System for quantifying blood flow in tissue with periodic updating of tissue baseline conditions

• US 20030219719A1
• Filed: 04/04/2003
• Published: 11/27/2003
• Est. Priority Date: 04/05/2002
• Status: Active Grant

• Current Assignee: Thermal Technologies Incorporated
• Original Assignee: Thermal Technologies Incorporated
• Inventors: Martin, Gregory T., Bowman, H. Frederick
• Granted Patent: US 7,758,511 B2
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: A61B 5/02055 Simultaneously evaluating both cardiovascular condition and temperature
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61B 5/028 by thermo-dilution
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant

Abstract

Disclosed are methods and apparatus for determining blood flow in tissue. Particularly methods and apparatus are disclosed for establishing baseline thermal properties for the tissue and providing one or more steps for periodically determining changes in the tissue thermal properties that correspond to a need for a new baseline and establishing the new baseline.

Claims

1. A method for determining perfusion in living tissue comprising the steps of:

(1) establishing baseline criteria, comprising

(A) determining an unperturbed temperature of the tissue;

(B) causing the temperature of the tissue to change from a first unperturbed temperature to a second temperature different from said first temperature for a time period, and

(C) determining a value or values for one or more thermal properties of tissue during a first selected portion of said time period;

(2) calculating a perfusion value for the tissue at a second selected portion of said time period using said thermal property value or values, and

(3) evaluating one or more physiological and artifactual conditions to determine if baseline criteria established by step (1) are materially affected by said conditions and if so repeating step (1).

2. A method for determining perfusion in living tissue comprising the steps of:

(1) establishing thermal baseline criteria corresponding to thermal conditions of the tissue comprising determining an unperturbed tissue temperature;

(2) causing the temperature of a volume of the tissue to change from the unperturbed temperature to a second temperature different from the unperturbed temperature during a time interval;

(3) calculating at least one of an intrinsic thermal conductivity value and a thermal diffusivity value for said volume of tissue during a first selected portion of said time interval;

(4) calculating perfusion in said volume of tissue at a second selected portion of said time interval using said value;

(5) determining need for new baseline criteria for the tissue comprising evaluating one or both of physiologic and artifact conditions; and

(6) repeating step (1) when indicated by step (5).

3. A method for the periodic recalibration of perfusion measurement in tissue comprising the steps of:

(a) performing calibration of one or both of a perfusion sensor in thermal contact with the tissue and a perfusion monitoring instrument;

(b) measuring perfusion in tissue;

(c) automatically recognizing one or more of physiologic and artifact conditions under which the calibration is no longer valid;

(d) automatically performing a recalibration of one or both of the sensor and the instrument when the recognition of conditions indicates that the calibration is no longer valid; and

(d) repeating step (b).

4. A method according to claim 3 wherein the physiologic conditions are one or more of tissue and vascular damage, tissue edema, tissue scar formation, influence of a large vessel, change in vascular status, blood volume, vasodilation, vasoconstriction, changes in perfusion, changes in blood pressure, changes in tissue pressure, changes in tissue temperature, changes in blood temperature and changes in tissue metabolism.

5. A method according to claim 3 or 4 wherein the artifact conditions are one or more of sensor motion relative to the tissue, excessive sensor-tissue contact force inducing capillary collapse, insufficient sensor-tissue contact force resulting in insufficient sensor-tissue thermal communication, artifactual transduction of perfusion, sensor cross-talk, ambient temperature changes, electrical interference, and instrumentation drift.

6. A method for determining blood flow in tissue with automatic recalibration comprising the steps of:

(1) providing an apparatus for determining properties of tissue, comprising;

a computer;

a display in electrical communication with the computer;

a detector circuit in electrical communication with the computer;

a power supply in electrical communication, with the display and detector circuit;

a keypad in electrical communication with the detector circuit; and

a probe in electrical communication with the detector circuit;

(2) inserting the probe into the tissue;

(3) operating the device to perform the following steps;

(A) measuring the unperturbed temperature of the tissue at a selected location;

(B) determining if the temperature at the location is stable, wherein if the temperature is not stable then repeating step (A);

(C) raising the temperature of the tissue at the location a predetermined amount;

(D) measuring the elevated temperature at the location and calculating perfusion;

(E) repeating step (D) for a period of time;

(F) determining if the temperature of the tissue at the location is stable, wherein if the temperature is not stable, then repeating step (A);

(G) determining if a function of the power required in step (C) to raise the temperature of the tissue is less than an established maximum value, wherein if not less, then repeating step (A);

(H) determining if the total time the measurements have been taken over is less than an established maximum, wherein if the total is not less than the established maximum, then repeating step (A);

(I) repeating step (D).

