WO2021007619A1

WO2021007619A1 - Methods and apparatuses for characterisation of body tissue

Info

Publication number: WO2021007619A1
Application number: PCT/AU2020/050731
Authority: WO
Inventors: Warren Smith
Original assignee: Ti2 Medical Pty Ltd; Focused Ultrasound Medical Research Foundation Limited
Priority date: 2019-07-16
Filing date: 2020-07-16
Publication date: 2021-01-21

Abstract

Methods and apparatus for characterization of body tissue at a joint are described. A first electrical signal is applied between a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode connected to tissue at a first side and a second side, respectively, of a joint of interest. One or more voltages are measured between a pair of sensing electrodes comprising a first sensing electrode and a second sensing electrode, the voltages resulting from the application of the first electrical signal. The first sensing electrode and the second sensing electrode are connected to tissue at the first side and the second side, respectively, of the joint, and the second current electrode is closer to the joint than the second sensing electrode. Bioimpedance across the joint is determined from the one or more voltage measurements.

Description

“Methods and apparatuses for characterisation of body tissue” Cross-Reference to Related Application

[0001] The present application claims priority to Australian provisional patent application no. 2019902504, filed 16 July 2019, the entire content of which is incorporated herein by reference.

Technical Field

[0002] The present disclosure relates to methods for characterisation of body tissue at a joint, including methods of bioimpedance analysis, and apparatus for use in such methods.

Background

[0003] Bioimpedance analysis involves the measurement of the response of body tissue to externally applied electrical waveform. For example, bioimpedance parameters such as resistance, reactance and phase angle can be recorded, for the purposes of determining blood flow and body composition (e.g., water and fat content).

[0004] Localized bioimpedance characterization of body components such as joints has received little investigation. The prevalence of joint disorders such as knee osteoarthritis, however, results in significant health burdens to both patients and health budgets. There is an incentive to develop low cost alternatives or aids to existing technologies such as radiographic imaging for diagnosing and monitoring joint disorders.

[0005] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each claim of this application.

[0006] Throughout this specification the word "comprise", or variations such as

"comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. Summary

[0007] According to one aspect, the present disclosure provides a method for characterization of body tissue at a joint, the method comprising:

applying a first electrical signal between a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode connected to tissue at a first side and a second side, respectively, of the joint;

measuring one or more voltages between a pair of sensing electrodes comprising a first sensing electrode and a second sensing electrode, the voltages resulting from the application of the first electrical signal, wherein the first sensing electrode and the second sensing electrode are connected to tissue at the first side and the second side, respectively, of the joint, and wherein the second current electrode is closer to the joint than the second sensing electrode; and

determining, from the one or more voltage measurements, bioimpedance across the joint.

[0008] An apparatus that may be used to carry out the method is also disclosed herein. In particular, in accordance with a one aspect, the present disclosure provides apparatus for characterization of body tissue at a joint, the apparatus comprising:

a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode adapted to connect to tissue at a first side and a second side, respectively, of the joint;

a signal generator adapted to apply a first electrical signal between the pair of current electrodes;

a pair of sensing electrodes, the pair of sensing electrodes comprising a first sensing electrode and a second sensing electrode adapted to be connected to tissue at the first side and the second side, respectively, of the joint, wherein the second current electrode is closer to the joint than the second sensing electrode; and

a monitoring device adapted to measure one or more voltages between the first sensing electrode and the second sensing electrode resulting from the application of the first electrical signal, and determine, from the one or more voltage measurements, bioimpedance across the joint.

[0009] In the method and/or apparatus, in some embodiments, the first current electrode may be further from the joint than the first sensing electrode. Accordingly, along the shortest notional path extending through each of the electrodes, the order of the electrodes may be (i) the first current electrode, (ii) the first sensing electrode, (iii) the second current electrode and (iv) the second sensing electrode.

[0010] The method and apparatus according to the present disclosure contrasts with a standard tetrapolar (four-electrode) method and apparatus by virtue, for example, of the positioning of the pairs of current and sensing electrodes. In a standard tetrapolar

arrangement, which itself contrasts with simple 2-electrode arrangement by allowing contributions of electrode contact impedance to be removed from measurements, an electrical signal is applied between two outer current electrodes connected to body tissue on opposite sides of a region of interest, and measurement is made of the voltage across two inner sensing electrodes located on opposite sides of the region of interest at positions inside of the outer current electrodes. Thus, the standard arrangement does not have any current electrode that is closer to a region of interest, let alone a joint of interest, than the adjacent sensing electrode.

