WO2003059164A2 - Dispositif de controle de l'ecoulement sanguin vers le cerveau - Google Patents

Dispositif de controle de l'ecoulement sanguin vers le cerveau Download PDF

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Publication number
WO2003059164A2
WO2003059164A2 PCT/IL2003/000042 IL0300042W WO03059164A2 WO 2003059164 A2 WO2003059164 A2 WO 2003059164A2 IL 0300042 W IL0300042 W IL 0300042W WO 03059164 A2 WO03059164 A2 WO 03059164A2
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WO
WIPO (PCT)
Prior art keywords
head
cunent
voltage
electrodes
brain
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Application number
PCT/IL2003/000042
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English (en)
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WO2003059164A3 (fr
Inventor
Shlomi Ben-Ari
Alon Rappaport
Aharon Shapira
Original Assignee
Orsan Medical Equipment Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to AU2003209608A priority Critical patent/AU2003209608A1/en
Application filed by Orsan Medical Equipment Ltd. filed Critical Orsan Medical Equipment Ltd.
Publication of WO2003059164A2 publication Critical patent/WO2003059164A2/fr
Publication of WO2003059164A3 publication Critical patent/WO2003059164A3/fr
Priority to US10/893,570 priority patent/US7998080B2/en
Priority to US11/572,141 priority patent/US8187197B2/en
Priority to US11/572,157 priority patent/US8702615B2/en
Priority to US11/921,937 priority patent/US8512253B2/en
Priority to US11/610,553 priority patent/US8211031B2/en
Priority to US13/165,890 priority patent/US20110251503A1/en
Priority to US13/484,519 priority patent/US20130109979A1/en
Priority to US13/941,587 priority patent/US20140163404A1/en
Priority to US14/197,394 priority patent/US20140358016A1/en

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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
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0265—Measuring blood flow using electromagnetic means, e.g. electromagnetic flowmeter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0295—Measuring blood flow using plethysmography, i.e. measuring the variations in the volume of a body part as modified by the circulation of blood therethrough, e.g. impedance plethysmography
    • 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
    • A61B5/0535—Impedance plethysmography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/242—Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents
    • A61B5/245—Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents specially adapted for magnetoencephalographic [MEG] signals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/6815—Ear
    • A61B5/6817—Ear canal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/16—Details of sensor housings or probes; Details of structural supports for sensors
    • A61B2562/164—Details of sensor housings or probes; Details of structural supports for sensors the sensor is mounted in or on a conformable substrate or carrier

Definitions

  • the field of the invention is medical instrumentation, for example for measuring blood flow to the brain.
  • BACKGROUND OF INVENTION There is a need to measure cerebral blood flow during several medical events and procedures, because any disturbance to the flow of blood to the brain may cause an injury to the function of the brain cells, and even death of brain cells if the disturbance is prolonged. Maintaining blood flow to the brain is especially important because brain cells are more vulnerable to a lack of oxygen than other cells, and because brain cells usually cannot regenerate following an injury. A number of common situations may cause a decrease in the general blood flow to the brain, including arrhythmia, myocardial infarction, and traumatic hemorrhagic shock. In such cases, data regarding the quantity of blood flow in the brain, and the changes in flow rate, may be vastly important in evaluating the risk of injury to the brain tissue and the efficacy of treatment. The availability of such data may enable the timely performance of various medical procedures to increase the cerebral blood flow, and prevent permanent damage to the brain.
  • TCD trans- cranial Doppler
  • TCD fails in about 15% of patients, due to the difficulty of passing sound waves through the cranium, and it requires great skill by professionals who have undergone prolonged training and practice in performing the test and deciphering the results.
  • Another disadvantage of TCD is that it measures only regional blood flow in the brain, and does not measure global blood flow.
  • Impedance measurements of the thorax are a known technique for monitoring intracellular and extracellular fluid in the lungs, in patients with congestive heart failure. This technique is effective because the resistive impedance of the thorax at low frequency depends on the volume of blood and other electrolytic fluids, which have a relatively high electrical conductivity, present outside cells. (The capacitive impedance of the thorax, on the other hand, depends largely on the volume of fluid inside cells.)
  • a complicating effect in measuring the impedance of the thorax is the changing volume of air in the lungs during the breathing cycle, since air has a very high resistivity, and various methods have been developed to compensate for this effect. See, for example, U.S. Patents 5,788,643, 5,749,369, and 5,746,214, the disclosures of which are incorporated herein by reference.
  • Photoplesthysmography is another technique used to monitor blood flow and blood volume, using the reflectivity of red or infrared light from the surface of the skin, for example the finger, or the earlobe. See, for example, J. Webster, "Measurement of Flow and Volume of Blood,” in John G. Webster (ed.), Medical Instrumentation: Application and Design (Wiley, 1997).
  • Magnetically inducing electrical fields in the body, including the head, is used in some existing medical procedures, principally for stimulation of the peripheral or central nervous system. See, for example, PCT publication WO 96/16692, the disclosure of which is incorporated herein by reference.
  • Peripheral nerve stimulation is also a well known unwanted side effect of the time-varying magnetic fields used in magnetic resonance imaging.
  • An aspect of some embodiments of the invention relates to using impedance measurements of at least part of the head to estimate blood flow to the brain.
  • the impedance of the head is measured by passing current through the head and measuring the associated voltage by electrodes.
  • current is passed through the head using one or more pairs of current-carrying electrodes, and a separate pair of voltage-measuring electrodes, on a separate high impedance circuit, is used to measure the voltage across the head.
  • sensitivity to the skull impedance is further reduced by inserting the voltage measuring electrodes into the ears.
  • the nose or other orifices, or thin bone areas in the skull are used.
  • electrodes of large area are used, or one or more electrodes are spread out over a large area (for example, by using an annular electrode) even if the total area of the electrodes themselves is not so large, in order to focus the current to go through the interior of the head, and not so much through the scalp.
