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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. Histopathological analysis of these lesions revealed 4 intradermal, 3 compound and 3 junctional nevi in the “benign” group, 7 superficial spreading, 14 lentigo maligna and 11 nodular melanomas in the “melanoma” group and 2 lentigo simplex, 4 dysplastic nevi, 6 melanomas in situ, 4 invasive lentigo melanomas and 2 invasive superficial spreading melanomas in the “equivocal” group. On the basis of MPM, a multiphoton microscopy score (MPMS) has been developed for quantitative assessment of melanoma features at the cellular level, that showed lower score for benign lesions compare with malignant ones. OCA revealed that the invasive melanoma has a higher vessel density and thicker blood vessels than melanoma in situ and benign lesions. Discriminant functions analysis of MPM and OCA data allowed to differentiate correctly between all equivocal melanocytic lesions. Therefore, we demonstrate, for the first time, that a combined use of MPM and OCA has the potential to improve early diagnosis of melanoma.

An important factor in assessing tumor status for determining therapeutic and surgical tactics is the study of its morphological structure. In particular, preoperative differentiation/grading of colorectal adenocarcinomas is very important for the adjustment of neoadjuvant therapy, surgical technique choice and survival prediction. To achieve the maximum benefit and to avoid unnecessary side effects, the ability to distinguish high-grade from low-grade colorectal adenocarcinoma, as well as identification of patients with high recurrence risk before the possible initiation of treatment will increase the quality and duration of patients' life. Taking into account the peculiarities of the biology of intestinal cancer, optical coherence elastography, as a method of studying tissue structure at a shallow depth, may be promising in the study of colorectal adenocarcinoma. Possibilities of optical coherence elastography in differentiating low-grade and high-grade types of colorectal adenocarcinoma are demonstrated in this study. The reported results are based on revealed qualitative criteria for assessment of OCE images in combination with quantitative statistically significant differences in characteristic stiffness values for low-grade and high-grade colorectal adenocarcinomas.

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.

A method, based on optical coherence angiography (OCA), for the intraoperative diagnosis of blood microcirculation in the ischemic intestine has been tested. The pilot clinical study involved 18 patients who had undergone urgent operations for thrombosis of segments II or III of the superior mesenteric artery, as well as for infringement of the bowel and the mesenteric vessels. In the OCA images regions of preserved blood microcirculation in the intestinal wall were characterized by the presence of branched networks of intramural microvessels and a bright background in the OCA images. Regions of the intestine in which the intramural vessels were interrupted or could not be visualized were considered as potentially non-viable. These data were used to determine the boundaries for intestinal resection. In comparison with the traditional method of intraoperative diagnosis of intestinal blood flow, the use of such OCA criteria meant the volume of bowel resection could be decreased by 21.5 [14.1; 36.0]% (p = 0.037). This observation demonstrates the great potential of OСA in the intraoperative detection of the boundaries of damaged and healthy intestinal wall in ischemic bowel disease.

A multimodal optical coherence tomography (MM OCT) combining microstructural cross-polarization (CP) imaging and compression OCT-elastography (OCE) was employed in this study. The research was carried out on the noninvasive and invasive subtypes of human breast cancer. This study demonstrates how CP OCT combined with OCTelastography identifies an example of DCIS cancer that progresses into invasive breast cancer. OCE images more clearly show the cross sections of the ducts filled with tumor cells for DCIS (high-contrast structures with clear boundaries and high stiffness values) surrounded by areas with lower stiffness corresponding to fibrous stroma regions. The regions of invasive breast cancer in OCE-scans look as zones with strongly increased stiffness, which well agrees with the histology. Percentage of pixels with different characteristic stiffness ("stiffness spectrum") in the OCTelastography images was assessed to quantitatively visualize stiffness of tumor. The demonstrated ability of MM OCT imaging for breast cancer subtypes differentiation and breast cancer margin assessment is important for improved managements of patients.