[0011] In methods and apparatus according to the present disclosure, during

measurements, the joint of interest may be placed in a bent configuration.

[0012] Indeed, in one aspect, the present disclosure provides a method for

characterization of body tissue at a joint, the method comprising:

applying a first electrical signal between a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode connected to tissue at a first side and a second side, respectively, of the joint, the joint being in a bent configuration;

measuring one or more voltages between a pair of sensing electrodes comprising a first sensing electrode and a second sensing electrode, the voltages resulting from the application of the first electrical signal, wherein the first sensing electrode and the second sensing electrode are connected to tissue at the first side and the second side, respectively, of the joint; and

[0013] In any aspects of the present disclosure, the placing of the joint in a bent configuration may be such that longitudinal axes of limbs immediately either side of the joint are, relative to each other, angled at more than 60°, angled between about 60° and 120°, angled between about 70° and 110°, angled between about 80° and 100°, angled at about 90°, or otherwise. The patient may be placed in a seated position during measurements. [0014] When a patient is seated, placing the joint at an angle such as those described above, e.g. at a 90° angle, may be relatively comfortable for the patient and may allow for accurate and repeatable placement of suitable electrode configurations.

[0015] The electrodes may be distributed in a row. The electrodes may be distributed across a linear or non-linear path. The electrodes may be distributed in a row but across a non-linear path., e.g. if the joint of interest is in a bent configuration during application of the signal/measuring of the voltage. Whether the joint is bent or otherwise, the electrodes may all be positioned in the same plane of body, e.g. in the same sagittal or parasagittal plane of the body.

[0016] The first current electrode may be spaced from the first sensing electrode by at least 1 mm, 2 mm, 5 mm, or 10 mm. The first current electrode may be spaced from the first sensing electrode by no more 300 mm, 150 mm, 100 mm, or 50 mm.

[0017] The second current electrode may be spaced from the closer of the first current and sensing electrodes by at least 40 mm, at least 50 mm, at least 70 mm, or at least 100 mm. This spacing may be dependent on the size of the joint of interest located at least partially therebetween.

[0018] The second sensing electrode may be spaced from the second current electrode by at least 1 mm, 2 mm, 5 mm, or 10 mm. The second current electrode may be spaced from the second sensing electrode by no more 300 mm, 150 mm, 100 mm, or 50 mm.

[0019] When the joint of interest is a knee, electrode placement may be made along the anterior surface of the leg along the longitudinal axes of the upper and lower legs. The electrodes may be positioned in a row. The electrodes may all be positioned substantially on the same parasagittal plane of the body, which plane may extend through the knee cap. The first current electrode and the first sensing electrode may be located on the upper leg (which may include the knee cap), to one side of the knee, and the second current electrode and the second sensing electrode may be located on the lower leg, to the opposite side of the knee. Alternatively, the first current electrode and the first sensing electrode may be located on the lower leg, to one side of the knee, and the second current electrode and the second sensing electrode may be located on the upper leg (which may include the knee cap), to the opposite side of the knee.

[0020] The electrode arrangements and/or the placement of the joint in a bent configuration in methods of the present disclosure may overcome a major challenge with regard to bioimpedance-based characterization of joints, e.g., major joints such as the knee. It may allow the applied electric current to course deeply within the joint, e.g., within the articular cavity of the joint, the primary spatial location of many joint disorders, yet without major and unquantified contributions from other tissues such as surrounding muscles, vasculature etc.

[0021] In one embodiment, the first sensing electrode is placed on the upper leg and fully on, partially on, or slightly proximal to (e.g. 0.1 mm to 30 mm, 1 mm to 20 mm, 1 mm to 10 mm proximal to) to the kneecap (patella). The first current electrode, is spaced proximahy apart from the first sensing electrode (i.e. further up the upper leg), e.g. by 1 mm, 2 mm, 5 mm, 10 mm or more from the first sensing electrode. The second current and sensing electrodes are placed on the lower leg, such that second current electrode, which is closest to the knee, is at least 40 to 100 mm distal from the first sensing electrode, and the second sensing electrode is spaced distahy apart (i.e. further down the lower leg), e.g. by 1 mm, 2 mm, 5 mm, 10 mm or more, from the second current electrode. For example, the second current electrode may be placed on the lower leg at least 40 to 100 mm distahy from the first sensing electrode and the second sensing electrode may be placed distahy apart by 1 mm, 2 mm, 5 mm, 10 mm or more from the second current electrode.

