Discriminant function analysis method and apparatus for disease diagnosis and screening with biopsy needle sensor

We claim:

1. An apparatus for precisely locating suspected neoplastic tissue in a living subject by measuring the electrical potentials which are a function of the electromagnetic fields present within the tissues of the subject in an area where the presence of the neoplastic tissue is suspected consisting essentially of;

reference electrode means adapted for contacting the subject at a reference location,

tissue locator electrode means adapted for insertion into the subject's tissues in the area where the presence of the neoplastic tissue is suspected and operative with said reference electrode means to detect the electrical potentials of the electromagnetic fields present between said reference electrode means and said tissue locator electrode means while said tissue locator electrode means is being inserted internally toward and into said suspected neoplastic tissue and to provide test potentials as a function of each of said electrical potentials detected; said tissue locator electrode means including biopsy means for removing a sample of said suspected neoplastic tissue, and

processing means connected to said reference electrode means and said tissue locator electrode means and operative to receive said test potentials, said processing means operating to sample a plurality of said test potentials to provide indications which are a function of said test potentials.

2. The apparatus of claim 1 wherein said tissue locator electrode means is a biopsy needle having a pointed end and includes an electrical potential sensing electrode mounted at said pointed end.

3. The apparatus of claim 2 wherein said biopsy needle includes a hollow shaft having a first end and a second end, said electrical potential sensing electrode being formed to provide a point at the first end of said hollow shaft, insulating means mounted on the first end of said hollow shaft between said electrical potential sensing electrode and said hollow shaft to electrically insulate said electrical potential sensing electrode from said hollow shaft, and an opening formed in said hollow shaft at the first end thereof for receiving a sample of the suspected neoplastic tissue.

4. A method of locating suspected neoplastic tissue in a human subject by comparing the differences in electrical potential between the tissues in an area where the presence of neoplastic tissue is suspected including the steps of:

(a) providing a locator electrode for insertion into the tissue of the human subject in the area of the suspected neoplastic tissue;

(b) attaching a reference electrode to a reference area of normal tissue sufficiently proximate to the suspected neoplastic tissue to permit said locator electrode to detect the electrical potentials of the electromagnetic fields present between sad reference and locator electrodes as said locator electrode passes through the tissue of the human subject,

(c) inserting said locator electrode and detecting the electrical potentials between said locator electrode and the reference electrode while said locator electrode is being inserted through the tissue into said area of suspected neoplastic tissue; and

(d) processing the detected electrical potentials during said locator electrode insertion to determine when the detected electrical potentials reach a value indicative of contact by said locator electrode with neoplastic tissue.

5. The method of claim 4 wherein said locator electrode is mounted on a biopsy needle and includes removing a sample of said neoplastic tissue with said biopsy needle when said locator electrode has contacted said neoplastic tissue.

6. The method of claim 4 which includes detecting the potentials between said locator electrode and reference electrode at a plurality of measurement locations as said locator electrode is inserted through the tissue,

comparing the potentials so obtained to identify therefrom a high and a low level potential, and

obtaining a differential value indicative of the difference between said high and low level potentials.

7. The method of claim 6 which includes a taking a plurality of potential measurements at each said measurement location,

obtaining average potential values for each said measurement location from the measurements taken,

comparing said average potential values to identify therefrom high and low level average potentials, and obtaining said differential value from the difference between said high and low level average potentials.

8. The method of claim 4 which includes detecting a plurality of electrical potentials between said reference electrode and said locator electrode after contact by said locator electrode with the neoplastic tissue while maintaining said locator electrode in contact with said neoplastic tissue,

comparing the electrical potentials obtained during contact of said locator electrode with said neoplastic tissue to identify a high and low level potential,

obtaining a differential value indicative of the difference between said high and low level potentials,

and using said differential value to determine the presence or absence of a disease condition.

9. The method of claim 4 which includes detecting a plurality of electrical potentials between said reference electrode and said locator electrode after contact by said locator electrode with the neoplastic tissue while maintaining said locator electrode in contact with said neoplastic tissue, and

using said electrical potentials obtained during contact of said locator electrode with said neoplastic tissue to determine the presence or absence of a disease condition.

