Edema detection

Abstract

A control method of a wearable device, wherein the wearable device comprises a signal generator, two stimulation electrodes and two sensing electrodes to monitor a degree of edema of a subject, the control method comprising: generating, with the generator, a signal causing a current to flow between the stimulation electrodes, and measuring, at time intervals over a test period, an impedance between the sensing electrodes arranged on the skin of the subject, thereby providing impedance measurements; validating each of the impedance measurements according to a set of models of impedance measurements; eliminating a measurement from the impedance measurements if the measurement fails the validation, thereby providing a subset of validated impedance measurements; converting each impedance measurement of the subset of validated impedance measurements into an edema index, thereby providing edema indices; averaging the edema indices and generating an average edema index for the test period; and generating an alert according to the average edema index.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 038,700, filed on June 12, 2020, the entire contents of which are incorporated herein by reference.

[0003] By combining references

[0004] This application also incorporates the entire contents of U.S. Patent Application No. 16 / 714,594 (Publication No. 2020-0187823), filed on December 13, 2019, and currently under examination, entitled "System and Method for Calibrating Dry Electrode Bioimpedance Sensing". Technical Field

[0005] The embodiments described herein generally relate to methods for monitoring the degree of edema in a subject and wearable devices. Background Technology

[0006] Measuring physiological data non-invasively to generate high user compliance is crucial for ensuring that numerous health monitoring applications collect and process continuous data. While devices exist for non-invasive and (in some cases) passive monitoring of individuals over a period of time, the balance between comfort and the necessary safety configuration of sensors (electrodes, etc.) creates additional obstacles to realizing the benefits of these physiological monitoring technologies.

[0007] Based on the problematic measurements, some physiological parameters are more difficult to measure than others, making data collection using non-invasive monitoring potentially challenging. The challenges of attempting non-invasive monitoring of physiological parameters are particularly significant, as these parameters are inherently difficult to measure and rely on perturbed equipment, the collection of erroneous data accompanying the acquisition of useful information, and the potential introduction of a large amount of erroneous data that can overwhelm the collection of valuable information. Therefore, using potentially valuable non-invasive monitoring devices requires the development and design of devices that prioritize the collection of valuable data and are capable of eliminating erroneous data, as well as data acquisition methods that retain valid data while removing other inaccurate or erroneous data. Summary of the Invention

[0008] One or more embodiments provide a wearable device and a method of using such a device for monitoring, for example, an individual's hydration level, the degree of edema due to excessive fluid retention or dehydration. The device and method include absolute or relative measurements of edema, measuring changes in edema over time using multiple indicators (including measuring the rate of change over time), and assessing the impact of any of these indicators on a physiological condition. This monitoring can be combined with other methods for emergency monitoring situations, such as dialysis, chemotherapy, exercise programs, postoperative monitoring, and any other physiological condition that may be accompanied by absolute or relative changes in the degree or pattern of edema, which may represent an underlying physiological condition of excessive fluid retention or dehydration that, as reflected in the measurements of edema, could lead to the onset or progression of numerous adverse medical events in an individual, including infections, hypertension, kidney disease, heart disease, etc. Monitoring the degree of edema is also useful for the long-term condition of individuals with chronic heart failure, chronic kidney disease, and similar conditions, in which subtle changes in absolute or relative measurements of edema may be the best indicator of disease progression or remission. The devices and methods described herein are preferably passive, for example, those that do not require active input from an individual or invasive monitoring that involves penetration of the skin or collection of biological samples from a patient.

[0009] The wearable device is designed to comfortably contact the skin of the individual being tested to obtain impedance measurements converted into an edema index. In such devices, for example, to avoid uncomfortable restriction or constraint on blood flow, the wearable device wrapped around the patient's skin lacks very tight contraction. This can lead to inaccurate data or an overemphasis on inaccurate or erroneous data along with valuable data, making it impossible to distinguish clinically useful information from content that may mislead diagnosis. However, using the device and methods for collecting and analyzing data described herein requires the device, data storage, and processing capabilities to reliably acquire an appropriate number of data points, particularly including impedance values ​​during the testing period, and the ability to remove inaccurate data points through a validation process. Accordingly, the development and processing of accurate data requires the identification and removal of erroneous or invalid data, which can be appropriately excluded from a larger set of measurements used to calculate the edema index based on medical or physiological grounds. The edema index can represent a variety of physiological conditions, including but not limited to datasets representing an individual's degree of hydration.

[0010] The necessary data processing and analysis steps provided alongside methods for absolutely or relatively monitoring the degree of edema in a subject include, but are not limited to, measuring, in absolute and over time, the absolute or relative impedance values ​​between at least two electrodes placed at different points on the skin region of the subject's limb, and measuring the rate of change of the edema index calculated as follows. Measurement sets can be repeated at selected time intervals during the testing period, which includes separate and discrete testing periods based on defined calibration tests and protocols, and the measurement sets can be configured to provide multiple impedance measurements as well as reference values ​​for control and calibration. Each measurement is validated based on a set of impedance measurement models collected during any testing, calibration, or control period.

[0011] This method involves determining whether impedance measurements included in any test, control, or calibration protocol fail a validation process that excludes individual or group of data points to identify and eliminate erroneous or invalid data from multiple impedance measurements, thereby providing a subset of validated impedance measurements. Each of the set or subset of validated impedance measurements is converted into an edema index, including any calibrated edema index, as described below, that generates a single or multiple edema indices derived from the absolute or relative degree or pattern of the impedance measurements. Multiple edema indices can be mathematically processed, including measurement averages, patterns, medians, thresholds, or mathematical or statistical measurements, in a manner that generates specific edema indices during baseline establishment, testing, or calibration. In some variations, approximately 10%, 20%, 30%, 40%, or more of multiple impedance measurements may fail validation, and the failed impedance measurements can be eliminated from the subset, or the final set of the validated set of impedance measurements, or the impedance values ​​of the subset. In some variations, the subset of validated impedance measurements may include at least 40% of multiple impedance measurements measured during testing.

[0012] Impedance can be measured repeatedly, approximately once per minute, approximately once every 10 minutes, approximately once every 20 minutes, approximately once every 30 minutes, approximately once every 60 minutes, or approximately once every 24 hours, or any time interval therein. Impedance measurements can be performed for periods of approximately 50 milliseconds, approximately 1 second, approximately 2 seconds, approximately 3 seconds, approximately 4 seconds, or any time interval therein. In some variations, the test period can be from approximately 1 hour to approximately 48 hours, or any value within that range.

