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 back of the eye or other tissue areas of the body, such as the skin and endoscopically accessible organs.

It is generally known that the absorption spectrum of the red blood pigment hemoglobin changes with oxygen saturation (for example from 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 patent-protected arrangements and methods are based on this principle (for example US 4,485,820; US 5,119,814; US 5,308,919; US 4,253,744; US 4,305,398; US 5,776,060; US 5,935,076 DE 199 20 157 A1; US ​​5,318,022).

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 199 20 157 A1; US ​​5,935,076; 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 model these processes for eliminating disturbance variables as comprehensively and as realistically as possible (DE 199 20 157 A1) and to model the optics of the living or dead biological tissue surrounding the blood vessels (DE 44 33 827 A1) do not have more precise measurement results than the aforementioned methods managed, 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.

To solve this task, transmission or Reflection measurement in a measurement spectrum spectral measurement values ​​at wavelengths isosbestic for hemoglobin and oxyhemoglobin and at least one other measurement value at a wavelength at which the reference values ​​of hemoglobin and oxyhemoglobin differ, generated and compared with known reference values ​​of the reference spectra of hemoglobin and oxyhemoglobin, by a) in the measurement spectrum at least two said spectral measurement values ​​(M_i1, M_i2), at isosbestic wavelengths for hemoglobin and oxyhemoglobin (λ_i1, λ_i2) and at least the other measured value (M_a) at a wavelength (λ_a), in which the reference values ​​of hemoglobin and oxyhemoglobin differ as far as possible in the reference spectra, are recorded, with at least two of the measured values ​​(M_i1 M_i2) for isosbestic wavelengths (λ_i1, λ_i2) an auxiliary function (F_H) is generated, b) in the reference spectra from those with the same isosbestic wavelengths (λ_i1, λ_i2) of the hemoglobin and oxyhemoglobin of the at least two measured values ​​determined in the measurement spectrum (M_i1, M_i2) corresponding reference values ​​(R_i1, R_i2) a reference function (F_R) of the same type is generated, c) from the auxiliary function (F_H) of the measurement spectrum on which the said at least two measurement values ​​(M_i1, M_i2) for isosbestic wavelengths (λ_i1, λ_i2) and from the reference function (F_R) of the reference spectra on which the at least two measured values ​​(M_i1, M_i2) corresponding at least two reference values ​​(R_i1, R_i2) are a correction function (F_K) with which a corrected auxiliary function (F_Hk) which is generated with the reference function (F_R) is identical in the reference spectra and d) the oxygen saturation of the blood from the corrected auxiliary function (F_Hk) of the corrected measurement spectrum converted other measured value (M_a") in relation to the reference values ​​for hemoglobin and oxihemoglobin at this wavelength (λ_a) is determined.

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:

Fig. 1 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

FIG. 2 diagram with spectral reference values ​​according to FIG. 1 with the linear reference function F shown_R as well as with corrected measured values ​​M '

FIG. 3 diagram with spectral reference values ​​according to FIG. 1 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, R 0% | a and R 100% | a) compared according to the following procedure: 1. All measurement and reference data are logarithmic. 1 shows the measurement and reference data in a 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. 2. 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_i2 with the measurement data M_i1 and M_i2 agree at these wavelengths. 3. 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. 4. 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. 2 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. 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 3 shows the spreading (possibly also compression) of the corrected measurement data M 'resulting from the linear reference function F which results in M ​​"_R, which is carried out in such a way that corrected measurement data and reference data at the isosbestic wavelength λ_ι3 (569 nm) match. This correction compensates for different absolute values ​​of the measurement and reference data that arise from different lighting and measurement conditions. 6. The location of M "_a The oxygen saturation OS indicates on a scale spanned linearly between R 0% | a and R 100% | a:

The scaled reading of the oxygen saturation (OS) between the values ​​0 and 1 is also shown in FIG. 3. The oxygen saturation OS read is 0.69 in the exemplary embodiment.<heading>List of the reference numerals used</heading> M measurement data M 'by addition of the corrected auxiliary function corrected measurement data M "by applying a factor corrected measurement data M' F_R Reference function OS oxygen saturation λ wavelength