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

• US 20060100488A1
• Filed: 12/06/2005
• Published: 05/11/2006
• Est. Priority Date: 05/20/2002
• Status: Active Grant

• Current Assignee: Epi-Sci, LLC
• Original Assignee: Epi-Sci, LLC
• Inventors: Davies, Richard J.
• Granted Patent: US 8,262,575 B2
• Time in Patent Office: Days
• US Class Current: 600/306
• 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 5/6806 Gloves
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

Methods and systems are provided for determining a condition of a selected region of epithelial tissue and/or an organ in a body as well as to diagnose disease, susceptibility, premalignancy or cancer and to measure response to therapy, introduction of a drug and to assess the margins of a tumor or resection. The methods utilize through the tissue or organ electrical measurements with alternating current applied using one or more surface or internal electrodes and measuring the electrical response using one or more surface electrodes, preferably in combination with one or more electrodes in direct or indirect contact with epithelium comprising the organ or tissue under test. The methods are also useful in combination with DC measurements on the surface of the organ or tissue under test. Measurement of impedance, admittance, electropotential and dielectric properties is particularly useful, particularly as a function of frequency and position on and in the tissue or organ.

Claims

1. A method for determining a condition of a region of epithelial tissue or the condition of an organ associated with such 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 an electrical signal between the current-passing electrodes;

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

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

(1) determining the condition of the selected region of tissue based on the electrical measurement, following the introduction of the at least one agent;

or

(2) detecting a possible tumor by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

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:

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.

25. The method of claim 1 wherein the electrical measurement is impedance or admittance.

26. The method of claim 1 wherein the electrical signal is alternating current.

27. The method of claim 1 further comprising the step of determining the rate of change of dielectric constant with frequency or log of frequency at each of the localized regions.

5. A method for determining a condition of a region of epithelial tissue or the condition of an organ associated with such tissue comprising:

placing at least one current-passing electrode 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 an electrical 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 electrical measurement 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 electrical measurement associated with the established signal following the introduction of the at least one agent; and

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

(1) determining the condition of the selected region of tissue based on the measured impedance, following the introduction of at least one agent;

or

(2) detecting a possible tumor by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

6. The method of claim 5, wherein placing of the at least one current-passing electrode includes the step of:

placing a probe in contact with or in proximity to the surface of the selected region of tissue, wherein the at least one current-passing electrode is 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.

28. The method of claim 5 further comprising the step of determining the rate of change of dielectric constant with frequency or log of frequency at each of the localized regions.

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 at the different points on the epithelial surface;

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

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, wherein the reference point includes an intravenous electrode or a skin electrode with low skin impedance; and

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

measuring variations in the dielectric constants over a plurality of the regions.

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

14. The method of claim 9, wherein the first voltage-measuring electrode includes an electroconductive medium (ECM) having a first concentration and the second voltage-measuring 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-measuring electrodes and the ECM concentrations.

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

29. The method of claim 9 further comprising the step of determining the rate of change of dielectric constant with frequency or log of frequency at each of the localized regions.

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 or the admittance or both, 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; and

applying at least, one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

measuring variations in the dielectric constants over a plurality of the regions.

30. The method of claim 24 further comprising the step of determining the rate of change of dielectric constant with frequency or log of frequency at each of the localized regions.

31. A method for determining the condition of a tissue, said method comprising steps selected from the group consisting of:

(A)

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

(2) 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

(3) comparing said first and second measurements to determine the condition of said tissue;

(B)

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

(2) administering at least one agent; and

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

(4) comparing said first and second measurements to determine the condition of said tissue;

(C)

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

(2) allowing a period of time to pass;

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

(4) comparing said first and second measurements to determine the condition of said tissue;

(D)

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

(2) 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

(3) comparing said first and second measurements to determine the condition of said tissue;

(E)

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

(2) administering at least one agent;

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

(4) comparing said first and second measurements to determine the condition of said tissue;

(F)

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

(2) allowing a period of time to pass;

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

(4) comparing said first and second measurements to determine the condition of said tissue;

(G)

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

(2) 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

(3) comparing said first and second measurements to determine the condition of said tissue;

(H)

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

(2) administering at least one agent;

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

(4) comparing said first and second measurements to determine the condition of said tissue; and

(J)

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

(2) allowing a period of time to pass;

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

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

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

establishing a connection between a first electrode and the epithelial tissue of a breast;

placing a second electrode in contact with the surface of the breast;

establishing a signal between the first and second electrodes;

measuring an electrical property between the first and second electrode;

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

(1) determining the condition of a region of epithelial tissue based on the signal between the first and second electrode;

(2) detecting a possible tumor by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

33. The method of claim 32, wherein the electrical property is impedance or admittance.

34. The method of claim 32, wherein the electrical property is a DC potential.

35. The method of claim 32, wherein the method of establishing a connection between the first electrode and the epithelial tissue is by a cannula.

