DE102016014071A1 - Method for transcutaneous detection of bilirubin - Google Patents

Abstract

A method for detecting the bilirubin content in the blood, in which light is irradiated to a vital tissue section in an exposure step, and at least a part of emerging from this tissue section light is detected, and these records of intensity and wavelength are evaluated by a data evaluation procedure In the evaluation procedure, the determination of the concentration of bilirubin by a system of equations (GL2) is carried out with absorption values at at least two wavelengths of the isosbestic points of hemoglobin.

Description

Field of the invention

The invention relates to a method for the transcutaneous detection of bilirubin within a vital tissue region, in which light is irradiated into that tissue region and light which reemerges out of this tissue region is analyzed.

Background of the invention

Bilirubin is a breakdown product of the blood, which is normally broken down by the body and excreted. If the liver does not work properly or if more hemoglobin is broken down, it causes jaundice. Since bilirubin is initially lipophilic (fat-soluble), part of the bilirubin deposits in the fatty layer of the skin. The skin therefore turns yellow. An elevated bilirubin concentration (hyperbilirubinemia) can be detrimental to the body. Thus, the hyperbilirubinemia must be treated beyond certain limits.

The bilirubin concentration is usually determined by a blood sample. This has the disadvantage of blood loss, risk of infection and pain, as well as the z.T. very long wait (24 hours and more) on the result. In order to be able to make a fast therapy decision, a real-time measurement is necessary. In addition, a non-invasive measurement is needed to avoid the risk of infection and blood loss. Devices are known which measure the bilirubin content of the skin transcutaneously, by reflection spectroscopy or in transmission. The bilirubin content in the blood may differ significantly.

Object of the invention

The invention has for its object to provide solutions by which it is possible to provide meaningful readings to the content of bilirubin in the blood.

Inventive solution

The object mentioned above is achieved according to the invention by a method for detecting the bilirubin content in the blood, in which light is irradiated onto a vital tissue section as part of an exposure step, and at least a part of the light emerging from this tissue section is detected, and records of intensity and recordings thereon Wavelength can be evaluated by an evaluation procedure, wherein in the evaluation procedure, the determination of the concentration of bilirubin by a system of equations, which is determined by absorption values (optical density) at the wavelengths of isosbestischen points of hemoglobin.

This advantageously makes it possible to precisely determine the bilirubin concentration by determining the absorption of the light by the skin tissue as well as the Hb concentration, whereby the Hb concentration can be determined under reduced influence of the degree of oxygenation.

The inventive concept makes it possible to determine the bilirubin concentration transcutaneously and non-invasively in the blood. This makes it possible to measure very high concentrations, regardless of skin thickness and during bilirubin therapy. The method of reflection spectroscopy is preferably used. The new measuring concept makes it possible to measure during and after phototherapy. This allows real-time therapy control as well as therapy control.

The equation system is preferably determined at the absorption values at wavelengths of 452 nm and 500 nm or at least in the narrow surrounding region of these wavelengths.

According to a particular aspect of the present invention, the system of equations is set using measurements of the wavelengths 529, 545, 570 and / or 584 nm. At these wavelengths, there is a particularly low influence of the Hb oxygenation level on the evaluation result. Preferably, measurements are made as accurately as possible at the indicated wavelengths, but it is also possible to choose the wavelength range slightly wider, e.g. +/- 0.7% i. the absorption value for the wavelength of 529 nm in a range of e.g. 526 to 533 nm of the evaluation.

In a particularly advantageous manner, in the context of the exposure step, light having defined wavelengths can be successively irradiated into the tissue region. This light can be generated here with light sources that are designed specifically for the delivery of light of this wavelength.

The detection of the turbidity influence of the ambient system of bilirubin is preferably carried out using light having the wavelengths 452, 500, 529, 545, 570, 584 nm which is irradiated into the tissue region.

When irradiating light with selected wavelengths, the optical density for this particular wavelength can then be determined in a simple manner by means of an intensity measurement.

