Method and device for non-invasive optical measurement of properties of living tissue

Abstract

Method for non-invasive optical measurement of properties of living tissue inside a body (1), with a measuring device (2) comprising at least a light source (3) and a detector (4, 4'), wherein the measuring device or at least a part of the measuring device is pressed against the surface, e.g. the skin, of the body (1), wherein the body (1) is illuminated by means of the light source (3) with light of at least one wavelength and wherein the light backscattered from the body (1) or the light passing through the body (1) is detected by the detector (4, 4') and the detector signal is evaluated to determine a property of the tissue, characterized in that the contact pressure of the measuring device (2) against the body (1) is checked before, during and / or after the measurement of the optical property, wherein to determine the contact pressure light with at least one wavelength is shone into the body (1) and the intensity (I r , I t ) of the light backscattered from or passing through the body (1), the intensity depending on the contact pressure, so that the measured intensity (I r , I t ) represents the contact pressure.

Description

[0001] The invention relates to a method for non-invasive optical measurement (or in-vivo measurement) of properties of living tissue (including flowing blood) inside a (human) body, with a measuring device comprising at least one light source and one detector. wherein the measuring device or at least a part of the measuring device is pressed against the surface, e.g. the skin, of the body, wherein the body is illuminated by means of the light source with light of at least one wavelength and wherein the light backscattered from the body or the light passing through the body is detected by the detector and the detector signal is evaluated to determine one property of the tissue or to determine several properties of the tissue.

[0002] The body in question is therefore preferably a human body. Non-invasive measurement refers, for example, to the non-invasive measurement of the concentration of blood components in blood vessels, such as the measurement of hemoglobin concentration, oxygen saturation, blood glucose level, or the like. However, the invention also encompasses measurement in tissue outside of a bloodstream, for example, in the course of in vivo tissue classification. In this process, light, for example from one or more laser light sources, is shone into the body, and the desired parameters are determined in various ways by measuring and evaluating the backscattered light. For this purpose, electromagnetic radiation (e.g., laser light radiation) from the visible and / or infrared range is typically used, for example, between approximately 550 nm and 2,000 nm. Frequently, to optimize the measurement methods, the backscattered light is measured under the influence of ultrasound radiation, for example, to...to mark the measurement location with ultrasound radiation.

[0003] A method for the optical measurement of the properties of flowing blood using ultrasound localization is known, for example, from EP 1 601 285 B1. The ultrasound radiation is focused onto the interior of a central blood vessel, and a light source and an adjacent detection unit for capturing the backscattered light are positioned on the skin surface above the blood vessel such that the distance between the light source and the majority of the photoreceptors of the detection unit corresponds to the depth of the blood tissue being examined. The target tissue is illuminated with at least two discrete wavelengths of light, and the backscattered light is measured. The ultrasound wave field causes changes in the optical properties, particularly the reflectance and scattering, through interaction with the blood and tissue.This leads to a modulation of the backscattered light with the frequency of the ultrasound radiation, so that the modulated portion can be extracted during the evaluation.

[0004] In connection with the determination of blood glucose concentration, DE 10 2006 036 920 B3 describes a method for the spectrometric determination of blood glucose concentration in pulsating blood. Implementing this method for the non-invasive in vivo determination of glucose concentration additionally requires a non-invasive determination of the blood temperature. Such a method for the non-invasive, optical determination of the temperature of a medium within a body is known, for example, from DE 10 2008 006 245 A1. In this optical temperature measurement as well, the measurement location within a body, e.g., a blood vessel, can be marked using pulsed ultrasound radiation.