7. In a method for determining flow in tissue, a method for automatic recalibration comprising the steps of:

(1) measuring the unperturbed temperature of the tissue at a selected location;

(2) determining if the temperature at the location is stable, wherein if the temperature is not stable then repeating step 1;

(3) raising the temperature of the tissue at the location a predetermined amount;

(4) measuring the elevated temperature at the location and calculating the perfusion;

(5) determining if the temperature of the tissue at the location is stable, wherein if the temperature is not stable, then repeating step 1;

(6) determining if a function of the power required in step (3) to raise the temperature of the tissue is less than an established maximum value, wherein if not less, then repeating step 1;

(7) determining if the total time over which the measurements have been taken is less than an established maximum, wherein if the total is not less than the established maximum, then repeating step 1;

(8) repeating step 3.

8. A method for monitoring perfusion in living tissue comprising:

determining baseline thermal conditions for a selected tissue location and establishing baseline criteria based thereon;

raising the temperature in said tissue location to a value above said thermal baseline;

computing values associated with one or more selected thermal properties of the tissue location;

computing blood flow using a value that is a function of the power required by said raising step and one or more of the selected thermal property values;

evaluating one or more conditions that may significantly change one or more of the thermal baseline and the selected thermal property values; and

determining the need for new baseline criteria using data from said evaluating step.

9. A method according to claim 8 further comprising the steps of:

repeating the second said computing step until the second said determining step indicates a need for new baseline criteria;

when a need for new baseline criteria is indicated discontinuing said raising step until said tissue location returns to an unperturbed state; and

repeating the first said determining step.

10. A method according to claim 8 wherein said evaluating step comprises evaluating selected artifact conditions for recognizing artifact conditions under which the established thermal baseline is no longer valid.

11. A method according to claim 10 wherein artifact conditions include one or more of:

ambient temperature changes,

electrical interference,

instrumentation drift,

excessive sensor-tissue contact force that can induce capillary collapse,

insufficient sensor-tissue contact force that can result in artifactual transduction of perfusion,

cross-talk between sensors, and

motion of the sensor relative to the tissue.

12. The method of claim 8 wherein said evaluating step comprises evaluating selected physiological conditions for recognizing conditions under which the established thermal baseline is no longer valid.

13. A method according to claim 12 wherein said evaluating step comprises evaluating selected artifact conditions for recognizing artifact conditions under which the established thermal baseline is no longer valid.

14. A method according to claim 12 wherein physiological conditions include one or more of:

tissue and vascular damage,

tissue edema,

tissue scar formation,

influence of a large vessel,

change in vascular status (e.g.;

blood volume, vasodilation, and vasoconstriction),

changes in perfusion,

changes in blood pressure,

changes in tissue pressure,

changes in tissue temperature,

changes in blood temperature, and

changes in tissue metabolism.

15. A method according to any one of claims 9, 10, 11, 12, 13, or 14 further comprising the step of automatically recalibrating baseline criteria for one or more of the probe and the instrumentation based on the results of the second said determining step.

16. In a method for determining blood flow in tissue comprising the steps of:

(1) causing temperature in the tissue to change from a first unperturbed temperature to a second temperature different from said first temperature during a time period;

(2) calculating at least one of an intrinsic thermal conductivity and a diffusivity of the tissue during a first selected portion of said time period;

(3) calculating a perfusion of the tissue at, at least a second selected portion of said time period, using said calculated intrinsic thermal conductivity and/or diffusivity;

(4) recalculating the intrinsic thermal conductivity and diffusivity of the tissue using said calculated perfusion;

(5) recalculating the perfusion of the tissue using said recalculated intrinsic thermal conductivity and diffusivity; and

(6) repeating steps (4) and (5) until the recalculated intrinsic thermal conductivity and diffusivity and the recalculated perfusion each converge to a substantially non-changing value;

the improvement comprising the steps of;

(a) prior to step (1), establishing baseline criteria corresponding to baseline thermal conditions of the tissue; and

(b) periodically determining the need for and establishing new baseline criteria.