According to a further aspect of the present invention, the light is irradiated into the tissue region at a plurality of spaced-apart irradiation sites. This makes it possible to draw conclusions about the presence of bilirubin in different tissue depths. Alternatively, or in combination with the aforementioned approach, it is also possible to tap the light at a plurality of spaced-apart detection points from the tissue area.

list of figures

• 1 eine Grafik zur Erläuterung der Bedeutung der ausgewählten Wellenlängen;
• 2 eine Grafik zur Veranschaulichung des Lichtweges im Gewebe.

Further details and features of the invention will become apparent from the following description taken in conjunction with the drawings. It shows:

• 1 a graph explaining the meaning of the selected wavelengths;
• 2 a graphic illustrating the light path in the tissue.

Detailed description of the figures

The representation after 1 shows the course of the extinction coefficient of the skin, bilirubin, and hemoglobin in different oxygenation states. The evaluation algorithm according to the invention is derived from the method described by Delpy et al. developed modified Lambert-Beer law.

wobei: A = Absorption; ε = Extinktionskoeffizient; c = Konzentration ; d = Quelle-Detektor-Abstand; DPF = Differential Pathlength Factor; G = Photonenverlust durch StreuungModified Lambert-Beer law: $$A\left(\lambda \right)=e\cdot c\cdot d\cdot DPF+G$$

where: A = absorption; ε = extinction coefficient; c = concentration; d = source-detector distance; DPF = Differential Pathlength Factor; G = photon loss due to scattering

The spectrum measured on the individual includes i.a. Information about tissues, hemoglobin and bilirubin. The present invention involves the separate calculation of blood, skin and bilirubin for the determination of bilirubin in the blood. For this purpose, the concentrations of the individual components are calculated.

In the reflection spectroscopic measurement of the skin in the VIS (visible wavelength range), a combination of skin, bilirubin, deoxygenated and oxygenated hemoglobin is measured. If all 4 concentrations are to be determined, this is possible via a system of equations with at least four equations. This has an increased potential for error in physiological data. The invention is based on the fact that with the selected wavelengths, the absorption values at the so-called isosbestic points of the deoxygenated and oxygenated hemoglobin are detected, i. the absorbance values at those wavelengths at which hemoglobin has identical values in each oxygenation state. When the concentrations at these points are determined, deoxygenated and oxygenated hemoglobin can be considered as a value, reducing the GLS to 3 equations, significantly reducing the error potential.

How out 1 Bilirubin at 584nm has no influence anymore. At 529nm only 0.3% of the maximum value at 452nm. If the concentration is initially limited to hemoglobin and skin, they can be determined by the isosbestic points at 529nm, 545nm, 570nm and 584nm with 2 equations.

The differential path factor DPF known from the literature amounts to a measuring arrangement used in the present case 3 , Depending on the measuring arrangement, this is in the range from 2 to 8. Now the value G of photon loss by scattering. Since the photon loss due to scattering, depending on the irradiated tissue, thus varies between the measurements and can not be determined, the concentrations for skin and hemoglobin are determined from the difference between two absorption values at two wavelengths, thus G. $$\frac{A\left({\lambda }_1\right)-A\left({\lambda }_2\right)}{d\cdot DPF}=\frac{e_1\left({\lambda }_1\right)-e_1\left({\lambda }_2\right)}{{\mathrm{<figure-callout\; id="1"\; label="m"\; filenames="DE102016014071A1\_0004.png,DE102016014071A1\_0005.png"\; state="\{\{state\}\}">m</figure-callout>}}_1}\cdot {\mathrm{<figure-callout\; id="1"\; label="c"\; filenames="DE102016014071A1\_0004.png,DE102016014071A1\_0005.png"\; state="\{\{state\}\}">c</figure-callout>}}_1+\frac{e_2\left({\lambda }_1\right)-e_2\left({\lambda }_2\right)}{{\mathrm{<figure-callout\; id="2"\; label="m"\; filenames="DE102016014071A1\_0005.png"\; state="\{\{state\}\}">m</figure-callout>}}_2}\cdot {\mathrm{<figure-callout\; id="2"\; label="c"\; filenames="DE102016014071A1\_0005.png"\; state="\{\{state\}\}">c</figure-callout>}}_2$$

Equation system GL1; where: d = source-detector distance; DPF = differential pathlength factor; m = molecular weight; ε = extinction coefficient; c = concentration

By determining the difference at two ranges 529nm - 545nm and 570nm - 584nm, the equation system can be solved with two unknowns. This results in the concentration cHb for hemoglobin and chaut for the skin content.

