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

• US 8,332,025 B2
• Filed: 12/06/2006
• Issued: 12/11/2012
• Est. Priority Date: 12/06/2005
• Status: Active Grant

• Current Assignee: Epi-Sci, LLC
• Original Assignee: Epi-Sci, LLC
• Inventors: Davies, Richard J.
• Primary Examiner(s): Hoekstra, Jeffrey G
• Assistant Examiner(s): Leedy, Megan
• Application Number:
  US12/086,021
• Publication Number:
  US 20090306535A1
• Time in Patent Office: 2,197 Days
• Field of Search: 600/547, 600/300, 600/372, 600/382, 600/442, 600/506, 600/536, 600/546, 600/554, 607/1, 607/2, 324/600
• US Class Current: 600/547
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body

Abstract

Methods and apparatus are provided for determining the condition of selected regions of epithelial and stromal tissue. A plurality of electrodes are used to measure surface and transepithelial electropotential of tissue, especially breast tissue, as well as surface electropotential and impedance at one or more locations and at several defined frequencies, particularly low frequencies. An agent may be introduced into the region of tissue to enhance electrophysiological response characteristics. Measured and derived electrical properties facilitating diagnosis include DC potential, impedance, subepithelial resistance, epithelial resistance, capacitance, characteristic frequency, depression angle and transepithelial potential. Ambient and varying pressure measurements applied to epithelial tissue are also used for diagnosis. Improved diagnosis of tissue condition can be made based on the electrical properties and tissue electrophysiological response to altered ion transport and pressure. Devices for practicing the disclosed methods are also provided.

Claims

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

(A) establishing a connection between a first electrode and the tissue;

(B) placing a second electrode in electrical contact on an outer tissue surface proximate the epithelial tissue;

(C) establishing at least one electrical signal between the first and second electrodes;

(D) measuring or deriving;

(1) impedance or DC or transepithelial potential values, or a combination thereof, between the first and second electrode; and

(2) at least one additional electrophysiological property selected from the group consisting of subepithelial resistance, epithelial resistance, capacitance, characteristic frequency, and depression angle; and

(E) determining the condition of a region of epithelial tissue based on the measured or derived properties;

wherein;

(i) the measured or derived value in (D)(1) is impedance or impedance and at least one of DC potential and transepithelial potential;

(ii) at least two response curves are obtained from impedance data; and

(iii) the curves include;

(a) a high frequency curve at a frequency of about 60,000 Hz to about 100 Hz;

(b) a intermediate frequency curve at a frequency of about 100 Hz to about 10 Hz; and

(c) a low frequency curve at a frequency of about 0.1 to about 6 Hz.

2. The method of claim 1, wherein the method of establishing a connection between the first electrode and the epithelial tissue is by an electroconductive media.

3. The method of claim 2, wherein the electroconductive media is a physiologic saline.

4. The method of claim 2, further comprising introducing an agent into the electroconductive media.

5. The method of claim 4, wherein the agent is a hormone.

6. The method of claim 1, wherein the epithelial or stromal tissue is associated with a breast, the breast comprising a nipple.

7. The method of claim 6, wherein the method of establishing a connection between the first electrode and the epithelial tissue is by a cannula.

8. The method of claim 7, wherein the cannula is a ductal probe.

9. The method of claim 6 for determining a condition of a region of epithelial breast tissue comprising:

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

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

(C) establishing an electrical 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; and

(F) determining the condition of the region of epithelial tissue based on the measured or derived electrical properties.

10. The method of claim 9, wherein the electrical connection between the first electrode and the epithelial tissue of the nipple of a breast is facilitated by placing over the nipple 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;

and further comprising the steps of;

(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; and

(J) determining the condition of the region of epithelial tissue based on the one or more measured or derived electrical properties and the affect on the properties of varying pressure conditions.

11. The method of claim 6 comprising:

(A) establishing a connection between the first electrode and epithelial tissue of the breast with at least one of;

(i) a ductal probe;

(ii) an electroconductive media;

(iii) a nipple cup placed over the nipple of the breast, the 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) wherein the second electrode is placed in contact with the surface of the breast; and

(C) determining the condition of the region of epithelial tissue based on the measured or derived electrical properties.