  • the impedance of the head is measured over time.
  • the change in impedance over a pulse cycle for example, is a measure of the change in blood volume during a pulse cycle, and hence the blood flow rate. Even if there are inaccuracies in the blood flow rate measured in this way, the technique is adequate for detecting a substantial drop in blood flow to the brain that occurs during surgery, or in determining whether CPR is being performed effectively.
  • inductive measurements are used to estimate the impedance of the head, and hence the blood volume and rate of blood flow to the brain.
  • One or more coils with alternating current flowing in them, adjacent to the head, are used to produce a changing magnetic field inside the head, and hence to induce an electric field, which drives eddy currents in the brain.
  • the magnitude of these eddy currents depends on the impedance of the brain, and hence on the blood volume of the brain.
  • the eddy currents in the brain are measured by the changing magnetic field, and hence voltage, which they induce in the driving coils, or in one or more separate measuring coils, which are place around the head, approximately parallel to the driving coils.
  • voltage-measuring electrodes on the skin are used to measure the induced electric field.
  • magnetic field sensors for example Hall sensors, flux gate magnetometers, or SQUTDs, are used to measure the magnetic field. Both the induced electric field and the magnetic field depend on the impedance of the brain, because the eddy currents in the brain affect the magnetic field.
  • An aspect of some embodiments of the invention concerns the use of photoplethysmography to estimate the rate of blood flow to the brain, either alone or in conjunction with impedance measurements.
  • photoplethysmography is performed inside the ear, which makes it more sensitive to the important internal blood flow in the head, as opposed to measurements in the earlobe which depend on peripheral blood flow.
  • a probe for photoplethysmography inside the ear is optionally combined with a voltage-measuring probe used inside the ear for impedance measurements.
  • a method of estimating blood flow in the brain comprising: a) causing currents to flow inside the head by producing electric fields inside the head; b) measuring at least changes in the electric fields and the currents; and c) estimating changes in the blood volume of the head, using the measurements of the electric fields and the currents.
  • using the measurements of electric fields and the currents comprises calculating the impedance of the head at at least two different times.
  • producing electric fields inside the head comprises placing at least two current-carrying electrodes on the head and applying at least two different voltages to the current-carrying electrodes.
  • the current-carrying electrodes are sufficiently large in area so that a significant amount of the current flows through the interior of the skull, and not through the scalp.
  • the electrodes are spread out enough in area so that a significant amount of the current flows through the interior of the skull, and not through the scalp.
  • measuring the electric fields comprises placing at least two voltage-measuring electrodes on the head, on a separate circuit from the current-carrying electrodes, and measuring the voltage difference between the voltage- carrying electrodes.
  • placing the voltage-measuring electrodes on the head comprises placing them inside the ears.
  • placing the current-carrying electrodes on the head comprises placing at least three current-carrying electrodes on the head, and applying different voltages to the current-carrying electrodes comprises applying at least three different voltages to the current-carrying electrodes so that a desired current distribution is produced in the head.
  • the desired current distribution is concentrated in a desired region of the brain, and estimatmg the blood flow in the brain comprises estimating the blood flow in the desired region of the brain.
  • producing electric fields inside the head comprises: a) placing at least one induction coil adjacent to the head; and b) running time-varying current through said at least one induction coils, thereby inducing the electric fields inside the head, whereby causing currents to flow inside the head comprises causing eddy currents to flow inside the head.
  • the frequency distribution of the time- varying current running through the at least one induction coils is such that the eddy currents flowing in the head do not reduce the magnetic field at any point in the head by more than a factor of 3.
  • measuring the currents inside the head comprises measuring the magnetic field produced by the eddy currents.
  • measuring the magnetic field produced by the eddy currents comprises: a) placing two voltage-measuring electrodes on the head; b) measuring the induced electric field by measuring the voltage difference between the voltage-measuring electrodes; and c) subtracting the part of the electric field induced by the magnetic field produced by the currents running in the at least one induction coils, thereby finding the part of the electric field induced by the magnetic field produced by the eddy currents.
  • the method also comprises using photoplethysmography on tissue inside the head.
  • the tissue is inside the ear.
  • the tissue is inside the nose.
  • the method is used to monitor the blood flow in a patient's brain during surgery.
  • the method is used to monitor the blood flow in a patient's brain during CPR, to verify that the CPR is being performed effectively.
  • the method is used to monitor the blood flow in the brain of a patient with a medical condition likely to lead to loss of blood flow to the brain.
  • an apparatus for estimating blood flow to the brain comprising: a) a power supply; b) an electric field source which uses the power supply to produce an electric field in the head, at a safe amplitude and frequency, thereby producing a current in the head; c) an electrical element which determines at least changes in the electric field in the head and at least changes in the current in the head, having sufficient precision to at least estimate changes in the impedance of the head; and d) a monitor which displays at least information telling a user when changes in the impedance of the head show a significant change in blood flow rate.
  • the electric field source comprises at least two current-carrying electrodes, adapted for forming a good electrical connection to the head, and connected to the power supply
  • the electrical element comprises: a) a controller in the power supply which controls one of the output voltage and the output current of the power supply, or a combination of the output voltage and output current; and b) a meter which measures one of voltage across the head, current through the head, or a combination of voltage across the head and current through the head which is not controlled by the controller.
  • the controller in the power supply controls the output current
  • the meter is a voltmeter, and there are two voltage-measuring electrodes, connected to the voltmeter, which voltage-measuring electrodes are adapted for forming a good electrical connection to the head.
  • the current-carrying electrodes comprise at least three current-carrying electrodes, and at least two of the current-carrying electrodes are connected in parallel to the same voltage.
  • the current-carrying electrodes are collectively sufficiently large in area so that a significant amount of the current flows through the interior of the skull, and not through the scalp.
