JP2003079626A - Brain function analysis method and system based on ultrasonic doppler method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a brain function analysis method and system based on an ultrasonic Doppler method by which one can observe a relation between a sensory stimulus (input) or a behavior (output) and a local brain activity (internal state) and dynamic time changes of their interactions. SOLUTION: The skull is partially removed and the velocity of bloodstream in tiny arteries of the brain is measured from the surface of the dura mater with an ultrasonic probe 6. Doppler sound data are turned into a waveform with a time-frequency analyzer, and peak values in all phases of the waveforms are traced. A plurality of results of task trials is added, percent changes of peak values at rest and at work are computed, and on the basis of data obtained, percent changes of bloodstream are plotted in color on a tomogram, and the tomogram is three-dimensionally reconstructed, using computer graphics software to obtain a functional image of the brain.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a brain function analysis method applying the ultrasonic Doppler method and a brain function analysis system thereof.

[0002]

2. Description of the Related Art Methods for capturing blood flow and metabolism, which change according to brain function, as images have been studied, and several measurement methods have been developed and studied. In particular, fMRI (Functional Magnetic Resonance Imaging), P
ET (Positron Emission Tomography) [Reference 1: Med
Phys 1987 Nov; 14 (6): p. 903
913, Reference 2: Neurosci Lett 19
84, Jul 27; 48 (2): p. 115-12
0)]. These were able to find the place where metabolism increased due to activity in the brain.

[0003]

For the analysis of brain function, it is ideal to analyze the brain function as widely as possible and with high temporal and spatial resolution. This is because using higher animals makes it easier to give feedback to humans, but animals with higher and more complicated brains have larger individual differences in their brains, and comparisons between subjects lack rigor. There is a dilemma. Therefore, it is necessary to compare the subjects with each other from the overall positional relationship of the brain.

However, the methods such as fMRI and PET described above have the advantage that the whole brain can be observed, but the time resolution is low, and for this reason, only evaluations before and after performing a certain work can be performed. . Recently in fMRI,
Attempts have been made to improve the time resolution [Reference 3: J Comput Assist Tomo].
gr 2001 Jan; 25 (1): p. 113-1
20], with this method, the spatial resolution is significantly reduced. To date, there has been no brain function measurement system that has a spatial resolution in a unit of 1 mm and a temporal resolution in a unit of 0.1 seconds for an awake subject.

Furthermore, both methods have a long imaging time, and it remains a question whether or not the influence of body movement (movement of the body) can be completely eliminated in the functional analysis of the subject performing the exercise task. In addition, the system itself is very expensive, and the maintenance cost is high.

Therefore, for future leap in brain research,
A new analysis system that can observe a wide range and has sufficient spatial and temporal resolution has been demanded.

In view of the above situation, the present invention observes the relationship between sensory stimulus (input) or action (output) and local brain activity (internal state), and the dynamic temporal change of their interaction. It is an object of the present invention to provide a brain function analysis method and a brain function analysis system that apply the ultrasonic Doppler method.

[0008]

[Means for Solving the Problems] In order to achieve the above-mentioned object, the present invention provides [1] a brain function analysis method to which an ultrasonic Doppler method is applied, in which a skull is partially removed and a superficial surface of a dura mater is superposed. Measuring the blood flow velocity in the micro-arteries of the brain with an ultrasonic probe,
Doppler sound data is converted into a waveform using a time-frequency analyzer, and the peak value of each phase thus converted is traced.
The results of multiple trials were added together, the rate of change in peak value during calmness and activity was calculated, and based on the obtained data, the rate of blood flow change was color plotted on the tomographic image,
It is characterized in that the tomographic image is three-dimensionally reconstructed using computer graphic software to obtain a functional image of the brain.

[2] In a brain function analysis system to which the ultrasonic Doppler method is applied, an ultrasonic probe placed at a skull excision portion corresponding to the brain of the subject and a subject for restraining the subject at a predetermined position. A localization device, means for giving an instruction to the subject, input means for outputting a signal in response to the instruction, a task control device for giving an instruction to the subject and taking in a signal from the input means, It is characterized by comprising an ultrasonic device for taking in an output signal from the ultrasonic probe, and a brain function data analyzer for taking in an output signal from the ultrasonic device and a task event signal from the task control device.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

FIG. 1 is a schematic diagram of a brain function analysis system showing an embodiment of the present invention.

