Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
  • A61B5/053—Measuring electrical impedance or conductance of a portion of the body
  • A61B5/0536—Impedance imaging, e.g. by tomography
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
  • A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
  • A61B6/502—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for diagnosis of breast, i.e. mammography
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
  • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
  • A61B8/0825—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of the breast, e.g. mammography

Definitions

• This invention relates to a method for detecting and diagnosing disease states in living organisms and specifically relates to diagnosis of disease by measuring electrical properties of body parts.
• x-ray techniques measure tissue physical density
• ultrasound measures acoustic density
• thermal sensing techniques measures differences in tissue heat generation and conduction.
• Other properties are electrical, such as the impedance of a body part that is related to the resistance that the body part offers to the flow of electrical current through it.
• One subset of the data so obtained is processed and analyzed by structuring the data values as elements of an n xn impedance matrix.
• the matrices can be further characterized by their eigenvalues and eigenvectors. These matrices and/or their eigenvalues and eigenvectors can be subjected to a pattern recognition process to match for known normal or disease matrix or eigenvalue and eigenvectors patterns.
• the matrices and/or their eigenvalues and eigenvectors derived from each homologous body region can also be compared, respectively, to each other using various analytical methods and then subjected to criteria established for differentiating normal from diseased states.
• a breast electrode array for diagnosing the presence of a disease state in a living organism, wherein the electrode array comprises a flexible body, a plurality of flexible arms extending from the body, and a plurality of electrodes provided by the plurality of flexible arms, wherein the electrodes are arranged on the arms to obtain impedance measurements between respective electrodes.
• the plurality of flexible arms are spaced around the flexible body and are provided with an electrode pair.
• the electrodes are selected so that the impedance data obtained will include elements of an n xn impedance matrix, plus other impedance values that are typically obtained with tetrapolar impedance measurements.
• Tetrapolar impedance measurements are associated with injecting current between so called current electrodes and measuring a voltage drop between associated electrodes.
• the differences between corresponding homologous impedance measurements in the two body parts are compared in a variety of ways that allow the calculation of metrics that can serve to either indicate the presence of disease or localize the disease to a specific breast quadrant or sector.
• the impedance differences are also displayed graphically, for example in a frontal plane representation of the breast by partitioning the impedance differences into pixel elements throughout the plane.
• the present invention is directed to an improved method for detecting and diagnosing disease states in a living organism by using a set of electrical impedance measurements.
• the method is based on the realistic distribution of electric current in the body part.
• the approximate current distribution is obtained by a numerical computation using a representation of a body part structure, or by the direct measurement performed on a physical model or a control subject's body part. This obtained current distribution is further used to correlate impedances obtained by direct measurements to different areas in the body part.
• the subject body part is subdivided into a number of small regions called finite elements.
• a weight factor obtained by computing or measuring the current density in the element, reflecting the position of the element within the body part, is calculated and stored.
• Each element has one weight factor for each current injection. Larger weight factors are associated with current injections that result in larger current densities in a particular element. Thus, current injecting scenarios associated with larger weights at a particular element are given greater consideration when detecting disease.
• the weights are typically calculated or measured with the assumption that there is no disease present. At the same time, baseline impedances associated with each of the current injections are obtained.
• the weights and baseline impedances for each of the current injection scenarios are stored in the database and used when a diagnosis is made following the measurement of the actual impedances of the subject's body part.
• the diagnostic is the sum over all current injections of weight multiplied by the ratio of baseline to measured impedance. This sum is referred to as a Weighted Element Value (WEVal).
• WEVal Weighted Element Value
• Elements are grouped according to known physical characteristics and a sum for each of the groups is obtained. Comparing sums of homologous regions may point to a presence of disease in the body part.
• the system includes an electrode array by which an electrical property of the body part may be measured, such as a measured impedance.
• the system further includes a grid module for representing the body part with a grid having a plurality of finite elements, and for obtaining a baseline electrical property using a model of the body part, such as a baseline impedance.
• the system also includes a weight module for using the model of the body part to compute a set of weights associated with a particular one of the plurality of finite elements, each weight in the set derived from a particular current injection electrode pair selection.
• a diagnostic module computes a diagnostic at the particular finite element to diagnose the possibility of disease in the body part, the diagnostic being a function of the measured electrical property, the baseline electrical property and the set of weights.
• Figure 1 A shows the components of a basic tetrapolar measurement
• Figure 1B is a block diagram of a system for detecting and diagnosing disease in a body part
• Figure 1C is a block data flow diagram of a method for detecting and diagnosing disease in a body part
• Figure 2 is a sample finite element grid produced by the grid module of Figure 1 B, the grid representing a body part that can be used to calculate baseline electrical properties;
• Figure 3 is a block data flow diagram of the grid module of Figure 1 B, in one embodiment of the present invention that employs a numerical finite element method;
• Figure 4 is a block data flow diagram of the diagnostic module of Figure 1B, in one embodiment of the present invention.