[0013] In some variations, the model set for impedance measurements may include a Cole-Cole model. Validating each of multiple impedance measurements may involve fitting and evaluating a single selected set or subset of impedance measurements against the Cole-Cole model of the impedance measurements. The Cole-Cole model provides several suitable edema indices / indices, such as Ro, Rinf, fchar, etc. The fit quality of an individual impedance measurement to the Cole-Cole model provides another measure of data quality: the ability to exclude measurements from the analysis whose fit quality is significantly lower than expected from the baseline. Examples of these measures include the total error term relative to the expected value given by the Cole-Cole model, the number of frequency points exceeding a certain threshold of the expected fit value, the overall shape of the data relative to the Cole-Cole fit, and the relationship between the edema index derived from the Cole-Cole model of the specified impedance measurements and the edema index of similar bioimpedance measurements (whether the similarity is determined by temporal proximity or by the proximity of some measurements in the index space defined by a combination of Cole-Cole features of edema indices Ro, Rinf, and fchar, etc.); metadata about the scan, such as time of day; features derived from the original scan itself, such as the variance of the phase shift of the impedance signal.

[0014] This method may also include recording the average edema index during the testing period. Measurements can be taken over an extended duration, ranging from at least one day to six months or longer. In some variations, specific statistical or mathematical calculations of the edema index or measure can be recorded for each testing period within the extended duration.

[0015] In some variations, the method may include outputting or sending an alarm when a selected edema index exceeds a preselected value or a range of values. In other variations, the method may also include outputting or sending an alarm when the edema index falls below a preselected value or threshold. The alarm may be an electronic report provided to the patient, caregiver, or healthcare provider. In some variations, the alarm may be an audio or visual report and may include data compiled by a wearable device or data processed according to a method using such a device.

[0016] In some variations, the different positions of at least two electrodes may be 1 cm apart on the skin of the object, or may be located anywhere on the individual's body, including configurations that place the electrodes as far apart as opposite limbs, for example, one electrode on the left foot and the other on the right wrist.

[0017] In some variations, the method may further include securing one or more straps having at least two electrodes to the subject's limb, thereby positioning the at least two electrodes at different points on the subject's skin. In some variations, the limb may be the subject's wrist or the subject's leg.

[0018] In any of the methods and apparatus described herein, impedance measurement (which may be referred to as bioimpedance measurement) can be performed by measuring the electrical properties of biological tissue using a pair or more sensing electrodes, and by determining an absolute, relative, or calibrated impedance measurement based on an applied forward current and an applied short-circuit current (the same current being applied simultaneously to both stimulating electrodes) applied in the forward direction between a pair of stimulating electrodes. The voltage of the sensing electrodes in both forward operation (e.g., forward current) and short-circuit operation (e.g., short-circuit current), and the current or voltage of the current-sensing resistor in the forward operation, can provide a calibrated impedance measurement of the tissue. Very accurate and reproducible results can be provided in sensing bioimpedance using such a 'short-circuit' current to calibrate a self-calibrating measurement of the forward (and / or, in some variations, reverse) current. The short-circuit current can be provided before or after the forward (and / or reverse) current, and can be provided immediately or for a short time (e.g., milliseconds, seconds, or minutes) after the forward (and / or reverse) current. The same current as that in the forward and / or reverse current configuration can be provided in a short-circuit configuration (e.g., the same amplitude, frequency, duration, etc.). In some variations, more than one property of the short-circuit current (e.g., amplitude, frequency, duration, etc.) may differ from that of the forward and / or reverse current.

[0019] For example, a method for determining bioimpedance, which may be termed "calibrated bioimpedance," may include: providing a first current between an electrode and a receiving electrode in a forward mode and storing voltages from a first sensing electrode and a second sensing electrode; simultaneously providing a second current to both a source electrode and a receiving electrode in a short-circuit mode and storing voltages from both the first and second sensing electrodes; and outputting a calibrated bioimpedance measurement, which is at least partially based on the voltages of the sensing electrodes in the forward and short-circuit modes. The first and second currents may have the same amplitude, frequency, and / or duration, or may be configured to identify and coordinate predetermined values ​​and subsequent data processing steps. The first and second currents may be provided to each other within a predetermined time (from as close as 100 microseconds to as far as an hour). The first and second currents may be provided substantially immediately after each other. The above method may include cycling between modes (e.g., between a forward mode and a short-circuit mode, or between a forward mode, a short-circuit mode, and a reverse mode, such as a normal mode).

[0020] Estimating calibrated bioimpedance measurements may include determining calibrated bioimpedance measurements based at least in part on the voltage difference between the first and second sensing electrodes in normal and short-circuit modes, the voltage ratio of the first sensing electrode in normal and short-circuit modes, and the current flowing through the current-sensing resistor in normal mode. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of a wearable device according to some embodiments of the present disclosure.

[0022] Figure 2 This is a block diagram of a wearable device according to some embodiments of the present disclosure.

[0023] Figure 3 A block diagram illustrating the positive signal path through the sensing electrodes of a wearable device according to some embodiments of the present disclosure.

[0024] Figure 4 A block diagram illustrating the reverse signal path through the sensing electrodes of a wearable device according to some embodiments of the present disclosure.

[0025] Figure 5 A block diagram illustrating a short-circuit signal path through a sensing electrode of a wearable device according to some embodiments of the present disclosure.

[0026] Figure 6 A schematic diagram of a five-element circuit model for bioimpedance measurement.

[0027] Figure 7 A schematic diagram of a Cole-Cole plot for bioimpedance.

[0028] Figure 8 This is a flowchart of a monitoring process performed according to some embodiments of the present disclosure.

[0029] Figure 9 This is a schematic diagram of bioimpedance measurement over time.

[0030] Figure 10A as well as Figure 10B A graph showing the least-squares fit of bioimpedance measurements based on the volume of extracted bodily fluids.

[0031] Figure 11 This is a circuit diagram corresponding to the forward and reverse signal paths of a wearable device according to some embodiments of the present disclosure.

