AU738011B2 - Impedance imaging devices and multi-element probe - Google Patents

Description

1 S F Ref: 377099D1

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIRCATION FOR A STANDARD PATENT

S

S *5 S S S

ORIGINAL

Name and Address of Applicant: Transscan Research P.O.B. 786 10550 Migal Haemek

ISRAEL

Development Co. Ltd.

Actual Inventor(s): Address for Service: Invention Title: Andrew L. Pearlman Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia Impedance Imaging Devices and Multi-Element Probe The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845 I IMPEDANCE IMAGING DEVICES AND MULTI-ELEMENT PROBE 1 2 FIELD OF THE INVENTION 3 The present invention relates to systems for imaging 4 based on the measurement of electrical potentials at an array of points, especially on the skin or other tissue 6 surface of a patient.

7 BACKGROUND OF THE INVENTION 8 The measurement of electrical potentials on the skin 9 has many uses. For example, electrocardiograms are derived 10 from measuring the potential generated by- the heart of a ii patient at various points on the skin.

"i .12 Skin potentials are also measured in apparatus for S• 13 determining the electrical impedance of human tissue, 14 including two-dimensional U.S. Patents 5,063,937, 4,291,708 and 4,458,694) or three-dimensional

U.S.

16 Patents 4,617,939 and 4,539,640) mapping of the tissue 17 impedance of the body. In such systems an electrical "18 potential is introduced at a point or points on the body and 19 measured at other points at the body. Based on these measurements and on algorithms which have been developed "21 over the past several decades, an impedance map or other ooo 22 indication of variations in impedance can be generated.

o 23 U.S. Patents 4,291,708 and 4,458,694 and "Breast Cancer 24 screening by impedance measurements" by G.-Piperno et al.

Fontiers Med. Biol. Eng., Vol. 2, No. 2, pp 111-117, the 26 disclosures of which are incorporated herein by reference, 27 describe systems in which the impedance between a point on 28 the surface of the skin and some reference point on the body 29 of a patientis determined. These references describe the use of a multi-element probe for the detection of cancer, 31 especially breast cancer, utilizing detected variations of 32 impedance in the breast.

33 In these references a multi-element probe is described 34 in which a series of flat, stainless steel, sensing elements are mounted onto a PVC base. A lead wire is connected 36 between each of these elements and detector circuitry. Based -1 1 on the impedance measured between the elements and a remote 2 part of the body, signal processing circuitry determines the 3 impedance variations in the breast. Based on the impedance 4 determination, tumors, and especially malignant tumors, can be detected.

6 The multi-element probe is a critical component in this 7 system and in other systems which use such probes. On one 8 hand the individual elements must make good contact with the 9 skin and with the corresponding points on -the sensing or

S

1 0 processing electronics while also being well isolated from 11 each other. On the other hand, use of gels t6 improve skin .12 contact carries the risk of cross-talk, dried gel build-up 13 on the elements and inter-patient hygienic concerns.

14 A paper titled "Capacitive Sensors for IN-Vivo Measurements of the Dielectric Properties of Biological 16 materials" by Karunayake P.A.P. Esselle and Stanislaw

S.

17 Stuchly (IEEE Trans. Inst Meas. Vol. 37, No. 1, p. 101- 18 105) describes a single element probe for the measurement of 19 in vivo and in vitro measurements of the dielectric 20 properties of biological substances at radio and microwave 21 frequencies. The sensor which is described is not suitable 22 for impedance imaging.

23 A paper entitled "Messung der elektrisdhen Impedance 24 von Organen- Apparative AusrUstung fUr Forschung und 25 klinishe Anwendung" by E. Gersing (Biomed. Technik 36 26 (1991), 6-11) describes a system which uses single element 27 impedance probes for the measurement of the impedance of an 28 organ. The device described is not suitable for impedance 29 imaging.

A Paper titled "MESURE DE L'IMPEDANCE DES TISSUS 31 HEPATIQUELES TRANSFORMES PAS DES PROCESSUS LESIONELS" by J.

32 Vrana et al. (Ann. Gastroentreol. Hepetol., 1992, 28, no. 4, 33 165-168) describes a probe for assessing deep-tissue by use 34 of a thin injection electrode. The electrode was positioned by ultrasound and specimens were taken for cytological and 36 histological assessment. The electrode was constituted on a 2 1 biopsy needle used to take the samples.

2 A paper titled "Continuous impedance monitoring during 3 CT-guided stereotactic surgery: relative value in cystic and 4 solid lesions" by V. Rajshekhar (British Journal of Neurosurgery (1992) 6, 439-444) describes using an impedance 6 probe having a single electrode to measure the impedance 7 characteristics of lesions. The objective of the study was 8 to use the measurements made in the lesions to determine the 9 extent of the lesions and to localize the-lesions more 10 accurately. The probe is guided to the tumor by CT and four S11 measurements were made within the lesion as the probe passed 12 through the lesion. A biopsy of the lesion was performed 13 using the outer sheath of the probe as a guide to position, 14 after the probe itself was withdrawn.

A paper titled "Rigid and Flexible Thin-Film Multi- 16 electrode Arrays for Transmural Cardiac Recording" by J. J.

S17 Mastrototaro et al. (IEEE TRANS. BIOMED. ENG. Vol. 39, No.

18 3, March 1992, 271-279) describes a needle probe and a flat 19 probe each having a plurality of electrodes for the 20 measurement of electrical signals generated in the heart.

21 A paper entitled "Image-Based Display of Activation 22 Patterns Derived from Scattered Electrodes" by D. S. Buckles i.'23 et al. (IEEE TRANS. BIOMED ENGR. Vol. 42, No. 1, January 24 1995, 111-115) describes a system for measurement of electrical signals generated on the heart by use of an array 26 of electrodes on a substrate. The heart with the electrodes 27 in place is viewed by a TV camera and an operator marks the 28 positions of the electrodes on a display. The system then 29 displays the heart (as visualized prior to the placement of the electrodes) with the position markings.

31 A paper entitled "Development of a Multiple Thin-Film 32 Semimicro DC-Probe for Intracerebral Recordings" by G. A.

33 Urban et al. (IEEE TRANS. BIOMED ENGR. Vol. 37, No. 34 October 1990, 913-917) describes an elongate alumina ceramic probe having a series of electrodes along its length and 36 circumference for measuring functional parameters- 3 4 (electrical signals) in the brain. Electrophysiological recording, together with electrosimulation at the target point during steriotactic surgery, was performed in order to ensure exact positioning of the probe after stereotactic calculation of the target point. Bidimensional X-Ray imaging was used in order to verify the exact positioning of the electrode tip.

Summary of the Invention In one aspect, the present invention provides an apparatus for impedance imaging of a region of a subject, the apparatus comprising: a first, multi-element, probe comprising a plurality of sensing elements and adapted for mounting on a first side of the region; a second probe, including one or more sensing elements, adapted for mounting on a surface of the subject; and a controller which generates at least one impedance image, including a plurality of pixels, based on signals sensed by at least some of the sensing elements of the first probe and at least one of the one or more sensing elements of the second •i probe.

In another aspect, the present invention provides a method of impedance imaging of a body region of a subject, the method comprising: e*o *positioning a first, multi-element probe, comprising a first plurality of sensing elements, on a first side of the region; positioning a second probe, comprising one or more second sensing oo. elements, on a surface of the subject; and generating at least one impedance image based on signals sensed by at least some of the first elements and by at least one of the one or more elements of the second probe, while the first and second probes are not moved from their positions.

THE NEXT PAGE IS PAGE 21 [R\LIBLL]l 1389speci..doc:vjp 1 BRIEF DESCRIPTION OF THE DRAWINGS 2 The invention will be more fully understood and 3 appreciated from the following detailed description, taken 4 in conjunction with the drawings in which: Fig. 1 is an overall view of an impedance mapping 6 system especially suitable for breast impedance mapping in 7 accordance with a preferred embodiment of the invention; 8 Fig. 2 is a perspective view of an imaging head 9 suitable for breast impedance mapping in accordance with a ^i;i 1 0 preferred embodiment of the invention; 11 Figs. 3A and 3B show partially expanded views of two 12 preferred probe head configurations suitable for use in the 13 imaging head of Fig. 2; 14 Fig. 4 is a top view of a portion of a multi-element 15 probe in accordance with a preferred embodiment of the 16 invention; 17 Fig. 5A is a partial, partially expanded cross- 18 sectional side view of the probe of Fig. 4 along lines

V-V,

19 suitable for the probe head configuration of Fig. 3B; Fig. 5B is a partially expanded cross-sectional side 21 view of an alternative probe in accordance with a preferred 22 embodiment of the invention; 23 Fig. 5C shows an alternative embodimenrt of a multi-- 24. element probe, in accordance with a preferred embodiment of the invention; 26 Fig. 6A is a perspective view of a hand held probe in 27 accordance with a preferred embodiment of the invention; 28 Fig. 6B shows a partially expanded bottom view of the 29 probe of Fig. 6A, in accordance with a preferred embodiment of the invention; 31 Fig. 7A is a perspective view of a fingertip probe in.

32 accordance with a preferred embodiment of the invention; 33 Fig. 7B shows a conformal multi-element probe; 34 Fig. 8 shows an intra-operative probe used determining the position of an abnormality in accordance with a 36 preferred embodiment of the invention; 21 1 Fig. 9 shows a laparoscopic probe in accordance with a 2 preferred embodiment of the invention; 3 Fig. 10 shows a biopsy needle in accordance with a 4 preferred embodiment of the invention; Fig. 11A illustrates a method of using the biopsy 6 needle of Fig. 10, in accordance with a preferred embodiment 7 of the invention; 8 Fig. 11B illustrates a portion of a display used in 9 conjunction with the method of Fig. 11A; Fig. 11C shows a biopsy guiding system in accordance 11 with a preferred embodiment of the invention; 12 Fig. 1 1 D shows a frontal biopsy guiding system in .13 accordance with a preferred embodiment of the invention; 14 Fig. 1 1 E shows a lateral biopsy guiding system in 15 accordance with a preferred embodiment of the invention; S*16 Fig. 12 shows, very schematically, the inter-operative 17 probe of Fig. 8 combined with a video camera use to more 18 effectively correlate an impedance measurement with 19 placement of the probe.