For the determination of bilirubin concentration, cHb and chaut in the following equation for the wavelengths 452 and 500nm used. $$c_{bil}=\left(\frac{A\left({\lambda }_1\right)-A\left({\lambda }_2\right)}{d\cdot DPF}+\frac{e_H\left({\lambda }_1\right)-e_H\left({\lambda }_2\right)}{m_H}\cdot c_H+\frac{e_{Hb}\left({\lambda }_1\right)-e_{Hb}\left({\lambda }_2\right)}{m_{Hb}}\cdot c_{Hb}\right)\cdot \frac{m_{bil}}{e_{bil}\left({\lambda }_1\right)-e_{bil}\left({\lambda }_2\right)}$$

Equation system GL2; where: A = absorption; d = source-detector distance; DPF = differential pathlength factor; m = molecular weight; ε = extinction coefficient; c = concentration From this the bilirubin concentration c _{Bil is} calculated.

The representation after 2 shows a preferred measuring arrangement for determining the bilirubin concentration in the blood. To a vital tissue area 1 a patient 2 becomes a measuring head 3 stated. This measuring head comprises a first light coupling conductor 4 , a second light launching conductor 5 and a sensor conductor 6 , The two light coupling conductors 4 . 5 are arranged such that their exit points in patient proximity different distances from the tapping point of the sensor conductor 6 Have on the patient, so that for the out of the respective light guide 4 . 5 emergent and passing through the tissue light of different lengths, as well as different tissue depths passing light paths a, b result. The longer light path a traverses an area with pronounced blood vessels 2a , the shorter path of light traverses primarily the epidermis and adipose tissue 2 B ,

The coupling of the light into the user takes place here by way of example by connecting a splitter 6 , with a semitransparent mirror 6a and also selectively switchable diaphragms 6b . 6c ,

The provision of the light via a light source 7 which is designed here so that it emits light in required wavelengths. The control of the light source 7 takes place in accordance with a control device LC.

That from the tissue area 1 over the sensor light guide 6 tapped light we subjected to an intensity measurement. This is a bolometer 8th intended. The measured values of the bolometer 8th are made available to a computer system C. The computer system C is configured with a program provided for processing the inventive concept, and in this case it stores the intensity values measured at the respective wavelengths in a table, so that pairs of values are internally present in this regard. After detecting the intensity values for specific wavelengths, first the first equation system GL1 is evaluated by means of which the concentrations for skin and hemoglobin are determined. With these results, the second equation system GL2 is completed and then evaluated with the further value pairs to the other wavelengths. This approach results in the concentration of bilirubin.

The evaluation of the intensity values may comprise comprehensive further evaluation procedures in which e.g. Based on the differences in the absorptions in the light paths a, b certain other parameters are determined. Furthermore, the measurement values of the absorptions can be calculated with different intensities. The intensities of the light provided for the light paths a, b, light can also be varied, so that there are numerous other optical phenomena that can be considered in models and the evaluation algorithm and increase the validity of the overall measurement.

The for controlling the light source 7 provided control device LC is implemented in the electronic control device C. The light source 7 and the bolometer 8th or just another means for detecting the intensity of the sensor conductor 6 returned light are preferably external hardware components which can be coupled via standardized interfaces to the electronic control device C. The splitter S, the measuring head 3 and possibly also the light source 7 and the bolometer 8th can be integrated in total in the measuring head. Preferably, however, the splitter S and the light source 7 , as well as the bolometer 8th combined into a single unit and a multicore light guide 9 potential-free with the measuring head 6 connected.

