RU2572299C2 - Method for assessing functional health of collagen tissue - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, urology, dentistry, gynaecology, X-ray diagnostics, laryngology and can be used to assess the functional health of collagen tissues, particularly collagen fibres of mucosal stroma. An internal structure of the collagen tissue is analysed at a depth of up to 2 mm by means of cross-polarised optical coherence tomography (CP-OCT); an OCT-image (OCT-I) of the analysed tissue are examined in orthogonal and straight polarisations; an average OCT-signal (OCT-S) and an average background signal are calculated in orthogonal polarisation; OCT-S value that is a difference of the average OCT-S in orthogonal polarisation and the average background OCT-S is derived, and the functional health of the tissue is assessed. The OCT-I is potentiated in orthogonal and straight polarisations to produce OCT-S power in relative units; the produced potentiated OCT-I is averaged in a transverse coordinate; the average background signal is deducted from the average OCT-S in orthogonal polarisation. That is followed by relating the OCT-S powers averaged in the transverse coordinate in orthogonal and straight polarisations. This relation is averaged in a longitudinal coordinate along the whole probing depth, for which the OCT-S power in orthogonal polarisation exceeds the average background OCT-S by a double standard deviation of the background OCT-S. The derived value is an integral depolarisation factor (IDF), which is used to assess the functional health of the examined collagen tissue. The normal IDF of the buccal mucosa makes more than from 0.08 to 0.09; the same value accompanying an acute inflammation is 0.03-0.05; with a fibrous tissue formation, it is 0.10-0.13; and one with a fibrosis-scar tissue is from 0.13 to 0.17. The normal IDF of the urinary bladder mucosa makes more than from 0.08 to 0.12; in an acute inflammation, it is more than 0.05 to 0.07; in a fibrous tissue formation, it is more than 0.11 to 0.17; in severe epithelium dysplasia - from 0.03 to 0.05; in epidermoid cancer with the onset of invasive growth - from 0.01 to 0.02. The normal IDF of the postoperative scar tissue of the urinary bladder makes more than 0.17 to 0.27, and in cancer, on the postoperative scar - from 0.03 to 0.09.

EFFECT: method provides the more accurate assessment of the functional health of the collagen tissue of mucosal stroma of the above body areas in the differential diagnostics of the above conditions.

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Description

The proposed method relates to medicine, namely to urology, dentistry, gynecology, to radiation diagnostics, laryngology, and can be used to assess the functional state of collagen-containing tissues, in particular collagen fibers of the stroma of the mucous membranes.

It is known that collagen at all levels of hierarchical organization - a molecule, fibril, secondary and tertiary bundles - has optical anisotropy. Collagen fibers in structure represent a quasicrystal with uniaxial packing of collagen molecules and, as a result, are able to depolarize a polarized light wave. It is known that the more organized and structured collagen fibers between each other and in depth, the greater their quantitative content in the tissue and the diameter of the fibers, the more strongly their depolarizing properties are manifested. It is known that the structure of the tissue (in particular, the structure of collagen) is damaged under the influence of a number of pathological processes - inflammation, neoplasia, etc., as well as under the influence of a number of external factors (radiation damage during radiation therapy; damage under the influence of intense laser radiation). Currently, non-invasive methods for assessing the structure of tissues based on the method of optical coherence tomography (OCT), a method for obtaining images of the structure of biological tissues using light from the near infrared range, are known. The method is based on the difference in optical properties (backscattering, absorption) of various tissue structures. OCT allows real-time imaging of subsurface structures to a depth of 2 mm with a resolution of 10-15 μm (1).

