The capabilities of cross-polarization optical coherence tomography (CP OCT) for early bladder-cancer detection are assessed in statistical study and compared with the traditional OCT. Unlike the traditional OCT that demonstrates images only in copolarization, CP OCT acquires images in cross-polarization and copolarization simultaneously. 116 patients with localized flat suspicious lesions in the bladder were enrolled, 360 CP OCT images were obtained and analyzed. CP OCT demonstrated sensitivity 93.7% (vs. 81.2%, <0.0001), specificity 84% (vs. 70.0%, <0.001) and accuracy 85.3% (vs. 71.5%, <0.001) in detecting flat malignant bladder lesions, which is significantly better than with the traditional OCT. Higher diagnostic efficacy of CP OCT in detecting early bladder cancer is associated with the ability to detect changes in epithelium and connective tissues.
The goal of the research was analysis of the effect of collagen condition in formation of cross-polarized CP OCT images. We used of the CP OCT technique for studying collagen condition on an example of oral mucosa. Special histologic picrosirius red (PSR) staining of cheek mucosa specimens was used with subsequent assessing of the result of collagen staining in polarized light. High correlation (r = 0.692, p = 0.0001) between OCT signal standard deviation (SD) in cross-polarized images and brightness of PSR stained collagen fibers in cheek mucosa specimens was demonstrated in patients with inflammatory intestine and oral mucosa diseases. We have found that the OCT signal SD in cross-polarized images reflects two boundary conditions of collagen disorganization, namely, loss of fiber properties at active inflammation which attenuates the signal and fibrosis that occurs due to synthesis of a new remodeled collagen which amplifies the OCT signal.
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.
The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal and diseased brain tissue using an experimental model of glioblastoma. Materials and Methods. The spectral domain MM OCT device developed at the Institute of Applied Physics of the Russian Academy of Sciences (Nizhny Novgorod, Russia) was used for the study. It provides two modes of investigation: cross-polarization OCT (CP OCT) and microangiographic OCT (MA OCT). The instrument features the following characteristics: rate of information gathering-20,000 A-scans per second; wavelength-1.3 µm; shot size-~4×2 mm; lateral resolution-20 µm; axial resolution-10-15 µm. The OCT investigation was performed on an experimental 101.8 rat brain glioblastoma tumor model inoculated and maintained in the Research Institute of Human Morphology. To evaluate the signal parameters typical of the tumor and of normal brain tissue, CP OCT and MA OCT images were compared with histological specimens (stained with hematoxylin and eosin). Analysis of the MA OCT images was performed on the basis of comparison with the findings of ZOOM-microscopy. Results. The model of the rat 101.8 glioblastoma helped to identify links between CP OCT images of areas of brain tissue and their morphological structure. We performed a comparative evaluation of the signals from the glial tumor and from normal brain tissue. MA OCT allowed the visualization of the blood vessels both in the tumor and in the normal brain tissues, revealing changes in the form and sizes typical of the tumor vessels. Conclusion. ММ OCT is an innovative technology with potential for use in intraoperational diagnoses of glial tumors of the brain. The ability to combine several modes of investigation enables information to be obtained simultaneously about the structure of the tissues and about any peculiarities of the structure of the different elements of their microvascular network.
There is considerable clinical and fundamental value in measuring the clonal heterogeneity of T and B cell expansions in tumors and tumor-associated lymphoid structures-along with the associated heterogeneity of the tumor neoantigen landscape-but such analyses remain challenging to perform. Here, we propose a straightforward approach to analyze the heterogeneity of immune repertoires between different tissue sections in a quantitative and controlled way, based on a beta-binomial noise model trained on control replicates obtained at the level of single-cell suspensions. This approach allows to identify local clonal expansions with high accuracy. We reveal in situ proliferation of clonal T cells in a mouse model of melanoma, and analyze heterogeneity of immunoglobulin repertoires between sections of a metastatically-infiltrated lymph node in human melanoma and primary human colon tumor. On the latter example, we demonstrate the importance of training the noise model on datasets with depth and content that is comparable to the samples being studied. Altogether, we describe here the crucial basic instrumentarium needed to facilitate proper experimental setup planning in the rapidly evolving field of intratumoral immune repertoires, from the wet lab to bioinformatics analysis.
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