Apparatus and method for measuring the blood oxygen saturation in a subject's tissue

Abstract

An apparatus and method for non-invasively determining the blood oxygen saturation within a subject's tissue by near-infrared spectroscopy is disclosed. Embodiments of the apparatus and method use the multi-distance method and take into account the attenuation of the light signal due to light absorbers other than hemoglobin and deoxyhemoglobin and the scattering properties of a subject's tissue.

Claims

1. An apparatus for non-invasively determining blood oxygen saturation within a subject's tissue, comprising: at least one light source for transmitting a light signal into the subject's tissue; at least one light detector for detecting the light signal from the at least one light source after it has passed through the subject's tissue, wherein the at least one light source and the at least one light detector are configured to measure an attenuation of the light signal at two or more light source to detector distances; and a processor connected to the light sources and the light detectors, and wherein, at least one light source and the at least one light detector are configured to measure the attenuation of the light signal at three or more distinct wavelengths in a range of 650 nm to 3 μm, and the processor includes an algorithm for: determining the attenuation of the light signal as a function of wavelength and light source to detector distance; calculating a slope of the attenuation of the light signal versus the light source to detector distance as a function of the wavelength; and calculating a blood oxygen saturation within the subject's tissue on the basis of said slope of the attenuation of the light signal and empirically determined data that account for attenuation of the light signal due to light absorbers other than hemoglobin and deoxyhemoglobin in the subject's tissue and due to light scattering in the subject's tissue; wherein the data accounting for attenuation of the light signal due to light absorbers include the wavelength-dependent extinction coefficients of one or more of meconium samples taken from new-born infants, transitional stool samples taken from new-born infants, and biliverdin.

2. The apparatus of claim 1, wherein the light source and the detectors are configured to measure the attenuation of the light signal at three or more distinct wavelengths selected from 695±5 nm, 712±5 nm, 733±5 nm, 743±5 nm, 762±5 nm, 783±5 nm, 790±5 nm, 805±5 nm, 880±5 nm, 895±5 nm, and 910±5 nm.

3. The apparatus of claim 1, wherein the minimum light source to detector distance is at least 0.8 cm.

4. The apparatus of claim 1, wherein the algorithm includes the step of calculating a relative absorption μ.sub.a,λ at a particular wavelength λ based on the following equation: ${\mu }_{a,\lambda }=\frac{1}{3{\mu }_{s,\lambda }}{\left(\ln 10\frac{\partial A}{\partial d}-\frac{1}{d}\right)}^2$ where μ.sub.s,λ is an empirically determined value that accounts for attenuation of the light signal due to light scattering in the subject's tissue at the particular wavelength λ, A.sub.λ is the attenuation at the particular wavelength λ, d is the mean light source to detector distance, and ∂A.sub.λ/∂d is the slope of the attenuation versus the light source to detector distance.

5. The apparatus of claim 4, wherein μ.sub.s,λ is
μ.sub.s,λ=(1−hλ) where h is assumed to be in the range of 10.sup.−4 to 10.sup.−3 nm.sup.−1.

6. The apparatus of claim 4, wherein the algorithm includes the step of calculating the relative concentrations of oxyhemoglobin and deoxyhemoglobin in the subject's tissue according to the following equation $\left(\begin{array}{c}{c}_{\mathrm{Hb}}\\ c_{{\mathrm{HbO}}_2}\\ c_{\mathrm{other}}\end{array}\right)={\left(\begin{array}{ccc}{\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_1}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_1}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_1}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_2}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_2}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_2}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_3}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_3}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_3}\end{array}\right)}^{-1}\left(\begin{array}{c}{\mu }_{a,{\lambda }_1}\\ {\mu }_{a,{\lambda }_2}\\ {\mu }_{a,{\lambda }_3}\end{array}\right)$ where C.sub.HbO2 and c.sub.Hb are the relative concentrations of oxyhemoglobin and deoxyhemoglobin, respectively, μ.sub.a,λn is the absorption determined at the particular wavelength λn according to the equation given above, c.sub.other is the concentration of light absorbers other than hemoglobin and deoxyhemoglobin present in the subject's tissue, and ε.sub.x,λn is the extinction coefficient for the light absorbing species x at the particular wavelength λn.

