System for assessing endothelial function

• US 20030191395A1
• Filed: 04/03/2003
• Published: 10/09/2003
• Est. Priority Date: 04/05/2002
• Status: Active Grant

• Current Assignee: Thermal Technologies Incorporated
• Original Assignee: Thermal Technologies Incorporated
• Inventors: Bowman, Harry Frederick, Martin, Gregory T.
• Granted Patent: US 7,682,317 B2
• Time in Patent Office: Days
• US Class Current: 600/474
• CPC Class Codes: A61B 2562/02 Details of sensors specially adapted for in-vivo measurements
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61B 5/6843 Monitoring or controlling sensor contact pressure
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: G16H 70/00 ICT specially adapted for the handling or processing of medical references

Abstract

The system assesses the endothelial function of a subject. Particularly, peripheral tissue perfusion measurements taken in a subject are compared to reference perfusion data and the comparison yields the assessment of endothelial function. The reference may be data indicative of peripheral tissue perfusion in a healthy person. Also, peripheral tissue perfusion measurements taken in a subject when perfusion is in an unperturbed state (the reference) can be compared to perfusion measurements taken promptly after a challenge to normal or unperturbed tissue perfusion of the subject.

Claims

1. A method of assessing endothelial function in a subject comprising the steps of:

assessing peripheral tissue perfusion at a selected site on the body of a subject;

accessing peripheral tissue perfusion reference data indicative of endothelial function of a healthy subject; and

comparing the results of said assessing step to the data accessed in said accessing step for obtaining values related to the endothelial function of the subject.

7. A method according to claim 1 wherein said accessing step comprises the steps of:

challenging blood flow at said site for a time interval; and

assessing peripheral tissue perfusion at said site following said challenging step for obtaining perfusion related data.

8. A method according to claim 7 wherein said assessing step comprises the steps of;

placing a thermal transducer on the skin surface at a selected location on the body of the subject;

applying to said thermal transducer pressure effective to establish thermal contact between said thermal transducer and the skin surface and ineffective to materially impair blood flow in the capillary bed adjacent the skin surface;

transferring thermal energy from said thermal transducer to said capillary bed; and

determining a tissue perfusion related value in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by said transferring step.

2. A method according to claim I wherein said accessing step comprises the step of accessing a model relating peripheral tissue perfusion to endothelial function.

3. A method according to claim 2 wherein said assessing step comprises the steps of:

placing a thermal transducer on the skin surface at a selected location on the body of the subject;

applying to said thermal transducer pressure effective to establish thermal contact between said thermal transducer and the skin surface and ineffective to significantly impair blood flow in the capillary bed adjacent the skin surface;

transferring thermal energy from said thermal transducer to said capillary bed; and

determining a tissue perfusion related value in said capillary bed as a function of the dissipation of thermal energy transferred by said transferring step.

4. A method according to claim 3 wherein said accessing step comprises the step of accessing preselected perfusion values representative of endothelial function for a healthy subject.

5. A method according to claim 3 wherein said accessing step comprises the step of accessing values derived from an algorithm or a mode relating peripheral tissue perfusion to endothelial function.

6. A method according to claim 2 wherein said comparing step comprises the step of correlating the tissue perfusion value resulting from said assessing step with a corresponding value accessed by said accessing step.

9. A method of comparing tissue perfusion related values comprising:

(a) applying thermal energy to the skin surface and the adjacent capillary bed of a subject and detecting the thermal response to the application of thermal energy;

(b) producing signals functionally related to the thermal energy applied by said applying step and the thermal response to the application of thermal energy;

(c) calculating a perfusion related value using the signals produced by step (b);

(d) storing the perfusion related value obtained by step (c);

(e) challenging blood flow to the skin surface and capillary bed to which thermal energy was applied by step (a);

(f) repeating steps (a) through (c) for obtaining a perfusion related value affected by step (e); and

(g) comparing the perfusion related value stored by step (d) and perfusion related value obtained by step (f).

10. A method according to claim 9 further comprising the step of providing information indicative of systemic endothelial function as a function of compared perfusion related values resulting from said comparing step.

11. A method according to claim 9 further comprising the step of providing information indicative of vascular health as a function of compared perfusion related values

12. A method for comparing tissue perfusion related values comprising:

(a) locating a thermal transducer on the skin surface of a subject;

(b) applying to said transducer pressure sufficient to produce thermal contact between said transducer and the skin surface and insufficient to produce substantial collapse of capillaries in the capillary bed adjacent the skin surface;

(c) energizing said transducer for causing the temperature of the capillary bed to rise in an arbitrarily selected manner as a function of time;

(d) calculating at least one selected intrinsic thermal property of the capillary bed using thermal data obtained at a first time period;

(e) calculating a value related to tissue perfusion of the capillary bed using said at least one calculated intrinsic thermal property and thermal data obtained at a second time period, the effects of flow in the capillary bed at said second time period being greater than the effects of flow in the capillary bed at said first time period;

(f) introducing a change to a selected physiological parameter related to tissue perfusion;

(g) repeating steps (c) through (e); and

(h) comparing a calculated perfusion related value obtained during a first physiological condition prior to said introducing step to a second calculated perfusion related value resulting from said introducing step.