Fig. 13 illustrates a laparoscopic probe according to 21 the invention used in conjunction with a fiber-optic 22 illuminator-imager; 23 Fig. 14 illustrates a display, according-to a preferred 24 embodiment of the invention showing both capacitive and 25 conductance images illustrative of atypical hyperplasia; 26 Fig. 15 illustrates a display, according to a preferred 27 embodiment of the invention showing both capacitive and 28 conductance images illustrative of a carcinoma; and 29 Fig. 16 illustrates a method useful for verifying a detected local impedance deviation as being non-artifactal 31 and for estimating the deviation; 32 Figs. 17A and 17B are a block diagram_of circuitry 33 suitable for impedance mapping in accordance with a 34 preferred embodiment of the invention.

36 22 1 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 2 Reference is made to Figs. 1 and 2 which illustrate an 3 impedance mapping device 10 suitable for mapping the 4 impedance of a breast.

Mapping device 10 includes an imaging head 12, which is 6 described below, which holds the breast and provides contact 7 therewith for providing electrical excitation signals 8 thereto and for receiving resultant electricil signals 9 therefrom. Signals to and from the head are generated and received by a computer/controller 14 which- produces 11 impedance maps of the breast under test for display on a 12 monitor 16. The impedance maps may be stored in 13 computer/controller 14 for later viewing or processing or 14 hard copies may be provided by a hard copy device 18 which 15 may be a laser printer, video printer, Polaroid or film 16 imager or multi-imager.

17 The entire mapping device 10 may be conveniently 18 mounted on a dolly 20 to facilitate placement of the imaging 19 head with respect to the patient.

20 Fig. 1 also shows a hand held probe 100, described in 21 more detail below, and a reference probe 13.

22 Fig. 2 shows imaging head 12 in more detail. Head 12 23 comprises a movable lower plate probe 22 and a stationary 24 upper plate probe 24 which is mounted on a pair of rails 26 to allow the distance between plate probes 22 and 24 to be 26 varied.

27 Movement- of plate probe 22 along rails 26 may be 28 achieved either by a motor (not shown) including suitable 29 protection against over-pressure as is traditional in X-ray breast imaging, or by hand.

31 Either or both of plate probes 22 and 24 are provided 32 with multi-element probes 28 and 30 respectively, which are 33 described more fully below, which electrically contact the 34 breast with a plurality of sensing elements to optionally provide electrical excitation to the breast and to measure 36 signals generated in response to the provided signals.

23 1 Alternatively, electrical excitation to the breast is .2 provided by reference probe 13 which is placed on the arm, 3 shoulder or back of the patient, or other portion of the 4 patient.

In practice, a breast is inserted between probes 28 and 6 30 and plate probe 24 is lowered to compress the breast 7 between the probes. This compression reduces the distance 8 between the probes and provides better contact between the 9 sensing elements and the skin of the breast- Although 10 compression of the breast is desirable, the degree of 11 compression required for impedance imaging is much lower 12 than for X-Ray mammography, and the mapping technique of the 13 present invention is typically not painful.

14 Alternatively or additionally, the probes are curved to conform with the surface of the breast.

16 Head 12 is provided with a a pivot (not shown) to allow 17 for arbitrary rotation of the head about one or more of its 18 axes. This allows for both medio-lateral and cranio-caudal 19 maps of the breast to be acquired, at any angular 20 orientation about the breast. Preferably, head 12 may be S21 tilted so that the surfaces of plate probes 22 and 24 are 22 oriented with a substantial vertical component so that 23 gravity assists the entry of the breast into the- space 24 between the maximum extent and to keep it from inadvertently falling out. This is especially useful when the patient 26 leans over the plates so that her breasts are positioned 27 downwardly between the plate probes.

28 Furthermore, in a preferred embodiment of the 29 invention, one or both of probes 28 and 30 may be rotated about an axis at one end thereof, by a rotation mechanism 27 31 on their associated plate probes 22 or 24, such as is shown 32 in Fig. 2 for probe 28. Additionally or alternatively, 33 probes 28 and/or 30 may be slidable, as for example along 34 members 31.

Such additional sliding and rotating flexibility is 36 useful for providing more intimate skin contact of the 24 1 probes with the breast, which has a generally conical shape.

2 Furthermore, such flexibility allows for better imaging of 3 the areas of the breast near the chest wall or the rib cage, 4 which are extremely difficult to image in x-ray mammography.

Figs. 3A and 3B show partially expanded views of two 6 probe head configurations suitable for use in the imaging 7 head of Fig. 2, in accordance with preferred embodiments of 8 the invention.

9 In the embodiment of Fig. 3A, a preferably removable i 1 0 multi-element probe 62, which is described below in more 11 detail, is attached to a probe head base 50 via a pair of S 12 mating multi-pin connectors 51 and 52. A cable 53 couples 13 connector 52 to computer 14. When multi-element probe 62 is 14 inserted into base 50 (that is to say, when connector 51 is 15 fully inserted into connector 52), the relatively stiff 16 bottom of probe 62 rests on ledges 54 formed in the base, 17 such that the surface 55 of the base and the surface of 18 element 62 are preferably substantially coplanar.

19 In the embodiment of Fig. 3B, a series of contacts 82 20 are formed on base 50 and a disposable multi-element probe 21 62' is attached to the contacts as described below with 22 reference to Fig. 5A and 5B. Cable 53 couples the contacts 23 to computer 14.

24 Figs. 4, 5A and 5B show top and side views of a portion of multi-element probe 62' and contacts 74, while Figs. 26 and 5B show a partially expanded cross-sectional side view 27 of probe 62' along lines V-V. While the embodiment shown in 28 Figs. 4, 5A and 5B is especially suitable for the probe head 29 configuration of Fig. 3B, much of the structure shown in these figures 5 is common to multi-element probes used in 31 other configurations described herein.

32 As shown in Figs. 4, 5A and 5B, disposable multi- 33 element probe 62' preferably incorporates a plurality of 34 sensing elements 64, separated by separator or divider elements 66.

36 As shown more clearly in Figs. 5A and 5B, sensing 25 1 elements 64, comprise a bio-compatible conductive material 2 (for example Neptrode E0751 or Neptrode E0962 Hydrogel 3 distributed by Cambrex Hydrogels, Harriman, NY) such as is 4 sometimes used for ECG probes in a well 70 formed, by a first, front, side of a mylar or other flexible, non- 6 conducting substrate 68, such as a thin mylar sheet and the 7 divider elements 66. A suitable thickness for the mylar 8 sheet is approximately 0.2 mm for probe 62'.-The substrate 9 is preferably pierced in the center of each well. The hole resulting from the piercing is filled with a conducting 11 material which is also present on the bottom of well 70 and 12 on a second, back, side of substrate 68 to form a pair of 13 electrical contacts 72 and 74 on either side of the 14 substrate and an electrically conducting feed-through 76 15 between the pair of contacts. As shown, a separate contact 16 pair and feed-through is provided for each sensing element.

17 Alternatively, the substrate may be formed of any 18 suitable inert material including plastics such as 19 polyethylene, polypropylene, PVC, etc.

Wells 70 may be formed in a number of ways. One method 21 of forming the wells is to punch an array of square holes in 22 a sheet of plastic, such as polypropylene, which is about 23 0.2-lmm thick. This results in a sheet containing only the 24 -divider elements. This sheet is bonded to substrate 68 which has been pre-pierced and in which the contacts and feed- 26 throughs have been formed. Another method of forming the 27 wells is to emboss a substrate containing the contacts and- 28 feed-throughs to form divider elements in the form of ridges 29 which protrude from the substrate as shown in Fig. 5B. Yet another method of producing the wells is by printing the 31 well walls using latex based ink or other bio-compatible- 32 material having a suitable firmness and flexibility. Another 33 method of production is by injection molding of the 34 substrate together with the divider elements. And yet another method of producing the wells is by laminating to 36 the substrate a preformed grid made by die cutting the array 26 1 of divider elements in a sheet of plastic, injection 2 molding, or other means.

3 The conductors and feed-throughs may be of any 4 conductive material which will provide reliable feed-through plating of the holes. One method of manufacturing the 6 contacts and holes is by screen printing of the contacts on 7 both sides of the substrate. If conductive paste having a 8 suitable viscosity is used, the paste will fill.the hole and 9 form a reliable contact between contacts 72 and 74. Although many conductive materials can be used, non-polarizing 11 conductors, such as silver/silver chloride are preferred.

A

S12 conductive paste suitable for silk screening the conductors 13 onto the substrate is Pad Printable Electrically conductive 14 Ink No. 113-37 manufactured and sold by Creative Materials Inc., Tyngsboro,

MA.

16 In general contacts 72 and 74 are only 10-200 microns 17 thick and wells 70 are generally filled with conductive 18 viscous gel material or hydrogel material to within about 19 0.2 mm of the top of the dividing elements. In general, if :20 low separators are used, the hydrogel may be omitted.

21 However, in the preferred embodiment of the invention, the 22 wells are at least partially filled by hydrogeL or a similar 23 material.

24 Hydrogel is available in both UV cured and heat cured.

compositions. In either case a measured amount of uncured 26 semi-liquid hydrogel is introduced into each well and the 27 hydrogel is cured. Alternatively, the wells are filled with-- 28 the uncured material and a squeegee which is pressed against 29 the top of the divider elements with a predetermined force is moved across the top of the divider elements. This will 31 result in the desired gap between the top of the hydrogel--: 32 and the top of the wells.

33 In an alternative embodiment of the invention, the 34 hydrogel material is replaced by a sponge material or similar supportive matrix impregnated with conductive 36 viscous gel or the well is simply filled with the conductive 27 1 gel to the desired height.

