WO2018124919A1

WO2018124919A1 - Device for non-invasively measuring microcirculatory blood flow

Info

Publication number: WO2018124919A1
Application number: PCT/RU2017/000064
Authority: WO
Inventors: Денис Григорьевич ЛАПИТАН; Дмитрий Алексеевич РОГАТКИН
Original assignee: Общество С Ограниченной Ответственностью "Центр Исследований И Разработок Эос-Медика" (Ооо "Циир Эос-Медика")
Priority date: 2016-12-26
Filing date: 2017-02-09
Publication date: 2018-07-05
Also published as: RU2636880C1

Abstract

The invention relates to medicine and medical technology, and more particularly to non-invasive optical devices for measuring blood flow in the microvasculature. The present device comprises a source of radiation for illuminating a biological tissue under examination, a light receiver for recording radiation backscattered from the biological tissue under examination, an electronic unit for filtering the signal recorded by the light receiver, containing an analog to digital converter and a digitized signal averaging unit for averaging a useful signal with a background illumination signal and for averaging the background illumination signal according to the measured values of the signals, respectively, a background illumination subtraction unit containing a random-access memory for storing the calculated average values of the background illumination signal and the overall signal respectively and a differencing unit for subtracting the averaged background illumination signal from the averaged overall signal, a unit for determining and displaying the perfusion index of the biological tissue under examination, which is capable of calculating the perfusion index of the biological tissue under examination on the basis of the normalized constant component of the useful signal of the first moment of the power spectral density of the useful signal and is further capable of displaying said value, and a control and synchronization unit which is capable of generating rectangular control pulses with a 50% duty cycle, the outputs of which are connected to the source of radiation and to the clock inputs of the analog to digital converter, the digitized signal averaging unit and the random-access memory respectively. The source of radiation is configured in the form of at least three infrared diodes which emit in a wavelength of 800-820 nm, said infrared diodes being arranged equidistantly in a radial direction around the light receiver and being mounted level with the working surface of said light receiver. The output of the light receiver is connected to the main data input of the analog to digital converter of the electronic filtering unit, the output of the analog to digital converter is connected to the main data input of the digitized signal averaging unit, the output of the digitized signal averaging unit is connected to the main data input of the random-access memory, the output of which is connected to the input of the differencing unit, and the output of the differencing unit is connected to the input of the unit for determining and displaying the perfusion index.

Description

DEVICE FOR NON-INVASIVE MEASUREMENT OF MICRO-CIRCULATION FLOW

BLOOD TECHNOLOGY AREA

The invention relates to medicine and medical equipment, namely, to optical non-invasive devices for measuring blood flow in the microvasculature. BACKGROUND

The dynamic parameters of blood circulation in small blood vessels of organs (arterioles, venules, capillaries, etc.), referred to in the specialized literature as parameters of blood microcirculation, in particular, blood microcirculation flow or perfusion of blood tissues, are important physiological parameters in assessing the functional state human tissues and organs, are important for identifying various dysfunctions, diseases, pathological disorders in tissues and organs and so on. Their assessment in medicine is important both in the normal (normal) state of the subject, and when using various functional load tests for the blood microcirculation system - tests with local heating, cooling, with physical exercises, i.e. in the movement of the subject, etc. (Krupatkin A.I., Sidorov V.V. Functional diagnostics of microcirculatory-tissue systems: a Guide for doctors. - M.: Librocom, 2013. p. 252-304). Therefore, the most promising methods of instrumental assessment of the dynamic parameters of blood microcirculation today are non-invasive methods that allow continuous monitoring of the parameters of blood microcirculation and assess their changes during stress tests (to assess the response of the microcirculation system to the applied load), that is, to conduct a full-fledged functional diagnosis of the blood microcirculation system .

The prior art optical non-invasive methods for assessing the parameters of blood microcirculation.

