System and method for calculating voltage applied to wound tissue

Abstract

The present disclosure provides a method. The method includes applying one or more electrical signals to the wound tissue and collecting electrical measurements from the array of electrodes. The method further includes processing the collected electrical measurements to generate one or more impedance maps of the wound tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over the region of the wound tissue. The method further includes calculating at least two voltages for the wound tissue based on the spatial distribution of the electrical measurements of the impedance map of the wound tissue. A system is also provided that includes an electrode array, circuitry functionally connected to the electrode array, and a processor. Further, a device for application to traumatic tissue is provided, the device comprising an electrode array configured for disposition on traumatic tissue, and circuitry functionally connected to the electrode array.

Description

Background Technology

[0001] Epithelial cells can be guided to move in the direction of an applied electric field. This phenomenon can be utilized to enhance re-epithelialization of wounds if electrical stimulation can be applied effectively. Further development of electrical stimulation in promoting re-epithelialization is desirable. Summary of the Invention

[0002] In a first aspect, a method is provided. The method includes applying one or more electrical signals to traumatic tissue via an electrode array; and collecting electrical measurements from the electrode array via circuitry functionally connected to the electrode array. The method further includes processing the collected electrical measurements via a processor to generate one or more impedance maps of the traumatic tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over a region of the traumatic tissue; and calculating at least a first voltage and a second voltage for the traumatic tissue based on the spatial distribution of the electrical measurements from the one or more impedance maps of the traumatic tissue.

[0003] In a second aspect, a system is provided. The system includes an electrode array configured to apply one or more electrical signals to wound tissue; circuitry functionally connected to the electrode array to collect electrical measurement results from the electrode array; and a processor. The processor is configured to: process the collected electrical measurement results to generate one or more impedance maps of the wound tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over a region of the wound tissue; and calculate at least a first voltage and a second voltage for the wound tissue based on the spatial distribution of the electrical measurement results from the one or more impedance maps of the wound tissue.

[0004] In a third aspect, a device for application to traumatic tissue is provided. The device includes an electrode array comprising at least two electrodes configured to be disposed on the traumatic tissue and configured to apply one or more electrical signals to the traumatic tissue; and a circuit functionally connected to the electrode array to collect electrical measurement results from the electrode array and transmit the collected electrical measurement results for processing.

[0005] These aspects advantageously provide calculated voltages tailored to specific traumatic tissues based on the impedance map of the traumatic tissue.

[0006] The foregoing overview of this disclosure is not intended to describe every embodiment or every specific implementation of this disclosure. The following description illustrates exemplary embodiments in more detail. Throughout the application, guidance is provided by a list of examples that may be used in various combinations. In each case, the drawn list is intended only as a representative group and should not be construed as an exclusive list. Attached Figure Description

[0007] Figure 1 This is a flowchart of an exemplary method according to one implementation scheme.

[0008] Figure 2 This is a schematic diagram depicting an exemplary electrode array according to one embodiment.

[0009] Figures 3A to 3B These are photographs and figures related to the estimation of the trauma boundary, based on an implementation scheme.

[0010] Figures 4A to 4C It is a schematic diagram depicting the application of an electric field to traumatic tissue according to one implementation scheme.

[0011] Figure 5 The invention describes how an inwardly pointing E-field can be achieved near the trauma boundary of traumatic tissue according to one implementation scheme.

[0012] Figure 6 This is a schematic diagram depicting an exemplary system according to one implementation scheme.

[0013] Figures 7A to 7B These are photographs of traumatic tissue on the back of a pig according to one implementation scheme and electrical conductivity maps of the traumatic tissue obtained by EIT.

[0014] Figure 7C It is applied according to an example of an implementation scheme. Figures 7A to 7B A schematic diagram of the system of traumatic tissue.

[0015] Figure 8 This is a flowchart of one implementation scheme of this disclosure.

[0016] Figures 9A to 9C It is a diagram of relative conductivity and topography during the progression of trauma according to one implementation scheme.

[0017] While the foregoing figures illustrate several embodiments of this disclosure, other embodiments are contemplated as indicated in the description. The figures are not necessarily drawn to scale. In all instances, this disclosure presents various aspects of the invention by way of example and not limitation. Detailed Implementation

[0018] Glossary

[0019] The terms "preferred" and "ideally" refer to embodiments of this disclosure that may provide certain benefits in certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are useless, nor is it intended to exclude other embodiments from the scope of this disclosure.

[0020] In this application, terms such as “a,” “an,” and “the” are not intended to refer only to a singular entity, but rather to include general categories whose specific examples may be used to illustrate the point. The terms “a,” “an,” and “the” are used interchangeably with the term “at least one.” The phrases “at least one of…” and “including at least one of…” followed by a list refer to any one of the items in the list and any combination of two or more items in the list.

[0021] As used herein, the term "or" is generally used in its usual sense, including "and / or," unless otherwise expressly stated. The term "and / or" means one or all of the listed elements or any combination of two or more of the listed elements.

[0022] Similarly, in this document, it is assumed that all figures are modified by the term “about,” and preferably by the term “precisely.” As used herein in conjunction with the quantity being measured, the term “about” refers to the variation in the quantity of the measurement as expected by a technician performing the measurement and at a level of care commensurate with the purpose of the measurement and the precision of the measuring equipment used.

[0023] As used herein as modifiers of characteristics or attributes, unless otherwise specifically defined, the term "generally" means that the characteristic or attribute will be easily recognized by a person skilled in the art but does not require absolute precision or perfect match (e.g., within + / -20% for quantifiable characteristics). Unless otherwise specifically defined, the term "substantially" means highly approximate (e.g., within + / -10% for quantifiable characteristics), but also does not require absolute precision or perfect match. Terms such as identical, equal, consistent, constant, and rigorous are understood to mean within the usual tolerances or measurement errors applicable to the specific situation, without requiring absolute precision or perfect match.