[0005] A modification of the described methods, which are based on ultrasound localization, is known from WO 2015 / 177156 A1. There, too, the body is irradiated with ultrasound radiation at a specific frequency to mark a blood vessel. The body, including the blood vessel, is illuminated with light of at least one wavelength, and the backscattered light is detected. The portion of the light reflected from the body outside the blood vessel is modulated at a frequency corresponding to the ultrasound frequency. Due to the Doppler effect in flowing blood, the portion of the light reflected from the blood vessel is modulated at a frequency shifted by the Doppler shift relative to the frequency of the ultrasound radiation. An evaluation unit can extract the signal component modulated by the shifted frequency from the detector signal measured at the detector.This method ensures that only those components of the backscattered light that are actually backscattered from the blood are included in the evaluation, since only these are modulated with a different modulation frequency due to the Doppler effect than the light components backscattered from the adjacent tissue. This allows for precise marking of the blood vessel, regardless of whether focused ultrasound radiation is used or not. In contrast to the method known from EP 1 601 285 B1, the method known from WO 2015 / 177156 A1 does not use ultrasound radiation to locate the blood vessel; instead, the utilization of the Doppler effect is directly incorporated into the evaluation of the optical measurement.

[0006] Various methods for the non-invasive, optical measurement of the properties of living tissue are known in the prior art, based on both transmission and reflection measurements. Implementing these known methods in practice presents numerous challenges, particularly regarding the transfer of measurement methods from laboratory conditions to practical application. This is especially true when measurements are not only intended to be performed under ideal conditions by a physician or medically trained personnel, but also to allow patients to perform their own measurements. This is where the invention comes in.

[0007] Furthermore, US patent 2012 / 0190944 A1 discloses a device or method for the non-invasive optical measurement of physiological properties, wherein the tissue to be examined is illuminated with light and the transmitted or reflected light is measured as a signal. Additionally, the pressure applied to the measuring device by the user is measured.

[0008] Finally, US patent 7,672,702 B1 discloses the non-invasive in vivo measurement for determining blood glucose concentration using Raman spectroscopy. This involves using a pressure sensor to measure the pressure exerted by a finger on the device's actuating surface.

[0009] The invention is based on the objective of creating a method that enables reliable, non-invasive optical measurement of properties of living tissue inside a body and is preferably characterized by improved ease of use and / or increased insensitivity to incorrect operation.

[0010] To solve this problem, the invention teaches a method with features of claim 1. In a generic method of the type described above, it is provided that the contact pressure of the measuring device against the body is checked before, during and / or after the measurement of the optical properties, also by optical means, so that with increased functionality the equipment effort is not increased or not significantly increased.

[0011] The invention is based on the well-known fact that conventional optical methods are fundamentally well-suited for the non-invasive optical measurement of properties of living tissue inside a body, both on the basis of transmission measurements and on the basis of reflection measurements. It is always advantageous to place a measuring device, comprising at least one light source and a detector, directly onto the body, e.g., onto the skin, in order to ensure that the light is properly directed into the body and that the light components passing through the body and / or the light components backscattered from the body are detected. The invention recognizes that varying contact pressure exerted by the measuring device on the body under investigation, and consequently on the tissue under investigation, can influence the measurement results. For example, if...When the properties of flowing blood, such as oxygen saturation or blood glucose levels, are examined using optical methods, varying contact pressure of the device can influence the conditions in the bloodstream and / or adjacent tissue, thus distorting the measurement. The positions and orientations of scattering particles within the bloodstream typically change in a pulsating manner, resulting in pulsating variations in the blood's absorption properties due to the pulsating changes in density and orientation. These conditions are affected and disrupted, for example, by altered contact pressure of the measuring device. This can lead to a "pulse disappearance" due to the increased contact pressure. Furthermore, an increased density of scattering centers in the tissue, caused by higher contact pressure, can alter the measurement.A "blockage" of a particular "optical situation" can also occur, so that the values ​​obtained during the measurement no longer correspond to the current values. Against this background, the invention recognizes that controlling the contact pressure is advantageous, particularly to prevent an unacceptably high influence on the measurement due to excessively high or low contact pressure. Thus, a permissible contact pressure range with a lower and an upper limit can be defined in a control unit of the measuring device and, for example, stored in the control unit. If it turns out during the measurement that the contact pressure is outside the permissible range, a (subsequent) measurement of the optical properties of the tissue or blood can be prevented. Alternatively or additionally, a warning signal can sound. This will be discussed further below.

