KR102174092B1 - Method for direct monitoring and spatial mapping of neuronal activity - Google Patents

Abstract

The present invention relates to a new method for direct monitoring and spatial mapping of a neural activity, and more specifically, to a magnetic resonance imaging method for monitoring a neural activity in vivo. The method comprises the steps of: presenting a stimulus which is repeated every period of a first time interval to an individual and receiving a plurality of magnetic resonance image signals according to the stimulus presentation; acquiring data on multiple types of K-space data at a plurality of viewpoints; reconstructing the multiple types of K-space data into multiple types of line data at the plurality of viewpoints; and generating an output image of the plurality of viewpoints based on the acquired multiple types of line data.

Description

Method for direct monitoring and spatial mapping of neuronal activity}

The present invention relates to a method for direct monitoring and spatial mapping of neural activity, and more specifically, to a magnetic resonance imaging method for monitoring neural activity in vivo.

Conventional magnetic resonance imaging techniques for direct monitoring and spatial mapping of neural activity were based on conventional commercialized magnetic resonance imaging techniques (eg, gradient echo or spin echo imaging techniques). As a representative brain function measurement method, blood oxygen saturation (BOLD) based functional magnetic resonance imaging (fMRI), electroencephalograph (EEG), and magnetoencephalography (MEG), etc. However, among these, it is non-invasive and has the highest spatial resolution of data, and the most widely used is BOLD-functional magnetic resonance imaging (BOLD-fMRI).

The BOLD-fMRI device can continuously measure changes in magnetic resonance (MR) signals, identify a region where the MR signal increases according to a certain external stimulus, and estimate the identified region as an activated brain region. . In other words, BOLD-fMRI can be said to be a method of measuring the functionally activated area and degree of the brain by repeatedly measuring the BOLD signal when the brain is active.

BOLD-fMRI is similar to the principle of Magnetic Resonance Imaging (MRI) to image the structure of the brain, the proton density or longitudinal relaxation time T1 of the tissue in vivo, transverse relaxation time. (transverse relaxation time) It reflects T2, but there is a difference in that the local blood flow in the active area of the brain increases and the oxygen concentration in the blood is additionally measured. Since BOLD-fMRI is based on these hemodynamic changes, despite the advantage of being able to provide information on a wide brain region with high spatial resolution, it provides only indirect information on neural activity and is very low in seconds compared to neural activity. It has a disadvantage in that it provides a time resolution of a degree.

Conventional magnetic resonance imaging techniques for direct monitoring of neural activity and spatial mapping are based on existing commercialized techniques, and failure cases have been reported. In the case of failure cases, conventional commercialized magnetic resonance imaging techniques have not provided sufficient signal sensitivity to directly measure nerve signals in vivo, and it has been reported that it is difficult to separate them from signals due to hemodynamic changes.

Even in the case of the prior art that reported successful cases that neural activity can be directly monitored and mapped, it has been found that there is no reproducibility or that signals other than neural activity signals are measured, so in the current academic world, direct monitoring of neural activity using magnetic resonance imaging And it is generally accepted that mapping is difficult.

In the end, the biggest problem of the prior art was that it was difficult to secure sufficient signal sensitivity to directly monitor and map neural activity.

NeuroImage, 2009.10.01.; 47(4): 1268-76 Magnetic Resonance in Medicine (MRM), 2007.02.; 57(2): 411-6. IEEE (Institute of Electrical and Electronics Engineers), 1994.02.; 41(1): 349-351.

The present invention was devised to solve the above problems, and the present inventors achieve high spatial resolution by using a line scan imaging technique having a short repetition time (TR) and a short echo time (TE). The present invention was completed to maximize the signal sensitivity to neuronal activity transmission by acquiring an image with ultra-high temporal resolution at the level of an action potential duration (≤~5 milliseconds) while maintaining. In addition, since the present invention uses a short TR and a short TE line scan imaging technique, it basically provides a T1-weighted image, and thus suppresses the BOLD signal that provides the T2-based image contrast as much as possible to the neural activity transmission signal. Is effectively separated from the BOLD signal.

Accordingly, an object of the present invention is to present a stimulus that is repeated every period of a first time interval to an individual, and receive a plurality of magnetic resonance image signals according to the stimulus presentation; Obtaining a plurality of line data in a K-space at a plurality of viewpoints by sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space; Reconstructing the plurality of K-space line data into a plurality of line data at a plurality of viewpoints; And generating output images of a plurality of viewpoints based on the obtained plurality of line data. A magnetic resonance imaging method for monitoring and spatial mapping of neural activity in a living body is provided.

