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WO2010023540A1 - Dispositif médical - Google Patents

Dispositif médical Download PDF

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Publication number
WO2010023540A1
WO2010023540A1 PCT/IB2009/006660 IB2009006660W WO2010023540A1 WO 2010023540 A1 WO2010023540 A1 WO 2010023540A1 IB 2009006660 W IB2009006660 W IB 2009006660W WO 2010023540 A1 WO2010023540 A1 WO 2010023540A1
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WO
WIPO (PCT)
Prior art keywords
interstitial fluid
electrodes
interstitial
treatment
conductivity
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2009/006660
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English (en)
Inventor
Albert Maarek
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LD TECHNOLOGY LLC
Original Assignee
LD TECHNOLOGY LLC
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Filing date
Publication date
Application filed by LD TECHNOLOGY LLC filed Critical LD TECHNOLOGY LLC
Priority to EP09809396A priority Critical patent/EP2361038A4/fr
Publication of WO2010023540A1 publication Critical patent/WO2010023540A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61B5/0537—Measuring body composition by impedance, e.g. tissue hydration or fat content
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4869—Determining body composition

Definitions

  • the present invention provides a medical device to analyze the composition of interstitial fluid in a human body and to provide a modelling of the human body. More specifically the device measures bio-impedance in interstitial fluid and enables a modelling of the human body and some parameters of the interstitial fluid to be deduced.
  • Bioelectric impedance measurements are used in a wide range of old and new noninvasive technologies and methods where a very small electric current is applied to the body via one or more surface electrodes and the resultant electricity pulse passing through the body is detected at other surface electrodes placed elsewhere on the body.
  • a drop in voltage occurs as the current encounters impedance or resistance inherent in the fluids and tissues it passes through as it courses through the various physiological "compartments" of the body. These compartments include the bloodstream, the intracellular space, the lymphatic system, the interstitial space, and others. This drop in voltage provides indirect information about the physical and chemical properties of the compartments that the current passes through.
  • A.C. alternating current
  • BIOS Bioelectrical Impedance Analysis
  • Most systems are used to indirectly estimate the fat content of the body by measuring total body water.
  • These systems typically employ A.C. electricity with a wide range of currents, frequencies, and intensities.
  • the amount of electricity delivered to the body is usually imperceptible and far below the level that would cause cellular or tissue damage.
  • Studies of A.C. BIA systems operating at 50 KHz or higher, have revealed that these frequency A.C. electric currents flow non-selectively through both intracellular and extra cellular spaces, and thus provide relatively non-specific information regarding the physical properties and chemical composition of specific body compartments.
  • the electric current produced by D.C. bioelectric impedance methods specifically passes through the interstitial fluid compartment.
  • the interstitial fluid compartment represents approximately 16% of the body's total water.
  • Interstitial fluid is extra cellular water and solutes surrounding cells, but outside of the bloodstream and lymphatic system. Interstitial fluid forms the microscopic interface between cells and capillaries.
  • interstitial fluid which constitutes the environment of the cells and is regulated by the cells activity and ionic distribution, has previously been measured by the suction blister or liquid paraffin techniques or by implantation of a perforated capsule or wick. The results have varied, depending on the sampling technique and animal species investigated.
  • Interstitial fluid differs from whole blood by the absence of red blood cells, and it differs from blood plasma in that there are far fewer proteins.
  • Any substance passing between cells and the bloodstream must traverse the interstitial space. These substances include oxygen, carbon dioxide, glucose, as well as thousands of other compounds.
  • interstitial fluid The interstitial fluid's role as a metabolic conduit and its proximity to the collective intracellular space of nearby cells suggests that the chemical composition of the interstitial fluid may reflect the physiology and pathophysiology of the nearby cells.
  • the volume of the interstitial fluid is closely related to the containing sodium pool.
  • the exchanges between the vascular sector and the interstitial fluid are complex.
  • the distribution of the electrolytes on each side of the membrane is regulated by "the Donnan equilibrium.”
  • Figure 1 shows a schematic process of the cell activity and ionic equilibrium in healthy subject When the sodium concentration decreases in the interstitial fluid, the sodium moves inside the cell and affects the tissue(s) as follows:
  • Figure 2 shows a schematic process of cell activity and under the opposite circumstances in a healthy subject
  • a method to analyze interstitial fluid comprising the steps of measuring bio impedance between at least two electrodes positioned on an individual's body and calculating the volume of interstitial fluid for that individual and deducing the concentration of certain metabolites in the interstitial fluid.
  • the invention provides a non-invasive method to analyze interstitial fluid in a body, the method comprising the steps of measuring bio impedance between at least two electrodes positioned on an individual's body and calculating the volume of interstitial fluid for that individual and deducing levels of conductivity within the interstitial fluid throughout the body and/or deducing the concentration of certain metabolites in the interstitial fluid.
