RU187874U1 - MEDICAL COMPLEX ON THE BASIS OF OPTICAL SPECTROMETER FOR STRUCTURAL AND FUNCTIONAL NON-INVASIVE EXPRESS DIAGNOSTICS OF THE STATE OF TISSUES OF WOMEN'S REPRODUCTIVE SYSTEM OF WOMEN - Google Patents

Abstract

The proposed device is intended for instant intravital determination of the morphological structure and functional state of the tissues of the organs of the reproductive system of women - the mucous membrane of the uterus (endometrium), cervix, ovaries, vagina and vulva. The device can be used to determine the structural and functional state of other organs and structures of the small pelvis - lymph nodes, peritoneum, bladder and rectum in normal and pathological conditions. The device records and analyzes the photoluminescence spectra and reflection spectra of tissues of the organs of the reproductive system of women in the diagnosis and monitoring of treatment of inflammatory, dystrophic, functional disorders, as well as precancerous and oncological diseases of the organs of the female reproductive system. The device is intended for use in medical diagnostic, therapeutic and prophylactic research medical purposes, can be used in any institutions of this profile. S THE creation of a medical diagnostic system for in vivo determination of morphometric and functional condition of the tissues of the reproductive system of women in real-time. Using the claimed device, an objective and accurate rapid diagnosis is carried out, which is the basis for choosing a treatment and for deciding on a woman’s readiness for pregnancy. This technical result is achieved by the fact that the claimed device (Fig. 1) includes: a housing (1) that blocks penetration of spurious electromagnetic radiation of the visible range from third-party emitters; a laser radiation source with a wavelength of 637 nm with a laser interference filter (2); white light source (3); optical fiber optical instrument (4) with replaceable protective disposable sterile caps (5); focusing and filtering system of radiation (6); spectrometer with a multichannel CCD detector (7); built-in microcontroller for processing the received photoluminescence and reflection signals (8); a computer with software (9), characterized in that the spectrometer has a wide spectral range of 400-1100 nm; the optical fiber optical instrument has three optical fiber cores that provide simultaneous measurement of the reflection and photoluminescence spectra from the studied tissues of the organs of the female reproductive system; replaceable protective disposable sterile caps prevent contamination of the optical fiber optical instrument during measurements; laser radiation with a wavelength of 637 nm due to the relatively deep penetration into the tissue allows you to record their spectral characteristics and establish their pathophysiological state; the software calculates the degree of saturation of the studied tissues with oxygen, the proliferative activity of tissue cells, the level of microcirculation in the vessels of the tissues, the structure of the various parts of the endometrium in the uterine cavity, the degree of deviation of the spectral characteristics of the studied tissues from the normal state.

Description

The utility model relates to medicine and medical technology.

The proposed device is intended for instant intravital determination of the morphological structure and functional state of the tissues of the organs of the reproductive system of women - the mucous membrane of the uterus (endometrium), cervix, ovaries, vagina and vulva. The device can be used to determine the structural and functional state of other organs and structures of the pelvic lymph nodes, peritoneum, bladder and rectum in normal and pathological conditions. The device registers and analyzes the photoluminescence spectra and the reflection spectra of tissues of the organs of the reproductive system of women in the diagnosis and monitoring of treatment of inflammatory, dystrophic, functional disorders, as well as precancerous and oncological diseases of the organs of the female reproductive system.

The device is intended for use in medical diagnostic, medical prophylactic and research medical purposes, can be used in any institutions of this profile.

Improving diagnostic methods is a strategic direction in the development of medical science and practice. Diagnosis of diseases and pathological processes of the endometrium in women with a uterine form of infertility is especially relevant. This is confirmed by the data of the Federal State Statistics Service, from which it follows that if current negative trends continue, by 2035 the population of Russia will decrease by 10 million people. up to 136 million people [http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/population/demography/]. Decree of the President of the Russian Federation No. 204 of May 7, 2018, in the first paragraph of which “provides for the sustainable natural growth of the population of the Russian Federation”, demonstrates the paramount importance of this problem [http://kremlin.ru/acts/bank/43027].