So there is a method for predicting the severity of the reaction of the mucous membrane of the oral cavity and pharynx during radiation or chemoradiotherapy of malignant neoplasms of the oropharyngeal region (2). This method consists in the fact that in the course of treatment, a clinical assessment of the condition of the oral mucosa before the first clinical signs of a radiation reaction appears, and on the day of their appearance, the oral mucosa is re-examined by optical coherence tomography. The obtained OCT image is compared with the OCT image before irradiation and mucositis of the III-IV degree is predicted by the disappearance of the boundary between the epithelium and the underlying connective tissue in the OCT image, and mucositis of the I-II degree - by maintaining this boundary. In this case, a clinical assessment of the condition of the oral mucosa is carried out in accordance with the CTCAE classification. The first clinical signs of radiation reaction of the oral mucosa are usually observed on the 6th-9th day of exposure. The study of the mucous membrane of the oral cavity by OCT is carried out at any point in the mucous membrane of the cheek, which falls into the irradiation zone, but both studies are carried out at the same point. It is preferable to select a point on the cheek in the middle of the line connecting the angle of the mouth and the mouth of the excretory duct of the salivary gland.

The method allows to predict the severity of the reaction of the mucous membrane of the oral cavity and pharynx in the early stages of radiation therapy using a non-invasive, non-traumatic and rapid study.

However, this method is not accurate enough due to the subjectivity of the assessment. For a more accurate assessment of the state of collagen-containing tissues, the method of cross-polarized optical coherent tomography (CP OCT) is used. At the same time, special attention is being paid to the use of cross-polarized optical coherence tomography (CP OCT) to obtain images of the structure of collagen fibers of the stroma of human mucous membranes under normal conditions and in various pathophysiological processes (3).

This method allows you to simultaneously register backscattering signals from the medium with the subsequent formation of the CP OCT image of the same region of the medium under study in direct and orthogonal polarizations. Comparison of images in two polarizations makes it possible to evaluate the depolarizing properties of tissue components.

The degree of scattering into orthogonal polarization depends on the size, structure, and anisotropy of optical inhomogeneities in biological tissue and can characterize, for example, the state of collagen fibers, the nature of the changes of which is different in different clinical situations.

A method for diagnosing cervical pathology is known, which includes preliminary colposcopy of the surface of the cervix (CM) and subsequent investigation of sections of CM with atypical colposcopic signs using cross-polarized optical coherence tomography (CP OCT) by directing a beam of low coherent optical radiation of direct polarization ( PP) of the visible or near infrared range on the surface to be examined, its scanning and registration of the OCT image reflecting the radiation intensity, of inverse scattered by the sample surface. Simultaneously with the investigation of sections of the surface of the CMM using PP radiation, these regions are examined by low-coherent optical radiation of a given wavelength range of orthogonal polarization (OP) at an angle of radiation deviation of 40-50 °. The OCT image is recorded in PP and OP. A benign pathology of the surface of the CM is diagnosed with a structural or structureless OCT image in a PP and an OCT image of a high signal intensity in an OP. Malignant pathology of CMM is diagnosed with a structureless and / or unstructured OCT image in a PP and an OCT image in an OP of low signal intensity and / or its absence (4).

This method provides a diagnosis of CM pathology, this approach allows to increase both the specificity of OCT diagnostics by reducing the false-positive interpretation of structureless images, and the sensitivity of the entire diagnostic approach.

However, this method is not accurate enough, since the assessment of the OCT signal is subjective.

A known method for the diagnosis of side effects of radiation therapy from the bladder (5).

This method includes conducting a study of the bladder by cross-polarization optical coherence tomography (CP OCT) before radiotherapy and once a week during the course of radiation treatment, while CP OCT scan is carried out in three zones: the back wall of the bladder, triangle Cast and the bladder neck and when observing in at least one zone of decrease in signal intensity in orthogonal polarization in subepithelial structures, the onset of radiation changes is diagnosed and the weekly stop th monitoring. Additional signs of the onset of radiation changes are a decrease, up to the disappearance, of the number of small structures with a low signal level, as well as a decrease in the contrast of the longitudinal structures inside the connective tissue layer in direct polarization.

This method allows in real time to assess the degree of radiation reaction of both urothelium and subepithelial structures of the bladder in the early stages of radiation therapy.

However, a visual assessment of the useful signal in the OCT image in the orthogonal polarization by its intensity is subjective because of the impossibility of visually correlating the signal intensity in direct and orthogonal polarizations. Both polarizations reflect the scattering ability of tissue components, but the ratio of structural centers scattering radiation into the initial and orthogonal polarizations can change with a change in the functional state of the tissue.

