RU2841984C1 - Method for diagnosing vulvovaginal atrophy in patients with genitourinary menopausal syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to gynaecology, X-ray diagnostics, and can be used in instant diagnosis of vulvovaginal atrophy and in therapeutic effectiveness monitoring. Multimodal optical coherent tomography (MM-OCT) is performed in two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and in one point of the upper vagina. An attenuation coefficient is calculated, and an epithelium thickness is determined. OCT-angiography and OCT-lymphangiography are performed, and a diameter, a structure and an area occupied by the vasculature in relation to the entire image are assessed, as well as an area of the vascular lymphographic mesh in relation to the entire image. If on the attenuation coefficient maps from all three points the average epithelium thickness is less than 400 mcm, on the OCT angiography images from all three points the large and small diameter vessels tree structure is not visualized, and the vessels make up less than 60% of the area of the entire image, on the OCT lymphangiography images from all three points, the vascular area is more than 20% of the area of the entire image, vulvovaginal atrophy is diagnosed.

EFFECT: method enables providing the more effective non-invasive diagnosis of vulvovaginal atrophy accompanying genitourinary menopausal syndrome in postmenopausal females by evaluating the structural, angiographic and lymphangiographic criteria with using the OCT.

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Description

The invention relates to medicine, namely to gynecology, radiation diagnostics and visualization methods, and can be used for assessment in express diagnostics (screening) of vulvovaginal atrophy and in monitoring the effectiveness of therapy.

Perimenopausal and postmenopausal age is one of the most difficult periods in a woman's life. The deficiency of sex hormones that occurs at this time against the background of decreased ovarian function is often manifested not only by the deterioration of the general condition of patients, but also by local symptoms of vulvovaginal atrophy (VVA) in the form of discomfort, dyspareunia, dryness, itching and burning of the mucous membranes of the vulvovaginal zone and atrophy of the bladder and urethra (dysuric manifestations, urinary tract infections), which significantly reduces the quality of life of patients in this age group and leads to various behavioral and social restrictions. The term "genitourinary menopausal syndrome" (GUMS) has been proposed to denote the complex of these symptoms [1-3].

The above changes are explained by a specific tissue stress of estrogen-dependent structures of the female body. Such structures include, in particular, the vaginal wall. The vaginal wall consists of three layers: the internal, or mucous membrane, the middle, or smooth muscle, and the external, or adventitial. The vaginal mucosa is lined with non-keratinizing stratified squamous epithelium and consists of four types of cells: basal, parabasal, intermediate, and superficial, forming about 30-40 rows. Under the epithelium is the proper plate of the mucosa, which is represented by connective tissue and contains collagen, elastic fibers, fibroblasts, blood and lymphatic vessels, and nerve fibers. Vaginal epithelial cells are very sensitive to estrogen deficiency, therefore, as the level of sex steroids decreases during the fading of ovarian stimulation, a decrease in the proportion of superficial and intermediate cells is observed during histological and cytological assessment [2-5]. The results of morphological studies indicate that estrogen deficiency causes structural changes in the tissues of the genitourinary system, manifested by thinning of the vaginal epithelium, decreased elasticity, decreased production of glycogen by the epithelium, which entails a decrease in the number of lactobacilli and a change in the pH of the vagina, increased susceptibility to infectious and inflammatory diseases, and also creates the prerequisites for the development of deeper tissue disorders, including a decrease in the vascularization of connective tissue elements and oncological processes [6].

