Methods and apparatus for non-invasive determination of patient's blood conditions

Abstract

A method and apparatus are presented for non-invasive determination of blood clotting related and blood circulation related parameters of a mammal. At least one stimulus ST is non-invasively induced in a blood containing medium in the mammal for a preset period of time tST. This at least one stimulus is selected to cause at least one of the following to occur: (a) inducing at least two of three Virchow's triad elements including abnormalities of blood flow; abnormalities of blood constituents and abnormalities of the blood vessel wall, and (b) inducing a change in red blood cell (RBC) aggregation or local blood viscosity. Measurements are non-invasively performed at a measurement location in the mammal by applying an external field thereto for a preset time period tm, a response of the measurement location to the applied field is detected, and measured data indicative thereof generated. At least a portion of the measured data and stimulus related data are processed so as to determine a relation between a time function of the at least one stimulus ST(t) and a time function of the measured data OR(t). This relation is indicative of at least one blood circulation and blood coagulation related parameter of the mammal.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

In order to understand the invention and to see how it may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

FIG. 1 is a schematic illustration of a system of the present invention for non-invasive measurement of a blood condition in a mammal;

FIG. 2 is an example of a method of the present invention for non-invasively determining a risk condition of blood;

FIG. 3 is a block diagram of specific example of the implementation of the method of FIG. 2; and

FIGS. 4A and 4B show experimental results of the technique of the present invention.

Claims

1. A non-invasive method for determination of blood clotting related and blood circulation related parameters of a mammal, the method comprising: (i) non-invasively inducing at least one stimulus ST in a blood containing medium in the mammal for a preset period of time tST, said at least one stimulus being selected to cause at least one of the following to occur: (a) inducing at least two of three Virchow's triad elements including abnormalities of blood flow; abnormalities of blood constituents and abnormalities of the blood vessel wall, and (b) inducing a change in red blood cell (RBC) aggregation or local blood viscosity;(ii) performing non-invasive measurements at a measurement location in the mammal by applying an external field thereto for a preset time period tm; detecting a response of the measurement location to the applied field; and generating measured data indicative thereof; and(iii) processing at least a portion of the measured data and processing stimulus related data so as to determine a relation between a time function of said at least one stimulus ST(t) and a time function of the measured data OR(t), said relation being indicative of at least one blood circulation and blood coagulation related parameter of the mammal.

2. A method according to claim 1, wherein said at least two induced Virchow's triad elements are an abnormality of blood flow, and an abnormality of the blood vessel wall.

3. A method according to claim 1, wherein the abnormality of blood flow comprises at least one of the following: an abnormality of the blood rheology; an abnormality of turbulence at bifurcations; an abnormality of turbulence at a stenotic region; a blood viscosity parameter; a localized viscosity of the blood.

4. A method according to claim 1, wherein the abnormality of the blood vessel wall comprises at least one of the following: an abnormality of the endothelium, an abnormality of a blood vessel wall thickness, an abnormality of blood vessel wall rigidity, an abnormality of blood vessel wall integrity; an abnormality of blood vessel wall roughness, and an abnormality of plaque concentration.

5. A method according to claim 1, wherein said at least one stimulus is induced in the mammal medium in the vicinity of the measurement location.

6. A method according to claim 1, wherein said at least one stimulus is induced in the mammal medium at a location distanced from the measurement location.

7. A method according to claim 1, wherein the first stimulus is induced in the mammal medium in the vicinity of the measurement location; and the second stimulus is induced in the mammal medium at a location distanced from the measurement location.

8. A method according to claim 1, wherein said inducing of the change in RBC aggregation or local blood viscosity comprises applying an over systolic pressure to the mammal medium to create a stasis state at the measurement location.

9. A method according to claim 1, wherein said inducing of the at least one stimulus includes application of a mechanical pressure of a preset time dependence ST(t)=P(t) to the mammal to at least one of a location different from the measurement location and a location in the vicinity of the measurement location.

10. A method according to claim 1, wherein said inducing of the at least one stimulus comprises application of heat H of a preset time dependence ST(t)=H(t) on patient's hand or finger to at least one of a location different from the measurement location and a location in the vicinity of the measurement location.

11. A method according to claim 1, wherein said inducing of the at least one stimulus comprises application of short strongly absorbable laser pulse I of a preset time dependence ST(t)=I(t) to at least one of a location in the vicinity of the measurement location and a location on the mammal remote from the measurement location.