36. The method of claim 35, wherein the cannula is a ductal probe.

37. The method of claim 32, wherein the method of establishing a connection between the first electrode and the epithelial tissue is by an electroconductive media.

38. The method of claim 37, wherein the electroconductive media is a physiologic saline.

39. The method of claim 37, further comprising introducing an agent into the electroconductive media.

40. The method of claim 39, wherein the agent is a hormone.

41. A method for determining the location of a tumor in a body comprising:

establishing a connection between a first electrode and the epithelial tissue of the duct of an organ;

placing a second electrode at a second location on the body;

establishing a signal between the first and second electrodes;

measuring an electrical property between the first and second electrodes;

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones, of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

and

(1) determining the condition of the selected region of epithelial tissue based on the signal between the first and second electrode;

(2) detecting a possible tumor by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

42. The method of claim 41, wherein the second location is on the surface of the body.

43. The method of claim 41, wherein the epithelial tissue is located within the breast.

44. The method of claim 41, wherein the epithelial tissue is located within the prostate.

45. A method for determining the location of a tumor margin comprising:

measuring a first electrophysiological characteristic of an area of tissue to be removed;

measuring a second electrophysiological characteristic of an area of normal tissue;

applying at least one probe comprising a plurality of probe elements to an area of tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the area of tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the area of tissue;

and

determining the location of a tumor margin based on the difference in the first electrophysiological characteristic of the area of tissue to be removed and the second electrophysiological characteristic of the area of normal tissue and including the measured dielectric constants.

46. The method of claim 45, wherein the first electrophysiological characteristic and the second electrophysiological characteristic is an impedance of the tissue.

47. The method of claim 45, wherein the first electrophysiological characteristic and the second electrophysiological characteristic is the DC potential of the tissue.

48. The method of claim 45, further including introducing at least one agent into the area of tissue to be removed and the area of normal tissue.

49. The method of claim 45, wherein the area of normal tissue is adjacent to the area of tissue to be removed.

50. A method for determining the resection margin of an area of tissue comprising:

measuring a plurality of electrophysiological characteristics of an area of tissue to be removed from an area of normal tissue; and

applying at least one probe comprising a plurality of probe elements to organ tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the organ tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the organ tissue; and

determining the location of a resection margin between the area of tissue to be removed and the area or normal tissue based on the difference in the electrophysiological characteristics of the area of tissue to be removed and known electrophysiological characteristics of normal tissue, including sensing or measuring variations in the dielectric constants over a plurality of the regions.

51. The method of claim 50, wherein the plurality of electrophysiological characteristics are impedance and DC potential.

52. The method of claim 50, wherein the plurality of electrophysiological characteristics are measurements of impedance taken from at least two locations within the area of tissue to be removed from an area of normal tissue.

53. The method of claim 50, wherein the plurality, of electrophysiological characteristics are used to produce an electrophysiological profile of the area of tissue to be removed from an area of normal tissue.

54. The method of claim 53, wherein the electrophysiological profile is displayed on a monitor.

55. A method for facilitating the removal of an area of tissue comprising:

measuring the electrophysiological characteristic of the area of tissue to be removed;

comparing the electrophysiological characteristic of the area of tissue to be removed to the electrophysiological characteristic of an area of normal tissue;

applying at least one probe comprising a plurality of probe elements to the area of tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the area of tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the area of tissue;

and

determining the location of the area of tissue to be removed based on the comparison between the first electrophysiological characteristic of the area of tissue to be removed and the electrophysiological characteristic of an area of normal tissue and including sensing or measuring variations in the dielectric constants over a plurality of the regions.

56. A method for determining the efficacy of a form of medical treatment comprising:

measuring a first electrophysiological characteristic of an area of tissue to be treated;

applying a treatment to the area of tissue to be treated;

measuring a second electrophysiological characteristic of the area of tissue to be treated;

comparing the first and second electrophysiological characteristics;

applying at least one probe comprising a plurality of probe elements to an area of tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the area of tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the area of tissue;

and

determining the efficacy of the medical treatment based on (1) the comparison between the first and second electrophysiological characteristics;

(2) by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

57. The method of claim 56, wherein the form of treatment is selected from the group of treatments consisting of ablation therapy, radiation therapy, cryotherapy, and drug therapy.

58. A method for determining the efficacy of a form of medical treatment comprising:

applying a treatment to an area of tissue;

measuring an electrophysiological characteristic of the area of tissue;

comparing the electrophysiological characteristic of the area of tissue to predetermined values;

determining the efficacy of the medical treatment based on the comparison between the electrophysiological characteristic and predetermined values.