2 During use of the probe, the probe is urged against the 3 skin which is forced into the wells and contacts the 4 hydrogel or alternative conductive material. Optionally a somewhat viscous conductive gel, such as Lectron II 6 Conductivity Gel (Pharmaceutical Innovations, Inc. Newark, 7 NJ), may be used to improve contact with the skin. In this 8 case, the dividing elements will reduce the. conduction 9 between the cells such that the substantial independence of the individual measurements is maintained. Alternatively, 11 the conductive gel may be packaged together with the probe, *12 with the conductive gel filling the space between the top of 13 the hydrogel and the top of the wells. The use of a 14 conductive gel is preferred since this allows for sliding 15 movement of the probe and its easy positioning while it is 16 urged against the skin. The separators substantially prevent 17 the conductive gel from creating a low conductance path 18 between adjoining sensing elements and also keep the 19 hydrogel elements from touching each other when the probe is 20 applied to the skin with some pressure.

21 In a further preferred embodiment of the invention, the 22 sensing elements are formed of a conductive fpam or sponge 23 material such as silicone rubber or other conductive rubber 24 -or other elastomer impregnated with silver or other conductive material, as shown in Fig. 5C. Fig. 5C shows the 26 sensing elements without walls 66. Elements which protrude 27 from the substrate as shown in Fig. 5C may achieve 28 substantial electrical isolation from one another by spacing 29 them far enough apart so that do not contact each other in use or by coating their lateral surfaces with insulating 31 material such as polyethylene or other soft non-conductive 32 plastic or rubber.

33 For relatively short rigid or compressible elements, it 34 has been found that reducing the size of the sensing elements such that no more than 70% (and preferably no more 36 than 50%) of the area of the array is covered is sufficient 28 1 to reduce the "cross-talk" between adjoining elements to an 2 acceptable level.

3 If sufficiently good isolation is achieved between 4 probe elements by their spacing alone, then foam or other elements without hydrogel and without walls 66 may be 6 provided. Sensing elements such as those shown in Fig. 7 conform and mate to uneven surfaces when pressed against 8 tissue.

9 Multi-element probe 62', which is preferably used for only one patient and then discarded, is preferably removably *11i attached to a probe holder which preferably comprises a 12 printed circuit board 80 having a plurality of contacts 82 13 corresponding to the contacts 74 on the back of the 14 substrate, each PC board contact 82 being electrically 15 connected to a corresponding contact 74 on the substrate.

16 To facilitate alignment of the matching contacts, an 17 alignment guide 90 is preferably provided on or adjacent to 18 PC board 80 (Fig. This guide may consist of a series of 19 guide marks or may consist of a raised edge forming a well 20 into or onto which the substrate is inserted. Conductors 21 within PC board 80 connect each of the contacts to one of 22 the pins of connector 51, which is preferably mounted on PC 23 board 24 Alternatively and preferably, as described below with 25 respect to Fig. 6B, the guide may consist of two or more 26 pins located on or near PC board 80, which fit into matching 27 holes in probe 62'.

28 Alternatively as shown in Fig. 5B, the back side of the 29 embossing of substrate 68 is used as the guide for one or more protruding elements 83 which are preferably mounted on 31 PC board 80. Preferably a plurality of protruding elements-.

32 are provided to give good alignment of the substrate with 33 the PC board. The elements may run along the periphery of 34 the probe and form a frame-like structure as shown in Fig.

5B or may run between the elements or may take the form of x 36 shaped protuberances which match the shape of the embossing 29 1 at the corners of the wells.

2 Protruding elements 83 may be formed of polycarbonate, 3 acetate, PVC or other common inert plastic, or of a 4 noncorrosive metal such as stainless steel.

A wire 84 is connected to each PC contact 82 and is 6 also connected to apparatus which provides voltages to 7 and/or measures voltages and/or impedances at the individual 8 sensing elements 64, as described below.

9 In a preferred embodiment of the invention, conductive i:i. 10 adhesive spots 86 preferably printed onto the back of the 11 substrate are used to electrically and mechanically connect 12 contacts 74 with their respective contacts 82. Preferably a 13 conductive adhesive such as Pressure Sensitive Conductive 14 Adhesive Model 102-32 (Creative Materials Inc.) is used.

Alternatively, the adhesive used for printing the 16 contacts/feed-throughs is a conducting adhesive and adhesive 17 spots 86 may be omitted. Alternatively, pins, which protrude 18 from the surface of PC board 80 and are connected to wires 19 84 pierce the substrate (which may be pre-bored) and contact :20 the gel or hydrogel in the wells. A pin extending from the .21 substrate may also be inserted into a matching socket in the 22 PC board to form the electrical connection between the 23 sensing element and the PC board. Alternatively, -the entire 24 back side of the substrate can be adhered to the printed.

circuit board surface using an anisotropically conductive 26 thin film adhesive which has a high conductivity between 27 contacts 74 and 82 and which has a low conductivity- 28 resulting in preferably many times higher resistance between 29 adjoining contacts than between matching contacts, in practice at least one hundred times different. An example of 31 such adhesive is tape NO. 3707 by MMM Corporation,-: 32 Minneapolis MN. However, due to the difficulty of applying 33 such material without trapped air bubbles, it may be 34 preferably to apply adhesive only to the contacts themselves. In practice a release liner of polyethylene,.

36 mylar or paper with a non-stick surface on one side is 30 1 provided on the lower side of the adhesive sheet. This liner 2 protects the adhesive layer prior to connection of "the 3 disposable multi-element probe to the probe holder and is 4 removed prior to the connection of the probe to the holder.

Preferably, the impedance between contacts 82 and skin 6 side of the conducting material in the wells should be less 7 than 100 ohms at 1 kHz and less than 400 ohms at 10 Hz.

8 Impedance between any pair of contacts 82, with the 9 multi-element probe mounted should preferably be greater than 10 kohm at 1 kHz or 100 kohm at 10 Hz.

11 Another suitable material for producing substrates is 12 TYVEX (DuPont) substrate which is made from a tough woven 13 polyolefin material available in various thicknesses and S14 porosities. If such material having a suitable porosity is 15 used, contacts 72 and 74 and feed-through 76 can be formed 16 by a single printing operation with conductive ink on one 17 side of the TYVEX sheet. Due to the porosity of the TYVEX, 18 the ink will penetrate to the other side of the TYVEX and 19 form both contacts and feed-through in one operation.

S20 For probe 62 in the embodiment of Fig. 3A, substrate S21 68 is replaced by a relatively rigid PC board which includes 22 conducting wires to attach each of electrical contacts 72 to t 23 one of the pins of connector 51 (Fig. 3 A) and -the rest of 24 the connecting structure of Fig. 5A may be omitted. It should be noted that the choice of using the structure of 26 Figs. 3A or 3B probes 62 or 62') is an economic one 27 depending on the cost of manufacture of the probes. Whil-e 28 probe 62 is structurally simpler, the disposable portion of 29 probe 62' is believed to be less expensive to manufacture in large quantities. Since it is envisioned that the probes 31 will be used in large quantities and will preferably not bi 32 reused, one or the other may be preferable.

33 The other side of the probe is also protected by a 34 cover plate 88 (Figs. 5A and 5B) which is attached using any bio-compatable adhesive to the outer edges of dividers 66 36 (Fig. 5A) and/or to the hydrogel, which is preferably 31 1 moderately tacky. In one preferred embodiment of the 2 invention, the inner surface of the cover plate 88 is 3 provided with an electrically conductive layer so that the 4 impedance of each sensing element from the outer surface of the hydrogel (or conductive gel) to contact 82, can be 6 measured using an external source. In addition, if a known 7 impedance is connected between the conductive layer and a 8 reference point or a source of voltage, the sensing elements 9 can be tested in a measurement mode similar to that in which they will finally be used.

11 Alternatively, a film RC circuit or circuits may be :12 printed on the inner surface of plate 88 to simulate an 13 actual impedance imaging situation. Alternatively, plate 88 14 may be provided with contacts at each sensing location, and circuitry which may simulate a plurality of actual impedance 16 imaging situations. Such circuitry may include external or 17 integral logic such as programmable logic arrays and may be 18 configurable using an external computer interface. The 19 simulation may provide a distinct RC circuit for each 20 sensing element or may provide a sequence of different 21 circuits to each sensing element to simulate the actual 22 range of measurements to be performed using -the probe.

23- Fig. 5B shows a preferred embodiment of cover sheet 88 24 (indicated on the drawing as 88') and its mode of attachment to both the multi-element sensor and the PC board. In this 26 embodiment a multi-element probe 62" is optionally further 27 attached to PC board 80 by an adhesive frame 210 which may 28 be conductive or non-conductive, and which assists in 29 preventing entry of water or gel under sensor 62". Sensor 62" is preferably further aligned to PC board 80 by one or.

31 more holes 222 with one or more pins 204, which are 32 permanently attached to PC board 80 or to a surface adjacent 33 to PC board 80. While pin 204 is shown as being round, using 34 rectangular, triangular, hexagonal pyramidical or other shapes provides additional alignment of the sensor. In 36 general the upper portion of the pin should be curved for 32 1 improved electrical contact as described below.

2 The upper exposed surface of pin 204 is conductive, 3 preferably curved and is preferably connected to a signal 4 reference source by a conductor 202 in PC board 80. Cover sheet 88' is made of a single integral sheet of easily 6 deformable polyethylene, Mylar or other suitable plastic.

7 Cover sheet 88' is preferably removably attached to the 8 upper side of multi-element probe 62" by a continuous frame 9 of adhesive 225, which need not be conductive, but which 1• .0 seals around a lip where cover 88' contacts probe 62" to 11 protect the quality and sterility of array 230 and to 12 maintain the moisture content of any medium filling wells 13 70. Cover 88' is coated on the side facing probe 62" with a 14 conductive layer 231, such as any of the various metallic coatings, for example, aluminum or the thin film coating 16 described above.

17 Cover 88' is preferably formed after conductive 18 coating, by embossing, vacuforming or other means, to have 19 depressions 233 in the cover located over corresponding 20 wells 70. The depressions are approximately centered on the 21 center of the wells and held a small distance "61" above 22 the surface of the hydrogel or gel, by means of. relatively 23-- high sidewalls 226 which are formed at the same time as 24 depressions 233. Furthermore, the surface of cover 88' preferably has a concave shape to match the rounded 26 conductive contact surface of pin 204, from which it is 27 held at a distance Distances 61 and 62 are selected to 28 minimize unintended physical contact between the conductive 29 inner surface of the cover, the contacts in the wells and pin 204, for example, during storage and handling prior to-- 31 use, which might cause corrosion over time due to 32 electrochemical processes.