[0032] Figure 12 This is a circuit diagram corresponding to a short-circuit signal path in a wearable device according to some embodiments of this disclosure. Detailed Implementation

[0033] Physiological monitoring is an essential component of healthcare for patients with chronic diseases, such as heart failure (also known as congestive heart failure (CHF)), but not limited to these. In many diseases, monitoring hydration levels, such as edema and / or dehydration, can provide initial attention to changes in an individual's physical condition. This initial attention to adverse changes in hydration levels offers opportunities for early intervention. Early intervention reduces the need for drastic adjustments to medications, dialysis regimens, or individual care, rather than responding to a delayed change in the individual's condition. In addition to the clear benefits to the individual, preventing serious and detrimental changes in condition is also cost-effective for the care environment of hospitalized or outpatient patients.

[0034] For example, patients with heart failure may experience worsening edema as the disease escalates or progresses from chronic to acute. Changes in predetermined edema markers can indicate alterations in pharmacological interventions, behavioral changes, or even surgical interventions. The ability to intervene in a way that does not affect the effectiveness of other medications an individual might use to control other diseases and allows for more limited changes in diuretic administration or the introduction of other medications provides a more stable support regimen. This is particularly important for elderly patients who frequently require balancing the care of multiple diseases, where changes in the absolute or relative extent of edema indices can provide crucial information about changes in more than one underlying pathology.

[0035] In another case, for postoperative patients who receive less professional healthcare intervention when they are sent home or to a rehabilitation center, it is important to monitor their hydration levels to prevent them from deteriorating into a state of dehydration that could lead to severe postoperative secondary infections.

[0036] In such or other situations, physiological monitoring is advantageous over a specific time period (e.g., during dialysis for a patient with renal failure) or a less specific time period (e.g., for a patient with heart failure). It is highly advantageous to use monitoring devices that require little or no input / assistance from the individual. Furthermore, the device needs to fit the individual comfortably in the hospital setting or to facilitate postoperative patient compliance. The device also needs to exclude certain features that typically provide higher efficiency, such as the hydrogel pads used in clinically employed monitoring devices for contacting the skin with the electrodes. As a result, measurements obtained using physiological monitoring devices can be affected by individual movement and may therefore be inaccurate or useless. The ability to separate erroneous or inaccurate data from valuable data under less-than-perfect physiological monitoring conditions is a valuable aspect of this invention.

[0037] Therefore, there is a need for edema monitoring methods capable of testing and eliminating erroneous, inaccurate, or unusable data points or datasets. As mentioned above, while prolonged wear of the device may provide such erroneous data, the continuous operation of the device for long-term data collection offers the offsetting advantage of obtaining a large amount of data, which can then be tested to determine which data should be included in measurements of edema and / or dehydration and which should be rejected as inaccurate or erroneous.

[0038] Bioelectrical impedance analysis measures the bioimpedance generated within body tissues when an alternating current tends to flow through them. Bioimpedance is a function of tissue properties and the frequency of the applied current signal. The human body contains several different components that are quantifiable, including minerals (such as those in bones and electrolytes), muscle, and lean tissue; and body water, which is divided into intracellular and extracellular water. Furthermore, discrete intracellular structures also affect the edema index, which can be separated from intracellular and extracellular measurements or processed using separate statistical indicators as part of the analytical methods described herein.

[0039] Because cell membranes are inherently capacitive, the capacitive reactance generated by an electric current allows current to flow through these structures individually or jointly, depending on the signal frequency and current path. Low-frequency currents flow through the extracellular fluid because cell membrane reactance does not allow low-frequency currents to flow, while high-frequency currents penetrate the cell membrane and flow through both the extracellular fluid and the cell (cell membrane and intracellular fluid). Therefore, by applying an alternating current at a specific frequency, bioimpedance measurements can assess large amounts of extracellular water (ECW), intracellular water (ICW), and total body water (TBW = ECW + ICW). This allows for the acquisition of measurements of edema and / or dehydration.

[0040] This article provides a method for monitoring the degree of edema and / or dehydration, and more generally, the degree of hydration in an individual, using wearable devices. The degree of hydration can be obtained from impedance measurements of an individual's body parts.

[0041] The wearable device can have any number of driving electrodes, sensing electrodes, or combinations of driving / sensing electrodes, allowing selection of two driving points and two sensing points. Wearable devices with a dual-electrode configuration provide an input current signal and perform voltage measurement on the same electrode. Therefore, the impedance measured by a dual-electrode device includes the voltage drop due to contact impedance. In a wearable device with a four-electrode configuration, two separate electrode pairs are used for input current and voltage measurement. A constant amplitude current signal can be input to two external electrodes (e.g., current electrodes or driving electrodes), and a frequency-dependent voltage signal can be measured across two points via two internal electrodes (e.g., voltage electrodes or sensing electrodes). In any case, the wearable device can be configured to measure the impedance between two electrodes located at different locations on an individual's limb. The individual's limb can be a part of the arm, such as the arm or wrist, or a part of the leg, such as the leg or ankle. In some variations, the wearable device is configured to be attached to an individual's wrist so that the two electrodes for sensing voltage (e.g., which can be converted to impedance measurement) are positioned at different points on the individual's skin. These two points can be at least 10 mm apart, or as far apart as physiologically permissible for the wearer. Sensing electrodes are positioned and the difference in the area between the two sensing electrodes is read. The detected voltage is converted into impedance (Z), which represents a measurement of hydration in the body part through which the input current passes. In the method presented herein, impedance is correlated with the edema index of the monitored individual.

[0042] Figure 1 Non-limiting examples of suitable wearable devices 100 are shown. Figure 1 A bioelectric measurement wearable device 100 is shown attached to an individual's wrist 102, wherein the wearable device 100 contacts the individual's skin 104. The wearable device 100 includes internal electronics 106 connected to electrodes 112, 114, 116, and 118 in contact with the skin 104. The first electrode 112 and the third electrode 116 are stimulation electrodes. The second electrode 114 and the fourth electrode 118 are sensing electrodes. All electrodes are dry contact electrodes, requiring no skin formulations, gels, or other materials to optimize skin electrode impedance.

[0043] Wearable device 100 can be electrically connected to other devices such as processors, medical recorders, or databases, where data can be processed locally within the device or nearby or using a remote processor. Wearable device 100 can also be configured to provide a visual signal when the battery is low. Wearable device 100 can also be configured to provide a visual or audible alarm when a measurement is verified to exceed and / or fall below a pre-selected threshold as described below. To achieve these functions, wearable device 100 can have one or more lights such as LEDs, a display such as a liquid crystal display (LCD), and / or a speaker. Figure 1 (Not shown in the image).