Quick and accurate diagnosis of the morphological and functional state of the endometrium and other organs of the reproductive system of women will determine the possibility of the onset and prediction of the course of pregnancy. No less significant is the early preclinical detection of endometrial hyperplastic processes and uterine cancer. Rapid diagnosis of borderline tumors and ovarian cancer is fundamental in the early diagnosis of cancer and a reduction in cancer incidence. Early diagnosis of these diseases is an extremely important and complex clinical problem.

Inflammatory processes of the endometrium (endometritis), post-inflammatory (scar-adhesive) and dystrophic changes lead to structural and functional changes in the endometrium, the results of which are infertility, miscarriage, pathology of pregnancy, childbirth and the postpartum period. The pathological condition of the endometrium determines not only the possibility of pregnancy, predicting its course, but also the state of the offspring - its pain and health.

The identification of tumor and tumor formations in the pelvic organs during diagnosis or during surgery requires immediate differentiation to determine treatment tactics and the volume of surgery. Tumor-like formations of various origins often manifest themselves in different ways, which can lead to confusion even for a very experienced doctor. As a result, there is a need for an extensive differential diagnosis, the volume of which can be reduced only by choosing accurate, informative and focused studies.

An important section of preventive medicine, the restoration of which is directed by the latest regulatory documents of the Ministry of Health, is the prevention of cancer, including organs of the reproductive system. Since cervical cancer takes the second place among oncological diseases of the female genital organs, rapid diagnosis of this disease and precancerous processes is extremely urgent.

Diagnosis of structural and especially functional disorders of the endometrium often causes difficulties associated with the polymorphism of manifestations and the lack of objective non-invasive "express" methods.

Known non-invasive methods for diagnosing the condition of the endometrium - hysteroscopy, ultrasound (ultrasound), dopplerometry do not reflect the precise pathomorphological and pathophysiological mechanisms that determine the state of the uterine mucosa (endometrium) - oxygenation, structure, microcirculation and metabolism. And morphological studies of endometrial biopsy are performed on "dead" tissue extracted from the body, and cannot fully reflect the intravital structural features of the endometrium.

The claimed device is aimed at intravital non-invasive instantaneous optical spectral express diagnostics (including photoluminescent spectroscopy and optical spectroscopy of white light reflection) using automated software. Due to the program analysis and comparison of the optical spectral characteristics of the pathological and normal tissue, an objective diagnosis is made and further treatment is predicted. Intravital optical spectroscopy of the endometrium is able to reflect the smallest characteristics of the structure and function of the endometrium (as well as other organs of the reproductive system), which opens up the possibility of personalized treatment. Spectral analysis of tissues makes it possible to objectively distinguish healthy tissues from pathological (including tumor) tissues.

An analogue of the claimed device is "Raman and photoluminescence spectroscopy", patent: US 7362426 B1. This patent describes a device and method for the simultaneous use of Raman and photoluminescent spectroscopy. In the optical response signal from the object of study, the components of the Raman signal and the photoluminescence signal are separately distinguished. The first detector allows one to obtain a component of Raman scattering of light, and the second detector allows a photoluminescence signal. The disadvantages of the device claimed in this patent are its large dimensions, the absence of a multi-channel optical fiber optical instrument for supplying laser radiation and radiation from a white light source to the object of study and collecting the optical response from it, as well as the impossibility of its use for diagnostic purposes directly on patients.

Another analogue of the claimed device is "Devices and methods for optical diagnosis of tissue", patent: US 5280788 A. This patent describes a device and method for using optical spectroscopy for the diagnosis of tissues. In particular, the patent claims one or more optical fibers used to deliver laser radiation to the tissue being diagnosed, collect the scattered optical radiation from the tissue, and deliver this radiation to the spectral analysis system. The disadvantages of the device claimed in this patent are the lack of replaceable protective disposable sterile caps for carrying out diagnostic procedures on patients, the lack of software that calculates the degree of saturation of the studied tissues with oxygen, proliferative activity of tissue cells, the level of microcirculation in the vessels, the structure of various sections of the endometrium in the uterine cavity , the degree of deviation of the spectral characteristics of the studied tissues from the normal state, as well as for conducting Nia analysis and comparison of the spectral characteristics of the pathological and normal tissue, and for setting an objective diagnosis and prognosis of further treatment.