33 Distances 61 and 62 are also preferably selected so 34 that application of a nominal force (preferably about one kilogram) against a flat outer surface 232 of cover 88', 36 such as by a weighted flat plate, will establish contact 33 1 between the inner coating 231 and the upper surface of pin 2 204 and with the sensing elements or the gel in the wells.

3 By establishing this contact, the conductive inner 4 surface 231 is connected, on the one hand to signals source contact 202 and with each sensing element. If the coating is 6 a conductor, the sensing elements are all excited by the 7 signal on line 202; if it is a thin film :circuit, the 8 contact is via the thin film circuit. In either event, if .9 line 202 is excited by a signal, the signal will be •'10 transmitted to each of the sensing elements, either 11 directly, or via a known impedance.

12 In either case, the multi-element array can be tested 13 by the system and any residual impedance noted and corrected 14 when the probe is used for imaging. If the residual 15 impedance of a given sensing element is out of a 16 predetermined specification, or is too large to be 17 compensated for, the multi-element probe will be rejected.

18 Furthermore, the computer may be so configured that imaging 19 may only take place after determination of the contact 20 impedance of the sensing elements or at least of 21 verification that the probe impedances ,are within a 22 predetermined specification.

23- While pin 204 is shown as being higher than the top of 24 the wells, the pin may be at the same height as the wells, jr~i~i, ~25 or even below the wells with the cover being shaped to 26 provide a suitable distance "62" as described above.

27 In an alternative embodiment of the invention, the 28 contact surface corresponding to pin 204 is printed on or 29 attached to the surface holding the sensing elements, with contact to the PC board being via a through contact i -f* 31 substrate 68, as for the sensing elements.

32 In yet another embodiment of the invention, the 33 conductive contact surface associated with pin 204 is on the 34 surface holding the sensing elements adjacent to pin 204- Pin 204 supports this surface and contacts the contact 36 surface via one, or preferably a plurality of through 34 1 contacts. Pin 204 is designed to match the contour of the 2 contact surface and preferably, by such matching, to provide 3 additional alignment of the probe on the PC board.

4 To avoid drying out of the Gel or other potential hazards of limited shelf life, the quality of any of the 6 aforementioned versions of the disposable electrode arrays 7 can be assured by incorporating an identification code, 8 preferably including manufacturer and serial number 9 information and date of manufacture. n a preferred 10 embodiment, the information is coded in a bar code printed 11 on each disposable probe, which is packaged together with at 12 least one other such probe (typically 5-50 probes) in the 13 same packet, which also has the same bar code. A bar code 14 reader, interfaced with the system computer, reads the manufacturing information on the packet and each probe, 16 checking for date and compliance and Permitting recording 17 only for a number of patients equal to the number of probes 18 in the packet.

19 In a preferred embodiment of the invention a bar code may be placed on the individual disposable electrode arrays 21 which can be read by a bar code reader installed in or under oeoe 22 the PC board, for example near reference numeral 83 of Fig.

23 24 While the invention has been described in conjunction with the preferred embodiment thereof, namely a generally 26 flat, somewhat flexible structure, suitable for general use 27 and for breast screening, other shapes, such as concave 28 structures brassiere cups) or the like may be 29 preferable, and in general the shape and configuration of the detectors will depend on the actual area of the body to 31 be measured. For example cylindrical arrays can be useful in- 32 certain situations, for example in intra-rectal examinations 33 of the prostate or colon or inside vessels. In this context, 34 a probe according to the invention is also useful for measurements inside the body, for example gynecological 36 measurements or measurements in the mouth, where the probe 35 1 is inserted into a body cavity and contacts the lining of 2 the cavity, and probes having shapes which correspond either 3 flexibly or rigidly to the surface being measured can be 4 used. For example, a multi-element probe in accordance with the invention may be incorporated into or attached to a 6 laparoscopic or endoscopic probe.

7 Furthermore, sterilized probes can be used in invasive 8 procedures in which the probe is placed against tissue 9 exposed by incision. In this context, theterm "skin" or i0 "tissue surface" as used herein includes such cavity lining 11 or exposed tissue surface.

12 In a preferred embodiment of the invention, PC board 13 and as many elements as possible of probe 62' (or the board 14 of probe 62) are made of transparent or translucent 15 material, so as to provide at least some visibility of the 16 underlying tissue during placement of probe 62. Those 17 elements of the probe and conductors in the PC board, to the 18 extent that they are opaque should be made as small as 19 practical to provide the largest possible view to a technician or clinician to aid in placement of the probe.

21 Furthermore, probe 62 is slidably displaceable when used 22 with the above-mentioned conductive gel to permit moderate .o.

23 lateral adjustment of the probe positioR, to aid in- 24_ placement, to ensure good contact between each element and the tissue surface to be measured, and to enable the user to 26 rapidly verify whether detected abnormalities are artifacts 27 due to poor contact or are genuine objects, since artifacts 28 remain stationary or disappear entirely when the probe is 29 moved while genuine objects just move in a direction opposite to the direction of movement of the probe.

31 The general shape and size of the multi-element probe_ 32 and the size of the conductive sensing elements will depend 33 on the size of the area to be measured and on the desired 34 resolution of the measurement. Probe matrix sizes of greater than 64 x 64 elements are envisioned for viewing large areas 36 and probes which are as small as 2 x 8 elements can be 36 1 useful for measuring small areas. Element size is preferably 2 between 2 mm square and 8 mm square; however, larger suzes 3 and especially smaller sizes can be useful under certain 4 circumstances. For the breast probe 62 described above, 24 x 32 to 32 x 40 elements appear to be preferred matrix sizes.

6 Fig. 6A shows a perspective view of a hand held probe 7 100 in accordance with a preferred embodiment of the 8 invention. Probe 100 preferably comprises tw6 probe heads, a 9 larger head 102 and a zoom sensor head 104. A handle 106 connects the sensor heads, houses switching electronics and 11 provides means for holding and positioning the probes.

12 Handle 106 also optionally incorporates a digital pointing 13 device 105 such as a trackball, pressure sensitive button or 9..

14 other such joystick device. Incorporation of a pointing device on the probe enables the operator to control the 16 system and input Positional information while keeping both 17 hands on either the probe or patient. As described below, 18 the digital pointing device can be used to indicate the 19 position on the patient's body at which the image is taken.

20 Fig. 6B shows a partially expanded bottom view of probe 21 100 of Fig. 6A, in accordance with a preferred embodiment of 22 the invention. Where applicable, like parts, of the probes '0 0 023 throughout this disclosure are similarly numbered. Starting 24 from the bottom of Fig. 6B, the top half of a housing 108A 25 has a well 110 formed therein. A clear plastic window 112 is 26 attached to the edge of well 110, and a printed circuit on a 27 relatively transparent substrate, such as Kapton, designated 28 by reference 80' (to show its similarity to the 29 corresponding unprimed element of Fig. 5) is placed on window 112. A flexible print cable 114 connects the contacts 31 on printed circuit 62' to acquisition electronics 116.

A

32 cable 118 connects the acquisition electronics to the 33 computer. A second Similarly constructed, but much smaller 34 zoom sensor probe head is attached to the other end of probe 100. Either of the larger or smaller heads may be used for 36 imaging.

37 1 A lower half of housing 108B, encloses electronics 116 2 and print 80', whose face containing a series of contacts 3 82', is available through an opening 120 formed in the lower 4 housing half 108B. A mounting frame 122 having two alignment pins 124 holds print 80' in place. Mounting and connecting 6 screws or other means have been omitted for simplification.

7 A disposable multi-element probe 62', similar to that 8 of Fig. 5 is preferably mounted on the mounting frame to 9 complete the probe.

I 10.. I Fig. 7A is a perspective view of a fingertip probe 130 i,11 in accordance with a preferred embodiment of the invention 12 as mounted on the finger 132 of a user. Probe 130 may be 13 separate from or an integral part of a disposable glove, 14 such as those normally used for internal examinations or 15 external palpation. The fingertip probe is especially useful 16 for localizing malignant tumors or investigating palpable 17 masses during surgery or during internal examinations. For 18 example, during removal of a tumor, it is sometimes 19 difficult to determine the exact location or extent of a 20 tumor. With the local impedance map provided by the 21 fingertip probe 130 and the simultaneous tactile information 22 about the issue contacted by the probe, thq tumor can be 23 located and its extent determined during surgery. In a like 24- fashion, palpable lumps detected during physical breast (or other) examination can be routinely checked for impedance 26 abnormality.

27 Fig. 7B shows a flexible probe array 140 which is showfi 28 as conforming to a breast being imaged. Probe array 140 29 comprises a plurality of sensing elements 141 which contact the tissue surface which are formed on a flexible substrate.

31 Also formed on the flexible substrate are a Plurality of-' 32 printed conductors 142 which electrically connect the 33 individual sensing elements 141 to conductive pads on the 34 edge of the substrate. A cable connector 144 and cable 145 provide the final connection link from the sensing elements- 36 to a measurement apparatus. Alternatively, the flexible 38 1 array may take a concave or convex shape such as a cup 2 (similar in shape to a bra cup) which fits over and contacts 3 the breast.

4 The flexible substrate is made of any thin inert flexible plastic or rubber, such as those mentioned above 6 with respect to Fig. 5A. Array 140 is sufficiently pliant 7 that, with the assistance of viscous gel or conductive 8 adhesive, the sensor pads are held in intimate contact with 9 the skin or other surface, conforming to its shape.

1 0 Fig. 8 shows an intra-operative paddle type probe 140 11 used, in a similar manner as probe 130, for determining the 12 position of an abnormality in accordance with a preferred 13 embodiment of the invention. This probe generally includes 14 an integral sensing array 143 on one side of the paddle.

Preferably, the paddle is made of substantially transparent 16 material so that the physical position of the array may be 17 determined and compared with the impedance map.