10. A method for determining the presence of absence of an internal disease condition present at an internal disease site in the area of a test site on a living subject which includes,

detecting during a first test period the respective electrical potentials of the electromagnetic field present in said subject between each of a plurality of measurement locations in the area of the test site and at least one reference location on the subject to obtain a representative potential for each measurement for each measurement location during the test period,

comparing such representative potentials at the end of the first test period to obtain therefrom relationships which are indicative of either the presence or the absence of the internal disease condition in the area of the test site,

inserting a locator electrode into the tissue of the subject in the area of the test site when the presence of the internal disease condition is sensed,

detecting the electrical potentials between said reference location and said locator electrode while said locator electrode is being inserted through the tissue toward the internal disease site, and

processing the detected electrical potentials during said locator electrode insertion to guide said locator electrode to said internal disease site and to determine when the detected electrical potential is indicative of contact by said locator electrode with said internal disease site.

11. The method of claim 10 wherein said locator electrode is mounted on a biopsy needle and includes removing a sample of neoplastic tissue from said disease site with said biopsy needle when said locator electrode has contacted said neoplastic tissue.

12. An apparatus for precisely locating neoplastic tissue in a living subject by measuring the electrical potentials which are a function of the electromagnetic fields which originate from within and are present on the skin surface of the subject in an area of a potential disease site and are present within the tissues of the subject comprising:

reference electrode means adapted for contacting the subject at one or more reference locations,

a plurality of screening electrode means adapted for contact with the skin surface of the subject at spaced locations in the area of the potential disease site and operative with said reference electrode means to detect the potentials of said electromagnetic fields which are present in the area of said potential disease site during a first test period and to provide test signals as a function of the potentials detected,

processing means connected to receive said test signals and operative to compare the test signals obtained during said first test period to identify potential relationships indicative of the presence of the neoplastic tissue; and

tissue locator electrode means for insertion into the subject's tissues in the area of the potential disease site and operative with said reference electrode means during a second test period to detect electrical potentials of the electromagnetic fields present between said reference electrode means and said tissue locator electrode means while said tissue locator electrode means is being inserted internally toward and into said neoplastic tissue and to provide locator potentials as a function of each of said electrical potentials detected; said processing means being connected to receive said locator potentials and operating to provide indications which are a functions of said locator potentials.

13. The apparatus of claim 12 wherein said processing means operates during said second test period to detect potential changes in said locator potentials as an indicator of when said tissue locator electrode means has reached the neoplastic tissue.

14. The apparatus of claim 12 wherein said processing means is operative during said first test period to receive a plurality of said test signals from a combination of said reference electrode means and said screening electrode means, said processing means being further operative to compare the test signals so obtained to identify a high and low level signal and to obtain a differential value indicative of the difference between said high and low level signals.

15. The apparatus of claim 12 wherein said processing means operates to sample and receive a plurality of said test signals from a combination of each of said screening electrode means and said reference electrode means during said first test period and to average the test signals for each said screening electrode means reference electrode means combinations to obtain an average signal value therefrom, said processing means operating to compare said average signal values obtained for said first test period to identify differential relationships therebetween.

16. The apparatus of claim 15 wherein said processing means operates to compare said average signal values obtained for said first test period and obtain therefrom the maximum and minimum average signal values and subsequently obtaining a differential value indicative of the difference between said maximum and minimum average signal values.

17. The apparatus of claim 16 wherein said processing means operates to compare said differential value to a first reference value, said processing means operating to provide an output indicative of the presence or absence of the neoplastic tissue in accordance with a relationship between said first reference value and said differential value.

18. The apparatus of claim 12 wherein said processing means operates during said second test period to detect the electrical potentials between said locator electrode means and said reference electrode means at a plurality of measurement locations as said location electrode means is inserted toward said neoplastic tissue, said processor means operating to compare the electrical potentials obtained during the second test period to identify therefrom high and low level potential values and to obtain differential values indicative of the difference between said high and low potential values.

Description Submit all comments and votes

TECHNICAL FIELD

The present invention relates generally to a method and apparatus for diagnosing, screening or sensing disease states, particularly the existence of neoplastic tissue in a living organism by detecting the potential of the electromagnetic field present between a reference and one or more test points on or within the living organism to measure the gradient of electrical activity which occurs as a function of biological activity.