12. A method according to claim 11, wherein the stimulus induces a micro-injury in at least one of endothelial cells, venulas and arterioles, the measured time function of the response being indicative of various stages of consequences of the injury.

13. A method according to claim 1, wherein said at least one stimulus comprises at least two of the following: mechanical pressure P application, heat H application, laser pulse I application, of preset time dependence, P(t), H(t) and I(t), respectively.

14. A method according to claim 13, wherein each of P(t), H(t) and I(t) is characterized by its own time scale tSTi, i being a number of the stimulus, different from the others, the measured response depending on all the time scales.

15. A method according to claim 14, wherein at least one of said times scales of the stimuli and/or the time period td varies from 0 till 540 seconds.

16. A method according to claim 13, wherein said relation indicative of said blood related parameter is a predetermined mathematical manipulation of the response function OR(t) and at least one of P(t), H(t) and I(t) functions.

17. A method according to claim 1, wherein said non-invasive measurements are optical measurements, the external field being in the form of electromagnetic radiation of at least one predetermined wavelength range, and the response being in the form of electromagnetic radiation of said at least one wavelength range indicative of scattering, reflective, and absorbing properties of the mammal medium at the measurement location.

18. A method according to claim 1, wherein said non-invasive measurements are photo-acoustic measurements, the external field being in the form of electromagnetic and/or acoustic radiation of at least one predetermined wavelength range selected to cause the acoustic response of the measurement location.

19. A method according to claim 1, wherein the applied field is an electric current and said non-invasive measurements are electrical measurements, the response being in the form of a change of impedance of the mammal medium.

20. A method according to claim 1, comprising controlling said inducing of the at least one stimulus such that the stimulus varies with time according to a predetermined function for a time period not exceeding said certain time tST.

21. A method according to claim 1, wherein said blood clotting related and blood circulation related parameter is indicative of concentration of at least one drug selected from blood thinners and products of metabolism of this drug in the mammal's blood.

22. A method according to claim 1, wherein said at least one blood circulation and blood coagulation related parameter is indicative of at least one of the following: a condition of thrombosis, a risk of bleeding, and a prothrombin time.

23. A method according to claim 17, wherein said measurement of the time dependence of the response is carried out for at least two different wavelengths of the applied electromagnetic field, the measured data being indicative of the response as the function of time and wavelength; and said relation between the time functions of at least one stimulus and the response being a function of wavelength of the applied field and the time parameters tST and td.

24. A method according to claim 23, wherein said relation is a predetermined mathematical manipulation of the at least one stimulus time function ST(t) and the response function of time and wavelength OR(t,λ), said mathematical manipulation being indicative of at least one of said blood clotting related parameters and blood circulation related parameters.

25. A method according to claim 23, wherein said at least two different wavelengths of the applied electromagnetic field are in a visible-NIR range.

26. A method according to claim 24, wherein the measured electromagnetic radiation response, OR, includes at least one of optical transmission T, optical reflection R and optical scattering of the medium.

27. A method according to claim 1, wherein said at least portion of the measured data to be processed includes the measured data indicative of the response measured from a predetermined moment of time td with respect to the end of inducing said at least one stimulus.

28. A method according to claim 27, wherein said predetermined moment of time td is selected to satisfy one of the following condition: it precedes the completeness of the inducing of said at least one stimulus, it substantially coincides with the completeness of the inducing of said at least one stimulus ends, and it occurs after the completeness of said inducing of the at least one stimulus.

29. A method according to claim 28, wherein while said external field is applied to the measurement location, the response from the measurement location is fixed a certain time td after the application of the external field to form said portion of the measured data.

30. A method according to claim 28, wherein said portion of the measured data is indicative of the response detected with a certain time delay td from the completeness of the inducing of said at least one stimulus.

31. A method according to claim 28, wherein said time delay td is selected to satisfy one of the following conditions: the time delay td is negative, said measured data portion corresponding to the measurements starting before said inducing of at least one stimulus is completed; the time delay td is substantially zero, said measured data portion corresponding to the measurements starting substantially when said inducing of the at least one stimulus is complete; and the time delay td is positive, said measured data portion corresponding to the measurements starting after the inducing of said at least one stimulus is complete.