A known method and device for video capillaroscopy (Gurfinkel Yu.l. Computer capillaroscopy as a channel of local visualization, noninvasive diagnostics, and screening of substances in circulating blood // Optical Technologies in Biophysics and Medicine-II, VV Tuchin — Editor. Proc . SPIE. 2000. V. 4241. P. 467-472), containing a video camera with a micro lens, which allows you to get an enlarged image of the capillaries of the nail bed, and a system for the fixed fixation of the finger under the micro lens. This is a direct, therefore very accurate method for assessing the parameters of blood microcirculation. Using a device for video capillaroscopy, a video image of the movement of blood cells along the capillary loops of the nail bed is received, and it is transmitted to computer and calculate the flow and speed of blood flow through the capillaries. However, this method and device have many drawbacks: the method estimates the blood flow only in the capillaries without taking into account other parts of the microvasculature (arterioles, venules, etc.); the flow is estimated only in the nail bed, while other organs and tissues are not very accessible to this method; during testing, the subject’s finger is fixed motionless under the micro-lens, which excludes the possibility of carrying out functional stress tests in motion.

Known methods and devices for optical infrared (IR) thermometry (Ring E FJ and Ammer K Infrared thermal imaging in medicine // Physiol. Meas. 33 (2012) R33-R46.). These methods and devices use optical IR radiation and the physical phenomenon of emitting IR radiation by heated bodies to estimate the surface temperature of the organ under study, which to a very large extent (although not completely) correlates with the parameters of blood supply to the surface tissues of the organ under study. Devices for IR thermometry consist of an IR video camera calibrated by the intensity of the received radiation at the temperature (C ⁰ ) of the examined surface of the biological tissue under the assumption that the spectral emissivity (degree of blackness) of the studied surface is equal to the spectral emissivity of an absolutely black body. However, both this method and the device have significant drawbacks: the method is not a direct method for measuring the dynamic parameters of microcirculation, but only indirectly, through the surface temperature, allows you to evaluate the parameters of microhemodynamics, therefore, has low accuracy. The temperature of the investigated surface may depend on the temperature of the external environment, evaporation of moisture from the surface of the tissue, and not only on microhemodynamics. Functional stress tests in motion are also difficult to implement in this case: the object must be motionless in the field of view of the IR video camera, local surface heating is not applicable, and so on. The method described above for a doctor does not allow to evaluate the dynamic parameters of microcirculation, since. it does not recount the values of the measured temperature as an indicator of blood flow (as an indicator of tissue perfusion with blood). The result of the measurements is the surface temperature.

Also known is a method and device for photoplethysmography (PPG) and photoplethysmographic objectification of pulse waves in the blood microcirculation system (Moshkevich BC Photoplethysmography: Equipment and research methods. - M .: Medicine, 1970. p.14-40). In this method, using the external source of low-intensity optical radiation, the studied area of living biological tissue is continuously illuminated, a photodetector located on the surface registers the backscattered or transmitted through the secondary tissue, attenuated, including due to absorption of light by blood, electric signal with the photodetector is amplified, filtered in the frequency range of pulse waves (from fractions to units of Hz), and the filtered signal is displayed on the monitor screen in the form of a graph. This signal due to the absorption of light by blood is a pulsogram on which pulse waves appear in the blood microcirculation system. The method can be considered direct and quite accurate in assessing the parameters of pulse waves (wave amplitude, pulse frequency, etc.). However, for a complete functional diagnosis of the blood microcirculation system, the method has a significant drawback in that it only evaluates pulse fluctuations in the microcirculation system and does not allow to evaluate the perfusion parameter (blood flow) in the tissue.

The most complete information about the parameters of blood microcirculation can be obtained today by methods and devices of laser Doppler flowmetry (LDF). The physical principle of the LDF method is based on the use of the Doppler effect - a shift in the frequency of radiation when light illuminates moving blood cells. The method is implemented by illuminating (probing) with laser radiation the biological tissue under study and registering the radiation backscattered from the biological tissue, which in this case will contain at least two components: backscattered radiation at the initial frequency of the probe laser radiation, which is formed from stationary inhomogeneities inside the cell biological tissue without Doppler frequency shifts, and backscattered radiation from moving blood cells, mainly red blood cells, with Doppler yoke frequency. As shown by Bonner and Nossel (Bonner RF, Nossal R. Model for laser Doppler measurements of blood flow in tissue // Appl. Opt. 1981. V. 20. P. 2097-2107), summing up on a photodetector, these two signals form low-frequency beats with frequencies w, recording and processing the spectrum of which with the calculation of the first moment from the spectral density of the photodetector power P (w) normalized to a constant signal generated from these beats, by the formula:

allows you to receive a signal V _BF , proportional to the coefficient of proportionality to _{0 the} product of the number of red blood cells and the average speed of their movement in the vessels, that is, the parameter of blood flow (perfusion of blood tissues). In a word, the LDF does not evaluate the Doppler frequency shift itself or the blood flow velocity, but a certain integral parameter - an index or microcirculation index (in Russian terminology), often called, especially in English, the index of tissue perfusion with blood, just perfusion or blood flow. These are synonymous names for the same parameter. We will use the term perfusion indicator for it below. This integral parameter - perfusion index V _SF - today it is the most informative in medicine for the functional diagnosis of the blood microcirculation system and contains, as a component, various frequency components of the physiological fluctuations of the blood flow - pulse waves, respiratory waves and so on (Laser Doppler flowmetry of blood microcirculation: Manual for doctors / Ed. A.I. Krupatkina, V.V. Sidorova. - M .: Medicine, 2005.p. 90-92). In the prior art, devices are known for evaluating and monitoring blood flow and determining perfusion index using the Doppler effect (US4596254 A, publ. 24.06.1986, US 4476875 A, publ. 16.10.1984). The principle of operation of these devices is very similar. All of them contain a monochromatic radiation source - a laser for illumination of the biological tissue under study, a fiber-optic system for delivering radiation to and from the biological tissue under investigation, a photodetector detecting radiation and the beating of the components of this radiation backscattered from the biological tissue (heterodyne detection principle), as well as an electrical amplification circuit the signal from the photodetector, its filtering and an analog or digital calculation unit according to the registered photo current from the photodetector of the V _B F diffusion system based on equation (1). However, all of these devices have several disadvantages. Since they use the Doppler effect, all of these devices are subject to the strict requirement of using a laser source that has a stable monochromatic radiation power. The devices use optical fibers (optical fiber bundles) to transport laser radiation to biological tissue and backscattered radiation from biological tissue to the photodetector. However, the optical fiber is very sensitive to the slightest movements, bends, therefore in existing LDF devices with optical fibers there is an acute problem of the influence of motion artifacts on the detected signal (TP Newson, A Obied, RS Wolton, et al. Laser Doppler velocimetry: the problem of fiber movement artifacts // J. Biomed. Eng. 9, 1987: 169-172). These movements make a significant contribution to the low-frequency region of the beat spectrum, distorting the results.

As a rule, commercial LDF systems use a high-pass filter (with a cutoff frequency of 20 Hz) to filter out the low-frequency part of the spectrum that is responsible for motion artifacts. But this only helps partially, since this kind of noise has a spectrum up to 3-5 kHz, overlapping the spectrum of the useful signal (Gush RJ, King TA. Investigation and improved performance of optical fiber probes in laser Doppler blood flow measurement // Med. Biol Eng. Comput. (1987) 678: 29-36). To reduce motion artifacts, a modified fiber optic probe is proposed. It is proposed to use a probe with a small aperture and keep it close to the skin during measurements, but this completely excludes the test subject's movement and, therefore, functional diagnostics of the blood microcirculation system. Another technical a solution that partially eliminated motion artifacts was the use of an integrated sensor in which the delivery of light to the tissue and its registration are carried out in one probe (deMul FFM et al. Mini laser-Doppler (blood) flow monitor with diode laser source and detection integrated in the probe // Applied Optics (1984) 23: 2970-2973). However, in all the works described above, the problem of motion artifacts is not completely resolved.

In addition, the photodetector of an LDF device must be sensitive enough to detect weak in intensity backscattered radiation with a Doppler frequency shift collected by a thin optical fiber with a small aperture, so often external light affects the readings of the device and reduces the accuracy of diagnostics.

To eliminate this effect, an LDF device with a differential measurement scheme, disclosed in US4476875 A, publ. 10.16.1984 .. A feature of this device and its circuit is that two photodetectors and two identical electronic signal processing units from the photodetector are used to register radiation backscattered from biological tissue. Accordingly, two optical fibers are used to deliver radiation to photodetectors, which collect radiation from separate adjacent volumes of illuminated biological tissue. The useful output signal is determined in the device by the difference of the signals of these two channels. Since the interference caused by external lighting is in-phase in both channels, they are effectively suppressed in the differential amplifier by subtracting the signals. But the blood flow-related variable components of the output signals from both channels, on the contrary, are amplified, since it is believed that they arise from various red blood cells in the blood stream and are mutually statistically independent realizations of the same stochastic process. Therefore, they are amplified in the circuit.

