RU2737714C1 - Method for assessing microcirculatory disorders in skin in patients with disturbed carbohydrate metabolism and device for its implementation - Google Patents

Abstract

FIELD: medicine; endocrinology.

SUBSTANCE: group of inventions can be used for detection of microcirculatory disorders in skin of limbs in patients with disturbed carbohydrate metabolism. That is ensured by recording a patient's arm and leg with a skin microcirculation level by evaluating the perfusion value by laser Doppler flowmetry or incoherent fluctuation spectroscopy. Pulse wave parameters are simultaneously evaluated by conducting a basic test and tests with functional occlusion and heat samples. Based on the obtained data, a diagnostic criterion (DC) is calculated. If DC > −1, the absence of microcirculatory disorders is stated. At DC value ≤ −1 and > −2 violations are evaluated as weak. At DC value ≤ −2 and > −3 disorders are considered to be moderate. At DC value ≤ −3 and > −4 disorders are considered to be severe. At DC values ≤ −4 microcirculatory disorders are evaluated as very severe. Also disclosed is an apparatus for detecting microcirculatory disorders in skin.

EFFECT: group of inventions enables detecting microcirculatory disorders in patients with carbohydrate metabolism disorders.

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Description

The group of inventions relates to medicine, namely to endocrinology, and is intended to detect microcirculatory disorders in the skin of the extremities in patients with disorders of carbohydrate metabolism.

Disorders of blood circulation in the extremities (hemodynamic disorders), including microcirculation of blood in small vessels of the extremities (microhemodynamics), are often a consequence of disorders of carbohydrate metabolism and lead to severe complications, in particular, in diabetes mellitus, up to amputation of the extremities and death. Therefore, cheap, non-invasive, screening methods for detecting microcirculatory disorders, applicable in any endocrinological clinic, polyclinic or even at home, as well as devices that implement them, are very important for medicine. When screening, it is very important to simultaneously assess vascular resistance, the tone of microvessels, their rigidity (elasticity), the reaction of the microvasculature to functional provocative tests, such as, for example, thermal and occlusive tests, objectifying the endothelial function of blood vessels and the neurogenic component of regulation of vascular tone (Krupatkin A.I. et al., Functional diagnostics of microcirculatory-tissue systems: A guide for physicians. - M .: Librokom, 2013. p. 252-304; Roustit M., Cracowski JL, Non-invasive assessment of skin microvascular function in humans: an insight into methods // Microcirculation, V. 19 (1), 2012, pp. 47-64), as well as the effective systolic and diastolic blood pressure (SBP and DBP, respectively), which, as you know, strongly affect both the central and for all peripheral hemodynamics. Only in aggregate, all these physiological parameters reliably characterize the state of the blood microcirculation system (Guyton A.K., Hall J.E. Medical Physiology. / Translated from English. Edited by V.I. Kobrin. - M .: Logosphere. 2008 . 1296 s.).

There are generally known optical non-invasive methods for detecting microcirculatory disorders in human extremities and devices for their implementation.

So, from the prior art there is a method for assessing microangiopathy using capillaroscopy of the nail fold at rest and after functional tests (RF patent No. 2559640, publ. 08/10/2015). The method consists in carrying out capillaroscopy at rest with the subsequent assessment of structural changes in the state of the capillaries, additionally, capillaroscopy and oximetry are performed with four functional tests with the effect of physical factors on the examined limb - cuff occlusion, test with cold effect, test with heat effect, test with raising the limb up , and after each of the samples, the oxygenation index SaO ₂ and the recovery time of the capillaroscopy indices t to the initial values are determined. The data obtained make it possible to diagnose the stage of microangiopathy. The disadvantages of this method are the long research time (30-45 minutes), a very small area of examination of the microvascular bed (about a dozen capillaries, no more); the actual values of the SBP and DBP pressures in the subject are not taken into account, the indicators characterizing the stiffness (elasticity) of small venules and arterioles are not taken into account (only capillaries are examined), there is no assessment of vascular resistance, there is no possibility of taking measurements at the same temperature of the skin surface in the physiological region normal (it is known that temperature strongly affects the cutaneous blood flow). All this makes the method not very accurate. Also, due to its long duration, it is difficult to implement in routine clinical practice.

Also known is a method for detecting microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism (US Pat. RF No. 2547800, publ. 10.04.2015). In this method, the assessment of microcirculation is carried out by the method of laser Doppler flowmetry (LDF) using combined functional tests - postural-thermal on the leg and postural-thermal on the arm. During the study, the sensor is heated to 42 ± 1 ° C and the position of the subject's body is changed. Further, a mathematical calculation of the obtained microcirculation indicators is carried out. The method allows detecting microcirculatory disorders in patients with disorders of carbohydrate metabolism. The disadvantage of this method is the duration of the study - without taking into account the time of adaptation to the temperature conditions of the room, the time for conducting the tests is 26 minutes, which makes this method unpromising for wide clinical use. Also, in this method, the measurement of microcirculation is carried out on the dorsum of the hand 4 cm distal to the wrist joint, and this area is characterized by a large individual variability in the thickness of the stratum corneum, which can reduce the measurement accuracy.

A known method for assessing microcirculatory disorders in patients with disorders of carbohydrate metabolism (RF patent No. 2677590, publ. 01/17/2019) using the method and device LDF. LDF devices (patents US 4596254 A, publ. 24.06.1986, US 4476875 A, publ. 16.10.1984, etc.) are generally well known today in the field of medical diagnostics. They use the Doppler effect of the radiation frequency shift on moving blood cells and the method of optical sensing of tissues with coherent low-intensity laser radiation in order to calculate, from the spectral power density of the variable component of the photocurrent P (w), a quadratic photodetector recording beats in the frequency range [w ₁ , w ₂ ] backscattered radiation emitted from tissues from stationary tissue structures and from moving blood components, and the constant component of the photocurrent i _{0 of} this photodetector of the parameter of tissue perfusion with blood V _BF according to the formula:

where w is the beat frequency, k ₀ is the dimensional proportionality coefficient. The cited method for assessing microcirculatory disorders in patients with carbohydrate metabolism disorders using this V _BF perfusion parameter includes assessing the level of cutaneous microcirculation of blood in the limb, namely in the hand, by conducting a baseline test and a test with a thermal functional test followed by a mathematical calculation of parameter changes perfusion based on the received data. At the same time, in the basic test, a physiologically constant temperature of the skin surface is maintained at 32-32.4 ° C due to an additional heating element, and during the thermal functional test, heating is carried out quickly to 41.8-42.2 ° C with a heating rate of 2 ° C per second, the temperature of the heating element at 41.8-42.2 ° C is kept constant until the end of the sample, the perfusion recording is stopped 120 seconds after heating is turned on, and then the slope of the linear regression function of the perfusion index multiplied by 10 is calculated for 120 seconds of heating and the obtained value of the slope parameter is substituted into the formula for calculating the final diagnostic indicator - the probability of the patient having microcirculatory disorders. This method reduces the examination time and increases the accuracy of determining microcirculatory disorders associated with the neurogenic component of the regulation of microhemodynamics (reaction to a thermal test). However, in this method, microcirculatory disorders are diagnosed only in terms of the likelihood of their presence, without dividing by severity, as in the example with angiopathies (mild, moderate, severe, etc.), the endothelial function of the vessels is not evaluated, the parameters of elasticity (stiffness ) of the walls of blood vessels, vascular resistance, and the actual values of the SBP and DBP pressures in the subject are not taken into account, which also strongly affect both central and peripheral hemodynamics.

Meanwhile, in the general case, there are known non-invasive methods for determining systolic and diastolic pressure (SBP, DBP), optical non-invasive methods for assessing vascular resistance and stiffness of the vessel walls, based, for example, on the methods of photoplethysmography (PPG), and their devices - photoplethysmographs (Moshkevich BC Photoplethysmography: Apparatus and research methods. - M .: Medicine, 1970. pp. 14-40; Allen J. Photoplethysmographyanditsapplicationinclinicalphysiologicalmeasurement. // Physiol. Meas. 2007. V. 28 (3). R1-R39.).

To determine SBP and DBP, it is known and standardized, for example, a non-invasive oscillometric method for measuring SBP and DBP, which is implemented today everywhere in automatic and semi-automatic blood pressure monitors (Parashin V.B., Simonenko M.N.Technical and metrological aspects of measuring blood pressure by the oscillometric method. // Medical technology, No. 1, 2010. - pp. 22-26). In this method, SBP and DBP are assessed by the magnitude of air pressure pulsations in the cuff worn on the patient's shoulder during pumping and / or depressurization in the pressure range up to 300 mm Hg. (Specific pressure values depend on the specific design of the tonometer and the selected inflation / pressure release method). Also known is a device for non-invasive pressure measurement using an inflatable cuff with a remote optical pulse oximetric sensor for calibration (patent No. US 9687161 B2, 2017).