Another object of the present invention is an image signal acquisition unit for presenting a stimulus repeated every period of a first time interval to an object and receiving a plurality of magnetic resonance image signals according to the stimulus presentation; And sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space to obtain line data on a plurality of K spaces at a plurality of viewpoints, and It provides a magnetic resonance imaging apparatus including; a control unit configured to reconstruct line data into a plurality of line data at a plurality of viewpoints and generate output images at a plurality of viewpoints based on the obtained plurality of line data.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems that are not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, the present invention provides a stimulus that is repeated every period of a first time interval to an individual, and receives a plurality of magnetic resonance image signals according to the stimulus presentation; Obtaining a plurality of line data in a K-space at a plurality of viewpoints by sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space; Reconstructing the plurality of K-space line data into a plurality of line data at a plurality of viewpoints; And generating an output image of a plurality of viewpoints based on the obtained plurality of line data. It provides a magnetic resonance imaging method for monitoring neural activity in vivo.

In one embodiment of the present invention, performing sampling of a magnetic resonance image signal in k space is a line scan imaging technique, a very short echo time imaging technique (UTE), a gradient magnetic field echo (GRE) imaging technique, and a fast spin echo (FSE). ) Technique, FLAIR (fluid attenuated inversion recovery) imaging technique, MS-EPI (multi-shot echo-planar imaging) technique, multiecho chemical shift imaging technique, magnetic resonance elastic imaging technique, magnetic resonance spectroscopy, 2D spoiled GE imaging technique, HASTE (Half-Fourier acquisition single-shot turbo spin-echo) imaging technique, and SS-EPI (Single-shot echo-planar imaging) technique. , But is not limited thereto.

In another embodiment of the present invention, the second time interval may be presented as an action potential duration interval of neural activity.

In another embodiment of the present invention, the first time interval may be presented as a time interval corresponding to a nerve signal transmission time on a specific nerve signal transmission path of a specific stimulus, and as a non-limiting example, the first time interval May be presented at intervals of 0.1 s to 10 s.

In another embodiment of the present invention, the second time interval may be a time resolution of an output image.

In another embodiment of the present invention, the magnetic resonance image signal may be generated by extracting a signal through Fourier analysis.

In another embodiment of the present invention, the output image may have a temporal resolution equal to the repetition time TR, and as a non-limiting example, may have a temporal resolution of 1 ms to 500 ms.

In another embodiment of the present invention, sampling the magnetic resonance image signal in K space may be sampling in a rectangular coordinate system or a spherical coordinate system.

In yet another embodiment of the present invention, the line data may be one in which hemodynamic changes and neural activity signals can be separated.

In another embodiment of the present invention, the output image may be edited by a method selected from the group consisting of image acceleration using multiple coils, 2D multi-slice images, 3D images, and compression sampling.

In still another embodiment of the present invention, the magnetic resonance imaging signal may be for functional magnetic resonance imaging (fMRI).

In addition, the present invention provides an image signal acquisition unit for presenting a stimulus repeated every period of a first time interval to an object and receiving a plurality of magnetic resonance image signals according to the stimulus presentation; And sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space to obtain line data on a plurality of K spaces at a plurality of viewpoints, and It provides a magnetic resonance imaging apparatus comprising; a control unit configured to reconstruct the line data into a plurality of line data at a plurality of viewpoints and generate output images at a plurality of viewpoints based on the obtained plurality of line data.

In one embodiment of the present invention, the control unit may further include reducing the image time by reconstructing the line data.

In another embodiment of the present invention, the control unit may use a method selected from the group consisting of image acceleration using multiple coils, 2D multi-slice images, 3D images, and compression sampling.

In another embodiment of the present invention, the device may be for monitoring neural activity in vivo.

According to the present invention, by obtaining a magnetic resonance image with a very high temporal resolution, an image capable of showing the transmission of neural signals in the entire neural network of the brain in time and space by directly detecting/mapping the transmission of neural signals according to stimulation is possible. Is expected.

In addition, according to the magnetic resonance imaging method of the present invention, it is expected that a new discovery of the mechanism of operation of the entire brain neural network, which has not been revealed by other techniques in the existing brain function imaging, is expected.

In addition, since the present invention uses a short TR and a short TE line scan imaging technique, it basically provides a T1-weighted image, thus suppressing the BOLD signal that provides the T2-based image contrast as much as possible to transmit neural activity. There is an excellent effect that the signal is effectively separated from the BOLD signal.