However, the differential circuit under consideration leads to the formation of spurious components in the spectrum of the useful signal. This significantly reduces the accuracy of the diagnosis. This basic scheme can be slightly improved (the scheme of the improved device is disclosed in RU2599371 C1, publ. 10.10.2016), however, the problems of the influence of optical fibers on the measurement results, the need to have a fairly expensive and highly stable laser source remain.

The closest analogue of the claimed invention is an LDF device for measuring blood microcirculation (US 6173197, publ. 09.01.2001, WO9820794 A1 publ. 05.22.1998), containing an optical head containing a monochromatic radiation source in the form of a low-intensity laser radiation source with a wavelength in red or near infrared wavelength range, the output of which is connected to a separate optical fiber delivering laser radiation to the examined biological tissue, and a photodetector, the input of which is also connected to its separate optical fiber, delivering radiation backscattered from biological tissue to the photodetector. The illuminating and receiving fibers form an optical fiber bundle, which, when the device is operated, is placed at the surface of the biological tissue under test with its distal end to illuminate a portion of the surface of the biological tissue and collect radiation backscattered from it into the aperture of the receiving optical fiber. Also, this device includes an electronic signal filtering unit, consisting of a band-pass filter with lower ω ₁ and upper ω ₂ cutoff frequencies approximately equal to ω ^ = 20 Hz and ω ₂ = 30 kHz, which isolates the variable (AC) component of the recorded signal, and a low-pass filter that extracts the constant (DC) component of the signal, a multiplexer with an analog-to-digital converter, and a perfusion metric calculation unit based on a DSP processor that calculates the perfusion metric (blood flow) n Fourier analysis of the frequency spectrum variable (AC) signal components at its normalization constant (DC) component and determining a weighted average of the signal power spectral density according to the formula (1), i.e., determines the desired perfusion rate V _B F- The yield the photodetector is connected simultaneously with the inputs of the band-pass filter and the low-pass filter, the outputs of these two filters are connected to the input of the multiplexer, and the output of the multiplexer is connected to the input of the block for calculating the perfusion index.

In the closest analogue, a 16-channel device is known as an embodiment, which instead of one photodetector and one band-pass filter with subsequent Fourier analysis of the frequency spectrum of the signal uses 16 photodetectors and 16 band-pass filters, each for its own frequency range within the general range of 20 Hz - 30 kHz, which eliminates the need to use Fourier analysis of the frequency spectrum of the signal, but requires an additional block of fast RAM for storing intermediate results.

The main and significant disadvantages of the closest analogue of the invention as applied to the problem under consideration are determining the perfusion index:

1. The presence of optical fibers in the device, which are large sources of errors and do not allow functional diagnostics of the blood microcirculation system in the patient’s movement.

To eliminate random artifacts from the movements of optical fibers in the specified device, signal processing methods are used, however, this technique does not allow a full-fledged functional diagnosis of the blood microcirculation system in the patient’s movement. 2. The absence in the device of methods and means that exclude, or at least reduce the influence on the results of measurements of external light (external background illumination, for example, from room lighting). External light will enter the receiving fiber and will be perceived by the photodetector, as well as subsequent electronic components and units of the device, as radiation backscattered from the biological tissue, which will give a false signal and will reduce the accuracy of diagnostics.

Among the additional disadvantages of the device can be called the need to use a laser radiation source, which increases the cost of the device design and makes it necessary to classify this device as a high-risk device containing a laser hazard source - a laser radiation source - in accordance with the international standard IEC 60825-1: 2007.

Thus, there is an urgent need for medicine in a device for non-invasively measuring the flow of blood microcirculation, devoid of these disadvantages.

SUMMARY OF THE INVENTION

The technical problem solved by the claimed invention consists in the impossibility to carry out functional diagnostics of the blood microcirculation system in the patient’s movement, to reduce the influence of external illumination on the measurement results and to eliminate the oscillations of the optical fiber.

The technical result of the present invention is to improve the accuracy, noise immunity and safety of an optical non-invasive device for non-invasive measurement of the blood microcirculation flow, used for functional diagnostics of the blood microcirculation system in the patient’s movement, including.