[0012] According to the invention, the contact pressure itself is also determined using optical means. For this purpose, light with at least one wavelength is shone into the body to determine the contact pressure, and the intensity of the light backscattered from or passing through the body is measured. The intensity depends on the contact pressure, so that the measured intensity represents the contact pressure. This makes it possible, for example, to define a permissible intensity range with a lower and an upper limit and to store and evaluate, for example, in a control unit of the measuring device, whether the measured intensity lies within or outside the permissible intensity range. Thus, the optical measurement for determining the tissue properties can be prevented if the intensity measured during pressure control lies outside the intensity range, i.e.,The actual measurement is only permitted if the intensity measured during pressure monitoring is within the intensity interval. Alternatively or additionally, a visual and / or audible warning signal can be generated.

[0013] The invention recognizes that the intensity of the transmitted light and / or the intensity of the backscattered light is ideally suited as a control parameter for the pressure applied in such measurements. This is because the pressure applied has a significant influence on the scattering capacity of the tissue. With increased pressure applied, the proportion of fluid in the tissue volume decreases considerably, and the concentration of scattering centers in this tissue volume increases, resulting in a higher scattering coefficient. For this purpose, light is shone onto the tissue, preferably in the infrared and / or visible wavelength range, for example, with a wavelength of 500 nm to 2,000 nm. Particularly preferred for this pressure control is light of a so-called isosbestic wavelength, e.g., light with a wavelength of approximately 800 to 810 nm, such as 805 to 808 nm.At this wavelength, absorption and backscattering are independent of the oxygen loading state, as the absorption curves for oxyhemoglobin and deoxyhemoglobin intersect. The absorption curves of the other major components of blood and / or tissue also exhibit absorption minima in this region. Consequently, changes in contact pressure primarily affect the scattering power of the tissue, making optical measurements in this range particularly suitable for pressure control. The change in transmission and backscattering in this wavelength range is a measure of the scattering center concentration, with the relationship being not linear but negatively logarithmic. Increased contact pressure reduces the intensity of the light in the transmission direction and increases the proportion of reflected light.Overall, measuring the intensity of the light - either in transmission or in reflection - allows the control of the pressing pressure, especially when using an isosbestic wavelength, e.g. at 805 to 808 nm.

[0014] For the respective optical measurements, an optimal position of the measuring device or sensor is determined during the calibration of the measuring system, and, for example, a suitable intensity interval is defined.

[0015] The described optical compression test is used according to the invention in conjunction with an optical measurement of the properties of living tissue, e.g., blood or the like. This can draw upon the generally known principles of non-invasive optical measurement of the properties of living tissue, e.g., blood. The compression test can be used, for example, to determine the oxygen saturation of blood. It can also be used to examine the glucose concentration of blood. For this purpose, the wavelengths described in EP 1 601 285 B1, EP 2 046 190 B1, EP 3 170 446 A1, and WO 2015 / 177156 A1 can be used. In particular, the optical measurements for determining the respective properties of the blood or tissue can be carried out using the wavelengths described in these publications.

[0016] In principle, it is possible to use light of a different wavelength for measuring the optical properties of tissue / blood than for optical pressure control. In this case, several light sources with different wavelengths can be used, or at least one light source that generates several different wavelengths of light. It may even be possible to use the same detector for both purposes, provided it has sufficient sensitivity to the different wavelengths.

[0017] However, it is also possible to perform both optical measurement and pressure control using the same wavelength of light, and consequently, the same light source and detector. For example, a wavelength in the range between 790 nm and 850 nm, such as approximately 805 nm to 808 nm, can be used to measure glucose concentration in flowing blood. At this wavelength, the absorption curves of oxyhemoglobin and deoxyhemoglobin intersect, meaning that absorption, and therefore the proportion of backscattered light, is independent of the oxygen load. In this respect, the findings described, for example, in EP 3 170 446 A1, which demonstrate that such a wavelength can be used as an indicator of glucose concentration, can be applied.Interestingly, pressure control is also possible with one and the same wavelength, since the intensity limits already mentioned are far outside the values ​​occurring in connection with optical (physiological) measurement.