18 Fig. 9 shows a laparoscopic probe 150 in accordance 19 with a preferred embodiment of the invention. Probe 150 may 20 have a disposable sensing array 152 mounted on its side or 21 the sensing array may be integral with probe 150, which is 22 disposable or sterilizable.

23 Multi-element probes, such as those shown in Figs. 7, 8 24- and 9, are preferably disposable or sterilizable as they are 25 generally are used inside the patients body in the presence 26 of body fluids. In such situations, there is generally no 27 need or desire for a conductive gel in addition to the 28 probes themselves. Generally, printed sensing elements, such 29 as those printed with silver-silver chloride ink, or sensing elements formed of conductive silicone, hydrogel or of a 31 conductive sponge may be used. While in general it i-- 32 desirable that the sensing elements on these- multi-element 33 probes be separated by physical separators 66 (as- shown in 34 Fig. under some circumstances the physical distance between the elements is sufficient and the separators may be 36 omitted.

39 1 When performing a needle biopsy, a physician generally 2 relies on a number of indicators to guide the needle to the 3 suspect region of the body. These may include tactile feel, 4 X-Ray or ultrasound studies or other external indicators.

While such indicators generally give a reasonable 6 probability that the needle will, in fact take a sample from 7 the correct place in the body, many clinicians do not rely 8 on needle biopsies because they may miss the-tumor.

9 Fig. 10 shows a biopsy needle 154, in accordance with a preferred embodiment of the invention, which is used to 11 improve the accuracy of placement of the needle. Biopsy 12 needle 154 includes a series of sensing elements 156 spaced 13 along the length of the probe. Leads (not shown) from each 14 of these elements bring signals from the elements to a detection and computing system such as that described below.

16 Elements 156 may be continuous around the circumference, in 17 which case they indicate which portion of the needle is 18 within the tumor to be biopsied. Alternatively, 19 the electrodes may be circumferentially segmented (a lead 20 being provided for each segment) so that information as to 21 the direction of the tumor from the needle may be derived 22 when the needle is not within the tumor. Such an impedance 23 sensing biopsy needle can be used, under guidance by 24 palpation, ultrasound, x-ray mammography or other image from other image modalities (preferably including impedance 26 imaging as described herein), taken during the biopsy or 27 prior to the biopsy to improve the accuracy of placement of 28 the needle. In particular, the impedance image from the 29 needle may be combined with the other images in a display.

While this aspect of the invention has been described using 31 a biopsy needle, this aspect of the invention is also 32 applicable to positioning of any elongate object such as an 33 other needle (such as a localizing needle), an endoscopic 34 probe or a catheter.

Returning now to Figs. 1-3 and referring additionally 36 to Figs. 11-14, a number of applications of multi-element 40 1 probes are shown. It should be understood that, while some 2 of these applications may require probes in accordance with 3 the invention, others of the applications may also be 4 performed using other types of impedance probes.

Fig. 11A shows the use of the biopsy needle in Fig. 6 together with an optional ultrasound imaging head in 7 performing a biopsy. A breast 160 having a suspected cyst or 8 tumor 162 is to be biopsied by needle 154. An ultrasound 9 head 164 images the breast and the ultrasound image, after 10 processing by an ultrasound processor 166 of standard design 11 is shown on a video display 168. Of course, the ultrasound 12 image will show the biopsy needle. The impedance readings 13 from probe 154 are processed by an impedance processor 170 14 and are overlaid on the ultrasound image of the biopsy needle in the display by a video display processor 172.

16 In one display mode, the portions, as shown in Fig. 11B 17 of the needle which are within the tumor or cyst and which 18 measure a different impedance from those outside the tumor, 19 will be shown in a distinctive color to indicate the portion 20 of the needle within the tumor or cyst. In a second display 21 mode, the impedance measured will be indicated by a range of 22 colors. In yet a third embodiment of the invention, in which 23 circumferentially segmented sensing element-: are employed, 24-- the impedance processor will calculate radial direction of 25 the tumor from the needle and will display this information, 26 for example, in the form of an arrow on the display.

27 The image sensing biopsy needle can also be used with 28 one or more imaging arrays (28, 30) such as those shown in 29 Fig. 6 or Fig. 3B to impedance image the region to be biopsied during the biopsy procedure. Alternatively, at 31 least one of the arrays can be an imaging array of the non.-.

32 impedance type. In one preferred embodiment,-shown in Fig.

33 11C, the needle is inserted through an aperture (or one of a 34 plurality of apertures) 174 in a multi-element probe which is imaging the region. The region may, optionally, be 36 simultaneously viewed from a different angle (for example at 41 1 90° from the probe with the aperture) with an other 2 impedance imaging probe. In the case that both arrays 28 and 3 30 are impedance imaging arrays, the biopsy needle or other 4 elongate object can either have impedance sensing or not, and the two images help direct it to the region. The probe 6 with one or more apertures is sterile and preferably 7 disposable. This biopsy method is shown, very schematically, 8 in Fig. liC. 9 In an alternative preferred embodiment of the 1 0 invention, only the perforated plate through which the 11 needle or elongate object is passed is an imaging array. In 12 this case the array through which the needle passes give a 13 two dimensional placement of the impedance abnormality while 14 an imaging or non-imaging impedance sensor on the needle gives an indication of when the needle has reached the 16 region of impedance abnormality, as described above.

17 Alternative guiding systems for frontal and lateral 18 breast biopsy or for guiding an elongate element to a 19 desired impedance region of the body are shown in Figs. 11D 000 *20 and 11E, respectively.

21 Fig. liD shows a system for in which two relatively 22 large plate multi-element probes 28, 30 are placed on 23 opposite sides of the desired tissue, shown as a -breast 160 24 of a prone patient 161. Sensor array probes 28 and 30 are.

held in position by positional controller 181 via rotatable 26 mounts 191. A mount 198 positions a biopsy needle 199 within 27 the opening between probe arrays 28 and 30, and is operative- 28 to adjust its height. A suspicious region 183 which is 29 located at positions 184 and 185 on arrays 28 and respectively as described herein, which information is 31 supplied to a CPU 197, which determines the position of the- 32 suspicious region for controller 181. The controller then 33 inserts the needle into the suspicious region, for example, 34 to take the biopsy. Biopsy needle 199 is preferably of the type shown in Fig. 10 to further aid in positioning of the, 36 needle. As indicated above, this is not required for some 42 1 embodiments of the invention.

2 Alternatively, biopsy needle 199 may be inserted 3 through holes formed between the elements of probes 28 4 and/or 30 as described above. Furthermore, while automatic insertion of the biopsy needle is shown in Fig. 11D, manual 6 insertion and guidance based on impedance images provided by 7 the probes is also feasible.

8 Fig. 11E shows a system similar to that of Fig. 11D in 9 which the imaging and biopsy needle insertion is from the side of the breast, rather than from the front. Operation of 11 the method is identical to that of Fig. 11D, except that an 12 additional probe 29 may be provided for further localization 13 of suspicious region 183. Alternatively, one or two of the 14 probes may be substituted by plates of inert material for 15 holding and positioning the breast.

16 It should be noted that while the breast has been used OV. 17 for illustrative purposes in Figs. 11A through 11E, the S"18 method described is applicable to other areas of the body, 19 with necessary changes due to the particular physiology 20 being imaged.

21 Fig. 12 shows, very schematically, the intra-operative 22 probe of Fig. 8 combined with a video camera 256 to more 23 effectively correlate the impedance measurement with the 24 placement of the probe on the body. An intra-operative probe 140 preferably having a number of optically visible 26 fiduciary marks 146 is placed on the suspect lesion or 27 tissue. A video camera 256 sequentially views the area 28 without the probe and the same area with the probe in place 29 and displays a composite image on a video display 258 after processing by a processor 260. Processor 260 receives the 31 impedance data from probe 140, determines the positions of 32 the fiduciary marks from the video image and, superimposes 33 the impedance image on the video image, with or without the 34 probe, which is displayed on display 258.

Fig. 13 shows a laparoscopic or endoscopic probe 250 36 used in conjunction with a fiber-optic illuminator/imager 43 1 252. In this embodiment, the laparoscopic impedance probe, 2 which is formed on a flexible, preferably extendible paddle, 3 is viewed by the illuminator/imager which is preferably a 4 video imager, which is well known in the art. Probe 250 can be either round or flat, depending on the region to be 6 imaged. When the imager views a suspicious lesion or tissue, 7 probe 250 is extended to determine the impedance properties 8 of the lesion. The combination of probe 256 and imager 252 9 may be incorporated in a catheter 254 or other invasive 1 0 element appropriate to the region of the body being 11 investigated.

12 Optically visible fiduciary marks 253 on probe 250 are 13 preferably used to determine the position of probe 250 14 within the video image of the tissue seen by fiber-optic illuminator/imager 252, in a manner similar to that 16 discussed above with respect to Fig. 12.

17 In a preferred embodiment of a system using any of the 18 biopsy needle, intra-operative probe, finger tip probe or 19 other embodiments described above, an audible sound 20 proportional to an impedance parameter measured by the 21 needle or other sensor in or on the body is generated by the o 22 system computer. This feature may be useful in situations 23 a where the probe is placed in locations which are difficult 24 to access visually, such as suspected lesions during surgery. Such an audible sound could include any kind of 26 sound, such as a tone whose frequency is proportional to the 27 measured parameter or similar use of beeps, clicks, musical 28 notes, simulated voice or the like. This feature can also be 29 used for non-surgical procedures such as rectal, vaginal or oral examinations, or other examinations.

31 Fig. 16 shows methods useful for estimating the depth- 32 of a lesion and also for determining if a image contains a 33 true lesion or an artifact.

34 A breast or other region 160 is imaged by a probe 270, for example, the probe of Figs. 1-3 or Figs. 6A and 6B. The 36 depth of a local impedance deviation can be estimated-by 44 1 palpating the breast or other region by a finger 272 or a 2 plunger 274. The displacement of the local deviation on- the 3 image will be maximized when the palpation is at the same 4 level as the lesion. It should also be understood that, where palpation causes movement of the local deviation on 6 the impedance image, this is an indication that the 7 deviation is "real" and not an artifact.