The closest in the set of essential features and the achieved technical result to the proposed method is a known method for differential diagnosis of intestinal diseases according to the condition of the soft tissues of the oral cavity, which is described in the source (6) and which is selected by the authors as a prototype.

This method includes examining the surface of collagen-containing tissue using cross-polarized optical coherence tomography (CP OCT), obtaining a CP OCT image, calculating the average intensity of the OCT signal in orthogonal polarization and the average background value, determining the value of the useful OCT signal by calculating the difference between the average value of the intensity of the OCT signal in orthogonal polarization and the average background value of the OCT signal, and the assessment of the functional state of the my tissue based on the amount of useful OCT signal.

This method allows the numerical analysis of images of cross-polarized optical coherence tomography in the differential diagnosis of bowel disease, such as Crohn's disease (CD) and ulcerative colitis (UC) according to the state of collagen fibers of the stroma of the buccal mucosa.

However, this method is not accurate enough. For these pathologies, the diagnostic accuracy is 0.78.

In addition, this method provides numerical analysis of images of cross-polarized optical coherence tomography of only collagen fibers of the stroma of the buccal mucosa.

The objective of the invention is to develop a method for assessing the functional state of collagen-containing tissue, namely collagen fibers of the stroma of the mucous membranes, which is highly accurate and allows to evaluate the functional state of collagen-containing tissue in dentistry and urology.

The problem is solved by the proposed method for assessing the functional state of collagen-containing tissue, including studying the internal structure of collagen-containing tissue to a depth of 2 mm using cross-polarized optical coherence tomography (CP OCT), registering the OCT image of the tissue in orthogonal and direct polarization, calculating the average the values of the OCT signal in orthogonal polarization and the average background value of the signal, determining the magnitude of the OCT signal, which is the difference between the average value of the OCT signal in orthogonal polarization and the average value of the background OCT signal and the assessment of the functional state of the tissue under investigation, according to the invention, the OCT image in orthogonal and direct polarizations is potentiated to obtain the power of the OCT signal in relative units, and the obtained potentized OCT is averaged - images along the transverse coordinate are subtracted from the averaged OCT signal in orthogonal polarization the average value of the background signal, then take the ratio measured along the transverse coordinate of the power of the OCT signal in orthogonal and direct polarizations, after which this ratio is averaged over the longitudinal coordinate over all sounding depths for which the power of the OCT signal in orthogonal polarization exceeds the average value of the background OCT signal by twice the standard deviation of the background OCT signal, the obtained value is an integral factor of depolarization (IFD), which assesses the functional state of the collagen-containing tissue under study, and for the mucous membrane of the mouth in the cheek region: normally, the IDF is more than 0.08 to 0.09, with acute inflammation - from 0.03 to 0.05, with the formation of fibrous tissue - from 0.10 to 0.13, with the formation of fibro scar tissue - over 0.13 to 0.17; for the mucous membrane of the bladder, the normal IFD value is more than 0.08 to 0.12, with acute inflammation - more than 0.05 to 0.07, with the formation of fibrous tissue - more than 0.11 to 0.17, with severe dysplasia epithelium - from 0.03 to 0.05, with flat cancer with the onset of invasive growth - from 0.01 to 0.02; for tissue of the postoperative scar in the bladder, the IFD value is normally greater than 0.17 to 0.27, and for cancer in the postoperative scar, from 0.03 to 0.09.

IFD is a dimensionless parameter; it is calculated as the ratio of the received powers of the OCT signal in the orthogonal and direct polarizations averaged over the image area; devoid of speckle noise and instrumental noise. The method for calculating the IFD takes into account the fundamental features of creating a CP OCT image. When calculating the IDF, the average value of the background signal is subtracted from the value of the average power of the OCT signal in the orthogonal polarization to exclude the influence of noise.

