WO1992012705A1 - Procedes et appareil de surveillance des fonctions cerebrales - Google Patents

Procedes et appareil de surveillance des fonctions cerebrales Download PDF

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Publication number
WO1992012705A1
WO1992012705A1 PCT/US1992/000464 US9200464W WO9212705A1 WO 1992012705 A1 WO1992012705 A1 WO 1992012705A1 US 9200464 W US9200464 W US 9200464W WO 9212705 A1 WO9212705 A1 WO 9212705A1
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WO
WIPO (PCT)
Prior art keywords
signals
blood flow
fluorometer
monitoring
tissue region
Prior art date
Application number
PCT/US1992/000464
Other languages
English (en)
Inventor
Abraham Mayevsky
Britton Chance
Original Assignee
Abraham Mayevsky
Britton Chance
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
Application filed by Abraham Mayevsky, Britton Chance filed Critical Abraham Mayevsky
Publication of WO1992012705A1 publication Critical patent/WO1992012705A1/fr

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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
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • 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
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14542—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring blood gases
    • 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, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14553—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
    • 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, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain

Definitions

  • the present invention relates to the monitoring of the body functions of a living subject and, more specifically relates to the intraoperative monitoring of brain functions.
  • Intraoperative monitoring of various brain functions during different surgical procedures would provide a significant contribution to the neurosurgeon as a routine diagnostic tool.
  • a standard technique of monitoring the brain has not been developed or adopted.
  • the present invention meets these objectives as well as the challenge of providing the answers to many questions regarding the underlying pathophysiology and treatment of stroke which do not appear to lie with continued attempts to model the human situation perfectly in animals, but rather with development of techniques such as those disclosed herein that enable the study of more basic metabolism, pathophysiology and anatomical imaging detail in living humans. See D.O. Wiebers, H.P. Adams and J.P. hisnant, "Animal models of stroke: Are they relevant to human disease?,” Stroke, 21, 1-3, 1990.
  • the present invention provides a multiprobe assembly comprising fiber optic probes and ion selective electrodes that, in particular combination, enable the assessment of relative cerebral blood flow, itochondrial redox state (NADH fluorescene) and ion homeostatis (K + , Ca * H + and Na + ) in real time, intraoperatively.
  • the present invention provides apparatus for collecting signals for intraoperatively determining the functional state of the tissue region of a living subject that comprise a flowmeter for measuring relative blood flow, a fluorometer for montioring NADH redox state, and a potassium ion specific electrode for determining the extracellular level of K + potassium ions.
  • the present invention is used to monitor the functional state of the brain that uses a laser doppler flowmeter and either a direct current or time-sharing fluorometer/reflectometer such as a phase modulated spectrophotometer.
  • the apparatus of the present invention may also include means for creating analog signals representative of relative blood flow, NADH redox state, and ion concentration levels.
  • additional ion specific electrodes are included which measure the extracellular levels of Ca 2+ calci.um i.ons and Na+ sodi.um i.ons, as well as other electrodes such as electrocortical electrodes which may be used with an EEG.
  • the above described apparatus are housed in a single housing to provide a multiprobe apparatus, which may be easily used intraoperatively without invasion of the brain tissue.
  • the present invention in addition to the multiprobe assembly described above, also discloses methods and apparatus whereby the analog signals collected by the multiprobe apparatus are converted to digital signals and analyzed by a multichannel analyzer for recording software to produce digital processed digital signals. These signals are preferably stored in a storage media and then may be retrieved and further processed by playback software to create display signals. Display signals may be displayed, produced as a hard copy, or transmitted to further processing software to make further determinations regarding the condition of the subject.
  • FIG. 1 pictorially represents the multiprobe apparatus of the present invention, partially in cross- section, configured for intra-operative monitoring of brain functions in real time.
  • FIG. 2 shows a cross-sectional plan view taken through line 2-2 of the combined light guide apparatus of the present invention for monitoring the CBF and NADH redox state and other parameters.
  • FIG. 3 is a functional block diagram of the data acquisition and signal processing system used in a preferred embodiment of the present invention.
  • FIG. 4 is a cross-sectional plan view of the distribution of fibers within a portion of the apparatus depicted in FIG. 2.
  • FIG. 5A is a plot of NADH state and hemoglobin saturation for an animal undergoing an episode of hypoxia.
  • FIG. 5B is a plot of relative cerebral blood flow and NADH redox state generated using the present invention that depicts the correlation between blood flow and NADH.
  • the present invention provides a multiprobe assembly capable of interoperative, real-time monitoring of cerebral blood flow, NADH redox state, and ion homeostasis activities within the brain.
  • a preferred embodiment of the multiprobe assembly is shown in FIG. 1 and generally designated 10.
  • the multiprobe assembly of the present invention will be described in a configuration used to monitor cerebral blood flow, NADH redox state and extracellular (K + , Ca 2+ , H + Na + and NA + ) ion concentrations within the brain, although the multiprobe assembly 10 could more generally be used to monitor other brain activities and may be simplified, as explained below.
  • like numerals represent like elements. Referring to FIG.
  • the multiprobe holder 12 which is preferably made of Delrin 12 or similar plastic material, contains a bundle of optical fibers 11, three ion specific electrodes 14, 16, 18, each combined with a surrounding DC steady potential electrode, electrocortical electrodes (shown in FIG. 2) , and a reference electrode 20.
  • the ion selective electrodes 14, 16, 18 are electrically connected to Ag/AgCl electrode holders 22 that are protected by a plexiglass sleeve 24.
  • the optical fiber bundle 11, also known as a light guide comprises two groups of fibers shown generally in FIG. 1 and explained in further detail below that are the laser Doppler fibers 26 used for flowmetry.
  • the second group of fibers 28 in the light guide 11 are used to monitor the NADH redox state.
  • the principle of NADH monitoring from the surface of the brain is that excitation light, preferably at a wavelength of 360 nm, is passed from the fluorometer 42, shown as a functional block in FIG. 1, to the brain 31. Emitted light at 450 nm together with the reflected light at the excitation wavelength is transferred back to the fluorometer 42.