[0024] As used herein, the term "impedance" refers to an electrical property that includes a complex number of quantities called "real" and "imaginary" quantities, such as Z = R + iX, where Z is impedance, R is the so-called real part and is resistance, and X is the so-called imaginary part and is reactance. Furthermore, the term "conductivity" as used herein is the mathematical reciprocal of resistance R. The term "relative conductivity" refers to conductivity relative to a measured or algorithmically estimated baseline value.

[0025] The term "electrical measurement results" refers to the measurement results of electrical characteristics such as conductivity, resistivity, complex impedance, impedance magnitude, admittance, impedance phase angle, reactance, etc., at one or more frequencies.

[0026] The term "impedance diagram" refers to a spatial representation of the distribution of one or more electrical measurements, which may exist in the form of a map or other suitable data structure.

[0027] The term "trauma tissue" refers to both the tissue surrounding the wound and the tissue in the wound bed. The term "wound bed tissue" refers to tissue with damage to the epithelium, damage to the subcutaneous tissue, and / or tissue with at least one of bruising, rash, or infection. The term "peri-trauma tissue" refers to tissue in the area surrounding the wound, which can be defined as the area of ​​skin extending beyond the wound bed by a certain distance (e.g., a few centimeters, such as 4 cm), or the surrounding skin extending from the wound bed.

[0028] The term "boundary" in traumatic tissue refers to at least one of the areas, volumes, or lines between the trauma bed and the surrounding tissue. Traumatic tissue may have more than one closed boundary.

[0029] The term "tissue characteristic map" or "clinical metric" refers to a spatial representation of one or more tissue characteristics, including, for example, wound edges / boundaries, wound depth information (e.g., a topographic map of wound depth relative to x and y coordinates), the presence of granulation tissue, granulation tissue thickness, wound healing stage (e.g., hemostasis, inflammation, proliferation, remodeling, etc.), epithelial coverage, epithelial layer thickness, biomass, bioburden, degree of infection, infection type, necrotic tissue, and healed tissue. Tissue characteristic maps can exist in the form of maps or other suitable data structures. In some cases, the representation or map of tissue characteristics may include healing metrics.

[0030] The term "healing metric" refers to an overall assessment of a wound, which represents a calculation of tissue characteristic data. Healing metrics may include wound length, wound width, wound depth (e.g., maximum, minimum, average, etc.), wound area, wound volume, granulation tissue thickness (e.g., maximum, minimum, average, etc.), total epithelial coverage (e.g., the percentage of the wound bed covered by new epithelium), epithelial thickness (e.g., maximum, minimum, average, etc.), total bioburden, biofilm thickness (e.g., maximum, minimum, average, etc.), biofilm amount, etc.

[0031] method

[0032] In the first aspect, a method is provided. (See reference) Figure 1 The method includes: One or more electrical signals are applied to the wound tissue 110 via an electrode array; Electrical measurement results 120 from the electrode array are collected via a circuit functionally connected to the electrode array; The collected electrical measurement results are processed by a processor to generate one or more impedance maps of the traumatic tissue, the one or more impedance maps representing the non-uniform electrical characteristics 130 measured over the region of the traumatic tissue; and At least a first voltage and a second voltage 140 are calculated for the traumatic tissue based on the spatial distribution of electrical measurements from one or more impedance maps of the traumatic tissue. In some cases, the first voltage and the second voltage are different from each other, while in other cases, the first voltage and the second voltage are the same. In a selected embodiment, at least four voltages are calculated for the traumatic tissue based on the spatial distribution of electrical measurements from one or more impedance maps of the traumatic tissue.

[0033] There are no particular limitations on the electrodes. Exemplary suitable electrode arrays include, for example, but not limited to, 15 pin electrodes on a rigid printed circuit board (PCB), 15 pin electrodes on a flexible Kapton PCB, 64 pad electrodes on a flexible Kapton PCB, 16 pin electrodes on a flexible transparent composite material, or 3MRED DOT 2670 skin electrodes attached to a flexible Kapton PCB via a snap-fit ​​connector. Reference Figure 2 An exemplary eight-electrode device 2000 is fabricated on a soft, flexible substrate 2100. Electrodes 2200 are 3M RED DOT 2360 electrodes (3M Company, St. Paul, MN). The device includes a UV-curable silicone encapsulant protective layer 2300 and a polyurethane film 2150, which is laser-etched and silver-coated to serve as leads 2400 and contacts 2500, with the electrodes 2200 embedded within the cured silicone encapsulant 2300. The substrate 2100 defines an open region 2600 that can be appropriately positioned on a desired portion of wound tissue.

[0034] Electrical impedance tomography (EIT) is used to measure and determine the spatial distribution of electrical impedance in a continuous two-dimensional (2D) or three-dimensional (3D) space. Typically, impedance measurements are obtained from electrical contacts sparsely distributed in a continuous 2D / 3D space, and this continuous 2D / 3D impedance map is reconstructed by solving the inverse problem from the finite element model (FEM) to space. For the method described herein, an array of electrodes is placed on the wound tissue to spatially map the resistance / conductivity profiles of the wound and surrounding tissue. In some cases, one or more electrodes are placed around the periphery of a wound bed on the tissue surrounding the wound, one or more electrodes are placed on the wound bed, or both.

[0035] Electronic devices for EIT mapping of traumatic tissue may include electrodes, a microcontroller for measurement control and data acquisition, a low-noise, high-precision current source as a power source, an analog-to-digital (ADC) preamplifier for noise filtering and signal amplification, and an input / output multiplexer for switching electrodes for current source and voltage measurements.

[0036] One or more signal generators may be electrically connected to an electrode array and configured to generate alternating electrical signals, such as electrical waveforms. These signals may be sine waves, square waves, pulse waves, triangle waves, sawtooth waves, etc. The signal generator may be configured to generate electrical signals of one or more frequencies, including those between 1 kHz and 2 kHz, 2 kHz and 4 kHz, 4 kHz and 55 kHz, and 55 kHz and 120 kHz. In some examples, the signal generator may be configured to generate electrical signals within a frequency range that may be greater than or less than the ranges described above. In some examples, the signal generator may be configured to generate electrical signals at predetermined frequencies, such as approximately 85 kHz (e.g., 85 kHz ± 10 kHz). In some cases, the signal generator is configured to generate electrical signals.