13. A method according to claim 12 wherein said introducing step comprises the step of challenging blood flow to the skin surface and the adjacent capillary bed and said comparing step comprises the step of comparing a perfusion related value obtained during an interval when blood flow to the capillary bed is unchallenged and a perfusion related value resulting from the challenge to blood flow to the capillary bed.

14. A method according to claim 13 wherein said challenging step comprises the step of chemically challenging blood flow to the skin surface and the adjacent capillary bed.

15. A method according to claim 13 wherein said introducing step comprises the steps of mechanically challenging blood flow to the skin surface and the adjacent capillary bed and terminating quickly the challenge and said comparing step comprises the step of comparing a perfusion related value obtained during an interval when blood flow to the capillary bed is unaffected by a challenging step and a perfusion related value resulting from said terminating step.

16. A method according to claim 12 further comprising the step of providing information indicative of systemic endothelial function as a function of compared perfusion related values resulting from said comparing step.

17. A method according to claim 12 further comprising the step of providing information indicative of vascular health as a function of compared perfusion

18. A method for assessing endothelial function in a living subject comprising the steps of:

determining an initial tissue perfusion related value at a selected location on the body of a subject;

constricting the blood flow to the selected location for a time interval;

releasing the constriction of blood flow to the selected location at the end of the time interval; and

comparing the initial tissue perfusion related value to the tissue perfusion related value resulting from said releasing step.

19. A method for assessing a physiological parameter related to tissue perfusion comprising the steps of:

determining a tissue perfusion related value in a capillary bed at a selected location on the body of a subject;

subsequent to determining the tissue perfusion value at said selected location, challenging blood flow to said capillary bed for a time interval;

releasing the challenge to blood flow to said capillary bed upon expiration of said time interval;

determining a tissue perfusion related value in said capillary bed resulting from said releasing step; and

comparing the results of the first said determining step and the second said determining step.

20. A method for non-invasively assessing endothelial function in a living subject comprising:

placing a thermistor on the skin surface at a selected location on the body of a subject;

applying to said thermistor pressure effective to establish thermal contact between said thermistor and the skin surface at the selected location and ineffective to significantly impair blood flow in the capillary bed adjacent the skin surface at the selected location;

transferring thermal energy from said thermistor to said capillary bed;

quantifying tissue perfusion in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by said transferring step;

subsequent to said quantifying step constricting blood flow to said capillary bed for a time interval;

releasing the constriction of blood flow to said capillary bed upon expiration of said time interval;

upon said releasing step transferring thermal energy from said thermistor to said capillary bed;

quantifying tissue perfusion in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by the second said transferring step; and

comparing the results of the first said quantifying step and the second said quantifying step.

21. A method for assessing a physiological parameter related to tissue perfusion comprising the steps of:

placing a thermal transducer in contact with the skin surface at a selected location on the body of a subject for facilitating the transmission of thermal energy between the capillary bed adjacent said skin surface and said transducer;

applying to said transducer pressure effective to establish thermal contact between said transducer and said skin surface and ineffective to significantly impair blood flow in said capillary bed;

transferring thermal energy from said transducer to said capillary bed;

quantifying tissue perfusion in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by said transferring step;

subsequent to said quantifying step constricting blood flow to said capillary bed for a time interval;

releasing the constriction of blood flow to said capillary bed upon expiration of said time interval;

upon said releasing step transferring thermal energy from said transducer to said capillary bed;

quantifying tissue perfusion in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by the second said transferring step; and

comparing the results of the first said quantifying step and the second said quantifying step.

22. A method of assessing a physiological characteristic of a living subject comprising the steps of;

assessing peripheral tissue perfusion; and

accessing a model relating peripheral tissue perfusion to the physiological characteristic; and

comparing the results of said assessing step and the model accessed in the accessing step.

23. A method of assessing a physiological characteristic of a living subject comprising the steps of:

assessing peripheral tissue perfusion as a proxy for said physiological characteristic;

challenging the peripheral tissue perfusion assessed;

assessing the changed peripheral tissue perfusion resulting from said challenging step; and

comparing the results of the first said assessing step and the second said assessing step.