• Figure 5 is a flowchart illustrating the method steps performed by the diagnostic system of Figure 1 B to diagnose disease.
• Figures 6A and 6B are sample WEVal plots for an actual subject that can be used to detect breast cancer.
• Figure 1A shows a schematic of components used to perform a tetrapolar impedance measurement, which measurements are used for detecting and diagnosing disease, as described in more detail below.
• Figures 1 B and 1C show a block diagram of a system 10 and an outline of a method for detecting and diagnosing disease in a body part, such as breast cancer. The method uses impedance measurements taken from a multi-channel impedance measuring instrument 11 with a pair of electrode arrays 12, like the one described in PCT/CA01/01788, a grid module 14 and a diagnostic module 16.
• a single electrical impedance measurement is performed using four electrodes.
• One pair of electrodes 1 is used for the application of current /, and the other pair of electrodes 2 is used to measure the voltage V that is produced across a material, such as breast tissue 3, by the current.
• the current / flowing between electrodes 1 is indicated by the arrows 4.
• Impedance consists of two components, resistance and capacitive reactance (or equivalently, the magnitude of impedance and its phase angle). Both components are measured and analyzed in the present invention. However, in examples described below, only resistance is used and interchangeably referred to as either resistance or the more general term impedance.
• bipolar instead of a tetrapolar, measurements can be performed as part of the general method for diagnosing disease discussed below. If bipolar measurements are performed, a correction factor can be used that corrects for the polarization effects arising from skin-to-electrode interface.
• Figure 1 B shows a schematic of the electrode array 12.
• Eight current injection electrodes 13, and eight associated voltage measurement electrodes 15 are shown.
• the electrodes are applied on the body part, each of the current injection electrodes being associated with the adjacent voltage measurement electrode. Impedance is measured between two voltage electrodes when the current is injected between associated current electrodes. Since there are nci - tv(/7 e -1)/2 P a ' rs of current injection electrodes, and an equal number of voltage measurement electrode pairs, the total number of independent current injections and related impedances is nci. It should be understood that the electrode array shown is but one possible electrode array. Other electrode arrays may also be used.
• the grid module 14 uses a numerical or physical model of a baseline (idealized or reference) body part to compute baseline values.
• baseline impedances and associated gradients for the baseline body part are calculated in the grid module 14.
• the associated gradients can be used to calculate current densities at each finite element.
• the baseline impedances for each of the nci current injections, and the associated current densities for each of the finite elements and for each of the nci current injections are stored in a baseline body parts database 17.
• the impedance is measured nci times resulting in the set of values, ⁇ Z , Z , ... , Z n a ), where ⁇ js the impedance measured between the voltage electrodes associated with the /* current injection electrode pair when current is injected between that current injection electrode pair, as required in tetrapolar impedance measurement.
• the grid module 14 includes software and/or hardware for representing the body part with a grid of elements that are so small that the voltage gradient during arbitrary current injection is approximately constant within any single element.
• the grid can be composed of triangles that "tile" the surface.
• the body part can be modeled by a three-dimensional grid whose elements are tetrahedrons, for example.
• Each finite element is associated with a plurality of nodes, typically on the perimeter of the finite element.
• each finite element is characterized by its electrical material property, namely resistivity and/or permittivity. Adjacent elements share the nodes associated with the common side or face.
• the grid module 14 also includes software and/or hardware for deriving the current density for each of the elements in the grid. It does this by calculating the current density using a numerical or physical model, or by using population study information, as discussed in more detail below.
• the diagnostic module 16 includes software and/or hardware for detecting the presence of a tumor in the body part at step (70). As described in more detail below, the diagnosis is based on a diagnostic that is a function of the impedance measurements obtained from a subject using the impedance measuring instrument 11 , and a weighting factor derived from the estimated value of the current density throughout the body part, obtained using grid module 14.
• Figure 2 shows a representation of the baseline body part divided into a grid 80 composed of a plurality of finite elements 82. Once the body part is subdivided using grid module 14 into a number of finite elements 82, there are several methods that can be used to calculate baseline values, such as the current density associated with a particular current injection and with a particular finite element 82 of the grid 80. Figure 2 shows one embodiment of the present invention in which several thousand finite elements 82 are used, as required to justify linearizing the equations used to numerically compute the relevant electrical properties.