[0037] Impedance maps can be obtained at a single frequency or multiple frequencies. In some implementations, impedance can be measured relative to different baselines established through different estimation schemes. A baseline may refer to a map representing the electrical conductivity values ​​of the tissue before trauma. Relative conductivity may refer to a map obtained by subtracting the tissue's current conductivity from the baseline map.

[0038] In some examples, baseline measurements of untraumatized tissue may include a uniform measurement capturing the background conductivity of intact tissue and a non-uniform measurement capturing the conductivity of traumatized tissue. Methods for estimating the baseline may include, for example, frequency difference EIT (fdEIT), measurement scale feature (MSF), best uniformity (BH) estimator, data-driven estimator, or a combination thereof. Data-driven estimators may include machine learning and deep causal learning methods using database references. Useful database references may be based on patient history or patient demographic information. Alternatively, methods that do not require baseline measurements of untraumatized tissue may be used to reconstruct conductivity maps of traumatized tissue. Because biological tissues can have different frequency responses, the impedance distribution of traumatized tissue can be imaged using fdEIT reconstruction methods, where the traumatized tissue is measured at at least two frequencies. Measurements at a first frequency (i.e., the reference frequency) can act as a proxy for baseline measurements, while measurements at a second frequency (i.e., the measurement frequency) act as non-uniform measurements. Therefore, in some implementations, one or more impedance maps of the traumatic tissue are estimated by algorithm using frequency difference electrical impedance tomography (fdEIT), measurement scale feature (MSF), best homogeneity (BH) estimator, data-driven estimator, or a combination thereof.

[0039] Different methods can be used when reconstructing conductivity maps. Exemplary methods include the one-step Gauss-Newton (GN) method and the iterative total variation (TV) method, applying appropriate hyperparameters in each case. Hyperparameters can be heuristically determined to optimize the contrast between the anomaly and the background. It should be noted that this heuristic selection can also be replaced by automatic selection based on any pre-determined strategy. The one-step GN method can provide real-time reconstruction results of acceptable quality with anomalies of shape and size. The TV method, as an iterative method, tends to be computationally slower than the GN method, but can also provide higher resolution for topological features.

[0040] As an alternative, baseline measurement estimation techniques can be used to calculate the uniform conductivity distribution of untraumatized tissue. Then, tdEIT can perform estimated baseline and non-uniform measurements to reconstruct the conductivity map of traumatized tissue. For example, the best uniform approximation or a predefined MSF can be used to estimate the baseline measurements. In a context with n E In an EIT system with one electrode, baseline measurement U 基线 n represents the state of the adjacent stimulus pattern. E (n) E -3) A vector of voltage measurement results.

[0041] In one implementation scheme, U is estimated through the following steps. 基线 First, a finite element model (FEM) reflecting the geometry of the wound tissue and the electrode arrangement is generated. Second, a simulated baseline measurement U0 is obtained from the FEM with a uniform conductivity distribution, where the baseline conductivity σ0 = 1. Third, a non-uniform measurement U is obtained from the wound tissue. 测量 Finally, the baseline measurement is estimated by scaling U0 using the ratio parameter µ. Therefore, the baseline vector will be represented as: When using the BH method for baseline estimation, the ratio parameter It can be represented as When using the MSF operator for baseline estimation, the ratio parameter It can be represented as , in A feature operator is defined as a method that maps measurement results to feature values. Exemplary MSF operators include arithmetic mean, range, intermediate range, electrode-based average range, and electrode-based average intermediate range. The mathematical representation of each operator is provided below: MSF1: Arithmetic Mean MSF2: Range MSF3: Middle Range MSF4: Average range based on electrodes MSF5: Average midrange based on electrodes

[0042] In some implementations, a new impedance map can be arithmetically calculated from an impedance map at a given frequency and from maps generated from different baseline estimation schemes. The measured impedance may vary due to variations in the electrical properties between tissue sites within an individual (e.g., different tissue locations in the same patient and / or animal), variations in tissue properties over time, and variations between individuals (e.g., between patients and / or animals). For example, the electrical properties of a tissue may vary based on tissue composition and thickness, tissue water content and / or tissue hydration, relative humidity of the environment at the time of measurement, etc. Additionally, the electrical properties of a tissue may depend on the specific tissue type residing at that location. For example, variations have been observed in muscle relative to fatty tissue, and in the case of traumatic tissue, variations have been observed in untraumatized, well-epithelialized tissue relative to open wound areas containing different types and amounts of healing tissue (e.g., different amounts of granulation tissue filling in the wound bed and / or different degrees of epithelial coverage in the wound bed).

[0043] In some implementations, the impedance map of the wound tissue can be converted into a quantitative measure of healing. In other words, a spatial map of impedance (e.g., conductance or resistance) obtained via EIT can be converted into a quantitative map of healing, such as wound shape, depth, size (e.g., area or volume), amount of granulation tissue, epithelial coverage, stage of wound, etc.

[0044] In some implementations, by calibrating impedance maps using a calibration model, one or more impedance maps can be converted into spatial maps of clinical metrics. Clinical metrics can include the relationship of various trauma information data relative to (x, y) coordinates in a Cartesian coordinate system (x, y, z), where the z-axis corresponds to the depth direction of the wound tissue. Example clinical metrics may include wound depth d(x, y), granulation tissue thickness t, etc. g (x, y), epithelial coverage c(x, y), biofilm thickness t bThe calibration methods include (x, y), bioburden (i.e., the number of contaminated organisms found in a given amount of material) b(x, y), degree of infection i(x, y), healing stage (e.g., inflammation, proliferation, or remodeling stage) indicator h(x, y), etc. Suitable calibration methods also include those described in detail in PCT application number PCT / IB2022 / 062138 (Zhu et al.), the entire contents of which are incorporated herein by reference.