[0044] Figure 2 This is a block diagram of wearable device 100. (Example) Figure 2 As shown, the internal electronics 106 of the wearable device 100 include: a controller 200; a signal generator 202 for generating test signals; a signal processor 204 for transmitting and receiving processed signals via electrodes 112, 114, 116, and 118; an optional multiplexer 206 for multiplexing and routing signals; a power supply 208 powered by a battery, etc.; and a current sensing resistor 210 for sensing current. For example, the current sensing resistor 210 is electrically connected to any line between the signal processor 204 and the multiplexer 206 to sense the current flowing therebetween. The controller 200 may include more than one processor and volatile and non-volatile memory. The controller 200 may also include interface circuitry configured to communicate with external devices such as a host computer and output alarms and related data via a wired or wireless network. In some variations, any of these components are combined or integrated together. As follows... Figure 3-6 As described and illustrated, the characterization of the skin electrode interface can be achieved by routing the test signal generated by the signal generator 202 to an optional multiplexer 206 or other controller and / or switching circuit, and to the stimulation electrodes 112 and 116 in the forward or short-circuit configuration (and in some variations in the reverse configuration).

[0045] For example, Figure 3 Show Figure 2The schematic illustration shows an example of the operation of the wearable device 100 in a forward configuration. In the forward configuration, the controller 200 may be configured to operate the wearable device 100 such that the signal 15 generated by the signal generator 202 is processed by and / or routed in the forward direction from the source electrode 112 to the receiving electrode 116 via the multiplexer 206. When current flows between the source electrode 112 and the receiving electrode 116, the controller 200 may detect signals from the sensing electrodes 114 and 118. In this example, data signals 16A and 16B may be processed and interpreted by the signal processor 204 and the controller 200. These data signals may correspond to the voltages at the sensing electrodes 114 and 118. Simultaneously, data from the current sensing resistor 210 (in the forward configuration) may be recorded during the period when the forward signal is applied. Figure 3-5 Signals (e.g., voltage and / or current) not shown in the diagram, and can be in Figure 2 The obtained positive characteristic data 17 is stored in the memory (not shown) of the controller 200 shown.

[0046] After operating the wearable device 100 in a forward configuration for one or more sets of samples (e.g., recording at one or more frequencies), the wearable device 100 can automatically (e.g., via the action of the controller 200) switch the operation to a short-circuit configuration. Alternatively or additionally, the wearable device 100 can be configured to switch the operation to a reverse configuration, in which, as... Figure 4 As shown, the source electrode and the receiving electrode 112, 114, 116, 118 can be reversed (for example, the source electrode can be used as the receiving electrode, and the receiving electrode can be used as the source electrode).

[0047] Figure 4 Show Figure 2 This schematic illustration shows an example of the operation of a wearable device 100 in a reverse configuration. Figure 4 In the reverse configuration, a signal 19 generated by signal generator 202, which may be the same as or different from the signal 15 supplied in the forward configuration, is processed by signal processor 204 and routed in the reverse direction by multiplexer 206 between receiving electrode 116 and source electrode 112. Sensing electrodes 114 and 118 can be used to record data signals 20A and 20B (e.g., voltage) generated by the reverse current, and these sensing data signals can be processed and interpreted by signal processor 204 and controller 200 together with the sensed current and / or voltage from current sensing resistor 210, and the resulting reverse characteristic data or second characteristic data 21 can be processed by... Figure 2 The controller 200 shown is stored.

[0048] As described above, after one or more operations performed by the wearable device 100 in the forward and / or reverse configuration or mode, the wearable device 100 can immediately and automatically (e.g., via the action of the controller 200) switch to operation in a short-circuit configuration, simultaneously sending current to the source electrode and the receiving electrode 112 and 116. In the short-circuit configuration or short-circuit mode, the same current can be provided to both the source electrode and the receiving electrode 112 and 116. The current provided is the same as or approximately the same as the current provided in the forward and / or reverse configuration. In some variations, the current may be different; for example, the current provided to the two electrodes when operating in the short-circuit configuration may be less than the current during operation in the forward and / or reverse configuration.

[0049] Figure 5 An example of the operation of the wearable device 100 described in the above short-circuit configuration / mode is shown. Figure 5 In this process, the parallel signal 24 (e.g., current) generated by the signal generator 202 can be processed by the signal processor 204 and routed by the multiplexer 206 in either the parallel or short-circuit direction to provide the same signal (e.g., current) to both the source electrode 112 and the receiving electrode 116. Signals sensed by the sensing electrodes 114 and 118, generated from the provided signals, can be received as data signals 25A and 25B and processed and / or interpreted by the signal processor 204 and the controller 200. Signals received during short-circuit operation (e.g., voltages at sensing electrodes 114 and 118) can correspond to short-circuit characteristic data 26 and can be... Figure 2 The controller 200 shown is stored.

[0050] In some variations, the controller 200 uses forward data 17 and short-circuit data 26 (and / or in some embodiments, reverse data 21 and short-circuit data 26) to characterize the interface 27 between the electrodes 112, 114, 116 and 118 and the skin, and to determine an accurate estimate of the biosignals (e.g., bioimpedance) of the skin in contact with the electrodes.

[0051] The wearable device 100 described above allows for frequent impedance measurements, providing multiple measurements, ranging from fewer than 10 measurements to many more (e.g., thousands) within a selected test period. Measurements can be performed at selected time intervals during the test period. Impedance measurements can be repeated from approximately once per minute to once every 48 hours. Data can be collected from 500 μs to 450 s for impedance measurements.

[0052] Measurements can be collected during the testing period, which can be approximately 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 18 hours, 24 hours, or any value in between. In some variations, the testing period can be approximately 1 hour to approximately 24 hours. Measurements taken during the testing period can be grouped together to obtain the average of the measurements or any other statistical grouping deemed to provide meaningful information to the caregiver (e.g., daily averages of the measurements). Grouped values ​​of measurements expressed as edema index or hydration value can be included in the individual's record and retained for the duration of the measurement.

[0053] In a non-limiting example, while measurements may be grouped for shorter testing periods (e.g., daily), monitoring of individuals can continue for a longer duration. The duration of monitoring can be short, such as one day, two days, or several days (e.g., when monitoring individuals undergoing kidney dialysis). In other variations, such as when monitoring individuals with heart failure, the duration of monitoring can be approximately one week, one month, two months, three months, six months, one year, or longer. In some variations, monitoring can be provided for approximately one month to approximately six months or longer. Average (or grouped) values ​​for each testing period can be recorded throughout the entire monitoring duration. In some variations, the recorded values ​​may be the average edema index instead of impedance values.