BACKGROUND ART

In recent years the theory that measurement of the potential level of the electromagnetic field of a living organism can be used as an accurate diagnostic tool is gaining greater acceptance. Many methods and devices have been developed in an attempt to implement this theory. For example, U.S. Pat. No. 4,328,809 to B. H. Hirschowitz et al deals with a device and method for detecting the potential level of the electromagnetic field present between a reference point and a test point of a living organism. Here, a reference electrode provides a first signal indicative of the potential level of the electromagnetic field at the reference point, while a test electrode provides a second signal indicative of the potential level of the electromagnetic field at the test point. These signals are provided to an analog-to-digital converter which generates a digital signal as a function of the potential difference between the two, and a processor provides an output signal indicative of a parameter or parameters of the living organism as a function of this digital signal.

Similar biopotential measuring devices are shown by U.S. Pat. Nos. 4,407,300 to Davis, and 4,557,271 and 4,557,273 to Stroller et al. Davis, in particular, discloses the diagnosis of cancer by measuring the electromotive forces generated between two electrodes applied to a subject.

Often, the measurement of biopotentials has been accomplished using an electrode array, with some type of multiplexing system to switch between electrodes in the array. The aforementioned Hirschowitz et al patent contemplates the use of a plurality of test electrodes, while U.S. Pat. Nos. 4,416,288 to Freeman and 4,486,835 to Bai disclose the use of measuring electrode arrays.

Unfortunately, previous methods for employing biopotentials measured at the surface of a living organism as a diagnostic tool, while basically valid, are predicated upon an overly simplistic hypothesis which does not provide an effective diagnosis for many disease states. Prior methods and devices which implement them operate on the basis that a disease state is indicated by a negatize polarity which occurs relative to a reference voltage obtained from another site on the body of a patient, while normal or nonmalignant states, in the case of cancer, are indicated by a positive polarity. Based upon this hypothesis, it follows that the detection and diagnosis of disease states can be accomplished by using one measuring electrode situated externally on or near the disease site to provide a measurement of the polarity of the signal received from the site relative to that from the reference site. Where multiple measuring electrodes have been used, their outputs have merely been summed and averaged to obtain one average signal from which a polarity determination is made. This approach can be subject to major deficiencies which lead to diagnostic inaccuracy, particularly where only surf ace measurements are taken.

First, the polarity of diseased tissue underlying a recording electrode has been found to change over time. This fact results in a potential change which confounds reliable diagnosis when only one external recording electrode is used. Additionally, the polarity of tissue is measured by skin surface recording is dependent not only upon the placement of the recording electrode, but also upon the placement of the reference electrode. Therefore, a measured negative polarity is not necessarily indicative of diseases such as cancer, since polarity at the disease site depends in part on the placement of the reference electrode.

As disease states such as cancer progress, they produce local effects which include changes in vascularization, water content, and cell division rate. These effects alter ionic concentrations which can be measured at the skin surface and within the neoplastic tissues. Other local effects, such as distortions in biologically closed electrical circuits, may occur. A key point to recognize is that these effects do not occur uniformly around the disease site. For example, as a tumor grows and differentiates, it may show wide variations in its vascularity, water content and cell division rate, depending on whether examination occurs at the core of the tumor (which may be necrotic) or at the margins of the tumor (which may contain the most metabolically active cells). once this fact is recognized, it follows that important electrical indications of disease are going to be seen in the relative voltages recorded from a number of sites at and near a diseased area, and not, as previously assumed, on the direction (positive vs. negative) of polarity.

Once the location of a disease state, such as suspected neoplastic tissue or cancer, has been identified, the conventional diagnostic approach has been to perform a biopsy so that the diseased tissue could be examined to confirm the diagnosis. During this procedure a needle is inserted from outside the patient's body into the suspected neoplasm or other diseased tissue to permit the removal of a sample for a pathology study. To insure the accurate insertion of the needle into the diseased tissue to be biopsied, it has been necessary to employ radiographic techniques which allow the practitioner to see the neoplasm and view the biopsy needle during insertion. Even then, it is not always a certainty that the needle has reached the neoplasm, and a method of confirming this to augment radiographic techniques would be beneficial.