To determine the vascular resistance and stiffness of the vessel walls, diagnostic methods are known based on the analysis of the photoplethysmogram signal, in particular, on the analysis of the pulse waveform and the speed of propagation of the pulse wave from the center to the periphery, i.e. to the limb (Tony J. Akl, Mark A. Wilson, M. Nance Ericson, and Gerard L. Cote, Quantifying tissue mechanical properties using photoplethysmography // Biomed. Optics Express, Vol. 5, No. 7, 2014. - p. 2362-2375; Usanov D.A., Skripal AB, Vagarin A.Yu., Rytik A.P. Methods and equipment for diagnosing the state of the cardiovascular system according to the characteristics of the pulse wave. - Saratov: Publishing house of Saratov University , 2009 .-- 96 p.). The head (forehead, earlobe) or chest is often used as one of the points of registration of the pulse wave to assess its speed, and the wrist or fingertip is used as the second (patent No. US 2010/0081892 A1, 2010). In this case, sometimes electrocardiography (ECG) data is used as the signal of the first point. When analyzing the pulse waveform, contour analysis of the PPG signal is most often carried out and different indices of the pulse waveform are calculated, characterizing the stiffness of the vessel walls, for example, the stiffness index SI, equal to the ratio of the pulse height of the pulse signal on the PPG-gram from the finger to the delay time interval between systolic and diastolic (reflected) impulses (SC Millasseaua, JM Rittera, K. Takazawaband P. J. Chowienczyka, Contour analysis of the photoplethysmographic pulse measure dat the finger // Journal of Hypertension, Vol. 24, No 8, 2006, pp. 1449 -1456). However, the use of these methods and diagnostic indicators in combination to solve the problem of detecting microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism is not known from open sources. The use of an optical sensor on the head in determining the speed of propagation of the pulse wave reduces the diagnostic accuracy, because the pulse wave does not propagate from the head to the limb. The use of an ECG signal complicates and increases the cost of the diagnostic hardware, because the use of an electrocardiograph is required, and the use of the delay time interval between the systolic and diastolic (reflected) pulses in calculating the pulse waveform index makes it impossible to calculate this index for patients who do not have a pronounced peak of the reflected wave (examples of such PPG grams are given in the same source ). All this does not allow direct use of these known methods and devices for detecting microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism, identifying the stages of disorders, etc.

Closest to the proposed group of inventions are a method for detecting microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism and a device for its implementation (Lapitan D.G., Development of a hardware-software complex for functional diagnostics of the blood microcirculation system, Abstract of the thesis., 05.11. 17, Devices, systems and medical products. - M .: Saint Petersburg, 2019, 19 p.; DG Lapitan, and O.A. Raznitsyn, A Method and a Device Prototype for Noninvasive Measurements of Blood Perfusion in a Tissue. / / Instruments and Experimental Techniques, 2018, Vol. 61, No. 5, pp. 745-750 (with supplementary materials), RF patent No. 2636880). The method includes recording on the limb, namely on the hand, the level of cutaneous microcirculation of blood using an optical method for assessing perfusion by conducting a basic test and tests with a functional occlusion test and a functional thermal test with rapid heating of the skin to a temperature of up to 41.5 ° C. 41.8 ° C for 5-6 seconds using an optical sensor for a finger with a wavelength of radiation from sources in the region of any of the isobestic points of hemoglobin in the spectral range of 520-600 nm and equipped with a heating element to heat the working surface of the sensor and the skin under it ; and the implementation of a mathematical calculation of physiological indicators of microcirculation based on the data obtained and the formation of the final diagnostic conclusion. This method is based on a related LDF, a new optical non-invasive method for assessing the index of tissue perfusion with blood - incoherent fluctuation spectroscopy (NFS), which allows you to obtain the parameter of tissue perfusion with blood V _{BF in a} slightly different way from the LDF method (Rogatkin D.A. Physical basis of modern optical methods studies of microhemodynamics in vivo. Lecture. // Medical Physics, No. 4, 2017. - pp. 75-93). The essence of the LFR method is to illuminate tissue with incoherent optical radiation, register with a photodetector (silicon photodiode) an optical signal backscattered from the microvascular bed, containing, with this method of illumination, a constant signal component as in the LDF method, which creates a constant component of the photodetector photocurrent i _o , and a component of low-frequency fluctuations signal in the frequency range [w ₁ , w ₂ ] of about 0.1-20 Hz, which are generated by changes in blood volume due to rhythmic processes in the microcirculation system, and the calculation of the perfusion parameter by formula (1) from the spectral power density P (w) of these low-frequency fluctuations ... At the same time, as it was proved in the original source, by choosing the coefficient k ₀ during calibration, the perfusion parameters of the LDF and LFS methods can be made equivalent from a medical and physical point of view.

The method for detecting microcirculatory disorders in the skin in patients with carbohydrate metabolism disorders, proposed in the prototype, consists in performing a basic test and a functional thermal test on the hand while fixing an optical sensor implementing the LFS method on the wrist. Basic test, i.e. the measurement of the initial, baseline perfusion parameter V _{BF_base is} carried out for 120 seconds with averaging V _{BF_base} over these 120 seconds. Then, the skin is rapidly heated to 41.5 ° C-41.8 ° C at a heating rate of 1.5 ° C per second using a heating plate built into the optical sensor, and the perfusion index is recorded for another 5 minutes. The average value of the blood perfusion parameter at the 2nd minute of heating V _{BF_2min} (120 seconds after the start of heating, averaged over measurements in the range of 120 ± 10 seconds) is used further to calculate the rate of increase in perfusion during heating by the formula:

where V _{BF_base} is the average value of the perfusion parameter in the baseline test. When V _perf <0.4, microcirculatory disorders associated with impaired nervous regulation of vascular tone in the microvasculature are diagnosed. The prototype also shows an example of performing a separate functional occlusion test on the arm using the cuff of a conventional tonometer and an example of registering a perfusion parameter by the NFS method during a functional occlusion test. First, as with the heat test, in the absence of cuff pressure, a baseline test is performed over a period of 60 seconds and a baseline, mean baseline perfusion parameter is measured prior to occlusion over those 60 seconds. Then the cuff is quickly manually inflated with a pressure in the range of 220-300 mm Hg. to block arterial blood flow in the arm, and this pressure is maintained in the cuff for 120 seconds, after which it is quickly released. The perfusion parameter is recorded continuously both during occlusion and for another 2-3 minutes after pressure release to determine the magnitude of postocclusive reactive hyperemia from the increase in the perfusion index after pressure release and its subsequent comparison with the initial, baseline perfusion level. However, the detection criteria for this test of microcirculatory disorders in the prototype are not described. The disadvantages of the prototype method, as well as a number of the above-mentioned analogs, are: assessment of microcirculatory disorders without taking into account the rigidity of the walls of blood vessels, vascular resistance; the lack of taking into account the current values of the SBP and DBP pressures in the subject during measurements, the lack of an assessment of the stage of the severity of microhemodynamic disorders, which reduces the diagnostic value of the method and reduces the information content of the diagnosis and its accuracy, as well as a long measurement time when performing two successive functional tests with a separate baseline test for each of the samples.

The device proposed for implementing the prototype method contains a radiation and heating control unit, a communication interface with a control computer, a data digitization unit from photodetectors and temperature sensors, a microprocessor, the first and second outputs of which are configured to be connected to the input of the radiation and heating control unit, and an input of the communication interface with the control computer, a block for digitizing data from photodetectors and temperature sensors, the output of which is configured to be connected to the input of the microprocessor; as well as a control computer and an optical sensor connected to the communication interface, which includes at least three optical emitters emitting narrowband optical radiation in the region of any of the isobestic points of hemoglobin in the spectral wavelength range of 520-600 nm, located radially at the same distance from each other around the photodetector, a photodetector and a heating element containing a heating plate, heaters and a temperature sensor, while the emitters and a photodetector are located in the through holes of the heating plate, the emitters and the heating plate are made with the possibility of being connected to the radiation and heating control unit, and the outputs of the photodetector and the temperature sensor made with the possibility of connection with the first and second inputs of the block for digitizing data from the photodetector and the temperature sensor.