8 In a similar manner, application of variable 9 compression to the imaging probe will result in a variation :e 10 of the distance from the probe to deviation under the probe.

11 This distance variation will cause a corresponding variation 12 in the size and intensity of the deviation, thus helping to 13 verify that the deviation is not artifactal.

14 Alternatively or additionally, the probe can be moved along the surface of the tissue without moving the tissue.

16 In this case, surface effects will have a tendency to either 17 disappear or to move with the probe (remain stationary in 18 the image) while real anomalies will move, on the image, in 19 the opposite direction from the movement of the probe.

20 Alternatively or additionally, the probe and the tissue 21 can be moved together without moving the underlying 22 structure (such as the bones). Tissue lesions will remain 4- :23 relatively stationary in the image while bone- artifacts will S24 move in the opposite direction.

In operation, a system according to the present 26 invention measures impedance between the individual sensing 27 elements and some reference point (typically the signal 28 source point) at some other place on the body. Generally, in 29 order to produce an interpretable impedance image, the sensing elements in the multi-element probe should detect 31 distortions in the electric field lines due solely to the- 32 presence of a local impedance difference between embedded 33 tissue of one type (for example, a tumor) and surrounding 34 tissue of another type (for example, normal adipose tissue).

To avoid distortion in the field lines, the reference 36 point is typically placed far from the sensor array, all 45 Q 1 sensing elements are all at ground or virtual ground, and 2 the current drawn by the elements is measured. Since the 3 probe is at ground (an equipotential) the electric field 4 lines (and the current collected by the elements) are perpendicular to the surface of the multi-element probe. In 6 principle, if there are no variations of impedance below the 7 probe, each element measures the integrated impedance below 8 the element. This first order assumption is used in the 9 determination of the position and/or severity of a tumor, 1i.. cyst or lesion. It is clear, however, that the multi-element 11 probe covers only a portion of even the organ which is being o 12 imaged. The area outside the area of the probe is not at 13 ground potential, causing the field lines to bend out at the 14 periphery of the probe, biasing the edge of the impedance 15 image.

16 To reduce this effect, a conductive "guard ring" is 17 provided around the edge of the imaged area to draw in and 18 straighten the field lines at the edge of the imaged area.

19 This guard ring, if one is desired, can consist of merely ignoring the, presumably distorted, currents drawn by the 21 elements at (or near) the edge of the probe and ignoring the 22 measurements made by these elements.

23 Furthermore, to possibly reduce the baseline impedance *o i 24 contributed to the local impedance image by tissue between 25 the remote signal source and the region near the probe, an 26 additional reference electrode may be placed on the 27 patient's body relatively near the multi-element probe. For 28 example, if the source is placed at the arm of the patient 29 and the breast is imaged from the front, a reference electrode for sensing a reference voltage can be placed at 31 the front of the shoulder of the patient. The measured 32 impedances are then reduced by the impedance value of the 33 reference electrode. Alternatively, the impedance values of 34 the elements of the multi-element probe are averaged to form a reference impedance, and the display of the impedance map 36 is corrected for this reference impedance.

46 1 One way to substantially avoid at least some of the 2 above- mentioned problems is to use the apparatus shown in 3 Figs. 1-3. As indicated above, the apparatus incorporates 4 two probe heads 28 and 30. The breast to be imaged is placed between the probe heads and the breast is compressed by the 6 heads (although generally to a lesser degree than in X-Ray 7 mammography) so that the breast forms a relatively flat 8 volume and fills the region between the probes. it should be 9 noted that, if the current is measured at each of the sensing elements in both probes, then two somewhat different 11 images of the same region are generated. Avoidance of the 12 problems also results when the two multi-element probes are .13 not parallel as described above.

14 It should be noted that when used on breasts, the 15 images produced by the pair of large, flat probes of Fig. 3 16 have the same geometric configuration as standard 17 mammograms. Furthermore if used in the same compression 18 orientations, the impedance images can be directly compared 19 to the corresponding mammograms. In one preferred embodiment of the invention, mammograms corresponding to the impedance 21 images to be taken are digitized, using film scanning or 22 other digitization means known in the art, and entered into 23 the system computer. If the mammogram is al-eady digital, 24 -such as may be provided by a digital mammogram, the image 25 file can be transferred from the mammogram.

26 The mammograms and impedance images can be overlaid or 27 otherwise combined to form a single image. Such an image- 28 could highlight those areas of the mammogram in which the 29 impedance is particularly low or high. Such a combined image thus presents two independent readouts (impedance and 31 radiographic density) of the same well defined anatomical_ 32 region in a known geometric orientation, to facilitate 33 interpretation, correlation with anatomy and localization" 34 It is well known that the resolution of objects in an impedance image is reduced with distance of the object from 36 the probe. Thus, it is possible to estimate the distance of 47 1 the object from the two probes based on the relative size of 2 the same object on the two different probes. As indicated 3 above, two opposing views of the breast may be taken. This 4 would provide further localization of the object.

In one mode, the sensing elements of one probe are all 6 electronically floating while the elements of the other 7 probe are at a virtual ground (inputs -to sensing 8 electronics), and a remote signal source is used, as 9 previously described. After an image is obtained from the 10 one probe, the roles of the two probes are reversed to 11 obtain an image from the other probe.

12 Alternatively, if all of the elements of one of the 13 flat probes are electrified to the same voltage and the 14 measuring probe is kept at virtual ground, the currents drawn from and received by the elements of both probes form 16 a two dimensional admittance image of the region between the 17 probes.

18 In a further preferred embodiment of the invention, one 19 or a few closely spaced sensing elements on one of the 20 probes is electrified, and the others are left floating.

.o 21 This would cause a beam-like flow of current from the 22 electrified elements to the other sensing elements on the r 23 other probe. The object would disturb this flow causing 24 impedance variations which are strongest for those elements which are in the path of the current disturbed by the 26 object. If a number of such measurements are made with, each- 27 with a different group of electrodes being electrified, then 28 good information regarding the Position of the object can be 29 obtained.

In practice, as indicated above, orthogonal views of- 31 the breast are taken giving additional position information.

32 In preferred embodiments of the invention the breast is 33 imaged at a plurality of frequencies and both the real and 34 imaginary parts of the impedance are calculated. The sensitivity of the detection of malignant tissue is a 36 function of frequency, and, for a particular frequency, is a 48 1 function of the impedance measure or characteristic used for 2 imaging, for example, real part of the impedance -(or 3 admittance), imaginary part of the impedance (or 4 admittance), absolute value of the impedance (or admittance), phase of the impedance (or admittance), the 6 capacitance or some function of the impedance or of 7 admittance components.

8 In a practical situation, an impedance-measure should 9 give the maximum contrast between a malignancy and nonmalignant tissue. It is therefore desirable to determine the 11 frequency or combination of frequencies which give maximum 12 detectability and to determine it quickly. One method of 13 determining the frequency is to perform swept frequency 14 measurements and to use the frequency or combination of 15 frequencies which results in the best contrast.

16 Alternatively, a number of images taken at relatively close 17 frequencies can be used. It is believed that for many 18 purposes, at least four samples should be taken in the range 19 between and including 100 and 400 Hz and, preferably, at least one or two additional images are taken at frequencies 21 up to 1000 Hz.

22 A second method is to use a pulsed excitation and 23 Fourier analysis to determine impedance over a range of 24 frequencies. The optimum frequency or frequencies determined from the swept or pulsed measurement are then used in a 26 single or multiple frequency measurement. A pulse shape 27 which has been found useful in this regard is a bi-polar 28 square pulse having equal positive and negative going pulses 29 of 5-10 millisecond duration and fast rise and fall times.

A number of measures of the impedance, as described 31 below, have been found useful for comparing different areas 32 of the image. Generally, it is useful to display a gray 33 scale or pseudo-color representation of the values of the 34 impedance measure, either on a linear scale or where the square of the impedance measure is displayed. Also useful is.

36 an "absorption scale" where the value of an impedance 49 1 measure, v, is displayed as: 2 3 where max is the maximum normalized value of v. Generally, 4 the display is most useful when the measure is normalized, either by division or subtraction of the minimum or average 6 value of the measure in the display.

7 Furthermore, the display may be automatically windowed 8 to include only those values of the impedance measure 9 actually in the image, or to include a relative window of selectable size about the average value of the impedance 11 measure. The range of values to be displayed may also be 12 determined using a baseline average value measured at a 13 region remote from irregularities, remote from o 14 the nipple of the breast. Alternatively, the baseline average may be a predetermined average value as measured for 16 a large group of patients. Alternatively, a reference region •17 on the image may be chosen by the user to determine the 18 baseline average to be used for windowing.

19 While the display may show the exact measure for each 20 pixel as is conventional, for example, in displays of 21 nuclear medicine images, in a preferred embodiment of the 22 invention the display is an interpolated iiage formed by 23_ quadratic or cubic spline interpolation of the impedance 24 measure values. This type of display removes the annoying checkerboard effect of the relatively low resolution 26 impedance image without any substantial loss of spatial or 27 contrast detail.

28 The measures of impedance which have been found useful 29 for comparing different areas of the image may be grouped as single frequency measures and polychromatic measures.

31 Single frequency measures include the admittance, 32 capacitance, conductance and phase of the admittance. These 33 measures may be measured at some predetermined frequency, at 34 which the sensitivity is generally high, or at a frequency of high sensitivity determined by a preliminary swept or 36 pulsed measurement.

50 1 Polychromatic impedance measures are generally based -on 2 a spectral curve based on fitting a set of capacitance-

(C)

3 and conductance values determined at a plurality of 4 frequencies using linear interpolation, quadratic interpolation, cubic spline, band limited Fourier 6 coefficients, or other methods known in the art.

7 One polychromatic measure is a spectral width measure.

8 For a give pixel or region of interest the value of both the 9 G and C parameters fall with frequency. The spectral width is the width of the spectrum (to a given percentage fall in 11 the chosen parameter) as compared to the value at some low 12 frequency, for example 100 Hz. If the parameter does not 13 fall by the given percentage in the measured range it is 14 assigned an impedance measure equal to the full measured bandwidth.