[0022] In one embodiment, voltage (V(Si-S2)), is measured between the pair of sensing electrodes (Si, S2) resulting from the application of the first electrical signal and

bioimpedance (Z oi) across the joint of interest (JOI) is determined from the voltage measurement (V(Si- S2)). (In general, the notation“V(Si- S2)” is intended to represent the voltage drop along the path between sensing electrodes Si and S2, and is thus a scalar difference in voltage between these electrodes.)

[0023] Where voltage V(Si- S2) is measured between the pair of sensing electrodes (Si, S2), during application of the first electrical signal having a waveform or waveform spectrum suitable for electrical bioimpedance measurement (such as a controlled current AC waveform I(t)), the bioimpedance Z oimay be determined using Equation 1:

ZJOI = V(Si- S₂) / 1( t) [1]

[0024] Through inclusion of phase-sensitive electronics in the apparatus, impedance Z can be resolved into real (resistive) and imaginary (reactive) components.

[0025] Characterisation of electrode-to-tissue contact at the first and second current electrodes may be carried out by measuring voltages between different combinations of the four electrodes. Methods and apparatus according to the present disclosure may provide for a low-cost, easy to use setup for tracking changes associated with application of particular therapies such as manual therapy, ultrasound, electrostimulation, EMF, acupuncture, low- level laser stimulation etc. In some embodiments, the present bioimpedance apparatus may form part of a broader therapeutic system, which may include therapeutic elements such as focussed ultrasound stimulators or electrostimulators. The bioimpedance apparatus may provide for feedback on therapeutic progress, e.g. as part of a closed loop therapeutic system.

[0026] The first electrical signal may be a non-therapeutic (non-stimulating) electrical signal. Accordingly, the first electrical signal may be applied for the purposes of

characterising body tissue only. However, alternatively, the first electrical signal may be a therapeutic (stimulating) electrical signal and/or a second electrical signal may be applied that is a therapeutic (stimulating) electrical signal. To provide a therapeutic, stimulating effect, the second electrical signal may have different characteristics to the first electrical signal. Thus, in one embodiment, a second electrical signal may be applied between the pair of current electrodes at a different time from the application of the first electrical signal, wherein the second electrical signal typically has different characteristics to the first electrical signal. The therapeutic electrical signal may provide electrostimulation therapy to the tissue region of interest or otherwise.

[0027] The methods and apparatuses described herein may have a variety of applications in relation to joints. For example, they may be employed for general bioelectrical impedance analysis applications such as body composition determination, fluid management, wound assessment and monitoring at joints, which may give more accurate impedance

determinations than existing arrangements. The methods and apparatuses may also be used in joint repair or joint wound healing applications, bone and muscle condition assessment and/or recovery applications at joints or otherwise. In some embodiments, the joint may be defective. For example, the joint may be wounded, diseased, strained, broken or otherwise.

[0028] In one embodiment, bioimpedance is measured, using the techniques described herein, on corresponding joints. A relative bilateral bioimpedance data comparison may therefore be achieved. For example, bioimpedance measurements at a first joint (e.g. the left knee or elbow), which is associated with a defect, may be compared with bioimpedance measurements at a second corresponding joint (e.g. the right knee or elbow), which is a normal, healthy joint. Brief Description of Drawings

[0029] By way of example only, embodiments are now described with reference to the accompanying drawings, in which:

[0030] Fig. 1 provides a representation of electrode positioning in a method and apparatus for characterization of body tissue at a joint according to an embodiment of the present disclosure;

[0031] Fig. 2 provides a representation of electrode positioning in a method and apparatus for characterization of body tissue at a joint according to an embodiment of the present disclosure;

[0032] Fig. 3 provides a representation of electrode positioning in a method and apparatus for characterization of body tissue at a joint according to an embodiment of the present disclosure;