The device is an electronic microprocessor control unit with an optical sensor connected to it (designated as "optical head" in the original source) and a control computer with a control program. The optical sensor consists of a radiation source for illumination of the biological tissue under investigation and a photodetector - a silicon photodiode - for recording radiation backscattered from the biological tissue under investigation. In this case, the radiation source is made for research purposes in the form of six LEDs, three of which emit narrow-band radiation in the green range of the spectrum in the wavelength range of 560-580 nm, and the other three emit narrow-band radiation in the near-infrared range of the spectrum in the wavelength range 800-820 nm. In the optical sensor, LEDs are located radially around the photodetector at a distance of 4 mm from its center to ensure uniform illumination of the biological tissue volume. The LED outputs are installed on the same level with the working surface of the photodetector to exclude the passage of light directly, bypassing the diagnosed tissue. In addition, both the LEDs and the photodetector are installed in the optical sensor in the holes of the titanium heating plate, which, due to the built-in heating elements and the temperature sensor located on it, allows heating the tested skin area and controlling the heating temperature. Such a plate evenly distributes heat from the heaters over the diagnosed area of the skin. To control the temperature of the plate, a proportional-integral-differentiating (PID) controller is used, which is implemented in software in the program of a control computer with a temperature sensor - a thermistor mounted on the plate. In this case, the emitters of the optical sensor operate in a pulsed mode, which additionally makes it possible to organize registration and subtraction of the background while the emitters are extinguished.

The device works as follows. The microprocessor control unit generates rectangular control pulses with an operating frequency of 320 Hz. At the moment of arrival of a pulse from the control unit, radiation sources are switched on in turn for the duration of this pulse (781.25 μs) and illuminate the tested biological tissue (skin) with their optical radiation, which is scattered and absorbed in the tissue, and the backscattered component of radiation comes out of the tissue back to the surface skin and are registered with a photodetector. From the output of the photodetector, the signal goes to a direct current amplifier, in which it is amplified, and then, amplified, it goes to the main information input of the analog-to-digital converter (ADC). The operation of the ADC is synchronized with the pulses from the control unit arriving at its synchronizing input, so that during the switching on of a group of LEDs, as well as during their switching off, the ADC has time to digitize the signal several (N) times, but not less than N = 5 times. The digitized N signal values during the control pulse duration correspond to the total useful signal with an admixture of the background illumination signal, and the digitized Signal values during the absence of the control pulse, when the emitters are turned off, correspond to the background illumination signal. In the block for averaging the digitized signal, the total signal and the background illumination signal are averaged over N measured values. Further, in the difference block, the illumination is compensated and the useful signal is extracted by subtracting the background illumination signal from the total signal at the time of the next pulse arrival. Thus, from the output of the difference unit to the input of the control computer and into its program for processing, there is already a useful optical signal, cleared of background illumination. In the control program of the computer, executed in the LabView software environment, the useful signal undergoes further digital processing, followed by the calculation of the perfusion parameter V _BF .

However, the prototype device has the following disadvantages:

- the use of the built-in controlled tonometer to determine SBP, DBP and create occlusion is not provided; an external manual tonometer is used for this;

- simultaneous and automatic execution of functional occlusal and thermal tests is not provided, which increases the total examination time when two tests are performed sequentially one after the other;

- there are no channels for recording the parameters of the pulse wave propagation velocity and the pulse waveform index, which would allow one to assess the rigidity (elasticity) of the vessel wall;

- the device uses only one remote optical sensor to register the perfusion parameter, which limits diagnostic capabilities and does not allow simultaneous measurements on the arm and leg, although it is known for patients with carbohydrate metabolism disorders that microcirculatory disorders can primarily manifest themselves on the legs.

Regarding the last drawback of the device, we can additionally say that adding a second sensor for the leg is possible, for such a device it is not difficult from a technical point of view, and technically, the device has the ability to organize additional processing of the signal from the sensor on the leg in the computer control program. However, this feature was not implemented in the prototype, since at the time of its creation, its authors did not have a key idea of how to implement an integral diagnostic method taking into account data from two sensors without simple duplication of information and without using a simple sequential summation of known methods, which increases the total examination time, while the standard time allotted for examination the patient in the clinic is 10-15 minutes.

Thus, there is a need for a method for detecting microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism and a device for its implementation, devoid of the above disadvantages.

The technical result of the proposed group of inventions is to eliminate the shortcomings of the prototype of the method and device, increase the information content of the examination and the reliability of the detection of microcirculatory disorders in the skin of the extremities in patients with carbohydrate metabolism disorders due to additional accounting for the set of indicators of SBP, DBP, vascular tone and elasticity, while reducing the measurement time and, accordingly, the labor costs of the medical staff for registration and processing of aggregate diagnostic data, as well as the issuance of a final diagnostic conclusion.

The specified technical result in relation to the method is achieved by the fact that in the method for assessing microcirculatory disorders in the skin in patients with carbohydrate metabolism disorders, including recording on the limbs, namely on the hand, the level of cutaneous microcirculation of blood using an optical method for assessing perfusion by conducting a basic test and tests with functional occlusion test and functional thermal test with rapid heating of the skin to temperatures up to 41.5 ° C-41.8 ° C for 5-6 seconds using an optical sensor for a finger with a wavelength of radiation in the area of any of the isobestic points of hemoglobin in spectral range 520-600 nm and equipped with a heating element for heating the working surface of the sensor and the skin under it; and the implementation of a mathematical calculation of physiological indicators of microcirculation based on the data obtained and the formation of the final diagnostic conclusion, it is proposed to pre-record the initial data of the patient: height (H, cm), weight (W, kg), gender, on the basis of which the body mass index (BMI) is calculated , coefficients Kimt and Kpol:

while measuring the distance L, cm between the middle of the shoulder and the finger pad of the patient's hand, on which the optical sensor is installed, before starting the basic test on the shoulder of the test arm, in addition to the optical sensor, fix the tonometer cuff, additionally examine the patient's leg as a test limb using the second sensor, which is fixed on the instep of the foot in the first interdigital space, while using optical sensors, perfusion indicators are simultaneously recorded using the optical method for assessing perfusion and pulse wave indicators by photoplethysmography, the basic test is carried out for 80 seconds with a surface temperature of the optical sensors for raising the foot of 32 ° С-33 ° С and for a finger 34 ° С-35 ° С, during the baseline test, 10 seconds after the start of measurements, within 30 seconds, the parameters of the base level of perfusion on the hand, averaged over 30 seconds, are recorded and determined using the optical method for assessing perfusion - BUPr and base level perf ultrasound on the leg - BUPn with appropriate optical sensors, and using the method of photoplethysmography on the arm, the pulse waveform index - IFPV, as the ratio of the wave decay time interval Δt ₂ to the rise time interval Δt ₁ :

the level at which Δt ₁ and Δt ₂ are calculated is determined as 0.15 of the maximum amplitude A _{1 of the} systolic pulse on the photoplethysmogram, after which an automated measurement of the systolic and diastolic blood pressure levels of SBP and DBP is carried out with the calculation of the pulse blood pressure PAP, when which using an optical sensor on the arm at the time of measuring SBP and DBP at the stage of pressure relief according to the time difference between the pulses of the pulse wave of blood in the shoulder from the cuff of the tonometer and in the finger from the optical sensor, the average index of the pulse wave velocity of ISPV is calculated by the formula:

where L is the distance between the middle of the shoulder and the finger pad of the patient's hand, on which the optical sensor of the device is installed, ΔT is the difference in time between the appearance of the systolic pulse of the pulse wave in the finger, recorded by the optical sensor, and the pressure pulse in the patient's shoulder, recorded by the pressure sensor of the tonometer; further, without removing the sensors and the cuff, without changing the surface temperature of the sensors, stop the study for 5 minutes to restore blood flow in the arm, after which a test with functional tests is carried out, which includes the simultaneous conduct of two tests - an occlusive test using the cuff of a tonometer on the arm and a thermal test using a sensor on the leg; in case of an occlusive test, arterial occlusion on the shoulder is carried out by pumping the pressure in the tonometer cuff to the value of SBP + ΔP at a rate of 10 to 15 mm Hg. per second, the pressure increment for occlusion (ΔР, mm Hg) is calculated by the formula:

ΔР = 50 + 10 * Kpol + 2.2 * Kimt;

the maximum value of SBP + ΔР is no more than 300 mm Hg, the occlusion is maintained at this pressure for 120 seconds, after which the pressure is released at a rate of 50 to 100 mm Hg. per second and 10 seconds after the start of the pressure release, the average post-occlusive blood perfusion level in the finger of the PUPr for the next 10 seconds of reactive hyperemia is recorded by an optical method for assessing perfusion on the hand; heating for the thermal test on the leg is performed from an initial temperature of 32 ° C-33 ° C, then the set temperature is maintained for 2 minutes and the average thermal level of blood perfusion on the leg TUPn is recorded by an optical method for assessing perfusion for the period from 110 to 120 seconds of the thermal test with the moment of the start of heating, the physiological coefficients of the basic vascular tone for the arm k ₁ and leg k ₂ are calculated according to the formulas

- coefficient of elasticity of the vessel wall k ₃ according to the formula

- coefficient of vascular endothelial function k ₄ :

- coefficient of neurogenic regulation of vascular tone k ₅ :

after that, the physiological indicators F _{i are} calculated, reflecting the standardized deviation of the estimated indicator in the examined patient from the control group, namely:

at the same time, the coefficients m _i and σ _i for them are determined in the control group of conditionally healthy subjects with the number n as follows:

where j is the serial number of the test subject from the control group, then, based on the physiological parameters F ₁ -F ₅ for each patient, the DC diagnostic criterion is calculated by the formula:

DC = 1.5 * F ₃ + 0.5 * F ₄ + 2 * F ₅ -F ₁ -F ₂

according to the DC diagnostic criterion, a conclusion is made about the severity of microcirculatory disorders in a patient: at DC> -1, they conclude that there are no microcirculatory disorders, with a DC value of ≤-1 and> -2, assess microcirculatory disorders as weak, with a DC value of ≤-2 and> -3, assess microcirculatory disorders as moderate, with DC values ≤-3 and> -4, assess microcirculatory disorders as severe, with DC ≤-4 assess microcirculatory disorders as very severe.