FIG. 1 is a road briefly showing a line scan imaging technique with a very high temporal resolution (≤ ~ 5 milliseconds) synchronized with a stimulus, and a line scan imaging technique combined with an ultrashort echo time (UTE) imaging technique. .
FIG. 2 is a schematic diagram showing a line scan imaging technique with very high temporal resolution (< ~5 milliseconds) synchronized with a stimulus, a diagram showing a line scan imaging technique combined with a gradient echo (GRE) imaging technique to be.
3 is a result of measuring the extracellular action potential of a squid giant axon in vitro according to electrical stimulation before magnetic resonance imaging experiments.
4 shows an image of nerve signal transmission in a squid giant axon according to electrical stimulation.
Figure 5 shows (a) a paradigm of stimulation presentation and data acquisition in a rat tail in vivo according to electrical stimulation, and (b) a rat tail setup for electrical stimulation presentation and magnetic resonance imaging experiments.
6 shows the nerve activity transmission image in the rat tail in vivo, the left column shows the nerve activity transmission in the 21st, 22nd, and 23rd image of the time series image, and the right column shows the pixels in the rat tail in the left column image It represents the horizontally added values.
7 shows an image of nerve activity in a rat head in vivo, and is a result of confirming nerve activation over time in the visual stimulus delivery route after presentation of the visual stimulus, particularly in Superior colliculus (SC) and Visual cortex (VC).
8 shows a single process for monitoring neural activity in vivo according to an embodiment of the present invention.
9 shows a single process for monitoring neural activity in vivo according to an embodiment of the present invention.
10 shows an example of a device for monitoring neural activity in a living body according to an embodiment of the present invention.
11 is a more detailed view of a control unit in the magnetic resonance imaging apparatus according to an embodiment of the present invention.

The terms used in the present invention have been selected from general terms that are currently widely used while considering functions in the present invention, but this may vary depending on the intention or precedent of a technician working in the field, the emergence of new technologies, and the like. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning of the terms will be described in detail in the description of the corresponding invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall contents of the present invention, not a simple name of the term.

When a part of the specification is said to "include" a certain component, it means that other components may be further included rather than excluding other components unless otherwise stated. In addition, terms such as "... unit" and "module" described in the specification mean units that process at least one function or operation, which may be implemented as hardware or software, or as a combination of hardware and software. .

Terms such as first and second may be used to describe various components, but the components should not be limited by the terms. These terms are used only for the purpose of distinguishing one component from another component. For example, without departing from the scope of the present invention, a first element may be referred to as a second element, and similarly, a second element may be referred to as a first element. The term and/or includes a combination of a plurality of related listed items or any of a plurality of related listed items.

When a certain embodiment can be implemented differently, certain steps may be performed differently from the described order. For example, two steps described in succession may be performed substantially simultaneously, or may be performed in an order opposite to the described order.

The present invention comprises the steps of: presenting a stimulus that is repeated every period of a first time interval to an individual, and receiving a plurality of magnetic resonance image signals according to the presentation of the stimulus; Obtaining a plurality of line data in a K-space at a plurality of viewpoints by sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space; Reconstructing the plurality of K-space line data into a plurality of line data at a plurality of viewpoints; And it provides a magnetic resonance imaging method for monitoring neural activity in a living body comprising the step of generating an output image of a plurality of viewpoints based on the obtained plurality of line data.

Throughout the specification, “Magnetic Resonance Imaging (MRI)” refers to an image of an object acquired using the principle of nuclear magnetic resonance.

Throughout the specification, the "magnetic resonance imaging method" may be a method of acquiring and processing a magnetic resonance image, but is not limited thereto. As a result, in order to obtain an MRI image, the magnetic resonance imaging method of the present invention may sample a magnetic resonance image signal in k space and form an output image based on the sampled line data, and the output image is It may be configured to display through a display means, but is not limited thereto.

Throughout the specification, “stimulation” may be an electrical stimulation, visual stimulation, auditory stimulation, etc., but is not limited thereto. The image pulse sequence can be programmed so that the time these stimuli are presented and the time to obtain one line from the magnetic resonance image are synchronized and another line is obtained when the next stimulus is presented.

For example, a line is scanned every 1 to 5 milliseconds (ms) after the stimulus enters to create one time series data set of 20 to 200, but these stimuli are totaled 64 to 256 times at 0.1 to 1 second (s) intervals. It may consist of a sequence that repeatedly obtains a 2D image data set having a number of pixels of 64 x 64 to 256 x 256.

Throughout the specification, “nerve” refers to an organ that a creature senses and copes with the surrounding environment and stimuli, and may be the spinal nerve or cranial nerve, and more specifically, the central nervous system, peripheral nervous system, autonomic nervous system, eyes, ears, nose , Or a tongue, but is not limited thereto.

Throughout the specification, "neural activity" refers to the activity of the nerve, and more specifically, refers to a signal of a neurotransmitter or an activity of a receptor involved in learning and memory.

