Method of optical measurement for determing various parameters of the patient's blood

• US 6,711,424 B1
• Filed: 11/05/2002
• Issued: 03/23/2004
• Est. Priority Date: 12/22/1999
• Status: Expired due to Term

• Current Assignee: OrSense Ltd.
• Original Assignee: OrSense Ltd.
• Inventors: Shvartsman, Leonid, Fine, Ilya
• Primary Examiner(s): Hindenburg, Max F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US10/168,951
• Time in Patent Office: 504 Days
• Field of Search: 600/309-310, 600/322-324, 600/335
• US Class Current: 600/322
• CPC Class Codes: A61B 5/022 by applying pressure to close blood vessels, e.g. against the skin; Ophthalmodynamometers
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/6825 Hand
• CPC Class Codes: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6838 Clamps or clips
• CPC Class Codes: G01N 2015/0092 Monitoring flocculation or agglomeration
• CPC Class Codes: G01N 2015/012 Red blood cells

Abstract

A method for optical measurements of desired parameters of the patient'"'"'s blood is presented. A state of the blood flow cessation is provided within a measurement region and maintained during a predetermined time period. Measurement sessions are performed within this predetermined time period. Each measurement session includes at least two measurements with different wavelengths of incident light. Obtained measured data is representative of the time dependence of light response of the blood in the measurement region. The analyses of the measured data enables the determination of the desired blood parameters extracted from optical characteristics associated with the erythrocytes aggregation process during the state of the blood flow cessation.

Claims

1. A method of optical measurements of at least one desired parameter of a patient'"'"'s blood, the method comprising the steps of:

providing a state of blood flow cessation of the patient'"'"'s blood within a measurement region, and maintaining the blood-flow cessation state during a predetermined time period;

performing measurement sessions within said predetermined time period, each measurement session including at least two measurements with different wavelengths of incident light, and obtaining measured data representative of the time dependence of light response of the blood in the measurement region;

analyzing the measured data for determining said at least one desired parameter, extracted from optical characteristics associated with erythrocytes aggregation process during the state of the blood flow cessation.

2. The method according to claim 1, wherein said state of the blood flow cessation in the measurement region is provided by applying an occlusion mode to the patient'"'"'s blood perfused fleshy medium.

3. The method according to claim 2, wherein the application of the occlusion mode comprises the application of over-systolic pressure to the patient'"'"'s blood perfused fleshy medium at a location upstream of said measurements region with respect to the direction of the normal blood flow in the patient'"'"'s body.

4. The method according to claim 3, and also comprising the step of preliminary optical measurements for detecting the existence of the blood flow cessation state.

5. The method according to claim 2, wherein said predetermined period of time is insufficient for irreversible changes to occur in the fleshy medium.

6. The method according to claim 5, wherein said predetermined period of time is from one second to several minutes.

7. The method according to claim 1, wherein said state of the blood flow cessation in the measurement region is provided by applying an occlusion mode to the flow of the patient'"'"'s blood sample into a cuvette, said measurement region being located in the cuvette.

8. The method according to claim 1, wherein the analyzing of the measured data comprises the step of:

determining a Rouleaux Geometry Factor (RGF) characterizing the changes of the light response of blood in the state of blood flow cessation as a function of time and wavelengths of the incident radiation, associated with the erythrocytes'"'"' aggregation.

9. The method according to claim 8, wherein the determination of the RGF comprises:

determining a ratio Δ

(log T)/Δ

t as a function of wavelength λ

obtained from several measurement sessions with the different wavelengths, Δ

t being a preset time interval of said predetermined period of time; and

determining a cut-off wavelength corresponding to the condition where T is the measured light response and Δ

(log T)/Δ

t=0.

10. The method according to claim 9, wherein said preset time interval is an asymptotic time interval characterized by relatively slow changes of the light response signal with time, as compared to an initial time interval of said predetermined period of time.

11. The method according to claim 9, wherein said desired parameter to be determined is an evaluated value of a parameter (n_Hb−

n_pl) for said patient, wherein n_Hb is the refraction index of hemoglobin in erythrocyte, and n_pl is the refraction index of plasma.

12. The method according to claim 11, wherein the evaluation of the parameter (n_Hb−

n_pl) comprises the utilization of theoretical data representative of a scattering function K(x(n_Hb−

n_pl)), wherein x=2π

a/λ

, a being the effective size of erythrocyte.