17. A method for determining blood flow in tissue comprising the steps of:

(1) establishing baseline criteria for the tissue, comprising;

determining the thermal conductivity of a heating means, said heating means having a predetermined resistance versus temperature relationship;

immersing said heating means in the tissue; and

determining the reference temperature of the tissue when the tissue is unheated;

(2) obtaining measurements of the tissue comprising the steps of;

applying power to said heating means sufficiently rapidly to heat said means to a temperature above said reference temperature so that the power necessary to maintain said temperature varies as a function of time;

determining the time varying relationship between the power required to maintain said heating means at said temperature after said temperature has been reached and the time during which said power is being applied thereto;

determining the temperature difference between said temperature and said reference temperature and determining the resistance of said heating means at said temperature;

determining the thermal conductivity of the tissue as a function of said temperature difference, of the resistance of said heating means at said temperature, of said applied power in accordance with said time varying power and time relationship, of said predetermined thermal conductivity of said heating means, and of at least one characteristic dimension of said heating means in accordance with a thermal model of said heating means and the tissue in which it is immersed wherein said heating means is treated as a distributed thermal mass and wherein heat conduction occurs in a coupled thermal system which comprises both the heating means and the adjacent region of the tissue which surrounds said heating means; and

(3) determining need for new baseline criteria for tissue comprising evaluating one or both of measurement artifact conditions and physiological conditions.

18. The method of claim 17, further comprising the step:

(4) repeating steps (1) and (2) when indicated by step (3)

19. A method in accordance with claim 17, wherein step (1), the step of determining said reference temperature includes the steps of

applying a constant current or voltage through said heating means in its unheated state;

measuring the voltage or current at said heating means in its unheated state;

determining the resistance of said heating means in its unheated state; and

determining said reference temperature in accordance with the said predetermined resistance versus temperature relationship of said heating means.

20. A method in accordance with claim 17, where in step (2), the step of maintaining said temperature at said fixed value further includes the steps of

preselecting a fixed value for said temperature difference;

determining said maintained temperature from said reference temperature and said preselected fixed temperature difference;

determining the resistance of said heating means at said maintained temperature in accordance with said predetermined resistance versus temperature relationship; and

maintaining the resistance of said heating means at a substantially constant value equal to said determined resistance whereby said maintained temperature remains at a substantially constant value.

21. A method in accordance with claim 17, wherein said reference temperature varies with time over a relatively long time period and further including the steps of

determining said reference temperature value over said time period;

maintaining said temperature at a fixed, predetermined value, said fixed value being greater than said reference temperature over said time period;

determining the time-varying temperature difference between said fixed temperature and said time-varying reference temperature;

determining the fixed value of the resistance of said heating means at said fixed temperature; and

determining the thermal conductivity of the tissue over said time period in accordance with the expression

$k<br><br>\left(t\right)=\frac{5}{\frac{\mathrm{\Delta <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>T<br><br>\left(t\right)<br><br>R_h<br><br>20<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{\pi <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>\stackrel{\_}{a}}{V_h^2<br><br>\left(t\right)}-\frac{1.0}{k_b}}$

where k(t) is the thermal conductivity of the tissue, Δ

T is said temperature difference, R_h is the said fixed resistance of said heating means at said fixed temperature, a is the radius of a spherical heating means having a volume equivalent to the actual volume of said heating means, V_h(t) is the voltage at said heating means where said power is applied, and kb is said predetermined thermal conductivity of said heating means.

22. A method in accordance with claim 21, wherein the step of determining said reference temperature includes the steps of

immersing a temperature sensing means in the tissue at a region sufficiently remote from the immersed heating means so that the temperature sensed by said sensing element is not affected by the raised temperature of said heating means, said sensing means having a predetermined resistance versus temperature relationship;

determining over said time period the voltage at said sensing means and the current through said sensing means;

determining the reference temperature sensed by said sensing means over said time period in accordance with the said predetermined resistance versus temperature relationship thereof.

23. A method in accordance with claim 17, wherein said reference temperature varies with time over a relatively long time period and further including the steps of

determining said reference temperature over said time period;

determining the said maintained temperature over said time period as a function of said reference temperature and a preselected fixed value of said temperature difference;

maintaining the resistance of said heating means over said time period at a value such as to maintain the temperature difference between said maintained temperature and said reference temperature at said preselected fixed value, said resistance varying as a function of time;

determining the thermal conductivity k(t) of the tissue over said time period in accordance with the expression;

$k<br><br>\left(t\right)=\frac{5}{\frac{\mathrm{\Delta <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>T<br><br>\left(t\right)<br><br>R_h<br><br>20<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{\pi <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>\stackrel{\_}{a}}{V_h^2<br><br>\left(t\right)}-\frac{1.0}{k_b}}$

where Δ

T is said temperature difference, R_h(t) is said resistance of said heating means at said maintained temperature, a is the radius of a spherical heating means having a volume equivalent to the actual volume of said heating means, V_h(t) is the voltage at said heating means when said power is applied and kb is the predetermined thermal conductivity of said heating means.