16 A second polychromatic measure is a spectral quotient 17 in which the impedance measure is the ratio of the measured 18 value of G or C parameters at two preset frequencies, which 19 may be user selected, or which may be selected based on the 20 swept or pulsed measurements described above. This measure, 21 as all of the others may be displayed on a per-pixel basis 22 or on the basis of a region of interest of pizels, chosen by 23-- the user.

24 A third type of polychromatic measure is based on a Relative Difference Spectrum determination. In this measure, 26 the capacitance or conductance for a given region of 27 interest (or- single pixel) is compared to that of a 28 reference region over the spectrum to determine a numerical 29 difference between the two as a function of frequency. The thus derived Relative Difference Spectrum is then analyzed.

31 For example, a spectral width measure as described above has- 32 been found to be a useful measure of abnormalities. Normally 33 the width is measured where the relative difference spectrum 34 passes from positive to negative, where the C or G is equal to that of the reference region.

36 A fourth type of polychromatic measure is based ori a 51 1 Relative Ratio Spectrum determination. This is similar to 2 the Relative Difference Spectrum, except that the ratio of 3 the values between the reference area and the region of 4 interest is used. A spectral width measure can be determined for this spectrum in the same manner as for the Relative 6 difference Spectrum. Normally, the width is measured where 7 the ratio is i.

8 A fifth polychromatic measure which my be useful is 9 the maximum of one of the other polychromatic measures, for example, the capacitance, conductance, Relative Difference •11 Spectrum, Relative Ratio Spectrum, etc.

12 In impedance measurements of the breast in both men and 13 women, normal breast tissue has a low capacitance and 14 conductivity, except in the nipples, which have a higher

C

and G values than the surrounding tissue with the maximum 16 obtained at the lowest frequency recorded, typically 100 Hz.

17 The nipple capacitance and conductance remains higher than ~18 the surrounding tissue up to about 1400 Hz for fertile 19 patients and up to about 2500 Hz for older patients (which is reduced to 1400 Hz for older patients by estrogen 21 replacement therapy). These frequencies represent the normal 22 range of spectral widths for the Relative and Difference 23 Spectra. Tumors can be recognized by very high C and G 24 relative ratio or relative difference values up to 2500 Hz or even higher.

26 Capacitance and conductance values are measured by 27 comparing the amplitude and phase of the signal received by 28 the sensing elements. Knowing both of these measures at the 29 same points is useful to proper clinical interpretation. For example, as illustrated below in Fig. 14, a region of 31 elevated conductivity and reduced capacitance (especially at 32 relatively low frequencies, most preferably less than 500 33 Hz, by generally below 2500 Hz and also below 10 kHz) is 34 associated with benign, but typically pre-cancerous atypical hyperplasia while, as shown in Fig. 15, cancer typically has- 36 both elevated capacitance and conductivity over, generally, 52 1 a wide frequency range, as compared to the surrounding 2 tissue. Proper differential diagnosis is aided by having the 3 frequency samples be close enough together so that changes 4 in the conductivity and capacitance in the low frequency range can be tracked. This also requires the display of both 6 capacitance and conductance or the use of an impedance 7 measure which is based on an appropriate combination of the 8 two.

9 Methods for calculating C and G are- given in the abovementioned US patents 4,291,708 and 4,458,694, the 11 disclosures of which are incorporated herein by reference.

A

12 preferred embodiment of the invention takes advantage of the 13 calibration capability inherent in the use of cover plates S. 14 as shown in Figs. 5A and 5B. It can be shown that if the 15 received waveform is sampled at a fixed spacing, 6, such 16 that N samples are taken in each cycle, then the real and 17 imaginary values of the impedance can be determined as: 18 19 G E(gn(V(n+ N)_Vn), and 21 CC E(Cn(V(n+ N)-Vn), 22 where gn and cn are constants determined by a calibration 23 procedure and Vn is the voltage measured at ttbe nth sampling.

S. 24 .point (out of The first sample is taken at zero phase of the reference signal.

26 One relatively easy way to determine the constants is 27 to perform a series of measurements when cover plate is in 28 contact with the sensing elements as described above and a 29 known impedance is placed between the transmitter and the cover plate. Since N coefficients are required for 31 determining gn and cn for each frequency, N values of 32 admittance and N measurements are required. For example, if 33 N=4 (four samples per cycle) four different measurements are 34 taken and the sampled signal values are entered into the above equations to give N equations, which are then solved 36 for the values of the coefficients. The higher the number of- 53 1 samples, the greater the accuracy and noise immunity of the 2 system, however, the calibration and computation times are 3 increased.

4 Alternatively, fewer samples are taken and values for a number of measurements are averaged, both in the calibration 6 and clinical measurements to reduce the effects of noise.

7 Artifactal abnormalities in the impedance image can be 8 caused by such factors as poor surface contact or 9 insufficient conductive coupling on some or all of the 1 0 sensing elements, the presence of air bubbles trapped 11 between probe and tissue and normal anatomical features such 12 as bone or nipple.

13 Bubbles can be recognized by their typically lower C ~14 and G values compared to background, often immediately surrounded by pixels with much higher C and G. Bubbles can 16 be verified and eliminated by removing the probe from the "17 skin and repositioning it, and or by applying additional 18 conductive coupling agent. Contact artifacts can be 19 determined and accounted for in real time by translating the 20 probe and viewing the image as described above. Artifacts *21 either disappear or remain fixed with respect to the pixels, 22 while real tissue features move, on the- image, in a 23- direction opposite from the motion of the probe.

24 Additionally, as described above, if the tissue beneath the skin is physically moved, while the probe and skeletal 26 structure is kept fixed, only real tissue features will- 27 move. If the Yfeature remains static, it is either a skin 28 feature or bone.

29 If as described above, the probe and the tissue are moved together without moving the underlying structure (such-- 31 as the bones). Tissue lesions and surface effects will 32 remain relatively stationary in the image while bone 33 artifacts will move in the opposite direction, thus 34 distinguishing them from other impedance deviations.

Fig. 14 shows one example of a display, according to a 36 preferred embodiment of the invention. In this display, 54 1 capacitance and conductivity images at two positions on a 2 breast are shown, together with an indication of the 3 positions on the breast at which these images were acquired.

4 In particular, as seen in Fig. 15, the display includes the capability of displaying up to five sets of capacitance 6 and conductance images in the five sets of smaller squares.

7 These images are associated with probe areas indicated as 8 numbers 1-5 on the breast image shown in the display. In 9 practice, the examiner manipulates a joystick or other digital pointing device, such as device 105 shown in Fig.

11 6A. This device is manipulated until a square is 12 appropriately placed on the breast image. The examiner then 13 presses a button which causes a pair of impedance images to S" 14 be stored and displayed on the screen in an appropriate 15 square, and the indicated position to be displayed on the 16 physiological (breast) drawing. The small images are 17 numbered from left to right. Preferably, the examiner can 18 scale the physiological image so that the dimensions of the 19 breast shown and the extent of the probe array are compatible. It should be understood that during the 21 placement of the probe, real time images (acquired about *22 once every 50-80 msec) of the capacitance and the 23 conductance are shown, for example in the large squares to 24 the left of the display.

:25 Fig. 14, which represents an actual imaging situation 26 shows, in the leftmost of the small images, a situation in 27 which a small atypical hyperplasia which was previously 28 detected by other means. This position shows an elevated 29 conductivity and a very slightly reduced capacitance. In position 2, which is also shown in the two large squares to 31 the right of the display, a previously unsuspected area-.

32 having a capacitance/conductance profile characteristic of 33 atypical hyperplasia is detected.

34 Fig. 15 shows a study typical of multiple suspected sites of carcinoma (in positions 2 and The images of 36 position 4 are shown in enlarged format at the left of the 55 1 image. In these sites, both the capacitance and conductance 2 are elevated with respect to their surroundings.

3 Alternatively, a composite image such as the image of 4 the sum of the capacitance and conductance images, their product, their sum or their ratio can be displayed to give a 6 similar indication of the type of detected anomaly. A color 7 coded composite image can also be displayed, where, for 8 example, the median value for each image would be black and 9 where positive and negative values would have a particular 1 0 color which, when combined would result in distinctive 11 colors for suspect impedance deviations.

12 The display shown in Figs. 14 and 15 can also be 13 utilized to show a plurality of images of the same region at .14 varying frequencies and one or more different impedance measures of a given region.

16 Figs. 17A and 17B show a block diagram of a preferred 17 embodiment of a system 200 which incorporates a number of 18 multi-element probes. It should be understood that the exact 19 design of system for impedance imaging will depend on the 20 types of probes attached to the system and the exact imaging 21 modalities (as described above) which are used.

22 As shown in Figs. 17A and 17B the preferred system can 23 incorporate biopsy needle probe 154, two plate probes 28, 24 such as those shown in Figs. 1-3, scan zoom probe 100 such i: 25 as that shown in Fig. 6A, conformal probe 139 such as that 26 shown in Fig. 7B, a bra-cup probe, finger/glove probe 130 27 such as that shown in Fig. 7A, laparoscopic probe 150 such 28 as that shown in Fig. 9 or an intra-operative probe 140 as 29 shown in Fig. 8. Furthermore, when three probes are used as in Fig. 11E, provision is made for attachment of a third 31 plate probe. The position of the plate and needle probes is 32 controlled by controller 181 as described in respect to Fig.

33 11D.

34 The probes as connected via a series of connectors indicated by reference numeral 302 to a selection switch 304 36 which chooses one or more of the probes in response to a 56 1 command from a DSP processor 306. Selection switch 304 2 switches the outputs of the probes, namely the signals 3 detected at the sensing elements of the probes (or amplified 4 versions of these signals) to a set of 64 amplifiers 308, one amplifier being provided for each sensing element. For 6 those probes, such as the large plate probes, which have 7 more than 64 sensing elements, the selection switch will (1) 8 sequentially switch groups of 64 sensing elements to 9 amplifier set 308, choose a subset of sensing elements on a coarser grid than the actual array by skipping some 11 elements, as for example every second element, sum 12 signals from adjacent elements to give a new element array of lower resolution and/or choose only a portion of the 14 probe for measurement or viewing. All of these switching activities and decisions are communicated to the switch by 16 DSP processor 306 which acts on command from a CPU 312. The 17 output of the amplifiers is passed to a multiplexer 307 18 where the signals are serialized prior to conversion to S 19 digital form by a, preferably 12-bit, A/D convertor 310.