In this chapter we consider applications of multimodal OCT for characterizing tumorous tissues. Namely, the following extensions of OCT are discussed: (1) polarization-sensitive OCT providing complementary images in the initial and cross-polarization channels (CP OCT), (2) OCT-based label-free angiography (OCA), and (3) compressional variant of OCT-based elastography (OCE). For each modality we briefly consider the principles of realization and present examples of various biomedical applications from utilization in laboratory experiments with model tumors on animals to demonstrations of possibilities of multimodal OCT in pre-clinical studies and usage in clinical conditions. Among such applications we present the results of using CP OCT for detection of tumorous and nontumorous regions in brain and breast tissues; application of OCA for monitoring the results of photodynamic therapy of murine model tumor CT26 and patients’ basal cell carcinoma; utilization of OCA for studying mucositis on patients during radiation therapy, as well as chemically induced cancer in hamster cheek pouch. In conclusion, we consider several examples of successful realization of compressional OCE for such applications as monitoring of tumor response to chemotherapy, visualization of morphological features of breast cancer and delineation of breast cancer from non-tumor tissue.

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. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Photodynamic therapy (PDT) is emerging as a common and efficacious method for basal cell carcinoma (BCC) treatment, and new non-invasive imaging technologies can further enhance it. Optical coherence angiography (OCA) was employed in this study. OCA is a non-invasive, label-free, real-time bioimaging method that has proven to be a helpful tool for visualizing normal and pathological vasculature, including vascular damage evaluation after using a vasculature-targeted therapy for predicting its success. In experimental study, it was shown that both the tumor and peritumorous vessels stasis (disappearance in OCA images) in 24 hours post treatment play significant roles in PDT success. On controllable mouse ear tumor model the following practical and robust OCA-based criterion of PDT success was formulated: there should be no visibly perfused vessels on OCA images inside the tumor borders, whereas in the 2 mm near-tumor proximity regions the vascular density should not exceed 1% from OCA image area in 24 hours post PDT. The criterion obtained on the experimental model was translated to clinical study. OCA monitoring of basal cell carcinoma reaction to PDT has shown that dramatic decrease in the vascular density in the tumor in 24 hours post PDT can predict tumor non-recurrence with high diagnostic accuracy for 12 months follow-up. The strong reaction of peritumorous vessels in 24 hours post PDT is associated with hypertrophic scar formation in 3-6 months, but the weak reaction of peri-tumorous vascular reaction leads to normotrophic scar formation.

Development of noninvasive diagnostic techniques in clinical practice, especially sufficiently fast methods suitable for intraoperative use, remains a topical and challenging problem in modern medicine. Compressional Optical Coherence Elastography (OCE) that has a high potential to be intraoperatively applied. This study reports preliminary results on application of compressional OCE for identification of tumor margins and even differentiation of breast cancer types with low- and high- histological grades, i.e., a step towards creation of a kind of OCE-based optical biopsy. The reported variant of OCE utilized B-scans with scales ~2-4 mm comparable with typical scales of histological samples. The approach is based on the ability of OCE to quantitatively visualize distribution of the Young modulus (stiffness) in studied tissue samples, which then is used to perform "elasto-spectroscopy" generically resembling the mass-spectroscopy procedures. The procedures of the OCE examination do not require any special preparation of tissue samples and thus can be applied intraoperatively on time intervals ~ a few minutes with immediately available results. In the reported study, the samples after OCE examinations were subjected to histological studies and classification made by an experienced histopathologist. Comparison between the OCE results and histological data made it possible not only to distinguish between normal tissue and tumor (for determining resection boundary), but also to formulate OCE-based criteria allowing for differentiation between carcinomas of low grades and fairly good treatment prognosis and high-grade invasive tumors with poor prognosis. Similarly, identification of not only invasive breast tumors, but also benign breast lesions, intermediate between norm and malignant tumors can be made.

In this study we combined cross-polarization optical coherence tomography (CP OCT), multiphoton tomography (MPT), based on second harmonic generation, and two-photon-excited fluorescence to visualize collagen fibers and tumor cells in the various morphological subtypes of breast cancer. The ability of CP OCT to visualize tissue birefringence and cross-scattering adds new information about the microstructure of such breast cancers, while the MPT provides verification of this microstructure. Mammary glands, both normal and tumorous, were assessed by MPT and CP OCT to establish the relationships between spatial organization features of the cellular component and the intercellular matrix. It was shown, that such multimodal optical imaging has great potential for distinguishing various breast cancer morphological subtypes and could provide useful tools for identifying positive breast cancer margins for surgery.

Emerging methods of anti-tumor therapies require new approaches to tumor response evaluation, especially enabling label-free diagnostics and in vivo 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. Despite different mechanisms of anti-angiogenic action for ChT and PDT, in both cases OCA demonstrated high sensitivity to blood perfusion cessation. The new method of OCE-based morphological segmentation revealed very similar histological structure alterations. The OCE results showed high correlation with conventional histology in evaluating percentages of necrotic and viable tumor zones. Such possibilities make OCE an attractive tool enabling previously inaccessible in vivo monitoring of individual tumor response to therapies without taking multiple biopsies.