Both incoherent fluctuation spectroscopy and laser Doppler flowmetry can be used as an optical method for assessing perfusion.

FIG. 1 shows a time sequence diagram of the registration of parameters during the basic test and functional tests.

FIG. 2 shows a diagram for calculating the parameters of the pulse wave.

FIG. 3 shows a block diagram of the proposed device.

FIG. 4 shows a schematic representation of one of the optical sensors.

FIG. 5 shows the cyclogram of the device.

FIG. 6 shows the attachment of optical sensors to the toe and instep.

The method is carried out as follows.

The initial data about the patient are recorded: height (N cm), weight (W kg), gender on the basis of which the body mass index (BMI), Kimt coefficients and Kpol coefficient and pressure increment for occlusion (ΔР, mm Hg) are calculated according to formulas:

The patient is placed in the supine position. The cuff of an automated tonometer built into the proposed device and controlled from it is attached to the patient's shoulder in the usual way. On the same hand, where the tonometer cuff is located, an optical sensor for the finger is attached to the patient's index or middle finger. Using a centimeter, measure the distance L between the middle of the shoulder and the finger pad of the subject's hand, on which the device sensor is installed. On the leg, on the instep of the foot in the first interdigital space, an optical sensor for raising the foot is fixed with an adhesive plaster or any other similar method. Measurements are carried out in two stages: a baseline test and functional occlusion and heat tests with a break after the baseline test of 5 minutes to restore blood flow in the arm.

The first is the basic test according to the time sequence (Fig. 1). The initial baseline test contains three phases: a phase of heating T ₁ for 10 seconds of skin areas under the sensors to temperatures t1 (first sensor) and t2 (second sensor) of the physiological norm in the range of 32 ° C-35 ° C to create standardized and identical temperatures skin measurement conditions; usually for a toe t1 = 34 ° C-35 ° C, for an instep t2 = 32 ° C-33 ° C; phase T ₂ measurements within 30 seconds of the average baseline (initial) microcirculation indicators fixed on the finger and on the instep of the foot with optical sensors, namely:

from the optical finger sensor located on the finger with the tonometer's cuff:

- by the optical method of assessing perfusion, the average baseline blood perfusion level in the skin of a finger over a time interval of 30 seconds (BUPr);

- by the PPG method, the average pulse waveform index (IPPW) in the skin of a finger over a 30 second time interval. IFPV is calculated as the ratio of the decay time of the pulse wave Δt ₂ to the rise time of the pulse wave Δt ₁ and characterizes the broadening of the pulse wave:

The level at which Δt ₁ and Δt ₂ are calculated is defined as 0.15 times the amplitude of the systolic pulse A ₁ . An illustration of the calculation of these parameters of the pulse waveform is shown in FIG. 2.

From the foot lift optical sensor located on the leg, the following is recorded:

- by the optical method of assessing perfusion, the average baseline perfusion level in the skin of the instep of the foot (BUPn) over a time interval of 30 seconds;

and in phase T _{3 with a} duration of 40 seconds of standard automated measurement with a tonometer with a cuff on the shoulder by the oscillometric method of SBP and DBP pressures when the pressure in the cuff is released, while in this phase of pressure relief according to the difference in the time of occurrence of pulse wave pulses in the shoulder from the cuff of the tonometer and in In addition, the average index of the pulse wave velocity (CPWV) along the arm is calculated on the finger from the optical sensor when the pressure is released for the finger. At time T2, the tonometer turns on the standard mode of automatic pressure measurement by the oscillometric method, during which SBP and DBP are recorded in the standard way. Based on the time delay of the passage of the pulse wave of blood from the shoulder to the tip of the finger, the average index of the pulse wave velocity (ISPV) is calculated by the formula:

where L is the distance between the middle of the shoulder and the tip of the subject's index / middle finger, ΔT is the difference in the time of the appearance of the systolic pulse of the pulse wave in the finger, recorded by the optical sensor, and the subject's shoulder, recorded by the tonometer cuff.

At the end of the pressure measurement (approximately 40 seconds from time T ₂ ), the baseline test step is considered complete.

After the baseline test, the proposed method contains a pause in measurements lasting 5 minutes to restore blood flow in the arm after measurements, the optical sensors are not removed, the set skin temperature is not changed, and after the end of the pause, functional thermal and occlusive tests are performed. In this case, the occlusion test in the proposed method is performed on the upper limb (arm) at an occlusion pressure in the cuff above the systolic blood pressure value, but not more than 300 mm Hg, choosing a specific value within this range based on the previously measured SBP level and adding to it, the AR parameter calculated by the formula (6).

Inflation of pressure into the cuff is carried out with an occlusion test faster than when measuring blood pressure, at a rate of 10 to 15 mm Hg. per second to exclude prolonged venous occlusion (the period when the air pressure in the cuff is above DBP, but below SBP). The occlusion after the creation of the desired pressure in the cuff is held for 120 seconds, after which the pressure is rapidly released at a rate of 50 to 100 mm Hg. per second and 10 seconds after the beginning of the pressure release, the average postocclusive blood perfusion level in the finger (PUPr) is recorded by the optical method of perfusion assessment for the next 10 seconds of reactive hyperemia (10 seconds after the beginning of the pressure release in the cuff, when postocclusive reactive hyperemia develops). A thermal test is performed on the lower limb (on the leg) simultaneously with the occlusive test on the upper limb by heating the skin under the optical sensor on the leg by heating the heating plate of the optical sensor from the initial temperature t2 to temperatures of 41.5 ° C-41.8 ° C at a speed of 1.5 ° C per second. Further, the heating temperature of the heating plate of the optical sensor is maintained at this level of 41.5 ° C -41.8 ° C for 120 seconds from the moment the heating is turned on and the average thermal level of blood perfusion in the leg (TUPn) for the period from 110 120 second thermal sample (Fig. 1).

All optical measurements in the proposed method are carried out by illuminating the skin surface under optical sensors with low-intensity and narrow-band optical radiation and recording backscattered radiation released from the skin and modulated in power (amplitude) due to light absorption by blood, with subsequent calculations of the blood perfusion parameter V _BF according to (1) is similar, for example, as it is done in the prototype method, through the spectral power density P (w) of low-frequency fluctuations of the recorded optical signal in the frequency range 0-20 Hz, caused by changes in blood volume due to rhythmic processes in the microcirculation system, and the constant component of the photocurrent i ₀ , and for the PPG method - with the subsequent calculation of the pulse waveform index (IPPW).

The spectral range of radiation sources for illuminating the skin is selected for this method in the region of maximum absorption of visible light by blood hemoglobin (range 520-600 nm) at any of the isobestic points of hemoglobin, for example, 569 nm (Rogatkin D.A. Physical bases of optical oximetry. Lecture. // Medical Physics, No. 2, 2012. - pp. 97-114) to exclude the influence on the measurement results of the blood oxygenation process.

After the end of the functional tests, a mathematical calculation of physiological coefficients (k _i ), physiological indicators (Ф _i ) and diagnostic criterion (DC) is carried out. Indexes i of physiological coefficients k _i and physiological parameters Ф _i correspond to various physiological factors: 1 - basic vascular tone in the arm, 2 - basic vascular tone in the leg, 3 - elasticity of the vascular wall, 4 - endothelial function, 5 - neurogenic regulation. Physiological coefficients of the basic vascular tone for the arm k ₁ and leg k _{2 are} calculated by the formulas:

- coefficient of elasticity of the vessel wall k ₃ according to the formula

- coefficient of vascular endothelial function k ₄ :

- coefficient of neurogenic regulation of vascular tone k ₅ :

after which physiological indicators (Ф _i ) are calculated, reflecting the standardized deviation of the estimated indicator in the examined patient from the control group, namely:

in this case, the coefficients m _i and σ _i , for which are determined in the control group of conditionally healthy subjects by the number n as follows:

Where j is the serial number of the subject from the control group.

