U.S. patent application number 12/002678 was filed with the patent office on 2008-08-14 for method for the spectroscopic determination of the oxygen saturation of blood in the presence of optical disturbance varibles.
Invention is credited to Martin Hammer, Dietrich Schweitzer, Eike Thamm.
Application Number | 20080194931 12/002678 |
Document ID | / |
Family ID | 28798595 |
Filed Date | 2008-08-14 |
United States Patent
Application |
20080194931 |
Kind Code |
A1 |
Schweitzer; Dietrich ; et
al. |
August 14, 2008 |
Method for the spectroscopic determination of the oxygen saturation
of blood in the presence of optical disturbance varibles
Abstract
The invention is directed to a method for the spectrometric
determination of the oxygen saturation of blood in the presence of
optical disturbance variables in which transmission measurements
and reflection measurements are carried out in at least two
wavelengths that are isosbestic for hemoglobin and oxyhemoglobin,
and at least one other wavelength at which the extinction of
hemoglobin and oxyhemoglobin differ. Corresponding auxiliary
functions are defined in the measurement spectrum (M) and in the
reference spectra of hemoglobin and oxyhemoglobin, at least two of
the measurement values or two of the reference values for the
isosbestic wavelengths lying on this auxiliary function. A
corrected measurement spectrum (M'') is generated by means of the
two auxiliary functions. The oxygen saturation is determined by
comparing the changed data of this corrected measurement spectrum
(M'') with the data of the reference spectra at the other
wavelength.
Inventors: |
Schweitzer; Dietrich;
(Neustadt/Orla, DE) ; Hammer; Martin; (Jena,
DE) ; Thamm; Eike; (Jena/Maua, DE) |
Correspondence
Address: |
REED SMITH, LLP;ATTN: PATENT RECORDS DEPARTMENT
599 LEXINGTON AVENUE, 29TH FLOOR
NEW YORK
NY
10022-7650
US
|
Family ID: |
28798595 |
Appl. No.: |
12/002678 |
Filed: |
December 18, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10511483 |
Sep 7, 2005 |
7333842 |
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PCT/EP03/04024 |
Apr 17, 2003 |
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12002678 |
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Current U.S.
Class: |
600/323 |
Current CPC
Class: |
A61B 5/14551 20130101;
A61B 5/14555 20130101 |
Class at
Publication: |
600/323 |
International
Class: |
A61B 5/145 20060101
A61B005/145 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 17, 2002 |
DE |
102 17 543.8 |
Claims
1-3. (canceled)
4. A method for determining the oxygen saturation of blood in the
presence of optical disturbance variables, the method comprising:
generating at least two transmission or reflection isosbestic
measuring values at wavelengths that are isosbestic for hemoglobin
and oxyhemoglobin; generating at least one transmission or
reflection non-isosbestic measuring value at a wavelength that is
non-isosbestic hemoglobin and oxyhemoglobin; using the two
isosbestic measuring values to determine a corrected function of
the optical disturbance; and using the correction function to
determine the oxygen saturation.
5. A method for determining the oxygen saturation of blood in the
presence of optical disturbance values, the method comprising:
generating at least one transmission or reflection non-isosbestic
measuring value for a non-isosbestic wavelength for hemoglobin and
oxyhemoglobin; wherein the non-isosbestic measuring value for
hemoglobin and the non-isosbestic measuring value for oxyhemoglobin
duffer as far as possible in the reference spectra.
Description
[0001] The invention is directed to a method for the spectrometric
determination of the oxygen saturation of blood in the presence of
optical disturbance variables such as those also presented by
pigmented and light-scattering surrounding tissue and/or also the
vascular wall itself. This problem of determining the oxygen
saturation of blood while excluding as far as possible the
influence of these factors affecting measurement accuracy occurs
particularly in noninvasive, in-vivo or in-vitro examinations of
blood vessels located in front of, behind, or in said pigmented and
scattering tissue, for example, in the examination of blood vessels
of the ocular fundus or other tissue areas in the body such as the
skin and organs that are accessible by endoscopy.
[0002] It is generally known that the absorption spectrum of the
red blood pigment hemoglobin changes with oxygen saturation (e.g.,
van Assendelft, O. W., Spectrophotometry of heamoglobin
derivatives, Assen: Royal Vangorcum, 1970). Accordingly, it is
possible to determine the oxygen saturation of a hemoglobin sample
by comparing the spectrum of the sample to the spectra of
completely oxygenated and completely reduced hemoglobin.