[0018] The invention also relates to a measuring device for the non-invasive optical measurement of properties of living tissue inside a body according to a method of the type described. The measuring device comprises at least one light source, one detector, and one control unit, wherein the measuring device, or at least a part of the measuring device, can be pressed against the surface of the body. The control unit is configured to carry out the described method. This means that, in particular, the control unit contains at least one upper limit and / or one lower limit for a minimum permissible contact pressure and / or a maximum permissible contact pressure, or for the respective measured quantities representing the corresponding contact pressure. In this respect, corresponding scattering or transmission intensities are stored in the control unit as upper and lower limits. The control unit is now configured as follows:The measuring device is programmed so that it only allows an optical measurement of the tissue properties if the measured contact pressure, or the corresponding optical intensities representing the contact pressure, lies within the defined range. Optionally, the measuring device can have a visual and / or audible indicator, which can, for example, generate a warning signal if the measured contact pressure, or the measured quantity representing the contact pressure, falls outside the predefined, permissible interval.

[0019] The measuring device can, moreover, have not only one light source but also several light sources, e.g., several laser diodes. Coherent laser light is preferably used. However, it is also within the scope of the invention to use non-coherent light, particularly for the light source used for pressure control. For example, continuous laser radiation with a continuous power output in the range of 0.1 to 10 mW, preferably 0.5 to 2 mW, e.g., approximately 1 mW, can be used. The detector is adapted to the corresponding wavelength range. Preferably, a detector is used that is suitable for both the wavelength for optical measurement and the wavelength for pressure control, so that a single sensor may be used. This could, for example, be a silicon PIN diode.Such a diode is used particularly when the light sources produce light in a region of the small biological window (700 nm to 1300 nm). If working in the extended biological window, an InGaAs diode, for example, can be used.

[0020] The invention will now be explained in more detail with reference to a drawing that illustrates only one embodiment. The drawing shows... Fig. 1 schematically simplified a device according to the invention and Fig. 2 a simplified flowchart for operating the device according to Fig. 1.

[0021] The measuring device according to the invention serves for the non-invasive optical measurement of properties of living tissue inside a body, e.g., for determining oxygen saturation or blood glucose concentration, or for determining tissue properties (e.g., for tissue classification). The in Fig. 1. A highly simplified measuring device 2 has at least one light source 3 and at least one detector 4 or 4'. This measuring device 2, or at least a part of it, can be pressed against the surface of the indicated body 1. In this case, Fig. Figure 1 shows the possibility of a reflection measurement, i.e., the detector 4 is indicated on the same side of the body 1 as the light source 3 in the direction of reflection. In a simplified dashed representation, an arrangement of the detector 4' for a transmission measurement is optionally shown.

[0022] With the in Fig. The device shown in Figure 1 allows, for example, the contact pressure of the measuring device 2 against the body 1 to be checked before measuring the optical property (e.g., oxygen saturation or blood glucose concentration). This control of the contact pressure is carried out optically using the [device / method - context needed]. Fig. The system consists of the light source 3 shown in Figure 1, the detector 4, and a control unit (not shown). For example, light (e.g., laser light) with a wavelength of approximately 805 nm is shone into the body using the light source 3, and the backscattered light is measured using the detector 4. The intensity I r of the backscattered light (with intensity I t The intensity of the transmitted light depends on the contact pressure; that is, the measured intensity represents the contact pressure. This is because the contact pressure influences the scattering power of the tissue. A lower limit value I is set for the intensity in the control unit of the measuring device. min and an upper limit I max stored so that the control unit can determine whether the measured intensity I t or I r within or outside the permissible intensity range. This procedure is in Fig. 2 illustrated.

[0023] After starting, the light source 3 is switched on (a) and the backscattered light component I is measured using the detector 4. r (or alternatively the transmitted light component I t measured with detector 4' (b). The control unit checks whether the determined intensity value I t or I r within the stored intensity interval [I min , I max] lies (c). If this is the case, the optical measurement (d) of the desired tissue properties, e.g., the measurement of oxygen saturation or blood glucose concentration, follows. If the intensity value representing the pressure is outside the defined intensity interval, a warning signal (e) is triggered and this optical measurement is not permitted (f). The user then has the option of applying the measuring device to the body in a different position and repeating the measurement.