This paper considers valuable visual assessment criteria for distinguishing between tumorous and non-tumorous tissues, intraoperatively, using cross-polarization OCT (CP OCT) – OCT with a functional extension, that enables detection of the polarization properties of the tissues in addition to their conventional light scattering. Materials and methods. The study was performed on 176 ex vivo human specimens obtained from 30 glioma patients. To measure the degree to which the typical parameters of CP OCT images can be matched to the actual histology, 100 images of tumors and white matter were selected for visual analysis to be undertaken by three “single-blinded” investigators. An evaluation of the inter-rater reliability between the investigators was performed. Application of the identified visual CP OCT criteria for intraoperative use was performed during brain tumor resection in 17 patients. Results. The CP OCT image parameters that can typically be used for visual assessment were separated: (1) signal intensity; (2) homogeneity of intensity; (3) attenuation rate; (4) uniformity of attenuation. The degree of match between the CP OCT images and the histology of the specimens was significant for the parameters “signal intensity” in both polarizations, and “homogeneity of intensity” as well as the “uniformity of attenuation” in co-polarization. A test based on the identified criteria showed a diagnostic accuracy of 87-88%. Intraoperative in vivo CP OCT images of white matter and tumors have similar signals to ex vivo ones, whereas the cortex in vivo is characterized by indicative vertical striations arising from the “shadows” of the blood vessels; these are not seen in ex vivo images or in the case of tumor invasion. Conclusion. Visual assessment of CP OCT images enables tumorous and non-tumorous tissues to be distinguished. The most powerful aspect of CP OCT images that can be used as a criterion for differentiation between tumorous tissue and white matter is the signal intensity. In distinguishing white matter from tumors the diagnostic accuracy using the identified visual CP OCT criteria was 87-88%. As the CP OCT data is easily associated with intraoperative neurophysiological and neuronavigation findings this can provide valuable supplementary information for the neurosurgeon during tumor resection.

Introduction of innovative noninvasive diagnostic techniques in clinical practice remains an actual topic of modern medicine. In the study, we assessed feasibility of multimodal OCT (MM OCT) that combines crosspolarization imaging and elastographic stiffness mapping to assess spatial structural organization and heterogeneity of breast cancer in the tumor center in comparison with normal mammary gland tissue. The research was carried out using human breast tissue mastectomy surgical samples including different histological types of breast cancer: ductal carcinoma in situ, invasive lobular and ductal carcinoma, fibroadenoma and normal tissue. The histological subtypes of breast cancer showed different structural and stiffness features of tumor tissue. In the case of invasive ductal carcinoma, the cross-polarization OCT image shows a more heterogeneous high-level OCT signal and higher stiffness in comparison with lobular breast cancer or fibroadenoma. These results indicate that assessing microstructures and elasticity changes yields complementary information about the microstructural features of breast cancer, which is important for selection of treatment tactics.

The objective of the investigation was to show the advisability of using optical coherence tomography (OCT) for noninvasive diagnostics and monitoring of treatments in gynecological practice for female patients of reproductive age. Materials and Methods. OCT studies were performed during standard gynecological procedures like laparoscopy and colposcopy, as well as in course of pelvic inflammatory diseases of cervical neoplasia, with the use of an OKT1300U (BioMedTech, Russia). 330 patients of reproductive age (aged 18–45) were examined. The methods used for numeric processing of the OCT images were based on an analysis of histograms and on calculation of the first derivative of the OCT signal over depth. Results. The use of OCT with numeric processing of the images increases the sensitivity of laparoscopy diagnosis of latent chronic salpingitis from 43.5 to 96.0%. In the case of minimal endometriosis, OCT can be used as a substitute for excisional biopsy for the visualization and verification of endometrioid heterotopias. The use of OCT in the case of cervical neoplasia in female patients of reproductive age enables a considerable decrease in surgical aggression during the diagnosis and treatment of cervical intraepithelial neoplasia and early forms of cancer. Conclusion. The use of OCT helps to maximize individualization and organ preservation during the diagnosis and treatment of gynecological pathology, and therefore to preserve the reproductive potential of young female patients.