24. A method in accordance with claim 23, wherein the step of determining said reference temperature includes the steps of

immersing a temperature sensing means in the tissue at a region sufficiently remote from the immersed heating means so that the temperature sensed by said sensing element is not affected by the raised temperature of said heating means, said sensing means having a predetermined resistance versus temperature relationship;

determining over said time period the voltage at said sensing means and the current through said sensing means;

determining the reference temperature sensed by said sensing means over said time period in accordance with the said predetermined resistance versus temperature relationship thereof.

25. A method in accordance with claim 17, wherein said reference temperature varies with time over a relatively long time period and further including the steps of

immersing a temperature sensing means in the tissue at a region sufficiently remote from the immersed heating means so that the temperature sensed by said sensing element is not affected by the raised temperature of said heating means, said sensing means having a predetermined resistance versus temperature relationship;

determining the resistance of said sensing means over said time period;

determining the reference temperature of said sensing means over said time period;

determining the desired resistance of said heating means over said time period as a function of the resistance of said sensing means and of a preselected fixed value of the resistance difference between the resistances of said sensing means and said heating means;

maintaining the resistance of said heating means at said desired resistance value over said time period so that said resistance difference remains at said preselected fixed value, the resistance of said heating means varying as a function of time;

determining the mean temperature of said heating means over said time period at the said desired resistance value of said heating means, said mean temperature varying as a function of time;

determining the temperature difference between said mean temperature and said reference temperature over said time period, said temperature difference varying as a function of time;

determining the thermal conductivity k(t) of the tissue over said time period in accordance with the expression;

$k<br><br>\left(t\right)=\frac{5}{\frac{\mathrm{\Delta <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>T<br><br>\left(t\right)<br><br>R_h<br><br>20<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{\pi <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>\stackrel{\_}{a}}{V_h^2<br><br>\left(t\right)}-\frac{1.0}{k_b}}$

where Δ

T(t) is said temperature difference, R_h(t) is said resistance of said heating means at said mean temperature, a is the radius of a spherical heating means having a volume equivalent to the actual volume of said heating means, V_h(t) is the voltage at said heating means when said power is applied and k_b is the predetermined thermal conductivity of said heating means.

26. A method in accordance with claim 25, wherein the step of determining said reference temperature includes the steps of

immersing a temperature sensing means in the tissue at a region sufficiently remote from the immersed heating means to that the temperature sensed by said sensing element is not affected by the raised temperature of said heating means, said sensing means having a predetermined resistance versus temperature relationship;

determining over said time period the voltage at said sensing means and the current through said sensing means;

determining the reference temperature sensed by said sensing means over said time period in accordance with the said predetermined resistance versus temperature relationship thereof.

27. A method for determining thermal properties of tissue comprising the steps of:

(1) establishing a baseline criteria for the tissue, comprising

(A) determining an unperturbed temperature of the tissue;

(B) causing the temperature of the tissue to change from a first unperturbed temperature to a second temperature different from said first temperature during a time period; and

(C) calculating a thermal property value for the tissue as a function of the intrinsic thermal conductivity and a diffusivity of the tissue during a first selected portion of said time period;

(2) obtaining measurements of the tissue comprising the steps of;

(A) calculating a perfusion of the tissue during a second selected portion of said time period using said calculated intrinsic thermal conductivity and diffusivity related value;

(B) re-calculating the intrinsic thermal conductivity and diffusivity of the tissue using said calculated perfusion;

(C) re-calculating the perfusion of the tissue using said recalculated intrinsic thermal conductivity and diffusivity related value; and

(D) repeating steps (2B) and (2C) until the re-calculated intrinsic thermal conductivity and diffusivity and the re-calculated perfusion each converge to a substantially non-changing value; and

(3) evaluating one or more measurement artifact conditions and physiological conditions to determine if baseline conditions established by step (1) are materially affected by said conditions.

28. The method of claim 27, further comprising the step:

(4) repeating step (1) when materially affected baseline conditions are indicated by step (3)

29. A method in accordance with claim 27, wherein step (1)(B) includes

immersing a temperature changing means in the tissue;

and

activating said temperature changing means so as to cause said means to change the temperature of the tissue.

