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WO2005013820A1 - Appareil et procede permettant de detecter directement l'activite electrique de tissus electriquement excitables dans des organismes biologiques - Google Patents

Appareil et procede permettant de detecter directement l'activite electrique de tissus electriquement excitables dans des organismes biologiques Download PDF

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Publication number
WO2005013820A1
WO2005013820A1 PCT/AU2004/001015 AU2004001015W WO2005013820A1 WO 2005013820 A1 WO2005013820 A1 WO 2005013820A1 AU 2004001015 W AU2004001015 W AU 2004001015W WO 2005013820 A1 WO2005013820 A1 WO 2005013820A1
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WIPO (PCT)
Prior art keywords
tissue
subject
detecting
magnetic resonance
resonance imaging
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Ceased
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PCT/AU2004/001015
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English (en)
Inventor
J. W. Prichard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Neurosciences Building
Brain Research Institute Foundation Pty Ltd
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Neurosciences Building
Brain Research Institute Foundation Pty Ltd
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Publication of WO2005013820A1 publication Critical patent/WO2005013820A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems

Definitions

  • This invention relates to apparatus and methods for the detection of the electrical activity of electrically excitable tissues in biological organisms. It has particular, although not exclusive application to the direct detection of the electrical activity of the of electrically excitable tissues in the bodies of mammals, such as humans.
  • One particular use to which the invention may be applied is in monitoring and analysing brain activity in humans and other mammals, and the background to the invention will therefore be described with particular reference to this application to which the invention is particularly suited.
  • EEG electroencephalogram
  • the development of the electroencephalogram (EEG) was a significant development in the study of brain function.
  • the EEG is a record of changes in the electrical potential difference of the brain of a subject between two points on the scalp.
  • the EEG is taken non-invasively, and allows an observer to follow electrical impulses across the surface of the brain and to observe changes over time.
  • an EEG can provide an indication of the subject's state of consciousness - namely, whether the subject "is asleep, awake or anaesthetised - because the characteristic patterns of current differ for each of these states.
  • a major drawback of the EEG however, is that the technique cannot show the structures or the anatomy of the brain. Nor can the EEG indicate which specific regions of the brain perform particular functions.
  • Magnetic resonance imaging is based on the principles of nuclear magnetic resonance (NMR), a spectroscopic technique used by scientists to obtain microscopic chemical and physical information about molecules. Magnetic resonance imaging is based on the absorption and emission of energy in the radio frequency range of the electromagnetic spectrum.
  • Cognitive neuroscience was revolutionised in the early 1990s by the introduction of the blood oxygenation level dependent (BOLD) method for identifying active neural regions through changes the activity causes in local deoxyhaemoglobin concentration (Ogawa, Lee et al. 1990; Kwong, Belliveau et al. 1992; Ogawa, Lee et al. 2000).
  • BOLD blood oxygenation level dependent
  • MRS magnetic resonance spectroscopy
  • the BOLD and MRS methods have elucidated, and continue to elucidate brain function, they measure events secondary to neural activity, rather than the activity itself.
  • the direct detection of neural activity would be desirable for both clinical practice, as well as for research purposes.
  • the techniques described earlier assist the clinician to identify that a particular pattern of neural activity exists. Since they measure secondary indicators of neural activity however, they do not assist the clinician to identify the location of a source of neural activity, with accuracy.
  • the present invention therefore aims to provide methods and apparatus for directly monitoring the electrical activity of electrically excitable tissues (such as the brain) of a subject, and thereby, to address one or more of the prior art problems previously discussed.
  • the invention generally provides a method of detecting the electrical activity of an electrically excitable tissue in a biological organism, the method comprising the step of directly detecting in the tissue, changes in the characteristics of an electrical indicator of the function of that tissue, over a period of time.
  • the biological organism is preferably a mammal.
  • the mammal may be a human or a non-human subject.
  • the electrically excitable tissue may be a neural tissue.
  • the neural tissue is the central nervous system of the subject, or a part of the central nervous system.
  • the electrically excitable tissue is the brain of the subject, or a part of the brain.
  • the electrically excitable tissue may be a peripheral tissue, such as a peripheral nerve or part of a peripheral nerve.
  • the electrically excitable tissue may be another body tissue or organ which has electrical activity.
  • the tissue may be the heart or a part of the heart of the subject.
  • the tissue might be the Purkinje system of the subject's heart, or a part of that system.
  • the tissue could be cardiac muscle tissue in the heart of the patient.
  • the tissue could be a muscle tissue.
  • the tissue could be either a skeletal muscle tissue, a smooth muscle tissue or, as mentioned in the preceding paragraph, a cardiac muscle tissue.
  • the means by which changes in that indicator are detected is by the use of nuclear magnetic resonance imaging.