[0054] In some variations, when the average / group measurement value exceeds or falls below a pre-selected threshold, an alarm can be output or sent from wearable device 100, an external device connected to the wearable device, or an external device storing the grouped or average measurement values ​​sent to a database. The alarm can be notified to patients, healthcare providers, or caregivers who may require intervention or further relevant monitoring of the individual. In some variations, the alarm may also include a visual or audible alarm from wearable device 100, an external device connected to the wearable device, or an external device storing the grouped or average measurement values ​​sent to a database. Accordingly, the data analysis equipment and methods can be integrated with patient-carried companion devices (e.g., mobile phones, computers, and other mobile monitoring devices) and institutional networks used by hospitals for local or decentralized monitoring of patients with medical histories or critical care conditions.

[0055] As described above, individual impedance measurements may be erroneous or may include erroneous factors because the wearable device 100 is not uncomfortablely and tightly fixed to any part of the individual's body, and the electrodes do not have hydrogel or other skin preparations to assist in electrical measurements. Additionally, the individual is not required to maintain a restrained or immobile posture. Under any of these conditions, the wearable device 100 may slip or move, resulting in erroneous measurements. Therefore, the wearable device 100 is capable of verifying any impedance measurement or all impedance measurements.

[0056] Impedance measurements can be performed at a single frequency or at multiple frequencies, and can be any single or multiple frequencies from 1 kHz to about 1 MHz, or in between.

[0057] It can be selected based on what can be chosen as Figure 6 A bioimpedance model of the five-element circuit model is shown to verify impedance measurements. In this model, ri represents extracellular fluid, and another branch represents the intracellular components of aqueous fluid containing structures. C1 represents the cell membrane and n intracellular (cytoplasmic) fluid. C2 represents the intracellular cell membrane, and r3 represents the corresponding fluid within intracellular structures (e.g., the nucleus, lysosomes, etc.) surrounded by the intracellular membrane. In some variations of these techniques, the C2-r3 branch of the circuit can be ignored and adjusted to the values ​​of C1 and r2 through modeling.

[0058] The following relationship can be used, based on Figure 7 The Cole-Cole model shown fits each data point or any selected subset thereof:

[0059]

Mathematical Formula 1

[0060]

[0061]

Mathematical Formula 2

[0062]

[0063] However, a data point or set of data points that does not produce a good fit according to the Cole-Cole plot can be eliminated from multiple impedance measurements, thereby providing a validated subset of impedance measurements. In some variations, approximately 5%, 10%, 15%, 20%, 30%, 40%, or more of the impedance measurements obtained during the test may fail validation, for example, fail to fit to the Cole-Cole plot.

[0064] Each validated impedance measurement can then be used to calculate an individual edema index using a combination of values ​​derived from the equation. One example of the edema index is using only the Ro term. Another example is the following relationship:

[0065]

Mathematical Expression 3

[0066]

[0067] Therefore, the wearable device 100 provides multiple edema indices during each test period, and these multiple edema indices can be averaged in any suitable manner to provide an average edema index during the test period. The advantage of this method is that it eliminates the need for numerous impedance measurements from any input source of the tested individual, allowing for the exclusion of a proportion of impedance measurements that do not fit the Cole-Cole plot. In some variations, the validated measurement can be greater than approximately 25%, approximately 30%, approximately 40%, approximately 50%, approximately 60%, approximately 70%, approximately 80%, or more of the impedance measurements performed during the test period. Figure 9 As shown, even though there are many data points that cannot be included due to the movement of the wearable device 100 on an individual's skin, including but not limited to the edema index obtained from the average edema index during the test period, the edema index is related to the individual's hydration status, as will be further explained later.

[0068] The testing period can be, for example, 24 hours, and the monitoring duration can be several days or many days. The average edema index can be used to track the degree of edema (or hydration) of an individual monitored by the wearable device 100.

[0069] Figure 8 This is a flowchart illustrating the steps of a monitoring method performed by wearable device 100. Initially, controller 200 controls signal generator 202 to generate a test signal that causes a specific current to flow at various frequencies between stimulation electrodes 112 and 116 disposed on the skin of a limb (e.g., an arm) of the subject, and measures the impedance between two sensing electrodes 114 and 118. The measured impedance can be stored in the memory of controller 200 (not shown).

[0070] In S502, controller 200 verifies the impedance measured in S501 by determining whether each impedance fits to the Cole-Cole model. For example, controller 200 determines whether it falls within the range of fitting the Cole-Cole model. Figure 7 The diagram shows more than one measured impedance within a specific range of the Cole-Cole diagram. In S503, the controller 200 eliminates the measured impedances that were not verified in S502 from subsequent analysis. In S504, the controller 200 converts the verified impedances into an edema index. For example, the conversion can be performed based on mathematical formula 3 described above. Subsequently, for example, the controller 200 calculates the average edema index in S505, and outputs the average edema index in S506 by storing the index in memory. The controller 200 can send the calculated edema index to an external device via a network interface (not shown).

[0071] Figure 8 All the steps shown can be performed by the wearable device 100. Alternatively, more than one of steps S503-S506 can be performed by an external device connected to the wearable device 100. In this case, the controller 200 sends the measured impedance to the external device via an interface circuit. Figure 8 The steps shown can be performed repeatedly during the selected test period.

[0072] Example

[0073] Experiment 1. Long-term individual monitoring. Subjects wore wearable devices and were passively monitored for 15 days. Figure 9 As shown, impedance measurements were collected for 10 to 20 minutes each day within selected time periods. Data were collected while individuals were awake, and the data were not uniformly distributed within each 24-hour time period. The data were validated according to the Cole-Cole model, as described above. Unvalidated data were primarily found in regions 401–426. Only validated data points were used to convert to an edema index, which was then averaged to generate the mean edema index for each time period (i.e., each day). The mean edema index for each day from day 1 to day 15 is represented by line 450.

[0074] like Figure 9 As shown, due to the individual's influenza, the mean edema index value, indicated by line 450, begins to decrease from day 1 (i.e., the mean edema value at point 455). The mean edema index decreases further due to increased dehydration caused by influenza, reaching point 460 on day 9 and dropping to point 465 on day 12. As the individual recovers, the mean edema index also rebounds, as shown in the figure, reaching point 470 on day 15.