[0045] In some embodiments, the obtained impedance maps can be used to determine wound boundaries and other wound tissue characteristics. For example, in some embodiments, one or more impedance maps of the wound tissue identify at least one boundary between the wound bed and the surrounding tissue. As described above, a "boundary" refers to at least one of the region, volume, or line between the wound bed and the surrounding tissue. For example, referring to Figure 3, an impedance map of the relative conductivity of the wound site can be used to estimate the location of the wound boundary by thresholding. Figure 3A Photograph 3100 shows a tissue model of a trauma phantom modeling a wound that has begun to re-epithelialize inward from the wound boundary, a type of wound that may benefit from E-field accelerated epithelialization. Point 3110 indicates the location of electrode placement, and circle 3120 indicates the location of the wound boundary (in this case, the boundary is a range that surrounds the non-epithelialized open wound tissue and does not contain epithelialized tissue). Figure 3200 also provides EIT acquisition of the relative conductivity of the trauma phantom. Figure 3A Also included are contour plots 3300 of the relative conductivity of the trauma phantoms with thresholds of -0.05, -0.06, -0.08, -0.10, -0.12, and -0.15. Note that the contour lines with the -0.06 threshold follow the trauma boundary 3320 relatively well. Photograph 3400 of the trauma phantom with a relative conductivity threshold of -0.06 highlights how well this threshold predicts the location of the trauma boundary 3420. Figure 3BA threshold contour map 3500 is plotted, with a threshold of -0.06 3520, representing 3D contour lines. Various mathematical methods can be applied here to detect wound edges based on variations in material properties (such as relative conductivity). Many methods for edge detection exist in the literature (such as the Canny edge detector, Deriche method, Sobel method, Prewitt method, Gaussian Laplacian operator, Hessian determinant, etc.), generally falling into two groups: search-based and zero-crossing-based. In this case, one approach is to apply a search-based method, such as the Canny edge detector or Sobel method, based on the gradient magnitude of conductivity, and search for the gradient direction to find the wound edge. Another approach is to apply zero-crossing methods to search for zero-crossing points in the second derivative expression (e.g., the Laplacian operator). Alternatively, we can combine edge detection methods, such as evaluating a combination of conductivity and its gradient, to determine the wound boundary.

[0046] For example, referring to Figure 4, epithelial cells 4100 can be guided to move in the direction D of the applied electric field (e.g., Figure 4A If electrical stimulation can be applied in a manner that creates an electric field (E-field) at the target therapeutic intensity, this phenomenon can be utilized to enhance the re-epithelialization of the wound (e.g., Figure 4B Although an electrode array providing voltages v1-v8 intersecting with the wound tissue 4200 can theoretically produce a sculpted E-field distribution (e.g., as... Figure 4C The electric field distribution depicted is inward-pointing, but the electrical properties of actual trauma are often spatially non-uniform and change over time (e.g., as the trauma heals).

[0047] Advantageously, the calculated voltage is generated according to at least some embodiments of the present disclosure, the calculated voltage being designed to achieve a predetermined electric field for the traumatic tissue based on near real-time determination of the impedance map of the traumatic tissue. Since the electrical properties of a particular traumatic tissue vary over time, the calculation can be updated simultaneously over time. Therefore, re-reference Figure 1 The method may also optionally include repeating each of the collection, processing, and calculation steps 160 after applying the first and second voltages to the traumatic tissue. Alternatively, grounding (i.e., zero voltage) may also be applied to the traumatic tissue. In some cases, the collection, processing, and calculation steps are repeated at a predetermined time after the first and second voltages are applied to the traumatic tissue. Typically, these processes can be performed on short timescales, such as seconds (or even faster), and therefore the predetermined time can be selected based on other criteria, such as the amount of time required for a measurable change in one or more electrical properties of the traumatic tissue. There are no particular limitations on the predetermined time and it may include any one or more of 1–60 minutes, 1–24 hours, 1–7 days, or 1–52 weeks.

[0048] A method for calculating voltage is described herein. Voltage optimization calculations can be performed to calculate voltage at a specified electrode placed around the wound tissue (e.g., at...). Figure 3A At position 3110, an appropriate voltage is selected. It should be noted that for these examples, to simplify calculations, the two electrodes at the 12 o'clock position are connected to the same voltage (v1), the two electrodes at the 3 o'clock position are connected to voltage (v2), the two electrodes at the 6 o'clock position are connected to voltage (v3), the two electrodes at the 9 o'clock position are connected to voltage (v4), and the center electrode is grounded (0 V). However, it should be noted that the described method can alternatively apply eight independent voltages to each of these eight electrodes, and any number of electrodes and applied voltages can be used. The voltage is calculated using a map of the electrical non-uniformity of the wound tissue (e.g., from an EIT map), such that an E-field distribution with a target intensity of 30 V / m is formed in the tissue around the wound boundary, which is also mapped using the EIT method. In some embodiments, the E-field distribution is designed to provide an inwardly pointing E-field direction.

[0049] This method utilizes the principle of superposition. That is, the voltage distribution manifested on wound tissue is the sum of the voltage distributions formed by the voltage contributions of each individual electrode. The algorithm converts voltage (v...) into... i A finite element simulation, performed in the AC / DC module of COMSL, is applied to each individual electrode (i.e., i can be equal to [1, 2, 3, 4]). The simulation is then applied to find the wound boundary voltage distribution and negative gradient. electric field, , The electric field must be decomposed into x and y components. Therefore: and (Corresponding to the i-th electrode, where i = [1, 2, 3, 4]). Using superposition, the field E can be expressed as: and , in It is the scaling factor for each individual electrode, which can be weighted using an algorithm. The voltage gradient norm is then calculated using the following formula: An optimization program based on MATLAB's optimization function is used to solve for these weighted scalar factors. The error e is: in It is the target field strength E, which is 30 V / m in our example. It should be noted that the target E-field strength can be any value determined to optimize epithelial cell migration, and can be informed through experiments, databases, algorithms, machine learning, deep causal learning, and physician / patient input (patient demographics, medical records, etc.). The optimal applied electrode voltage, after scaling, is then determined as follows: (Corresponding electrode i = [1, 2, 3, 4]).

