Method for the spectroscopic determination of the oxygen saturation of blood in the presence of optical disturbance variables

The invention relates to a method for the spectrometric determination of the oxygen saturation of blood in the presence of optical disturbances, such as those that also form pigmented and light-scattering surrounding tissue and / or the blood vessel wall itself. This problem of determining oxygen saturation of blood as possible without the influence of these factors influencing the measurement accuracy occurs in particular in the case of non-invasive in vivo or in vitro examinations of blood vessels which lie in front of, behind or in said pigmented and scattering tissue, for example the examination of blood vessels in the fundus of the eye or other tissue areas of the body, such as the skin and organs accessible by endoscopy.

It is generally known that the absorption spectrum of the red blood pigment hemoglobin changes with oxygen saturation (for example van Assendelft OW, Spectrophotometry of heamoglobin derivatives, Assen: Royal Vangorcum, 1970). This makes it possible to determine the oxygen saturation of a hemoglobin sample by comparing the spectrum of the sample with the spectra of completely oxygenated and completely reduced hemoglobin.

Recent work on oximetry at the back of the eye according to the Lambert-Beers law, ie taking only absorption into account, is by Smith et al (Smith MH, Denninghoff KR, Lompado A., Hillman LW, Effect of multiple light paths in retinal vessel oximetry, Appl. Opt. 39, 2000, 1183-1193). Numerous patented arrangements and procedures are based on this principle (for example<de-docref CY="US" DNUM="4485820">US 4,485,820</de-docref>; <de-docref CY="US" DNUM="5119814">US 5,119,814</de-docref>; <de-docref CY="US" DNUM="5308919">US 5,308,919</de-docref>; <de-docref CY="US" DNUM="4253744">US 4,253,744</de-docref>; <de-docref CY="US" DNUM="4305398">US 4,305,398</de-docref>; <de-docref CY="US" DNUM="5776060">US 5,776,060</de-docref>; <de-docref CY="US" DNUM="5935076">US 5,935,076</de-docref><de-docref CY="DE" DNUM="19920157" KI="A1">DE 199 20 157 A1</de-docref>; <de-docref CY="US" DNUM="5318022">US 5,318,022</de-docref>). In the in vivo measurement, however, the hemoglobin is not isolated, but is included in the erythrocytes. The scattering of light on the erythrocytes has a significant influence on the absorbance spectrum of the blood. According to the results of Twersky's multiple scattering theory (Twersky V., Absorption and multiple scattering by biological suspensions, J. Opt. Soc. Amer. 60, 1970, 1084-1093), the influences of scattering and absorption can be separated. On this basis, Pittman and Duling have described a method that determines the oxygen saturation in whole blood from measurements carried out in transmission at the wavelength 555 nm and at the isosbestic points at 522 nm and 546 nm (Pittman RN, Duling BR. A new method for the measurement of percent oxyhemoglobin. J. Appl. Physiol. 38, 1975, 315-320). This method has been used by Delori to determine oxygen saturation in retinal vessels (Delori F. C., Noninvasive technique for oximetry of blood in retinal vessels. Appl. Opt, 27, 1988, 113-1125).

However, studies by Hammer et al (Hammer M., Leistritz S., Leistritz L., Schweitzer D., Light paths in retinal vessel oxymetry, IEEE Trans Biomed Eng 48 (5), 2001, 592-8) show that the Reflection spectra measured in retinal vessels are influenced not only by the absorption of hemoglobin and the scatter in the blood and the tissue surrounding the vessels, but also by the melanin localized in the retinal pigment epithelium and in the choroid. The same applies to vessels in the skin or other pigmented organs.