Throughout the specification, “neural activity monitoring” may refer to direct detection, temporal and spatial mapping or imaging of the neural activity, more specifically measuring the degree of nerve activation, and temporal and spatial distribution of nerve activation It means mapping or imaging neurotransmitters and interpreting neuronal activities in terms of functions such as receptors involved in learning and memory. Here, spatial mapping or imaging means representing a region in which nerve activation appears as a spatial distribution on an image.

Throughout the specification, sampling the magnetic resonance image signal in k-space is a line scan imaging technique, a very short echo time imaging technique (UTE), a gradient magnetic field echo (GRE) imaging technique, a fast spin echo (FSE) technique, and a FLAIR. (fluid attenuated inversion recovery) imaging technique, multi-shot echo-planar imaging (MS-EPI) technique, multiecho chemical shift imaging technique, magnetic resonance elastic imaging technique, magnetic resonance spectroscopy, 2D spoiled GE imaging Technique, HASTE (Half-Fourier acquisition single-shot turbo spin-echo) imaging technique, and SS-EPI (Single-shot echo-planar imaging) technique, which may be performed by one or more selected methods, but is limited thereto. It is not.

The present invention may have a high spatial resolution equal to that of conventional commercial magnetic resonance imaging technologies. In other words, a plurality of magnetic resonance imaging signals mentioned in the first step of the magnetic resonance imaging method for monitoring neural activity in vivo are sampled by one line at a second time interval shorter than the first time interval in the K space. When acquiring the line data on the K space of a plurality of viewpoints, the number of samples of one line and the number of stimuli that are repeated every period of the first time interval are increased, thereby providing a high spatial resolution equal to that of conventional magnetic resonance imaging techniques. Can be made.

On the other hand, the present invention can provide a much higher temporal resolution compared to conventional commercialized magnetic resonance imaging techniques. The second time interval mentioned above substantially corresponds to the repetition time (TR) in the magnetic resonance image, and the second time interval corresponds to the time resolution of the present invention. Therefore, it is possible to reduce the second time interval time up to the repetition time (TR) allowed by the device in hardware and software, and thus increase the time resolution up to this time interval. In currently commercialized research and clinical magnetic resonance imaging equipment, this repetition time (TR) can be reduced from a few hundred microseconds (μs) to a few milliseconds (ms).

Throughout the specification, the term "pulse sequence" refers to a sequence of RF pulses and gradient pulses in a specific sequence that are repeatedly applied to obtain image data in an MRI system. The pulse sequence may include a time parameter of the RF pulse, for example, a repetition time (TR) and an echo time (Echo Time Echo, TE). Throughout the specification, a "gradient magnetic field pulse" means a signal applied to a gradient magnetic field coil installed to cause an intentional change in magnitude in a magnetic field in an imaging space in order to encode a position of a proton spindle.

Throughout the specification, “line data” refers to data obtained by sampling a line in a k-space of the resonance frequency signal of hydrogen atoms constituting a living body (human or subject).

Referring to FIG. 1, one line in the K-space corresponds to a magnetic resonance image signal acquired for one stimulus.

Referring to FIG. 1, a stimulus that is repeated every period of a first time interval is presented to a living body, and a received magnetic resonance image signal is acquired as line data in a K-space every second time interval shorter than the first time interval, The process of reconstructing the acquired data into a plurality of line data in a plurality of K-spaces is included. In the present invention, a short repetition time (TR) and a short echo time (Echo Time Echo, TE) are proposed as examples for neural activity monitoring, but the repetition time and the echo time are not limited in the range.

An object (subject, object) according to an embodiment of the present invention may include all or part of a body. If a part of the body with neural activity is included, the target is not limited, but for example, the individual may include organs such as the liver, heart, uterus, brain, breast, and abdomen, but is not limited thereto. A part of the body may or may not be separated from the individual, but is not limited thereto. Here, the individual may be a representative example of the human body, but is not limited thereto, and other animals (for example, monkeys, mice, cows, horses, pigs, dogs, sheep, goats, tigers, rabbits, snakes, chickens, pigs Or mammals such as cats; mollusks such as squid, octopus, octopus, octopus, shellfish, oysters, snails; annular animals such as earthworms, leeches, and lugworms; etc.) may also be applicable.

As an embodiment of the present invention, the second time interval may be presented as an action potential duration interval of neural activity, but is not limited thereto.

In another embodiment of the present invention, the first time interval may be 0.1 seconds (s) to 10 seconds (s), 0.5 s to 10 s, or 0.1 s to 5 s, but is limited thereto. It is not. In addition, more specifically, times between 0.1 second (s) and 1 second, i.e., 0.1 seconds and 0.15 seconds, 0.2 seconds, 0.25 seconds, 0.3 seconds, 0.35 seconds, 0.4 seconds, 0.45 seconds, 0.5 seconds, 0.55 seconds , 0.6 seconds, 0.65 seconds, 0.7 seconds, 0.75 seconds, 0.8 seconds, 0.85 seconds, 0.9 seconds, 0.95 seconds, 1 second. In addition, times of 1 second or more, 2 seconds to 5 seconds, and may be 10 seconds, but are not limited thereto.