  • the current-carrying electrodes are collectively sufficiently spread out in area so that a significant amount of the current flows through the interior of the skull, and not through the scalp.
  • the voltage-measuring electrodes are adapted to be placed inside an opening in the head.
  • the voltage-measuring electrodes are adapted to be placed inside the ears.
  • the voltage-measuring electrodes are conical and padded, thereby allowing them to be pressed firmly enough into the ears to make good electrical contact, without damaging the ear drums.
  • a probe adapted for measuring blood flow photoplethysmographically in the ears, which probe is combined with the voltage- measuring electrodes.
  • the at least two current-carrying electrodes comprise at least three current-carrying electrodes
  • the power supply is capable of simultaneously applying at least three different voltages to the current-carrying electrodes, whereby a desired current distribution is produced inside the head.
  • the current-carrying electrodes are adapted to be placed in locations on the head such that the desired current distribution is concentrated in a desired region of the brain.
  • the power supply produces a time-varying power supply current
  • the means for producing an electric field in the head comprises at least one induction coil, connected to the power supply, which induces an electric field in the head by producing a time-varying magnetic field in the head, the current in the head thereby being an eddy current
  • the means for determining at least changes in the electric field in the head comprises a controller in the power supply, which determines the rate of change of the power supply current, and thereby determines the rate of change of the magnetic field in the head, and the induced electric field in the head
  • the means for determining at least changes in the current in the head comprises a sensor which senses the magnetic field produced by the current in the head.
  • the power supply is capable of operating over at least part of the range between 10 kHz and 100 kHz.
  • the power supply is capable of operating over at least part of the range between 100 kHz and 1 MHz.
  • the power supply is capable of operating over at least part of the range between 1 MHz and 10 MHz.
  • the power supply is capable of operating over at least part of the range between 10 MHz and 100 MHz.
  • the senor comprises at least one of the at least one induction coils.
  • the senor comprises a separate sensing coil which measures the voltage induced by changes in magnetic flux passing through it.
  • the sensor comprises a solid-state magnetic field sensor.
  • the senor comprises voltage-measuring electrodes which measure an electric field induced by the time-varying magnetic field produced by the at least one induction coil.
  • the sensor comprises voltage-measuring electrodes which measure an electric field induced by the time-varying magnetic field produced by the at least one induction coil.
  • the probe is sufficiently wide at its base that it cannot damage the eardrum when inserted into the ears.
  • the probe is surrounded by a holding element which, when inserted into the ear, holds the probe in a position and orientation to allow repeated optical measurements of the same location.
  • the apparatus is portable enough for use in the field by emergency medical technicians.
  • a head motion sensor there is also: a) a head motion sensor; and b) a controller which uses data from the head motion sensor to reduce motion artifacts in estimating the blood flow.
  • FIG. 1 is a schematic cross-sectional view of a head with electrodes, according to an exemplary embodiment of the invention
  • Fig. 2 is a schematic plot of typical impedance data according to the same of a different exemplary embodiment of the invention.
  • Fig. 2A is a schematic cross-sectional view showing an electrode and an optical probe inserted into an ear.
  • Figs. 3A, 3B, and 3C are schematic perspective views of a head with induction coils according to three other exemplary embodiments of the invention.
  • Fig. 4 is a schematic view of the head showing the brain and induction coils, according to the same embodiment of the invention as Fig. 3B; and Figs. 5 A, 5B, and 6 are perspective views of a head with electrodes, and a monitor, according to three different exemplary embodiments of the invention.
  • FIG. 1 shows a cross-section of a head 100 seen from the top, including a skull 102 with two openings 104 associated with the ears, and an interior region 106 which includes the brain. It is desired to measure changes in the electrical impedance of interior region 106, without having the measurements dominated by the much greater impedance of the skull.
  • Two positive current-carrying electrodes 108 are shown in contact with the skin on the right side of the head, one in front of the ear and one behind the ear.
  • two negative current-carrying electrodes are shown in contact with the skin on the left side of the head.
  • This may be varied, for example there is only one electrode on each side, or there are more than two electrodes on each side, or the electrodes are above or below the ears, or on the ears, and the number of positive electrodes need not equal the number of negative electrodes.
  • annular electrode instead of having one large electrode on each side of the head, or several small electrodes at the same voltage on each side covering a large total area, there is, on at least one side of the head, an annular electrode with a wide diameter, even if it has a thin annulus with a small total area.
  • the current will tend to be focused to go through the interior of the head, rather than through the scalp, as if the whole area inside the annular electrode, or the whole area covered by the spread out distribution of electrodes, were one large electrode. All of these options can be used on either one or both sides of the head.
  • the electrode configuration causes at least 90% of the current to go through the interior of the head.
  • at least 50% of the current goes through the interior of the head, or at least 20%, or at least 10%, or at least 1%.
  • Having a significant amount of current going through the interior of the head means having enough current going through the interior of the head so that the impedance measurements are sufficiently dependent on blood volume that they can be used to measure the blood flow.
  • electrodes 108 and 110 are kept in good electrical contact with the skin by a conductive gel, such as those used in ECG measurements.
  • a constant current is driven from electrodes 108 to electrodes 110 by power supply 112.
  • power supply 112 produces a constant voltage, or some combination of constant voltage and constant current, but the current is measured.
  • different electrodes even on the same side of the head, have different voltages applied to them by the power supply, in order to produce a desired distribution of current flowing through the head.
  • current could be concentrated in one region of the brain, to measure blood flow in that region, or current could be distributed uniformly to measure global blood flow.
  • the current density is more than twice as great in one region of the brain than it is in other regions.
  • the current density is 50% greater, or 20% greater, or 10% greater, in one region of the brain than in other regions.
  • the current distribution in the brain produced by different shapes, sizes, locations and voltages of electrodes are optionally evaluated using finite element analysis software, or any other numerical or analytic method known to the art.