The prototype of the claimed device is a "Device of Raman-fluorescence diagnostics of human tissues in normal and pathological conditions", patent RU 144665 U1. This patent describes a Raman fluorescence diagnostic device for measuring, recording and interpreting Raman spectra and / or photoluminescence spectra of microbes, tumors, body fluids, skin integuments, mucous membranes and body tissues (in vivo and in vitro), for diagnosis and treatment of a wide range of diseases and functional disorders of the human and animal body, as well as for the analysis of the contents of tablets, capsules, powders and liquids. The device contains a fiber optic cable for exposure to laser radiation and to collect a signal of Raman scattering of light and photoluminescence of tissues. The disadvantage of this device is the inability to register a reflection signal from the studied tissues, which contains information on the concentrations of the most important substances (hemoglobin, oxidized hemoglobin, glycated hemoglobin, the main tissue fluorophores) for the diagnosis of diseases of the female genital area. Also a disadvantage of this device is the lack of protective caps for fiber-optic cable, which does not allow reliable and reproducible recording of the optical response from the studied tissues and measuring their amplitude-spectral characteristics.

The technical result that eliminates these disadvantages and is achieved by using the described device is the creation of a medical diagnostic complex for in vivo determination of the morphometric and functional state of the tissues of the organs of the reproductive system of women in real time. Using the claimed device, objective and accurate express diagnostics is carried out, which is the basis for choosing a treatment and for deciding on a woman’s readiness for pregnancy.

This technical result is achieved by the fact that the claimed device (Fig. 1) includes: a housing (1) that blocks the penetration of spurious electromagnetic radiation of the visible range from third-party emitters; a laser radiation source with a wavelength of 637 nm with a laser interference filter (2); white light source (3); optical fiber optical instrument (4) with replaceable protective disposable sterile caps (5); focusing and filtering system of radiation (6); spectrometer with a multichannel CCD detector (7); built-in microcontroller for processing the received photoluminescence and reflection signals (8); a computer with software (9), characterized in that the spectrometer has a wide spectral range of 400-1100 nm; the optical fiber optical instrument has three optical fiber cores that provide simultaneous measurement of the reflection and photoluminescence spectra from the studied tissues of the organs of the female reproductive system; replaceable protective disposable sterile caps prevent contamination of the optical fiber optical instrument during measurements; laser radiation with a wavelength of 637 nm due to the relatively deep penetration into the tissue allows you to record their spectral characteristics and establish their pathophysiological state; the software calculates the degree of saturation of the studied tissues with oxygen, the proliferative activity of tissue cells, the level of microcirculation in the vessels of the tissues, the structure of the various parts of the endometrium in the uterine cavity, the degree of deviation of the spectral characteristics of the studied tissues from the normal state.

The essence of the work of the medical complex is as follows: using the claimed device, the tissues of the organs of the reproductive system of women are subjected to sequential exposure to continuous radiation from a white light source (miniature incandescent lamp) and low-intensity laser radiation with a wavelength of 637 nm. In this case, the optical response from the tissues and the spectral analysis of this radiation are collected. Laser radiation with a wavelength of 637 nm and white light from an incandescent lamp to tissues is delivered through a three-wire optical instrument with a disposable protective sterile cap on. Fiber-optic veins have internal diameters of 200 μm (laser radiation with a wavelength of 637 nm is supplied through this channel), 400 μm (white light from a tiny incandescent bulb is supplied through this channel) and 200 μm (through this channel optical feedback signals from the studied tissues are transmitted to spectrometer). In order to diagnose the functional and structural state of the endometrium, a fiber-optic instrument with a protective disposable sterile cap put on it is inserted transcervically (through the cervical canal) into the uterine cavity and fixed in its bottom. In the process of traction (reduction) of the fiber towards the internal pharynx, the spectra are recorded at three points - the bottom of the uterine cavity, the middle part of the uterine cavity and in the region of the internal pharynx. The photoluminescence and reflection spectra are also recorded at the intact point (comparison point) - on the skin of the patient's inner thigh. The recorded data in graphical and digital form is analyzed by a hardware program and as a result, the indices of oxygenation, proliferative activity, microcirculation, structuredness and pathological index are calculated.

