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

• US 8,262,575 B2
• Filed: 12/06/2005
• Issued: 09/11/2012
• 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): Hindenburg, Max
• Assistant Examiner(s): DANEGA, RENEE A
• Application Number:
  US11/294,916
• Publication Number:
  US 20060100488A1
• Time in Patent Office: 2,471 Days
• Field of Search: 600/442, 324/600
• US Class Current: 600/442
• 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 organ or mucosal epithelial tissue comprising:

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

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

(C) establishing an electrical signal between the current-passing electrodes;

(D) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal;

(E) introducing at least one agent into the selected region of tissue while electrically probing said tissue, said agent comprising one or more pharmacological agent, hormone, chemical compound or mixture thereof, added to an electroconductive medium (ECM) or otherwise introduced to the tissue, which modulates, inhibits or stimulates electrical activity of said tissue and selected to differentially alter, reveal and accentuate electrophysiological characteristics indicative of abnormal or cancerous tissue compared to benign tissue;

(F) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal while introducing the at least one agent; and

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

(H) selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of said 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); and

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.

2. A method for determining a condition of a region of organ or mucosal epithelial tissue comprising:

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

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

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

(D) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal;

(E) introducing at least one agent into the selected region of tissue while electrically probing said tissue, said agent comprising one or more pharmacological agent, hormone, chemical compound or mixture thereof, added to an electroconductive medium (ECM) or otherwise introduced to the tissue, which modulates, inhibits or stimulates electrical activity of said tissue and selected to differentially alter, reveal and accentuate electrophysiological characteristics indicative of abnormal or cancerous tissue compared to benign tissue;

(F) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal while introducing the at least one agent; and

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

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

(1) determining the condition of the selected region of tissue based on the electrical measurement, 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); and

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.

3. A method for determining a condition of a region of organ or mucosal epithelial tissue comprising:

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

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

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

(D) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal;

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

(F) selectively applying an electrical signal to the probe elements for;

(1) determining the dielectric constants of the localized or selected regions of said tissue; and

(2) measuring the impedance of the localized or selected regions of tissue; and

(G) detecting the presence of a possible tumor by sensing or measuring variations in the dielectric constants and impedance over said regions.

4. The method of claim 3, wherein placing of the at least one current-passing electrode or 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 at least one current-passing electrode is situated on the probe.

5. The method of claim 3, wherein the step of determining the condition of the selected region of tissue includes rating the tissue as normal, at-risk, pre-cancerous, or cancerous.

6. The method of claim 3 wherein said electrical signal is at a frequency of about 0.2 Hz to about 6000 Hz.

7. A method for determining a condition of a region of organ or mucosal epithelial tissue comprising:

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

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

(C) establishing an electrical signal between the current-passing electrodes;

(D) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal;

(E) introducing at least one agent into the selected region of tissue while electrically probing said tissue, said agent comprising one or more pharmacological agent, hormone, chemical compound or mixture thereof, added to an electroconductive medium (ECM) or otherwise introduced to the tissue, which modulates, inhibits or stimulates electrical activity of said tissue and selected to differentially alter, reveal and accentuate electrophysiological characteristics indicative of abnormal or cancerous tissue compared to benign tissue;

(F) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal while introducing the at least one agent; and

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

(H) selectively applying an electrical signal to the probe elements for determining the dielectric constants of the localized regions of said 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);

wherein said electrical signal is at a frequency of about 0.2 Hz to about 6000 Hz.

8. A method for determining a condition of a region of organ or mucosal epithelial tissue comprising:

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

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

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

(D) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal;

(E) introducing at least one agent into the selected region of tissue while electrically probing said tissue, said agent comprising one or more pharmacological agent, hormone, chemical compound or mixture thereof, added to an electroconductive medium (ECM) or otherwise introduced to the tissue, which modulates, inhibits or stimulates electrical activity of said tissue and selected to differentially alter, reveal and accentuate electrophysiological characteristics indicative of abnormal or cancerous tissue compared to benign tissue;

(F) measuring, at one or more of the measuring electrodes, an electrical measurement associated with the established signal while introducing the at least one agent; and

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

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

(1) determining the condition of the selected region of tissue based on the electrical measurement, 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);

wherein said electrical signal is at a frequency of about 0.2 Hz to about 6000 Hz.