7. A method for non-invasively determining the blood oxygen saturation within a subject's tissue, comprising: transmitting a light signal from at least one light source into the subject's tissue; and detecting the light signal after it has passed through the subject's tissue at one or more detection points and at least two different light sources to detector distances; wherein the method further includes: measuring the attenuation of the light signal at three or more distinct wavelengths in the range of 650 nm to 3 μm, determining the attenuation of the light signal as a function of the wavelength and the light source to detector distance; calculating the slope of the attenuation of the light signal versus the light source to detector distance as a function of the wavelength; and calculating the blood oxygen saturation within the subject's tissue on the basis of said slope of the attenuation of the light signal and empirically determined data that account for attenuation of the light signal due to light absorbers other than hemoglobin and deoxyhemoglobin in the subject's tissue and due to light scattering in the subject's tissue; wherein the data accounting for attenuation of the light signal due to light absorbers include the wavelength-dependent extinction coefficients one or more of meconium samples taken from new-born infants, transitional stool samples taken from new-born infants, and biliverdin.

8. The method of claim 7, wherein the subject's tissue is the subject's abdomen.

9. The method of claim 7, wherein the subject is an at most a one year old infant.

10. The method of claim 7, wherein the minimum light source to detector distance is set to at least 0.8 cm.

11. The method of claim 7, wherein the step of calculating the blood oxygen saturation within the subject's tissue involves calculating the relative absorption μ.sub.a,λ at a particular wavelength λ based on the following equation: ${\mu }_{a,\lambda }=\frac{1}{3{\mu }_{s,\lambda }}{\left(\ln 10\frac{\partial A}{\partial d}-\frac{1}{d}\right)}^2$ where μ.sub.s,λ is an empirically determined value that accounts for attenuation of the light signal due to light scattering in the subject's tissue at the particular wavelength λ, A.sub.λ is the attenuation at the particular wavelength λ, d is the mean distance between light source and detectors, and ∂A.sub.λ/∂d is the slope of the attenuation versus the light source to detector distance.

12. The method of claim 11, wherein μ.sub.s,λ is
μ.sub.s,λ=(1−hλ) where h is assumed to be in the range of 10.sup.−4 to 10.sup.−3 nm.sup.−4.

13. The method of claim 11, where the step of calculating the blood oxygen saturation within the subject's tissue includes the step of calculating the relative concentrations of oxyhemoglobin and deoxyhemoglobin in the subject's tissue according to the following equation $\left(\begin{array}{c}{c}_{\mathrm{Hb}}\\ c_{{\mathrm{HbO}}_2}\\ c_{\mathrm{other}}\end{array}\right)={\left(\begin{array}{ccc}{\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_1}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_1}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_1}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_2}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_2}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_2}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_3}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_3}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_3}\end{array}\right)}^{-1}\left(\begin{array}{c}{\mu }_{a,{\lambda }_1}\\ {\mu }_{a,{\lambda }_2}\\ {\mu }_{a,{\lambda }_3}\end{array}\right)$ where C.sub.HbO2 and c.sub.Hb are the relative concentrations of oxyhemoglobin and deoxyhemoglobin, respectively, μ.sub.a,λn is the absorption determined at the particular wavelength λn according to the equation given above, c.sub.other is the concentration of light absorbers other than hemoglobin and deoxyhemoglobin present in the subject's tissue, and ε.sub.x,λn is the extinction coefficient for the light absorbing species x at the particular wavelength λn.

Description

DETAILED DESCRIPTION

(1) In one embodiment, the apparatus comprises a single light source and two or more light detectors positioned at fixed distances from the light source. Alternatively, the apparatus comprises a single light detector and two or more light sources positioned at fixed distances from the light detector. In these embodiments, the light source to detector distances do not change during the measurement.