[0003] Recent work in oxymetry in the ocular fundus using the
Lambert-Beerschen law, i.e., taking only absorption into account,
has been published by Smith et al. and others (Smith, M. H.,
Denninghoff, K. R., Lompado, A., Hillman, L. W., Effect of multiple
light paths in retinal vessel oxymetry, Appl. Opt. 39, 2000,
1183-1193). Numerous patented arrangements and methods are based on
this principle (e.g., U.S. Pat. No. 4,485,820; U.S. Pat. No.
5,119,814; U.S. Pat. No. 5,308,919; U.S. Pat. No. 4,253,744; U.S.
Pat. No. 4,305,398; U.S. Pat. No. 5,776,060; U.S. Pat. No.
5,935,076; DE 199 20 157 A1; U.S. Pat. No. 5,318,022).
[0004] However, the hemoglobin does not exist in isolation in
in-vivo measurement, but is enclosed in the erythrocytes. The
scattering of light on the erythrocytes has a considerable
influence on the extinction spectrum of the blood. However, based
on the findings of the multiple scattering theory of Twersky
(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 describe a method for determining the
oxygen saturation in whole blood from measurements taken in
transmission at a wavelength of 555 nm and at isosbestic points at
522 nm and 546 nm (Pittman, R. N., Duling, B. R., 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 of oximetry of blood in retinal vessels, Appl. Opt. 27,
1988, 113-1125).
[0005] However, investigations by Hammer at 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 on retinal vessels are
influenced not only by the absorption of the hemoglobin and the
scattering in the blood and in the tissue surrounding the vessels,
but also by the melanin located in the retinal pigment epithelium
and in the choroid. This is also true of vessels in the skin or
other pigmented organs.
[0006] Correcting falsification of the hemoglobin spectra by means
of other chromophores and correction for spectroscopic oxymetry
have been attempted in previous literature by scaling the spectra
measured on a vessel to measurements next to the vessel (e.g., DE
199 20 157 A1; U.S. Pat. No. 5,935,076; Delori, F. C., Noninvasive
technique for oximetry of blood in retinal vessels, Appl. Opt. 27,
1988, 113-1125; Schweitzer, D., Hammer, M., Kraft, J., Thamm, E.,
Konigsdorffer, E., Strobel, J., In Vivo Measurement of the Oxygen
Saturation at the Normal Human Eye, IEEE Trans. Biomed. Eng. 46,
1999, 1454-1465). However, this approach does not take into account
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 beam
propagation in the blood vessel and the tissue surrounding it.
[0007] The exact light propagation in the biological tissue cannot
always be fully described physically. Even efforts to recreate
these processes for eliminating disturbances in the most
comprehensive and realistic manner possible (DE 199 20 157 A1) and
to model the optics of the living or dead biological tissue
surrounding the blood vessel (DE 44 33 827 A1) have not led to more
exact measurements than the methods mentioned above, which are
already relatively time-consuming and require intensive
computation. In view of this, the methods are only conditionally
suitable especially for routine examinations and screening
examinations. In particular, the determination of oxygen saturation
at every point of a two-dimensional, graphic recording, which is
important for clinical practice, requires a method that is fast on
the one hand and that compensates for optical and spectrometric
disturbances due to the tissue environment on the other hand.
[0008] Therefore, it is the object of the invention to determine
the oxygen saturation with high accuracy by a method which is as
simple and as fast as possible.