  • DC current is applied to the head, in practice, for safety reasons, AC current is generally applied, optionally at frequencies between 20 and 100 kHz, and the "positive" and "negative" electrodes 108 and 110 in Fig. 1 really represent two different phases of the AC voltage applied by the power supply, 180 degrees apart.
  • the cureent is optionally limited, for example to 0.5 milliamperes or 1 miUiampere, depending to some extent on the area and location of the electrodes.
  • This is a potential advantage of using a constant current rather than a constant voltage power supply.
  • the current is not too much lower than this, for example not less than 0.1 miUiampere, since the impedance measurement may be less accurate at lower current.
  • the current is applied at frequencies between 20 and 40 kHz, which is high enough to run the maximum current safely, but is still low enough so that the current is largely confined to the blood and other extracellular fluid, and is excluded from the interiors of cells by the high resistance cell membranes. This makes the measured impedance maximally sensitive to blood volume.
  • the current is run between 70 and 100 kHz, instead of or in addition to 20 to 40 kHz.
  • the cell membranes may already begin to short out due to their finite capacitance, and a significant amount of the current may flow inside the cells, as well as in the blood and extracellular fluid.
  • the impedance may be somewhat less sensitive to changes in blood volume in the higher frequency range, the spatial distribution of current may be different than at lower frequency, due to the inhomogeneous distribution of blood and extracellular fluid throughout the brain.
  • Obtaining impedance data at high frequency especially if it supplements data obtained at lower frequency, may provide additional data about the distribution of blood flow in the brain, or the distribution of pooled blood from a cerebral hemonhage, for example.
  • the current is also run at intermediate frequencies, 40 to 70 kHz, to provide additional data on blood distribution, or is only run at intermediate frequencies.
  • voltage-measuring electrodes 114 are inserted into the ears through openings 104, reaching locations that are relatively well connected electrically with the interior of the skull, and measure the voltage across the interior of the head associated with the current flowing between current-carrying electrodes 108 and 110.
  • electrodes 114 are conical Ag/AgCl electrodes padded with a sponge soaked in a conductive gel. The conical shape prevents the electrodes from pressing against and possibly damaging the ear drums, when they are pushed with some force into the ear canals in order to make good electrical contact.
  • Electrodes 114 are attached to a high impedance recording device 116, so very little current flows through electrodes 114. This means that the voltage measured by recording device 116 depends mostly on the voltage drop across the interior of the head produced by power supply 112, and does not depend very much on the impedance of the skull, or on the impedance associated with the contact between electrodes 114 and the head, or between electrodes 108 or 110 and the head. If the voltage were instead measured between electrodes 108 and 110, then the voltage might be dominated by the skull, or by the contact between the electrodes and the skin. Alternatively, electrodes 114 are not placed inside the ears, but on the surface of the head.
  • the voltage measured by recording device 116 is not sensitive to the voltage drop across the skull, or at least is less sensitive to the voltage drop across the skull than if the voltage were measured between electrodes 108 and 110, and the voltage measured by recording device 116 is sufficiently sensitive to the impedance of the interior of the head that changes in blood volume can be detected.
  • electrodes 114 are placed on the temples, where the skull is thinner than at most other parts of the head, in order to make the voltage measured by recording device 116 less dependent on the skull impedance, and more sensitive to the impedance of the interior of the head.
  • Dividing the voltage measured by recording device 116 by the current produced by power supply 112 gives a measure of the electrical impedance of interior region 106, which is related to the blood volume in the brain.
  • the voltage produced by power supply 112 is used in addition to, or instead of, the voltage measured by recording device 116 in calculating the impedance, possibly as a check on the reasonableness of the voltage measured by recording device 116. But often, the voltage produced by power supply 112 is influenced more by the skull impedance, and less by the impedance of the interior of the head, than the voltage measured by recording device 116. If AC current is used, then of course the current and voltage are each expressed by a complex number, representing the amplitude and phase.
  • the capacitance of the cell membranes will start to look like a short circuit, and current will flow almost as easily through the cells as it flows through the blood and other fluid surrounding the cells.
  • the impedance of the head will be less sensitive to blood volume than it is at lower frequencies, because it will depend on the total volume of the brain, including the cells, not just on the volume of the blood and the extracellular fluid.
  • frequencies below about 100 kHz are used to measure the impedance of the head.
  • measurements of the relative phase of the voltage measured by recording device 116 or by power supply 112, and the current produced by power supply 112, particularly at higher frequencies such as 100 kHz, are used to measure the impedance of the head.
  • phase measurements are potentially useful at frequencies comparable to 100 kHz, where the impedance of the head has a substantially capacitive component due the cell membranes, especially if the capacitive part of the impedance is insensitive to blood volume, or has a different dependence on blood volume than the resistive impedance of the head.
  • the measured impedance is still useful for measuring blood volume if it depends significantly on blood volume as well.
  • the impedance is never actually calculated, but the blood volume is determined directly from the voltage data, particularly if the current produced by power supply 112 is always the same.
  • feedback to the power supply is used to keep the voltage measured by recording device 116 constant (i.e. constant amplitude and phase), and the current produced by power supply 112 is used directly to determine the blood volume. Variants on these methods, for example, keeping some linear combination of voltage and current the same, will be apparent to those skilled in the art.
  • Fig. 2 shows a plot 200 of resistive impedance vs. time, measured as described in Fig. 1, over a period of time covering several pulse cycles.
  • the vertical axis 202 represents impedance, or resistance
  • the horizontal axis 204 represents time.
  • the average resistance R over time has a value given by level 206 on the vertical axis, and the variation in resistance ⁇ R, associated with the pulse cycle, is shown by interval 208.
  • the resistance decreases during the systolic phase of the pulse, when the blood volume V of the brain is higher, and increases during the diastolic phase when the blood volume V is lower.