The technical result is achieved due to the fact that the device for non-invasive measurement of the flow of microcirculation of blood in the tissue includes a radiation source for illumination of the studied biological tissue, a photodetector for recording radiation backscattered from the studied biological tissue, an electronic filtering unit of the signal detected by the photodetector, containing an analog-to-digital converter and digitized signal averaging unit for averaging the useful signal with the background illumination signal and signal averaging the background illumination according to the measured values of the signals, respectively, the background illumination subtracting unit comprising a random access memory for storing the calculated average values of the background illumination signal and the common signal, respectively, and a difference unit for subtracting the averaged background illumination signal from the averaged common signal, an indicator determining and indicating unit perfusion of the investigated biological tissue, configured to calculate the perfusion rate of the studied biological tissue based on the normalized first component of the useful signal of the first moment of the spectral power density of the useful signal and display the specified value, the control and synchronization unit, configured to generate rectangular control pulses with a duty cycle of 50%, the outputs of which are connected to the radiation source and to the synchronizing inputs respectively -digital converter, averaging unit of the digitized signal and random access memory, while the radiation point is made in the form of at least three IR diodes emitting in the wavelength range of 800-820 nm, located at an equal distance from each other radially around the photodetector and mounted flush with the working surface of the photodetector, while the output of the photodetector is connected to the main information input analog-to-digital converter of the electronic filtering unit, the output of the analog-to-digital converter is connected to the main information input of the averaging unit of the digitized signal, the output of the averaging unit is digitizing The signal is connected to the main information input of random access memory, the output of which is connected to the input of the difference block, and the output of the difference block is connected to the input of the block for determining and indicating the perfusion index.

In addition, the control and synchronization unit is configured to generate rectangular control pulses with an operating frequency of at least 320 Hz.

In addition, the device may further comprise a direct current amplifier located between the photodetector and the analog-to-digital converter.

In addition, the radiation source and photodetector are installed in the optical head, made in the form of a microchip with the possibility of mounting on the patient's body.

The use in the invention for recording and analysis of other components of radiation backscattered from biological tissue, other than the Doppler component, allows you to not use lasers, since for the formation of these components rather narrow-band LED sources of radiation, which reduces the danger in the use of the inventive device.

The use of a background light subtraction unit with a difference block made with the possibility of subtracting the averaged background light signal from the averaged common signal and a control unit made with the ability to control and synchronize the operation of the elements of the device allows minimizing the influence of external light on the measurement results of the perfusion index.

The design of the radiation source in the form of at least three IR diodes emitting in the wavelength range of 800-820 nm, located at an equal distance from each other radially around the photodetector and mounted flush with the working surface of the photodetector allows you to exclude from the device delivery of radiation to the patient’s test surface in the form of an optical fiber, which introduces large errors in the measurement results and does not allow functional diagnostics of the blood microcirculation system in the patient’s movement. In this embodiment, the inventive device is compact and may be applicable when using functional load tests.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of the present description, illustrate embodiments of the invention and, together with the above general description of the invention and the following detailed description of embodiments, serve to explain the principles of the present invention. In the drawings, like numbers are used to denote like parts.

In FIG. 1 shows a graph of the power spectral density of the photocurrent: amplitude-modulated component of the spectrum P _am (w) (1) component of the beat amplitude-modulated and Doppler spectral components _{P a m, d (w)} ( 2), the Doppler component spectrum Ρ <ι ( ω) (3), the total spectrum of the photocurrent power density Ρ (ω) (4).

In FIG. 2 schematically shows the design of the proposed device.

In FIG. 3 shows the location of the emitters and the photodetector in the optical head.

In FIG. 4 schematically shows the location of the optical head of the claimed device on the human body.

In FIG. 5 is a timing chart of the path of control pulses and moments of digitization of a signal in an analog-to-digital converter unit.

NOTATION

1 - an optical head, 2 - a radiation source in the form of an IR diode, 3 - a photodetector, 4 - an electronic filtering unit, 5 - an analog-to-digital converter, 6 - averaging unit for a digitized signal, 7 - a unit for subtracting the background illumination, 8 - random access memory device, 9 - difference block, 10 - perfusion indicator calculation unit, 11 - control unit, 12 - tested biological tissue

TERMS (DEFINITIONS)

Under the dynamic parameters of blood circulation in small blood vessels of organs (arterioles, venules, capillaries, etc.) in this application understand blood flow in small vessels, the amplitude and frequency of pulse waves of blood flow, the coefficient of variation of blood flow and other parameters associated with the movement of blood.