  • the changes in the reflected light are correlated to changes in tissue blood volume and also serve for correction of hemodynamic artifacts appearing in the NADH measurement.
  • FIG. 2 Further details of the multiprobe assembly 10 are shown in FIG. 2. As shown, the ion selective electrodes 14, 16, 18 are preferably arrayed around the light guide 11, further details of which are explained below with reference to FIG. 4. Also disposed within the housing of the multiprobe assembly 10 are electrocortical electrodes 19 which are fed to an EEG amplifier 40, and a thermocouple electrode 21 for monitoring temperature. Adjacent the multiprobe assembly is the push-pull cannula 32 for monitoring KC1 concentration.
  • the light guide 11 depicted in FIG. 2 is itself comprised of several components. Referring now to FIG. 4, ten 200 ⁇ excitation fibers 66 and ten 200 ⁇ emission fibers 68, such as those manufactured by General Fiber, Inc.
  • the fibers 62, 64 used for the laser Doppler flowmetry are randomly mixed between and around the fibers 62, 64 used for the laser Doppler flowmetry and which comprise the bundle 26 discussed above.
  • the first group 26 are fluorometer emission and excitation fibers 66, 68 and the second group 26, comprised of fibers 62, 64 are used to measure cerebral blood flow in real-time using a laser Doppler flowmeter technique or other suitable analytical method.
  • one 50 ⁇ input fiber 62 and two lOO ⁇ output fibers 64 are preferably in a triangular arrangement with approximately 0.7 mm separation between each vertex of the triangle.
  • the laser Doppler flowmeter input fiber 62 and output fibers 64 are connected to the standard commercial plug of the laser Doppler flow meter such as that manufactured by TS, Inc. or Perimed, Inc., for example.
  • the electrodes 14, 16, 18 of the multiprobe assembly 10 are preferably held to the cannula using epoxy glue so that the multiprobe assembly 10 can be used during the awake state or to avoid artifacts in the operating room environment.
  • dental acrylic cement 30, or a similar material was used to noninvasively interface the multiprobe assembly 10 to the surface of the cortex 31 by cementing it to the skull.
  • the multiprobe assembly 10 can be removed without damage from the brain at the end of the measurements and repetitive applications can be performed in a short period of time with minimal technical support. Furthermore, such noninvasive surface contact with the tissue permits for monitoring of the human brain.
  • the multiprobe assembly 10 is most preferably located on the exposed cortex 31 using a micromanipulator.
  • an EEG amplifier 40 monitors various brain functions and a six channel electrometer 44 monitors the ion concentration changes.
  • Data acquisition may commence immediately after the multiprobe assembly 10 is located on the cortex 31.
  • the analog signals from the laser Doppler flowmeter 38, EEG amplifier 40, fluorometer 42, and electrometer 44 are digitized at the input of the acquisition set up 45.
  • the acquisition set up 45 comprises a data processor 46 (386 Dell processor) which includes an analog-to-digital converter which provides for up to 16 channels (DA7AQ ATC) .
  • the data processor 46 further includes other appropriate hardware, such as a multichannel analyzer and the hardware necessary to input digitized waveforms into the control and data acquisition system (CODAS) recording software 48.
  • a display 52 and storage device 54 which may include both hard disk and/or floppy disk storage, are also provided, along with an interfacing keyboard control 50 that is connected to the acquisition software 48.
  • the CODAS playback software 58 retrieves the recorded data from the storage device 54.
  • the data are then analyzed by further software 62 appropriately chosen for the required computation and the capabilities of the processors being used. The selection and use of such software 62 is well known to those skilled in the art.
  • An interactive keyboard control 50 is again provided.
  • the data may be displayed on the display 52, or printed out as a hard copy report using a printer 56.
  • the fluorometer 42 uses the concepts of phase modulated spectroscopy to determine the concentration of scattering constituents within the tissues. These systems use pulses of light, preferably of two wavelengths, which are time shared into the tissue. The migrating light is then collected and signals generated which permit concentration determinations to be made. Further details of such systems are known in the art and may also be found in the co-pending patent application referenced above, which is incorporated herein by reference.
  • the fluorometer 42 in a preferred embodiment can be calibrated as follows: the reflectance and fluorescence signals obtained from photomultipliers (RCA 93IB) are calibrated to a standard signal (0.5 V) by variation of photomultiplier dynode voltage obtained from the high voltage power supply. The fluorometer or the standard 0.5 gain is increased as required by a factor of two or four to give 50% or 25% of the full scale respectively. The changes in fluorescence and reflectance signals are calculated relative to the calibrated signals under normoxic conditions. This type of calibration is not absolute, but provides reliable and reproducible results from different subjects and between different fluorometers.
  • the multiprobe analyzer 10 may be constructed for use on humans. Due to the short time available for monitoring under the complex conditions of the operating room environment, this embodiment requires only three probes. In order to monitor the functional state of the human brain, it would be necessary to include at a minimum the laser Doppler flowmeter 38 discussed above to measure relative cerebral blood flow; the fluorometer/reflectometer system 42 to monitor the intramitochondrial NADH redox state and the potassium (K + ) ion specific electrode 14 to provide data on the extracellular level of K + ions.
  • the most crucial test of the correlation between the intramitochondrial NADH redox state and the signals to be obtained from the phase modulation spectrophotometer are in a hypoxia or oxygen lack where the inspired oxygen or the animal is reduced to the point where it can no longer maintain hemoglobin oxygenated nor NADH oxidize. This is depicted in the traces of FIG. 5A.
  • the abscissa is time and the ordinate is NADH fluoresence increase upward, and hemoglobin desaturation [using 816-754 nm pulses].
  • the third trace is the sum of the pathlength of the phase changes, which may be regarded as a blood volume signal.
  • the NADH returns to the initial baseline prior to hypoxia, and the hemoglobin trace swings to a much more oxygenated state than prior to hypoxia, termed "hyperemia," which is caused by the blood volume flowing through the opened capillaries of the brain being greatly increased, a typical response to the restoration of oxygen in tissue following a hypoxia.
  • hypoemia a much more oxygenated state than prior to hypoxia
  • FIG. 5B there is shown a graphic plot of the percent change in NADH vs. the percent change in relative cerebral blood flow under three different conditions.
  • the data represented in FIG. 5 were derived using a multiprobe assembly and related processing equipment as described above.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Optics & Photonics (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Physiology (AREA)
  • Neurology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