Currently, diagnostics of atrophic conditions of the vulva and vagina is mainly based on subjective, indirect assessment of the tissue condition, including anamnesis data (various questionnaires), visual assessment of the mucosa (vaginal health index - VHI), colpovaginoscopy and vulvoscopy, cytological examination with calculation of the epithelial maturation index and morphological analysis of tissue biopsies. However, subjective data from questionnaires, gynecological examination and the results of laboratory methods do not always correlate with each other, which, in turn, complicates the personalization of treatment approaches and optimization of the management of patients with GUMS. And, finally, the arsenal of non-invasive methods used does not allow reliable and unambiguous differentiation of manifestations of vulvovaginal atrophy (VVA) from other pathological processes: lichen sclerosus, vaginal lichen planus, contact dermatitis, some malignant diseases. In this regard, it is necessary to resort to tissue biopsy with inevitable trauma to the mucous membrane and possible worsening of local symptoms. All of the above necessitates an objective assessment of the state of the epithelium and underlying connective tissue of the vulvovaginal zone.

For clinical scoring of the vaginal condition during a gynecological examination, the vaginal health index (VHI) is calculated using a special scale [7]. A number of parameters are measured: the presence of discharge, the pH value of the vagina, the elasticity of the wall, the degree of moisture, the state of the epithelium, each of which is assessed in points. The sum of these points is the VHI value. This test rather gives an idea of the functioning of the vaginal mucosa than of its structure. It is believed that a conditionally healthy state of the epithelium is marked by high points (from 20 to 25), 15-20 - minor atrophy, 15 points and below - severe atrophic changes in the vaginal mucosa. This method has a significant drawback due to the fact that responsibility for the test results is assigned to the gynecologist, which determines its subjectivity. In addition, due to subjectivity, the results of visual methods do not have a reliable correlation with real changes in the tissue of the vaginal mucosa and symptoms of GUMS.

Colpovaginoscopy is also used to assess the condition of the epithelium - a method of visual assessment of the epithelial layer of the vaginal wall [8]. The study is conducted using a binocular microscope and is supplemented by epithelial tests. Colpovaginoscopic signs of atrophy are: pale thinned epithelium, the presence of subepithelial vessels, petechial hemorrhages, contact bleeding, weak staining with a test with Lugol's solution [9]. This method allows for quick visual confirmation of the presence of atrophic changes in GUMS, however, the analysis of the test and stratification by the severity of the lesion are very relative, which is determined by the experience of the doctor, the skill of conducting colpovaginoscopy and the subjectivity of the interpretation of the results obtained.

Cytological examination of vaginal wall scraping is also used to assess the epithelium condition. Epithelial formula (EF) is calculated, where the number of cells of all layers and the epithelial maturation index are counted. EF shows the number of cells, where the first number indicates the number of basal cells, then parabasal, then intermediate and the last one is superficial cells. In general, EF in case of atrophy may look like this: 40/60/0/0. However, the results of this test do not provide an opportunity to assess the thickness of all layers of the vaginal wall and their structure, but only the representation of epithelial layer cells with an indirect characteristic of its condition. In addition, the assessment of the cytological preparation can also be subjective and insufficiently accurate, since the material during cell collection can often be unrepresentative, the method does not take into account the influence of exogenous (urogenital infections) and endogenous (immune disorders, blood steroid levels) factors. In addition, routine cytological assessment of the preparation may lead to incorrect results due to changes in cell morphology under the influence of hypoestrogenism: cells do not mature, have a high nuclear-cytoplasmic ratio, which can imitate atypical changes in the epithelium and be falsely interpreted as neoplasia. Despite its informativeness, histological examination is associated with the risks of iatrogenic complications (bleeding, inflammation) and aggravation of existing symptoms, and is limited in frequency of performance due to the patient's reluctance, which prevents optimal monitoring of the tissue condition during therapy.

Considering that traditional methods cannot fully provide an adequate assessment of the condition of the vaginal mucosa, it is currently necessary to search for new, informative and safe diagnostic approaches for non-invasive assessment of the condition of the vaginal wall in GUMS during clinical examination, including modern bioimaging capabilities.