  • the indicator used in the method is the spin-echo acquisition sequence.
  • the indicator is the gradient echo sequence.
  • a preferred means for this purpose is a magnetic resonance imaging (MRI) scanner.
  • the MRI scanner also comprises, or co-operates with means suitable for detecting the electrical activity in the specific tissue under study.
  • the output of readings taken by the MRI scanner would be displayed on a display means, such as a computer monitor or other visual monitor. The output would preferably also be recorded via recording means.
  • Such means could take the form of an electronic file stored on a computer hard disk or another electronic recording medium (such as a compact disk).
  • the output could be recorded on a video tape or cassette, or a Digital Versatile Disk (DVD), capable of being played back as and when desired.
  • DVD Digital Versatile Disk
  • the output of the readings could be displayed via a printing means, such as a computer printer.
  • the method might also be useful for the method to be performed in association or in conjunction with other measurements taken on the subject.
  • an electrencephalogram and/or other observations for example, readings on the subject's blood pressure or blood chemistry
  • the method would permit the simultaneous detection and recording of changes over time in the spin-echo acquisition sequence or gradient echo of the tissue under observation, as well as other observations on the subject.
  • the method might also be useful for the method to be performed in association with other one or more other procedures being carried out on the subject.
  • the method aspect of the invention could be used to detect the impact of specific stimuli on changes in the spin-echo acquisition sequence (or gradient echo or other indicator of function) in the tissue under study in the subject.
  • Such stimuli could take the form of:
  • Psychological stimuli such as stimuli designed to induce a specific psychological or emotional state in the subject
  • Physiological stimuli such as visual, aural, olfactory, proprioceptive, nociceptive, or temperature-related stimuli (eg, the application of heat or cold temperatures to the subject); or
  • Pharmacological stimuli such as those produced by applying one or more pharmacological agents to the subject.
  • the invention also generally provides an apparatus for detecting the function of an electrically excitable tissue in a biological organism, the apparatus comprising means for directly detecting in the tissue, changes in a direct indicator of electrical activity over a period of time.
  • the changes in the indicator over time are detected by using nuclear magnetic resonance imaging means.
  • the indicator used is the spin echo acquisition sequence or the gradient echo, as described earlier.
  • the means by which changes in that indicator are detected is by the use of nuclear magnetic resonance imaging.
  • a preferred means for this purpose is a magnetic resonance imaging (MRI) scanner, as described above.
  • the apparatus may have any one or more of the features described above in connection with the general disclosure of the method aspect of the invention, and the preferred features of the method.
  • the MRI scanner used in the invention has a magnetic field of between 0.5 tesla and 7.0 tesla.
  • a scanner with a magnetic field of 3.0 and 7.0 tesla is particularly preferred.
  • the MRI scanner also comprises, or co-operates with means suitable for detecting the electrical activity in the specific tissue under study.
  • means suitable for detecting the electrical activity in the specific tissue under study For example, in a subject undergoing a brain scan, the subject would be fitted with a head coil or like means for detecting brain electrical activity.
  • a birdcage radiofrequency head coil is particularly preferred.
  • the MRI scanner also comprises, or co-operates with means for analysing, recording and/or displaying readings detected in the subject by the scanner.
  • those means would be computerised means.
  • the scanner also comprises, or co-operates with computer hardware and/or software for analysing, recording and/or displaying readings detected in the subject by the scanner.
  • Those means could also analyse, record and detect other measurements taken in the subject (such as, for example, measurements of the subject's EEG, blood pressure and/or blood chemistry).
  • the MRI scanner and any associated means for analysing, recording and/or displaying readings detected in the subject by the scanner would be capable of taking readings observed over very short periods of time.
  • those means would be able to analyse events occurring over time periods as short as between 25 and 100 milliseconds.
  • the invention also provides a method of detecting or diagnosing the presence or status of a pathological condition in an electrically excitable tissue in a subject, the method comprising the step of detecting in the tissue, changes in the characteristics of a direct electrical indicator of the function of that tissue over a period of time, wherein a pattern of the changes detected correspond with the presence or status of a particular pathological condition.
  • the invention also provides an apparatus for detecting or diagnosing the presence or status of a pathological condition in an electrically excitable tissue in a subject, the apparatus comprising means for detecting in the tissue, changes in the characteristics of a direct electrical indicator of the function of that tissue over a period of time, wherein a pattern of the changes detected correspond with the presence or status of a particular pathological condition.
  • Pathological conditions for this purpose include:
  • Demyelinating diseases such as multiple sclerosis
  • the dementias (and including specifically, Alzheimer's disease);
  • Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis.
  • Fig 1 depicts a chart tracing which shows measurement of the blink reflexes and brain electrical responses in a subject to a visual stimulus, relative to the timing of events in the MR sequence;