Indices are calculated as follows.

The oxygenation index (I _oxygen ) shows the degree of saturation of endometrial tissue with oxygen and is calculated as:

I _oxygen = (1 - I ₅₇₈ / I ₆₁₂ ) * 100%,

where I ₅₇₈ is the intensity value in the reflection spectrum at 578 nm, and I ₆₁₂ is the intensity value in the reflection spectrum at 612 nm. The wavelength of 578 nm corresponds to the absorption peak of oxidized hemoglobin, and the length of 612 nm is at the periphery of its absorption.

Normally, the value of this index exceeds 15% (Fig. 3). In case of lower values, a message appears in the program window about the presence of hypoxia in the endometrial tissue in the patient.

The oxygenation index is determined for three points inside the uterus - the bottom of the uterine cavity, the middle of the uterine cavity, the area of the internal pharynx.

The proliferation activity index (I _{proliferation} ) is defined as the integral intensity of the tissue spectrum, normalized to the integral intensity of the spectrum of intact skin on the inner thigh, and multiplied by 100%. With a normal menstrual cycle, the patient has a directly proportional dependence of the value of proliferative activity on the phase and day of the cycle (Fig. 2, 4). This value is usually less than 100%, with the exception of cases with pathology - in this case additional photoluminescent lines appear, broadening the main peak. The proliferative activity index is determined for three points inside the uterus - the bottom of the uterine cavity, the middle of the uterine cavity, the area of the internal pharynx.

The microcirculation index (I _{microcirculation} ) is calculated as the ratio of the oxygenation index to the proliferative activity index. If the proliferative activity of endometrial tissue cells does not correspond to the day of the menstrual cycle (increased or decreased), then this probably indicates an increased or decreased density of blood vessels in the endometrial tissue. The oxygenation index is proportional to the density of blood vessels and the concentration of oxidized hemoglobin in the blood. Therefore, the ratio of the oxygenation index to the proliferative activity index shows a violation of microcirculation and its degree. The microcirculation index is determined for three points inside the uterus - the bottom of the uterine cavity, the middle of the uterine cavity, the area of the internal pharynx.

The structure structure index (I _structure ) displays the degree of difference between the three intrauterine spectra and is calculated as the integral intensity of the maximum spectrum, normalized to the sum of the moduli of the differences in the integrated intensities of the three pairs of intrauterine spectra. If all three measured spectra practically coincide, then the structured index is of great importance. As the differences between the spectra increase, the structuredness index decreases. A high structured index (more than 2) indicates a good structuredness of the various departments of the endometrium lining the uterine cavity.

The pathological index (I _pathology ) displays the degree of deviation of the spectral characteristics from the norm at the bottom of the uterine cavity in relation to the pathological process of an inflammatory or tumor nature. With atypical changes in the tissue or the presence of an inflammatory pathological process, the spectrum is greatly broadened due to the presence of additional photoluminescent lines. A pathological index is defined as the ratio of the integrated intensity of two given spectral ranges in one spectrum:

I _pathology = I ₆₆₀ / I ₇₀₀ ,

where I ₆₆₀ is the integrated intensity in the spectral window 655-675 nm of the spectrum of the bottom of the uterine cavity, and I ₇₀₀ is the integrated intensity in the spectral window 695-705 nm of the spectrum of the bottom of the uterine cavity.

Normally, the value of this index lies in the range: 1.8-2.3. If the measured values deviate from normal, a message is displayed in the program window indicating the presence of pathological processes in the endometrium.

The results obtained are an assessment of the structure and function of tissues of organs of the reproductive system of women and the basis for choosing further treatment.

Clinical example.

Using the claimed device, diagnostic studies were carried out when monitoring treatment in 1727 women with various diseases of the female genital organs and infertility. All women were patients at the Reproductive Health Clinic and had 2 to 16 failed IVF attempts before treatment.

As a result of the application of the claimed device using spectral diagnostic methods, individual treatment parameters were selected and the optimal period for embryo transfer was determined. As a result of monitoring diagnostics and treatment support using the claimed device, pregnancy occurred in 64.5% of women and ended in childbirth in 39.2% of patients.