In this regard, a number of authors note that the use of ultrasound diagnostics to determine the thickness of the vaginal mucosa may be useful as a possible tool for dynamic monitoring and evaluation of treatment effectiveness. H. Peker et al. (2021) describe the use of 3D high-frequency ultrasound (US) to measure the thickness of the anterior and posterior vaginal walls [10]. However, a significant disadvantage of this method is its operator dependence and some subjectivity, as well as the inability to assess the structure of connective tissue, the state of collagen and elastic fibers, and microcirculation, which, in turn, serve as important markers of the state of the vaginal wall, due to limitations in the resolution of the equipment.

Another group of authors proposed a method for assessing the state of vaginal vessels using ultrasound Doppler, based on determining the resistance index (RI) of the vessels [11], where high RI values indicate a decrease in blood supply in the subepithelial layer, which may reflect atrophic changes in the epithelium. Despite the simplicity of the diagnostic test, the method is not sensitive enough in diagnosing atrophic conditions of the vaginal epithelium, and the frequency of false-negative results is high. According to our unpublished data, normal RI values do not always exclude the presence of pathology.

In our opinion, one of the most promising diagnostic methods for assessing VVA is multimodal optical coherence tomography (MM-OCT), which combines a multifaceted intravital non-invasive study of the structural and functional features of biological tissues. The OCT method is based on the use of optical radiation of the near infrared range (1310 nm), allows you to obtain structural and angiographic images of tissues with high resolution (about 15 μm) in real time, without the use of contrast agents and demonstrates the structure of the mucosa to a depth of 1.5-2 mm, which includes epithelium and vascularized connective tissue. The OCT method is also called "optical biopsy", since it quite accurately reflects the morphology of the tissue based on the differences in the scattering properties of its various components.

The closest analogue to the proposed one is the method for assessing atrophic changes in the vaginal wall using OCT at different periods of a woman’s life [12]. Chinese researchers compared lifetime OCT images of premenopausal, perimenopausal and postmenopausal women in their initial status, as well as for assessing changes in vaginal tissues after a course of _CO2 laser treatment. The obtained OCT images were correlated with histological examination of a biopsy specimen obtained from a cadaveric preparation of the corresponding area of other patients. The authors demonstrated the capabilities of OCT to obtain structural 360-degree OCT images of the entire length of the vagina in about 60 seconds. The characteristics of the device used were as follows: central wavelength of 1300 nm, scanning depth of up to 2 mm. A catheter-type vaginal probe was placed in a special oblong transparent case with a diameter of 12 mm and a length of 150 mm, which minimized vaginal folding. The obtained OCT images reliably determined the epithelium and proper lamina of the vaginal mucosa. Based on 30 randomly selected OCT images along the vaginal wall, the average thickness of the vaginal epithelium in women at different periods of life was calculated. The authors of the same research group also conducted a study in which the condition of the vaginal wall was assessed using OCT at three points at different levels of the vagina [13]. It was shown that atrophic changes in GUMS predominantly affect the lower parts and vestibule of the vagina.

The disadvantages of this method are: the duration of the procedure (about 1 minute), the impossibility of assessing the structure of the connective tissue lamina propria, the vascular and lymphatic component of the vaginal mucosa. In addition, the method includes the analysis of random images and averaging the thickness of the vaginal epithelium (TVE) in different parts of the vagina without taking into account the features of the wall structure and the probability of damage by atrophy of different parts of the vagina to varying degrees. Comparison with cadaveric material obtained from other patients obviously does not provide confidence in the adequacy of histotomographic comparisons. The method does not provide for subdivision into degrees of atrophy severity due to the lack of strict optical criteria for these tissue conditions.

The objective of the present invention is to create a method for assessing the degree of atrophic changes in the vaginal wall mucosa in GUMS based on the developed optical (structural, angiographic and lymphangiographic) criteria. This will allow the invention to be used for diagnosing VVA, as well as, taking into account individual parameters, to create a personalized treatment algorithm and conduct a non-invasive assessment of the response to treatment.

The technical result is an increase in the efficiency and speed of non-invasive diagnostics of vulvovaginal atrophy (VVA) in women of menopausal age, avoiding tissue trauma; assessment of the severity of vaginal epithelium atrophy, vascularization of subepithelial connective tissue, including at treatment stages.