  • the relative change in blood volume over a pulse period ⁇ V/V is comparable to ⁇ R/R.
  • the exact relation between ⁇ V/V and ⁇ R/R can be calibrated for a given configuration of electrodes by comparing measured values of ⁇ R/R with measurements of blood flow performed by other means known to the art.
  • the blood flow to the brain is found by multiplying ⁇ V/V by the total brain blood volume V (estimated, for example, from a known average value for humans) and the pulse rate.
  • the estimated values of blood flow obtained by this technique are still adequate for some applications of interest, such as determining whether CPR is working at all, or detecting a sudden decrease in blood flow to the brain during surgery. If CPR is not being administered properly, or if blood flow to the brain is reduced by a stroke or another sudden event suffered during surgery, then the blood flow to the brain may be essentially zero, or much lower than normal, and this may be detected even if the technique does not measure absolute values of blood flow very accurately.
  • Fig. 2 A shows a closeup view of voltage-measuring electrode 114 inserted into ear canal 104.
  • Electrode 114 is connected to recording device 116, which analyzes the voltage data and displays information about the head impedance and the blood flow.
  • Electrode 114 is surrounded by a sponge 218, soaked in an electrically conducting gel.
  • Electrode 114 is conical in shape, and too wide at the base to reach the ear drum when it is inserted into the ear.
  • a light source 220 for example a red or infrared laser or laser diode, sends light through optical fiber 222.
  • Light ray 224 reflects off a surface 226 inside the ear, for example the ear drum, or another surface whose color is affected by blood flow and/or oxygenation of the blood.
  • Sponge 218 holds optical fiber 222 firmly enough in place so that if the measurements are repeated, light ray 224 always reflects from substantially the same place, so any changes in reflectivity are due to changes in blood flow or oxygenation, rather than due to fiber 222 changing its position or orientation.
  • the reflected light goes into another optical fiber 228, which carries it to an analyzer 230. Fiber 228 is also held firmly in place by sponge 218.
  • Analyzer 230 uses information about the reflectivity of surface 226 to measure or estimate blood flow rate, and/or the degree of oxygenation of the blood, and optionally displays the information.
  • Analyzer 230 and light source 220 are optionally based on any existing system of photoplethysmography, known to those skilled in the art.
  • a fiber optic cable comprising a plurality of optical fibers, is used instead of optical fiber 222 and/or optical fiber 228.
  • fibers 222 and 228 are bundled together with the wire connecting electrode 114 to recording device 116.
  • analyzer 230 is packaged together with recording device 116.
  • data from analyzer 230 is combined with data from recording device 116, and a single estimate of blood flow is displayed, based on the combined data.
  • a probe comprising fibers 222 and 228, and sponge 218 or a similar element to hold the probe in place, is used for optical measurements in the ears, even if voltage-measuring electrodes 114 are not placed in the ears.
  • a different method of inducing currents in the brain and measuring voltages is illustrated in Figs. 3A, 3B, and 3C, which show coils placed around the head in different orientations, to induce cunents in the brain.
  • Other magnetic induction methods may be used as well, including different coil configurations, or the use of rotating or oscillating permanent magnets or electromagnets to produce time-varying magnetic fields in the head.
  • Fig. 3A Measuring the induced cunents, by measuring their effects on the induced magnetic and electric fields, gives information about the impedance of the brain, and hence the blood volume of the brain.
  • coils 302, one on each side of the head have AC cunent flowing in them, driven by power supply 304, and generate an AC magnetic field inside the head.
  • the changing magnetic flux induces electric fields in the head which are parallel to the cunents in coils 302, but in the opposite direction.
  • the AC magnetic field optionally is large enough so that the induced electric fields are large enough to produce measurable effects, as discussed below, but small enough not to produce peripheral or central nerve stimulation.
  • the threshold for nerve stimulation is increased by using trains of short pulses, or other methods known to the art, so that higher AC magnetic fields can be used.
  • the induced electric fields cause eddy cunents to flow in the brain, of an amplitude which depends on the impedance of the brain.
  • the eddy cunents in turn generate their own magnetic field and an associated induced electric field, reducing the magnetic flux inside the brain.
  • Coils 306 measure a voltage associated with the AC magnetic flux produced by coils 302, and this voltage is recorded by recording device 308.
  • the reduction in magnetic flux caused by the eddy currents flowing in the brain can be detected by recording device 308, since the induced voltage will be lower, i.e. the mutual inductance between coils 302 and coils 306 will be reduced.
  • the eddy cunents will also give the mutual inductance an imaginary (dissipative) part, which may be easier to detect than the reduction in the real part of the mutual inductance.
  • An estimate of the absolute impedance of the brain may be made by observing how the mutual inductance of coils 302 and 306 changes with the frequency of the AC cunent. Even without making such an absolute estimate of the impedance of the brain, changes in impedance of the brain over time, during the pulse cycle, may be detected by observing the changes in mutual inductance during the pulse cycle.
  • the electric fields induced by coils 302 are measured by electrodes placed on or in the head, similar to the voltage-measuring electrodes shown in Figs. 1 and 2A.
  • the electrodes are shaped and sized, for example, to be placed in the ears or in the nose, or to be placed on the temples or elsewhere on the head, with electrically conducting gel.
  • the induced electric field depends on the impedance of the brain, because it is modified by the eddy cunents which depend on the impedance of the brain.
  • the frequency of the AC cunent in coils 302. For a brain resistivity of 2 ohm-meters, typical of body tissue, the magnetic field produced by the eddy cunents, which depends on the impedance of the brain, will be comparable to the magnetic field produced by the induction coils when the skin depth of the brain is comparable to its radius, about 10 cm. This occurs at a frequency of about 50 MHz. At frequencies well above 100 kHz, however, the impedance of the cell membranes may be effectively shorted out, so that cunent flows freely inside as well as outside the cells, so the resistivity of the brain is somewhat lower, and eddy cunents become important at about 30 MHz.