A new technical result of the proposed method is to increase the accuracy of assessing the functional state of collagen-containing tissue, namely collagen fibers of the stroma of the mucous membranes, which is confirmed by: - increased diagnostic accuracy in the differential diagnosis of Crohn’s disease and ulcerative colitis: in the prototype, when calculating the average signal intensity in orthogonal polarization, this the value is 0.78, for IFD - 0.86;

- the ability to assess the functional state of collagen-containing tissue not only in dentistry, but also in urology, gynecology, laryngology, and radiation diagnostics.

This technical result is due to the fact that:

- calculation of the ratio of the average value of the useful OCT signal in orthogonal polarization to the average value of the signal in direct polarization makes it possible to numerically evaluate the tissue's ability to depolarize the polarized light wave, since this parameter cannot be calculated only on the basis of the OCT image in orthogonal polarization; allows to exclude the influence of the absolute values of the power of the probe radiation and the structural elements of the device (instrumental noise), and also to level the effect of the decay of the useful OCT signal with depth in the biological tissue due to scattering and absorption;

- transverse averaging of the OCT signal (averaging over each transverse coordinate of the image) in each polarization allows us to level the speckle noise, which is an integral component of the OCT signal;

- line-by-line division of values averaged over the transverse coordinate in orthogonal and direct polarizations. This action takes into account that the total CP OCT image consists of two conjugate images: in orthogonal polarization and in direct polarization, the pixels of which are located equidistantly (they have a mutual correspondence between the sounding depth).

The proposed method is as follows.

A study is made of the internal structure of collagen-containing tissue to a depth of 2 mm using cross-polarization optical coherence tomography (CP OCT), registration of the OCT image of the tissue in orthogonal and direct polarization, and potentiation of the OCT image in orthogonal and direct polarization to obtain the power of the OCT- the signal in relative units, averaging the resulting potentized OCT image along the transverse coordinate, subtracting from the average OKT signal in the orthogonal polarization of the average in values of the background signal, then finding the ratio of the powers of the OCT signal averaged over the transverse coordinate in the orthogonal and direct polarizations, after which this ratio is averaged over the longitudinal coordinate over all sensing depths for which the power of the OCT signal in orthogonal polarization exceeds the average value of the background OCT signal twice the standard deviation of the background OCT signal, according to the following formula:

$$\mathrm{AND}FD=\frac{\mathrm{one}}{N}{\displaystyle \sum _{i=\mathrm{one}...N,{\text{P}}_{\text{i}}^{\perp }>〈P_{f\mathrm{about}n}〉+2s_{f\mathrm{about}n}}}\frac{P_i^{\perp }-〈P_{f\mathrm{about}n}〉}{P_i^{\left|\right|}}$$

- мощность ОКТ-сигнала в прямой поляризации в i-том пикселе после усреднения по поперечной координате, $$P_i^{\perp }$$

- мощность ОКТ-сигнала в ортогональной поляризации в i-том пикселе после усреднения по поперечной координате, N - число пикселов в усредненном по поперечной координате ОКТ-сигнале в ортогональной поляризации, для которых мощность ОКТ-сигнала превышает среднюю величину фонового ОКТ-сигнала $$\langle P_{фон}\rangle$$

на удвоенное стандартное отклонение фонового ОКТ-сигнала 2s_фон, полученная величина является интегральным фактором деполяризации (ИФД), по которой оценивают функциональное состояние исследуемой коллагенсодержащей ткани, так для слизистой оболочки полости рта в области щеки: в норме величина ИФД составляет свыше 0,08 до 0,09, при остром воспалении - 0,03 до 0,05, при образовании фиброзной ткани - 0,10 до 0,13, при образовании фиброзно-рубцовой ткани - свыше 0,13 до 0,17; для слизистой оболочки мочевого пузыря в норме величина ИФД составляет - свыше 0,08 до 0,12, при остром воспалении - свыше 0,05 до 0,07, при образовании фиброзной ткани - свыше 0,11 до 0,17, при тяжелой дисплазии эпителия - от 0,03 до 0,05, при плоском раке с началом инвазивного роста - от 0,01 до 0,02; для ткани послеоперационного рубца в мочевом пузыре величина ИФД в норме составляет свыше 0,17 до 0,27, а при раке на послеоперационном рубце - от 0,03 до 0,09.Where: $$P_i^{\left|\right|}$$