Under the "perfusion indicator" in this application, we mean a value proportional to the coefficient of proportionality of the product of the number of red blood cells and the average speed of their movement through the vessels, that is, the parameter of blood flow (perfusion of blood tissues).

The terms perfusion, perfusion index, microcirculation index, blood flow in this document are synonyms.

As used herein, the term “cellular tissue” refers to tissues surrounding and lining blood vessels — the epithelium, muscles, epidermis and dermis of the skin, and the like.

The terms biological tissue and biological tissue are synonymous.

DETAILED DESCRIPTION OF THE INVENTION

It is known that the variable blood supply to cellular biological tissues (skin, mucous membranes of organs) arising as a result of various physiological processes in the body, such as the rhythmic work of the heart, vasodilation and vasoconstriction of blood vessels, etc., causes amplitude modulation of backscattered optical radiation inside the biological tissue, thus creating noise in the input signal of the LDF device ([1-4]). However, this amplitude-modulated component of the backscattered radiation also carries similar information about blood microcirculation with respect to the perfusion index, if the perfusion index V _B F is calculated according to formula (1), substituting in it the normalized spectral power density of the beat current Doppler component and a component that does not have a Doppler frequency shift, the power spectral density of a variable component (AC) of the photocurrent from recording the amplitude-modulated component of inverse scattered radiation, which must also be normalized to the constant component (DC) cumulatively detected photocurrent.

The total spectral power density of the photocurrent P (w) (curve 4 in Fig. 1), as shown by studies [1-4], is in the general case a complex sum of components that are formed from the registration of various components of backscattered radiation - backscattered radiation at the initial frequency of the probe (illuminating) radiation, which is formed from stationary inhomogeneities inside the cell biological tissue without Doppler frequency shift and without amplitude modulation, backscattered radiation from moving shaped elements Blood Doppler frequency shift (together forming the heartbeat and formation the Doppler components Pd (w) are shown in FIG. 1, curve 3), of backscattered radiation with amplitude modulation at different frequencies (the amplitude-modulated component of the spectrum P _at (and>) is shown in Fig. 1, curve 1), as well as the contributions from different beats of different components with amplitude modulation and components with a Doppler frequency shift (the component of the beats of the amplitude-modulated and Doppler components of the spectrum Pam, d (w) is shown in Fig. 1, curve 2).

Thus, if biological tissue is illuminated with narrow-band optical radiation, not laser, for example, LED radiation, and the photodetector registers back-scattered optical radiation in the frequency range of amplitude modulation, beats, and other signal fluctuations from 0 to (approximately) 160 Hz, then the power spectral density the resulting photocurrent can be used to calculate the perfusion index by the formula (1) as in the case of the LDF method. The results will be similar.

The proposed device that implements the above method for measuring the flow of blood microcirculation is shown schematically in FIG. 2.

The device consists of a radiation source (2) for illuminating the biological tissue under study and a photodetector (3) for detecting radiation backscattered from the biological tissue under study, for example, a silicon photodiode. In this case, the radiation source is made in the form of at least three light emitting diodes emitting narrow-band radiation in the near infrared range of the spectrum in the wavelength range of 800-820 nm (the region of the isobestic hemoglobin point), for example, at least three infrared diodes (IR diodes) ( 2). The radiation source and photodetector are located in the optical head (1). The device also includes

an electronic filtering unit (4) containing an analog-to-digital converter (5) and an averaging unit for the digitized signal (6), a background illumination subtracting unit (7) containing random access memory (8) and a difference unit (9), a determination and indication unit perfusion index (10) and control and synchronization unit (1 1).

In this case, the analog-to-digital converter (5), the averaging unit of the digitized signal (6) and random access memory (8) are configured to synchronize operation by pulses of the control and synchronization unit (1 1), for which, in addition to the main information input, they have an additional synchronization input (management). The control and synchronization unit (11) is _configured to generate rectangular control pulses with an operating frequency of at least F _pa6 = 320 Hz and a duty cycle of 50%, while the output of the control and synchronization unit (1 1) is connected to the input of each IR diode (2) and with the synchronization inputs of the analog-to-digital converter (5), the averaging unit of the digitized signal (6) and random access memory (8), the output of the photodetector (3) is connected to the main information input of the analog-to-digital converter (5), the output of the analog-to-digital converter (5) is connected to the main information input of the averaging unit of the digitized signal (6), the output of the averaging unit of the digitized signal (6) is connected to the main information input of the random access memory (8) ), the output of which in turn is connected to the input of the difference block (9), and the output of the difference block (9) is connected to the input of the block for calculating the perfusion index (10).