[0009] In order to meet the above-stated object, spectral
measurements are generated by transmission measurement and
reflection measurement in a measurement spectrum at wavelengths
that are isosbestic for hemoglobin and oxyhemoglobin and at least
one other measurement value is generated at a wavelength at which
the reference values of hemoglobin and oxyhemoglobin differ, and
these measurements are compared with known reference values of the
reference spectra of hemoglobin and oxyhemoglobin in that:
[0010] a) at least two said spectral measurement values (M.sub.i1,
M.sub.i2) at wavelengths (.lamda..sub.i1, .lamda..sub.i2) that are
isosbestic for hemoglobin and oxyhemoglobin and at least the other
measurement value (M.sub.a) at a wavelength (.lamda..sub.a) at
which the reference values of hemoglobin and oxyhemoglobin differ
as far as possible in the reference spectra are detected in the
measurement spectrum, wherein an auxiliary function (F.sub.H) is
generated at least from two of the measurement values (M.sub.i1,
M.sub.i2) for isosbestic wavelengths (.lamda..sub.i1,
.lamda..sub.i2),
[0011] b) a reference function (F.sub.R) is generated in the
reference spectra from the reference values (R.sub.i1, R.sub.i2)
corresponding to the at least two measurement values (M.sub.i1,
M.sub.i2) determined in the measurement spectrum for the same
isosbestic wavelengths (.lamda..sub.i1, .lamda..sub.i2) of
hemoglobin and oxyhemoglobin, which reference function (F.sub.R) is
of the same type,
[0012] c) a correction function (F.sub.K) is generated from the
auxiliary function (F.sub.H) of the measurement spectrum in which
said at least two measurement values (M.sub.i1, M.sub.i2) lie for
isosbestic wavelengths (.lamda..sub.i1, .lamda..sub.i2) and from
the reference function (F.sub.R) of the reference spectra in which
the at least two reference values (R.sub.i1, R.sub.i2)
corresponding to the at least two measurement values (M.sub.i1,
M.sub.i2) lie, and a corrected auxiliary function (F.sub.Hk)
identical to the reference function (F.sub.R) in the reference
spectra is generated in a corrected measurement spectrum by means
of this correction function (F.sub.K), and
[0013] d) the oxygen saturation of the blood is determined from the
other measurement value (M.sub.a'') converted to the corrected
auxiliary function (F.sub.Hk) of the corrected measurement spectrum
in relation to the reference values for hemoglobin and
oxyhemoglobin at this wavelength (.lamda..sub.a).
[0014] It is advantageous when the spectral measurement values and
reference data are determined logarithmically and the auxiliary
function and reference function are formed by a straight line on
which two of the measurement values or reference values lie for
isosbestic wavelengths. The correction function formed from the
linear auxiliary function and reference function can also give a
linear corrected auxiliary function of the corrected measurement
spectrum. A constant multiplier is applied to the rest of the
spectral measurement values, i.e., the spectral measurement value
for the third isosbestic wavelength and the other measurement value
at a wavelength at which the reference values of hemoglobin and
oxyhemoglobin differ as far as possible in the reference spectra.
This constant multiplier is determined in such a way that the third
isosbestic measurement value of the corrected measurement spectrum
that is corrected by scaling conforms to the corresponding
reference value of the reference spectra. In this specific 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 measurement value that is converted to the corrected
auxiliary function of the corrected measurement spectrum.
[0015] For purposes of a clear two-dimensional representation of
the oxygen saturation of the blood, four monochromatic individual
images are generated at said wavelengths and the oxygen saturation
is determined for each image point.
[0016] Surprisingly, it has been shown that in comparison with the
examination methods mentioned in the introduction, the oxygen
saturation of the blood can be determined by the proposed method
with the same accuracy but with substantially less effort
(minimally, four measurement values are required) for measurement,
calculation and evaluation. The method makes possible a
two-dimensional, spatially dependent representation of the
measurements allowing a manageable and fast evaluation. Only a few
measurement values are required and only linear transformations are
used. With these advantages of low expenditure and time-efficient
measurement evaluation, the proposed method is also suitable for
screening examinations as well as for routine and early detection
examinations.
[0017] The invention will be described more fully in the following
with reference to an embodiment example shown in the drawing.
[0018] FIG. 1 is a graph showing measurement values and reference
values in logarithmic form in the wavelength range between 400 nm
and 700 nm, including three isosbestic wavelengths
.lamda..sub.i1=522 nm, .lamda..sub.i2=586 nm, .lamda..sub.i3=569 nm
and the other wavelength .lamda..sub.a=555 nm;
[0019] FIG. 2 is a graph with spectral reference values according
to FIG. 1 showing linear reference function F.sub.R and corrected
measurement values M';
[0020] FIG. 3 is a graph with spectral reference values according
to FIG. 1 showing linear reference function F.sub.R with corrected
measurement values M'' and with scaling for reading off oxygen
saturation.