- power of the OCT signal in direct polarization in the i-th pixel after averaging over the transverse coordinate, $$P_i^{\perp }$$

is the power of the OCT signal in orthogonal polarization in the i-th pixel after averaging over the transverse coordinate, N is the number of pixels in the OCT signal averaged over the transverse coordinate in the orthogonal polarization, for which the power of the OCT signal exceeds the average value of the background OCT signal $$〈P_{f\mathrm{about}n}〉$$

the doubled standard deviation of the background OCT signal 2s _background , the obtained value is an integral depolarization factor (IPF), which assesses the functional state of the collagen-containing tissue under study, so for the mucous membrane of the oral cavity in the cheek area: the normal value of the IPD is over 0.08 to 0.09, with acute inflammation - 0.03 to 0.05, with the formation of fibrous tissue - 0.10 to 0.13, with the formation of fibro-scar tissue - over 0.13 to 0.17; for the mucous membrane of the bladder, the normal IFD value is more than 0.08 to 0.12, with acute inflammation - more than 0.05 to 0.07, with the formation of fibrous tissue - more than 0.11 to 0.17, with severe dysplasia epithelium - from 0.03 to 0.05, with flat cancer with the onset of invasive growth - from 0.01 to 0.02; for tissue of the postoperative scar in the bladder, the IFD value is normally greater than 0.17 to 0.27, and for cancer in the postoperative scar, from 0.03 to 0.09.

In FIG. 1 presents a CP OCT image of the mucous membrane of the oral cavity (in the cheek area) in the norm, where:

A - OCT image in orthogonal polarization;

B - OCT image in direct polarization;

z is the vertical coordinate (the depth at which the signal is recorded) is indicated by a yellow vertical arrow;

x is the transverse coordinate, indicated by the yellow horizontal arrow.

In FIG. 2 shows diagrams of the powers of the OCT signal averaged over the transverse coordinate, calculated from the CP OCT image of FIG. one:

A is a diagram of the powers of the OCT signal averaged over the transverse coordinate as a function of the sounding depth (longitudinal coordinate) for the OCT image in orthogonal polarization;

B is a diagram of the powers of the OCT signal averaged over the transverse coordinate depending on the sounding depth (longitudinal coordinate) for the OCT image in direct polarization;

The horizontal dashed line indicates the level of the average value of the background OCT signal in the orthogonal polarization, increased by twice the standard deviation of the background OCT signal. Above this line is the OCT signal, which is taken to calculate the IDF.

The proposed method was a study of 150 sections of the mucous membranes of the oral cavity (in the cheek) and the bladder (of which 20 sections of the mucous membranes of the oral cavity (in the cheek) and the bladder are normal and 130 sections of the mucous membranes of the oral cavity (in the cheek) and bladder with pathology).

All the results were confirmed by clinical studies, in particular, morphological studies of histology.

The proposed method was implemented using a cross-polarized optical coherence tomograph (KP OCT device) “OKT 1300-U” (IAP RAS, Nizhny Novgorod), which received a CP OCT image, and a package of application programs for solving problems of technical calculations - for example, MATLAB R2012a (version 7.14.0.739), with the help of which the IFD value is automatically calculated.

Examples of specific uses of the proposed method

Dentistry

Example 1

Patient B., 60 years old.

Diagnosis: lichen planus on the left cheek mucosa.

From the anamnesis - the duration of the disease is more than 10 years.

The histological conclusion: acute inflammation of the mucous membrane of the cheek is a chronic stomatitis with the formation of lymphoid follicles with growth centers, which indicates the autoimmune nature of inflammation. Lichen planus.