The technical result is achieved by conducting an MM-OCT study, including calculation of the signal attenuation coefficient, OCT angiography and OCT lymphangiography, at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina; signal attenuation maps are obtained in the B-scan projection, and angiographic and lymphangiographic images are obtained in the en-face projection; the thickness of the epithelium is determined on the obtained attenuation coefficient maps, the diameter, structure and area occupied by the vascular network in relation to the entire image are estimated on the OCT angiography images, and the area of the vascular lymphographic network in relation to the entire image is estimated on the OCT lymphangiography images; If the average epithelial thickness on the attenuation coefficient maps from all three points is less than 400 μm, the tree-like structure of vessels of different (large and small) diameters is not visualized on the OCT angiography images from all three points, and the vessels make up less than 60% of the entire image area, and the vessel area on the OCT lymphangiography images from all three points is more than 20% of the entire image area, then the condition of the vaginal wall mucosa is assessed as vulvovaginal atrophy, and the smaller the epithelial thickness and the smaller the vascular network area on the OCT angiography images, and the larger the vascular network area on the OCT lymphangiography images, the higher the degree of atrophy.

The method is illustrated by figures, where Fig. 1 shows a diagram of the selection of points, which was used in the protocol of the conducted study (1 - a point in the vestibule of the vagina, 2 - a point in the vestibule of the vagina, symmetrical to point 1 relative to the axis of the vagina, at which, after conducting the MM-OCT study, biopsy material was collected, 3 - a point in the upper section of the vagina); Fig. 2 shows the external appearance of the MM-OCT device; Fig. 3 shows the "pencil" type OCT probe used in the study.

The method is carried out as follows: the patient is placed on a gynecological chair, the cervix and vaginal walls are examined using a gynecological mirror, a vaginal OCT probe is installed alternately at the points of interest and the examination is carried out.

The examination is carried out at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper part of the vagina, for example, as shown in Fig. 1.

A multimodal OCT system (BioMedTech, Nizhny Novgorod, Russia) is used for the study, which allows for simultaneous acquisition of attenuation coefficient maps, angiographic and lymphangiographic images (Fig. 2). The main characteristics of the system are: central wavelength - 1310 nm, axial resolution - 10 μm, transverse resolution - 15 μm, scanning depth - up to 2 mm, scanning speed - 20,000 A-scans per second. The OCT system is equipped with a rigid fiber-optic probe, which ends with an end-on "pencil"-type objective (length 8 cm) and is intended for contact tissue examination (Fig. 3).

The rigid probe (Fig. 3) is additionally fixed on the holder to eliminate the appearance of motion artifacts in the images. The probe is installed in turn at each point to obtain OCT images and held for 26 seconds to obtain a three-dimensional OCT array measuring 3.4 × 3.4 × 1.25 mm with simultaneous visualization of the tissue structure, angio- and lymphatic circulation. Thus, 3 volumetric OCT images are obtained from each patient, from which two-dimensional structural, angiographic and lymphangiographic images are obtained.

Quantitative processing of structural OCT images is performed using the built-in software of the OCT system, which allows calculating the attenuation coefficients of the optical signal, which describes the loss of the OCT signal with depth due to scattering and absorption of probing radiation when interacting with various structures and is used in the assessment of various tissues [14]. This indicator allows objectifying the visualization of the biological structure and differentiating conditionally normal and pathologically altered tissues. Based on the attenuation coefficient values, the OCT system allows constructing color-coded maps of the distribution of the coefficient values in the B-scan projection, which has a size of 512 × 256 pixels. Color-coded maps are analyzed in the B-scan projection, which use a rainbow scale, where blue denotes low values of the signal attenuation coefficient (0-2 mm ^-1 ), and red - high (11-12 mm ^-1 ). Visualization of blood vessels is based on the analysis of the spectral structure and does not require the use of contrast agents [15, 16]. Visualization of lymphatic vessels is based on the analysis of the three-dimensional distribution of the attenuation coefficient with depth resolution, corrected for noise, and is described in detail in [17].