In another embodiment of the present invention, the second time interval may be a time resolution of an output image, but is not limited thereto.

In another embodiment of the present invention, the magnetic resonance image signal may be generated by extracting a signal through Fourier analysis, but is not limited thereto.

In another embodiment of the present invention, the magnetic resonance image signal may have noise removed through Fourier analysis, but is not limited thereto.

In another embodiment of the present invention, the output image may have a second time interval or time resolution of 1 ms to 500 ms, but is not limited thereto. More specifically, the output image is 1 ms to 400 ms, 1 ms to 300 ms, 1 ms to 200 ms, 1 ms to 100 ms, 1 ms to 70 ms, 1 ms to 50 ms, 1 ms to 30 ms, 1 ms To 20 ms, 1 ms to 15 ms, 1 ms to 10 ms, 1 ms to 8 ms, 1 ms to 7 ms, 1 ms to 5 ms, 2 ms to 7 ms, 2 ms to 5 ms, 3 ms to 7 It may have a second time interval or time resolution of ms, 3 ms to 5 ms, or 4 ms to 5 ms, but is not limited thereto.

In addition, the output image may specifically have a time resolution of 1 millisecond (ms) to 30 milliseconds, but is not limited thereto. More specifically, the output image is 0.5 msec, 1 msec, 2 msec, 3 msec, 4 msec, 5 msec, 6 msec, 7 msec, 8 msec, 9 msec, 10 msec Second, 20 milliseconds, and may have a time resolution of 30 milliseconds, but is not limited thereto.

In still another embodiment of the present invention, the sampling of the MRI signal in K space may be to sample the MRI signal in a rectangular coordinate system or a rectangular coordinate system, but is not limited thereto.

In another embodiment of the present invention, the line data may be one in which hematologic changes and neural activity signals can be separated, but is not limited thereto.

In another embodiment of the present invention, the output image may be edited by a method selected from the group consisting of image acceleration using multiple coils, a two-dimensional multi-slice image, a three-dimensional image, and compression sampling, but is not limited thereto. .

In yet another embodiment of the present invention, the magnetic resonance imaging signal may be for functional magnetic resonance imaging (fMRI), but is not limited thereto.

In addition, the present invention provides an image signal acquisition unit for presenting a stimulus repeated every period of a first time interval to an object and receiving a plurality of magnetic resonance image signals according to the stimulus presentation; And sampling the plurality of magnetic resonance image signals one line at a second time interval shorter than the first time interval in K space to obtain line data on a plurality of K spaces at a plurality of viewpoints, and It provides a magnetic resonance imaging apparatus comprising; a control unit configured to reconstruct the line data into a plurality of line data at a plurality of viewpoints and generate output images at a plurality of viewpoints based on the obtained plurality of line data.

In relation to the apparatus according to an embodiment of the present invention, the contents of the above-described method may be applied. Accordingly, description of the same contents as those of the above-described method in relation to the apparatus is omitted.

10 shows an example of a magnetic resonance imaging apparatus 1200 according to an embodiment of the present invention.

According to another embodiment of the present invention, an apparatus 1200 for obtaining neural activity information in an object using a magnetic resonance imaging system includes an image signal acquisition unit 1210 for receiving a magnetic resonance image signal for the object, and The control unit 1220 may include a controller 1220 that samples the obtained signal as line data on the K-space, reconstructs the sampled line data into a plurality of line data on the K-space, and outputs the reconstructed line data as an image.

11 is a more detailed illustration of a control unit in the magnetic resonance imaging apparatus 1200 according to an embodiment of the present invention.

The control unit includes an image information acquisition unit 1310 that samples the received magnetic resonance image signal in the K-space, and a line data acquisition unit that reconstructs data sampled in the K-space into a plurality of line data in a plurality of K-spaces ( 1320), and an image output unit 1330 that outputs the reconstructed line data as an image.

The magnetic resonance imaging device according to an embodiment of the present invention may be for monitoring neuronal activity in a living body.

Meanwhile, the above-described embodiments of the present invention can be written as a program that can be executed in a computer, and can be implemented in a general-purpose digital computer that operates the program using a computer-readable recording medium.

Such computer-readable recording media include magnetic storage media (e.g., ROM, floppy disk, hard disk, etc.), optical reading media (e.g., CD-ROM, DVD, etc.), and carrier waves (e.g., Internet). It may include a storage medium such as transmission).