[0021] The reflection or transmission of tissue at a point or with
spatial resolution in an image is measured at three isosbestic
wavelengths .lamda..sub.i1, .lamda..sub.i2 and .lamda..sub.i3
(.lamda..sub.i1=522 nm, .lamda..sub.i2=586 nm, .lamda..sub.i3=569
nm) as measurement data M.sub.i1, M.sub.i2 and M.sub.i3 and at a
different wavelength .lamda..sub.a (555 nm), at which the
absorption coefficients of oxygenated and reduced hemoglobin
differ, as measurement value M.sub.a and is compared with the
reflection or transmission of hemoglobin or whole blood with oxygen
saturations of 0% and 100%, respectively, at these wavelengths
(reference data R.sub.1, R.sub.2, R.sub.3, R.sub.a.sup.0% and
R.sub.a.sup.100%) according to the following method:
[0022] 1. All measurement data and reference data are
logarithmized. FIG. 1 shows the measurement data and reference data
represented logarithmically, which are, in this example, the
reflection of a retinal vein (measurement data) and the
transmission of a layer of whole blood with a thickness of 0.1 mm
(reference data). For the sake of clarity, the complete spectra
between 400 nm and 700 nm are shown. The wavelengths
.lamda..sub.i1=522 nm, .lamda..sub.i2=586 nm, .lamda..sub.i3=569 nm
and .lamda..sub.a=555 nm used in this example are shown.
[0023] 2. A linear auxiliary function F.sub.H of the wavelength is
calculated in the measurement spectra such that its values at the
isosbestic wavelengths .lamda..sub.i1 and .lamda..sub.i2 agree with
the measurement data M.sub.i1 and M.sub.i2 at these
wavelengths.
[0024] 3. A linear reference function F.sub.R of the wavelength is
calculated in the reference spectra in such a way that its values
at the isosbestic wavelengths .lamda..sub.i1 and .lamda..sub.i2
agree with the reference data R.sub.i1, R.sub.i2 at these
wavelengths.
[0025] 4. The measurement data are corrected additively at each
wavelength by the difference of the linear functions F.sub.H and
F.sub.R in such a way that at the isosbestic wavelengths
.lamda..sub.i1 and .lamda..sub.i2 they agree with the reference
data: M'.sub..lamda.=M.sub..lamda.+F.sub.R-F.sub.H.
[0026] FIG. 2 again shows the reference data, the linear reference
function F.sub.R of the wavelength and the corrected measurement
data M'. This correction compensates for extinctions which exist in
addition to the absorption of the hemoglobin and whose spectra in
the wavelength range of 522 nm to 586 nm can be assumed or
approximated as linear in the logarithmic scale. The embodiment
example under consideration concerns absorptions of melanin and the
anterior optical media and the scattering in the blood and in the
surrounding tissue.
[0027] 5. The corrected measurement data M' are scaled by a factor
of less than or greater than 1 around the linear reference function
F.sub.R in such a way that they agree with the reference value
R.sub.i3 at the isosbestic wavelength .lamda..sub.i3:
M .lamda. '' = F R ( .lamda. ) + ( M .lamda. ' - F R ( .lamda. ) )
( R i 3 - F R ( .lamda. 3 ) ) M i 3 ' - F R ( .lamda. 3 ) .
##EQU00001##
[0028] FIG. 3 shows the spread (or scaling) of the corrected
measurement data M' resulting in M'' around the linear reference
function F.sub.R which is carried out in such a way that corrected
measurement data and reference data agree at the isosbestic
wavelength .lamda..sub.i3 (569 nm). This correction compensates for
different absolute values of the measurement data and reference
data that occur due to different illumination conditions and
measurement conditions.
[0029] 6. The position Of M''.sub.a on a scale contained linearly
between R.sub.a.sup.0% and R.sub.a.sup.100% indicates the oxygen
saturation OS:
O S = M a '' - R a 0 % R a 100 % - R a 0 % . ##EQU00002##
[0030] The scaled readout of the oxygen saturation (OS) between the
values 0 and 1 is likewise shown in FIG. 3. The oxygen saturation
OS in the embodiment example is 0.69.
Reference Numbers
[0031] M--measurement data [0032] M'--measurement data corrected by
the addition of the corrected auxiliary function [0033]
M''--measurement data M' corrected by applying a factor [0034]
F.sub.R--reference function [0035] OS--oxygen saturation [0036]
.lamda.--wavelength
* * * * *