and Monte Carlo (MC) simulations, this paper estimates light propagation in the brain and the minimum source-detector distance to allow sensing of the cerebral cortex. We present optical sensing of a pulsating aqueous intralipid suspension in a vessel located at different depths within a multilayered phantom of the human forehead. Experimental results are compared with the MC simulations accounting for the optical properties of the phantom. The thickness and morphology of the different tissue layers were obtained from an anatomical magnetic resonance image of a test subjects head. Results from these three methods correlate with each other and show that the brain cortex can be sensed with optical methods based on NIRS.

Biodistribution of intact fluorescent CdSe/CdS/ZnS quantum dots coated by mercaptopropionic acid after intravenous injection into mice

Semiconductor quantum dots (QD) have been widely used for fluorescent bioimaging. However their biosafety has attracted increasing attention, since the data about their in vivo behavior in biological systems are still limited. In this paper we have investigated the short- and long-term biodistribution of intact fluorescent CdSe/CdS/ZnS QD coated by 3-mercaptopropionic acid in mice. The results showed that intravenously injected QD accumulated mainly in the lungs, liver and spleen and were retained in these tissues for over 22 days. QD caused signs of acute toxicity in mice including death. The investigated QD possibly caused vascular thrombosis. The results of a toxicological assay indicated that some histopathological changes occurred in the lung tissue after the injection of QD. Our study highlights the need for careful evaluation of QD safety before their use in biological applications.

Effects of gamma irradiation on collagen damage and remodeling

Abstract Purpose: To evaluate the dose-time dependences of structural changes occurring in collagen within 24 hours to three months after gamma-irradiation at doses from 2–40 Gy in vivo. Materials and methods: Rats tail tendon was chosen as in vivo model, with its highly ordered collagen structure allowing the changes to be interpreted unambiguously. Macromolecular level (I) was investigated by differential scanning calorimetry (DSC); fibers and bundles level (II) by laser scanning microscopy (LSM), and bulk tissue microstructural level (III) by cross-polarization optical coherence tomography (CP-OCT). Results: For (I), the formation of molecular cross-links and breaks appeared to be a principal mechanism of collagen remodeling, with the cross-links number dependent on radiation dose. Changes on level (II) involved primary, secondary and tertiary bundles splitting in a day and a week after irradiation. Bulk collagen microstructure (III) demonstrated early widening of the interference fringes on CP-OCT images observed to occur in the tendon as result of this splitting. At all three levels, the observed collagen changes demonstrated complete remodeling within ∼ a month following irradiation. Conclusion: The time course and dose dependencies of the observed collagen changes at different levels of its hierarchy further contribute to elucidating the role of connective tissue in the radiotherapy process.

Optical properties of mouse biotissues and their optical phantoms

Based on spectrophotometric measurements in the range of 700–1100 nm performed with the use of an integrating sphere, we have obtained absorption and scattering spectra of internal organs of mouse, as well as of aqueous solutions of India ink and Lipofundin, which are basic model media for creating optical phantoms of biological tissues. To retrieve the spectra of optical characteristics, we have used original formulas that relate the parameters of the medium with measured spectrophotometric characteristics and that are constructed based on classical analytical models of propagation of light in turbid media. As a result of comparison of spectra of biotissues and model media, we have developed a mixture of Lipofundin and India ink serving as mouse optical phantoms for problems of optical medical diagnostics.