(2) In yet another embodiment, the apparatus comprises a single light source and a single light detector, wherein the light source and/or the light detector are movable in order to vary the light source to detector distance during the measurement. This embodiment has the advantage that the attenuation of the light signal as a function of the light source to detector distance can be sampled over a wide range and a large number of data points.

(3) The light sources and the light detectors are configured to measure of the attenuation of the light signal at three or more distinct wavelengths in the range of 650 nm to 3 μm, preferably in the range of 650 nm to 1 μm, more preferably in the range of 680 nm to 950 nm. For example, each light source may be a collection of individual light sources each emitting light at a narrow spectral bandwidth. In this case, the detectors may be broadband detectors that can detect light at least at these spectral ranges. Alternatively, the light sources may be broadband light sources and a diffraction grating or specific emission filters may be used to detect the light in a wavelength-specific manner.

(4) In order to increase the accuracy of the measurement, attenuation is preferably measured at four or more distinct wavelengths, more preferably at five or more, most preferably at seven or more. In a particularly preferred embodiment the light detectors are configured to measure of the attenuation of the light signal at seven distinct wavelengths in the range of 650 nm to 1 μm.

(5) In the case of performing the measurement on a subject's abdomen, in particular the abdomen of a new-born infant, it has been found that measuring in the range of 815 to 875 nm does not increase the accuracy of the measurement. Therefore, the light detectors are configured to measure of the attenuation of the light signal at seven distinct wavelengths in the range of 650 nm to 1 μm, excluding the range of 815 to 875 nm.

(6) In the case of performing the measurement on a subject's abdomen, several combinations of wavelengths have been found that offer an increased measurement accuracy. These wavelengths can be selected to better distinguish between Hb, HbO.sub.2, and other absorbers present in a subject's abdomen, such as stool. These optimized combinations of wavelengths are set out in the following.

(7) In one embodiment, the light detectors are configured to measure of the attenuation of the at three or more distinct wavelengths selected from 695±5 nm, 712±5 nm, 733±5 nm, 743±5 nm, 762±5 nm, 783±5 nm, 790±5 nm, 805±5 nm, 880±5 nm, 895±5 nm, and 910±5 nm. Preferably, the wavelengths are selected from 712±5 nm, 733±5 nm, 762±5 nm, 783±5 nm, 805±5 nm, 880±5 nm, 895±5 nm, and 910±5 nm.

(8) In one embodiment, the light detectors are configured to measure of the attenuation of the light signal at 712±5 nm, 736±5 nm, 762±5 nm, 784±5 nm, and 910±5 nm.

(9) In one embodiment, the light detectors are configured to measure of the attenuation of the light signal at 712±5 nm, 736±5 nm, 762±5 nm, 784±5 nm, 895±5 nm, and 910±5 nm.

(10) In order to measure the attenuation at a given number of distinct wavelengths, it is sufficient that the light sources and the light detectors are configured to measure the attenuation at distinct wavelength ranges, which at least include the specified wavelength. The spectral bandwidth of each wavelength range may vary, as long as the wavelength ranges can be clearly distinguished. Preferably, the attenuation is measured at distinct wavelength ranges having a bandwidth of ±25 nm or less, more preferably ±15 nm or less, most preferably ±5 nm or less.

(11) In a preferred embodiment, the apparatus is configured to measure the attenuation at more than two light source to detector distances in order to improve the accuracy of the calculated slope of the attenuation of the light signal versus the light source to detector distance as a function of the wavelength. In a preferred embodiment, the apparatus is configured to measure the attenuation at three light source to detector distances.

(12) The minimum and maximum light source to detector distances can be optimized based on the sensitivity of the detectors and the optical properties of the subject's tissue. In the case of an apparatus for measuring the blood oxygen saturation in the abdomen of a new-born infant, the minimum light source to detector distance is preferably at least 0.8 cm, more preferably at least 0.9 cm, and most preferably at least 1.0 cm. Preferably, the shortest distance between the light source and the detectors is in the range of 0.8 to 2 cm, more preferably at least 0.9 to 1.5 cm, and most preferably 0.95 to 1.2 cm. The longest light source to detector distance is preferably in the range of 2 to 10 cm, preferably 3 to 8 cm, most preferably 4 to 6 cm.