  • a black box sends via cables and electrodes a continuous tension of 1.28V to at least 6 zones of the skin and returns in numerical form by the intermediary of a USB port to a computer the intensity of the traversed zones between pairs of electrodes to a data-processing software.
  • the mothod provides a modeling of the body based on conductivity readings in interstitial fluid.
  • the method may further comprise the step of comparing the levels of conductivity measured with algorithnms from data bases and extrapolating the results based these algorithms and the individual's age, height, weight and sex.
  • the invention also provides pparatus to carry out the method, the apparatus comprising electrodes to be placed symmetrically on the right and on the left on the level of the face, the hands and the feet, a black box, cables connecting the electrodes to the black box and a USB cable connecting the black box to a computer wherein the computer comprises software to enable a scan to be driven and results to be stored and analysed.
  • the apparatus may further comprise other monitoring equipment and software to cross analyse the results.
  • the invention also provides the use of a method or apparatus as described herein to monitor a treatment.
  • the treatment being monitored may be chosen from the group consisting of thyroid treatment, hypo tensor treatment with converting enzyme inhibitor or beta blockers, antidepressant treatment with SSRI, and anticoagulant treatment for atherosclerosis.
  • the method described may also be used in the adjuct diagnosis of ADHD children
  • the apparatus can be used to evaluate the conductivity of 22 parts of the human body in bipolar mode between six tactile electrodes using a direct current and a range of frequencies to provide information relating to Interstitial Na+/K+ ATPase pump activity, estimation of tissue pCO2 related with hypoxia, microcirculation blood flow, sympathetic system activity, modeling of the human body and/or estimation of body composition parameters including total body water, fat free mass and fat mass. By comparing the concentration of measured metabolites to certain standards further deductions can be made.
  • EIS Electro Interstitial Scan
  • E.I.S Electro Interstitial Scan
  • the device according to the invention named "Electro Interstitial Scan” (“E.I.S”) comprises a black box which sends via cables and electrodes a continuous tension of 1.28V to 6 zones of the skin; the black box returns in numerical form by the intermediary of a USB port to the computer the intensity of the traversed zones between 2 electrodes to an expert data- processing software.
  • electrodes are placed symmetrically on the right and on the left on the level of the face, the hands and the feet.
  • the apparatus allows measurements to be taken which can be used to provide calculations of certain constants within the interstitial fluid and which also allow modeling of the human body.
  • the modelling is based on the Maxwell equation which has previously been used with imaging. This is applied together with the Venn Diagram calculation and the bioimpedance measurements to localize body systems.
  • the constants in the interstitial fluid are calculated by applying the Cottrell equation and Ohm's Law to the bioimpedance measurements.
  • Figure 1 shows a schematic process of the cell activity and ionic equilibrium in healthy subject
  • Figure 2 shows a schematic process of cell activity and under the opposite circumstances in a healthy subject
  • Figure 3 shows this arrangement of electrodes and the series of reading that are taken to analyze the interstitial fluid through out the body.
  • Figure 4 a histogram of the number of values N of each body part, the software removes the extreme values for keep the more frequent mean values for R.
  • Figure 5 is called the ESG for absolute values
  • Example of ESG (scale 100/-100) is shown as Figure 6.
  • the boundary value problem to be solved is a time harmonic quasi-static electric field in the steady state taking into account both, the specific electric conductivity ⁇ and the electric permittivity ⁇ is represented in Figure 7
  • FIG. 9 Volumes 2+14+15+17 of the ESG Graph are shown in Figure 10
  • Blood pressure readings (diastolic) are shown in Figure 11
  • Volumes 6+8+19+21 of the ESG Graph are shown as Figure 12
  • Blood pressure readings (diastolic) are shown as Figure 13 Volumes 6+13+19 of the ESG Graph are shown in Figure 14
  • Prothrombin Time is shown as Figure 15 Volumes 6+13+19 of the ESG Graph are shown as Figure 16
  • the 22 parts of the ESG graph are shown as Figure 18 for a group of children diagnosed as ADHD according to existing conventional methods
  • Volumes 9 and 10 of the ESG graph are shown in Figure 19
  • Categorized histograms by group: Volume 10 is shown in Figure 21
  • the EIS System is a programmable electro medical system (PEMS) including:
  • USB plug and play hardware device including black box, 6 tactile electrodes and cables and software installed on a computer.
  • the six electrodes are placed on the skin as described above.
  • a direct current (tension 1.28V) is sent alternatively and records the resistance of 22 parts of the human body in bipolar mode.
  • Figure 3 shows this arrangement of electrodes and the series of reading that are taken to analyze the interstitial fluid through out the body.
  • the measurement is runs a number of times in N parameters.
  • N is a normalized reading taking into account the sex and age of the subject.
  • the coefficient has been determined following studies on more than 20000 subjects of a ranges of ages and both sexes.
  • Item for the measurement N is determined by the formula of the TWB and an empirically-derived coefficient related to the age, height, weight, and the gender of the subject.
  • the hardware by the microprocessor and the set of resistances transmits the Intensity of each body parts measured to the software via the USB port.
  • the software removes the extreme values to keep the more frequent mean values for R.
  • the minimum 0 conductivity 0 S.m
  • the maximum 100 conductivity 140 10-6 S.m-i
  • Item for the measurement A is determined by the arithmetic average of measurements of absolute values.