[0075] Experiment 2. Measurement of edema during dialysis. A group of individuals undergoing dialysis wore a wearable device 100 and were monitored for more than three hours during the dialysis process. Measurements were taken every 10 to 20 minutes, and the measurements were fitted according to the Cole-Cole model described in this paper. Figure 10A and Figure 10BEach section illustrates an individual's dialysis process. The section shows the time progression along the X-axis, and the volume of water extracted (liters, L) from time t = 0 to 3 hours is shown decreasing from a value of 0.00 to the final extracted volume (i.e., the intersection of the left-hand Y1 axis and the X-axis). The Y1 axis shows the reverse ultrafiltration volume recorded during the dialysis process. The individual's hydration level, measured using the methods described herein, is shown on the right-hand Y2 axis, decreasing from a value of 1.00 to the final value at t = 3 hours. The right-hand Y2 axis shows the Ro value immediately after the start of the dialysis process divided by each Ro value during the dialysis process (i.e., normalized impedance). For ease of illustration, only the graph of the Y2 axis in each section is labeled "R". The least squares value R², representing the goodness of fit, ranges from a high value of 0.973 to a low value of 0.135.

[0076] like Figure 10A and Figure 10B As shown in the set of images, the correspondence between individuals and between the dialysis process and subsequent dialysis processes did not reach a complete correspondence. However, the overall R² value of 0.752 was obtained during the measurement of the entire group of individuals, indicating a substantial correspondence for the entire group.

[0077] Calibration of bioimpedance

[0078] As mentioned above, Figure 5 The short-circuit configuration of the wearable device 100 shown can be used to calibrate bioimpedance. For example, this calibration is performed in... Figure 8 The impedance measurement shown is performed during or after the measurement.

[0079] Impedance mismatch between the subject's skin 104 and sensing electrodes 114 and 118 can be determined by the controller 200 of the wearable device 100 during calibration and used to adjust the interpretation of biosignals from electrodes 114 and 118. The wearable device 100 performs a set of calibration measurements. For example, calibration measurements may include the differential voltage between sensing electrodes 114 and 118, the total current through electrodes 114 and 118 (e.g., the current through current-sensing resistor 210), and the voltage at the input of one of sensing electrodes 114 and 118 in both forward (or reverse) and short-circuit configurations. Any suitable set of measurements can be used to calibrate the impedance of the electrode / skin interface 27.

[0080] For example, as described above, a first set of measurements can be performed using current flowing in either the forward or reverse direction to provide forward data 17 or reverse data 21. Short-circuit data 26 can be collected as described above (e.g., immediately after collecting data from the forward and / or reverse direction, immediately before collecting data, or intermittently), and the first set of data, such as forward data 17, and short-circuit data 26 can be combined to calculate a first impedance of the target tissue calibrated using the short-circuit data.

[0081] In some variations, the measurement and calculation process is repeated using previously unused current directions (e.g., reverse data 21) and corresponding short-circuit data 26. The reverse data 21 and short-circuit data 26 can be combined to calculate the second impedance of the target tissue. The accuracy of the resulting bioimpedance measurement can then be improved by combining the first impedance data with the second impedance data, for example, by averaging them together, by weighting the reverse direction relative to the forward direction, etc.

[0082] Specifically, bioimpedance can be calibrated by the ratio of the differential voltage at sensing electrodes 114 and 118 to the voltage at the input of one of sensing electrodes 114 and 118 in both forward and short-circuit configurations.

[0083] For example, Figure 11 and 12 Show respectively Figure 2-5 The diagram shows the operation of the wearable device 100 in normal forward configuration and short-circuit configuration. Figure 11 and 12 In the circuit, current source electrodes / receivers 112 and 116 have impedances Z1 and Z3, respectively. Voltage sensing electrodes 114 and 118 have impedances Z4 and Z5, respectively. The object tissue has impedance Z2, and the current sensing resistor 210 has impedance Z6. Z8 and Z9 refer to the input impedances of the buffer amplifier. As described above, Figure 11 This illustrates the system in a positive configuration or pattern. Figure 12 The system is shown in a configuration or mode in which a current is simultaneously applied to both the source electrode 112 and the receiver electrode 116 in a short-circuit configuration or mode.

[0084] As described above, the wearable device 100 has a source electrode 112, a receiving electrode 116, and at least two sensing electrodes 114 and 118. The wearable device 100 also has the ability to switch between a forward or normal configuration and a short-circuit configuration (and in some variations, a reverse configuration). Therefore, the wearable device 100 can be configured to guide current in the forward direction (and / or the reverse direction) and simultaneously guide current to both the two source electrodes and the receiving electrodes 112 and 116, enabling measurement via the sensing electrodes 114 and 118. Figure 11 and 12 The leakage currents 18 and 19 are shown.

[0085] Therefore, the wearable device 100 can be configured to measure the differential voltage multiplied by the gain of the amplifier at the sensing electrode: (G(V4-V5)) = β. In the normal (i.e., forward) configuration, the differential voltage multiplied by the gain at the sensing electrode can be represented by the subscript "N.". In the short-circuit configuration, the differential voltage multiplied by the gain at the sensing electrode can be represented by the subscript "B.". Therefore:

[0086]

Mathematical Expression 4

[0087] β N =G(V 4，N -V 5，N )

[0088]

Mathematical Expression 5

[0089] β B =G(V 4，B -V 5，B )

[0090] The differential voltage across the current-sensing resistor 210 is: (G(V6-V7))=α. Therefore, the forward configuration is:

[0091]

Mathematical Expression 6

[0092] α N =G(V6-V7)=I 6，N Z6G

[0093] The various gains shown above can be set to the same gain (e.g., the gain of the amplifier used) or different gains. For convenience, these gains are presented as the same gain in this document; however, it should be understood that they can be different.