The OCT system allows to present the obtained three-dimensional vascular networks as 2D images in the projection of maximum intensity for blood vessels and the projection of average intensity for lymphatic vessels in the depth range of 0-400 μm. The boundary of the epithelium and the lamina propria is taken as the reference point. Blood vessels are presented in a red palette, lymphatic vessels in a white palette on a black background. Semi-quantitative assessment of the vascular component (blood and lymphatic vessels) is carried out visually with a step of 20% - 0, 20, 40, 60, 80, 100%, the area of the vascular network is estimated to the area of the entire image.

The thickness of the epithelium is determined by the attenuation coefficient maps. The thickness is calculated as a segment from the epithelial surface and perpendicular to it, to the border of the epithelium and the lamina propria of the mucosa. The average value is calculated for nine measurements, three measurements for each of the three attenuation coefficient maps in the B-scan projection (the two outer and central B-scans were selected from the 3D data array). The epithelium has low attenuation coefficient values and is therefore shown in blue. The lamina propria of the mucosa has high coefficient values, shown in yellow-green-red. The border between the layers is contrasting and easily determined.

Thus, on the obtained attenuation coefficient maps, the thickness of the epithelium is determined, on the OCT angiography images, the diameter, structure and area occupied by the vascular network in relation to the entire image are assessed, on the OCT lymphangiography images, the area of the vascular lymphographic network is assessed in relation to the entire image.

If the average epithelial thickness on the attenuation coefficient maps from all three points is less than 400 μm, the dendritic structure of vessels of different (large and small) diameters is not visualized on the OCT angiography images from all three points, while the vessels make up less than 60% of the entire image area, and the area of the vessels on the OCT lymphangiography images from all three points is more than 20% of the entire image area, then the condition of the vaginal wall mucosa is assessed as vulvovaginal atrophy, and the smaller the epithelial thickness and the smaller the area of the vascular network on the OCT angiography images, and the larger the area of the vascular network on the OCT lymphangiography images, the higher the degree of atrophy is assessed.

The method was used in a study involving 35 women with GUMS, confirmed by standard clinical and laboratory methods, and 3 patients with a conditional age norm without a GUMS clinic using MM-OCT according to the proposed method.

The obtained OCT images were compared with clinical manifestations and histological picture after targeted biopsy of the corresponding zones. Morphological examination of biopsy specimens included a detailed description of the structure of the mucous membrane with characteristics of the epithelial layer (the presence of glycogen in cells) and the lamina propria, including the vascular component, collagen fibers, components of the inflammatory process. Hematoxylin and eosin staining was performed to assess the overall picture, and the PAS reaction was used to detect glycogen. Histological preparations were analyzed using the EVOS M7000 visualization system (Thermo Fisher Scientific Inc., USA) in transmitted light.

600 OCT images were analyzed and clinical-histo-tomographic comparisons were performed to develop optical criteria of the conditional norm and pathology with stratification by the degrees of severity of VVA manifestations. In the resulting array of images, the optical criteria of the conditional norm/pathology were those features that were present in all analyzed points of the zone of interest, in particular: epithelial thickness, area occupied by blood and lymphatic vessels in relation to the frame area.

We provide examples of specific use of the method.

Example No. 1. Patient S., 57 years old

Early perimenopause, no complaints, does not use hormonal therapy.

According to the examination data: the mucous membrane of the vaginal entrance is uniformly pink, the folds are pronounced, the discharge is moderate, light mucous, the IVZ is 24 points. According to the colpovaginoscopy data, no atrophic changes were detected. According to the cytological examination of the vaginal walls: EF 0/0/40/60.