[0033] Fig. 4 provides an anterior view of electrode positioning relative to a knee in a method and apparatus for characterization of body tissue at a knee according to an embodiment of the present disclosure;

[0034] Fig. 5 provides a parasagittal cross-sectional, anatomical, view of the electrode positioning relative to the knee of Fig. 4;

[0035] Fig. 6 provides a lateral view of the electrode positioning relative to the knee of Fig. 4;

[0036] Fig. 7 provides a lateral view of electrode positioning relative to a knee in a method and apparatus for characterization of body tissue at a knee according to an embodiment of the present disclosure;

[0037] Fig. 8 provides a schematic representation of apparatus for characterization of body tissue at a joint according to an embodiment of the present disclosure;

[0038] Fig. 9 provides a representation of bilateral electrode positioning in a method and apparatus for characterization of body tissue at a joint according to an embodiment of the present disclosure; and

[0039] Fig. 10 provides a graph of the resistance difference between left and right knees associated with application of an ice pack to the medial surface of the left knee between times 13.7 and 33.0 min. Description of Embodiments

[0040] In a method and an apparatus for characterization of body tissue of a joint according to one embodiment of the present disclosure, electrodes are provided in accordance with the arrangement shown in Fig. 1. In particular, at least four electrodes are provided, including a pair of current electrodes Ii, h and a pair of sensing electrodes Si, S2 which electrodes Ii, I_¾ Si, S2 are all in electrical contact with a surface 11 of tissue 10 of a patient at or adjacent a joint of interest 12. The joint of interest may be any joint, e.g. a synovial joint such as a knee joint, elbow joint, wrist joint, ankle joint, shoulder joint, finger joint, toe joint, joint of the pelvic girdle, or otherwise.

[0041] The pair of current electrodes Ii, I2 include a first current electrode Ii, and a second current electrode I2, which are adapted to apply an electrical signal from a signal generator 20 to the tissue 10 including the joint of interest 12. The pair of sensing electrodes Si, S2 include a first sensing electrode Si, and a second sensing electrode S2 and are provided for the purpose of sensing voltages. Nonetheless, the current electrodes Ii, I2 can also provide a voltage sensing function in some embodiments, e.g. for the purpose of measuring contact impedances at different electrodes.

[0042] Application of the electrical signal to the tissue permits measurement of bioimpedance Z oi across the joint of interest (JOI) 12. In this embodiment, the joint of interest 12 is positioned at and directly underneath the tissue surface 11. The first current electrode Ii and the second current electrode I2 are connected to tissue at a first side and a second side, respectively, of the joint of interest 12. The first sensing electrode Si and the second sensing electrode S2 are connected to tissue at the first side and the second side, respectively, of the joint of interest 12, and such that the second current electrode Eis closer to the joint than the second sensing electrode S2. Across the surface 11 of the body tissue (and as shown from left to right in Fig. 1), the order of the electrodes in this embodiment is (i) the first current electrode Ii, (ii) the first sensing electrode Si, (iii) the second current electrode I2 and (iv) the second sensing electrode S2.

[0043] In Fig. 1, the electrodes Ii_, I2, Si, S2 are illustrated in a substantially linear configuration. In some embodiments, however, as represented in Fig. 2, the electrodes Ii_, I2, Si, S2 may be distributed across a partially non-linear path, e.g. if the joint of interest is in a bent configuration during application of the signal/measuring of the voltage. Nonetheless, in some embodiments, whether the joint is bent or otherwise, the electrodes T, I2, Si, S2 may all be positioned in a row and/or in the same plane of body, e.g. in the same sagittal or parasagittal plane of the body. As shown in Fig. 2, despite the bending of the joint, along the shortest notional path 13’ extending through each of the electrodes, the order of the electrodes remains the same as in Fig. 1.

[0044] In Figs. 1 and 2, the electrodes are all positioned on the same surface 11 of the body, e.g. the same anterior, posterior, medial, lateral, superior or posterior surface of the body. In some embodiments, however, as illustrated in Fig. 3, the electrodes may be positioned on opposing surfaces of the body, e.g. such that the first current electrode Ii and first sensing electrode Si are on a first (e.g. anterior) surface 11 of the body and the second current electrode F and the second sending electrode S2 are located on a second (e.g.

posterior) surface 14 of the body the body, opposite to the first surface 11. As shown in Fig. 2, despite the opposing locations of the electrodes, along the shortest notional path 13” extending through each of the electrodes, the order of the electrodes remains the same as in Figs. 1 and 2.