[0094] The voltage at the input of one of the sensing electrodes 114 and 118, for example, V4, is γ. The forward and short-circuit configurations are as follows:

[0095]

Mathematical Expression 7

[0096] γ N =V 4，N

[0097]

Mathematical Expression 8

[0098] γ B =V 4，B

[0099] The following set of equations describes the current flowing in the positive direction:

[0100]

Mathematical Expression 9

[0101] V4-V5=(V2-Z4I4)-(V3-Z5I5)

[0102]

Mathematical Formula 10

[0103] V4-V5=(V2-V3)+(Z5I5-Z4I4)

[0104] V2-V3 represent the measurements to be performed, and (Z5I5-Z4I4) represent the error terms. Use the following equation:

[0105]

Mathematical formula 11

[0106] V2 - V3 = Z2I2

[0107]

Mathematical formula 12

[0108] I2 = I6 + I9

[0109] The following relationship can be derived:

[0110]

Mathematical formula 13

[0111] V4 - V5 = Z2(I6 + I9) + Z5I5 - Z4I4

[0112] Due to this relationship: I5 = I9 and I4 = I8,

[0113]

Mathematical formula 14

[0114] V4 - V5 = Z2(I6 + I9) + Z5I9 - Z4I8

[0115] As described above, normal (e.g., forward / reverse) current operation can be indicated by the subscript N in the measurement terms. Under this condition, I6 >> I9, and the relationship simplifies to:

[0116]

Mathematical formula 15

[0117] V 4，N -V 5，N = Z2I 6，N + Z5I 9，N - Z4I 8，N

[0118] For the short - circuit mode where current is supplied to both the source electrode and the receiving electrodes 112 and 116 simultaneously, I6 + I9 = I2 is approximately equal to Is, and Is is also approximately equal to I9. However, due to the relationship Z2 << Z4 and Z2 << Z5, Z2I2 can be set to zero. This assumption simplifies the relationship to:

[0119]

Mathematical formula 16

[0120] V 4，B -V 5，B = Z5I 9，B - Z4I 8，B

[0121] Substitute:

[0122]

Mathematical formula 17

[0123]

[0124] The result is:

[0125]

Mathematical formula 18

[0126]

[0127] The voltage ratio (e.g., V4 / V5) is fairly consistent with the operating mode. This has been empirically verified. In some variations, an additional measurement at Vs can be used to avoid the need for this approximation. Using the relationship:

[0128]

Mathematical Expression 19

[0129]

[0130] Rearranged as follows:

[0131]

Mathematical Expression 20

[0132]

[0133] Multiplying both sides of mathematical expression 18, the result is:

[0134]

Mathematical Expression 21

[0135]

[0136] It can be simplified to:

[0137]

Mathematical Expression 22

[0138]

[0139] Given:

[0140]

Mathematical Expression 23

[0141]

[0142] and

[0143]

Mathematical Expression 24

[0144]

[0145]

Mathematical Expression 25

[0146]

[0147] It is produced by subtracting mathematical expression 25 from mathematical expression 15:

[0148]

Mathematical Expression 26

[0149]

[0150] The result of the cancellation is:

[0151]

Mathematical Expression 27

[0152]

[0153] Finally, the impedance (Z2) related to the solution is obtained as follows:

[0154]

Mathematical formula 28

[0155]

[0156] Therefore, measuring all terms in the above equation provides the calibrated impedance of the object's tissue.

[0157] The above equation can be used in Mathematical formula 28, and the result is:

[0158]

Mathematical formula 29

[0159] Z2 = (β N - β B * (γ N / γ B )) / (α N / Z6)

[0160] The previous analysis assumes that I6 >> I9 under normal operation. Therefore, the Z2I9 term in Mathematical formula I4 can be set to zero. In the case of providing current to both sides of the current path (for example, in the case of a short circuit), I6 + I9 = I2, and Is and I9 are approximately the same, Z2 << Z4 and Z2 << Z5, allowing Z2I2 = Z2(I6 + I9) in Mathematical formula 11 to be set to zero. Finally, the voltage ratio of V2 to V5 is the same in normal and short - circuit modes. Therefore, the ratio of V4,n / V4,B is approximately equal to the ratio of V5,n / V5,B.

[0161] When a feature or element in this document is referred to as being "on" another feature or element, it can be directly on the other feature or element, or there can also be intermediate features and / or elements. Conversely, when a feature or element is referred to as being "directly on" a feature or element, there are no intermediate features or elements. It should also be understood that when a feature or element is referred to as being "connected", "attached" or "coupled" to another feature or element, it can be directly connected, attached or coupled to the other feature or element, or there can also be intermediate features or elements. Conversely, when a feature or element is referred to as being "directly connected", "directly attached" or "directly coupled" to another feature or element, there are no intermediate features or elements. Although described or shown with respect to one embodiment, the features and elements so described or shown can be applied to other embodiments. Those skilled in the art should also understand that a structure or feature configured "adjacent" to another feature can have overlapping parts or parts located under the adjacent feature.

[0162] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention. For example, the singular forms “a,” “an,” and “the” used herein are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that when the terms “comprising” and / or “including” are used in this specification, they specifically refer to the presence of the stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or combinations thereof. The term “and / or” as used herein includes any one or all combinations of more than one of the related listed terms and may be abbreviated to “ / ”.

[0163] For ease of description, this document uses spatially related terms such as “below,” “below,” “lower than,” “above,” “over,” etc., to describe the relationship between one element or feature shown in a figure and another. It should be understood that, in addition to the orientation shown in the figure, spatially related terms are intended to cover different orientations of the device in use or operation. For example, if the device in the figure is reversed, an element described as “below” or “under” relative to other elements or features is oriented as “above” relative to other elements or features. Thus, the exemplary term “below” can encompass both above and below orientations. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatially related descriptors used herein shall be interpreted accordingly. Similarly, the terms “up,” “down,” “vertical,” “horizontal,” etc., used herein are for illustrative purposes only, unless otherwise specified.

[0164] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms unless the context otherwise requires. These terms can be used to distinguish a feature / element from another feature / element. Therefore, without departing from the teachings of the invention, the first feature / element described below may be referred to as the second feature / element, and similarly, the second feature / element described below may be referred to as the first feature / element.

[0165] Throughout this specification and the following claims, unless the context otherwise requires, the word "comprising" and variations such as "including" and "containing" mean that various components may be used together in a method and article (e.g., a composition and apparatus, including devices and methods). For example, the term "comprising" will be understood to imply the inclusion of any specified element or step, but does not exclude any other element or step.