In the optical head (1) (Fig. 3), the IR diodes (2) are located at an equal distance from each other radially around the photodetector (3) to ensure uniform illumination of the volume of biological tissue around the photodetector and are installed flush with the working surface of the photodetector (3). In this case, the optical head itself (1), in which both the radiation source and the photodetector are located, is made in the form of a microchip with the possibility of mounting on the human body using a strap or adhesive plaster (the mounting method is not the subject of the invention) so that the working surface of the photodetector ( 3) and radiation sources in the form of IR diodes (2) will touch the examined surface of the body (biological tissue) (12) as shown in FIG. four.

The proposed device operates as follows. The control and synchronization unit (11) generates rectangular control pulses with an operating frequency of Fpa6, for example, 320 Hz and a duty cycle of 50%. The radiation sources in the form of IR diodes (2) at the moment of arrival of the pulse from the control and synchronization unit (11) are turned on for the duration of this pulse and illuminate the tested biological tissue (12) - the skin or mucous membranes of the organs - with their optical radiation, which is scattered and is absorbed into the tissue, and its backscattered components exit the tissue back to the surface and are recorded by a photodetector (3). From the output of the photodetector (3), the signal enters the main information input of the analog-to-digital converter (5), the operation of which is synchronized with the pulses from the control and synchronization unit (1 1) that arrive at its synchronizing input so that during the pulse, as well as in its the absence of an analog-to-digital converter (5) manages to digitize a signal from the photodetector output several times (N) times, but not less than N = 5 times (Fig. 5). The digitized N signal values for the duration of the control pulse will correspond to the total useful signal with an admixture of the backlight signal ΙΙΣί, and the digitized N signal values for the absence of the control pulse when the emitters are turned off will correspond to the background light signal UR, where i = 1, 2, 3, N.

Then, in the averaging block of the digitized signal (6), in synchronization with the control pulses, the measured values are averaged, and _I and UR are determined by the N measured values (each in its own cycle - at the moment of the action of the pulses and at the moment of their absence) with finding, respectively, the average values υ _Σορ and U _FCP by the formulas

j i = N

^U Fc _P = - ^ ^U Fi (3)

The found average values of 1) _Σορ and U _{Fcp are} further stored each in its own cycle (at the moment of operation of the pulses and at the moment of their absence) by control pulses in the random access memory (8), and in the difference block (9), backlight compensation and selection of useful 11 _p signal by subtracting and _Psr from U _Icp at the time of the arrival of the next pulse according to the formula:

U _n = υ _Άρ - U _Fcp (4) Thus, from the output of the difference block (9), the input of the block for determining and displaying the perfusion index (10) already receives a useful signal U _n , cleared of background illumination. In this case, the applied procedure of multiple digitization and subsequent averaging is equivalent to the filtering procedure of the signal at frequencies above F _pa6 (above 320 Hz in this particular case). The filtering quality will be determined by the number of digitizations N. As a result, the useful signal U „will contain constant (DC) and variable (AC) components of the signal in the frequency range 0-320 Hz, which, according to the well-known Nyquist theorem, allows us to analyze the frequency spectrum of the signal in the range from 0 to F _pa 6 2 Hz, that is, in this particular case in the frequency range from 0 to 160 Hz.

In the unit for determining and indicating the perfusion index (10), the useful signal U _n undergoes the last digital processing: based on the digital frequency Fourier analysis, the constant (DC) component of the signal (the zero term of expansion in the Fourier series) is extracted, then all the variable signal components (AC) in the spectral power density of the signal power, P (w) are normalized to DC, and the spectral power density of the photocurrent P (w) normalized in this way is substituted into formula (1) with ^ ^ = 0 Hz and ω ₂ = 160 Hz to determine the weighted average, i.e. e. to determine the desired perfusion index V _B F-

If the signal power from the photodetector (3) is not enough for high-quality digitization of the signal, a direct current amplifier (DC) can be located between the photodetector and the analog-to-digital converter (5).