13. The method according to claim 8, wherein the determination of the RGF comprises:

determining a ratio or Δ

T/Δ

t as a function of wavelength λ

obtained from several measurement sessions with the different wavelengths, Δ

t being a preset time interval of said predetermined period of time; and

determining a cut-off wavelength is that corresponding to the condition where T is the measured light response and Δ

T/Δ

t=0.

14. The method according to claim 1, wherein the analyzing of the measured data comprises the steps of:

determining a parametric slope, said at least two wavelengths being selected in accordance with said desired parameter to be determined; and

using reference data in the form of a calibration curve of the parametric slope as a function of values of the desired parameter.

15. The method according to claim 14, wherein the determination of the parametric slope comprises the determination of a function T_λ

2(T<sub>λ

1</sub>), wherein T<sub>λ

2</sub> and T<sub>λ

1</sub> are the measured data corresponding to the wavelengths λ

₂ and λ

₁ of the incident radiation, respectively, the function T<sub>λ

2</sub>(T<sub>λ

1</sub>) being determined for a preset time interval of said predetermined time period.

16. The method according to claim 15, wherein said preset time interval is an initial time interval characterized by relatively strong changes of the light response signal with time, as compared to a next, asymptotic time interval of said predetermined period of time.

17. The method according to claim 15, wherein said preset time interval is an asymptotic time interval characterized by relatively slow changes of the light response signal with time, as compared to an initial time interval of said predetermined period of time.

18. The method according to claim 14, wherein the determination of the parametric slope comprises the determination of a function log T_λ

2(log T<sub>λ

1</sub>), wherein T<sub>λ

2</sub> and T<sub>λ

1</sub> are the measured data corresponding to the wavelengths λ

₂ and λ

₁ of the incident radiation, respectively, the function T<sub>λ

2</sub>(T<sub>λ

1</sub>) being determined for a preset time interval of said predetermined time period.

19. The method according to 14, wherein said desired parameter is the concentration of a certain substance in blood.

20. The method according to claim 19, wherein said calibration curve is determined from values of the parametric slope and values of the concentration obtained for different patients.

21. The method according to claim 19, wherein said substance is hemoglobin.

22. The method according to claim 21, wherein the at least two selected wavelengths are in the ranges of 600-1000 nm and 1100-1400 nm.

23. The method according to claim 19, wherein said substance is glucose.

24. The method according to claim 23, wherein the at least two selected wavelengths are in the ranges of 1500-1600 nm and 600-1300 nm.

25. The method according to claim 14, wherein said desired parameter is oxygen saturation.

26. The method according to claim 25, wherein said at least two wavelengths are in the ranges of 600-780 nm and 820-980 nm.

27. The method according to claim 25, wherein said calibration curve is determined from values of the parametric slope and values of the oxygen saturation obtained for different patients.

28. The method according to claim 25, wherein said calibration curve is plotted by applying at least two multiple-occlusion measurement sessions with said at least two selected wavelengths to the blood of said patient in the measurement region, determining the parametric slope values for each occlusion, and concurrently determining the oxygen saturation in the blood perfused fleshy medium of said patient outside said measurement region.

29. The method according to claim 1, wherein the analyzing of the measured data comprises the determination of Erythrocyte Aggregation Rate, as Δ

T/Δ

t where T is the measured light response and Δ

t being a preset time interval of said predetermined period of time.

30. The method according to claim 29, wherein Δ

t is within an initial time interval of the predetermined period of time characterized by relatively strong changes of the light response signal with time, as compared to a next, asymptotic time interval of said predetermined period of time.

31. The method according to claim 29, wherein Δ

t is an asymptotic time interval of the predetermined period of time characterized by relatively slow changes of the light response signal with time, as compared to an initial time interval of said predetermined period of time.

32. A method of optical measurements of desired parameters of a patient'"'"'s blood extracted from optical characteristics associated with erythrocytes aggregation process during a state of the blood flow cessation, the method comprising the steps of:

providing the state of the blood flow cessation within a measurement region, and maintaining the blood-flow cessation state during a predetermined time period;

performing measurement sessions within said predetermined time period, each measurement session including at least two measurements with different wavelengths of incident light, and obtaining measured data representative of the time dependence of light response of the blood in the measurement region;

analyzing the measured data for determining said at least one desired parameter, by determining at least one parametric slope value and a Rouleaux Geometry Factor (RGF) for said patient, the RGF characterizing the changes of the light response of blood at the state of the blood flow cessation as a function of time and wavelengths of the incident radiation, associated with the erythrocytes'"'"' aggregation.