  • the impedance of the brain at such high frequencies is less sensitive to blood volume than it is below 100 kHz, due to the conduction pathway going inside the cells, but the impedance is still somewhat sensitive to blood volume, since the 03 00042 total volume of fluid in the brain, inside and outside cells, still increases when the blood volume increases.
  • frequencies of about 10 MHz, or a few tens of MHz, or even about 100 MHz are used, since the blood volume may have the greatest effect on eddy cunents in this frequency range.
  • eddy cunents may largely exclude magnetic flux from the interior of the brain, and the mutual inductance of the coils may be less sensitive to blood volume.
  • the frequencies used are low enough so that the eddy cunents do not reduce the magnetic field at any point inside the head by more than a factor of 1.5.
  • the eddy currents do not reduce the magnetic field by more than a factor of 3, or by more than a factor of 6.
  • the small change in the real part of the mutual inductance might be difficult to detect, but the change in the dissipative part, which is proportional to frequency well below 30 MHz, might be relatively easy to detect, even below 100 kHz, if it is the dominant dissipative term.
  • frequencies between a few tens of kHz, about 100 kHz, or a few hundred kHz are used, since they are easier to work with than frequencies of a few tens of MHz, and may still provide sufficient sensitivity to blood volume.
  • frequencies of a few hundred kHz, about 1 MHz, or a few MHz are used, since they may provide the best trade-off between sensitivity and ease of use.
  • Eddy currents at different frequencies may have different spatial distributions in the brain, both because of skin effects (differing mostly at frequencies above 1 MHz), and because of the finite capacitance of cell membranes (differing mostly at frequencies below 1 MHz). Eddy currents may also have a different distribution in the brain than cunents produced by electrodes placed on the head. Different distributions of cunent may provide different data about the distribution of blood in the head, for example in a patient with a cerebral hemonhage where blood can pool locally at one or more locations.
  • eddy currents are induced at more than one frequency, or both coils and electrodes are used to induce currents in the brain, in order to obtain more data about the distribution of blood in the brain.
  • the cunents in induction coils 302 are of a magnitude small enough not to cause peripheral or central nerve stimulation, or to cause deleterious health effects or discomfort from heating of the brain or other body tissues.
  • the maximum safe currents which depend on the frequency and duration of the cunents, are well known to those skilled in the art, in the field of magnetic resonance imaging for example.
  • the currents used are only a few times less than the maximum safe cunents, or even only a few percent less than the maximum safe cunents, and not many times less, in order not to sacrifice precision of the measurements.
  • coils 302 are used to detect the induced voltage, i.e. the self-inductance of coils 302 is used, instead of the mutual inductance between coils 302 and 306.
  • the voltage in coils 306 will not be sensitive to the resistance of coils 302, or the resistance of coils 306 if recording device 308 has a high impedance.
  • the dissipative part of the mutual inductance may be the dominant dissipative term in the voltage measured the recording device 308, making it easy to measure.
  • self-inductance of coils 302 were used, the dissipative part of the inductance would likely be small compared to the resistance of the coils, and difficult to measure.
  • the magnetic fields produced by the coil cunents and by the eddy cunents in the brain are measured by magnetic sensors such as Hall sensors, flux gate magnetometers, or SQUIDs.
  • magnetic sensors will give more local magnetic field measurements than large coils encircling the head, and may give data that is weighted toward local changes in blood flow, possibly complementing the more global data from large coils.
  • Global data is also optionally obtained by averaging the results from several local magnetic sensors.
  • Fig. 3 A shows two coils 302 on the sides of the head, and two coils 306, near the midplane of the head, but going around opposite sides of the neck. However, the coils need not be ananged symmetrically as shown.
  • coils 302 are close to the midplane of the head, and coils 306 are located on the sides of the head.
  • An optimal configuration of coils can optionally be found by using magnetic finite element methods, or other numerical or analytic methods known to the art.
  • Figs. 3B and 3C show coils 302 and 306 oriented in other directions with respect to the head.
  • another consideration in choosing the coil orientation is the ability to keep the coils positioned rigidly with respect to the head. Changes in position of the coils will affect their mutual inductance and self-inductance, and may appear as spurious changes in calculated brain impedance.
  • Fig. 4 shows coils 402 ananged in front and back of a head, as in Fig. 3B, and a coil 406 going around the head from to top to under the chin, to measure the flux induced by coils 402.
  • the brain 410 is shown inside the head.
  • Cunents 414 reduce the magnetic flux inside the brain, and reduce the total flux passing through coils 402 and 406. Cunents 414 also change the phase of the flux passing through coils 402 and 406, relative to the phase of cunent 412 in coils 402.
  • This change in amplitude and phase of the flux is detected by coil 406 as a change in the amplitude and phase of the voltage of coil 406, relative to the amplitude and phase of cunent 412.
  • the amplitude and phase of the voltage in coil 406 provides information about the impedance of brain 410.
  • a C-shaped element of high magnetic permeability extends between the two coils 302 in any of Figs. 3A, 3B, or 3C, in order to increase the magnetic field induced in the brain, for a given cunent in coils 302. This would reduce the size and cost of the required power supply, and reduce the ohmic heating of the coils, to produce a given magnetic field and induced electric field in the brain.
  • Such a C-shaped element could, however, have the potential disadvantage of introducing an additional source of dissipation, due to eddy cunents and hysteresis in the magnetic material, that might make it more difficult to detect the eddy cunents introduced in the brain by coils 302, and many high permeability alloys have lower permeability at high frequencies, especially above 1 MHz.
  • the C-shaped element is laminated, to reduce eddy currents and increase the effective permeability at a given frequency.
  • the C-shaped element is made of vanadium permendur, or a similar alloy with low magnetic anisotropy, because its penneability may not fall off as much at high frequencies as is the case with other high permeability materials.