  • Fig 2 depicts a brain scan in a human subject, showing (through the areas shown in white) the signal change in response to a visual stimulus - compared to a signal change without the visual stimulus, the change being overlaid on the anatomy of the brain structures.
  • the spin-echo sequence (Hahn, 1950) is useful in MRI and MRS because the second half of the sequence corrects the signal loss due to local magnetic field inhomogeneities during the first half (these are referred to as T2 * losses as they are known in the NMR literature.
  • the spin-echo sequence is useful in MRI and MRS because the second half of it corrects the signal loss due to local magnetic field inhomogeneities during the first half - T2 * losses, as they are known in the NMR literature.
  • the spin-echo procedure can only correct T2* losses than remain the same throughout the acquisition, typically tens of milliseconds. Transient inhomogeneities which are not uniform during the whole acquisition period cannot be corrected and must cause changes in the final signal obtained.
  • the exemplary practice of the invention discussed in this specification comprise studies performed in human subjects in a General ElectricTM LX 3 tesla magnetic resonance scanner equipped with a birdcage radiofrequency head coil.
  • a range of acquisition parameters was explored, including repetition times (TRs) of 1-20 sec and excitation times (TEs) of 25, 50, or 100 milliseconds.
  • TRs repetition times
  • TEs excitation times
  • Single 4 or 5 mm slices oriented to include various components of the visual system were used.
  • Acquisition was by a General Electric spin-echo echoplanar imaging (EPI) sequence which lasted 88 or 25 msec with matrices of 128 2 or 64 2 .
  • EPI General Electric spin-echo echoplanar imaging
  • Visual stimuli were flashes from an array of 1-6 bright white light emitting diodes positioned in various parts of the visual field in the initial experiments and visible to the subject in a right-angle mirror attached to the head coil. Later these were delivered through 1 mm, 10 m fibre optic cables to eliminate erratic unwanted flashes caused by gradient switching and pulses through the head coil.
  • stimuli were black-white checkerboard patterns which were flashed from a black background, reversed at 40 Hz, or moved laterally as independent right and left hemifields towards the centre of the visual field and back in eight 17 msec steps.
  • Figure 2 illustrates an experiment which minimised the likelihood of such artefacts.
  • the stimulus was movement of each hemifield of a checkerboard pattern toward the centre of the visual field in a single run of 210 scans at a repetition time (TR) of 1 second.
  • TR repetition time
  • the stationary checkerboard pattern was present during all rest periods, to hold total luminosity constant throughout the measurement.
  • the first 10 scans of the series were excluded to allow for T1 stabilisation, leaving 100 interleaved rest-motion pairs for analysis.
  • Figure 2 shows significant differences between stimulus and rest acquisitions in what appear to be several parts of the visual system, including the optic nerves, optic chiasm, lateral geniculate bodies, and optic radiations. Few significant differences are present elsewhere.
  • Motion and BOLD artefacts are not likely to have caused the signals evident in Figure 2.
  • Artefacts of eye movement due to blink or startle reflexes might mimic physiological activity in the retina and optic nerves, which move slightly with eye movement, but the signals in the immobile chiasm and more posterior structures cannot be explained that way.
  • Head movement artefact would be distributed around regions of high image contrast, not, as in the Figure, mostly along the visual pathways.
  • BOLD responses can hardly have occurred from 1 second to the next repeatedly throughout the experiment in such a way as to produce the observed patterns of activation. Any BOLD response cumulative throughout the run should have achieved an early plateau and been subtracted out by subtraction from stimulus acquisitions of stimulus-free ones obtained one second earlier.
  • the method we disclose in this specification brings NMR measurements of brain activity onto the same time scale as the activity itself. By stepping the stimulus along the acquisition sequence in millisecond increments, the method can make finely resolved temporal maps of brief responses which do not adapt..
  • the method should also work well in the somatosensory system, where one might hope to map activity from spinal nerve roots to cerebral cortex by appropriate coil placement. Scanner noise will make auditory responses more difficult to detect initially, but a number of solutions to the problem are possible. Motor activity which can be timed accurately should be detectable, as should peripheral nerve activity in the depths of the body where it is beyond reach of direct measurement by conventional electrophysiological methods.
  • a principal application of the present method will be investigation of normal neurophysiology in most parts of the nervous system. Being non-invasive, such measurements can be repeated as often as necessary within limits of personal tolerance in any subject with no contraindication to MRI examination. Detailed study of central conduction times, routes, and refractory periods will lead to new understanding of how the human brain works. Animal experimentation offers another approach to the same problem along different dimensions of normal activity. The invention can also be used in many other applications. One of the broadest is in neuropharmacology, as the method of the present invention can be used in the study of central drug' effects.
  • Alzheimer's disease and other degenerative diseases of the nervous system can be probed in a new way; subtle effects on brain physiology may well be detectable early in the course of such diseases and serve as surrogate markers of efficacy in trials of new treatments.