30. A method in accordance with claim 27, wherein in step (1)(C) the intrinsic thermal conductivity and diffusivity are calculated at a first selected portion of said first time period.

31. A method in accordance with claim 30, wherein in step (2)(A) the perfusion is calculated at a second selected portion of said first time period.

32. A method in accordance with claim 27, wherein step (1)(B) includes

immersing a heating means in the tissue;

applying power to said heating means to heat the tissue from said first unperturbed temperature to said second temperature;

and step (1)(C) includes

shutting off the power to said heating means to cause the temperature of the tissue to decay to said final unperturbed temperature prior to the second selected portion of said time period.

33. A method for determining thermal properties of tissue comprising the steps of

establishing baseline thermal criteria corresponding to baseline thermal conditions of the tissue;

inducing a temperature change in the tissue as a function of time;

calculating at least one selected intrinsic thermal property of the tissue using data obtained at a first time period;

calculating separately a perfusion rate of the tissue using data obtained at a second time period and said at least one calculated intrinsic thermal property, the effects of the perfusion of the tissue at said second time period being greater than the effects of the perfusion of the tissue at said first time period; and

determining the need for new baseline criteria for the tissue when baseline thermal conditions materially change.

34. A method according to claim 33 wherein said determining step comprises the step of evaluating one or more physiological and artifactual conditions that may adversely affect the validity of the established baseline criteria

35. A method according to claim 34 wherein the artifactual conditions comprise one or more of:

ambient temperature changes,

electrical interference,

instrumentation drift,

excessive sensor-tissue contact force that can induce capillary collapse,

insufficient sensor-tissue contact force that can result in artifactual transduction of perfusion,

cross-talk between sensors, and

motion of the sensor relative to the tissue.

36. A method according to claim 34 wherein the physiological conditions comprise one or more of:

tissue and vascular damage,

tissue edema,

tissue scar formation,

influence of a large vessel,

change in vascular status (e.g.;

blood volume, vasodilation, and vasoconstriction),

changes in perfusion,

changes in blood pressure,

changes in tissue pressure,

changes in tissue temperature,

changes in blood temperature, and

changes in tissue metabolism.

37. A method according to any one of claims 33, 34, 35 or 36 further comprising the step of automatically recalibrating baseline criteria for one or more of the probe and the instrumentation based on the results of said determining step.

38. A method according to claim 33 wherein said determining step comprises evaluating one or more conditions that may adversely affect the validity at the changed temperature of the established baseline thermal criteria.

39. A method for determining the perfusion in live tissue with automatic recalibration comprising the steps:

1) measuring the temperature of the tissue at a selected location;

2) determining if the temperature at the selected location is stable, wherein if the temperature is not stable then repeating step 1;

3) raising the temperature of the tissue at the selected location a predetermined amount;

4) measuring the power provided in step (3) to maintain the raised temperature;

5) measuring the temperature at the selected location and calculating the perfusion;

6) repeating step 5 for a period of time;

7) determining if the temperature of the tissue at the selected location is stable, wherein if the temperature is not stable, then repeating step 1;

8) determining if a function of the power measured in step (4) is less than an established maximum value, wherein if not less than the established maximum, then repeating step 1;

9) determining if the total time the measurements have been taken over is less than an established maximum, wherein if the total is not less than the established maximum, then repeating step 1;

10) repeating step 5.

40. A method for determining thermal properties of tissue with automatic recalibration comprising the steps:

1) providing an apparatus for determining properties of tissue, comprising;

a computer,

a display in electrical communication with the computer,

a detector circuit in electrical communication with the computer,

a power supply in electrical communication with the computer, display and detector circuit;

a keypad in electrical communication with the detector circuit, and

a probe in electrical communication with the detector circuit;

2) inserting the probe into the tissue;

3 having/operating the device perform the following steps;

A) measuring the temperature of the tissue at a selected location;

B) determining if the temperature at the selected location is stable, wherein if the temperature is not stable then repeating step 1;

C) raising the temperature of the tissue at the selected location a predetermined amount;

D) measuring the temperature at the selected location and calculating the perfusion;

E) repeating step D for a set period of time;

F) determining if the temperature of the tissue at the selected location is stable, wherein if the temperature is not stable, then repeating step 1;

G) determining if the rate of perfusion is less than an established maximum value, wherein if rate of perfusion is not less than the established maximum, then repeating step A;

H) determining if the total time the measurements have been taken over is less than an established maximum, wherein if the total is not less than the established maximum, then repeating step A;

I) repeating step D.