(13) The algorithm calculates the blood oxygen saturation within the subject's tissue on the basis of the slope of the attenuation of the light signal versus the light source to detector distance as a function of the wavelength. Thus, the algorithm calculates the blood oxygen saturation level using the multi-distance method.

(14) In a preferred embodiment, the algorithm included in the processor calculates the relative absorption μ.sub.a,λ at a particular wavelength λ based on the following equation:

(15) ${\mu }_{a,\lambda }=\frac{1}{3{\mu }_{s,\lambda }}{\left(\ln 10\frac{\partial A}{\partial d}-\frac{1}{d}\right)}^2$

(16) where μ.sub.s,λ is an empirically determined value that accounts for attenuation of the light signal due to light scattering in the subject's tissue at the particular wavelength λ, A.sub.λ is the attenuation at the particular wavelength λ, d is the mean light source to detector distance, and ∂A.sub.λ/∂d is the slope of the attenuation versus the light source to detector distance.

(17) It should be noted that the above formula calculates the relative absorption μ.sub.a,λ, which is equal to the absolute absorption multiplied with a factor k. This factor can be determined using calibration measurements. Using the relative absorption, is sufficient to calculate the relative concentrations of chromophores. Since the blood oxygen saturation as defined above is the ratio of the HbO.sub.2 concentration to the total hemoglobin concentration, it is not necessary to determine the absolute concentration of HbO.sub.2 and Hb. therefore, it is not necessary to determine the factor k, and k has been omitted from the above formula for μ.sub.a,λ.

(18) The absorption μ.sub.a,λ can then be used to calculate the concentrations of HbO.sub.2, Hb and other light absorbers using the Lambert-Beer law.

(19) The reduced scattering μ.sub.s,λ is an empirically determined value that accounts for attenuation of the light signal due to light scattering in the subject's tissue. To calculate the relative absorption μ.sub.a,λ according to above-mentioned formula, it is sufficient to know the relative reduced scattering μ.sub.s,λ, which is defined as
μ.sub.s,λ=(1−hλ)

(20) where h is a scattering parameter of a particular tissue. The scattering parameter h can be determined from measuring the scattering properties of reference tissue. For example, h is determined by measuring the scattering properties of the abdomen of a number of new-born infants. In a preferred embodiment, the parameter h is assumed to be in the range of 10-4 to 10-3 nm-1, preferably 2.Math.10-4 to 8.Math.10-4 nm-1, more preferably 5.Math.10-4 to 8.Math.10-4 nm-1. In a particularly preferred embodiment, h is assumed to be 6.4.Math.10-4 nm-1. It has been found that these values accurately account for scattering in the abdomen of a new-born infant.

(21) The absolute reduced scattering can be determined by multiplying μ.sub.s,λ as defined above with a factor k. For the present invention, however, it is not necessary to determine k.

(22) The parameters h and k can be experimentally determined by frequency domain absorption measurements as described, for example, in Sergio Fantini, Maria Angela Franceschini, Joshua B. Fishkin, Beniamino Barbieri, and Enrico Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204-5213 (1994).

(23) In one embodiment, the algorithm calculates the blood oxygen saturation by calculating the relative concentrations of HbO.sub.2 and Hb according to the following equation:

(24) $\left(\begin{array}{c}{c}_{\mathrm{Hb}}\\ c_{{\mathrm{HbO}}_2}\\ c_{\mathrm{other}}\end{array}\right)={\left(\begin{array}{ccc}{\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_1}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_1}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_1}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_2}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_2}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_2}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_3}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_3}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_3}\end{array}\right)}^{-1}\left(\begin{array}{c}{\mu }_{a,{\lambda }_1}\\ {\mu }_{a,{\lambda }_2}\\ {\mu }_{a,{\lambda }_3}\end{array}\right)$

(25) where c.sub.HbO2 and c.sub.Hb are the relative concentrations of oxyhemoglobin and deoxyhemoglobin, respectively, μ.sub.a,λn is the absorption determined at the particular wavelength λn according to the equation given above, c.sub.other is the concentration of light absorbers other than hemoglobin and deoxyhemoglobin present in the subject's tissue, and ε.sub.x,λn is the extinction coefficient for the light absorbing species x at the particular wavelength λn.