[0166] As used herein in the specification and claims, including as in the embodiments, unless otherwise expressly stated, all figures may be understood to begin with the word “about” or “approximately”, even if such terms are not explicitly stated. The terms “about” or “approximately” may be used when describing size and / or location to indicate that the described value and / or location is within a reasonable range of expected values ​​and / or locations. For example, a numerical value may be + / - 0.1% of a specified value (or range of values), + / - 1% of a specified value (or range of values), + / - 2% of a specified value (or range of values), + / - 5% of a specified value (or range of values), + / - 10% of a specified value (or range of values), etc. Any numerical value given herein should also be understood to include approximately or approximate that value, unless the context otherwise requires. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical ranges listed herein are intended to include all subranges contained therein. It should also be understood that, as those skilled in the art would appropriately understand, when a value is disclosed, the terms "less than or equal to the value," "greater than or equal to the value," and possible ranges between values ​​are also disclosed. For example, if the value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" are also disclosed (e.g., X is a numerical value). It should also be understood that data is provided in various different formats throughout the application, and that this data represents endpoints and start points, as well as a range of any combination of data points. For example, if specific data point "10" and specific data point "15" are disclosed, then it should be understood that greater than, greater than or equal to, less than, less than or equal to, equal to 10 and 15, and between 10 and 15 are also disclosed. It should also be understood that each unit between two specific units is disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0167] Although various illustrative embodiments have been described above, any of the various embodiments may be modified without departing from the scope of the invention as set forth in the claims. For example, the order in which the various described method steps are performed may generally be modified in alternative embodiments, and one or more method steps may be skipped entirely in other alternative embodiments. Optional features of the various device and system embodiments may be included in some embodiments but not in others. Therefore, the foregoing description is presented primarily for illustrative purposes and should not be construed as limiting the scope of the invention as set forth in the claims.

[0168] The examples and accompanying drawings contained herein illustrate specific embodiments in which the subject matter can be practiced in an illustrative and non-limiting manner. As stated above, other embodiments can be utilized and derived therefrom, allowing for structural and logical substitutions and modifications without departing from the scope of this disclosure. These embodiments of the subject matter of the invention may be referred to herein individually or collectively by the term "invention," which is for convenience only and is not intended to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one, which is actually disclosed. Therefore, although specific embodiments have been described and illustrated herein, any arrangement designed to achieve the same purpose may replace the specific embodiments shown. This disclosure is intended to cover any and all changes or modifications to the various embodiments. Combinations of the above embodiments and other embodiments not specifically described herein will be apparent to those skilled in the art upon reading the foregoing description.

Claims

1. A method of operating a controller that controls a wearable device capable of monitoring a degree of edema of a subject, the wearable device including a signal generator, at least two stimulating electrodes, and at least two sensing electrodes, the controller generating, with the signal generator, a first signal that causes a current to flow between the at least two stimulating electrodes, and measuring, at selected time intervals over a test period, an impedance configured between the at least two sensing electrodes, thereby obtaining a plurality of impedance measurements; the controller excluding, from a set of the plurality of impedance measurements, impedance measurements of the set of the plurality of impedance measurements that exceed a threshold based on an expected value imparted by a Cole-Cole model, by fitting the set of the plurality of impedance measurements to the Cole-Cole model, thereby obtaining a subset of impedance measurements that conform to the Cole-Cole model; the controller converting each impedance measurement of the subset of impedance measurements to an edema index, thereby obtaining a plurality of edema indices; the controller generating, from the plurality of edema indices, a specific edema index that is a mean, a mode, or a median of the plurality of edema indices for the test period.

2. The method of claim 1, wherein the at least two stimulating electrodes include a source electrode and a sink electrode, the controller supplies a first current between the source electrode and the sink electrode in a first direction, and simultaneously supplies a second current to the source electrode and the sink electrode in the first direction and a second direction opposite the first direction, thereby measuring the impedance, determining the impedance includes calculating the impedance based at least in part on a voltage between the at least two sensing electrodes when supplied with the first current and the second current.

3. The method of claim 2, wherein calculating the impedance includes determining the impedance based at least in part on a voltage difference between the at least two sensing electrodes when supplied with each of the first current and the second current, a voltage ratio at a first sensing electrode when supplied with the first current and the second current, and a current flowing through a current sense resistor when supplied with the first current.

4. The method of any one of claims 1-3, wherein the measuring of the impedance is repeated every ten minutes to every twenty minutes.

5. The method of any one of claims 1-3, wherein the measuring of the impedance is for 1 second to 4 seconds.

6. The method of any one of claims 1-3, wherein the test period is 1 hour to 24 hours.

7. The method of any one of claims 1-3, wherein the controller records the specific edema index.

8. The method of any one of claims 1-3, further comprising: extending the test period to a prescribed duration.

9. The method of claim 8, wherein the extended period is 1 month to 6 months. ​ 10. The method of any one of claims 1 to 3, wherein the wearable device is configured to arrange the at least two sensing electrodes on a wrist of the subject.

11. The method of any one of claims 1 to 3, wherein the controller outputs an alert from at least one of the wearable device and an external device when the specific edema index exceeds or falls below a preselected value.

12. The method of any one of claims 1 to 3, wherein the controller comprises an interface circuit that causes at least one of the wearable device and an external device to output an alert.

13. The method of claim 11, wherein the alert is an electronic report.

14. The method of claim 11, wherein the alert is an audible or visual report.

15. The method of any one of claims 1 to 3, wherein the subset of impedance measurements comprises at least 40% of the plurality of impedance measurements measured during the test period.

16. The method of any one of claims 1 to 3, wherein the wearable device is configured to arrange the at least two sensing electrodes at least 1 cm apart on the subject's skin.

17. The method of any one of claims 1 to 3, wherein the wearable device comprises a strap of the at least two sensing electrodes, the strap being securable to the subject's skin such that the at least two sensing electrodes are arranged at different points on the subject.

18. A controller that controls a wearable device for monitoring a degree of edema in a subject, the wearable device comprising at least two stimulating electrodes, at least two sensing electrodes, and a signal generator, the controller is configured to control the signal generator to generate a first signal that causes a current to flow between the at least two stimulating electrodes, measure impedance between the at least two sensing electrodes at selected time intervals during a test period, thereby providing a plurality of impedance measurements, from a set of the plurality of impedance measurements, exclude impedance measurements in the set of the plurality of impedance measurements that exceed a threshold based on an expected value assigned by a Cole-Cole model by fitting the set of the plurality of impedance measurements to the Cole-Cole model, thereby obtaining a subset of impedance measurements that conform to the Cole-Cole model; convert each impedance measurement in the subset of impedance measurements to an edema index, thereby obtaining a plurality of edema indices, generate a specific edema index from the plurality of edema indices, the specific edema index being a mean, a mode, or a median of the plurality of edema indices during the test period.

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