32. A method according to claim 28, wherein the measured data includes said data portion and data indicative of the detected response before performing said inducing of the at least one stimulus.

33. A method according to claim 1, wherein the detected response is indicative of at least one blood parameter selected from: a blood viscosity, a blood rheological property, a blood density; RBC aggregation rate, prothrombin time; a blood coagulation parameter; a plasma protein parameter; an erythrocyte sedimentation rate; a fibrin concentration; a fibrinogen concentration; and a drug concentration or concentration of certain product of drug metabolism.

34. An apparatus for use in non-invasive determination of blood clotting related and blood circulation related parameters in a mammal, the apparatus comprising: (a) a measurement unit configured and operable for applying an external field to a measurement location in a blood containing medium of the mammal, detecting a response from the measurement location to the applied field, and generating measured data indicative thereof;(b) a stimulus inducing device configured and operable to induce at least one stimulus in the blood containing medium in the mammal, said at least one stimulus being of a kind causing at least one of the following to occur: (i) inducing at least two of three Virchow's triad elements in the medium including abnormalities of blood flow; abnormalities of blood constituents and abnormalities of the blood vessel wall; and (ii) inducing a change in the RBC aggregation;(c) a control unit configured for selectively operating said stimulus inducing device to maintain each of said at least one stimulus for a preset period of time tST, for operating the measurement unit to perform measurements and generate the measured, said control unit being preprogrammed to process and analyze the measured data to determine a time function of at least a portion of the measured data and a time function of said at least one stimulus and determine a relation between the time variations of said at least one stimulus and the at least portion of the measured data, said relation being indicative of the blood clotting related and blood circulation related parameters in the mammal.

35. An apparatus according to claim 34, wherein the measurement unit is an optical unit comprising a source of electromagnetic radiation of at least one predetermined wavelength range, and an electromagnetic radiation detector for detecting said response and generating said measured data.

36. An apparatus according to claim 34, wherein said stimulus inducing device is configured and operable to induce an abnormality of blood flow, and an abnormality of the blood vessel wall.

37. An apparatus according to claim 34, wherein said stimulus inducing device is configured and operable to apply at least one of the following to a location on the mammal: electromagnetic radiation of predetermined wavelength and power; and pressure of a predetermined profile.

38. An apparatus according to claim 36, wherein said stimulus inducing device is configured and operable to induce the abnormality of blood flow by inducing a change in red blood cell (RBC) aggregation.

39. An apparatus according to claim 37, wherein said stimulus inducing device is configured and operable to apply the pressure and the stimulating electromagnetic radiation to the blood containing medium in the mammal to the same or different locations thereon, located in the vicinity of or distanced from the measurement location.

40. An apparatus according to claim 39, wherein said stimulus inducing device comprises a light source for generating the stimulating electromagnetic radiation and a light guide unit operable to guide said stimulating electromagnetic radiation to the medium and to apply said pressure.

41. An apparatus according to claim 34, wherein the control unit operates to create said portion of the measured data corresponding to the measured data indicative of the response measured from a predetermined moment of time td with respect to the completeness of the application of said at least one stimulus.

42. An apparatus according to claim 41, wherein said predetermined moment of time td is selected to satisfy one of the following condition: it preceded the completeness of the application of said at least one stimulus, it substantially coincides with the completeness of the application of said at least one stimulus ends, and it occurs after the completeness of the application of the at least one stimulus.

43. An apparatus according to claim 34, wherein the control unit operates to control the operation of the stimulus inducing device to apply the stimulus during certain time tST such that the stimulus varies with time according to a predetermined function for a time period t not exceeding said certain time tST.

44. An apparatus according to claim 43, wherein the control unit operates to create said portion of the measured data corresponding to the measured data indicative of the response measured from a predetermined moment of time td with respect to the completeness of the application of said at least one stimulus and continuing for the time period t larger than td.

45. An apparatus according to claim 44, wherein said measurement unit is configured for generating the electromagnetic radiation of at least two different wavelengths, the control unit operating to determine the light response as a function of time and wavelength and determine said relation between the time functions of at least one stimulus and the response in the form of a function of wavelength of the applied radiation and the time parameters tST and td.

46. An apparatus according to claim 35, wherein said stimulus inducing device comprises said source of the electromagnetic radiation.