The correction of the falsification of the hemoglobin spectra by other chromophores and their correction for spectroscopic oximetry has been attempted in the previous literature by standardizing the spectra measured on a vessel to measurements next to the vessel (e.g. <de-docref CY="DE" DNUM="19920157" KI="A1">DE 199 20 157 A1</de-docref>; <de-docref CY="US" DNUM="5935076">US 5,935,076</de-docref>; Delori FC, Noninvasive technique for oximetry of blood in retinal vessels. Appl. Opt. 27, 1988, 113-1125; Schweitzer D., Hammer M., Kraft J., Thamm E., Königsdörffer E., Strobel J., In Vivo Measurement of the Oxygen Saturationm at the Normal Human Eye, IEEE Trans. Biomed. Closely. 46, 1999, 1454-1465). However, this approach leaves the extremely complicated relationships (Hammer M., Leistritz S., Leistritz L., Schweitzer D., Light paths in retinal vessel oxymetry, IEEE Trans Biomed Eng 48 (5), 2001, 592–8) of the radiation propagation in the Disregard the blood vessel and the surrounding tissue.

The exact spread of light in the biological tissue can still not be completely described physically. Even efforts to comprehend these processes for eliminating disturbance variables as comprehensively and as realistically as possible (<de-docref CY="DE" DNUM="19920157" KI="A1">DE 199 20 157 A1</de-docref>) and to model the optics of the living or dead biological tissue surrounding the blood vessels (<de-docref CY="DE" DNUM="4433827" KI="A1">DE 44 33 827 A1</de-docref>) have not led to more precise measurement results than the aforementioned methods, which are already relatively time-consuming and computationally intensive. With this effort, the procedures are only of limited suitability for routine and preventive examinations. In particular, the determination of the oxygen saturation at every point of a two-dimensional, photographic image, which is of interest for clinical practice, requires a method that is fast on the one hand, but on the other hand compensates for optical and spectrometric disturbances from the vascular environment.

The invention is therefore based on the object of nevertheless determining the oxygen saturation in a method which is as simple and fast as possible with high accuracy.

This object is achieved by a method for determining the oxygen saturation of blood with the features specified in claim 1.

It is advantageous if the spectral measured values ​​and reference data are recorded logarithmically and the auxiliary and reference functions are each formed by a straight line on which two of the measured or reference values ​​for isosbestic wavelengths lie. The correction function formed from the linear auxiliary and reference functions gives rise to a likewise linear corrected auxiliary function of the corrected measurement spectrum. The remaining spectral measurements, ie the spectral measured value for the third isosbestic wavelength and the other measured value, at a wavelength at which the reference values ​​of hemoglobin and oxyhemoglobin differ as widely as possible in the reference spectra, are applied with a constant multiplier, which is determined in this way, that the third isosbestic measurement value of the corrected measurement spectrum corrected by this stretching corresponds to the corresponding reference value of the reference spectra. In this special case, the difference between the reference values ​​for hemoglobin and oxyhemoglobin can be scaled linearly between 0 and 1. The oxygen saturation of the blood is determined in relation to this scale from the other measured value converted to the corrected auxiliary function of the corrected measurement spectrum.

For a clear two-dimensional representation of the oxygen saturation of the blood, four monochromatic single images are generated at the wavelengths and the oxygen saturation determined for each pixel.

Surprisingly, it has been shown that the proposed method can be used to determine the oxygen saturation of the blood with the same accuracy, but with significantly less effort (at least four measured values ​​required) for measurement, calculation and evaluation in comparison to the examination methods mentioned at the beginning. The method enables a two-dimensional location-dependent representation of the measurement results for clear and quick evaluation. It only requires a few measurements and only uses linear transformations. With these advantages of low effort and time-effective measurement evaluation, the proposed method is also suitable for screening and for routine or preventive examinations.

The invention will be explained below with reference to an embodiment shown in the drawing.

Show it:

<figref idref="S12">1</figref>: Diagram with spectral measurement and reference values ​​in logarithmic representation in the wavelength range between 400 nm and 700 nm, including three isosbestic wavelengths λ_i1 = 522 nm, λ_i2 = 586 nm, λ_i3 = 569 nm and the other wavelength λ_a = 555 nm

<figref idref="S12">2</figref>: Diagram with spectral reference values ​​according to <figref idref="S12">1</figref> with linear reference function F shown_R as well as with corrected measured values ​​M '

<figref idref="S13">3</figref>: Diagram with spectral reference values ​​according to <figref idref="S12">1</figref> with linear reference function F shown_R, with corrected measured values ​​M '' and with scaling for reading the oxygen saturation