The concentration value of the bilirubin determined via the electronic control device C can be based on a medical evaluation. The temporal development of this value can be recorded and documented in the context of a therapy. Furthermore, the concentration value determined as a real-time value can be used as a control variable for therapeutic or medical systems S. Thus, in particular based on the determined in real time Bilirubinwertes a therapy time and, if necessary. In the course of a phototherapy, the exposure intensity can be tuned, the exposure zones can be selected and operated in a coordinated manner, the intensity distribution can be selected according to wavelength, the distance between the patient and the illumination can be tuned, a medication or filtering can be tuned, a different peripheral system can be tuned ( eg humidity, temperature). Furthermore, drug correlations can be recorded and documented and current values and course can be displayed.

The inventive method is based on a spatially resolved spectroscopy and in this case includes the sequential use of multiple excitation light sources or excitation light wavelengths. By different distances of the excitation from the exit of the light from the skin each result in different lengths of light paths a, b. By modeling it is possible to get information from different depths of the tissue 2a . 2 B to distinguish from each other. This information makes it possible to distinguish between lipid-bound bilirubin and bilirubin present in the blood during skin measurement. This distinction is of particular advantage in order to measure during a therapy aimed at reducing bilirubin content in the blood. That's how it changes in the skin 2 B dissolved bilirubin during therapy only slowly, the bilirubin in the blood 2a but very fast. By using the spatially resolved spectroscopy according to the invention together with a modeling of the skin, portions of adipose tissue 2 B and the blood vessels 2a be differentiated from each other.

Claims (12)

A method for detecting the bilirubin content in the blood, in which light is irradiated to a vital tissue section in an exposure step, and at least a part of emerging from this tissue section light is detected, and these records of intensity and wavelength are evaluated by a data evaluation procedure In the evaluation procedure, the determination of the concentration of bilirubin by a system of equations (GL2) is carried out with absorption values at at least two wavelengths of the isosbestic points of hemoglobin. Method according to Claim 1 , characterized in that the system of equations with absorption values at wavelengths of 452nm and 500nm is determined. Method according to Claim 1 or 2 , characterized in that the system of equations is set using measurements of the wavelengths 529, 545, 570 and / or 584 nm. Method according to at least one of Claims 1 to 3 , characterized in that in the context of the exposure step, light with defined wavelengths is successively irradiated into the tissue region. Method according to at least one of Claims 1 to 4 Characterized in that light with the wavelengths 452, 500, 529, 545, 570 is irradiated into the tissue area. Method according to at least one of Claims 1 to 5 , characterized in that the intensity of the remission light of the wavelength-specific irradiated light is detected. Method according to at least one of Claims 1 to 6 , characterized in that the light is irradiated at a plurality of spaced-apart Einstrahlstellen in the tissue region. Method according to at least one of Claims 1 to 7 , characterized in that the light is tapped at a plurality of spaced apart detection points from the tissue area. Method according to at least one of Claims 1 to 8th , characterized in that a separate calculation of blood and bilirubin for the determination of bilirubin in the blood takes place and for this purpose the concentrations of the individual components is calculated. Method according to at least one of Claims 1 to 9 Characterized in that the concentrations for skin and hemoglobin from the difference between two absorbance values at two isosbestic wavelengths of hemoglobin are determined, at least one wavelength here is larger than 500nm. A method for detecting the bilirubin content in the blood, in which light is irradiated to a vital tissue section in an exposure step, and at least a part of emerging from this tissue section light is detected, and these records of intensity and wavelength are evaluated by a data evaluation procedure In the evaluation procedure, the determination of the concentration of bilirubin by a system of equations (GL2) is based on the concentration of Hb and skin tissue, these two absorption values being determined for at least two wavelengths of the isosbestic points of hemoglobin. Method according to Claim 11 Characterized in that the system of equations mentioned (GL2) underlying concentrations of Hb and skin tissue by the system of equations (GL1) are determined to be used at isobestic wavelengths of Hb wherein for the determination of the equation system (GL1) Hb absorptions.

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