An example of calculating the coefficients m _i and σ _i ,

To calculate the coefficients m _i and σ _i required for further calculations, a sample of 40 apparently healthy volunteer subjects less than 35 years of age without microcirculatory disorders was recruited. A similar sample can be independently selected by specialists using the proposed group of inventions, they can also use the data given below.

The gender, age, height and body weight of the patients, as well as the BMI, Kpol, Kimt, ΔР indices calculated according to the formulas (3), (4), (5), (6), respectively, are presented in Table 1.

All 40 conditionally healthy volunteers according to the method described above were registered indicators BUPr, BUPn, IFPV, SBP, DBP, SPV, PUPr, TUPn, the values of the indicators are given in Table 2.

From these indicators, the parameters of PAP were calculated by the formula PAP = SBP-DAP and physiological coefficients k ₁ -k ₅ by formulas (9) - (12). The values of the calculated parameters are shown in Table 3.

Further, using formulas (13) and (14), the coefficients m _i and σ _i were calculated, which are shown in table 4.

Further, on the basis of physiological parameters F ₁ -F ₅ for each patient, the DC diagnostic criterion is calculated according to the formula:

According to the DC diagnostic criterion, a conclusion is made about the severity of microcirculatory disorders in a subject with carbohydrate metabolism disorders: with DC> -1, they conclude that there are no microcirculatory disorders, with a DC value of ≤-1 and> -2, they conclude about weak microcirculatory disorders, with values DC ≤-2 and> -3, conclude about moderate microcirculatory disorders, with a value of DC ≤-3 and> -4, conclude about severe microcirculatory disorders, with values DC ≤ -4 conclude about very severe microcirculatory disorders.

The device (Fig. 3), which implements the proposed method, consists of an automatic blood pressure tonometer 1 with a conventional shoulder cuff 2 attached to it, which measures blood pressure by a known oscillometric method, but is controlled by an external microprocessor 3.0 of the microprocessor controller 3 of the proposed device, connected to the tonometer through the interface for controlling the tonometer 3.1 built into the microprocessor controller and the interface for receiving data from the tonometer 3.2 into the microprocessor 3.0 on the magnitude of SBP, DBP and amplitude pulsations of pressure in the tonometer cuff during pumping and depressurization, an optical sensor for a finger 4 and an optical sensor for raising a foot 5 , also connected to the microprocessor 3.0 of the microprocessor controller 3 through the built-in control unit for emitters and heaters 3.4 of optical sensors, as well as through the built-in unit for digitizing data 3.5 from photodetectors 4.2 and 5.2 and from temperature sensors 4.4 and 5.4 o optical sensors 4 and 5, respectively. In this case, the microprocessor controller 3 also contains a communication interface with the control computer 3.3, connected to an external control computer 6, which, in turn, contains a control program with which it is possible to process the obtained parameters and control the operation of the device. The optical sensor for the finger 4 and the optical sensor for raising the foot 5 contain radiation sources 4.1 and 5.1, respectively, photodetectors 4.2 and 5.2, respectively, as well as heating elements including heating plates with heaters 4.3 and 5.3 and temperature sensors 4.4 and 4.5 located on the heating plates. the surfaces of the heating plates. In this case, in each optical sensor, radiation sources 4.1 and 5.1, at least 3 pieces, for example, LEDs, are located radially around photodetectors 4.2 and 5.2, for example, silicon photodiodes with signal amplifiers, to ensure uniform illumination of the tested skin under the optical sensor, and and the radiation sources 4.1 and 5.1 and the photodetectors 4.2 and 5.2 are located in the through holes (cavities) of the heating plate as shown in FIG. 4, so that it is possible to illuminate the patient's skin under the optical sensor, which is installed during operation on the surface of the limb skin in contact with the plane of the heating plate. The spectral region of operation of the radiation sources is selected according to the proposed method in the region of maximum absorption of visible light by blood hemoglobin (range 520-600 nm) at any of the isobestic points of hemoglobin, for example, 569 nm [Rogatkin DA Physical foundations of optical oximetry. Lecture. // Medical Physics, No. 2, 2012. - p. 97-114] to exclude the influence of the blood oxygenation process on the measurement results. The heating plates of both optical sensors are made of materials with high thermal conductivity that allow contact with the patient's skin, for example, in the form of metal plates made of titanium or stainless steel, to ensure their rapid and maximum uniform heating from the electric heaters installed on them. Heaters on plates 4.5 and 5.5, for example, conventional surface mount resistors, are installed symmetrically at the corners of the plate to ensure uniform heating of the plates, and temperature sensors 4.4 and 5.4. installed closer to the center of the plates as shown in FIG. 4 to register the temperature of the surface of the plates in the area of the optical sensing elements - emitters and photodetector. In this case, heaters 4.5 and 5.5 are made with the ability to control their heating according to the commands of the microprocessor 3.0 by supplying them through the control unit for heaters 3.4 of a pulse-width (PWM) power supply - a pulse power supply with a controlled duty cycle, and feedback on controlling the surface temperature of the heating plates and maintaining it in the ranges set in the method is provided with the help of temperature sensors 4.4 and 5.4 and the organization in the program of the microprocessor 3.0 of a proportional-integral-differentiating algorithm for temperature control (PID controller algorithm) known from the prior art. The rest of all nodes and blocks of the device associated with the microprocessor are made with the possibility of operating in a pulse-periodic mode on commands and requests from the microprocessor 3.0, which forms the sequence diagram of the device operation shown in Fig. 5.

The device operates as follows.

The doctor-operator of the device enters into the control program the initial data about the patient: height (N cm), weight (W kg), on the basis of which the body mass index (BMI), Kimt coefficients and Kpol coefficient and the pressure increment for occlusion are calculated in the control program (ΔР, mm Hg) according to formulas (3) - (5) method. The patient is in the supine position. The cuff 2 of the tonometer 1 is attached in the usual way to the patient's shoulder. On the same hand where the cuff 2 of the tonometer 1 is located, the optical sensor 4 is attached to the index or middle finger of the hand with an adhesive plaster or any other similar method (Fig. 6). The optical sensor 5 is attached with an adhesive plaster or any other similar method on the instep of the foot in the first interdigital space as shown in FIG. 6. Alternatively, the optical sensor 4 can be attached to a finger due to its “clothespin” design, similar to the known pulse oximeter sensors.

At the command of the physician-operator of the device "start" from the program from the control computer 6 to the microprocessor controller 3, the command to start measurements is given along with the value of the pressure increment for occlusion (ΔP, mm Hg). When the command to start measurements is received, the microprocessor 3.0 of the microprocessor controller 3, according to a given internal program, forms a sequence diagram of the operation of the units and blocks of the device as shown in FIG. 5 and a general sequence diagram (sequence) of the baseline test and functional tests according to the proposed method (Fig. 1). For this, the microprocessor controller 3 generates a cycle with a duration T of the _{cycle of} operation of the nodes and units of the device with a T _{cycle of} ≤ 6.25 ms to ensure the resolution of the signal from the photodetectors in frequency in the frequency range up to 80 Hz according to the Kotelnikov theorem, within which the PWM control signals for the heaters are continuously generated optical sensors, emitters 4.1 and 5.1 are switched on simultaneously at the beginning of the cycle and when the emitters are on, sequential interrogation of signals from photodetectors 4.2 and 5.2 is performed N times with the formation of the average for N interrogations of the signal from each photodetector when the emitters are on, then the emitters 4.1 and 5.1 are switched off and performed when turned off emitters, sequential interrogation N times of signals from photodetectors 4.2 and 5.2 with the formation of the average for N interrogations of the signal from each photodetector when the emitters are turned off, and when the emitters are turned off, the microprocessor 3.0 issues at the moments of time due to the general sequence of the baseline test and functional tests according to the proposed method (Fig. 1), commands to start measuring pressure, start / end occlusion with pressure in the cuff SBP + ΔP using command codes and AP pressure values transmitted to tonometer 1 via the tonometer control interface 3.1, receives data from the tonometer on SBP and DBP values, as well as on the times of the maxima of the air pressure pulse in the cuff during inflation / release during pressure measurement during the basic test, receives data from temperature sensors 4.4 and 5.4 and generates PID controller commands, and at the end of the cycle transfers all received data to the control computer and receives new commands from him, if they are generated by him (for example, a command to emergency stop the device). All further data processing is carried out in the control program of the computer and all further calculations are carried out, namely:

- for each photodetector, an array of registered signals is formed from ≥160 points per second by subtracting the average recorded signal with the emitters turned off from the average recorded signal with the emitters turned on;

- for each photodetector, according to the generated array of registered signals, the parameter of tissue blood perfusion as a function of time is calculated by the optical method for assessing perfusion, in the same way as in the prototype;

- during the time period T ₁ -T _{2 of the} basic test for the photodetector 4.1 of the optical sensor for the finger, according to the generated array of registered signals by the known PPG method, the pulse waveform is isolated and the average pulse waveform index (IPPW) in the skin of the finger is determined over a time interval of 30 seconds according to the formula (7) method;

- when carrying out pressure measurements with a tonometer, when the pulses of air pressure in the cuff are recorded by the oscillometric method, the average pulse wave velocity index (CPWV) is calculated from the difference in the time of occurrence of the pulse wave pulses from the tonometer cuff and in the finger from the optical sensor for the finger;

- after receiving data from the tonometer about the measured SBP and DBP, the pulse pressure is calculated PAP = SBP-DBP;

- at the end of the baseline test and functional tests with occlusion and heating, according to the registered signals from optical sensors and the parameters of tissue blood perfusion calculated from these signals, the average for the time interval T ₁ -T _{2 is} calculated the base level of perfusion in the skin of the finger (BUPr), the average for time interval T ₁ -T _{2 the} base level of perfusion in the skin of the instep of the foot (BUPn), the average post-occlusive blood perfusion level in the finger (PUPr), the average thermal level of blood perfusion in the leg (TUPn), and all calculations are performed according to the formulas (8 ) - (15) of the method and a diagnostic conclusion is issued on the presence and severity of microcirculatory disorders in the skin in patients with disorders of carbohydrate metabolism.

This design of the optical sensors and the device as a whole, as well as the proposed cyclogram and the principle of operation of the device, for the first time allow one device to simultaneously implement optical methods of photoplethysmography (PPG) and the optical method for assessing perfusion, including during simultaneous functional tests with heating and occlusion on the leg and the patient's hand in automatic mode. Adding to the design of a blood pressure tonometer, which measures pressure by an oscillometric method with a shoulder cuff, and recording the time delay between the pressure pulse in the cuff of the tonometer on the shoulder and the corresponding pulse on the photoplethysmogram from the optical sensor on the finger, during the pressure measurement procedure, it is possible to determine the speed of propagation of the pulse wave along hands, and, accordingly, assess the elasticity of the vascular wall, which cannot be done separately by any of the methods used. This increases the information content of the examination and the reliability of detecting microcirculatory disorders in the skin of the extremities in patients with disorders of carbohydrate metabolism.

High-precision and objective assessment of microcirculatory disorders in patients with disorders of carbohydrate metabolism is confirmed by the following clinical examples.

Example 1. Patient A., age 27 years old, male, underwent a study of microcirculation according to the above method on the proposed device. The patient's height is 178 cm, body weight is 75 kg, the distance L between the middle of the shoulder and the pad of the finger was 55 cm.

The calculated indices were: BMI - 23.7 kg / m ² , Kpol - 1, Kimt - 5.2, ΔР - 71 mm Hg.

The finger probe was placed on the patient's right index finger, the foot lift probe was installed in the first interdigital space of the dorsum of the right foot.

The initial temperature of the sensor on the foot was set at 32.0 ° C, on the finger - 34.0 ° C.

The following describes how to take measurements on a patient. The points on the cyclogram (Fig. 1) corresponding to the described test period are shown in the form (T _x -T _y ).

After pressing the "Start" button, the sensors warmed up to the set temperature for 10 seconds (T ₀ -T ₁ ), after which, within 30 seconds (T ₁ -T ₂ ), the indicators BUPr - 15.22, BUPn - 2, 95, IFPV -2.204. Then, within 40 seconds (T ₂ -T ₃ ), the parameters of SBP were measured - 123 mm Hg, DBP - 73 mm Hg, ISPV - 12.571, and the parameters of PAP were calculated - 50 mm Hg. and ΔР - 71 mm Hg. This was followed by a pause to restore blood flow lasting 5 minutes (T ₃ -T ₄ ). Further functional tests were carried out. The sensor on the foot warmed up to 41.8 ° C in 6.5 seconds (T ₄ -T ₇ ) and 120 seconds after the heating was turned on (T ₄ -T ₈ ), the TUPn parameter was estimated - 16.69. In parallel, an occlusion test was performed. In ~ 16 seconds (T ₄ -T ₅ ) at a speed of ~ 12 mm Hg. the cuff pressure of the device was inflated to 194 mm Hg. (SAD + ΔP). The pressure was held at this level for 120 seconds (T ₅ -T ₆ ), after which the pressure in the cuff was released and within 20 seconds (T ₆ -T) the parameter PUPr was estimated at 11.24.

Further, the physiological coefficients k ₁ -k ₅ , physiological parameters F ₁ -F ₅ and the diagnostic criterion DC were calculated.

k ₁ - 3.29, k ₂ - 16.9, k ₃ - 0.175, k ₄ - 0.739, k ₅ - 5.66, F ₁ - -0.039, F ₂ - -0.117, F ₃ - -1.051, F ₄ - -1.341, Ф ₅ - 0.826, DC - -0.439.

Since the DC criterion fell into the range "> -1", it was concluded that there were no microcirculatory disorders. This observation was confirmed by the results of a clinical examination: the patient had no nephropathy, retinopathy, or arterial hypertension. The glycemic indicators were normal. Additional examination with thermal and occlusive tests on a hardware-software complex for functional diagnostics of the blood microcirculation system confirmed the absence of microcirculatory disorders in the patient.

Example 2. Patient B., 62 years old, female, was examined in the above described way on the proposed device.

The patient's height is 162 cm, body weight is 50 kg, the distance L between the middle of the shoulder and the pad of the finger was 49 cm.

Settlement rates were: BMI - 19.1 kg / m ^2, Kpol - 0 Kimt - 0.6,? P - 51 mm Hg

A finger probe was placed on the patient's right middle finger, and a foot lift was placed in the first interdigital space of the dorsum of the right foot.

The initial temperature of the sensor on the foot was set at 33.0 ° C, on the finger - 34.9 ° C.

The following is a description of taking measurements on a patient. The points on the cyclogram (Fig. 1) corresponding to the described test period are shown in the form (T _x -T _y ).

After pressing the "Start" button, the sensors warmed up to the set temperature for 10 seconds (T ₀ -T ₁ ), after which, within 30 seconds (T ₁ -T ₂ ), the indicators BUPr - 20.11, BUPn - 2, 24, IFPV - 0.941. Then, within 40 seconds (T ₂ -T ₃ ), the parameters of SBP were measured - 115 mm Hg, DBP - 68 mm Hg, ISPV - 10.359, and the PAP parameter was calculated - 47 mm Hg. This was followed by a pause to restore blood flow lasting 5 minutes (T ₃ -T ₄ ). Further functional tests were carried out. The sensor on the foot warmed up to 41.5 ° C in 5.7 seconds (T ₄ -T ₇ ) and 120 seconds after the heating was turned on (T ₄ -T ₈ ) the parameter TUPn was estimated - 9.18 In parallel, an occlusion test was performed. In ~ 12 seconds (T ₄ -T ₃ ) at a speed of ~ 14 mm Hg. the cuff pressure of the device was inflated to 166 mmHg. (SAD + ΔP). The pressure was held at this level for 120 seconds (T ₅ -T ₆ ), after which the pressure in the cuff was released, and within 20 seconds (T ₆ -T), the PUPr parameter was estimated at 30.28.

Further, the physiological coefficients k ₁ -k ₅ , physiological parameters F ₁ -F ₅ and the diagnostic criterion DC were calculated.

k ₁ - 2.34, k ₂ - 20.98, k ₃ - 0.091, k ₄ - 1.51, k ₅ - 4.1, Ф ₁ - -0.363, Ф ₂ - 0.383, Ф ₃ - -1, 68, F ₄ - -0.228, F ₅ - -0.034, DC - -2.724.

Since the OS criterion fell into the range "-3 <DC≤-2", the microcirculatory disorders in this patient were assessed as moderate.

According to the results of clinical examination, the patient had episodes of increased blood pressure, early disorders of carbohydrate metabolism, while there was no retinopathy and nephropathy. Additional examination with thermal and occlusive tests on a hardware-software complex for functional diagnostics of the blood microcirculation system confirmed the presence of microcirculatory disorders in the patient.

Example 3. Patient B., with a long history of type 2 diabetes mellitus, age 72 years, height 170, body weight 83 kg, distance L between the middle of the shoulder and the pad of the finger was 54 cm, was examined using the described method on the proposed device.