The reflection or transmission of tissue in one place or with local resolution in an image is at three isosbestic wavelengths λ_i1, λ_i2 and λ_i3 (λ_i1 = 522 nm, λ_i2 = 586 nm, λ_i3 = 569 nm) as measurement data M_i1, M_i2 and M_i3 as well as at a different wavelength λ_a (555 nm), in which the absorption coefficients of oxygenated and reduced hemoglobin differ, as the measured value M_a measured and with the reflection or transmission of hemoglobin or whole blood with oxygen saturations of 0% and 100% at these wavelengths (reference data R₁, R₂, R₃, <de-math>R<chf>0%<chfbr type="none">α</chfbr></chf> and R<chf>100%<chfbr type="none">α</chfbr></chf>)</de-math> compared according to the following procedure: <ul><li>1. All measurement and reference data are logarithmic. <figref idref="S12">1</figref> shows the measurement and reference data in logarithmic representation, in this example the reflection of a retinal vein (measurement data) and the transmission of a 0.1 mm thick layer of whole blood (reference data). For the sake of clarity, the complete spectra between 400 nm and 700 nm are shown. The wavelengths λ used in this example_i1 = 522 nm, λ_i2 = 586 nm, λ_i3 = 569 nm and λ_a = 555 nm are shown.</li><li>2nd A linear auxiliary function F_H the wavelength is calculated in the measurement spectrum so that its values ​​at the isosbestic wavelengths λ_i1 and λ_i1 with the measurement data M_i1 and M_i2 agree at these wavelengths.</li><li>3rd A linear reference function F_R of the wavelength is calculated in the reference spectra so that their values ​​at the isosbestic wavelengths λ_i1 and λ_i2 with the reference data R_i1 and R_i2 agree at these wavelengths.</li><li>4th The measurement data are at each wavelength by the difference of the linear functions F_H and F_R additively corrected so that at the isosbestic wavelengths λ_i1 and λ_i2 agree with the reference data: M '_λ = M_λ + F_R - F_H. <br /><figref idref="S12">2</figref> again shows the reference data, the linear reference function F_R the wavelength and the corrected measurement data M '. In addition to the absorption of hemoglobin, this correction compensates for existing extinctions whose spectra in the wavelength range 522 nm to 586 nm can be assumed or approximated as linear on a logarithmic scale. In the exemplary embodiment considered here, these are the absorptions of the melanin and the front eye media as well as the scatter in the blood and in the surrounding tissue.</li><li>5. The corrected measurement data M 'are thus around the linear reference function F_R stretched or compressed that at the isosbestic wavelength λ_i3 with the reference value R_i3 to match: <de-figure num="1"><img file="DE10217543B4_D0001.tif" /></de-figure><figref idref="S13">3</figref> shows the spreading (possibly also compression) resulting in M ​​″ of the corrected measurement data M ′ around the linear reference function F_R, which is carried out in such a way that corrected measurement data and reference data at the isosbestic wavelength λ_i3 (569 nm) match. This correction compensates for different absolute values ​​of the measurement and reference data that arise from different lighting and measurement conditions.</li><li>6. The location of M ''_a on a linear between <de-math>R<chf>0%<chfbr type="none">α</chfbr></chf> and R<chf>100%<chfbr type="none">α</chfbr></chf></de-math> spanned scale indicates the oxygen saturation OS: <de-figure num="1"><img file="DE10217543B4_D0002.tif" /></de-figure></li></ul>

The scaled reading of the oxygen saturation (OS) between the values ​​0 and 1 is also in <figref idref="S13">3</figref> shown. The oxygen saturation OS read is 0.69 in the exemplary embodiment.

List of the reference numerals used

<ul><li><dl><dt>M</dt><dd>- measurement data</dd><dt>M '</dt><dd>- Measurement data corrected by adding the corrected auxiliary function</dd><dt>M ''</dt><dd>- Measurement data M 'corrected by applying a factor</dd><dt>F_R</dt><dd>- reference function</dd><dt>OS</dt><dd>- oxygen saturation</dd><dt>λ</dt><dd>- wavelength</dd></dl></li></ul>