An MM-OCT study was performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper vagina. Fig. 4 shows images illustrating this example, where (a) is a histological image (PAS reaction), (b) is a structural OCT image (B-scan), (c) is a color-coded map of the OCT signal attenuation coefficient (B-scan), (d) is OCT angiography, (d) is OCT lymphangiography. In this and the following figures illustrating specific examples of use, the letter "E" denotes the epithelium, and the letters "LP" denote the lamina propria. The segment on the B-scans, highlighted by the white dotted line, corresponds to the segment of the biopsy and histological examination. White arrows denote the lymphatic vessels on the histological preparations and B-scans. Angiographic and lymphangiographic images were obtained from a depth of 0-400 μm. Rainbow scale is a color coding of the values of the attenuation coefficient of the OCT signal. Bar 500 μm;

As a result of the analysis of structural, angiographic and lymphangiographic images, the following values were obtained:

- thick epithelium (435 µm) (Fig. 4 b, c);

- blood vessels of different diameters (large and small), occupying more than 60% of the image area (Fig. 4 g);

- visually single lymphatic vessels in the form of short fragments (the area of the lymphatic vessels is no more than 20%) (Fig. 4 d).

Based on a set of OCT criteria, a conclusion was made about the normal state of the vaginal wall mucosa.

A comparison was made between the OCT study and the histological study (the area of interest is highlighted by a square on the structural OCT image and corresponds to the histological image, Fig. 4a), where:

- the epithelial layer, 420 µm thick, consists of several rows of cells of different types (basal, parabasal, intermediate and superficial), the upper layers of the epithelium contain glycogen in the form of a continuous layer, the basement membrane is clear and smooth;

- in the proper plate of the mucosa there are numerous blood vessels of different diameters, single lumens of lymphatic vessels.

The obtained results indicate the normal condition of the vaginal wall, which fully correlates with the conclusions of the proposed method.

Example No. 2. Patient G., 47 years old

Perimenopause, for 2 years I have been bothered by a feeling of dryness in the vagina, frequent urination, I have not sought help.

According to the examination data: the mucous membrane is pale pink, moderately thinned, the folding is reduced, the discharge is scanty yellowish, IVZ is 15 points. According to the colpovaginoscopy data, slight atrophic changes in the vaginal mucosa were revealed. According to the results of the cytological examination of the vaginal walls, EF is 0/17/52/31.

An MM-OCT study was performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina. Fig. 5 shows images illustrating this example, where (a) is a histological image (PAS reaction), (b) is a structural OCT image (B-scan), (c) is a color-coded map of the OCT signal attenuation coefficient (B-scan), (d) is OCT angiography, (d) is OCT lymphangiography.

According to MM-OCT data:

- the epithelium of the vaginal wall is thin (310 µm) (Fig. 5 b, c);

- blood vessels occupy less than 60% of the image area, their normal branching structure is preserved, and they are predominantly of medium and small diameter;

- multiple dilated lymphatic vessels are united into a network, the area of lymphatic vessels is 80% of the image area (Fig. 5 d).

Based on the obtained results, a conclusion was made about the presence of mild VVA.

The proposed method confirmed the suspected clinical diagnosis, which was also confirmed by the results of the histological examination (Fig. 5a):

- epithelial layer, 374 µm thick, the upper layers of the epithelium contain glycogen in the form of a discontinuous layer, the basement membrane is clear and smooth;

- in the proper plate of the mucosa there are blood vessels of different diameters, a large number of dilated lymphatic vessels.

Thus, MM-OCT allowed for an objective intravital assessment of the state of the epithelium, lamina propria, and vascular network and confirmed the diagnosis of mild VVA in GUMS.

Example No. 3. Patient V., 70 years old

Postmenopausal 25 years old, for 10 years has been bothered by a constant feeling of dryness and burning in the vagina, pain during intercourse, frequent urination, episodes of urinary incontinence, did not seek help.