Early response of cancer cells to chemotherapeutic drugs were studied using novel fluorescence tools and microscopy techniques. We applied two-photon fluorescence lifetime imaging (microscopy and in vivo imaging) to assess metabolic and oxygen changes in cancer cells in different tumor models. The dynamics of energy metabolism, intracellular pH, oxygen under chemotherapy were evaluated. In patients with skin neoplasia using of optical imaging, including FLIM, we have showed possibilities to distinguish benign and malignant pigmented lesions.

Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

We discuss the application of compressional OCT-based elastography for measuring elastic response of biological tissues in the strain range from fractions of one per cent up to strains over ~10% and greater. Such fairly large strains are not typical of phase-sensitive OCT-based elastographic methods and can be measurable due to application of interframe strain-estimation method in which interframe phase gradients are estimated without the necessity of preliminary measuring total displacements of scattering particles in combination with summation of interframe strains. For estimating applied stresses, intervenient soft layer of translucent silicone is used a a reference fairly linear material. The obtained results based on comparison of strains in the reference layer and tissue demonstrate highly nonlinear character of elasticity of biological tissues even for rather moderate strains on order of several per cent.

The main goal of the study was a vasculature targeted PDT. A new approach named M-mode-like OCT (MML OCT) was applied to monitor early response to PDT. Due to the chosen filtering parameters (96 Hz filter threshold), this approach visualizes only vessels with flowing blood. Without flowing blood even filled vessels are not visualized because flow-less blood causes speckle variations with significantly lower frequencies (

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.

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. Initially the specific stiffness ranges for the analyzed tissue components (adipose tissue, fibrous and hyalinized tumor stroma, lymphocytic infiltrate and agglomerates of tumor cells) are determined via comparison of OCE and morphological/molecular data. Then assessment of non-tumor/tumor regions and tumor subtypes is made based on percentage of pixels with different characteristic stiffness (“stiffness spectrum”) in the OCE image, also taking into account spatial localization of different-stiffness regions. Examples of high contrast among benign (or non-invasive) and several subtypes of invasive breast tumors in terms of their stiffness spectra are given.

The combined use of fluorescence cystoscopy and cross-polarization optical coherence tomography (CP OCT) with quantitative estimation of the OCT signal was assessed in 92 bladder zones. It demonstrated the diagnostic accuracy in detecting superficial bladder cancer of 93.6%, sensitivity 96.4%, specificity 92.1%, positive predictive value 87% and negative predictive value 97.9%. Quantitative estimation of OCT signal standard deviation in cross-polarization (CP OCT SD index) makes the visual criteria of CP OCT image assessment more objective. The level of CP OCT SD index for diagnosing superficial bladder cancer, including cancer in situ, was 4.32 dB and lower. When tumor is located on a postoperative scar, CP OCT SD index may be higher than the threshold level of 4.32 dB due to strong scattering and depolarization in scar fibrous tissue. A high inverse correlation was found between CP OCT SD index and the level expressed by p63, Ki-67, p53, CD44v6 markers.

A combination of approaches to the image analysis in cross-polarization optical coherence tomography (CP OCT) and high-resolution imaging by nonlinear microscopy and atomic force microscopy (AFM) at the different stages of atherosclerotic plaque development is studied. This combination allowed us to qualitatively and quantitatively assess the disorganization of collagen in the atherosclerotic arterial tissue (reduction and increase of CP backscatter), at the fiber (change of the geometric distribution of fibers in the second-harmonic generation microscopy images) and fibrillar (violation of packing and different nature of a basket-weave network of fibrils in the AFM images) organization levels. The calculated CP channel-related parameters are shown to have a statistically significant difference between stable and unstable (also called vulnerable) plaques, and hence, CP OCT could be a potentially powerful, minimally invasive method for vulnerable plaques detection.