In this figure, 1 is a monkey as a subject, 2 is a localization device for restraining the monkey (subject) 1 at a predetermined position, and 3 is a display as means for giving an instruction to the subject 1. Panel 4 is an input device (key switch) for outputting a signal in response to the instruction, 5 is a control computer (control PC) for giving a task to the subject 1, and 6 is an ultrasonic probe. , 7 is an ultrasonic device, and 8 is a brain function data analyzing computer (analyzing PC) for taking in the output signal from the ultrasonic device 7 and the task event signal from the controlling PC 5.

The brain function data analysis PC 8 is shown in FIG.
As shown in FIG. 2A, a sound signal output from the ultrasonic device 7 is taken in, and as shown in FIG.
Frequency analysis is performed, the peak value of the phase waveform is traced as shown in FIG. 2C, and the results of a plurality of trials (here, 20 to 50 trials) are shown in FIG. 2D. Is added to calculate the rate of change in peak value during rest and during activity. A series of monkey button-pressing actions is called a trial.

The analysis of the brain function data will be described below with reference to FIG.
And, it will be described in detail with reference to FIG.

Three Japanese macaques (female, weighing 4.8 to 5.6 kg) were used in the experiment. The monkeys were trained to sit in a monkey chair and then trained on a full-scale motor task.

The exercise task used was the right hand with a delay period,
There were three types of button separation tasks for the left hand and both hands.

A display panel 3 is located 40 cm in front of the monkey 1, and a total of three LEDs, that is, two clue stimulating LEDs 3A and one action start stimulating LED 3B are arranged in an inverted triangle. The distance between each LED is 2.5 cm, and it is designed so that the monkey does not move its eyes during the assignment. When the left and right LEDs 3A are lit only on one side, it is a clue stimulus that pushes either the left or right key switch 4, and when both of the clue stimulus LEDs 3A are lit, it is a clue stimulus that pushes both key switches 4. . In order to limit the movement to only the distal upper limbs during the exercise task, a fixation device for fixing the shoulder, back, and upper arm and elbow was prepared and used on a monkey chair.

The key switch 4 has a stroke of 1.6 mm.
It was attached to the tip of the monkey fixing device on the monkey chair in parallel with the monkey's body axis with the push switch of.

Explaining the exercise task on the time axis, after the cue stimulus lights for 2 seconds, the LED lights up after a random delay period (see FIGS. 3 and 4, details will be described later).

When the monkey presses the correct button within 1 second after the action start stimulus lights up, fruit juice is given to the monkey as a reward. The left / right timing deviation when pressing the buttons with both hands is allowed within 200 ms. If the monkey presses a button before the action-initiating stimulus, if the monkey presses a button different from the one indicated, or if the monkey does not press any button, the monkey will hear a bell sound that informs them of the wrong answer. It was

The first head is to set the brain stereotaxic apparatus by judging that the left and right classifications are learned when the success rate of 90% or more is reached even if the trials are randomly presented in the three kinds of classifications. I had an operation.

For the second and third animals, surgery was performed before the success rate reached 90% in order to observe changes due to learning. An intramuscular injection of ketamine hydrochloride and xylazine followed by an intravenous injection of pentobarbital was performed for general anesthesia. The skull is exposed widely, the stainless steel screw is buried, it is used as an anchor, and the surface treatment is performed with 10% citric acid. 4-META
An adhesive resin of the system was used to increase adhesion to the bone and then completely covered with acrylic resin. Furthermore, two pipes for fixing the head were mounted parallel to the front and back at intervals of 10 cm so that the stereo fixed surface could be reproduced.

After the post-operative monkey was recovered, it was confirmed that the monkey performed a motor task without any problem, and a partial removal over the upper 1/3 of the skull (about 6 cm × 6 cm) was performed to obtain data by the ultrasonic Doppler method. , The upper 1/3 of the monkey skull). After the removal, a rectangular chamber was made of acrylic resin and Delrin resin in the same area. An analgesic for pain relief and an antibacterial agent for prevention of infection were administered.

Ultrasonic probe 6 by ultrasonic Doppler method
The data was collected by using a manipulator for a stereo device to manufacture a fixing attachment so that the stereo surface could be exposed. As a result, reproducibility was secured and it became possible to measure the same site over time and over time.

Further, in order to confirm that the obtained data is confined only to the upper extremity flexor-extensor group that presses the key switch 4, the surface electrodes are used during the exercise task and the left and right upper extremity distal flexor groups are used. Extensor group, upper limb proximal flexor group, extensor group, latissimus dorsi,
The serratus anterior muscle and the muscle groups around the spine were measured. The obtained electromyogram was added according to the event of the exercise task, and it was confirmed that there was no problem.