The calculated indicators were: BMI - 28.7 kg / m ² , Kpol - 1, Kimt - 10.2, ΔР - 82 mm Hg.

The finger probe was placed on the patient's right index finger, the foot lift probe was installed in the first interdigital space of the dorsum of the right foot.

The initial temperature of the sensor on the foot was set at 32.8 ° C, on the finger - 34.1 ° C.

The following describes how to take measurements on a patient. The points on the cyclogram (Fig. 1) corresponding to the described test period are shown in the form (T _x -T _y ).

After pressing the "Start" button, the sensors heated up to the set temperature for 10 seconds (T ₀ -T ₁ ), after which, within 30 seconds (T ₁ -T ₂ ), the indicators BUPr - 27.1, BUPn - 2, 85, IFPV - 1.277. Then, within 40 seconds (T ₂ -T ₃ ), the parameters of SBP were measured - 134 mm Hg, DBP - 72 mm Hg, ISPV - 5.517 and the PAP parameter was calculated - 62 mm Hg. This was followed by a pause to restore blood flow lasting 5 minutes (T ₃ -T ₄ ). Further functional tests were carried out. The sensor on the foot warmed up to 41.8 ° C in 5.9 seconds (T ₄ -T ₇ ) and 120 seconds after the heating was turned on (T ₄ -T ₈ ), the TUPn parameter was estimated as 3.39. In parallel, an occlusion test was performed. In ~ 14.4 seconds (T ₄ -T ₅ ) at a speed of ~ 15 mm Hg. the cuff pressure of the device was inflated to 216 mm Hg. (SAD + ΔP). The pressure was held at this level for 120 seconds (T ₅ -T ₆ ), after which the pressure in the cuff was released and within 20 seconds (T ₆ -T) the parameter PUPr was estimated at 27.81.

Further, physiological coefficients k ₁ -k ₅ , physiological parameters F ₁ -F ₃ and diagnostic criterion DC were calculated.

k ₁ - 2.29, k ₂ - 21.75, k ₃ - 0.231, k ₄ - 1.026, k ₅ - 1.19, Ф ₁ - -0.379, Ф ₂ - 0.47, Ф ₃ - -0.633, F ₄ - -0.923 F ₅ - -1.640, DC - -4.79.

Since the DC criterion fell into the range "DC≤-4", it was concluded that there were very strong microcirculatory disorders.

This observation was confirmed by the results of a clinical examination: the patient was diagnosed with arterial hypertension, coronary heart disease, diabetic retinopathy, diabetic nephropathy, glycated hemoglobin values exceeded the target values. Additional examination with thermal and occlusive tests on a hardware-software complex for functional diagnostics of the blood microcirculation system confirmed the presence of microcirculatory disorders in the patient.

Example 4. Patient G., 42 years old, female, was examined in the above described way on the proposed device.

The patient's height was 174 cm, body weight was 62 kg, the distance L between the middle of the shoulder and the pad of the finger was 50 cm.

The calculated indicators were: BMI - 20.5 kg / m ² , Kpol - 0, Kimt - 2, ΔР -54 mm Hg.

A finger probe was placed on the patient's right middle finger, and a foot lift was placed in the first interdigital space of the dorsum of the right foot.

The initial temperature of the sensor on the foot was set at 32.3 ° C, on the finger - 35.0 ° C.

The following is a description of taking measurements on a patient. The points on the cyclogram (Fig. 1) corresponding to the described test period are shown in the form (T _x -T _y ).

After pressing the "Start" button, the sensors warmed up to the set temperature for 10 seconds (T ₀ -T ₁ ), after which, within 30 seconds (T ₁ -T ₂ ), the indicators BUPr - 41.99, BUPn - 3, 53, IFPV - 1.179. Then, within 40 seconds (T ₂ -T ₃ ), the parameters of SBP were measured - 111 mm Hg, DBP - 73 mm Hg, ISPV - 4.281, and the PAP parameter was calculated - 38 mm Hg. This was followed by a pause to restore blood flow lasting 5 minutes (T ₃ -T ₄ ). Further functional tests were carried out. The sensor on the foot warmed up to 41.5 ° C in 6.3 seconds (T ₄ -T ₇ ) and 120 seconds after the heating was turned on (T ₄ -T ₈ ), the TUPn parameter was estimated - 4.92.An occlusion test was carried out in parallel. In ~ 16.5 seconds (T ₄ -T ₅ ) at a speed of ~ 10 mm Hg. the cuff pressure of the device was inflated to 165 mm Hg. (SAD + ΔP). The pressure was held at this level for 120 seconds (T ₅ -T ₆ ), after which the pressure in the cuff was released and within 20 seconds (T ₆ -T) the parameter PUPr was estimated at 62.7.

Further, the physiological coefficients k ₁ -k ₅ , physiological parameters F ₁ -F ₅ and the diagnostic criterion DC were calculated.

k ₁ - 0.9, k ₂ - 10.76, k ₃ - 0.275, k ₄ - 1.49, k ₅ - 1.39, Ф ₁ - -0.851, Ф ₂ - -0.885, Ф ₃ - -0.306 , F ₄ - -0.246, F ₅ - -1.527, DC - -1.900.

Since the DC criterion fell into the range "-2 <DC≤-1", it was concluded that the patient had mild peripheral hemodynamic impairments.

According to the results of clinical examination, the patient had no retinopathy and nephropathy, episodes of increased blood pressure were noted. The patient smokes, which could also affect the results of the study. Additional examination with thermal and occlusive tests on a hardware-software complex for functional diagnostics of the blood microcirculation system revealed a decrease in microcirculation parameters.

Example 5. Patient D., 53 years old, female, suffering from type 2 diabetes mellitus, was examined in the above described way on the proposed device.

The patient's height was 165 cm, body weight was 107 kg, the distance L between the middle of the shoulder and the pad of the finger was 48 cm.

The calculated indicators were: BMI - 39.3 kg / m ² , Kpol - 0, Kimt - 20.8, ΔР - 96 mm Hg.

A finger probe was placed on the patient's right middle finger, and a foot lift was placed in the first interdigital space of the dorsum of the right foot.

The initial temperature of the sensor on the foot was set at 32.4 ° C, on the finger - 34.3 ° C.

The following is a description of taking measurements on a patient. In the form (T _x -T _y ) are the points on the cyclogram (figure 1), corresponding to the described test period.

After pressing the "Start" button, the sensors heated up to the set temperature for 10 seconds (T ₀ -T ₁ ), after which, within 30 seconds (T ₁ -T ₂ ), the indicators BUPr - 33.05, BUPn - 2 were recorded, 62, IFPV - 1.633. Then, within 40 seconds (T ₂ -T ₃ ), the parameters of SBP were measured - 120 mm Hg, DBP - 80 mm Hg, ISPV - 9.778, and the PAP parameter was calculated - 40 mm Hg. This was followed by a pause to restore blood flow lasting 5 minutes (T ₃ -T ₄ ). Further functional tests were carried out. The sensor on the foot warmed up to 41.8 ° C in ~ 5.9 seconds (T ₄ -T ₇ ) and after 120 seconds from the moment the heating was turned on (T ₄ -T ₈ ), the TUPn parameter was estimated - 4.65 In parallel, an occlusion test was performed ... In ~ 15.4 seconds (T ₄ -T ₅ ) at a speed of ~ 14 mm Hg. the cuff pressure of the device was inflated to 216 mm Hg. (SAD + AR). The pressure was held at this level for 120 seconds (T ₅ -T ₆ ), after which the pressure in the cuff was released, and within 20 seconds (T ₆ -T) the parameter RLP was estimated at -31.75.

Further, the physiological coefficients k ₁ -k ₅ , physiological parameters F ₁ -F ₅ and the diagnostic criterion DC were calculated.

k ₁ - 1.21, k ₂ - 15.27, k ₃ - 0.1671, k ₄ - 0.96, k ₅ - 1.77, Ф ₁ - -0.747, Ф ₂ - -0.326, Ф ₃ - -1.113, F ₄ - -1.018, F ₅ - -1.317, DC - -3.739.

Since the DC criterion fell into the range "-4 <DC≤-3", it was concluded that the patient had severe peripheral hemodynamic disturbances.

According to the results of the clinical examination, the patient had grade 2 obesity, a high level of glycated hemoglobin, diabetic nephropathy, but there was no diabetic retinopathy, which is consistent with the results of the examination by the proposed method. Additional examination with thermal and occlusive tests on a hardware-software complex for functional diagnostics of the blood microcirculation system confirmed the presence of microcirculatory disorders in the patient.

From December 2018 to March 2019, using the proposed device according to the proposed method, 18 patients with disorders of carbohydrate metabolism, aged from 27 to 77 years, were studied. In all cases, a reliable and high-precision detection of microcirculatory disorders in this group of patients was achieved.