In this study we demonstrate the capability of cross-polarization optical coherence tomography (CP OCT) to assess collagen and elastin fibers condition in atherosclerotic plaques basing on ratio of the OCT signal levels in cross- and со- polarizations. We consider the depolarization factor (DF) and the effective birefringence (Δn) as quantitative characteristics of CP OCT images. We revealed that calculation of both DF and Δn in the region of interest (fibrous cap) yields a statistically significant difference between stable and unstable plaques (0.46±0.21 vs 0.09±0.04 for IDF; (4.7±1.0)•10–4 vs (2.5±0.7)•10–4 for Δn; p

Recently proposed in vivo label-free optical coherence angiography techniques based on phase and amplitude speckle variability often require additional signal pre- and post processing operations to enhance vessel-contrast. We observe here 1) contrast enhancement by optimizing the signal normalization/weighing before processing; 2) algorithm based on Kasai estimator for phase compensation between processed A-scans to reduce masking role of motion artifacts; and 3) image projection through the imaging depth for en face plotting. We demonstrate the efficiency of proposed additional algorithms as for the microcirculation imaging of hamsters cheek in vivo as for the preliminary microcirculation imaging of patients after radiotherapy. This technical framework complete in details our recent publications on M-Mode like OCT algorithms and its implementation.

We report a novel hybrid method of robust strain mapping in compressional optical coherence elastography using combined phase measurements on sub-wavelength-scale and cumulative pixel-scale displacement tracking. This hybrid nature significantly extends the range of measurable displacements and strains in comparison with conventional direct phase-resolved measurements. As a result, the proposed strain-mapping method exhibits significantly increased robustness with respect to both additive noise and decorrelation noise produced by displacements and strains. The main advantages of the proposed approach are illustrated by numerical simulations. Experimental examples of obtained strain maps for phantoms and real biological tissues are also presented.

We combined cross-polarization optical coherence tomography (CP OCT) and non-linear microscopy based on second harmonic generation (SHG) and two-photon-excited fluorescence (2PEF) to assess collagen and elastin fibers in the development of the atherosclerotic plaque (AP). The study shows potential of CP OCT for the assessment of collagen and elastin fibers condition in atherosclerotic arteries. Specifically, the additional information afforded by CP OCT, related to birefringence and cross-scattering properties of arterial tissues, may improve the robustness and accuracy of assessment about the microstructure and composition of the plaque for different stages of atherosclerosis.

We combined cross-polarization optical coherence tomography (CP OCT) and non-linear microscopy based on second harmonic generation (SHG) and two-photon-excited fluorescence (2PEF) to assess collagen and elastin fibers and other vascular structures in the development of atherosclerosis, including identification of vulnerable plaques, which remains an important clinical problem and imaging application. CP OCT's ability to visualize tissue birefringence and cross-scattering adds new information about the microstructure and composition of the plaque. However its interpretation can be ambiguous, because backscattering contrast may have a similar appearance to the birefringence related fringes. Our results represent a step towards minimally invasive characterization and monitoring of different stages of atherosclerosis, including vulnerable plaques. CP OCT image of intimal thickening in the human coronary artery. The dark stripe in the cross-polarization channel (arrow) is a polarization fringe related to the phase retardation between two eigen polarization states. It is histologically located in the area of the lipid pool, however this stripe is a polarization artifact, rather than direct visualization of the lipid pool.

Illustration of exceptionally high tolerance of the proposed method to noises: contrast of only 25% in the stiffness of the layers is clearly seen in the strain map even for equal intensities of the OCT signal and additive noise (SNR = 0 dB). A novel hybrid method which combines sub-wavelength-scale phase measurements and pixel-scale displacement tracking for robust strain mapping in compressional optical coherence elastography is proposed. Unlike majority of OCE methods it does not rely on initial reconstruction of displacements and does not suffer from the phase-wrapping problem for super-wavelength displacements. Its robustness is enabled by direct fitting of local phase gradients obviating the necessity of phase unwrapping and error-prone numerical differentiation. Furthermore, axial displacements significantly exceeding not only the optical wavelength, but pixel scales (i.e., multiple wavelengths) can be efficiently tracked and compensated. This feature strongly reduces errors in phase-gradient estimation and ensures high robustness with respect to both additive and decorrelation noises.

In this paper we report on our recent achievement in application of conventional and cross-polarization OCT (CP OCT) modalities for in vivo clinical diagnostics in different medical areas including gynecology, dermatology, and stomatology. In gynecology, CP OCT was employed for diagnosing fallopian tubes and cervix; in dermatology OCT for monitoring of treatment of psoriasis, scleroderma and atopic dermatitis; and in stomatology for diagnosis of oral diseases. For all considered application, we propose and develop different image processing methods which enhance the diagnostic value of the technique. In particular, we use histogram analysis, Fourier analysis and neural networks, thus calculating different tissue characteristics as revealed by OCT’s polarization evolution. These approaches enable improved OCT image quantification and increase its resultant diagnostic accuracy.

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.

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.