41. A method comprising the steps:

1) measuring T1 and T2;

2) determining if T1 and T2 are stable;

3) if T1 and T2 are not stable, then repeating step 1;

4) if T1 and T2 are stable, then setting T2 to T2+DT;

5) measuring TI and calculating P2;

6) determining if P2 data has been acquired for a selected time period;

7) if 10 seconds of P2 data not acquired, then repeat step 5;

8) if 10 seconds of P2 data has been acquired, then calculating K_m;

9) calculating w;

10) determining if T1 is stable;

11) if T1 is not stable, then repeating step 1;

12) if T1 is stable, then determining if dP2/dt is less than dP/dt(max);

13) if dP2/dt is not less than dP/dt(max), then repeating step 1;

14) if dP2/dt is less than dP/dt(max), then determining if t is less than t(max);

15) if t is not less than t(max), then repeating step 1;

16) if t is less than t(max), then repeating step 5.

42. A method for determining thermal properties of tissue comprising the steps of:

(1) establishing baseline criteria corresponding to the baseline thermal conditions of the tissue, comprising;

contacting the tissue with a heating means having a predetermined resistance versus temperature relationship; and

determining a reference temperature for the tissue when the tissue is unheated;

(2) obtaining measurements of the tissue comprising the steps of;

applying power to said heating means sufficiently rapidly to heat said heating means to a temperature above said reference temperature so that the power necessary to maintain said temperature varies as a function of time;

determining the time varying relationship between the power required to maintain said heating means at said temperature after said temperature has been reached and the time during which said power is being applied thereto;

determining the temperature difference between said heating means temperature and said reference temperature and determining the resistance of said heating means at said temperature;

determining the thermal conductivity of the tissue as a function of said temperature difference, of the resistance of said heating means at said temperature, and of said applied power in accordance with said time varying power and time relationship; and

(3) evaluating one or more physiological and measurement artifact conditions to determine if baseline criteria established in step (1) are materially affected thereby and if so

(4) repeating step (1).

43. A method for determining thermal properties of tissue comprising the steps of:

(1) establishing baseline criteria corresponding to the baseline thermal conditions of the tissue, comprising;

determining the thermal conductivity of a heating means as a function of temperature;

contacting the tissue with said heating means; and

determining a reference temperature of the tissue when the tissue is unheated;

(2) obtaining measurements of tissue comprising the steps of;

applying power to said heating means sufficiently rapidly to heat said heating means to a temperature above said reference temperature so that the power necessary to maintain said temperature varies as a function of time;

determining the time varying power and time relationship between the power required to maintain said temperature and the time during which said power is applied to said heating means;

determining the temperature difference between said temperature and said reference temperature;

determining the thermal conductivity of the tissue as a function of said temperature difference, and of said applied power in accordance with said time varying power and time relationship; and

(3) evaluating one or more physiological and measurement artifact conditions to determine if baseline criteria established in step (1) are materially affected thereby and if so

(4) repeating step (1).

44. A system for monitoring perfusion in living tissue comprising:

a sensor adapted for thermal contact with tissue at a selected location;

means for determining system baseline criteria corresponding to baseline thermal conditions of the tissue;

a heater for changing the temperature of tissue at said location;

means for determining a perfusion related value for tissue at said location as a function of data from said sensor and the output of said heater; and

means for evaluating one or more conditions that may affect system baseline criteria and assessing the validity at the changed temperature of the system baseline criteria.

45. A system according to claim 44 wherein said evaluating means evaluates conditions selected from one or more physiological conditions and artifactual conditions that may change to affect system baseline criteria as a basis for assessing the validity of the system baseline criteria.

46. A system according to claim 45 wherein said calibrating means evaluates one or more conditions selected from artifactual probe and instrument conditions.

47. A system according to claim 45 wherein the artifactual conditions evaluated comprise one or more of:

ambient temperature changes,

electrical interference,

instrumentation drift,

excessive sensor-tissue contact force that can induce capillary collapse,

insufficient sensor-tissue contact force that can result in artifactual transduction of perfusion,

cross-talk between sensors, and

motion of the sensor relative to the tissue.