Biopsy procedures are perferably performed in a surgical suite, an operating room or other area that is sterile as possible. If the pathology report indicates the need for immediate surgery, it is diserable for the patient to be near surgical facilities. In many cases patients have had to be moved from the radiology area to the surigical suite with the biopsy needle in place because the necessary radiology equipment for positioning the needle was located only in the radiology area.

There is a need, therefore, for a discriminant analysis method and apparatus which not only externally diagnoses and screens disease sites, but which also internally identifies and locates diseased tissue, particularly neoplastic tissue so that the appropriate further diagnostic and treatment steps may be taken.

DISCLOSURE OF THE INVENTION

It is a primary object of the present invention to provide a novel and improved biopsy method and apparatus for providing disease diagnosis and particularly for cancer diagnosis. Such method and apparatus operate to determine the relationships between a set of voltages taken internally from the area of a disease site within a living organism.

Another object of the present invention is to provide a novel and improved biopsy method and apparatus for the discriminant analysis of a disease site within a living organism wherein voltage potentials are measured in the area of the disease site over time. A maximum voltage differential is obtained from an average of multiple readings taken over time which constitutes a minimum voltage that is subtracted from a maximum voltage where two or more electrodes are recording voltages simultaneously or concurrently from a specific disease site or organ.

A further object of the present invention is to provide a novel and improved biopsy method and apparatus for providing an indication of the location of a biopsy needle relative to neoplastic tissue for cancer diagnosis. Relative voltages are recorded from a number of internal sites near a disease area using a combination biopsy needle and electrode as the needle electrode is inserted through tissue into a cancerous lesion. Signal measurements taken from such sites are used to locate the biopsy needle precisely in the neoplastic tissue to permit a biopsy to be taken.

A still further object of the present invention is to provide a novel and improved biopsy method and apparatus involving discriminant analysis to facilitate the accurate location of a disease site and the placement of biopsy instruments for cancer diagnosis. Recordings at or near suspected neoplastic tissue are taken and the voltage levels recorded are analyzed in terms of a discriminant mathematical analysis to locate the site of a possible malignancy. Additional voltage measurements are taken as a biospy instrument is inserted through tissue toward the disease site to position a biopsy instrument accurately within the neoplastic tissue without external visual aids, such as radiography. The aim of the method and apparatus is to measure the gradient of electrical activity which occurs as a function of the biological activity of the specific organ system.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of the apparatus of the present invention;

FIG. 2 is a cross-sectional diagram of an electrode for the apparatus of FIG. 1;

FIG. 3 is a flow diagram of the measurement operation of the apparatus of FIG. 1 used to obtain a maximum voltage differential and a low individual channel value;

FIG. 4 is a flow diagram of the disease decision analysis provided by the apparatus of FIG. 1;

FIG. 5 is a flow diagram of an auxiliary decision sequence used with the flow diagram of FIG. 4;

FIG. 6 is a block diagram of a second embodiment of the apparatus of the present invention; and

FIG. 7 is a cross sectional diagram of a biopsy needle electrode used with the present invention.

BEST MODE FOR CARRYING OUT THE INVENTION

FIG. 1 discloses a basic block diagram of the apparatus of the present invention indicated generally at 10 for performing a discriminant analysis for disease screening or diagnosis. For purposes of illustration, the apparatus 10 will be described in connection with methods involving the screening for, or diagnosing of breast cancer. However, it should be recognized that the method and apparatus of the invention can be similarly employed for screening or diagnosis at other disease sites involving other portions or organs of a living human or animal.