[0045] A more detailed illustration of example positioning of the electrodes F_, I2, Si, S2 relative to a knee is provided in Figures 4 and 5. In this example, the electrodes Ii_, I2, Si, S2 are placed along the anterior surface along the longitudinal axes of the upper leg 41 and lower leg 42. The electrodes Ii_, I2, Si, S2 are positioned substantially on the same parasagittal plane 40 of the body, extending through the knee cap (patella) 43. The first current electrode Ii and the first sensing electrode Si are located on the upper leg 41 (including the knee cap 43), and the second current electrode I2 and the second sensing electrode S2 are located on the lower leg 42, to the opposite side of the knee.

[0046] In this embodiment, the first sensing electrode Si is placed on the upper leg 41 and fully on, partially on, or slightly proximal to (e.g. 0.1mm to 30 mm, 1 mm to 20 mm, 1 mm to 10 mm proximal to) to the kneecap 43. The first current electrode, may be spaced proximally apart from the first sensing electrode (i.e. further up the upper leg), e.g. by 1 mm,

2 mm, 5 mm, 10 mm or more from the first sensing electrode.

[0047] The second current electrode I2 and second sensing electrode S2 may be placed on the lower leg 42, such that the second current electrode I2 is at least 40 to 100 mm distal from the first sensing electrode Si, and the second sensing electrode S2 is spaced distally apart (i.e. further down the lower leg 41), e.g. by 1mm, 2 mm, 5 mm, 10 mm or more, from the second current electrode I2. [0048] One or more parts of the anatomy may be used as anatomical references for location of one or more of the electrodes. For example, in one embodiment, with reference to Fig. 5, a depression 44 may be readily located, e.g. by sliding a finger down the centre of the quadriceps muscle 45 of the upper leg 31. The depression 45 may be superficial to the connection between the quadriceps tendon 46 and the patella 43, i.e. the depression may be just proximal to the patella 43. The depression 45 may be used to align one of the electrodes such as the most proximal electrode (T in this embodiment).

[0049] In methods according to the present disclosure, during measurements, the joint of interest may be placed in a bent configuration, e.g. such that longitudinal axes of limbs immediately either side of the joint are, relative to each other, angled at more than 60°, angled between about 60° and 120°, angled between about 70° and 110°, angled between about 80° and 100°, angled at about 90°, or otherwise. The patient may be placed in a seated position during measurements. An illustration of the bending of a knee joint, specifically to a 90° angle, is provided in Fig. 6

[0050] When a patient is seated, placing the joint at an angle such as those described above, e.g. a 90° angle, may be relatively comfortable for the patient and may allow for accurate and repeatable placement of suitable electrode configurations.

[0051] In one embodiment, while the order and positioning of electrodes may be substantially maintained as per the embodiment of Figs. 1 to 6, the direction may be reversed. For example, as shown in Fig. 7, the first current electrode Ii and the first sensing electrode Si are located on the lower leg 42, and the second current electrode F and the second sensing electrode S2 are located on the upper leg 41 (including the knee cap 43), to the opposite side of the knee.

[0052] The electrode arrangement of the present disclosure may overcome a major challenge with regard to bioimpedance-based characterization of joints, e.g., major joints such as the knee. It may allow the applied electric current to course more deeply within the joint, e.g., within the articular cavity of the joint (see e.g. the articular cavity 47 of the knee between the femur 48 and tibia 49 as illustrated in Fig. 5), the primary spatial location of many joint disorders, yet without major and unquantified contributions from other tissues such as surrounding muscles, vasculature etc.

[0053] In any of the embodiments, to measure the bioimpedance Z oi across the joint of interest, the voltage V(Si-S2), is measured between the pair of sensing electrodes Si, S2 during application of the electrical signal. Since substantially only the current applied between the current electrodes Ii, h that is coursing through the joint of interest 12 is monitored between the sensing electrodes Si, S2, the voltage measurement between the sensing electrodes Si, S2 is dictated by the impedance of the tissue 10 at the joint of interest 12, substantially independent of the impedance of the tissue 10 outside of the joint of interest 12. Where voltage V(Si- S2) is measured between the pair of sensing electrodes (Si, S2), during application of the first electrical signal having a waveform or waveform spectrum suitable for electrical bioimpedance measurement (such as a controlled current AC waveform I(t)), the bioimpedance Z oi may be determined using Equation 1 :

ZJOI = V(Si- S₂) / 1( t) [1]

[0054] Apparatus employing an electrode configuration in accordance with Figs. 1 , 2 and 3 is shown schematically in Fig. 8.