48. A system according to claim 45 wherein the physiological conditions evaluated comprise one or more of:

tissue and vascular damage,

tissue edema,

tissue scar formation,

influence of a large vessel,

change in vascular status (e.g.;

blood volume, vasodilation, and vasoconstriction),

changes in perfusion,

changes in blood pressure,

changes in tissue pressure,

changes in tissue temperature,

changes in blood temperature, and

changes in tissue metabolism.

49. A system according to any one of claims 44, 45, 46, 47 or 48 further comprising means for indicating a need for new system baseline criteria in response to the assessment of said evaluating means.

50. A system according to any one of claims 44, 45, 46, 47 or 48 further comprising means for automatically recalibrating system baseline criteria for one or more of the probe and the instrumentation based on the evaluation of said evaluating means.

51. Apparatus for determining the perfusion of blood in living tissue comprising:

means in thermal contact with the tissue for sensing the reference temperature of the tissue when the tissue is unheated;

means in thermal contact with the tissue for heating the tissue;

means for applying power to said heating means sufficiently rapidly to raise the temperature of said heating means to a temperature above said reference temperature so that the power necessary to maintain said heating means temperature varies as a function of time;

data processing means for determining the temperature difference between said heating means temperature and said reference temperature, for determining the resistance of said heating means at said heating means temperature and for determining the time varying relationship between the power required to maintain said heating means at said heating means temperature after said temperature has been reached and the time during which said power is being applied thereto;

said data processing means further being responsive to said temperature difference, said heating means resistance and said time varying power and time relationship for determining a perfusion related value;

means for evaluating conditions that affect the reference temperature of the tissue and recognizing conditions under which the reference temperature is no longer valid; and

means for providing an output in response to said evaluating and recognizing means.

52. Apparatus according to claim 51 further comprising means for automatically calibrating said sensing means in response to said output.

53. Apparatus according to claim 51 wherein said recognizing means comprises means for recognizing one or more physiological and artifactual conditions.

54. Apparatus according to claim 53 wherein the artifactual conditions comprise one or more of:

ambient temperature changes,

electrical interference,

instrumentation drift,

excessive sensor-tissue contact force that can induce capillary collapse,

insufficient sensor-tissue contact force that can result in artifactual transduction of perfusion,

cross-talk between sensors, and

motion of the sensor relative to the tissue.

55. A system according to claim 53 wherein the physiological conditions comprise one or more of:

tissue and vascular damage,

tissue edema,

tissue scar formation,

influence of a large vessel,

change in vascular status (e.g.;

blood volume, vasodilation, and vasoconstriction), changes in perfusion,

changes in blood pressure,

changes in tissue pressure,

changes in tissue temperature,

changes in blood temperature, and

changes in tissue metabolism.

56. Apparatus for determining thermal properties of living tissue comprising:

means adapted to contact tissue for sensing a reference temperature of the tissue when the tissue is unheated;

means for heating tissue including tissue contacted by said heating means, said heating means having a predetermined thermal conductivity and a predetermined thermal diffusivity;

means for applying power to said heating means sufficiently rapidly to raise the temperature of said heating means above said reference temperature so that the power necessary to maintain said heating means temperature varies as a function of time;

data processing means for determining the temperature difference between said heating means temperature and said reference temperature, for determining the resistance of said heating means at said heating means temperature and for determining the time varying relationship between the power required to maintain said heating means at said temperature after said temperature has been reached and the time during which said power is being applied thereto;

said data processing means further being responsive to said temperature difference, said heating means resistance, said applied power in accordance with said time varying power and time relationship, said predetermined thermal conductivity of said heating means, and a change in said reference temperature for determining the thermal conductivity of the tissue.

57. Apparatus in accordance with claim 56, wherein said sensing means and said heating means comprises a single element capable of sensing the temperature of the tissue and of heating the tissue.

58. Apparatus in accordance with claim 57 wherein said single element is a thermistor bead element.

59. Apparatus in accordance with claim 57, and further including means for maintaining said heating means temperature at a fixed, predetermined value above said reference temperature, said reference temperature being determined and said heating means temperature being maintained over a relatively short time interval during which said reference temperature remains substantially constant whereby said temperature difference and the resistance of said heating means also remain substantially constant.

60. Apparatus in accordance with claim 56, wherein said heating means and said sensing means comprise respectively

a first heating element adapted to be immersed at a first region of the tissue;

and

a second element adapted to be immersed at a second region of the tissue sufficiently remote from said first region as to be not materially affected by the heating of said first element.