24. A method according to claim 23 wherein said physiological characteristic is endothelial function.

25. A method of assessing endothelial function of a subject comprising the steps of:

sensing a peripheral tissue perfusion value at a selected location;

storing the peripheral tissue perfusion value obtained by said sensing step;

challenging blood flow to the selected location;

sensing the changed peripheral tissue perfusion value at the selected location resulting from said challenging step; and

calculating data indicative of systemic endothelial function using the stored peripheral tissue perfusion value and the peripheral tissue perfusion value resulting from the second said sensing step.

26. A method according to claim 25 wherein said challenging step comprises the step of chemically challenging blood flow to the selected location.

27. A method according to claim 25 wherein said challenging step comprises the steps of mechanically challenging blood flow to the selected location and terminating quickly the challenge and said calculating step promptly follows said terminating step for sensing the hyperemic reaction.

28. Apparatus for assessing endothelial function comprising:

means for assessing peripheral tissue perfusion at a selected site on the body of a subject;

a model relating peripheral tissue perfusion values to endothelial function; and

a data processor correlating perfusion values from said assessing means with perfusion values provided by said model for obtaining values relating to endothelial function.

29. Apparatus according to claim 28 wherein said model comprises means for relating peripheral tissue perfusion values to one or more endothelial function values.

30. Apparatus according to claim 29 wherein said relating means comprises an algorithm.

31. Apparatus according to claim 28 wherein said assessing means comprises;

a thermal transducer adapted for placement on the skin surface at a selected site on the body of the subject for transferring thermal energy to the capillary bed underlying the skin surface;

means for applying force to said thermal transducer effective to establish thermal contact between said thermal transducer and the skin surface and ineffective to significantly impair blood flow in the capillary bed underlying the skin surface; and

means for determining a tissue perfusion related value in said capillary bed as a function of the dissipation from said capillary bed of thermal energy transferred by said thermal transducer.

32. Apparatus according to claim 31 wherein said correlating means comprises means for associating tissue perfusion values from said determining means with a corresponding value from said model.

33. Apparatus according to claim 31 wherein said means for applying force to said thermal transducer comprises:

mounting means surrounding said thermal transducer for contacting the skin surface at the selected site and presenting said thermal transducer for thermal contact with the skin surface; and

means interposed between said mounting means and said thermal transducer for applying to said thermal transducer force effective to establish thermal contact between said thermal transducer and the skin surface and ineffective to significantly impair blood flow in the capillary bed underlying the skin surface.

34. Apparatus according to claim 33 wherein said interposed means comprises a resilient member.

35. Apparatus according to claim 33 wherein said interposed means comprises an inflatable member and means for inflating said inflatable member more or less to apply more or less pressure to the skin surface.

36. Apparatus according to claim 35 further comprising one or more thermal sensors on said mounting means for monitoring the baseline temperature of the skin surface around said thermal transducer, wherein said assessing means comprises means for adjusting peripheral tissue perfusion values to compensate for baseline temperature shifts.

37. Apparatus for assessing endothelial function comprising:

means for challenging blood flow at a selected site on the body of a subject for a time interval;

means for assessing tissue perfusion at said site before and after a challenge to blood flow at said site; and

a data processor for comparing tissue perfusion before and after a challenge to blood flow at said site for obtaining values related to endothelial function of the subject.

38. Apparatus according to claim 37 wherein said assessing means comprises:

a thermal transducer adapted for application to the skin surface of the subject;

means for applying to said thermal transducer pressure effective to establish thermal contact between said thermal transducer and the skin surface and ineffective to significantly impair blood flow in the capillary bed adjacent the skin surface;

means for transferring thermal energy from said thermal transducer to said capillary bed; and

determining a tissue perfusion related value in said capillary bed as a function of the dissipation of thermal energy transferred by said transferring step.

39. A system for comparing perfusion related values comprising:

thermal transducer means for applying thermal energy to the skin surface of a subject and detecting the thermal response to the application of thermal energy;

means for applying to said transducer means pressure sufficient to produce thermal contact between said transducer means and the skin surface of a subject and insufficient to produce substantial collapse of capillaries in the capillary bed adjacent the skin surface;

means for producing signals functionally related to the thermal energy applied by said transducer means and the thermal response to the application of thermal energy;

data processing. means for calculating a tissue perfusion related value using the signals produced by said signal producing means;

data storage means for storing perfusion related data obtained during a first physiological condition related to tissue perfusion; and

means for comparing perfusion related data stored by said data storage means and perfusion related data obtained during a second physiological condition related to tissue perfusion.

40. A system according to claim 39 wherein said transducer means comprises a thermistor.

41. A system according to claim 39 further comprising means responsive to said comparing means for providing information indicative of endothelial function.

42. A system according to claim 39 further comprising means responsive to said comparing means for providing information indicative of vascular health.