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  • Physics & Mathematics (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

L'invention concerne de manière générale un procédé permettant de détecter l'activité électrique d'un tissu électriquement excitable dans un organisme biologique. Le procédé comporte l'étape consistant à détecter directement dans le tissu, sur une certaine durée, des changements de caractéristiques d'un indicateur électrique de la fonction de ce tissu.
PCT/AU2004/001015 2003-08-11 2004-07-30 Appareil et procede permettant de detecter directement l'activite electrique de tissus electriquement excitables dans des organismes biologiques Ceased WO2005013820A1 (fr)

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Application Number Priority Date Filing Date Title
AU2003904264A AU2003904264A0 (en) 2003-08-11 2003-08-11 Apparatus and method for direct detection of electrical activity of electrically excitable tissues in biological organisms
AU2003904264 2003-08-11

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WO2005013820A1 true WO2005013820A1 (fr) 2005-02-17

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2278783A (en) * 1993-06-11 1994-12-14 Daniel Shellon Gluck Method of magnetically stimulating neural cells
GB2279755A (en) * 1990-11-12 1995-01-11 Instrumentarium Corp ESR enhanced brain activity MRI
US20010056231A1 (en) * 2000-03-13 2001-12-27 Andrzej Jesmanowicz High resolution MRI imaging of brain functions
US6430431B1 (en) * 1999-11-11 2002-08-06 Mcw Research Foundation, Inc. MRI system for measuring vision capabilities
US6535625B1 (en) * 1999-09-24 2003-03-18 Magnetus Llc Magneto-acoustic imaging
WO2003060462A2 (fr) * 2002-01-04 2003-07-24 Dune Medical Devices Ltd. Procede et systeme d'examen de tissus en fonction de leurs proprietes dielectriques
WO2003082405A1 (fr) * 2002-03-25 2003-10-09 Musc Foundation For Research Development Procedes et systemes utilisant la stimulation magnetiques transcranienne pour ameliorer la performance cognitive
WO2003092796A1 (fr) * 2002-05-03 2003-11-13 Musc Foundation For Research Development Procede, appareil et systeme permettant de determiner des effets et d'optimiser des parametres de stimulation du nerf vague
WO2004016167A1 (fr) * 2002-08-16 2004-02-26 The General Hospital Corporation Imagerie fonctionnelle non invasive de l'activation du systeme nerveux peripherique chez les humains et les animaux

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2279755A (en) * 1990-11-12 1995-01-11 Instrumentarium Corp ESR enhanced brain activity MRI
GB2278783A (en) * 1993-06-11 1994-12-14 Daniel Shellon Gluck Method of magnetically stimulating neural cells
US6535625B1 (en) * 1999-09-24 2003-03-18 Magnetus Llc Magneto-acoustic imaging
US6430431B1 (en) * 1999-11-11 2002-08-06 Mcw Research Foundation, Inc. MRI system for measuring vision capabilities
US20010056231A1 (en) * 2000-03-13 2001-12-27 Andrzej Jesmanowicz High resolution MRI imaging of brain functions
WO2003060462A2 (fr) * 2002-01-04 2003-07-24 Dune Medical Devices Ltd. Procede et systeme d'examen de tissus en fonction de leurs proprietes dielectriques
WO2003082405A1 (fr) * 2002-03-25 2003-10-09 Musc Foundation For Research Development Procedes et systemes utilisant la stimulation magnetiques transcranienne pour ameliorer la performance cognitive
WO2003092796A1 (fr) * 2002-05-03 2003-11-13 Musc Foundation For Research Development Procede, appareil et systeme permettant de determiner des effets et d'optimiser des parametres de stimulation du nerf vague
WO2004016167A1 (fr) * 2002-08-16 2004-02-26 The General Hospital Corporation Imagerie fonctionnelle non invasive de l'activation du systeme nerveux peripherique chez les humains et les animaux

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