According to the examination data: the mucous membrane is pale pink, sharply thinned, translucent, has multiple petechial hemorrhages along the vaginal walls, no folding, virtually no discharge, IVZ 8 points. Colpovaginoscopic signs of pronounced atrophic changes in the vaginal mucosa were revealed. According to the cytological examination of the vaginal walls: epithelial formula 30/55/15/0. Based on the results of standard examinations, a diagnosis of GUMS was made.

An MM-OCT study was performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina. Fig. 6 shows images illustrating this example, where (a) is a histological image (PAS reaction), (b) is a structural OCT image (B-scan), (c) is a color-coded map of the OCT signal attenuation coefficient (B-scan), (d) is OCT angiography, (d) is OCT lymphangiography.

According to MM-OCT data:

- thin epithelium of the vaginal wall (130 µm) (Fig. 6 b, c);

- a sharply reduced number of blood vessels, predominantly small in diameter, with a linear arrangement, occupying 20-40% of the image area (Fig. 6 g);

- multiple dilated lymphatic vessels, united into a network, occupy 60% of the image area (Fig. 6 d).

Based on the results obtained, a conclusion was made about the presence of severe atrophic damage to the vaginal wall.

The proposed method confirmed the presumed clinical diagnosis, which was also described by the histological examination data, the epithelial thickness was 103 μm (Fig. 6a). MM-OCT allowed an objective intravital assessment of the state of the epithelial layer, the lamina propria, its vascular network and reliably determine the signs of severe atrophic damage to the vaginal wall.

Example No. 4. Patient K., 46 years old

Postmenopause for 2 years, for 2 years I have been bothered by a constant feeling of dryness and burning in the vagina, episodes of urine leakage, I have not sought help.

According to the examination data, the mucous membrane is uniformly pink, there is no folding, the discharge is light and scanty, IVZ is 19 points. An examination for sexually transmitted infections was conducted, no data on STIs were obtained. According to the colpovaginoscopy data, no signs of atrophy were found. Results of the cytological examination of the vaginal walls: EF 0/15/55/30.

An MM-OCT study was performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina. Fig. 7 shows images illustrating this example, where (a) is a histological image (PAS reaction), (b) is a structural OCT image (B-scan), (c) is a color-coded map of the OCT signal attenuation coefficient (B-scan), (d) is OCT angiography, (d) is OCT lymphangiography.

According to MM-OCT data:

- the epithelium of the vaginal wall is thinned (340 µm) (Fig. 7 b, c);

- blood vessels are predominantly of medium and small diameter, occupying 40-60% of the image area, the tree-like structure of the vascular network is preserved (Fig. 7 g);

- multiple dilated lymphatic vessels, united into a network, occupying 80% of the image area (Fig. 7 d).

Analyzing the obtained data, a conclusion was made about the presence of a mild atrophic lesion of the vaginal wall, despite the low information content of routine diagnostic approaches. The patient underwent a targeted biopsy in the area of MM-OCT probing, according to histology data, signs of atrophic vaginitis outside of exacerbation were described, the thickness of the epithelium was 335 μm (Fig. 7a).

Thus, the proposed method revealed signs of vaginal epithelium atrophy, which is confirmed by the results of the histological examination. OCT allowed an objective intravital assessment of the state of the epithelial layer, the lamina propria, and the vascular network. Based on the examination results, timely adequate treatment was prescribed, which improved the patient's quality of life.

Example No. 5. Patient L., 64 years old

Postmenopausal 20 years, for 7 years has been bothered by a persistent feeling of dryness and discomfort in the vagina, frequent urination, no treatment was carried out.

According to the examination data: the mucous membrane is uniformly pale pink in color, sharply thinned, during examination, when in contact with a speculum, the vaginal walls bleed contactally, there is no folding, there is practically no discharge, IVZ is 11 points. Colpovaginoscopic signs of pronounced atrophic changes in the vaginal mucosa were also revealed. According to the cytological examination of the vaginal walls: EF 55/40/5/0. Based on the results of standard examinations, mainly visual, the diagnosis of VVA in GUMS was verified.

