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

• US 8,280,504 B2
• Filed: 04/01/2005
• Issued: 10/02/2012
• Est. Priority Date: 05/20/2002
• Status: Expired due to Fees

• Current Assignee: Epi-Sci, LLC
• Original Assignee: Epi-Sci, LLC
• Inventors: Davies, Richard J.
• Primary Examiner(s): DOUGHERTY, SEAN PATRICK
• Application Number:
  US11/096,665
• Publication Number:
  US 20050203436A1
• Time in Patent Office: 2,741 Days
• Field of Search: 324/554, 600/442, 600/506, 600/536, 600/547, 600/554, 604/20
• 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 ductal epithelial tissue of the breast comprising:

(A) placing at least one current-passing electrode in contact with or in proximity to a surface of the breast, at least one of said current-passing electrode is in electrical communication with said ductal epithelium;

(B) placing a plurality of measuring electrodes in contact with or in proximity to said surface;

(C) establishing an electrical signal between said at least one current-passing electrode and at least one of said measuring electrodes;

(D) measuring, at one or more of said measuring electrodes, an impedance associated with said signal;

(E) introducing at least one agent into said ductal epithelial tissue so as to instantaneously reveal and accentuate changes in impedance in said ductal epithelial tissue and measuring, at one or more of said measuring electrodes, an impedance associated with said signal following the introduction of said at least one agent; and

(F) determining the condition of said ductal epithelial tissue based on said impedance.

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

placing a probe in contact with or in proximity to said surface, wherein said current-passing electrode is situated on said 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 said surface, wherein said measuring electrodes are situated on said probe.

4. The method of claim 1, wherein

said at least one agent is introduced into said ductal epithelial tissue via a nipple cup electrode.

5. The method of claim 1, wherein step (A) comprises:

placing at least two current-passing electrodes in contact with or in proximity to said surface.

6. The method of claim 5, further including the steps of:

(G) introducing at least one agent into said epithelial tissue so as to instantaneously reveal and accentuate changes in impedance in said epithelial tissue and measuring, at one or more of said measuring electrodes, an impedance associated with said signal following the introduction of said at least one agent; and

(H) determining the condition of said tissue based on said impedance, following the introduction of said at least one agent.

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 said surface, wherein said measuring electrodes are situated on said probe.

8. The method of claim 5, wherein the step of determining the condition of said 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 ductal epithelial tissue of the breast, said breast having a surface, using a combination of DC electrical measurements and impedance spectroscopy, comprising the steps of:

(A) measuring a DC potential at the surface of the ductal epithelial tissue with a first and a second voltage-measuring electrode, wherein said voltage-measuring electrodes are spaced apart from one another and associated with a reference point;

(B) placing a pair of current-passing electrodes in contact with or in proximity to said ductal epithelial tissue;

(C) detecting, via said voltage-measuring electrodes, an electrical signal at different points on said epithelial tissue;

(D) applying an electrical signal to said pair of current-passing electrodes at a plurality of frequencies at said different points on said epithelial tissue;

(E) monitoring an electrical signal at said voltage-measuring electrodes associated with each of said plurality of frequencies;

(F) determining impedance of said epithelial tissue associated with the voltage-measuring electrodes based on each of the plurality of frequencies;

wherein said reference point includes an intravenous electrode or a skin electrode with low skin impedance and wherein at least one of which electrodes is in electrical communication with said ductal epithelium.

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

11. The method of claim 10, wherein the sinusoidal alternating currents are applied sequentially.

12. The method of claim 9 further including the steps of:

(G) introducing at least one agent into said region of epithelial tissue so as to instantaneously reveal and accentuate changes in;

(i) DC potential;

or (ii) impedance;

or both (i) and (ii) in said epithelial tissue following the introduction of said at least one agent;

(H) measuring, at one or more of said voltage-measuring electrodes, a DC potential at the surface of the epithelial tissue as in (A) and impedance associated with said signal as in (D), (E) and (F) following the introduction of said at least one agent; and

(I) determining the condition of said region of epithelial tissue based on the change in said DC potential and said impedance following the introduction of said at least one agent.

13. 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.

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

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

16. The method of claim 9, further including a modified nipple cup adapted to receive at least one of said electrodes in order to facilitate electrical contact with the ductal epithelium of the breast.

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

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

18. A method for measuring electrical properties of ductal epithelial tissue of the breast, said breast having a surface, using a combination of DC electrical measurements and impedance spectroscopy, comprising the steps of:

(A) measuring a DC potential of the ductal epithelial tissue with a first and a second voltage-measuring electrodes, wherein the voltage-measuring electrodes are associated with a reference point;

(B) placing at least one current-passing electrode in contact with or in proximity to said ductal epithelial tissue;

(C) detecting, via said voltage-measuring electrodes, a resulting electrical signal at different points on said epithelial tissue;

(D) applying an electrical signal to at least one of said current-passing electrodes and at least one of the voltage-measuring electrodes at a plurality of frequencies at said different points on said epithelial tissue;

(E) monitoring an electrical signal at said voltage-measuring electrodes associated with each of said plurality of frequencies;

(F) determining impedance of said region of epithelial tissue associated with said voltage-measuring electrodes based on each of said plurality of frequencies and said resulting electrical signal associated with each of said plurality of frequencies;

(G) introducing at least one agent into said region of ductal epithelial tissue so as to instantaneously reveal and accentuate changes in;

(i) DC potential;

or (ii) impedance;

or both (i) and (ii) in said epithelial tissue following the introduction of said at least one agent;

(H) measuring, at one or more of said voltage-measuring electrodes, a DC potential of the epithelial tissue as in (A) and impedance associated with said signal as in (D), (E) and (F) following the introduction of said at least one agent; and

(I) determining a condition of said region of ductal epithelial tissue based on said change step (G).

19. An apparatus for determining the condition of tissue of a ductal epithelium of the breast using a combination of surface DC electrical measurements and impedance spectroscopy and specific ionic conductance, the apparatus comprising:

(A) a first pair of spaced electrodes for applying an electrical signal to the ductal epithelium;

(B) a second pair of spaced electrodes for detecting an electrical signal at different points on the ductal epithelium;

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

(D) a means for measuring an electrical signal at the second pair of electrodes at said plurality of frequencies;

(E) a means for obtaining a measure of the impedance of a part of the ductal epithelium based on said electrical signal in (D); and

(F) a means for obtaining a difference signal representing a change in impedance with frequency,

wherein each electrode of the second pair of electrodes includes an electroconductive medium concentration that differs from the other for estimating said specific ionic conductance of said epithelium.

20. The apparatus of claim 19, further comprising:

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

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

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

21. The apparatus of claim 19, wherein said means for applying said 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 said first pair of electrodes.

22. The apparatus of claim 19, wherein the means for measuring the resulting electrical signal includes:

at least one adjustable gain voltage amplifier.

23. The apparatus of claim 19, wherein said means for obtaining the difference signal includes a microprocessor computing device.

24. The apparatus of claim 23, wherein said microprocessor computing device includes a low-pass filter.

25. The apparatus of claim 23, wherein said microprocessor computing device includes at least one of a band-pass filter and a high pass filter.