[0055] The apparatus comprises integrated drive and voltage sensing circuitry 31, the circuitry 31 being connected to the pair of current electrodes Ii, I2 to deliver electrical signal current from a power supply 32 across a joint region of interest 12 of a patient 1 and to sense voltages between the pair of sensing electrodes Si, S2 while the signal is delivered. The drive and voltage circuitry 31 is connected to a processor 33, which provides a monitoring device and is configured to control the delivery of the electrical signal, determine the voltage measurements, and process the measurements to determine one or more bioimpedance measurement ZJOI, across the joint of interest in accordance with e.g. Equation 1.

Measurements may also be made to determine the quality of electrode contacts, e.g. by determining transverse impedances between different electrode combinations.

[0056] A user interface 34 (e.g. keyboard, touch screen, etc.) is connected to the processer 33 to allow the user to start and stop the process and/or control other characteristics of the process. The processor 33 is also connected to a display 35 to display at least the determined bioimpedance(s) and/or other indicators about the configuration of the apparatus. Particularly where a touch screen is employed, the display and user interface may be provided by substantially the same element. The processor 33 may also be connected to a loudspeaker 36 to provide an alert signal, e.g. if the apparatus senses an issue, e.g. based on quality of electrode contact. An alert may additionally, or alternatively, be issued on the display 35.

[0057] In this embodiment, the circuitry 31, power supply 32, processor 33, user interface 34, display, 35, and loud-speaker 36 are integrated into a single bioimpedance analysis unit 3, manufactured to carry out the process described above However, any one or more of these components may be located separately and connected by wires and/or other appropriate communication links including wireless communication links. For example, the processor 33, user interface 34, loud-speaker 36 and display 35 may be provided by more standard personal computing apparatus configured to run bespoke software in order to implement the process described above, which computing apparatus is connected to the integrated drive and voltage sensing circuitry 31 and power supply. In general, a wide variety of apparatus configurations may be used in order to carry out the process described above, including configuring the apparatus as wearable apparatus and/or use of inductive charging for example.

[0058] Poor electrode contact of the current electrodes is of particular concern in relation to the use of the signal generator. If contact impedance is very high as a result of poor contact, the signal generator may not be able to deliver the selected amount of current (if a current controlled mode is used), or the current delivered may be excessively low (if a voltage controlled mode is used). Where poor electrode contact is determined, the processor 33 controls the circuitry 31 to cut off and/or adjust the electrical signal.

[0059] In this embodiment, the electrical signal is applied for non-therapeutic effect.

That is, the electrical signal is applied for the purpose of analysing bioimpedance. However, the apparatus may be adapted such that the same or additional electrical signals are applied by the current electrodes for therapeutic purposes. These signals may have very different characteristics to those required for bioimpedance analysis, in order to provide therapeutically relevant electrostimulation of the tissue.

[0060] Referring to Fig. 9, in one embodiment, the techniques to characterise tissue of a joint as describe above are carried out bilaterally, e.g. on both a right arm 51 and a left arm 52 of a body 5. In this embodiment, the right arm has a damaged elbow joint 53, the damaged joint 53 being a first joint of interest. On the other hand, the left arm has a healthy elbow joint 54, the healthy joint 54 being a second region of interest. The configuration of the electrodes Ii, Si, Ii, S2 on the left arm is essentially a mirror image of the configuration on the right arm. Accordingly, bioimpedance measurements at a joint of interest, in particular the elbow joint 53, of the right arm can be compared with bioimpedance measurements at the corresponding healthy joint of interest 54 of the left arm 52.