[0050] Refer again Figure 1 The method may optionally further include applying at least a first voltage and a second voltage 150 to the wound tissue via an electrode array. The electrode array comprises at least two electrodes, but any number may be used. For example, the electrode array may include 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more electrodes. Regardless of the number of electrodes in the array, the electrodes may be configured to function independently and / or have any positive or negative voltage.

[0051] In some cases, applying at least first and second voltages generates an electric field oriented at least partially inward from the boundary toward the trauma bed. For example, refer to Figure 5 An inwardly pointing E-field can be achieved near the wound boundary of a specific traumatic tissue. Photograph 5200 is a trauma phantom showing the location of each electrode v1-v8 and ground v0. Figure 5300 shows the E-field lines when the electrodes are excited at the mentioned optimized voltage. Note that the E-field lines (i.e., the lines with arrows) typically begin to point inward at least at the wound boundary 5100. Figure 5400 depicts the E-field distribution when the electrodes are excited at the optimized voltage. Note that a target E-field strength close to 30 V / m is achieved along the wound boundary.

[0052] However, there are no particular limitations on the magnitude of the electric field. In some cases, applying (e.g., at least first and second) voltages produces electric fields with voltages of 0 volts per meter (V / m) or greater, 2V / m, 5V / m, 10V / m, 15V / m, 20V / m, 25V / m, 30V / m, 35V / m, 40V / m, 45V / m, 50V / m, 55V / m, 60V / m, 65V / m, 70V / m or 75V / m or greater, and 1,000V / m or less, 950V / m, 900V / m, 850V / m, 800V / m. Electric fields on the order of 750V / m, 700V / m, 650V / m, 600V / m, 550V / m, 500V / m, 450V / m, 400V / m, 350V / m, 300V / m, 250V / m, 200V / m, 175V / m, 150V / m, 125V / m, 100V / m, 90V / m, 85V / m, 80V / m, 75V / m, 70V / m, 65V / m, 60V / m, 55V / m, or less than 50V / m. In some embodiments, the E-field strength ranges from 10V / m to 100V / m (inclusive).

[0053] Refer again Figure 4C and Figure 5 In some embodiments, the application includes grounding 0 volts (V) to electrodes positioned on the trauma bed. Including Figure 5 In the selected embodiment of the example shown, the electrodes positioned on the trauma bed are located substantially at the center of the trauma bed.

[0054] Systems and devices

[0055] In a second aspect, a system is provided. The system includes: An electrode array configured to apply one or more electrical signals to wound tissue; A circuit, functionally connected to the electrode array, for collecting electrical measurement results from the electrode array; and The processor is configured to: The collected electrical measurements are processed to generate one or more impedance maps of the wound tissue, the one or more impedance maps representing the non-uniform electrical properties measured over a region of the wound tissue; and At least a first voltage and a second voltage are calculated for the traumatic tissue based on the spatial distribution of electrical measurements from one or more impedance maps of the traumatic tissue.

[0056] In a third aspect, a device for application to wounded tissue is provided. The device includes: An electrode array comprising at least two electrodes configured to be disposed on the wound tissue and configured to apply one or more electrical signals to the wound tissue; and A circuit, functionally connected to the electrode array, for collecting electrical measurement results from the electrode array and transmitting the collected electrical measurement results for processing.

[0057] Figure 6 This is a schematic diagram depicting an exemplary system 6000 according to one embodiment. In the depicted embodiment, system 6000 includes a device 6102 and a computing device 6106. In some cases, device 6102 is a diagnostic or monitoring device. In some cases, device 6102 is a dressing. Device 6102 may be communicatively coupled to computing device 6106, for example, via a wired or wireless connection. Computing device 6106 may include processing circuitry 6216 coupled to a display 6218, an output 6221, and a user input 6222 of a user interface 6228. In some examples, display 6218 may include one or more display devices (e.g., a monitor, PDA, mobile phone, tablet computer, any other suitable display device, or any combination thereof). For example, display 6218 may be configured to display physiological information and information indicating epithelial tissue characteristics determined by system 6000.

[0058] Device 6102 can be of any type of structure. In some examples, device 6102 may include a bandage comprising a flexible backing material, an adhesive for bonding to the skin of patient 614, and electrodes 6130. In some examples, device 6102 may include a foam dressing comprising electrodes 6130. In some examples, device 6102 may include a material fixed to tissue or physically held in place via, for example, an adhesive. In other examples, device 6102 may be a diagnostic patch, such as a material comprising any of the electrodes 6130. In some examples, additional materials may be applied to patient 614 for wound measurement / monitoring, such as sterile saline-soaked gauze, gel, etc., placed between device 6102 and tissue site 6150.

[0059] Device 6102 includes an electrode array 6130. When device 6102 is positioned on wounded tissue to be tested, the electrode array can apply an electrical signal from a signal generator to a first tissue site 6152 located outside a second tissue site 6150. The second tissue site 6150 may correspond to injured tissue or a wound bed, such as tissue with damage to the epithelium and / or subcutaneous tissue. The second tissue site 6150 may also correspond to tissue with bruising, rashes, infection, etc. In the presence of observable open wounds, the second tissue site 6150 may also correspond to currently undamaged tissue for which damage needs to be monitored (e.g., monitoring venous leg ulcers (VLU) or pressure ulcers (PU)). The first tissue site 6152 may optionally correspond to tissue in a region surrounding the wound, which may be defined as a skin area extending beyond the wound bed by a distance (e.g., several centimeters, such as 4 cm), or the surrounding skin extending from the wound bed. In some examples, the additional material may include therapeutic agents such as drugs, and / or may be at least partially conductive and may enhance the conductivity between electrode 6130 and the first tissue site 6152.