04/16/2009 the proposed method was a study of the mucous membrane of the cheek in a pathological focus, which included a study of the internal structure of collagen-containing tissue to a depth of 2 mm using cross-polarized optical coherence tomography (CP OCT), registration of the OCT image of the tissue in orthogonal and direct polarizations, potentiation of the OCT image in orthogonal and direct polarizations to obtain the power of the OCT signal in relative units, averaging the obtained potentiometer of the transformed OCT image, subtracting the average value of the background signal from the averaged OCT signal in orthogonal polarization, then finding the ratio of the power of the OCT signal averaged over the transverse coordinate in the orthogonal and direct polarizations, averaging this ratio along the longitudinal coordinate over all sensing depths, for which the power of the OCT signal in orthogonal polarization exceeds the average value of the background OCT signal by twice the standard deviation of the background OCT signal, as follows General formula:

- мощность ОКТ-сигнала в прямой поляризации в i-том пикселе после усреднения по поперечной координате,

- мощность ОКТ-сигнала в ортогональной поляризации в i-том пикселе после усреднения по поперечной координате, N - число пикселов в усредненном по поперечной координате ОКТ-сигнале в ортогональной поляризации, для которых мощность ОКТ-сигнала превышает среднюю величину фонового ОКТ-сигнала 〈Р_фон〉 на удвоенное стандартное отклонение фонового ОКТ сигнала 2s_фон, был вычислен интегральный фактор деполяризации (ИФД), величина которого составила 0,03.Where:

- power of the OCT signal in direct polarization in the i-th pixel after averaging over the transverse coordinate,

is the power of the OCT signal in orthogonal polarization in the i-th pixel after averaging over the transverse coordinate, N is the number of pixels in the OCT signal averaged over the transverse coordinate in the orthogonal polarization, for which the power of the OCT signal exceeds the average value of the background OCT signal 〈P _background 〉 to twice the standard deviation of the background OCT signal 2s _background , the integral factor of depolarization (IPD) was calculated, the value of which was 0.03.

The obtained IFD value of 0.03 is included in the found 95% confidence interval of values for the acute inflammation group (0.03-0.05).

Based on the result, acute inflammation of the mucous membrane of the cheek was diagnosed.

Example 2

Patient B., 69 l.

Diagnosis: ulcerative colitis.

To verify the digestive system disease, we performed complex general clinical, endoscopic (including ileocolonoscopy with examination of the terminal ileum and multiple biopsies), laboratory and morphological studies, based on which an unconditional diagnosis was made: ulcerative colitis.

Anamnesis: ulcerative colitis for more than 5 years. A disease of moderate severity with a lesion of a segment of the colon, a chronic, recurrent form.

The histological conclusion on the mucous membrane of the cheek: in the underlying stroma moderate fibrosis (sclerosis) is moderate, as a result of incomplete repair of connective tissue after chronic inflammation, scanty diffuse lymphoid infiltration.

A visual examination of the mucous membrane of the cheek is pink, there is no edema, but a visual examination does not make it possible to judge the state of the subepithelial structures (including collagen fibers). 05.21.2009, the proposed method was a study of the mucous membrane of the cheek, as in example 1.

The obtained IFD value was 0.11.

Based on the obtained result, fibrotic changes in the subepithelial fibrous structures (collagen fibers) in the cheek area were diagnosed - the obtained IPD is included in the found 95% confidence interval for the fibrous tissue formation group (0.08-0.12), which indicates an increased in comparison with the norm (95% confidence interval of IFD values 0.08-0.09) of the ability of collagen fibers to change the initial state of polarization of the probe radiation.

Example 3

Patient A., 29 l.

Diagnosis: Crohn's disease.

To verify the digestive system disease, comprehensive clinical, endoscopic (including ileocolonoscopy with examination of the terminal ileum and multiple biopsy), laboratory and morphological studies were carried out, on the basis of which an unconditional diagnosis of Crohn's disease was established.

Clinical manifestations in the intestines of this patient are accompanied by changes in the oral mucosa. A biopsy confirmed the presence of fibro-cicatricial changes in the connective tissue (diffuse replacement sclerosis) as a result of the replacement of the primary connective tissue at the site of the inflammatory follicle. A visual examination of the mucous membrane of the cheek is pink, there is no edema, but a visual examination does not make it possible to judge the state of the subepithelial structures (including collagen fibers).