[0061] In any embodiment described herein, one or more of the current and sensing electrodes may use a wet-type contact (e.g. using a conductive paste or hydrogel etc.). The contact may be adhesive or non-adhesive. Alternatively or additionally, any one or more of the current and sensing electrodes may use a dry-type contact (e.g. using metal, metal oxide, conductive textile, conformal“tattoo-like” thin-film, microstructured carbon or ultrafine microneedle arrays etc.). Any one of more of the electrodes can be active electrodes which have small or unit amplification close to the electrode. This may allow the electrodes to be used without electrode gel, for example. Any one or more of the electrodes may rely on an adhesive contact with the patient, and/or tattoo-like van der Waal’s contact and/or may be held in position using straps, bands, gloves, socks or belts or patient pressure (e.g. through a patient gripping or standing or resting on the electrodes).

[0062] Any one more of the electrodes may be fixed to the patient or be moveable. Any one or more of the electrodes may be provided by the same or different moveable probes, which are brought into contact with the patient.

[0063] Any one or more of the electrodes may take the form of metal plates, discs, strips, ellipses, heart-shapes, squares, rectangles or otherwise. Arrays of such electrodes may also be employed. The electrodes may have a width or diameter of between 0.1 and 15 mm, between 2 mm and 10 mm, between 10 mm and 20 mm, between 10 mm and 100 mm, or otherwise.

[0064] In some embodiments, the electrodes may be comprised in electrode devices that include anisotropically conductive material, e.g. as described in PCT Application No.

PCT/AU2018/051366, the entire contents of which is incorporated herein by reference. In these or other electrode devices, insulative template or mask layers may be used to define one or more electrodes across larger conductive substrates.

[0065] Electrodes can be independently mounted, or two or more electrodes can be fabricated onto/into a single carrier material such as a dressing. All or part of any one of the electrodes may be disposable, and discarded following testing to reduce the likelihood of cross-contamination between patients. Alternatively, any one or more of the electrodes may be disinfected after use, and suitably dried.

[0066] Physical contact is preferably avoided between the examiner and the patient during measurement to prevent the introduction of short-circuit contributions into the electrical measurement. The examiner may wear insulating gloves to prevent this possibility.

[0067] Standard medically-approved leads and cables may be used to connect the electrodes to the control apparatus. The leads may be directly connected to the control apparatus or connected to a wireless transmission unit for wireless transfer of data and/or electrical signals. [0068] The electrical signals for the non-therapeutic electrical characterisation of the body tissue may have a variety of different waveforms (frequencies, current levels) etc. The electrical signals may be a continuous AC waveform or pulsed. The electrical signals may have a frequency range of 1 kHz to 100 MHz, preferably 3 kHz to 1MHz. Signals may be in the form of a single frequency, a set of frequencies (i.e. multi-frequency) or a continuous sweep (spectrum) of frequencies. For controlled current drive, applied current may be between 0.2 mA and 2 mA, e.g., between 5 mA and 250 mA or between 5 mA and 500 mA, or otherwise. For controlled voltage drive, the applied voltage may be between 0.05V to 5.0 V, e.g. between 0.2 V to 2.0 V, or otherwise. A constant current drive may be preferable to counteract slight variations in the surface profile / quality of electrode contact at the connection positions. The electrical signals for the therapeutic (stimulating) treatment of the body tissue can be direct current (DC) and/or alternating current (AC). The therapeutic schemes include constant DCs, DC pulses, and ACs. A significant number of choices of different amplitudes, frequencies (AC and pulsed DC), duty cycles, durations, current strengths, etc. can be used. Current is typically very small for DC stimulation (hundreds of mA). Low- voltage pulsed currents can be pulses with durations up to 1 s and voltages up to 150 V, for example. Monophasic and biphasic pulsed currents can be low voltage and high voltage up to several hundred volts with short duration (ps), for example.

Examples

[0069] Bioimpedance measurements were made using electrodes configured in relation to a normal knee, in accordance with the arrangement shown in Figs. 4 to 6, also referred to herein as a“hybrid” arrangement. An electrical signal was applied between current electrodes Ii, . at a frequency of 50 kHz with the subject in seated position and with leg bent at 90°. Biompedance was calculated based on voltage measurements between the sensing electrodes Si, S2.

[0070] A comparison was made based on the same experimental configuration except with the electrodes positions in a standard tetrapolar arrangement (“standard” arrangement).

In the standard arrangement, electrodes were positioned outside of the adjacent sensing electrodes, rather than one of the current electrodes being located inside of the adjacent sensing electrode, as per the hybrid arrangement.