[0060] One or more signal generators may be electrically connected to the electrode array 6130 and configured to generate alternating electrical signals, such as electrical waveforms. The electrical signals may be as described in detail above with respect to the first aspect.

[0061] exist Figure 6 In the depicted embodiments, device 6102 further includes processing circuitry 6116 and memory 6124. In some embodiments, device 6102 may process electrical signals without transmitting them to computing device 6106. For example, processing circuitry 6116 may also include a signal monitor to detect electrical signals applied to a first tissue site 6152 adjacent to the second tissue site 6150. In other embodiments, electrical signals or information corresponding to electrical signals may be transmitted to computing device 6106 for processing, for example, via a wired or wireless connection between device 6106 and computing device 6102.

[0062] Memory 6116 and memory 6224 may include any volatile or non-volatile media, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, etc. The memory may be a storage device or other non-transitory medium. Processing circuitry 6216 or 6124 may use the memory to, for example, store reference information or initialization information corresponding to physiological monitoring (such as trauma monitoring). In some examples, processing circuitry 6216 or 6124 may store physiological measurement results or data previously received from electrical signals in the memory for later retrieval. In some examples, processing circuitry may store determined values ​​(such as information indicating epithelial tissue characteristics) or any other calculated values ​​in the memory for later retrieval.

[0063] Figure 7A and 7B Each of these is a photograph of a tissue part that can be used according to an implementation plan. Figure 7C This illustrates the application to wounded tissue sites (such as...) Figures 7A to 7B A schematic diagram of the 7000 system (for the site of traumatic tissue). Figures 7A to 7B As shown in the example, tissue site 7150 corresponds to at least partially open wound tissue. Peri-traumatic tissue site 7152 corresponds to the area surrounding open wound tissue 7150.

[0064] In this example, system 7000 includes an electrode array 7210 disposed on a wound peri-trauma tissue site 7152. The electrode array 7210 is supported by a substrate 720. In the depicted example, substrate 720 includes a central portion 7202 that substantially covers (e.g., an open wound bed tissue 7150) and a periphery 7204 of the central portion 7202. The electrode array 7210 is disposed on the inner surface of the dressing periphery 7204.

[0065] Using the previously described EIT method, Figure 7A and Figure 7B The trauma sites shown can be mapped in a manner that characterizes the spatial distribution of the electrical conductivity of the trauma bed relative to the intact skin found in the surrounding tissue of the trauma site. To collect this data, a euthanized Yorkshire pig was first prepared by shaving the hair from the right back flank (where the trauma bed would be created and the peritracheal electrode would be placed) and abdomen (where a single large reference electrode would be placed). Two circular trauma bed sites, each 5 cm in diameter, were delineated on the right back flank of the animal, with a 15 cm distance between adjacent trauma centers. One trauma bed was created via a full-thickness surgical excision (i.e., down to the dorsal fascia), and was semi-circular in shape. Figure 7A (left side), and another trauma bed was created by full-thickness resection, which is circular ( Figure 7B(Left). A large viscous return electrode was placed on the shaved abdomen of the animal, which was connected to the electrical ground of the EIT electronics. Eight 3M Red Dot 2670 electrodes were cut into circular shapes and placed around each of the two wound beds on the intact tissue surrounding the wound (eight electrodes per wound), with uniform spacing around the wound periphery. Figure 7A and Figure 7B (Left photo). These electrodes are snap-fitted to the input terminals of the EIT electronics via electrocardiogram (ECG) leads. The EIT electronics use a Keithly 6211 current source to inject a sinusoidal current at 40 kHz into the rotating electrode pairs, while voltage measurements are taken from other electrodes in the array. This tomographic mapping scheme produces a spatial map of the conductivity of the traumatic tissue, which is presented here relative to the intact skin surrounding the trauma. Figure 7A and Figure 7B The right side shows the conductivity measurement plot. For the semi-circular wound bed, it can be seen that the generated relative conductivity plot shows areas of changing conductivity values ​​in the region corresponding to the semi-circular wound bed. Figure 7A Right figure: Non-zero color within the dashed semicircular area). Similarly, for a circular trauma bed, the generated relative conductivity map shows the region of changed conductivity values ​​in the area corresponding to the circular trauma bed in the figure ( Figure 7B Right side: Non-zero color in the dashed circular area). This example demonstrates the ability to capture an impedance map on animal tissue, which can then be used to generate a map of the wound boundary. The impedance map and the wound boundary map can then be fed into an algorithm that determines the optimal voltage to be applied to the system electrodes to produce a targeted therapeutic E-field intensity around the wound boundary.

[0066] It should be understood that in some examples, additional electrodes may be placed on the wound tissue (such as on an open wound bed). In some examples, the electrodes may be placed only on the tissue surrounding the wound, or on both the wound bed tissue and the tissue surrounding the wound. In some examples, electrodes residing in the wound periphery are desirable because (i) the electrodes are less invasive as they do not need to contact the sensitive wound bed tissue, and (ii) the electrical interface with the intact tissue surrounding the wound may be more stable than that of the wound bed tissue, which changes over time (e.g., with healing).

[0067] In some examples, electrodes are provided for 4-probe measurements, with 2 electrodes for the current source and 2 electrodes for voltage measurement; the minimum number of electrodes is 4. In some examples, 8 or more electrodes are provided to obtain the mapping results. A greater number of electrodes allows for higher resolution and accuracy.