Complex and non-invasive detection of microcirculatory disorders, as well as their clear gradation according to severity degrees, allows you to quickly and physiologically objectify microcirculation parameters in order to select the optimal way of treating microcirculatory changes in patients with carbohydrate metabolism disorders in the future, as well as to evaluate them over time. Conducting functional tests according to the proposed group of inventions is simple for both the patient and the operator conducting the study. The results obtained allow us to state that the method and device are highly sensitive and combine a comprehensive and objective assessment of the current state of the microvasculature in the above category of patients.

The design features of the proposed device, in particular, optical sensors, allow simultaneous thermal and occlusion tests, determination of blood perfusion by an optical method for assessing perfusion simultaneously with photoplethysmography, which makes it possible to evaluate in one diagnostic procedure simultaneously the basic tone of the vessels on the arm and leg of the patient, elasticity vascular walls, endothelial function and neurogenic regulation of the microvasculature.

A technical and economic improvement should be considered a reduction in terms and simplification of the study, due to a non-invasive comprehensive assessment carried out using the proposed device, since registration of microcirculation indicators in this case does not require the patient to participate in painful, lengthy and complex procedures, which in itself can be a distorting factor for the current state of microcirculation and reduce the objectivity of the recorded indicators.

The use of this method and device allows highly efficient recording of the optical characteristics of the investigated cutaneous microcirculation both on an outpatient basis and in a hospital setting, which is optimal for patients with disorders of carbohydrate metabolism, and to obtain highly reliable data.

Claims (27)

1. A method for assessing microcirculatory disorders in the skin in patients with carbohydrate metabolism disorders, including recording on the limb, namely on the arm, the level of cutaneous microcirculation of blood using an optical method for assessing perfusion by conducting a basic test and tests with a functional occlusion test and a functional heat test with rapid heating of the skin to a temperature of 41.5 ° C-41.8 ° C for 5-6 seconds using an optical sensor for a finger with a wavelength of radiation in the region of any of the isobestic points of hemoglobin in the spectral range of 520-600 nm and equipped with a heating element for heating the working surface of the sensor and the skin under it; and the implementation of a mathematical calculation of the physiological indicators of microcirculation based on the data obtained with the formation of the final diagnostic conclusion, characterized in that the initial data of the patient are pre-recorded: height (H, cm), weight (W, kg), gender, on the basis of which the body mass index is calculated (BMI), coefficients Kimt and Kpol:

measure the distance L, cm between the middle of the shoulder and the finger pad of the patient's hand, on which the optical sensor is installed, before starting the basic test on the shoulder of the test arm, in addition to the optical sensor, fix the tonometer cuff, additionally, as a test limb, examine the patient's leg using a second optical sensor, which fixed on the instep of the foot in the first interdigital space, while using optical sensors simultaneously record perfusion indicators using the optical method for assessing perfusion and pulse wave indicators by photoplethysmography, the basic test is carried out for 80 seconds with a surface temperature of optical sensors for raising the foot of 32 ° C -33 ° C and for a finger 34 ° C-35 ° C, during the baseline test 10 seconds after the start of measurements, within 30 seconds, the parameters of the base level of perfusion on the hand, averaged over 30 seconds, are recorded and determined using the optical method for assessing perfusion - BUPr and base level n leg perfusion - BUPn with appropriate optical sensors, and using the method of photoplethysmography on the arm, the pulse waveform index - IFPV, as the ratio of the wave decay time interval Δt ₂ to the rise time interval Δt ₁ :

the level at which Δt ₁ and Δt ₂ are calculated is determined as 0.15 of the maximum amplitude A _{1 of the} systolic pulse on the photoplethysmogram, after which an automated measurement of the systolic and diastolic blood pressure levels of SBP and DBP is carried out with the calculation of the pulse blood pressure PAP, when which with the help of an optical sensor on the arm at the time of measuring SBP and DBP at the stage of pressure relief according to the difference in time of the pulses of the pulse wave of blood in the shoulder from the cuff of the tonometer and in the finger from the optical sensor the average index of the pulse wave velocity of ISPV is calculated by the formula

where L is the distance between the middle of the shoulder and the finger pad of the patient's hand, on which the optical sensor of the device is installed, ΔT is the difference in time between the appearance of the systolic pulse of the pulse wave in the finger, recorded by the optical sensor, and the pressure pulse in the patient's shoulder, recorded by the pressure sensor of the tonometer; further, without removing the sensors and the cuff, without changing the surface temperature of the sensors, stop the study for 5 minutes to restore blood flow in the arm, after which a test with functional tests is carried out, which includes the simultaneous conduct of two tests - an occlusive test using the cuff of a tonometer on the arm and a thermal test using a sensor on the leg; in case of an occlusive test, arterial occlusion on the shoulder is carried out by pumping the pressure in the tonometer cuff to the value of SBP + ΔP at a rate of 10 to 15 mm Hg. per second, the pressure increment for occlusion (ΔР, mm Hg) is calculated by the formula

the maximum SBP + ΔP value is no more than 300 mm Hg, the occlusion is maintained at this pressure for 120 seconds, after which the pressure is released at a rate of 50 to 100 mm Hg. per second and 10 seconds after the start of the pressure release, the average post-occlusive blood perfusion level in the finger of the PUPr hand is recorded by an optical method for assessing perfusion on the hand for the next 10 seconds of reactive hyperemia; heating for the thermal test on the leg is performed from an initial temperature of 32 ° C-33 ° C, then the set temperature is maintained for 2 min and the average thermal level of blood perfusion on the leg TUPn is recorded by the optical method for assessing perfusion for the period from 110 to 120 seconds of the thermal test with the moment of the start of heating, the physiological coefficients of the basic vascular tone for the arm k ₁ and leg k ₂ are calculated according to the formulas

- coefficient of elasticity of the vessel wall k ₃ according to the formula

- coefficient of vascular endothelial function k ₄ :

- coefficient of neurogenic regulation of vascular tone k ₅ :

after that, the physiological indicators F _{i are} calculated, reflecting the standardized deviations of the estimated indicator in the examined patient from the control group, namely:

in this case, the coefficients m _i , and σ _i for them are determined in the control group of conditionally healthy subjects by the number n as follows:

where j is the serial number of the test subject from the control group, then, based on the physiological parameters of F ₁ -F ₅ for each patient, the DC diagnostic criterion is calculated according to the formula

according to the DC diagnostic criterion, a conclusion is made about the severity of microcirculatory disorders in a patient: at DC> -1, a conclusion is made about the absence of microcirculatory disorders, with a value of DC ≤ -1 and> -2, microcirculatory disorders are evaluated as weak, with a value of DC ≤ -2 and> -3, assess microcirculatory disorders as moderate, with a DC value ≤ -3 and> -4, assess microcirculatory disorders as severe, with DC ≤ -4 evaluate microcirculatory disorders as very severe. 2. The method according to claim 1, characterized in that incoherent fluctuation spectroscopy is used as an optical method for assessing perfusion. 3. The method according to claim 1, characterized in that laser Doppler flowmetry is used as an optical method for assessing perfusion. 4. A device for implementing the method according to claim 1, comprising a radiation and heating control unit, a communication interface with a control computer, a data digitization unit from photodetectors and temperature sensors, a microprocessor, the first and second outputs of which are configured to be connected to the input of the radiation control unit and heating and the input of the communication interface with the control computer, a unit for digitizing data from photodetectors and temperature sensors, the output of which is configured to be connected to the input of the microprocessor; as well as a control computer and an optical sensor connected to the communication interface, which includes at least three optical emitters emitting narrowband optical radiation in the region of any of the isobestic points of hemoglobin in the spectral wavelength range of 520-600 nm, located radially at the same distance from each other around the photodetector, a photodetector and a heating element containing a heating plate, heaters and a temperature sensor, while the emitters and a photodetector are located in the through holes of the heating plate, the emitters and the heating plate are made with the possibility of being connected to the radiation and heating control unit, and the outputs of the photodetector and the temperature sensor are made with the possibility of connection with the first and second inputs of the unit for digitizing data from the photodetector and the temperature sensor, characterized in that it additionally includes a tonometer control interface, the input of which is made with the possibility of connection with the third output of the microprocessor; an interface for receiving data from a tonometer, the output of which is configured to be connected to the input of a microprocessor, a tonometer, the input of which is adapted to be connected to the output of the interface for controlling the tonometer, and the first and second outputs of the tonometer are made to be connected to the cuff of the tonometer and the input of the interface for receiving data from the tonometer ; Also, the device is equipped with at least one additional optical sensor, with each corner of the heating plate of a square shape in each of the optical sensors equipped with a heater, and the temperature sensor is located in the center of the plate next to the photodetector.

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