On décrit des procédés et un appareil servant à recueillir des signaux afin de déterminer de façon peropératoire l'état de fonctionnement d'une zone tissulaire, telle que le cerveau d'un patient vivant. De préférence, la présente invention se rapporte à un débitmètre (38) servant à mesurer le flux sanguin relatif, un fluorimètre (42) servant à surveiller l'état de redox de NADH, et une électrode (14) spécifique des ions potassium servant à déterminer le niveau extracellulaire d'ions potassium K+. En outre, selon certains modes de réalisation, des électrodes additionnelles spécifiques d'ions sont prévues pour surveiller le taux de sodium et de l'hydrogène de calcium. Ces électrodes, ainsi qu'un élément de guidage de lumière contenant des fibres (28) qui sont utilisées dans un débitmètre laser à effet doppler, et des fibres utilisées dans un fluorimètre tel qu'un spectrophotomètre à modulation de phase, sont de préférence placées dans un ensemble unique à sondes multiples qui peut être utilisé de manière peropératoire et avantageuse sur le patient sans invasion des tissus cérébraux. On décrit aussi des procédés et des appareils de traitement des signaux recueillis afin de les stocker et de les afficher.
PCT/US1992/000464 1991-01-22 1992-01-21 Procedes et appareil de surveillance des fonctions cerebrales WO1992012705A1 (fr)