  • Figs. 5 A and 5B illustrate portable embodiments of the invention that are potentially suitable for use in the field, in contrast to non-portable embodiments of the invention that are suitable for use in a hospital setting during surgery, for example.
  • Assemblies 502 contain both cunent-carrying and voltage-measuring electrodes, either placed on the temples, as in Fig. 5A, or on the ears, and with the voltage-measuring electrodes optionally inserted into the ears, as in Fig. 5B.
  • assembly 502 on each side of the head covers the ears, resembling earmuffs, with cunent-carrying electrodes outside the ears and voltage-measuring electrodes inside the ears.
  • some of the electrodes are placed on the temples or elsewhere on the head, and some of them are placed on or in the ears.
  • assemblies 502 contain coils which induce eddy cunents in the brain, and coils or other magnetic sensors which detect the eddy cunents.
  • assemblies 502 contain coils, they are substantially bigger than shown in Figs. 5 A and 5B, in order to produce a magnetic field that is more uniform in the brain, rather than concentrated near the assemblies, and in order to reduce the ohmic power generated by the coils when producing a given magnetic field.
  • the coils are small, and are inserted into the ears, particularly for making local measurements of impedance near the ears.
  • Monitor 504 optionally displays the blood volume or blood flow rate as a function of time, determined from the impedance measurements.
  • monitor 504 has warning lights, for example a green light which lights up when the blood flow rate to the brain is satisfactory, and a red light which lights up, and/or a buzzer which sounds, when the blood flow rate is too low, or changes suddenly.
  • monitor 504 has five or fewer warning lights, to minimize the information that an emergency medical technician has to sift through, when looking at the monitor.
  • a power supply is packaged together with monitor 504.
  • monitor 504. there is a separate power supply, not shown in Figs. 5 A and 5B.
  • Fig. 6 shows a similar embodiment of the invention, but with monitor 504 mounted on the patient's forehead.
  • monitor 504 mounted on the patient's forehead.
  • any of recording device 116 in Figs. 1 and 2A, power supply 112 in Fig. 1, analyzer 230 in Fig. 2A, power supply 304 in Figs. 3A, 3B, and 3C, recording device 308 in Figs. 3A, 3B and 3C, and monitor 504 in Figs. 5A, 5B and 6, comprise a controller, which controls the currents sent to the cunent-carrying electrodes or coils, and analyzes the data.
  • the controller includes any of a CPU, power electronics, an AC/DC converter, and non-volatile memory to store software and data.
  • different elements of the controller are located in different places, for example the power supply and the recording device, and/or the controller or parts of the controller are packaged separately.
  • motion of the head relative to the electrodes, coils, or sensors can produce a spurious change in measured blood volume, and hence a spurious calculated blood flow.
  • Various methods are optionally used to reduce such motion artifacts.
  • the effect of any motion that is not conelated with the pulse cycle is optionally reduced by averaging over time. Such averaging will not eliminate motion artifacts in the calculated blood flow due to motion that is conelated with the pulse, such as motion associated with the administration of CPR.
  • Motion artifacts are also optionally reduced by keeping the head immobilized, and keeping the electrodes, coils, and sensors rigidly in place against the head.
  • motion artifacts are compensated for by using an accelerometer to detect motion of the head, and modeling the motion artifacts, or by only using data taken when the head is not moving too much.
  • a pulse detected in the neck is used to distinguish motion artifacts from the real effects of blood flow in the brain, even if the pulse in the neck is not usable for measuring blood flow directly.
  • Potential applications of these techniques for measuring blood flow in the brain may best be served by adapting the device to each application. For example:
  • the device is optionally made portable, with a self-contained power supply, perhaps battery operated, and/or has a monitor with only limited information displayed.
  • the device optionally is portable enough and rugged enough for home use, using a battery or AC power from a wall outlet, and/or has a monitor that is simple enough to be used by the patient or a family member with little training, and optionally also displays additional information that could be used, for example, by a visiting nurse.
  • the device For monitoring blood flow to the brain prior to and during surgical procedures, especially carotid endarectomy, the device need not be portable or could be moved around on a cart, and optionally displays data that would be of interest to the surgeon or other medical personnel in the operating room, so that changes can be made in the surgical procedure in real time, in response to a decrease in blood flow, for example.
  • the device For monitoring patients suffering from diseases such as stroke, syncope, and sickle cell anemia, where disturbances in cerebral blood flow often occur, the device optionally measures local blood flow in different regions of the brain, and optionally comes in different versions, one for hospital use, for example in an intensive care unit, and one for long term monitoring at home.
  • the device For cardiopulmonary resuscitation (CPR), to verify that it is working effectively, the device optionally integrates the blood flow in the brain after every few chest compressions, for example every time the lungs are expanded, and prominently displays the result on a large dial or array of lights, so the person administering CPR can immediately see whether the chest compressions are too weak or too strong, or too slow or too fast, or whether the heart has started beating on its own.
  • a portable version of the device is optionally used by emergency medical technicians in the field or in an ambulance.
  • a less portable version, on a cart for example, is optionally used in a hospital emergency room.

Abstract

L'invention concerne un procédé d'estimation de l'écoulement sanguin dans le cerveau comprenant les étapes suivantes : a) produire, au moyen de champs électriques à l'intérieur de la tête, des courants de façon qu'ils circulent à l'intérieur de la tête; b) mesurer au moins des variations dans les champs électriques et les courants ; et c) estimer les variations dans le volume sanguin de la tête, au moyen des mesures des champs électriques et des courants.
