Method and system for detecting electrophysiological changes in pre-cancerous and cancerous tissue

• US 20030216661A1
• Filed: 05/20/2002
• Published: 11/20/2003
• Est. Priority Date: 05/20/2002
• Status: Active Grant

• Current Assignee: Epi-Sci, LLC
• Original Assignee: Richard J. Davies
• Inventors: Davies, Richard J.
• Granted Patent: US 6,922,586 B2
• Time in Patent Office: Days
• US Class Current: 600/547
• CPC Class Codes: A61B 5/0531 Measuring skin impedance
• CPC Class Codes: A61B 5/0538 invasively, e.g. using a catheter
• CPC Class Codes: A61B 5/2415 Measuring direct current [DC] or slowly varying biopotentials
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence
• CPC Class Codes: A61B 5/4381 Prostate evaluation or disorder diagnosis
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6806 Gloves
• CPC Class Codes: A61B 5/6834 using vacuum

Abstract

A method and system are provided for determining a condition of a selected region of epithelial tissue. At least two current-passing electrodes are located in contact with a first surface of the selected region of the tissue. A plurality of measuring electrodes are located in contact with the first surface of the selected region of tissue as well. Electropotential and impedance are measured at one or more locations. An agent may be introduced into the region of tissue to enhance electrophysiological characteristics. The condition of the tissue is determined based on the electropotential and impedance profile at different depths of the epithelium, tissue, or organ, together with an estimate of the functional changes in the epithelium due to altered ion transport and electrophysiological properties of the tissue.

Claims

1. A method for determining a condition of a region of epithelial tissue comprising:

placing at least two current-passing electrodes in contact with or in proximity to a surface of the selected region of tissue;

placing a plurality of measuring electrodes in contact with or in proximity to the surface of the selected region of tissue;

establishing a signal between the current-passing electrodes;

measuring, at one or more of the measuring electrodes, an impedance associated with the established signal;

introducing at least one agent into the selected region of tissue;

measuring, at one or more of the measuring electrodes, an impedance associated with the established signal following the introduction of the at least one agent; and

determining the condition of the selected region of tissue based on the measured impedance, following the introduction of the at least one agent.

2. The method of claim 1, wherein placing of the current-passing electrodes includes the step of:

placing a probe in contact with or in proximity to the surface of the selected region of tissue, wherein the current-passing electrodes are situated on the probe.

3. The method of claim 1, wherein placing of the measuring electrodes includes the step of:

contacting a placing a probe in contact with or in proximity to the surface of the selected region of tissue, wherein the measuring electrodes are situated on the probe.

4. The method of claim 1, wherein the step of determining the condition of the selected region of tissue includes:

rating the tissue based on one of the following ratings;

normal, at-risk, pre-cancerous, or cancerous.

5. A method for determining a condition of a region of epithelial tissue comprising:

placing at least one current-passing electrodes in contact with or in proximity to a surface of the selected region of tissue;

placing a plurality of measuring electrodes in contact with or in proximity to the surface of the selected region of tissue;

establishing a signal between at least one current-passing electrode and at least one of the measuring electrodes;

measuring, at one or more of the measuring electrodes, an impedance associated with the established signal;

introducing at least one agent into the selected region of tissue;

measuring, at one or more of the measuring electrodes, an impedance associated with the established signal following the introduction of the at least one agent; and

determining the condition of the selected region of tissue based on the measured impedance, following the introduction of at least one agent.

6. The method of claim 5, wherein placing of the current-passing electrodes includes the step of:

placing a probe in contact with or in proximity to the surface of the selected region of tissue, wherein the current-passing electrodes are situated on the probe.

7. The method of claim 5, wherein placing of the measuring electrodes includes the step of:

placing a probe in contact with or in proximity to the surface of the selected region of tissue, wherein the measuring electrodes are situated on the probe.

8. The method of claim 5, wherein the step of determining the condition of the selected region of tissue includes:

rating the tissue based on one of the following ratings;

normal, at-risk, pre-cancerous, or cancerous.