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US64378291A 1991-01-22 1991-01-22
US643,782 1991-01-22

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5541081A (en) * 1994-03-22 1996-07-30 President And Fellows Of Harvard College Process for assessing oocyte and embryo quality
EP0799598A1 (fr) * 1996-04-02 1997-10-08 Barnikol, Wolfgang, Prof. Dr.Dr. Mesure de la pression partielle et de la conductibilité de l'oxygène dans les tissus vivants
US7006676B1 (en) 2000-01-21 2006-02-28 Medical Optical Imaging, Inc. Method and apparatus for detecting an abnormality within a host medium utilizing frequency-swept modulation diffusion tomography
EP1733683A1 (fr) * 2004-04-06 2006-12-20 National University Corporation Okayama University Appareil de contrôle de l'ischémie cérébrale
RU2746173C1 (ru) * 2020-03-04 2021-04-08 Федеральное государственное бюджетное военное образовательное учреждение высшего образования "Военно-медицинская академия имени С.М. Кирова" Министерства обороны Российской Федерации (ВМедА) Способ объективной интраоперационной оценки жизнеспособности кишки

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4450841A (en) * 1982-03-03 1984-05-29 Thomas Jefferson University Stroke treatment utilizing extravascular circulation of oxygenated synthetic nutrients to treat tissue hypoxic and ischemic disorders
US4796639A (en) * 1987-11-05 1989-01-10 Medical Graphics Corporation Pulmonary diagnostic system
US4945896A (en) * 1989-01-24 1990-08-07 Gade George F Surgical retractor assembly having tissue viability sensor embedded therein

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4450841A (en) * 1982-03-03 1984-05-29 Thomas Jefferson University Stroke treatment utilizing extravascular circulation of oxygenated synthetic nutrients to treat tissue hypoxic and ischemic disorders
US4796639A (en) * 1987-11-05 1989-01-10 Medical Graphics Corporation Pulmonary diagnostic system
US4945896A (en) * 1989-01-24 1990-08-07 Gade George F Surgical retractor assembly having tissue viability sensor embedded therein

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5541081A (en) * 1994-03-22 1996-07-30 President And Fellows Of Harvard College Process for assessing oocyte and embryo quality
EP0799598A1 (fr) * 1996-04-02 1997-10-08 Barnikol, Wolfgang, Prof. Dr.Dr. Mesure de la pression partielle et de la conductibilité de l'oxygène dans les tissus vivants
US7006676B1 (en) 2000-01-21 2006-02-28 Medical Optical Imaging, Inc. Method and apparatus for detecting an abnormality within a host medium utilizing frequency-swept modulation diffusion tomography
EP1733683A1 (fr) * 2004-04-06 2006-12-20 National University Corporation Okayama University Appareil de contrôle de l'ischémie cérébrale
EP1733683A4 (fr) * 2004-04-06 2009-04-22 Univ Okayama Nat Univ Corp Appareil de contrôle de l'ischémie cérébrale
US7558609B2 (en) 2004-04-06 2009-07-07 National University Corporation Okayama University Cerebral-ischemia supervisory monitor
RU2746173C1 (ru) * 2020-03-04 2021-04-08 Федеральное государственное бюджетное военное образовательное учреждение высшего образования "Военно-медицинская академия имени С.М. Кирова" Министерства обороны Российской Федерации (ВМедА) Способ объективной интраоперационной оценки жизнеспособности кишки

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