[0068] It should be understood that any suitable form of electrode device can be used to allow the electrode array to be placed on the tissue site in a predetermined pattern. In some examples, the electrode array may be placed on the periphery of a dressing, such as, for example, on the cover of a negative pressure wound therapy (NPWT) dressing. In some examples, the electrode array may be integrated into a non-dressing device. In one example, a flexible circuit substrate may be decorated with snap-fit ​​connectors to which multiple electrodes can be connected. In one example, the device may include a flexible printed circuit board (PCB) having an internal group of metal needle electrodes that can dock with a wound bed, or having multiple metal needle electrodes that connect to the tissue surrounding the wound. Similar configurations can also be implemented in a rigid PCB format. Additional suitable electrodes are those described above with respect to the first aspect. Electrodes can be placed at any location on the wound tissue, such as inside the wound bed, outside the wound bed, or both.

[0069] Refer again Figure 7C The system 7000 also includes electronic components 7220 electrically connected to the electrode array 7210. Electronic components 7220 may include various control circuits, processors, memory, power supplies, etc. For example, electronic components 7220 may include... Figure 6 One or more of the processing circuit 6116, memory 6124, processing circuit 6216 and memory 6224 shown.

[0070] Electronic component 7220 is configured to apply an electrical signal to a tissue site via electrode array 7210, collect electrical measurement results from electrode array 7210, process the collected electrical measurement results to generate one or more impedance maps of a wound bed (e.g., open wound tissue 7150 and subcutaneous wound tissue 7154), the one or more impedance maps representing non-uniform electrical characteristics measured over a region of wound tissue; and calculate at least a first voltage and a second voltage for the wound tissue based on the spatial distribution of the electrical measurement results from the one or more impedance maps of the wound tissue. As described above, the one or more impedance maps may also include a baseline map representing untraumatized tissue.

[0071] In some preferred embodiments, the circuitry is also functionally connected to an electrode array to allow voltage to be delivered through the electrode array, for example, to the wound tissue. In selected embodiments, the electrode array includes a first electrode configured to apply a first voltage to the wound tissue and a second electrode configured to apply a second voltage to the wound tissue. Having the option to use the same electrodes to collect electrical measurements and deliver voltage to the wound tissue is advantageous because the overall device is simpler compared to requiring different sets of electrodes or separate devices to create an impedance map and apply electrical stimulation to the wound tissue.

[0072] refer to Figure 8A schematic diagram depicting a flowchart of one embodiment according to the present disclosure is provided. In this case, a device (e.g., according to the third aspect) is placed on wound tissue 810, and then, based on electrical measurements collected from the device, conductivity processing 820 of the electrical measurements is performed. This processing generates a conductivity map 830 of the wound tissue, and optionally also generates a wound boundary map 832, which can be used to calculate a voltage 840. Furthermore, this embodiment may optionally include applying the calculated voltage to wound tissue 850. In some cases, advantageously, after applying the voltage to wound tissue 850, the process is repeated to collect new electrical measurements from the device located on wound tissue 810 to capture differences in electrical measurements due to changes in the conductivity of the wound tissue over time (e.g., changes due to increased epithelialization as the wound tissue heals).

[0073] refer to Figures 9A to 9C A schematic side view (top row) of tissue phantoms used for conductivity mapping experiments is provided. Each phantom represents a wound in a progressive healing process, from... Figure 9A Move to Figure 9B Move to Figure 9C The images are progressively enhanced. A top-view photograph of the tissue-simulated trauma phantom is also provided (second row). Additionally, Figures 9A to 9C The image shows an EIT plot of the relative conductivity of the trauma phantom (third row), and a superimposed image of the phantom on the EIT plot (bottom row). In these cases, relative conductivity indicates the difference between the conductivity of the wound bed and the conductivity of the epithelialized skin surrounding the wound (e.g., if the conductivity of the skin surrounding the wound is 2 × 10⁻⁶). -6 S / m, and considered as having a relative conductivity of 0; then a relative conductivity of 0.2 means that the conductivity is 20% higher than that of the skin, which is 2.4 × 10 -6 S / m; while a relative conductivity of -0.2 indicates a conductivity 20% lower than that of skin, which is 1.6 × 10⁻⁶. -6 S / m).

[0074] Implementation Plan

[0075] In a first embodiment, this disclosure provides a method. The method includes applying one or more electrical signals to wound tissue via an electrode array; and collecting electrical measurements from the electrode array via circuitry functionally connected to the electrode array. The method further includes processing the collected electrical measurements via a processor to generate one or more impedance maps of the wound tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over a region of the wound tissue; and calculating at least a first voltage and a second voltage for the wound tissue based on the spatial distribution of the electrical measurements from the one or more impedance maps of the wound tissue.

[0076] In a second embodiment, this disclosure provides a method according to a first embodiment, wherein the first voltage and the second voltage are different from each other.

[0077] In a third embodiment, this disclosure provides a method according to a first or second embodiment, further comprising applying at least the first voltage and the second voltage to the wound tissue via the electrode array.

[0078] In a fourth embodiment, this disclosure provides a method according to a third embodiment, wherein the application includes applying 0 volts (V) ground to an electrode positioned on a trauma bed.

[0079] In a fifth embodiment, this disclosure provides a method according to a fourth embodiment, wherein the electrode positioned on the trauma bed is located at the center of the trauma bed.

[0080] In a sixth embodiment, this disclosure provides a method according to any one of the second to fifth embodiments, the method further comprising repeating each of the collection, processing and calculation steps after the first voltage and the second voltage are applied to the traumatic tissue.

[0081] In a seventh embodiment, this disclosure provides a method according to a sixth embodiment, wherein the collection, processing, and calculation steps are repeated at predetermined times after the first voltage and the second voltage are applied to the traumatic tissue.

[0082] In the eighth embodiment, this disclosure provides a method according to any one of the second to seventh embodiments, wherein applying at least the first voltage and the second voltage generates an electric field having an order of magnitude from 0 volts per meter to 1,000 volts per meter (V / m).

[0083] In a ninth embodiment, this disclosure provides a method according to any one of the first to eighth embodiments, wherein the one or more impedance maps of the traumatic tissue identify at least one boundary between the trauma bed and the tissue surrounding the trauma.