61. Apparatus in accordance with claim 60 wherein said first and second elements are thermistor bead elements.

62. Apparatus in accordance with claim 60, for use over a relatively long time period during which said reference temperature varies with time and wherein said second element determines said reference temperature over said time period;

and further including

means for maintaining said first element temperature and the resistance of said first element at said first element temperature at fixed predetermined values over said time period during which said reference temperature varies whereby the temperature difference there between varies over said time period.

63. Apparatus in accordance with claim 60, for use over a relatively long time period during which said reference temperature varies with time wherein said second element determines said reference temperature over said time period;

and further including

means for determining the first element temperature over said time period as a function of said reference temperature and a preselected fixed value of said temperature difference;

means for maintaining the resistance of said first element over said time period at a value such as to maintain the temperature difference between said first element temperature and said reference temperature at said preselected fixed value, said resistance varying as a function of time; and

means for determining the thermal conductivity of the tissue over said time period as a function of said temperature difference, said resistance of said first element, the power applied to heat said first element and said thermal conductivity of said first element.

64. Apparatus in accordance with claim 63, wherein said data processing system includes

means for determining the intrinsic thermal conductivity k_m of the tissue when no fluid is flowing therein;

means for determining the effective thermal conductivity k_eff(t) of the tissue when a fluid having a predetermined heat capacity is flowing therein;

means for determining the ratio of k_eff(t)/k_m over said time period; and

means for determining the rate of flow ω

(t) of said fluid in the tissue as a function of said ratio.

65. Apparatus in accordance with claim 60, for use over a relatively long time period during which said reference temperature varies with time wherein said second element determines said reference temperature over said time period;

and further including

means for determining the resistance of said second element over said time period;

means for determining the desired resistance of said first element over said time period as a function of the resistance of said second element and of a preselected fixed value of the resistance difference between the resistances of said second and said first elements;

means for maintaining the resistance of said first element at said desired resistance so that said resistance difference is maintained at said predetermined fixed value, the resistance of said second element varying as a function of time;

means for determining the temperature of said first element over said time period at said desired resistance of said first element, said temperature varying as a function of time;

means for determining the temperature difference between said first element temperature and said reference temperature over said time period, said temperature difference varying as a function of time;

means for determining the thermal conductivity of the tissue over said time period as a function of said temperature difference, said resistance of said first element, the power applied to heat said first element and the conductivity of said first element.

66. Apparatus in accordance with claim 65, wherein said data processing system includes

means for determining the intrinsic thermal conductivity k_m of the tissue when no fluid is flowing therein;

means for determining the effective thermal conductivity k_eff(t) of the tissue when a fluid having a predetermined heat capacity is flowing therein;

means for determining the ratio of k_eff(t)/k_m over said time period; and

means for determining the rate of flow ω

(t) of said fluid as a function of said ratio.

67. An apparatus for determining thermal properties of living tissue, comprising:

a computer;

a display in electrical communication with the computer;

a detector circuit in electrical communication with the computer;

a power supply in electrical communication with the detector circuit;

a keypad in electrical communication with the detector circuit; and

a probe in electrical communication with the detector circuit.

68. The apparatus of claim 67, further comprising an external serial port in electrical communication with the detector circuit.

69. The apparatus of claim 67, further comprising an external output, selected from the formats of analog and/or digital.

70. The apparatus of claim 67, wherein the computer is a single board computer.

71. The apparatus of claim 67, wherein the computer comprises a first and second serial port.

72. The apparatus of claim 67, wherein the display is a flat panel display.

73. The apparatus of claim 67, wherein the first power supply is an isolated power supply.

74. The apparatus of claim 67, wherein the second power supply is an un-isolated power supply.

75. The apparatus of claim 67, wherein the detector circuit comprises:

an isolated component comprising;

a processor,

a control circuit in electrical communication with the processor, and

at least one analog to digital converter.

76. A method for determining perfusion in living tissue comprising the steps of:

(1) establishing baseline criteria, comprising

(A) determining an unperturbed temperature of the tissue;

(B) causing the temperature of the tissue to change from a first unperturbed temperature to a second temperature different from said first temperature for a time period, and

(C) determining a value or values for one or more thermal properties of tissue during said time period;

(2) calculating a perfusion value for the tissue during said time period using said thermal property value or values, and

(3) evaluating one or more physiological and artifactual conditions to determine if baseline criteria established by step (1) are materially affected by said conditions and if so repeating step (1).

77. A method according to claim 76 wherein said thermal properties include one or both of thermal conductivity and thermal diffusivity.