(26) The relative concentrations calculated according to this formula are equal to the absolute concentrations multiplied by a factor k. However, to calculate the blood oxygen saturation StO.sub.2 it is sufficient to use the relative concentrations and the following equation:

(27) ${\mathrm{StO}}_2=\frac{c_{{\mathrm{HbO}}_2}}{c_{{\mathrm{HbO}}_2}+c_{\mathrm{Hb}}}$

(28) The values for ε.sub.x,λn represent data accounting for attenuation of the light signal due to light absorbers. These data can be determined empirically by measuring the absorption spectra of the respective light absorbers in isolation.

(29) In order to improve the accuracy when measuring the blood oxygen saturation of new-born infants, it is necessary to account for absorption due to meconium and transitional stool.

(30) In one particular embodiment, ε.sub.other,λn is determined by measuring the absorption spectra of isolated samples of stool, transitional stool, meconium, and/or biliverdin. In a preferred example, ε.sub.other,λn is determined by measuring the absorption spectra of isolated samples of meconium.

(31) Meconium is the earliest stool of a mammalian infant. Meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. It has been found that averaged absorption spectra of meconium samples taken from number of different subjects can be used as a source of extinction data for the above calculation. In one embodiment, the data accounting for attenuation of the light signal due to light absorbers therefore include the wavelength-dependent extinction coefficients of meconium samples taken from new-born infants.

(32) Transitional stool is produced by a new-born infant during its first days of life. Transitional stool differs from meconium in its composition and comprises high amounts of biliverdin. Therefore, the data accounting for attenuation of the light signal due to light absorbers preferably include the wavelength-dependent extinction coefficients of transitional stool samples taken from new-born infants, preferably during the first two weeks after birth, more preferably during the first week after birth, most preferably during the first five days after birth.

(33) In another preferred embodiment, the data accounting for attenuation of the light signal due to light absorbers therefore include the wavelength-dependent extinction coefficients of biliverdin.

(34) In another aspect, the present invention also provides a method for non-invasively determining the blood oxygen saturation within a subject's tissue, comprising the steps of transmitting a light signal from at least one light source into the subject's tissue; and detecting the light signal after it has passed through the subject's tissue at one or more detection points and at least two different light source to detector distances; characterized in that the method further comprises the steps of measuring the attenuation of the light signal at three or more distinct wavelengths in the range of 650 nm to 3 μm, determining the attenuation of the light signal as a function of the wavelength and the light source to detector distance;

(35) calculating the slope of the attenuation of the light signal versus the light source to detector distance as a function of the wavelength; and

(36) calculating the blood oxygen saturation within the subject's tissue on the basis of said slope of the attenuation of the light signal and empirically determined data that account for attenuation of the light signal due to light absorbers other than hemoglobin and deoxyhemoglobin in the subject's tissue and due to light scattering in the subject's tissue.

(37) This method is particularly suited to determine blood oxygen saturation in the abdomen of new-born infants, as it allows to account for the presence of light absorbing species, such as meconium and transitional stool, and can provide accurate measurements of the blood oxygen saturation. In a preferred embodiment, the method is therefore carried out on the subject's abdomen. The subject preferably is an infant. Preferably, the infant is at most one year old, more preferably at most six months old, most preferably at most three months old. The method is particularly useful for non-invasively measuring the blood oxygen saturation of preterm infants.

(38) The light source to detector distance is preferably set as discussed above for the apparatus of the invention.