The proposed device, therefore, does not contain optical fibers and laser radiation sources, it compensates for the effect on the detected signal of external background illumination, the device can be miniature in the part of the optical head, which can be fixed motionless on the human body, move synchronously with the body without creating mutual displacements of the body relative to the head, does not interfere with movement, and so on, that is, suitable for full functional diagnostics in the movement of the subject. In the future, the head can be made with wireless communication with the rest of the device, for example, it can be connected with it via Bluetooth (such solutions are generally known today), which will further give the subject freedom of movement and open the way to portable individual systems for daily monitoring of perfusion rate. Therefore, it can be stated that in this proposed device all the stated objectives of the invention are achieved.

The above description of an exemplary embodiment provides an overview of the principles of design, operation, manufacture and use of the device of the present invention. At least one example of these embodiments is illustrated by the accompanying drawings. Those skilled in the art will appreciate that the specific devices described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments, and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such modifications and changes are intended to be within the scope of the present invention. Used Books:

1. Lapitan D. G., Rogatkin D. A. Variable blood supply to biological tissue as a noise source in the input optical signal of a medical laser Doppler flowmeter // Optical Journal, vol. 83, Ns1, 2016. - P. 41-46.

(email: http://www.medphyslab.com/images/publications/stat_oj_06_r.pdf)

2. Lapitan D.G., Rogatkin D.A. Evaluation of the Doppler component contribution in the total backscattered flux for noninvasive medical spectroscopy // Proc. SPIE, Vol. 9129, 2014 .-- 91292X.

(electronic resource: http://www.medphyslab.com/images/publications/stat_spie_9129-2x_e.pdf) 3. Lapitan D. G., Rogatkin D. A. Ways of development of diagnostic devices for the human blood microcirculation system // Report collection 12th International Scientific Conference “Physics and Radioelectronics in Medicine and Ecology” (FREME'2016), Book

2 - Vladimir-Suzdal, July 2016 .-- p. 92-95.

(electronic resource: http://www.medphyslab.com/images/publications/stat_freme2016_r.pdf) 4. D. Lapitan. Doppler scattering model with variable blood filling in laser Doppler flowmetry // Biomedical Radioelectronics, 2017.

(accepted for publication in 2017).

(email: http://www.medphyslab.com/images/publications/stat_lapitan_preprint_r.pdf)

Claims

CLAIM

1. A device for non-invasive measurement of the flow of blood microcirculation in tissue, including

a radiation source for illumination of the studied biological tissue,

a photodetector for detecting radiation backscattered from the biological tissue under investigation,

an electronic filtering unit for a signal registered by the photodetector, comprising an analog-to-digital converter and an averaging unit for digitizing a signal for averaging a useful signal with a backlight signal and averaging the backlight signal from the measured signal values, respectively,

a background light subtracting unit comprising a random access memory for storing the calculated average values of the background light signal and the common signal, respectively, and a difference unit for subtracting the average background light signal from the average common signal,

a unit for determining and indicating a perfusion index of a biological tissue under investigation, configured to calculate a perfusion index of a biological tissue under investigation based on a normalized component of the useful signal of the first moment of the spectral power density of the useful signal and displaying the specified value

a control and synchronization unit configured to generate rectangular control pulses with a duty cycle of 50%, the outputs of which are connected to a radiation source and to the synchronizing inputs of an analog-to-digital converter, an averaging unit of a digitized signal, and a random access memory,

wherein the radiation source is made in the form of at least three IR diodes emitting in the wavelength range of 800-820 nm, located at an equal distance from each other radially around the photodetector and mounted flush with the working surface of the photodetector,

the output of the photodetector is connected to the main information input of the analog-to-digital converter of the electronic filtering unit, the output of the analog-to-digital converter is connected to the main information input of the averaging unit of the digitized signal,

the output of the averaging block of the digitized signal is connected to the main information input of random access memory, the output of which is connected to the input of the difference block,

and the output of the difference block is connected to the input of the block for determining and indicating the perfusion index.

2. The device according to claim 1, characterized in that the control and synchronization unit is configured to generate rectangular control pulses with an operating frequency of at least 320 Hz.

3. The device according to claim 1, characterized in that it further comprises a DC amplifier located between the photodetector and the analog-to-digital converter.

4. The device according to claim 1, characterized in that the radiation source and the photodetector are installed in the optical head, made in the form of a microchip with the possibility of mounting on the patient’s body.