Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1999-12-21
2001-10-02
Casler, Brian L. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C324S307000, C324S309000
Reexamination Certificate
active
06298258
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to a method for spatially resolved measurement of the electrical activity of nerve cells by means of magnetic resonance and a device for the implementation of the method.
2. Description of the Prior Art
Basically three methods are known for measuring the electric activity of living nerve cells.
Electric potentials are measured with the electroencephalogram (EEG). An extremely good time resolution is hereby possible. Attempts are made to achieve a spatial resolution with this method, but it is extremely difficult to determine the location of activity sources (foci) from the measured potentials, for example, at the scalp. A series of imponderable parameters seems to make an exact localization unpromising. The possibility of introducing needles into the brain for the localization is extremely limited and is associated with considerable unpleasantness and risks.
In magnetic encephalography (MEG), the magnetic fields that are triggered by neuronal functions are measured with highly sensitive magnetic field sensors (known as SQUIDs). For example, U.S. Pat. Nos. 5,392,210, 5,136,242 and 5,417,211 disclose such methods. A location determination is only incompletely possible here and a specific, extremely complex device is required. Therefore, this method has not yet gained prevalence.
A promising approach for the determination of nerve activities lies in the application of the magnetic resonance. This method is frequently designated as fMRI (functional magnetic resonance imaging). Brain activities can be displayed in local signal boosts of images that are acquired with T2-weighted sequences and T3-weighted sequences. In this technique, however, the signal change does not directly arise from the nerve activities, but arises from an activity-produced increase of the blood oxygen content. The currently applied methods of activity measuring by means of MR nevertheless offer advantages vis-a-vis the other above mentioned methods; in particular, a relatively precise localization of the activity is possible. A disadvantage, however, is that the primary effect, namely a current flow, or the magnetic field associated therewith, is not directly determined, but a secondary effect, namely the blood oxygenation that accompanies the nerve activity, is monitored. For example, one disadvantage is that a change in blood oxygenation follows the triggering neuronal event only with a delay.
The literature Bandettini et al., “Processing Strategies for Time-Course Data Sets in Functional MRI of the Human brain”, Magnetic Resonance in Medicine, 1993, volume 30, page 161-173 describes an fMRT method wherein, for improvement of the signal-to-noise ratio, a cross correlation is carried out between the stimulation function and the time curve of MR images that are acquired with a single-shot-EPI method.
The method known from German OS 195 29 639 for the time resolved and spatially resolved presentation of functional brain activities also uses a time cross correlation between a stimulation function with image information for improvement of the signal-to-noise ratio. The stimulation function is non-periodic and exhibits as few as possible secondary maximums in its auto-correlation function. Thus, periodic disturbances (for example heartbeats, respiration) can be separated from the activity signal.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a method and a device with which nerve activities can be tracked better than in the techniques described above.
The above object is achieved in accordance with the principles of the present invention in a method for spatially resolved measurement of electrical activity of nerve cells by means of magnetic resonance, and an apparatus for implementing the method, wherein a time series of sets of magnetic resonance signals is obtained, wherein the phase shifts of the MR signals are determined, and wherein phase shifts arising due to magnetic field changes caused by the electrical activity of nerve cells are identified by correlating the phase shifts of the MR signals with events which cause such electrical activity of nerve cells.
In contrast to conventional fMRI methods, the secondary effect of a signal boost due to an increased blood oxygenation is not determined in the inventive method and apparatus, but instead the phase shift of the MR signals induced by an activity-caused magnetic field change is determined. The magnetic field change, in turn, derives from the electric activity of living nerve cells. The magnetic field oscillations in the environment of the nerve cells are in the order of magnitude of 1 through 100 pT. Such magnetic field oscillations are too weak for a direct detection on the basis of the phase shift of the nuclear magnetic resonance signals. The phase shifts that arise from these magnetic field oscillations are dependent on the echo times. Given echo times of approximately 50 ms, the activity-produced phase shifts of the nuclear magnetic resonance signal lie in the range of 0.05 through 0.7 degrees. Phase shifts of less than 5 through 15 degrees, however, are submerged in the noise level that is usually present. Therefore, a useful signal is only received by acquiring during repeatedly occurring events that cause an electric activity, a series of MR signals and these signals are evaluated by a correlation analysis. The number of event-correlated MR signals necessary therefor can be 50 through approximately 10,000 depending on the intensity of the electric nerve activity.
Advantageously, the number of the events necessary for the correlation is produced by triggering the electric activity of nerve cells by external stimuli according to a stimulation function, and the thereby-caused phase shifts are determined by a time correlation with the stimulation function. Alternatively, a correlation between multiply successively occurring events and the measured phase shift of the nuclear magnetic resonance signals is also possible. For example, such events can be epileptic attacks. Then, an event-gating is used.
Advantageously, the signal-to-noise ratio can be determined by means of a time correlation of the phase shift of the nuclear magnetic resonance signals with a model over the time curve of the current through the nerve cells.
Further, an improvement of the signal-to-noise ratio is possible by a local correlation of the phase shift of the nuclear magnetic resonance signals with a model over the magnetic field curve of current dipoles of the electric activity of the nerve cells. The location of current dipoles that correspond to electric activities of nerve cells can also be determined on the basis of such a model.
REFERENCES:
patent: 4719425 (1988-01-01), Ettinger
patent: 5136242 (1992-08-01), Abraham-Fuchs
patent: 5392210 (1995-02-01), Scholz
patent: 5417211 (1995-05-01), Abraham-Fuchs et al.
patent: 5662112 (1997-09-01), Heid
“Processing Strategies for Time-Course Data Sets in Functional MRI of the Human Brain,” Bandettini et al., Magnetic Resonance in Medicine, vol. 30, 1993, pp. 161-173.
Heid Oliver
Mueller Edgar
Casler Brian L.
Schiff & Hardin & Waite
Siemens Aktiengesellschaft
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