05/15/2009 the proposed method was a study of the surface area of the mucous membrane of the cheek to a depth of 2 mm in the middle of the line connecting the excretory duct of the salivary gland and the angle of the mouth on the right at the level of 7 tooth (second molar), as in example 1.

The obtained IFD value was 0.23.

Based on the result, fibro-cicatricial changes (diffuse substitution sclerosis) of subepithelial fibrous structures (collagen fibers) in the cheek area were diagnosed - the obtained IPD value exceeded the 95% confidence interval for the fibro-scar tissue formation group (0.11-0, 15), which indicates an increased compared with the norm (range of IPD values 0.08-0.09) ability of collagen fibers to change the initial state of polarization of the probe radiation due to the significant about an increase in their number and marked densification of connective tissue. There is an opinion about the involvement of the oral mucosa in the inflammatory process in Crohn's disease, which is associated with systemic manifestations of the disease. The tendency of the gastrointestinal mucosa to fibrosis (the formation of fibro-scar tissue) in Crohn's disease can be considered proven. Thus, the proposed method allowed non-invasively accurate assessment of the functional state of collagen-containing tissue in favor of Crohn's disease.

Urology.

Example 4

Patient B. 75 l.

Diagnosis: Relapse of bladder cancer Tl (m) NxM0 G1.

Anamnesis: since 2003, suffering from bladder cancer, then transurethral resection of the bladder (TUR) was performed with ureterocystone anastomosis on the left.

At the next examination (cystoscopy from 06/18/2009), a tumor 2 cm in diameter was detected on the lower back wall, a suspicious zone around the right mouth, and a small villous growth in the center of the right side wall. Shown TOUR.

06/22/2009, the proposed method conducted a study, as in example 1, while examining two sections of the mucous membrane of the bladder.

The IFD value obtained for the first image was 0.07, which is close to the upper boundary of the found 95% confidence interval for the acute inflammation group (0.04-0.060).

The IFD value obtained for the second image was 0.02, which is included in the found 95% confidence interval for the cancer group with the onset of invasive growth (0.02-0.03), which indicates an even more significant decrease compared with the acute inflammation group (range of IFD values 0.04-0.06) and normal (range of IFD values 0.09-0.11) the ability of collagen fibers to change the initial state of polarization of the probe radiation due to deep disorganization of collagen fibers under an invasively growing tumor, up to lnogo cleavage.

Based on the results obtained, two conditions were diagnosed in two zones: acute inflammation and bladder cancer with the onset of invasive growth.

Example 5

Patient D., 75 l.

Diagnosis: Chronic cystitis, leukoplakia in the region of the Lieto triangle. Anamnesis: suffers from cystitis for about 40 years, exacerbations occur 2-3 times a year, last exacerbation from 04/21/2006.

On July 31, 2006, during a TOUR, a suspicious zone was identified on the left side wall. A biopsy was taken from this area. The histological conclusion: in the submucosal layer - moderate fibrosis of collagen fibers, as a result of repair of connective tissue after chronic inflammation, moderate uneven lymphoplasmacytic infiltrates.

07/11/2006, the proposed method was a study of the mucous membrane of the bladder, as in example 1.

The obtained IFD value was 0.14.

This IFD value is included in the found 95% confidence interval for the fibrous tissue formation group (0.12-0.15).

Example 6

Patient E., 65 l.

Diagnosis: Relapse of bladder cancer T1-2N0M0 G1, cancer

prostate gland T3NxMx.

Anamnesis: since 2005, suffering from bladder cancer.

TUR of the bladder was performed twice, after which there were scars on the mucous membrane, around one of them during the next examination (cystoscopy from November 6, 2007) a zone of small villous growth of 0.5 cm in diameter was detected, suspicious of a tumor.