43. A system for comparing tissue perfusion related values comprising:

thermal transducer means for applying thermal energy to the skin surface of a subject and detecting the thermal response to the application of thermal energy;

means for applying to said transducer means pressure sufficient to produce thermal contact between said transducer means and the skin surface of a subject and insufficient to produce substantial collapse of capillaries in the capillary bed adjacent the skin surface;

means for causing the temperature of the capillary bed to rise in an arbitrarily selected manner as a function of time;

means for calculating at least one selected intrinsic thermal property of the capillary bed using data obtained at a first time period;

means for calculating a value related to tissue perfusion of the capillary bed using data obtained at a second time period and said at least one calculated intrinsic thermal property, the effects of flow in the capillary bed at said second time period being greater than the effects of flow in the capillary bed at said first time period; and

means for comparing a perfusion related value obtained during a first physiological condition related to tissue perfusion to a second perfusion value obtained during a subsequent physiological condition related to tissue perfusion.

44. A system according to claim 43 wherein said transducer means comprises a thermistor.

45. A system according to claim 43 wherein said comparing means comprises means for comparing a perfusion related value obtained during an interval when blood flow to the capillary bed is unchallenged and a perfusion related value obtained following a challenge to blood flow to the capillary bed.

46. A system according to claim 43 wherein said comparing means comprises means for comparing a perfusion related value obtained during an interval when blood flow to the capillary bed is unchallenged and a perfusion related value obtained after blood flow to the capillary bed has been mechanically challenged for an interval and quickly released.

47. A. system according to claim 43 wherein said comparing means comprises means for comparing a perfusion related value obtained during an interval when blood flow to the capillary bed is unchallenged and a perfusion related value obtained after blood flow to the capillary bed has been chemically challenged.

48. A system according to claim 43 further comprising means responsive to compared perfusion related values in said comparing means for providing information indicative of systemic endothelial function.

49. A system according to claim 43 further comprising means responsive to compared perfusion related values in said comparing means for providing information indicative of vascular health.

50. A thermal transducer comprising:

transducing means for applying thermal energy to tissue and detecting the thermal response of tissue to the application of thermal energy;

a support circumscribing a central space and forming a tissue contacting surface; and

means for mounting said transducing means within said central space in a position for contact with tissue when said surface is in contact with tissue and, when said surface is in contact with tissue, transmitting to said transducing means pressure sufficient to establish effective thermal contact between said transducing means and tissue in contact therewith and insufficient to cause substantial collapse of capillaries and vessels in the tissue in effective thermal contact with said transducing means.

51. A transducer according to claim 50 wherein said transducing means comprises a thermistor.

52. A transducer according to claim 50 wherein said surface is disposed radially outward from said transducing means, effectively outside the thermal response zone of said transducing means.

53. A transducer according to claim 52 wherein said surface is formed of thermally insulating material, further comprising one or more thermal sensors mounted along said surface for detecting baseline temperature at one or more locations adjacent said transducing means.

54. A transducer according to claim 50 wherein said surface is formed of thermally insulating material, further comprising three or more thermal sensors mounted along said surface means at substantially equal intervals for detecting baseline temperature at a plurality of locations around said transducing means.

55. A non-invasive thermal probe comprising;

transducing means for applying thermal energy to tissue and detecting the thermal response of tissue to the application of thermal energy;

support means surrounding said transducing means and spaced therefrom outside the direct thermal response zone of said transducing means; and

means for mounting said transducing means within said surrounding support means and positioning an operative surface of said transducing means for contact with tissue when said support means is in contact with tissue;

said mounting means comprising

means for pressing said transducing means to the surface of tissue when said support means is in contact with tissue for producing effective thermal contact between said transducing means and the surface of the tissue contacted and producing insufficient contact between said transducing means and the surface of the tissue contacted to cause substantial collapse of capillaries and vessels within the direct thermal response zone of said transducing means.

56. A probe according to claim 55 wherein said pressing means is resilient.

57. A probe according to claim 55 wherein said support means comprises thermally insulating material forming an annular tissue contacting face, further comprising a plurality of thermal sensors mounted on said support means along said face for detecting baseline temperatures at a plurality of locations around said transducing means.

58. A non-invasive thermal probe comprising:

transducer means for contacting subject tissue and facilitating the transmission of thermal energy between the subject tissue and said transducer means;

means supporting said transducer means defining loci for contacting the surface of said tissue around said transducer means outside the direct thermal response zone of said transducing means when said transducer means is in contact with the subject tissue; and

means on said supporting means for transmitting to said transducing means, when said loci are in contact with the surface of tissue, pressure sufficient to establish effective thermal contact between said transducing means and tissue in contact therewith and insufficient to cause substantial collapse of capillaries and vessels in the tissue in effective thermal contact with said transducing means.

59. A transducer according to claim 58 further comprising thermal sensor means mounted on one or more of said loci for detecting baseline temperature