59. A method for determining the efficacy of a form of medical treatment comprising:

applying a treatment to the area of tissue to be treated;

measuring a first electrophysiological characteristic of the area of treated tissue;

measuring a second electrophysiological characteristic of a second area of tissue;

comparing the first and second electrophysiological characteristics;

applying at least one probe comprising a plurality of probe elements to the area of tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the area of tissue;

selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the area of tissue;

and

determining the efficacy of the medical treatment based on (1) the comparison between the first and second electrophysiological characteristics;

(2) by sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

60. The method of claim 59, wherein the second area of tissue is normal tissue.

61. The method of claim 59, wherein the second area of tissue is adjacent to the area of tissue to be treated tissue.

62. The method of claim 59, further comprising introducing an agent into the area of tissue to be treated.

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

(A) establishing a connection between a first electrode and the epithelial tissue of the nipple of a breast with a ductal probe, an electroconductive media or both;

(B) placing a second electrode in contact with the surface of the breast;

(C) establishing a signal between the first and second electrodes;

(D) establishing that the nipple ducts of the breast are open by;

(1) measuring the impedance between the first and second electrode at about 5 different frequencies in the range of about 200 Hz to about 60,000 Hz sufficient to establish an impedance curve;

(2) treating the nipple using at least one method selected from the group consisting of (a) applying suction and release of suction to the nipple;

(b) applying alcohol; and

(c) applying a dekeratinizing agent;

(3) again measuring the impedance between the first and second electrode at about 5 different frequencies in the range of about 200 Hz to about 60,000 Hz sufficient to establish an impedance curve and comparing the impedance curve obtained to that obtained in (D)(1) above;

(4) repeating steps (2) and (3) until the impedance curve obtained in step (D)(3) is substantially unchanged in order to confirm that the ducts are open;

(E) measuring between the first and second electrode;

(1) a DC potential; and

(2) impedance at about 5 different frequencies in the range of about 10 Hz to about 200 Hz and impedance at from about 5 to about 50 different frequencies in the range of about 0.1 Hz to about 10 Hz;

(F) applying at least one probe comprising a plurality of probe elements to breast tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the breast tissue;

(G) selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the breast tissue;

and

(H) determining the condition of the region of epithelial tissue based on (1) the DC potential and impedance measurements between the first and second electrode;

(2) sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).

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

(A) placing over the nipple of a breast a cup having an interior, and first and second openings, and an electrode disposed within the interior, the cup having a source of suction in communication with the first opening, the second opening having been placed over the nipple;

(B) establishing a connection between the electrode and the epithelial tissue of the nipple of a breast with a ductal probe, an electroconductive media or both;

(C) placing a second electrode in contact with the surface of the breast;

(D) establishing a signal between the first and second electrodes;

(E) establishing that the nipple ducts of the breast are open by;

(1) measuring the impedance between the first and second electrode at about 5 different frequencies in the range of about 200 Hz to about 60,000 Hz sufficient to establish an impedance curve;

(2) treating the nipple using at least one method selected from the group consisting of (a) applying suction and release of suction to the nipple;

(b) applying alcohol; and

(c) applying a dekeratinizing agent;

(3) again measuring the impedance between the first and second electrode at about 5 different frequencies in the range of about 200 Hz to about 60,000 Hz sufficient to establish an impedance curve and comparing the impedance curve obtained to that obtained in (D)(1) above;

(4) repeating steps (2) and (3) until the impedance curve obtained in step (E)(3) is substantially unchanged in order to confirm that the ducts are open;

(F) measuring a DC potential between the first and second electrode;

(G) applying suction to the cup sufficient to effect ductal collapse in a normal or non-malignant duct; and

measuring impedance at about 5 different frequencies in the range of about 10 Hz to about 200 Hz and impedance at from about 5 to about 50 different frequencies in the range of about 0.1 Hz to about 10 Hz; and

(H) altering the suction level and again measuring impedance at about 5 different frequencies in the range of about 10 Hz to about 200 Hz and impedance at from about 5 to about 50 different frequencies in the range of about 0.1 Hz to about 10 Hz;

(J) applying at least one probe comprising a plurality of probe elements to breast tissue such that individual ones of the probe elements are arranged for sensing or measuring characteristics of individual localized regions of the breast tissue;

(K) selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of the breast tissue;

and

(L) determining the condition of the region of epithelial tissue based on (1) the DC potential, and the impedance measurements under varying pressure conditions;

(2) sensing or measuring variations in the dielectric constants over a plurality of the regions;

or both (1) and (2).