[0024] The in Fig. The algorithm shown in Figure 2 can, for example, be stored in the control unit.

[0025] The Fig. Figure 1 shows only the components required for the compression pressure control. Preferably, the components required in this way, and any additional components required for the optical examination of the tissue (e.g., an additional light source and, optionally, an additional detector), are integrated into a single housing, so that the compression pressure control is part of the measuring device, which is used in a generally known manner for determining the properties of the tissue / blood. In particular, such a device can contain one or more light sources for generating different wavelengths of light in order to enable the respective measurements. The components shown in Fig. The components shown in Figure 1, in particular the light source 3 and the detector 4, can also be used for both pressure control and optical-physiological measurement, if necessary.

[0026] Furthermore, the invention can also be combined with measurement methods based on tissue marking with ultrasound radiation. The necessary components for such ultrasound localization can therefore also be integrated into the measuring device 2. Reference is made to the prior art, e.g., EP 1 601 285 B1, EP 3 170 446 A1, or WO 2015 / 177156 A1. The practical application of this technology in Fig. The device shown is only schematically simplified; the required components (e.g., power supply and cables, control cables, etc.) are shown in the diagram. Fig. 1 not shown.

Claims

[1] Method for non-invasive optical measurement of properties of living tissue inside a body (1), with a measuring device (2) comprising at least a light source (3) and a detector (4, 4'), wherein the measuring device or at least a part of the measuring device is pressed against the surface, e.g. the skin, of the body (1), wherein the body (1) is illuminated by means of the light source (3) with light of at least one wavelength and wherein the light backscattered from the body (1) or the light passing through the body (1) is detected by the detector (4, 4') and the detector signal is evaluated to determine a property of the tissue, characterized by , that the contact pressure of the measuring device (2) against the body (1) is checked before, during and / or after the measurement of the optical property, wherein to determine the contact pressure light with at least one wavelength is shone into the body (1) and the intensity (I r , I t ) of the light backscattered from or passing through the body (1), the intensity depending on the contact pressure, so that the measured intensity (I r , I t ) represents the contact pressure. [2] Method according to claim 1, characterized by that a permissible intensity interval with a lower limit (I min ) and an upper limit (I max ) is defined and stored, for example, in a control unit of the measuring device (2) and it is evaluated whether the measured intensity (I) r , I t ) within or outside the permissible intensity interval (I min , I max ) lies. [3] Method according to claim 2, characterized by, that optical measurement for determining tissue properties is prevented if the measured intensity (I r , I t ) outside the intensity interval (I min , I max ) lies. [4] Method according to claim 1 or 2, characterized by that the measuring device generates an optical and / or acoustic warning signal if the measured intensity (I r , I t ) outside the intensity interval (I min , I max ) lies. [5] Method according to any one of claims 1 to 4, characterized by , that for measuring the optical properties light with at least one first wavelength and for determining the contact pressure light of the same first wavelength or light of at least one other second wavelength is used. [6] Method according to any one of claims 1 to 5, characterized by, that light, e.g. laser light, with a wavelength of 500 to 2000 nm, e.g. 700 to 1000 nm, preferably 800 to 810 nm is used for controlling or monitoring the contact pressure. [7] Measuring device for non-invasive optical measurement of properties of living tissue inside a body (1), with at least one light source (3), one detector (4, 4') and one control unit, wherein the measuring device (2) or at least a part of the measuring device is pressed against the surface of the body (1), characterized by that the control unit is configured to carry out the method according to one of claims 1 to 6. [8] Measuring device according to claim 7, characterized by that the control unit contains at least one upper limit (I max ) and / or a lower limit (I min) for a minimum permissible contact pressure and / or a maximum permissible contact pressure or for the respective contact pressure, representing measured quantities (e.g. scattering or transmission intensities) are stored. [9] Measuring device according to claim 7 or 8, characterized by , that the measuring device (2) has an optical and / or acoustic display with which a warning signal can be generated if the determined contact pressure or the measured quantity representing the determined contact pressure is outside a predefined interval (I min , I max ) lies.

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