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Complementary Study of Collagen State in Bladder Diseases Using Cross-Polarization Optical Coherence Tomography, Nonlinear and Atomic Force Microscopy

Complementary Study of Collagen State in Bladder Diseases Using Cross-Polarization Optical Coherence Tomography, Nonlinear and Atomic Force Microscopy

Kiseleva E.B., Gubarkova E.V., Dudenkova V.V., Timashev P.S., Kotova S.L., Timofeeva L.B., Kirillin М.Yu., Belkova G.V., Solov’eva A.B., Strel’tsova O.S., Gladkova N.D.
Keywords: cross-polarization optical coherence tomography; CP OCT; urothelial carcinoma; urothelial carcinoma recurrence; collagen state; nonlinear microscopy; second harmonic generation; atomic force microscopy.
СТМ, 2017, volume 9, issue 1, pages 7-20.

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The aim of the study is to demonstrate the potential of cross-polarization optical coherence tomography (CP OCT) as a minimally invasive real-time technique for detection of bladder cancer against a background of severe inflammation.

Materials and Methods. For the verification of CP OCT diagnostic data related to the condition of collagen comparison with high-resolution microscopy inspection was performed and correlation of the results was calculated. The CP OCT study was performed on samples of tissue with muscle-invasive urothelial carcinoma T2–3N0–хM0 (G2, 3) in 18 patients ranging in age from 50 to 64 obtained in course of cystectomy with urine diversion into the intestinal vessel. In total, 60 regions of interest were selected and divided into four groups in accordance with the results of the histological analysis: areas with mild inflammation (group 1, control), 12 areas; areas with severe inflammation (group 2), 18 areas; areas with poorly differentiated urothelial carcinoma with invasion into the muscular layer (group 3), 24 areas; areas with cancer recurrence at the post-operative scar (group 4), 6 areas. Tissue changes at micro-structural level registered by CP OCT were investigated in detail with high-resolution microscopy (nonlinear microscopy and atomic force microscopy). Quantitative processing of all the obtained images enabled their direct comparison.

Results. By two high-resolution techniques and classical histology the spatial and structural features of the bladder extracellular matrix organization exhibiting different pathologies were demonstrated. Depolarization factor maps derived from CP OCT images of both invasive carcinoma and carcinoma recurrence in the area of post-operative scar tissue characterize the cross-scattering properties of the bladder connective tissue in these conditions and demonstrate a statistically significant difference in the integral depolarization factor value for carcinoma and severe chronic inflammation (р<0.05). A high statistically significant positive correlation (r=0.867, p<0.001; Spearman correlation) between the integral depolarization factor and the conformance parameter of the second harmonic signal distribution detected from collagen at the level of the mucous membrane was demonstrated. This is indicative of a high level of correspondence between the level of cross-scattering and the collagen fibers ordering. In cases of severe inflammation, invasive growth of urothelial carcinoma, and cancer recurrence in the area of the surgical scar the structural disorganization of fiber structures determined at tissue level in the subsurface region of the bladder was revealed.

Conclusion. The comparison of CP OCT images with data from the high-resolution techniques (nonlinear microscopy in second harmonic generation mode and atomic force microscopy) demonstrated that CP OCT have the potential to become a powerful, minimally invasive, real-time tool for detection of bladder cancer against a background of severe inflammation in the area of the post-operative scar. These results will stimulate further development of CP OCT technique and promote its active introduction into clinical practice.

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