An MM-OCT study was performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina. In Fig. 8 - images illustrating this example are presented, where (a) is a histological image (PAS reaction), (b) is a structural OCT image (B-scan) before treatment, (c) is a color-coded map of the OCT signal attenuation coefficient (B-scan) before treatment, (d) is OCT angiography before treatment, (e) is OCT lymphangiography before treatment, (e) is a structural OCT image (B-scan) 1 month after the end of treatment, (g) is a color-coded map of the OCT signal attenuation coefficient (B-scan) 1 month after the end of treatment, (h) is OCT angiography 1 month after the end of treatment, (i) is OCT lymphangiography 1 month after the end of treatment.

According to MM-OCT data:

- sharply thinned epithelium of the vaginal wall (110 µm) (Fig. 8 b, c);

- a sharply reduced number of blood vessels, predominantly small in diameter with their linear structure, occupying 20% of the area of the entire image (Fig. 8 g);

- multiple dilated lymphatic vessels, united into a network, occupy 60% of the image area (Fig. 8 d).

According to histological data, a picture of atrophic vaginitis outside of exacerbation is described (Fig. 8a):

- epithelial layer, 95 µm thick, cellular composition is represented by basal, parabasal and single intermediate cells, glycogen is absent, the basement membrane is clear and smooth;

- in the proper plate of the mucosa there are small-diameter blood vessels and a large number of dilated lymphatic vessels.

The patient underwent a course of physiotherapy using a neodymium laser. One month after the end of the course of treatment, the patient's symptoms of GUMS subjectively disappeared, but according to questionnaires and visually during a gynecological examination - without significant dynamics. Control laboratory and instrumental tests were performed: IVZ - 23 points, EF 40/50/7/3. According to MM-OCT images, positive dynamics were revealed:

- an increase in the thickness of the epithelial layer to 220 µm (from 110 µm before treatment) (Fig. 8 e, g);

- an increase in the number of blood vessels, a visual increase in their diameter, restoration of the tree-like structure with uniform branching, the area occupied by blood vessels amounted to more than 40% of the area of the OCT angiographic image (versus 20% before treatment) (Fig. 8 h);

reduction in the number of dilated lymphatic vessels, which occupy 20-40% of the image area (versus 60% before treatment) (Fig. 8 and).

Thus, the results of the control MM-OCT objectively demonstrated positive dynamics of the vaginal mucosa condition after the treatment, which coincided with the subjective sensations of the patient and allows the use of the proposed method, including as a fast and non-invasive tool for assessing the effectiveness of treatment (monitoring).

References

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Claims (3)

A method for diagnosing vulvovaginal atrophy in patients with genitourinary menopausal syndrome, characterized by the fact that multimodal optical coherence tomography (MM-OCT) with calculation of the signal attenuation coefficient, OCT angiography and OCT lymphangiography are performed at two symmetrical points of the vaginal vestibule relative to the vertical axis of the vagina and at one point of the upper section of the vagina; signal attenuation maps are obtained in the B-scan projection, angiographic and lymphangiographic images in the en-face projection; epithelial thickness is determined on the obtained attenuation coefficient maps; the diameter, structure and area occupied by the vascular network in relation to the entire image are estimated on the OCT angiography images; the area of the vascular lymphographic network in relation to the entire image is estimated on the OCT lymphangiography images; if the average epithelial thickness on the attenuation coefficient maps at all three points is less than 400 μm, the tree-like structure of large and small diameter blood vessels is not visualized on the OCT angiography images at all three points, and the vessels make up less than 60% of the area of the entire image, and the area of the vessels on the OCT lymphangiography images at all three points is more than 20% of the area of the entire image, then vulvovaginal atrophy is diagnosed, Moreover, the smaller the thickness of the epithelium and the smaller the area of the vascular network in OCT angiography images, and the larger the area of the vascular network in OCT lymphangiography images, the higher the degree of atrophy.