9. A method for measuring electrical properties of an epithelium, having a surface, using a combination of DC electrical measurements and impedance spectroscopy, comprising the steps of:

measuring a DC potential at the surface of the epithelium with a first and a second voltage-measuring electrodes, wherein the voltage-measuring electrodes are associated with a reference point;

placing a pair of current-passing electrodes in contact with or in proximity to the epithelium adjacent to the voltage-measuring electrodes;

detecting, via the voltage-sensing electrodes, a resulting electrical signal at different points on the epithelial surface;

applying an electrical signal to the pair of current-passing electrodes at a plurality of frequencies;

monitoring the resulting electrical signal at the voltage-sensing electrodes associated with each of the plurality of frequencies; and

determining the impedance of the epithelium associated with the voltage-sensing electrodes based on each of the plurality of frequencies and the resulting electrical signal associated with each of the plurality of frequencies.

10. The method of claim 9, wherein the reference point includes an intravenous electrode or a skin electrode with low skin impedance.

11. The method of claim 9, further including the steps of:

positioning a depth electrode;

detecting, via the depth electrode, a resulting electrical signal;

monitoring the resulting electrical signal at the depth electrode associated with each of the plurality of frequencies; and

determining the impedance of the epithelium associated with the depth electrode and one of the first or second voltage-sensing electrodes based on each of the plurality of frequencies and the resulting electrical signal associated with each of the plurality of frequencies; and

determining a difference in the impedance associated with the voltage-sensing electrodes and the impedance associated with the depth electrode.

12. The method of claim 11, wherein the step of determining the difference in the impedance includes the step of:

subtracting the impedance associated with the voltage-sensing electrodes from the impedance associated with the depth electrode and one of the first or the second voltage-sensing electrodes.

13. The method of claim 11, wherein the step of positioning the depth electrode includes the step of:

placing the depth electrode in contact with or in proximity to the surface of the epithelium at a different location than the voltage-sensing electrodes.

14. The method of claim 9, wherein the first voltage-sensing electrode includes an electroconductive medium (ECM) having a first concentration and the second voltage-sensing electrode includes the ECM having a second concentration, further including the step of:

estimating an ionic conductance of the epithelium based on the impedance associated with the voltage-sensing electrodes and the ECM concentrations.

15. The method of claim 9, wherein the first voltage-sensing electrode includes an electroconductive medium (ECM) including a first agent and the second voltage-sensing electrode includes the ECM including a second agent, further including the step of:

estimating an ionic conductance of the epithelium based on the impedance associated with the voltage-sensing electrodes and the ECM agents.

16. The method of claim 9, wherein the applied electrical signal includes low and high frequency sinusoidal alternating currents.

17. The method of claim 16, wherein the sinusoidal alternating currents are applied sequentially.

18. The method of claim 16, wherein the sinusoidal alternating currents are applied in a composite form.

19. The method of claim 9, wherein the resulting electrical signal is a real part of a resulting potential difference measured over a current path across the current-passing electrodes.

20. The method of claim 9, wherein the plurality of frequencies falls within the range of 0.2-6000 Hz.

21. The method of claim 9, wherein the plurality of frequencies falls within the range of 2 to 800 kHz.

22. The method of claim 9, further including the step of:

filtering the resulting electrical signal using a low-pass filter.

23. The method of claim 9, further including the step of:

reducing a DC component of the resulting signal using a band-pass filter.

24. A method for measuring electrical properties of an epithelium, having a surface, using a combination of DC electrical measurements and impedance spectroscopy, comprising the steps of:

measuring a DC potential at the surface of the epithelium with a first and a second voltage-measuring electrodes, wherein the voltage-measuring electrodes are associated with a reference point;

placing at least one current-passing electrodes in contact with or in proximity to the epithelium adjacent to the voltage-measuring electrodes;

detecting, via the voltage-measuring electrodes, a resulting electrical signal at different points on the epithelial surface;

applying an electrical signal to at least one of the current-passing electrodes and at least one of the voltage measuring electrodes at a plurality of frequencies;

monitoring the resulting electrical signal at the voltage-measuring electrodes associated with each of the plurality of frequencies; and

determining the impedance of the epithelium associated with the voltage-measuring electrodes based on each of the plurality of frequencies and the resulting electrical signal associated with each of the plurality of frequencies.