(39) Preferably, the attenuation of the light signal is measured at three or more distinct wavelengths selected from 695±5 nm, 712±5 nm, 733±5 nm, 743±5 nm, 762±5 nm, 783±5 nm, 790±5 nm, 805±5 nm, 880±5 nm, 895±5 nm, and 910±5 nm. Preferably, the wavelengths are selected from 712±5 nm, 733±5 nm, 762±5 nm, 783±5 nm, 805±5 nm, 880±5 nm, 895±5 nm, and 910±5 nm.

(40) In one embodiment, the attenuation of the light signal is measured at 712±5 nm, 736±5 nm, 762±5 nm, 784±5 nm, and 910±5 nm.

(41) In one embodiment, the attenuation of the light signal is measured at 712±5 nm, 736±5 nm, 762±5 nm, 784±5 nm, 895±5 nm, and 910±5 nm.

(42) The step of calculating the blood oxygen saturation preferably involves the same steps as discussed above for the algorithm of the inventive apparatus.

(43) Preferably, the step of calculating the blood oxygen saturation within the subject's tissue involves calculating the relative absorption λ.sub.a,λ at a particular wavelength λ based on the following equation:

(44) ${\mu }_{a,\lambda }=\frac{1}{3{\mu }_{s,\lambda }}{\left(\ln 10\frac{\partial A}{\partial d}-\frac{1}{d}\right)}^2$

(45) where μ.sub.s,λ is an empirically determined value that accounts for attenuation of the light signal due to light scattering in the subject's tissue at the particular wavelength λ, A.sub.λ is the attenuation at the particular wavelength λ, d is the mean distance between light source and detectors, and ∂A.sub.λ/∂d is the slope of the attenuation versus the light source to detector distance.

(46) Preferably, μ.sub.s,λ is
μ.sub.s,λ=(1−hλ)

(47) where h is assumed to be in the range of 10-4 to 10-3 nm-1.

(48) Preferably, the step of calculating the blood oxygen saturation includes the step of calculating the relative concentrations of oxyhemoglobin and deoxyhemoglobin in the subject's tissue according to the following equation

(49) $\left(\begin{array}{c}{c}_{\mathrm{Hb}}\\ c_{{\mathrm{HbO}}_2}\\ c_{\mathrm{other}}\end{array}\right)={\left(\begin{array}{ccc}{\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_1}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_1}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_1}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_2}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_2}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_2}\\ {\mathrm{.Math.}}_{\mathrm{Hb},{\lambda }_3}& {\mathrm{.Math.}}_{{\mathrm{HbO}}_2,{\lambda }_3}& {\mathrm{.Math.}}_{\mathrm{other},{\lambda }_3}\end{array}\right)}^{-1}\left(\begin{array}{c}{\mu }_{a,{\lambda }_1}\\ {\mu }_{a,{\lambda }_2}\\ {\mu }_{a,{\lambda }_3}\end{array}\right)$

(50) where C.sub.HbO2 and c.sub.Hb are the relative concentrations of oxyhemoglobin and deoxyhemoglobin, respectively, μ.sub.a,λn is the absorption determined at the particular wavelength λn according to the equation given above, c.sub.other is the concentration of light absorbers other than hemoglobin and deoxyhemoglobin present in the subject's tissue, and ε.sub.x,λn is the extinction coefficient for the light absorbing species x at the particular wavelength λn.

(51) Preferably, the blood oxygen saturation St0.sub.2 is calculated from the relative concentrations of HbO.sub.2 and Hb according to the following equation:

(52) ${\mathrm{StO}}_2=\frac{c_{{\mathrm{HbO}}_2}}{c_{{\mathrm{HbO}}_2}+c_{\mathrm{Hb}}}$

(53) Preferably, the data accounting for attenuation of the light signal due to light absorbers include the data accounting for attenuation of the light signal due to light absorbers include the wavelength-dependent extinction coefficients one or more of meconium samples taken from new-born infants, transitional stool samples taken from new-born infants, and biliverdin.