In one embodiment of the present invention, the control unit may further include reducing the image time by reconstructing the line data.

In another embodiment of the present invention, the control unit may use a method selected from the group consisting of image acceleration using multiple coils, 2D multi-slice images, 3D images, and compression sampling.

In the present invention, the “image signal acquisition unit” applies a magnetic field and high frequency to hydrogen atoms of a biological tissue of the subject, and acquires magnetic resonance image data from the subject in response thereto. That is, the image signal acquisition unit is a unit that acquires magnetic resonance image data, and is a device already known in the field of magnetic resonance imaging, such as a main magnetic field coil, a gradient coil, an RF coil, and a magnet room, and implemented with components. Since it may correspond to a device that is obvious to a person skilled in the art, a detailed description will be omitted.

In the present invention, the “control unit” arranges digital data in a k-space (for example, also referred to as a Fourier space or a frequency space) of a memory, and converts the data into a two-dimensional or three-dimensional Fourier transform. Can be reconstructed into image data.

In addition, the control unit can perform image data synthesis processing, difference calculation processing, and the like as necessary. The synthesis processing may include an addition processing for a pixel, a maximum intensity projection (MIP) processing, and the like. In addition, the controller may store not only the reconstructed image data but also the image data subjected to the synthesis process or the difference calculation process in a memory (not shown) or an external server.

The device according to the present invention includes a processor, a memory for storing and executing program data, a permanent storage such as a disk drive, a communication port for communicating with an external device, a user interface such as a touch panel, keys, and buttons. Devices, etc. Methods implemented as software modules or algorithms may be stored on a computer-readable recording medium as computer-readable codes or program instructions executable on the processor. Here, the computer-readable recording medium is a magnetic storage medium (e.g., readonly memory (ROM), random-access memory (RAM), floppy disk, hard disk, etc.) and optical reading medium (e.g.

These include CD-ROM and DVD (Digital Versatile Disc). The computer-readable recording medium is distributed over network-connected computer systems, so that computer-readable codes can be stored and executed in a distributed manner. The medium is readable by a computer, stored in memory, and executed on a processor.

This embodiment can be represented by functional block configurations and various processing steps. These functional blocks may be implemented with various numbers of hardware or/and software configurations that perform specific functions. For example, the embodiment is an integrated circuit configuration such as memory, processing, logic, and a look-up table, which can execute various functions by controlling one or more microprocessors or by other control devices. Can be hired. Similar to how components can be implemented with software programming or software elements, this embodiment includes various algorithms implemented with a combination of data structures, processes, routines or other programming components, including C, C++, Java ( Java), an assembler, or the like may be implemented in a programming or scripting language. Functional aspects can be implemented with an algorithm running on one or more processors. In addition, the present embodiment may employ a conventional technique for electronic environment setting, signal processing, and/or data processing. Terms such as “mechanism”, “element”, “means”, and “composition” can be used widely, and are not limited to mechanical and physical configurations. The term may include a meaning of a series of routines of software in connection with a processor or the like.

The specific implementations described in this specification are examples, and do not limit the technical scope in any way. For brevity of the specification, descriptions of conventional electronic configurations, control systems, software, and other functional aspects of the systems may be omitted. In addition, the connection or connection members of the lines between the components shown in the drawings exemplarily represent functional connections and/or physical or circuit connections. Connections, or circuit connections, may be represented.

Throughout the specification of the present invention, when a certain part "includes" a certain constituent element, it means that other constituent elements may be further included rather than excluding other constituent elements unless otherwise stated. The terms "about", "substantially", etc. of the degree used throughout the specification of the present invention are used at or close to the numerical value when manufacturing and material tolerances specific to the stated meaning are presented, and the present invention To aid in understanding of, accurate or absolute figures are used to prevent unreasonable use of the stated disclosure by unscrupulous infringers.

Throughout the specification of the present invention, the term "combination of these" included in the expression of the Makushi format refers to one or more mixtures or combinations selected from the group consisting of components described in the expression of the Makushi format, the It means to include one or more selected from the group consisting of components.

Hereinafter, a preferred embodiment is presented to aid the understanding of the present invention. However, the following examples are provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.

[ Example ]

Example 1. Ultra-high-resolution line scan-based imaging method ( Ultrashort Time-resolution Line-scan-based Imaging Method)

Increasing the temporal resolution to the level of the duration of the action potential (4-5 milliseconds) is expected to increase the possibility of effectively measuring the transient effect of the action potential. In the case of the stimulus presentation experiment design, it was expected that the neural signal sensitivity could be greatly improved as it was possible to obtain consistent coherence of neural signals generated in the same neural activity site.