25. An apparatus for determining the condition of tissue of an epithelium using a combination of surface DC electrical measurements and impedance spectroscopy, the apparatus comprising:

a first pair of spaced electrodes for applying an electrical signal to the epithelium;

a second pair of spaced electrodes for detecting a resulting electrical signal at different points on the epithelium;

a means for applying the electrical signal to the first pair of electrodes at a plurality of frequencies;

a means for measuring the resulting electrical signal at the second pair of electrodes at said plurality of frequencies;

a means for obtaining a measure of the impedance of a part of the epithelium based on the resulting electrical signal; and

a means for obtaining a difference signal representing a change in impedance with frequency.

26. The apparatus of claim 25, further comprising:

one or more additional pairs of electrodes placed at different locations than the first or second pairs of electrodes; and

a means for measuring a resulting electrical signal between the additional pairs of electrodes; and

a means for estimating an impedance for different layers of the epithelium by subtracting the impedance values from two pairs of electrodes at each frequency.

27. The apparatus of claim 25, wherein the second pair of electrodes includes different ECM concentrations for estimating the specific ionic conductance of the epithelium.

28. The apparatus of claim 25, wherein the second pair of electrodes includes different ECM agents for estimating the specific ionic conductance of the epithelium.

29. The apparatus of claim 25, wherein the means for applying the electric signal includes:

a signal generator for producing simultaneously a plurality of low and high frequency constant alternating current signals; and

a connection means for supplying such signals to the first pair of electrodes.

30. The apparatus of claim 25, wherein the means for measuring the resulting electrical signal includes:

at least one adjustable gain voltage amplifier.

31. The apparatus of claim 25, wherein the means for obtaining the difference signal includes a microprocessor computing device.

32. The apparatus of claim 31, wherein the microprocessor computing device includes a low-pass filter.

33. The apparatus of claim 31, wherein the microprocessor computing device includes at least one of a band-pass filter and a high pass filter.

34. An apparatus for diagnosing abnormal tissue using a combination of DC electrical measurements and impedance spectroscopy and variably spaced electrodes with electroconductive medium having ionic compositions to monitor the effects of various pharmacological agents and hormones, the apparatus comprising:

a first pair of spaced electrodes for applying an electrical signal to an epithelium;

at least one pair of voltage-sensing electrodes having electroconductive medium of different ionic composition to measure DC potential at different ionic concentrations;

a second pair of spaced electrodes for detecting a resulting electrical signal at different points on the epithelium;

a means for applying an agent;

a means for examining temporal changes in electrical properties of the epithelium responsive to the agent;

a signal generating device for applying electrical signal to the first pair of electrodes at a plurality of frequencies;

a monitoring device for monitoring the resulting electrical signal at the second pair of electrodes at the plurality of frequencies;

a computing device configured to perform the following steps;

obtaining the specific ionic conductance and permeability of the epithelium based on the resulting electrical signals at different electroconductive medium compositions;

comparing the resulting electrical signals, specific ionic conductances and permeabilities over an area of suspected abnormality with adjacent and more distant regions of the epithelium;

obtaining from the resulting electrical signal a measure of impedance of a part of the epithelium at the plurality of frequencies;

comparing the impedance over the area of suspected abnormality with the adjacent and more distant regions of the epithelium;

obtaining a difference signal representing an impedance change with frequency;

comparing the impedance over the area of suspected abnormality with the adjacent and more distant regions of the epithelium;

subtracting the impedance measurement made between a first set of electrodes from the impedance measurement made between a second set of electrodes to estimate the impedance at different layers of the epithelium, wherein the distance between the first set of electrodes is less than the distance between the second set of electrodes;

comparing the impedance at different layers of the epithelium over the area suspected of abnormality with adjacent and more distant regions of the epithelium;

comparing electrical properties of the epithelium influenced by agents at different layers of the epithelium over the area suspected of abnormality with adjacent and more distant regions of the epithelium; and

comparing electrical properties of the epithelium at different times influenced by variations in temporal factors at different layers of the epithelium over the area of suspected abnormality with adjacent and more distant regions of the epithelium.

35. A method for determining the condition of a tissue, comprising:

measuring a first DC potential of an area of tissue using a first electroconductive medium;

measuring a second DC potential of said area of tissue using a second electroconductive medium that differs in its ionic concentration from said first electroconductive medium; and

comparing said first and second measurements to determine the condition of said tissue.