Patient groups were as follows:

I - chronic endometritis in 61% of patients;

II - intrauterine synechia - adhesions and adhesions in 14% of patients;

III - dystrophy and hypofunction due to hormonal insufficiency (age-related involution, operated ovaries, ovarian exhaustion syndrome) in 15% of patients;

IV - endometrial atrophy for various reasons (menopause, iatrogenic, etc.) in 10% of patients.

The onset of pregnancy in groups:

I - 83.7% (of which 3.2% on their own);

II - 46.7% (of which 0.6% on their own);

III - 35.5% (all by IVF);

IV - 16.2% (all by IVF).

Cases with gestation and childbirth were divided into groups as follows (here percentages were calculated in relation to the number of pregnant women in each group):

I - 66%;

II - 39%;

III - 47.8%;

IV - 28.6%.

In FIG. 2, FIG. 3, FIG. 4 shows the spectral characteristics and indices of a patient with chronic endometritis before and after treatment. As a result of monitoring diagnostics and treatment support using the claimed device, the functional and morphometric conditions of the endometrium were restored and normalized.

In FIG. Figure 2 shows the photoluminescence spectra of various sections of the endometrium of a patient with chronic endometritis before treatment. The study was performed on the 21st day of the menstrual cycle. The proliferative activity of the endometrium in the bottom of the uterine cavity corresponds to the 5th day of the menstrual cycle, in the area of the internal pharynx to the 7th day, and in the middle of the uterine cavity to the 13th day. This patient showed impaired structuring of different parts of the endometrium (structural index was 0.8), the proliferative activity of endometrial cells was significantly reduced and did not correspond to the day of the menstrual cycle, and endometrial hypoxia was recorded (oxygenation index was 4%).

In FIG. Figure 3 shows the reflection spectrum of the bottom of the uterine cavity of a patient with chronic endometritis after treatment. I _oxygen = 20%, which indicates a high oxygen content in the endometrium and its good functional condition.

In FIG. Figure 4 shows the photoluminescent spectra of different parts of the endometrium in a patient with chronic endometritis after treatment, corresponding to its normal functional and morphometric state. After treatment and monitoring diagnostics, the following indices of proliferative activity of endometrial cells were recorded: in the bottom of the uterine cavity - 70%, in the area of the internal pharynx - 65%, in the middle of the uterine cavity - 60%. The proliferative activity of all measured sections of the endometrium corresponded to the 23rd day of the patient's menstrual cycle (diagnosis was made on that day of the cycle). The structuredness index was 3, indicating a good structuredness of the various parts of the endometrium in the patient after treatment.

This clinical example clearly demonstrates how, using the inventive device, a structural and functional non-invasive rapid diagnostic diagnosis of the state of tissues of the organs of the reproductive system of women is carried out accompanied by the prescribed course of treatment. As a result of spectral diagnostics, the functional and morphometric conditions of the tissues of the organs of the female reproductive system are restored and normalized.

Claims (1)

Device for structurally functional non-invasive express diagnostics of the state of tissues of organs of the reproductive system of women, including a case blocking the penetration of spurious electromagnetic radiation of the visible range from third-party emitters, a laser radiation source with a wavelength of 637 nm with a laser interference filter, a white light source, optical fiber optical instrument with replaceable protective disposable sterile caps, focusing system and filtering radiation, spectrometer with multi-channel with an CCD detector, an integrated microcontroller for processing the obtained photoluminescence and reflection signals, a computer with software, characterized in that the spectrometer has a spectral range of 400-1100 nm, an optical fiber instrument has three optical fiber conductors that provide simultaneous measurement of the reflection and photoluminescence spectra from the studied tissues organs of the female reproductive system, while replaceable protective disposable sterile caps prevent contamination of the optical fiber optic measurement, laser radiation with a wavelength of 637 nm due to the relatively deep penetration into the tissue allows you to record their spectral characteristics and establish their pathophysiological state, the software calculates the degree of saturation of the studied tissues with oxygen, proliferative activity of tissue cells, the level of microcirculation in tissue vessels, structuredness different sections of the endometrium in the uterine cavity and the degree of deviation of the spectral characteristics of the studied tissues from the norm lnal condition.

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