In FIG. 1, a human subject 12 may have a cancerous lesion 14 on one breast 16. This cancerous lesion has a core 18 and an outer zone 20 surrounding the core where various differing local effects, such as changes in vascularization, water content and cell division rate occur. Assuming first, for purposes of discussion, that the location of the lesion 14 is not known, and the device 10 is to be used to screen the breast 16 to determine whether or not a disease condition exists, skin surface potentials will be measured in an area of the breast, including the zone 20 using an electrode array 22. In FIG. 1, the electrode array includes a central electrode 24 surrounded by four periperal electrodes 26. However, the device and method of this invention contemplate the use of a variety of different electrode arrays depending upon the intended application for which the device 10 is used. For example, in the diagnosis of clinically symptomatic breast or skin lesions, the electrode array should cover various areas of the lesion as well as relatively normal tissue near the lesion site. For breast cancer screening (where patients are asymptomatic) the array should give maximum coverage of the entire breast surface. The aim in both of these cases is to measure the gradient of electrical activity which occurs as a function of the underlying biological activity of the organ system. The number of electrodes used in the measurement will also be a function of specific application, and breast cancer screening may require the use of as few as twelve or as many as forty or more electrodes for each breast, while in screening for prostate cancer, as few as two measurement electrodes might be used.

The core electrode 24 and the peripheral electrodes 26 are mounted upon a flexible backing sheet 28 which permits the electrodes to be positioned against the curved surface of the breast 16 while still maintaining the position of the electrodes in a predetermined pattern. However, other electrode arrays may be employed wherein each individual electrode can be individually positioned, and the relative position between electrodes can be altered. The electrode array 22 is used in conjunction with a reference electrode 30, and all of these electrodes may be of a known type used for detecting the potential level of the electromagnetic field present in a living organism. Ideally, the electrodes 24, 26 and 30 should be of a type which do not cause a substantial battery effect between the organism under test and the electrode. A common electrode suitable for use as the electrodes 24, 26 and 30 is illustrated in FIG. 2, and includes a layer of silver 32 having an electrical lead 34 secured in electrical contact therewith. In contact with the silver layer 32 is a layer 37 of silver chloride, and extending in contact with the silver chloride layer is a layer of bridging material 38, such as sodium chloride, which contacts the surface of a living organism.

The device 10 is a multi-channel device having electrode leads 34 extending separately from the central electrode 24, the peripheral electrodes 26, and the reference electrode 30 to a low pass filter 36. This filter operates to remove undesirable high frequency AC components which appear on the slowly varying DC voltage signal outputs provided by each of the electrodes as a result of the electromagnetic field measurement. The low pass filter 36 may constitute one or more multiple input low pass filters of known type which separately filter the signals on each of the input leads 34 and then pass each of these filtered signals in a separate channel to a multiple input analog-to-digital converter 40. Obviously, the low pass filter 36 could constitute an individual low pass filter for each of the specific channels represented by the leads 34 which would provide a fillering action for only that channel, and then each filtered output signal would be connected to the input of the analog-to-digital converter 40.

The converter 40 is a multiple input multiplex analog-to-digital converter of a known type, such as that manufactured by National Semiconductor, Inc. and designated as ADC808. For multiple channels, it is possible that more than one multiple input analog-to-digital converter will be used as the converter 38. For example, if an 8-input analog-to-digital converter is used and there are 24 input and output channels from the low pass filter 36, then the analog-to-digital converter 38 might include three 8-input converters.

The analog-to-digital converter 38 converts the analog signal in each input channel to a digital signal which is provided on a separate output channel to the multiple inputs of a central processing unit 42. The central processing unit is a component of a central control unit indicated generally at 44 which includes RAM and ROM memories 46 and 48. Digital input data from the analog-to-digital converter 40 is stored in memory and is processed by the CPU in accordance with a stored program to perform the diagnostic and scanning methods of the present invention. The information derived by the CPU as a result of this processing is then fed to a suitable indicator device 50 which may constitute a printer, a CRT display device, or a combination of such conventional indicators.

The operation of the discriminant analysis device 10 will be clearly understood from a brief consideration of the broad method steps of the invention which the device is intended to perform. When the lesion 14 has not been identified and a screening operation is performed to determine whether or not a lesion is present, a screening electrode array 22 is positioned in place with the central- electrode 24 in the center of the site being screened and the peripheral electrodes 26 over various diverse areas of the site. If a breast 16 is screened, the electrode array may cover either the complete breast or a substantial area thereof. The reference electrode 30 is then brought into contact with the skin of the subject 12 in spaced relationship to the electrode array 22, and this reference electrode might, for example, be brought into contact with a hand of the subject. Then, the electromagnetic field between the reference electrode and each of the electrodes 24 and 26 is measured, filtered, converted to a digital signal and stored for processing by the cen