[0084] In a tenth embodiment, this disclosure provides a method according to a ninth embodiment, wherein applying at least the first voltage and the second voltage generates an electric field oriented at least partially inward from the boundary toward the trauma bed.

[0085] In the eleventh embodiment, this disclosure provides a method according to any one of the first to tenth embodiments, wherein at least four voltages for the traumatic tissue are calculated based on the spatial distribution of electrical measurement results from the one or more impedance maps of the traumatic tissue.

[0086] In a twelfth embodiment, this disclosure provides a method according to any one of the first to eleventh embodiments, wherein one or more impedance maps of traumatic tissue are estimated by an algorithm and baseline measurements of untraumatized tissue are not required, wherein one or more impedance maps of traumatic tissue are estimated by an algorithm using frequency difference electrical impedance tomography (fdEIT), measurement scale feature (MSF), best homogeneity (BH) estimator, data-driven estimator, or a combination thereof.

[0087] In a thirteenth embodiment, this disclosure provides a system. The system includes an electrode array configured to apply one or more electrical signals to wound tissue; circuitry functionally connected to the electrode array to collect electrical measurement results from the electrode array; and a processor. The processor is configured to: process the collected electrical measurement results to generate one or more impedance maps of the wound tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over a region of the wound tissue; and calculate at least a first voltage and a second voltage for the wound tissue based on the spatial distribution of the electrical measurement results from the one or more impedance maps of the wound tissue.

[0088] In the fourteenth embodiment, this disclosure provides a system according to the thirteenth embodiment, wherein the electrode array includes a first electrode configured to apply the first voltage to the wound tissue and a second electrode configured to apply the second voltage to the wound tissue.

[0089] In a fifteenth embodiment, this disclosure provides an apparatus for application to wounded tissue. The apparatus includes an electrode array comprising at least two electrodes configured to be disposed on the wounded tissue and configured to apply one or more electrical signals to the wounded tissue; and a circuit functionally connected to the electrode array to collect electrical measurement results from the electrode array and transmit the collected electrical measurement results for processing.

[0090] In a sixteenth embodiment, this disclosure provides an apparatus according to a fifteenth embodiment, wherein the circuit is also functionally connected to the electrode array to allow voltage to pass through the electrode array.

[0091] Although the invention has been described with reference to preferred embodiments, those skilled in the art will recognize that changes in form and detail may be made without departing from the spirit and scope of the invention.

Claims

1. A method, the method comprising: One or more electrical signals are applied to the wounded tissue via an electrode array; Electrical measurements from the electrode array are collected via circuitry functionally connected to the electrode array. The collected electrical measurement results are processed by a processor to generate one or more impedance maps of the traumatic tissue, the one or more impedance maps representing non-uniform electrical characteristics measured over a region of the traumatic tissue; as well as At least a first voltage and a second voltage are calculated for the traumatic tissue based on the spatial distribution of electrical measurement results from one or more impedance maps of the traumatic tissue.

2. The method of claim 1, wherein the first voltage and the second voltage are different from each other.

3. The method according to claim 1 or claim 2, further comprising applying at least the first voltage and the second voltage to the wound tissue via the electrode array.

4. The method of claim 3, wherein the application comprises applying 0 volts (V) ground to an electrode positioned on a trauma bed.

5. The method of claim 4, wherein the electrode positioned on the trauma bed is located at the center of the trauma bed.

6. The method according to any one of claims 2 to 5, further comprising repeating each of the collection, processing, and calculation steps after applying the first voltage and the second voltage to the traumatic tissue.

7. The method of claim 6, wherein the collection, processing, and calculation steps are repeated at a predetermined time after the first voltage and the second voltage are applied to the traumatic tissue.

8. The method according to any one of claims 2 to 7, wherein applying at least the first voltage and the second voltage generates an electric field having an order of magnitude from 0 volts per meter to 1,000 volts per meter (V / m).

9. The method according to any one of claims 1 to 8, wherein the one or more impedance maps of the traumatic tissue identify at least one boundary between the trauma bed and the tissue surrounding the trauma.

10. The method of claim 9, wherein applying at least the first voltage and the second voltage generates an electric field oriented at least partially inward from the boundary toward the trauma bed.

11. The method according to any one of claims 1 to 10, wherein at least four voltages for the traumatic tissue are calculated based on the spatial distribution of the electrical measurement results of the one or more impedance maps of the traumatic tissue.

12. The method of any one of claims 1 to 11, wherein the one or more impedance maps of the traumatic tissue are estimated by an algorithm and do not require baseline measurements of the untraumatized tissue, wherein the one or more impedance maps of the traumatic tissue are estimated by an algorithm using frequency difference electrical impedance tomography (fdEIT), measurement scale feature (MSF), best homogeneity (BH) estimator, data-driven estimator, or a combination thereof.

13. A system comprising: An electrode array configured to apply one or more electrical signals to wound tissue; A circuit, functionally connected to the electrode array, for collecting electrical measurement results from the electrode array; and Processor, the processor being configured to: The collected electrical measurement results are processed to generate one or more impedance maps of the traumatic tissue, the one or more impedance maps representing non-uniform electrical properties measured over the region of the traumatic tissue; as well as At least a first voltage and a second voltage are calculated for the traumatic tissue based on the spatial distribution of electrical measurement results from one or more impedance maps of the traumatic tissue.

14. The system of claim 13, wherein the electrode array includes a first electrode configured to apply the first voltage to the wound tissue and a second electrode configured to apply the second voltage to the wound tissue.

15. A device for application to wounded tissue, the device comprising: An electrode array comprising at least two electrodes configured to be disposed on the wound tissue and configured to apply one or more electrical signals to the wound tissue; and A circuit, functionally connected to the electrode array, for collecting electrical measurement results from the electrode array and transmitting the collected electrical measurement results for processing.

16. The apparatus of claim 15, wherein the circuitry is further functionally connected to the electrode array to allow voltage to pass through the electrode array.

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