• the preferred method used by the grid module 14 to associate a voltage gradient with a particular finite element 82 is a numerical finite element method that assumes that the resistivity of the body part is uniform.
• the method numerically solves Laplace's equation, known to those of ordinary skill, to compute the electric potential at the nodes of the finite element grid from which the electric voltage gradient can be obtained. Due to uniform resistivity, current density is proportional to the voltage gradient everywhere in the body part.
• a second method that can be used by the grid module 14 is related to the last method, except that instead of assuming a uniform resistivity, more realistic resistivities and/or permittivities can be used that reflect the known internal structure of the body part.
• the current density is proportional to the electric voltage gradient in each of the elements, but the voltage gradient to current density ratio depends on the resistivity and/or reactivity associated with the particular finite element 82.
• the third method involves using a physical model of a typical breast.
• This typical breast acts as a baseline representation of the body part.
• the model is designed so that the measured impedance matrix is close to the average impedance matrix for the normal subject with the body part of the particular size.
• Each finite element 82 obtained using the grid module 14 is associated with the particular location (x, y and z coordinates) in the physical model.
• the current density at each of the finite elements 82 and for each of the current injections is obtained using one of the available instruments for measuring the current density.
• the current density instrument for example, can be combined with magnetic resonance imaging (MRI) to measure and display the current density superimposed on the MRI image at any location of the body part model.
• MRI magnetic resonance imaging
• the fourth method is similar to the third method except that the measurement of the current density for each current injection and at the location of each of the finite elements 82 defined by the grid module 14 is performed on the body part of an actual control subject.
• the same combination of instruments as above can be used to measure and display the current density superimposed on the MRI image at any location in the actual body part.
• Figure 3 shows a block data flow diagram of the grid module 14 in the preferred embodiment of the invention where it includes a finite element analysis module 28 and a gradient module 30.
• the grid module 14 uses the finite element method to compute the baseline impedance. More generally, the baseline impedance refers to the impedance calculated by the grid module 14 (denoted by Z., for the/ 1 electrode pair) using an appropriate physical or numerical model, as distinguished from the measured impedance, Z , obtained by a measurement on a subject using an electrode array.
• the finite element analysis module 28 includes hardware and/or software that employs various boundary conditions, corresponding to the injections of current between the various pairs of current injection electrodes 13 ( Figure 1 B), to compute the electric potential at all the nodes in the grid.
• the node voltage v. is the voltage that arises at the nodey when a current injection i is applied, where the z th current injection refers to the injection of current between the z 'th current injection electrode pair.
• the finite element analysis module 28 includes a finite element grid generator 29, a boundary conditions generator 31 and a finite element equation solver 33.
• the finite element grid generator 29 generates a grid 80 of finite elements 82 that spans a representation of the body part. Position on the representation of the body part can be discretized if each finite element is associated with several nodes, typically on the perimeter of the finite element.
• the boundary conditions generator 31 assigns boundary conditions corresponding to the various n CI current injections.
• the finite element equation solver 33 employs the numerical finite element method for solving Laplace's equation. Many different types of such methods can be used, such as a Lax differencing scheme for solving partial differential equations. Several other techniques known to those of ordinary skill in the art can be utilized.
• the grid module 14 In addition to finding the electric potential as a function of node position, the grid module 14 also finds voltage differences between voltage measurement electrodes 15. In particular, using boundary conditions corresponding to the current injected by the first pair of current injection electrodes yields V v the voltage drops between the first pair of voltage measurement electrodes. Using boundary conditions corresponding to the current injected by the second pair of current injection electrodes yields V 2 , the voltage drop between the second pair of voltage measurement electrodes. Continuing in this manner yields all n a voltages ⁇ V v V 2 , ... , V render a ⁇ . Each time
• the finite element method yields the potential at every node of the grid as well.
• the node voltage v. t is the voltage that arises at the node/ when a current injection i is applied.
• the gradient module 30 utilizes the calculated node voltages to find an estimated current density at the element k for the current injection /, J ik .
• the grid module 14 similarly obtains all nci impedances ⁇ Z , Z 2 j ... , z n ⁇ and all the current densities ⁇ J ⁇ k . J i k ' ⁇ ' J nak > at tne f' nite element k. In particular, to obtain J jk , where
• J lk is the magnitude of the current density in the / th finite element for the current injection i
• the gradient module 30 uses the electric potential at each node associated with finite element k. To this end, the magnitude of the gradient of the electric potential, which is equal to the magnitude of the electric field, is first obtained by a voltage gradient calculator 37.
• E
• the finite element analysis module 28 can either assume the body part to have a uniform resistance and/or reactance, or the resistance and/or reactance can be taken to be non- uniform to reflect the known structure of the body part.