  • Modeling of the body and localisation of the body system is carried out on the EIS measurements of bioimpedance using Maxwell's equation and the Venn Diagram Calculation. Maxwell has been applied for imaging before using many electrodes but the present invention is the first application of this equation for modelling using a very small number of electrodes (6 in the case of the EIS taking 22 measurements).
  • the boundary value problem to be solved is a time harmonic quasi-static electric field in the steady state taking into account both, the specific electric conductivity ⁇ and the electric permittivity ⁇ represented in Figure 7. Only linear material properties are considered. Therefore, the complex formalism can be advantageously exploited.
  • Vx E O (1 )
  • V V D 1 (9)
  • the boundary value problem (6), (9) and (10) will be solved by the finite element Galerkin technique using nodal tetrahedral finite elements of second order [4]. To this end the electric scalar potential V will be approximated by a linear combination of nodal shape functions as ⁇
  • nn means the number of nodes in the finite element mesh.
  • the EIS modeling choose a set Rn of necklace representatives, one from each necklace, so that the supposed of ⁇ (x) induced by Rn has symmetric chain decomposition.
  • the chronoamperometry and the Cottrell equation is used in laboratory tests devices for the measurement of weak concentration of biochemical values.
  • the working electrode potential is suddenly stepped from an initial potential to a final potential, and the step usually crosses the formal potential of the analyte.
  • the solution is not stirred.
  • the initial potential is chosen so that no current flows (i.e., the electrode is held at a potential that neither oxidizes nor reduces the predominant form of the analyte).
  • the potential is stepped to a potential that either oxidizes or reduces the analyte, and a current begins to flow at the electrode. This current is quite large at first, but it rapidly decays as the analyte near the electrode is consumed, and a transient signal is observed.
  • the current decay may appear to be exponential (in the case of adsorbed redox species), it actually decays as the reciprocal of the square root of time. This dependence on the square root of time reflects the fact that physical diffusion is responsible for transport of the analyte to the electrode surface.
  • R is different according to the interstitial fluid resistance and the measured part body:
  • R is calculated by average of the physical readings 5 and 7 of the ESG providing by the EIS device
  • R is calculated by average of the physical readings 5 and 7 of the ESG providing by the EIS device
  • R is calculated by average of the physical readings 13 and 14 of the ESG providing by the EIS device
  • the interstitial oxygen delivery is based on the calculation of the volume of the interstitial fluid.
  • Ht represents the height of the subject
  • R is the calculated resistance at the level of the volume 7 of the ESG providing by the
  • Ht represents the height of the subject
  • R is the calculated resistance at the level of the volume 7 of the ESG providing by the
  • Sex 0 for men, 1 for women
  • the volume of the interstitial fluid measured is compared with an average equal to 16% total weight.
  • the level is related to the resistance calculated by average of the physical readings 11 and 12 of the ESG providing by the EIS device
  • the oxygen delivery level is proportional to the volume of the interstitial fluid
  • Calculations of the biochemical values (Na+, K+, H+ ) are obtained by application of the formula of Cottrell (as above) and calculated according to the estimated volume of the interstitial fluid
  • the TSH level is proportional to the resistance of the reading 11 and 12 of the ESG Graph .
  • the EIS System is a programmable electro medical system (PEMS) including USB plug and play hardware device including black box, 6 tactile electrodes and cables.
  • PEMS programmable electro medical system
  • These six electrodes are placed on the skin, 2 on the forehead, 2 in contact with the palms of the hands and 2 in contact with the soles of the feet.
  • the electrodes of the hands and the feet comprise stainless steel, preferably of rank ASI 340.
  • the electrodes of the face are gelled on the whole of their surface.
  • the EIS software is installed on a computer. Through the 6 tactile electrodes, a direct current 1.28 V (ZO) is sent alternatively and records 22 parts of the human body in bipolar mode. These measured parts represent the interstitial fluid resistance.
  • ZO direct current 1.28 V
  • the measuring accuracy of conductivity depends on: Sending imposed voltage and resistances included in the electronic card
  • the precision of the sending imposed voltage is 1.28V +/- 0.04 thus possible errors +/- 3.1%.
  • the precision of resistances is +/- 5 Ohms for the resistances spread out between 11 KOhms and 390 KOhms thus maximum possible error +/- 0.4%.
  • the precision is thus of the order: of +/- 3.5 % to the maximum Accuracy of the estimated volume of the interstitial fluid volume 5-19 yr SEE 1.69 liters 20-80 yr SEE 1.69 liters
  • the E.I .S system uses the Bioelectrical Impedance technique in DC current in bipolar mode for monitoring some treatments of diseases , screening the ADHD children and estimates some physiological and biochemical values in interstitial fluid.
  • the hardware will have as a function to record of:
  • the software will have a function to:
  • This device should not be used in association with or presence of cardiac pacemakers, patients connected to electronic life support devices, or any implanted electronic device.
  • This device should not be used on pregnant women.
  • the effects on the fetus, as well as accuracy of readings are unknown.
  • Presence of MRI or MR or CT scan Presence of MRI or MR or CT scan.
  • the impedance and clinical data will be transferred from their respective Microsoft Excel databases into the STATISTICA program database.
  • the first step will be to run the STATISTICA version of the Shapiro- WiIk W test to examine whether the impedance data has a normal (Gaussian) distribution. Skewed (non-Gaussian) data will be analyzed with nonparametric methods and data with a normal