Accordingly, if a line scan imaging technique that acquires one line of data for each temporal resolution is used, a temporal resolution at the level of an action potential can be implemented even with a magnetic resonance image (Fig. 1).

For that purpose, in the present invention, the line scanning method is combined with an ultra-short echo time (UTE) imaging technique (FIG. 1) and a gradient echo (GRE) imaging technique (FIG. 2). , The experiment was performed by increasing the time resolution corresponding to the repetition time (TR) to 4.5 milliseconds (ms).

Example 2. Data Processing and Analysis

In the case of the UTE imaging technique, after gridding that converts the old coordinate system data to the Cartesian coordinate system data, in the case of the GRE imaging technique, it directly uses Fast Fourier Transform (FFT), which was developed in-house MATLAB (ver.8.2. 0; R2013b) The image was reconstructed using the program. After filtering the time course data, a series of 2D spatial mappings of the response to action potentials or currents were obtained from time series images. A notch filter was applied to remove 60-Hz electrical noise, and a weak low-pass filter cut off at 80 Hz was applied to reduce noise.

Example 3. Experiment

For a preliminary experiment to confirm the effectiveness of the present invention, an ultra-high magnetic field animal magnetic resonance imaging device (9.4-T Bruker (BioSpec 94 /30, Ettlingen, Germany) scanner was used. In vitro) Squid Giant Axon ( giant axon), in vivo rat tail, and rat head.In the case of in vitro squid axon and in vivo rat tail, the action potentials generated after electrical stimulation were shown in the squid axon and rat tail. In the case of an experiment on a rat head in vivo, we tried to image the temporal relationship between nerve activation sites along the visual stimulation pathway after presenting visual stimulation. The purpose of this study was to confirm the neuronal activation response in the V1 region of (SC) and visual cortex (VC) and its temporal progenitor relationship.

Example 4. In vitro squid giant In the axon Direct imaging of neuronal activity at in vitro squid giant axon

By applying the present invention to the squid giant axon, the possibility of direct detection and mapping of neural activity was confirmed (FIGS. 3 and 4). Squid giant axis color extracted from live squid is placed in a cylindrical phantom containing a buffer solution, placed in a magnetic resonance imaging device in a direction perpendicular to the longitudinal axis of the main magnetic field, and then, using a line scan imaging technique combined with a two-dimensional UTE imaging technique. A single slice was taken with a coronal section. The scan parameters are as follows: TR / TE = 4.5 / 0.25 ms, temporal resolution = 4.5 ms, spatial resolution = 1.56 x 1.56 mm ² , slice thickness = 5 mm, number of radial views = 202. Signal leveling (signal) averaging) did not try. Before the magnetic resonance imaging experiment, the extracellular action potential was measured to confirm whether the squid giant axon is alive, and therefore, transmits the action potential well when the electrical signal is applied (FIG. 3).

During the transmission of the action potential according to the electrical stimulation in the squid giant axon, a signal change of about ~10% was confirmed in the image at the time when the action potential passed among the time series images with a time resolution of 4.5 milliseconds (FIG. 4).

Example 5. Direct imaging of neuronal activity at in vivo mouse tail

In addition, by applying the present invention to the rat tail in vivo, the possibility of direct detection and mapping of neural activity in the in vivo situation was confirmed (Fig. 4). After setting the rat tail in the same direction as the main magnetic field and setting the experiment to present electrical stimulation at the tip of the tail (Fig. 5), the thickness including the rat tail to confirm that neural activity is transmitted over time in a time series image Photographing was carried out by grabbing a coronal slice of. Line scan imaging technique combined with 2D GRE imaging technique was used. The scan parameters are as follows: TR / TE = 4.5 / 2 ms, temporal resolution = 4.5 ms, spatial resolution = 0.1 x 0.1 mm ² , slice thickness = 5 mm. Ten signals were equalized (signal averaging).

When the electrical stimulation was presented, the signal change seen as the transmission of neural activity on the rat tail was confirmed in the 21st, 22nd, and 23rd images of the 4.5 millisecond time-resolution time series images (FIG. 6).

Example 6. Direct imaging of neuronal activity in the in vivo rat head vivo mouse brain)

In addition, by applying the present invention to a rat head in vivo, it was investigated whether the present invention can operate as a brain function image through direct detection and mapping of neural activity. After presenting the visual stimulus, the temporal relationship between nerve activation sites was imaged along the visual stimulus path. Among the visual stimulation pathways, a single slice of the coronal section is captured so that the nerve activation response in the V1 region of the superior colliculus (SC) and the visual cortex (VC) can be checked at the same time, and the line combined with the 2D GRE imaging technique The scan imaging technique was applied. The scan parameters are as follows: TR / TE = 4.5 / 2 ms, temporal resolution = 4.5 ms, spatial resolution = 0.25 x 0.25 mm ² , slice thickness = 1 mm. Four signals were equalized (signal averaging).