[0071] With reference to Table 1, the hybrid arrangement resulted in relatively low knee resistance measurements compared to the standard arrangement. The resistance

measurements were even lower when the leg/knee was placed in a bent configuration. By providing for a lower resistance measurement, the hybrid arrangement can provide for greater sensitivity when sensing resistance changes that may be indicative of knee abnormalities.

Table #1

*Tabulated data are average ± range of repeated measurements

[0072] Moreover, with reference to Table 2, the hybrid electrode arrangement was also found to result in lower resistance values for a patient with diagnosed bilateral osteoarthritis in both knees. Table 2 below shows comparative data between the patient (Subject #1) and a subject with normal knees (Subject#2).

Table #2

* Subject has diagnosed bilateral knee osteoarthritis

[0073] Further, an experiment was conducted in which an ice pack was applied to the medial surface of the left knee (centred on the medial femoral condyle) but the right knee left untreated. The experiment revealed the sensitivity of the hybrid arrangement with subject in seated position to changes in resistance associated with the imposition of cooling applied at a distance from the electrodes. Fig. 8 presents the findings as left-right difference in resistance measured with a 2-minute time offset using two bioimpedance devices. The expected increase in knee resistance associated with the application of the ice pack can be seen to be about 1.6 W relative to the baseline during which time the ice pack was not applied to the left knee. Resistance difference can be seen to continue to increase slightly even after the ice pack was removed.

[0074] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

1. A method for characterization of body tissue at a joint, the method comprising:

applying a first electrical signal between a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode connected to tissue at a first side and a second side, respectively, of a joint of interest;

2. The method of claim 1, wherein the first current electrode is further from the joint than the first sensing electrode.

3. The method of claim 1 or 2, wherein the applying and the measuring are conducted when the longitudinal axes of limbs immediately either side of the joint are, relative to each other, angled at more than 60°, angled between about 60° and 120°, angled between about 70° and 110°, angled between about 80° and 100°, or angled at about 90°.

4. The method of claim 1, 2 or 3, wherein the electrodes are connected to tissue on the same surface of the body.

5. The method of claim 1, 2 or 3, wherein the first current electrode and the first sensing electrode are connected to tissue on a first surface of the body and the second current electrode and the second sensing electrode are connected to tissue on a second surface of the body that is opposite to the first surface of the body.

6. The method of any one of the preceding claims, wherein the first and second current and sensing electrodes are positioned in a row.

7. The method of any one of the preceding claims, wherein the first and second current and sensing electrodes are positioned on the same plane of the body.

8. The method of claim 7, wherein the plane of the body is a parasagittal plane of the body.

9. The method of any one of the preceding claims, wherein the first current electrode is spaced from the first sensing electrode by at least 1 mm, 2 mm, 5 mm, or 10 mm.

10. The method of any one of the preceding claims, wherein the second current electrode is spaced at least 40 mm from the first sensing electrode.

11. The method of any one of the preceding claims, wherein the second sensing electrode is spaced from the second current electrode by at least 1 mm, 2 mm, 5 mm, or 10 mm.

12. The method of any one of the preceding claims, wherein the joint is a synovial joint.

13. The method of any one of the preceding claims, wherein the joint is a knee.

14. The method of claim 13, wherein the first current electrode and the first sensing electrode are located on an upper leg, to a first side of the knee, and the second current electrode and the second sensing electrode are located on a lower leg, to a second side of the knee.

15. The method of claim 13, wherein the first current electrode and the first sensing electrode are located on a lower leg, to a first side of the knee, and the second current electrode and the second sensing electrode are located on an upper leg, to a second side of the knee.

16. The method of claim 13, 14 or 15, wherein the first sensing electrode is placed on the upper leg and fully on, partially on, or proximal to the kneecap.

17. Apparatus for characterization of body tissue at a joint, the apparatus comprising:

a pair of current electrodes, the pair of current electrodes comprising a first current electrode and a second current electrode adapted to connect to tissue at a first side and a second side, respectively, of a joint of interest;

18. A method for characterization of body tissue at a joint, the method comprising:

19. The method of claim 18, wherein the longitudinal axes of limbs immediately either side of the joint are, relative to each other, angled at more than 60°, angled between about 60° and 120°, angled between about 70° and 110°, angled between about 80° and 100°, or angled at about 90°.