• Figure 4 shows a block data flow diagram of the diagnostic module 16 of Fig. 1 B, in one embodiment of the present invention.
• the diagnostic module 16 includes a weight module 22, an averaging module 24 and a comparator 26.
• the diagnostic module 16 computes a Weighted Element Value (WEVal) parameter (diagnostic) at each of the finite elements 82 of the grid 80 representing the body part, and utilizes the diagnostic to diagnose the possibility of disease in the body part.
• WEVal Weighted Element Value
• the diagnostic is a function of the impedances and current densities calculated and/or measured for the baseline body part and impedances measured on the body part of the subject.
• the weight module 22 includes software and/or hardware for calculating weights for the element k and the current injection i, w jk , given by
• the quantity J lk is the magnitude of the current density, which exists at the finite element k when the reference current is applied between the first pair of current injection electrodes.
• the quantity J 2k is the magnitude of the current density, which exists at the finite element k when the reference current is applied between the second pair of current injection electrodes, and so on.
• Th e averaging module 24 includes software and/or hardware for calculating a weighted average of a function f(Z t ,Z* ) .
• the diagnostic at the finite element k is defined to be
• the diagnostic (f k ) is referred to as the Weighted Element Value (WEVal).
• the quantity Z is the impedance between the first pair of electrodes for the baseline body part.
• the quantity Z 2 is the impedance between the second pair of electrodes for the baseline body part, and so on.
• the Z can be obtained using a numerical calculation or using a physical model (an artificial reproduction or the real body part of a control subject).
• the z, M are obtained by direct measurement on the body part of a subject using an electrode array.
• the function f(Z l ,Z i ) is
• the diagnostic module 16 can condition the raw measurements Z, such as by standardizing with a factor, etc, to find the diagnostic.
• the function can be given by
• ⁇ used to condition the raw data, which conditioned data may be used to compute the diagnostic.
• some body parts have homology in the body. For example, in females, the right breast has a homolog, namely the left breast.
• (f k ) is averaged over all the finite
• (f ⁇ ght ) can refer to an average over finite elements belonging to a particular region within the right breast.
• ⁇ A (k) is the characteristic function for a region A of the body part:
• V k and V ⁇ are the volumes (if the grid is three dimensional) or the areas (if the grid is two-dimensional) of finite element k and region A, respectively.
• the measured impedances in the body part are expected to be somewhat different from the values measured in the homologous body part. However, these differences are expected to be more pronounced if only one of these body parts contains a malignant tumor.
• the comparator 26 includes hardware and/or software for comparing ⁇ ton) to (/ ⁇ ght ) to diagnose the possibility of disease. For example, if breast cancer is being diagnosed and if it is assumed that at least one breast is non- cancerous, then a difference between (/ left ) and (/ light ) may be due to a change in the electrical properties of one breast brought about by the presence of a cancer.
• the comparator 26 calculates the absolute difference (f )- (/ eft )
• the principles of the present invention can be applied to diagnose disease in a body part without comparison to a homolog.
• the diagnostic WEVal can be compared to a population average, to the baseline value, or to some other standard to diagnose disease.
• Figure 5 shows a flowchart that illustrates the main steps 50 utilized by system 10 to diagnose the possibility of disease in a body part.
• the first part of the procedure is preparatory and establishes standard or idealized baselines for a typical body part and results are stored in the database to be used as a reference for numerous subjects.
• the baseline body part is represented with a grid of finite elements. The grid can be two- dimensional, or three-dimensional.
• a current injections are simulated to yield a database (54) of impedances and associated voltage gradients. These steps may be repeated to collect several typical sets of data depending on the size, body fat, or some other characteristic of the subject or the body part. This concludes the preparatory part.
• a plurality of electrodes is applied to the body part, such as a breast and, at step (57), the plurality of electrodes measure impedance of the body part between electrode pairs.
• a diagnostic is computed at each of the finite elements, the diagnostic being a function of the measured impedance and the values of impedance and gradients from the database. Subsequently, at step (60), the diagnostic is utilized to diagnose the possibility of disease in the body part.
• FIGS 6A and 6B sample results in the form of two gray scale plots are shown illustrating the value of the system and method of the present invention in diagnosing breast cancer.
• the right breast 72 and the left breast 74 are represented in the frontal plane as two circular plots, with darkness of gray increasing as the homologous difference of the diagnostic becomes more profound.
• This patient had an invasive ductal adenocarcinoma in the mid outer right breast.
• each breast was represented by a circle with a 2D grid of finite elements.
• the finite elements comprising the grid are not shown.

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• 2004
  • 2004-03-25 AU AU2004224834A patent/AU2004224834A1/en not_active Abandoned
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