33. A method of optical measurements of at least one desired parameter of blood of a specific patient extracted from optical characteristics associated with erythrocytes aggregation process during a state of the blood flow cessation, the method comprising the steps of:

providing reference data in the form of a function describing diffraction effects on particles, K(x(n_Hb−

n_H2O), wherein x=2π

a/λ

;

a is the size of erythrocyte, n_Hb is the refraction index of hemoglobin and n_pl is the refraction index of water, λ

is the wavelength of incident radiation;

providing the state of the blood flow cessation and maintaining said state during a predetermined period of time;

performing measurement sessions within said predetermined time period, each measurement session including several measurements with different wavelengths of incident radiation, and obtaining measured data representative of the time dependence of light response signals;

analyzing the measured data for determining a Rouleaux Geometry Factor (RGF) for the specific patient, the RGF characterizing the changes of the light response of blood at the state of the blood flow cessation as a function of time and wavelengths of the incident radiation, associated with the erythrocytes'"'"' aggregation.

34. A method of optical measurements of at least one desired parameter of blood of a specific patient extracted from optical characteristics associated with erythrocytes aggregation process during the state of the blood flow cessation, the method comprising the steps of:

providing reference data in the form of at least one calibration curve corresponding to a parametric slope as a function of values of said desired parameter;

providing the state of the blood flow cessation within a measurement region, and maintaining the blood-flow cessation state during a predetermined time period;

performing timely separated measurement sessions within said predetermined time period, each measurement session including at least two measurements with different wavelengths of incident light, and obtaining the time dependence of transmission signals, wherein the at least two wavelengths are selected in accordance with the desired parameter to be determined;

analyzing the obtained data for determining the parametric slope value for said specific patient;

using said calibration curve for determining the value of said desired parameter for said specific patient.

35. A measurement apparatus for performing optical measurements of at least one desired parameter of the patient'"'"'s blood, the apparatus comprising:

an occlusion assembly operable to apply pressure to a location on a blood containing medium and maintain said pressure for a predetermined time period;

illumination/detection assembly operable for applying optical measurements with at least two different wavelengths of incident radiation to a measurement region in the medium, and generating data representative of light response signals from the measurement region; and

a control unit for operating the occlusion and illumination/detection assemblies to allow application of the optical measurements during said predetermined time period, for processing the generated data to determine measured data in the form of at least two time variations of the light response signals corresponding to said at least two wavelengths, respectively, and for analyzing the measured data to determine the at least one desired parameter of the patient'"'"'s blood;

the apparatus being characterized in that;

the occlusion assembly is applicable to a first location on the medium upstream of a second location that contains said measurement region, with respect to the blood flow direction in the medium, the application of the pressure to the first location resulting in creation of a state of temporary blood flow cessation in the measurement region thereby causing a Rouleaux effect at the state of blood flow cessation;

the control unit comprises;

a memory for storing reference data in the form of a calibration curve of a value of a certain parameter associated with the Rouleaux effect as a function of values of the desired blood parameter;

a processor operable to analyze the measured data in the form of the two time variations to calculate a value of said parameter associated with the Rouleaux effect, and to utilize the reference data to determine the value of the desired parameter of the patient'"'"'s blood, the analyzing of the measured data from within a preset time interval of said predetermined period of time utilizing optical characteristics of blood associated with the erythrocytes aggregation process during the state of the blood flow cessation.

36. A method of optical measurements of at least one desired parameter of a patient'"'"'s blood, the method comprising the steps of:

providing a flow of the patient'"'"'s blood sample into a cuvette;

applying a pressure to a location upstream of the cuvette with respect to the direction of the blood flow, to create a state of blood flow cessation in a measurement region inside the cuvette, and maintaining the blood-flow cessation state during a predetermined time period, the creation of the state of the blood flow cessation in the measurement region causing a Rouleaux effect;

applying optical measurement sessions to said measurement region within said predetermine time period, each measurement session including at least two measurements with different wavelengths of incident light, detecting light response signals from the measurement region, and obtaining measured data in the form of at least two time variations of the light response signals corresponding to said at least two wavelengths, respectively, said variation being caused by the Rouleaux effect;

analyzing the measured data to calculate a value of a certain parameter associated with the Rouleaux effect as a function of time and wavelength of the incident radiation;

utilizing the calculated value of said parameter associated with the Rouleaux effect and utilizing predetermined reference data in the form of a calibration curve of a value of said parameter associated with the Rouleaux effect as a function of values of the desired blood parameter, and determining the desired parameter of the patient'"'"'s blood.