36. A method for determining the condition of a tissue, comprising:

measuring a first DC potential of an area of tissue using a first electroconductive medium;

administering at least one agent; and

measuring a second DC potential of said area of tissue after said step of administering at least one agent;

comparing said first and second measurements to determine the condition of said tissue.

37. A method for determining the condition of a tissue, comprising:

measuring a first DC potential of an area of tissue using a first electroconductive medium;

allowing a period of time to pass;

measuring a second DC potential of said area of tissue after said period of time has passed; and

comparing said first and second measurements to determine the condition of said tissue.

38. A method for determining the condition of a tissue, comprising:

measuring a first impedance of an area of tissue using a first electroconductive medium;

measuring a second impedance of said area of tissue using a second electroconductive medium that differs in its ionic concentration from said first electroconductive medium; and

comparing said first and second measurements to determine the condition of said tissue.

39. A method for determining the condition of a tissue, comprising:

measuring a first impedance of an area of tissue using a first electroconductive medium;

administering at least one agent;

measuring a second impedance of said area of tissue after said step of administering at least one agent; and

comparing said first and second measurements to determine the condition of said tissue.

40. A method for determining the condition of a tissue, comprising:

measuring a first impedance of an area of tissue using a first electroconductive medium;

allowing a period of time to pass;

measuring a second impedance of said area of tissue after said period of time has passed; and

comparing said first and second measurements to determine the condition of said tissue.

41. A method for determining the condition of a tissue, comprising:

measuring a first DC potential and impedance of an area of tissue using a first electroconductive medium;

measuring a second DC potential and impedance of said area of tissue using a second electroconductive medium that differs in its ionic concentration from said first electroconductive medium; and

comparing said first and second measurements to determine the condition of said tissue.

42. A method for determining the condition of a tissue, comprising:

measuring a first DC potential and impedance of an area of tissue using a first electroconductive medium;

administering at least one agent;

measuring a second DC potential and impedance of said area of tissue after said step of administering at least one agent; and

comparing said first and second measurements to determine the condition of said tissue.

43. A method for determining the condition of a tissue, comprising:

measuring a first DC potential and impedance of an area of tissue using a first electroconductive medium;

allowing a period of time to pass;

measuring a second DC potential and impedance of said area of tissue after said period of time has passed;

comparing said first and second measurements to determine the condition of said tissue.

44. An apparatus for determining the condition of a tissue, comprising:

means for measuring at least one electrical property of an area of tissue using a first electroconductive medium;

means for measuring said at least one electrical property of said area of tissue using a second electroconductive medium that differs in its ionic concentration from said first electroconductive medium; and

means for comparing said measurements to determine the condition of said tissue.

45. The apparatus of claim 44, wherein said at least one electrical property is DC potential.

46. The apparatus of claim 44, wherein said at least one electrical property is impedance.

47. The apparatus of claim 44, further comprising means for measuring a plurality of electrical properties of an area of tissue, wherein at least one electrical property is DC potential and at least one electrical property is impedance.

48. An apparatus for determining the condition of a tissue, comprising:

means for measuring at least one electrical property of an area of tissue using a first electroconductive medium;

at least one agent;

means for measuring said at least one electrical property of said area of tissue after said agent is administered; and

means for comparing said measurements to determine the condition of said tissue.

49. The apparatus of claim 48, wherein said at least one electrical property is DC potential.

50. The apparatus of claim 48, wherein said at least one electrical property is impedance.

51. The apparatus of claim 48, further comprising means for measuring a plurality of electrical properties of an area of tissue, wherein at least one electrical property is DC potential and at least one electrical property is impedance.

52. An apparatus for determining the condition of a tissue, comprising:

means for making a first measurement of at least one electrical property of an area of tissue using a first electroconductive medium;

means for making a second measurement of said at least one electrical property of said area at a subsequent time to said first measurement; and

means for comparing said first and second measurements to determine the condition of said tissue.

53. The apparatus of claim 52, wherein said at least one electrical property is DC potential.

54. The apparatus of claim 52, wherein said at least one electrical property is impedance.

55. The apparatus of claim 52, further comprising means for measuring a plurality of electrical properties of an area of tissue, wherein at least one electrical property is DC potential and at least one electrical property is impedance.