PCT/IL2003/000042 2002-01-15 2003-01-15 Dispositif de controle de l'ecoulement sanguin vers le cerveau WO2003059164A2 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AU2003209608A AU2003209608A1 (en) 2002-01-15 2003-01-15 Device for monitoring blood flow to brain
US10/893,570 US7998080B2 (en) 2002-01-15 2004-07-15 Method for monitoring blood flow to brain
US11/572,141 US8187197B2 (en) 2002-01-15 2005-06-15 Cerebral perfusion monitor
US11/572,157 US8702615B2 (en) 2002-01-15 2005-06-15 Device for monitoring blood flow to brain
US11/921,937 US8512253B2 (en) 2002-01-15 2006-01-17 Cerebral perfusion monitor
US11/610,553 US8211031B2 (en) 2002-01-15 2006-12-14 Non-invasive intracranial monitor
US13/165,890 US20110251503A1 (en) 2002-01-15 2011-06-22 Device for monitoring blood flow to brain
US13/484,519 US20130109979A1 (en) 2002-01-15 2012-05-31 Non-invasive intracranial monitor
US13/941,587 US20140163404A1 (en) 2002-01-15 2013-07-15 Cerebral Perfusion Monitor
US14/197,394 US20140358016A1 (en) 2002-01-15 2014-03-05 Device for Monitoring Blood Flow to the Brain

Applications Claiming Priority (2)

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US34827802P 2002-01-15 2002-01-15
US60/348,278 2002-01-15

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WO2004026136A1 (fr) * 2002-09-17 2004-04-01 Beth Israel Deaconess Medical Center, Inc. Cartographie d'impedance en radiofrequence
WO2006006143A1 (fr) * 2004-07-15 2006-01-19 Orsan Medical Technologies Ltd. Dispositif permettant de surveiller l'ecoulement sanguin vers le cerveau
WO2006134501A1 (fr) * 2005-06-15 2006-12-21 Orsan Medical Technologies Ltd. Appareil de surveillance de perfusion cerebrale
WO2007036586A2 (fr) * 2005-09-27 2007-04-05 Universidad Politécnica De Valencia Appareil et procede destines a l'obtention d'informations relatives a l'hemodynamique cerebrale
EP1847215A1 (fr) * 2006-04-21 2007-10-24 Hitachi, Ltd. Système et procédé de mesure d'un corps vivant
JP2008546438A (ja) * 2005-06-15 2008-12-25 オルサン メディカル テクノロジーズ リミテッド 脳潅流モニタ
US8211031B2 (en) 2002-01-15 2012-07-03 Orsan Medical Technologies Ltd. Non-invasive intracranial monitor
US9307918B2 (en) 2011-02-09 2016-04-12 Orsan Medical Technologies Ltd. Devices and methods for monitoring cerebral hemodynamic conditions
CN111528826A (zh) * 2020-05-25 2020-08-14 陈聪 一种获取脑阻抗血流图数据的方法

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Cited By (20)

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US7998080B2 (en) 2002-01-15 2011-08-16 Orsan Medical Technologies Ltd. Method for monitoring blood flow to brain
US8702615B2 (en) 2002-01-15 2014-04-22 Osran Medical Technologies, Ltd. Device for monitoring blood flow to brain
US8512253B2 (en) 2002-01-15 2013-08-20 Orsan Medical Technologies, Ltd Cerebral perfusion monitor
US8211031B2 (en) 2002-01-15 2012-07-03 Orsan Medical Technologies Ltd. Non-invasive intracranial monitor
US8187197B2 (en) 2002-01-15 2012-05-29 Orsan Medical Technologies Ltd. Cerebral perfusion monitor
WO2004026136A1 (fr) * 2002-09-17 2004-04-01 Beth Israel Deaconess Medical Center, Inc. Cartographie d'impedance en radiofrequence
EP1786316A1 (fr) * 2004-07-15 2007-05-23 Orsan Medical Technologies Ltd. Appareil de surveillance de perfusion cerebrale
WO2006006143A1 (fr) * 2004-07-15 2006-01-19 Orsan Medical Technologies Ltd. Dispositif permettant de surveiller l'ecoulement sanguin vers le cerveau
JP2008506444A (ja) * 2004-07-15 2008-03-06 オーサン メディカル テクノロジーズ リミテッド 脳への血流をモニタする装置
EP1786316A4 (fr) * 2004-07-15 2010-03-03 Orsan Medical Technologies Ltd Appareil de surveillance de perfusion cerebrale
JP2008546438A (ja) * 2005-06-15 2008-12-25 オルサン メディカル テクノロジーズ リミテッド 脳潅流モニタ
WO2006134501A1 (fr) * 2005-06-15 2006-12-21 Orsan Medical Technologies Ltd. Appareil de surveillance de perfusion cerebrale
ES2276609A1 (es) * 2005-09-27 2007-06-16 Universidad Politecnica De Valencia Aparato y metodo de obtencion de informacion relativa a la hemodinamica cerebral.
WO2007036586A3 (fr) * 2005-09-27 2007-05-18 Univ Valencia Politecnica Appareil et procede destines a l'obtention d'informations relatives a l'hemodynamique cerebrale
WO2007036586A2 (fr) * 2005-09-27 2007-04-05 Universidad Politécnica De Valencia Appareil et procede destines a l'obtention d'informations relatives a l'hemodynamique cerebrale
EP1847215A1 (fr) * 2006-04-21 2007-10-24 Hitachi, Ltd. Système et procédé de mesure d'un corps vivant
EP2505137A1 (fr) 2006-12-14 2012-10-03 Orsan Medical Technologies Ltd. Moniteur intracrânien non invasif
EP3045109A1 (fr) 2006-12-14 2016-07-20 Orsan Medical Technologies Ltd. Moniteur intracranien non invasif
US9307918B2 (en) 2011-02-09 2016-04-12 Orsan Medical Technologies Ltd. Devices and methods for monitoring cerebral hemodynamic conditions
CN111528826A (zh) * 2020-05-25 2020-08-14 陈聪 一种获取脑阻抗血流图数据的方法

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