Among the visual stimulation pathways, the neuronal activation reactions appearing in the V1 region of the superior colliculus (SC) and the visual cortex (VC) and their temporal relationship were confirmed by images (Fig. 7). The neuronal activation response in the SC area appeared approximately 30 milliseconds earlier than the neuroactive response in the V1 area, and the time series images were imaged with a clear temporal precedence relationship. With this high spatial and temporal resolution, the temporal relationship between neuronal activation regions in the brain was imaged and shown.

In summary, according to the method of the present invention, it was confirmed that the temporal precedence relationship between the neuronal activation regions of the brain can be clearly identified with high spatial and temporal resolution, and thus can be usefully used for acquisition and processing of magnetic resonance images.

The above description of the present invention is for illustrative purposes only, and those of ordinary skill in the technical field to which the present invention pertains will be able to understand that it is possible to easily transform it into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative and non-limiting in all respects.

Claims (15)

Presenting a stimulus that is repeated every period of a first time interval to an individual, and receiving a plurality of magnetic resonance image signals according to the presentation of the stimulus;
Sampling the plurality of magnetic resonance image signals by one line at a second time interval shorter than the first time interval in the K space to obtain a plurality of data on the K space at a plurality of viewpoints;
Reconstructing the plurality of K-space data into a plurality of line data at a plurality of viewpoints; And
Generating output images of a plurality of viewpoints based on the obtained plurality of line data; Magnetic resonance imaging method for monitoring neural activity in a living body comprising.
The method of claim 1,
Sampling a magnetic resonance image signal in k space is a line scan imaging technique, a very short echo time imaging technique (UTE), a gradient magnetic field echo (GRE) imaging technique, a fast spin echo (FSE) technique, and a FLAIR (fluid attenuated inversion) technique. recovery) imaging technique, MS-EPI (Multi-shot echo-planar imaging) technique, multiecho chemical shift imaging technique, magnetic resonance elastic imaging technique, magnetic resonance spectroscopy technique, 2D spoiled GE imaging technique, HASTE ( Half-Fourier acquisition single-shot turbo spin-echo) imaging technique and SS-EPI (Single-shot echo-planar imaging), characterized in that performed by one or more selected from the group consisting of a method, magnetic resonance imaging method.
The method of claim 1,
The second time interval is characterized in that presented as an action potential duration interval of neural activity, magnetic resonance imaging method.
The method of claim 1,
The first time interval is characterized in that presented at intervals of 0.1 s to 10 s, magnetic resonance imaging method.
The method of claim 1,
The second time interval is characterized in that the time resolution of the output image, magnetic resonance imaging method.
The method of claim 1,
The magnetic resonance imaging method, characterized in that generated by extracting the signal through Fourier analysis.
The method of claim 1,
The magnetic resonance imaging method, characterized in that the output image has a temporal resolution of 1 ms to 500 ms.
The method of claim 1,
Sampling the magnetic resonance image signal in k-space comprises sampling the magnetic resonance image signal in a rectangular coordinate system or a spherical coordinate system.
The method of claim 1,
The line data, magnetic resonance imaging method, characterized in that the hemodynamic change and neural activity signal can be separated.
The method of claim 1,
The output image is edited by a method selected from the group consisting of image acceleration using multiple coils, two-dimensional multi-slice images, three-dimensional images, and compression sampling.
The method of claim 1,
The magnetic resonance imaging method, characterized in that for functional magnetic resonance imaging (Functional Magnetic Resonance Imaging, fMRI).
An image signal acquisition unit for presenting a stimulus that is repeated every period of a first time interval to an object and receiving a plurality of magnetic resonance image signals according to the stimulus presentation; And
By sampling the plurality of magnetic resonance image signals one line at each second time interval shorter than the first time interval in k space to obtain a plurality of line data on k spaces at a plurality of viewpoints,
Reconstructing the plurality of k-space line data into a plurality of line data at a plurality of viewpoints,
A magnetic resonance imaging apparatus comprising: a control unit for generating an output image at a plurality of viewpoints based on the obtained plurality of line data.
The method of claim 12,
The control unit further comprises shortening the image time by reconstructing the line data, magnetic resonance imaging apparatus.
The method of claim 12,
The control unit uses a method selected from the group consisting of image acceleration using multiple coils, two-dimensional multi-slice images, three-dimensional images, and compression sampling.
The method of claim 12,
The device is a magnetic resonance imaging device, characterized in that for monitoring nerve activity in vivo.

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