During the operation, 11/15/2007, a biopsy of two suspicious areas of the bladder was taken. A biopsy from the scar zone on the posterior wall (1st zone) revealed a coarse fibrous scar tissue in the subepithelial layer - the result of tissue healing after electrocoagulation. A biopsy from the periphery of the tumor (2nd zone) revealed an inverted papilloma with dysplasia of 2-3 tbsp; there is no growth of a cancer tumor.

November 15, 2007 during the operation of the proposed method was a study of the mucous membrane of the bladder, as in example 1.

The obtained IFD values were: for the 1st zone 0.27, which corresponds to the formation of scar tissue (95% confidence interval of the IFD values is 0.20-0.25), for the 2nd zone 0.04, which corresponds to the state of severe dysplasia epithelium (cancer in situ) (95% confidence interval of IFD values is 0.03-0.05).

Example 7

Patient J., 73

Diagnosis: Relapse of bladder cancer on the scar T2N0M0 G3-4. Anamnesis: since 2004 - bladder cancer. TUR of the bladder was performed twice for a non-healing ulcer, after which a scar remained on the mucous membrane, around which at the next examination (cystoscopy from 04/06/2008) a tumor was found on the rumen. Shown TOUR.

The histological conclusion: urothelial cancer 2-3 tbsp. malignancy with invasive growth in the submucosal and muscle layers, in the underlying tissue - sharp plethora, edema, focal abundant lymphoplasmacytic infiltrates.

04/10/2008, the proposed method was a study of the mucous membrane of the bladder, as in example 1.

The obtained IFD value was 0.04, which corresponds to the state of cancer in the postoperative scar (0.04-0.07).

As can be seen from the obtained data, the proposed method allows to accurately evaluate the functional state of collagen-containing tissue, namely collagen fibers of the stroma of the mucous membranes, both in dentistry and in urology, which gives reason to use the proposed method in other areas of medicine, for example, gynecology , radiation diagnostics, laryngology.

Information sources

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2. RF patent No. 2320271, application 2006122923/14 dated 06/27/2006 on "A method for predicting the severity of the reaction of the mucous membrane of the oral cavity and pharynx during radiation or chemoradiotherapy of malignant neoplasms of the oropharyngeal region."

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Claims (1)

A method for assessing the functional state of collagen-containing tissue, including studying the internal structure of collagen-containing tissue to a depth of 2 mm using cross-polarized optical coherence tomography (CP OCT), registering the OCT image of the tissue under investigation in orthogonal and direct polarizations, calculating the average value of the OCT signal in orthogonal polarization and the average background value of the signal, determining the magnitude of the OCT signal, which is the difference between the average value of the OCT signal in the orthogonal polarization and the average value of the background OCT signal and assessing the functional state of the tissue under study, characterized in that the OCT image is potentiated in orthogonal and direct polarizations to obtain the power of the OCT signal in relative units, the obtained potentiated OCT image is averaged over the transverse coordinate , subtract from the average OCT signal in orthogonal polarization the average value of the background signal, then take the ratio of the powers averaged over the transverse coordinate T-signal in orthogonal and direct polarizations, after which this ratio is averaged over the longitudinal coordinate over all sounding depths for which the power of the OCT signal in orthogonal polarization exceeds the average value of the background OCT signal by twice the standard deviation of the background OCT signal, the obtained value is integral depolarization factor (IFD), which assesses the functional state of the collagen-containing tissue under study,
and for the mucous membrane of the oral cavity in the cheek region, the normal IFD value is over 0.08 to 0.09,
in acute inflammation - from 0.03 to 0.05,
with the formation of fibrous tissue - from 0.10 to 0.13,
with the formation of fibro-scar tissue - over 0.13 to 0.17;
for the mucous membrane of the bladder, the normal IFD value is - over 0.08 to 0.12,
in acute inflammation - over 0.05 to 0.07,
with the formation of fibrous tissue - over 0.11 to 0.17,
with severe dysplasia of the epithelium - from 0.03 to 0.05,
with flat cancer with the onset of invasive growth, from 0.01 to 0.02;
for tissue of the postoperative scar in the bladder, the value of IFD is normally greater than 0.17 to 0.27,
and for cancer in the postoperative scar - from 0.03 to 0.09.

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