A

programmable gain amplifier 309, preferably providing a gain 21 which is dependent on the amplitude of the signals, is 22 optionally provided to match the signal to the range of the 23 A/D convertor. The output of A/D 310 is sent to the DSP for 24 processing as described above. In a preferred embodiment of the invention DSP 306 is based on a Motorola MC 68332 26 microprocessor.

27 While 64 amplifiers has been chosen for convenience and- 28 lower cost, any number of amplifiers can be used.

29 The DSP calculates the impedance results and send the results to CPU 312 for display on a graphic data display 16, 31 printing on a printer 18 or other output signals generation-.

32 as described above by a light indicator 314 or a sound 33 indicator 316.

34 Alternatively, the DSP directs signal sampling and averages together the samples or pre-processes them, sending_ 36 the averaged or pre-processed samples to CPU 312, which then 57 1 performs the impedance calculations.

2 The CPU may also receive images from video camera 256, 3 for example, when used with an intra-operative probe, from 4 an endoscopic optics and camera system 320, for example when the camera views the outer surface of the laparoscopic probe 6 or from an ultra sound imager 322, for example in biopsy 7 performance as shown in Figs. 11A and l1B. When an image is 8 acquired from one of these cameras a frame grabber 324 is 9 preferably provided for buffering the camera from the

CPU.

i 10 As described above, the CPU combines these images with the 11 impedance images provided by one or more probes for display S12 or other indication to the operator.

13 Fig. 15 also shows a programmable reference signal 14 generator 326 which receives control and timing signals from 15 the DSP. The reference signal generator generates excitation S" 16 signals which are generally supplied, during impedance 17 imaging, to reference probe 13, which, as described above, 18 is placed at a point (or at more than one point) on the body S"19 remote from the region of impedance measurement. Signal 20 generator 312 may produce a sinusoidal waveform, pulses or S21 spikes of various shapes (including a bipolar square shape) 22 or complex polychromatic waveforms combining desired *":231 excitation frequencies. Appropriate impedance calculations, S.24 -in DSP 306 or in CPU 312, are implemented in accordance with the waveform of the excitation.

26 Where a breast is imaged and one of the two plates is 27 used as the source of excitation, as described above, the- 28 output of signal generator is sent to the exciting plate 29 (signal paths not shown for simplicity). A current overload sensor 330 is preferably provided after the signal generator 31 to avoid overloads caused by short circuits between the 32 reference probe and the imaging probe or ground 33 Also shown on Fig. 17A is an internal cali-bration 34 reference 332 which is preferably used for internal calibration of the system and for testing and calibration of 36 the probes.

58 1 For internal testing and calibration, calibration 2 reference 232 receives the signals generated by the 3 programmable reference signals generator as passed to the 4 selection switch, in series with an internal admittance in the calibration reference, as selected by the DSP processor.

6 The DSP processor computes the admittance from signals 7 received from the A/D convertor and compares the computed 8 admittance with the actual admittance provided by internal i 9 calibration reference 332. This comparison can be provide an indication that the system requires adjustment or repair or 11 can be used to calibrate the system.

12 Similarly, the output of calibration reference 332 may 13 be provided to probe cover 88 for calibration and quality 14 assurance of a plate or scan probe as described above. Under 15 this situation, the DSP instructs selection switch 304 to 16 choose the input from the respective probe.

17 Also provided is a user interface 334 such as a 18 keyboard, mouse, joystick or combinations thereof, to allow S19 the operator to enter positional information via the screen and to choose from among the probes provided and from the 21 many options of calculation, display, etc.

22 Although described together as the preferred embodiment 23 of the invention, it is not necessary to use-the probes of 24 the invention, the methods of calculation of impedance and 25 impedance characteristics of the invention and the preferred 26 apparatus of the invention together. While it is presently 27 preferred that they be used together they may each be used- 28 with probes, calculation methods and apparatus for impedance 29 imaging as applicable and as available.

Certain aspects of the invention have been described 31 with respect to a biopsy needle or with respect to placement- 32 of such a needle. It should be understod that such 33 description and aspects of the invention are equally 34 applicable to positioning needles, catheters, endoscopes, etc.

36 Although various embodiments, forms and modifications 59 1 have been shown, described and illustrated above in some 2 detail in accordance with the invention, it will -be 3 understood that the descriptions and illustrations are by 4 way of example, and that the invention is not limited thereto but encompasses all variations, combinations and 6 alternatives falling within the scope of the claims which 7 follow: 8 9 13 *14 16 17 18 19 S21 22 23 24 26 27 28 29 31 32 33 34 36 60

Claims (33)

1. Apparatus for impedance imaging of a region of a subject, the apparatus comprising: a first, multi-element, probe comprising a plurality of sensing elements s and adapted for mounting on a first side of the region; a second probe, including one or more sensing elements, adapted for mounting on a surface of the subject; and a controller which generates at least one impedance image, including a plurality of pixels, based on signals sensed by at least some of the sensing elements of the first probe and at least one of the one or more sensing elements of the second probe.

2. Apparatus according to claim 1, wherein the second probe is adapted for mounting on a second side of the region.

S3. Apparatus according to claim 2, wherein the second side of the region is opposite the first side of the region. 15

4. Apparatus according to claim 1, wherein the second probe is adapted for- mounting on a portion of the body remote from the region.

Apparatus according to any one of claims 1 to 4, further comprising at least one electrode, not included in the first or second probes, adapted for applying electrical signals to the subject, wherein the at least one image is generated based on 20 electrical signals applied to the subject from the at least one electrode.

6. Apparatus according to claim 5, wherein the at least one electrode is •adapted for mounting on a portion of the body remote from the region.

Apparatus according to claim 5 or 6, further comprising a source of electrical energy which provides a voltage difference between the at least one electrode and at least one element of the first or second probe.

8. Apparatus according to any one of the preceding claims, wherein the second probe comprises a multi-element probe.

9. Apparatus according to claim 8, wherein the controller generates at least one first impedance image based on signals sensed by at least some of the elements of the first probe and at least one second impedance image based on signals sensed by at least one of the elements of the second probe.

10. Apparatus according to claim 9, wherein the first and second impedance imag are sequentially generated. LIBD]02349.doc:tyb 62

11. Apparatus according to claim 9, wherein the first and second impedance images are generated substantially simultaneously.

12. Apparatus according to claim 6, further comprising a7 source of electrical energy which alternately applies electrical signals to at least one of the elements of the first and second multi-element probes, wherein the at least one first image is generated based on one or more signals applied to elements of the second probe and the at least one second image is generated based on one or more signals applied to elements of the first probe.

13. Apparatus according to claim 12, wherein the first image is generated based on signals sensed by a number of elements of the first probe greater than the number of electrified elements of the second probe used in generating the first image.

14. Apparatus according to any one of the preceding claims, wherein the first probe comprises a two-dimensional array of sensing elements.

15. Apparatus according to any one of the preceding claims, wherein the Is first probe comprises at least 64 sensing elements.

16. Apparatus according to any one of the preceding claims, wherein the first probe is adapted to be mounted on a breast.

17. Apparatus according to any one of the preceding claims, wherein each of the pixels of the at least one image corresponds to an element of the first or second g* 20 probe.

S18. A method of impedance imaging of a body region of a subject, the method comprising: positioning a first, multi-element probe, comprising a first plurality of sensing elements, on a first side of the region; positioning a second probe, comprising one or more second sensing elements, on a surface of the subject; and generating at least one impedance image based on signals sensed by at least some of the first elements and by at least one of the one or more elements of the second probe, while the first and second probes are not moved from their positions.

19. A method according to claim .18, wherein positioning the second probe comprises positioning a multi-element probe including a second plurality of elements, on T a second side of the region.

LIBD]02349.doc:tyb 63 A method according to claim 19, wherein generating the at least one impedance image comprises generating first and second impedance images based, respectively, on signals sensed by at least some of the first and second plurality of elements.

21. A method according to claim 20, further comprising applying an electrical stimulus to the subject from an electrode separate from the first and second probes, and wherein both the first and second impedance images are generated responsive to electrical stimulus from the same electrode.

22. A method according to claim 21, wherein applying the electrical stimulus comprises applying from an electrode positioned on a surface of the subject remote from the region.

23. A method according to any one of claims 20 to 22, wherein the first and second impedance images are sequentially generated.

-24. A method according to any one of claims 20 to 22, wherein the first and 15 second impedance images are generated responsive to different stimulus. A method according to any one of claims 20 to 24, wherein the first S• impedance image is generated while substantially all the elements of the second probe are floating.

S'

•26. A method according to any one of claims 20 to 25, further comprising 20 applying an electrical stimulus to the subject from the first probe, and wherein the second impedance image is generated responsive to the electrical stimulus from the first probe.

.27. A method according to claim 26, wherein applying the electrical stimulus from the first probe comprises electrifying fewer than all the elements of the first probe.

28. A method according to claim 26 or claim 27, wherein applying the electrical stimulus from the first probe comprises electrifying fewer elements than a number of elements of the second probe used in forming the at least one second image.

29. A method according to any one of claims 20 to 28, further comprising applying an electrical stimulus to the subject from the second probe, and wherein the first impedance image is generated responsive to the electrical stimulus from the second probe. A

30. A method according to any one of claims 19 to 29, wherein the second iside f the region is opposite the first side of the region. [R:\LIBLL]I 1389spec.doc:vjp 64

31. A method according to any one of claims 18 to 30, wherein the first probe comprises a two-dimensional matrix of elements.

32. A method according to any one of claims 18 to 31, wherein the region comprises a breast.

33. A method according to any one of claims 18 to 32, further comprising identifying an anomaly on the at least one impedance image and determining a depth of the anomaly beneath the first or second probe responsive to the at least one image. Dated 5 July, 2001 Transscan Research Development Co. Ltd. 10 Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON a a [R:\LIBLL]I 1389speci..doc:vjp