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention porte sur un procédé non invasif d'analyse d'un fluide interstitiel. Le procédé consiste à mesurer une bio-impédance entre au moins deux électrodes posées sur le corps du patient ; à calculer le volume de fluide interstitiel pour ce patient et en déduire des taux de conductivité dans tout le corps et/ou en déduire la concentration de certains métabolites dans le fluide interstitiel. On peut utiliser le procédé pour surveiller des traitements. Dans un mode de réalisation, l'invention évalue la conductivité de 22 parties du corps humain en mode bipolaire entre six électrodes tactiles à l'aide d'un courant continu et d'une plage de fréquences.
PCT/IB2009/006660 2008-09-01 2009-08-28 Dispositif médical Ceased WO2010023540A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09809396A EP2361038A4 (fr) 2008-09-01 2009-08-28 Dispositif médical

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0815752.1 2008-09-01
GB0815752A GB0815752D0 (en) 2008-09-01 2008-09-01 Medical device
US19450908P 2008-09-29 2008-09-29
US61/194,509 2008-09-29

Publications (1)

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WO2010023540A1 true WO2010023540A1 (fr) 2010-03-04

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GB (1) GB0815752D0 (fr)
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6434422B1 (en) * 1999-09-03 2002-08-13 Tanita Corporation Method and apparatus for judging recovery of physical condition in puerperium
US20020123674A1 (en) * 2001-03-01 2002-09-05 Gianni Plicchi Process and implantable device for the intrapulmonary assessing of density dependant physical properties of the lung tissue

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5086781A (en) * 1989-11-14 1992-02-11 Bookspan Mark A Bioelectric apparatus for monitoring body fluid compartments
ES2151774B1 (es) * 1997-03-06 2001-07-01 Nte Sa Aparato y procedimiento para la medida de volumenes y composicion corporal global y segmental en seres humanos.
FI972067A0 (fi) * 1997-05-14 1997-05-14 Tiit Koeoebi Apparaturer och foerfaranden foer utvaendig maetning av fysiologiska parametrar
US6125297A (en) * 1998-02-06 2000-09-26 The United States Of America As Represented By The United States National Aeronautics And Space Administration Body fluids monitor
CN101926647B (zh) * 2003-09-12 2013-06-05 肾脏研究所有限公司 生物阻抗方法和仪器
US9724012B2 (en) * 2005-10-11 2017-08-08 Impedimed Limited Hydration status monitoring

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6434422B1 (en) * 1999-09-03 2002-08-13 Tanita Corporation Method and apparatus for judging recovery of physical condition in puerperium
US20020123674A1 (en) * 2001-03-01 2002-09-05 Gianni Plicchi Process and implantable device for the intrapulmonary assessing of density dependant physical properties of the lung tissue

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LD TECHNOLOGY, THE EIS - A NEW MEDICAL DEVICE AIMS TO IMPROVE HEALTHCARE EXPERIENCE THROUGH SAFE, NONINVASIVE ELECTRO-INTERSTITIAL SCANS, 15 March 2008 (2008-03-15), XP008144066, Retrieved from the Internet <URL:http://www.devicewatch.org/reports/eis/press_release.pdf> [retrieved on 20100104] *
See also references of EP2361038A4 *

Also Published As

Publication number Publication date
EP2361038A4 (fr) 2012-08-01
EP2361038A1 (fr) 2011-08-31
GB0815752D0 (en) 2008-10-08

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