As the ultrasonic device 7, a LOGIQ 700 MR manufactured by GE medical was used. First, the chamber is filled with physiological saline, and the ultrasonic probe 6 attached to the manipulator is inserted into the chamber to obtain a frontal cross-sectional image. The cross-sectional image was made to show the same surface every time using the front edge of the chamber. In addition, the blood flow information obtained by the ultrasonic Doppler method changes the intensity obtained depending on the running direction of the blood vessel. Therefore, vertically or in the case of the supplementary motor area (SMA), the blood flow information of the hemisphere is collected. It was fixed by tilting 10 degrees to the opposite side.

Although the ultrasonic output from the probe was 13 MHz for the normal observation of total cutting, the observation at a high frequency increased the spatial resolution and the observation accuracy in a shallow place, but reached the deep portion. It has a difficult property. Since the cerebral cortex was observed this time, the highest frequency of the device was used.

The area from which data is to be collected is determined under the color flow display. The frequency from the ultrasonic probe 6 at this time is 7.5 MHz, and fr is used to increase the time resolution.
No average average was used. This operation was simple because it was possible to observe the microvessels entering the cortex from the surface of the brain on the device.

Data was collected in the power Doppler mode. In the LOGIQ 700 MR, two-dimensional array transmission is performed in order to improve the spatial resolution in the power Doppler mode. The frequency from the ultrasonic probe 6 at this time is fixed at 6.2 MHz. wall fille
r is 16 in vscale ratio 1/4 mode
Although Hz was used and Velocity scale was adjusted appropriately, 3 cm / s, which is generally the lowest, was used because the flow velocity value of minute blood vessels in the cortex is low.

Therefore, the LOGIQ which is the ultrasonic device 7 is used.
A sound signal emitted from 700 MR [see FIG. 2 (a)] was taken into the analysis PC 8 using an A / D board, subjected to JTFA analysis [see FIG. 2 (b)], and cut out at a threshold value at which a change becomes clear. The curve is the data for one implementation. The analyzed curve is data showing pulsatile flow velocity. Oxygen demand of the cerebral cortex is shown at the maximum value (Vmax) of one beat (do)
ppe J Neurosci methods 19
97 75 147-54 Neuroimage 1
998 7 4pt2 S448), the peak value of the obtained curve was traced on a program [see FIG. 2 (c)]. Furthermore, in order to further clarify the characteristics and reduce noise, analysis was performed with the same threshold value, and the traced curve was added according to the task event. Furthermore, in order to compare with the data from other regions, the rate of increase / decrease with respect to the average value was calculated at all points on the time axis, using 0.5 seconds before the instruction signal as a control period [Fig. See d)].

Using the brain function analysis system of the present invention, changes in blood flow were recorded from the cerebral cortex of the monkey during the performance of the exercise task. In other words, we train monkeys to perform a delayed two-handed push-button segregation task,
Changes in blood flow in the supplementary motor cortex, dorsal part of premotor cortex and ventral part of premotor cortex were analyzed by ultrasonic Doppler method.

FIG. 3 shows L (left) -R (right) -in each movement region by a brain function analysis system showing an embodiment of the present invention.
It is a figure which shows the increase amount (Vmax) of the blood flow velocity with respect to the control period at the time of performing both (left, right) in B (both) discrimination task, and FIG.
FIG. 3 (b) shows the primary somatosensory area, FIG. 3 (c) shows the supplementary motor area, FIG. 3 (d) shows the dorsal part of the premotor area, and FIG. 3 (e).
Shows the increase amount (Vmax) of the blood flow velocity on the ventral side of the pre-exercise field.

FIG. 4 shows L (left) -R (right) -in each movement region by the brain function analysis system showing the embodiment of the present invention.
It is a figure which shows the increase amount (Vmax) of the blood flow velocity with respect to the control period at the time of performing the same side (left) in B (both) discrimination task, FIG.4 (a) is the primary motor area, FIG.4 (b).
In the primary somatosensory area, in FIG. 4 (c) the supplementary motor area,
FIG. 4 (d) shows the dorsal part of the pre-motor area, and FIG. 4 (e) shows the increase amount of the blood flow velocity of the ventral side of the pre-motor field (Vma).
x) is shown.

(1) In the primary motor cortex, an increase in blood flow associated with exercise execution was observed bilaterally and bilaterally.

(2) In the supplementary motor cortex, a biphasic increase in blood flow associated with both cue stimulation and exercise execution was observed ipsilaterally, contralaterally, and bilaterally.

(3) In the premotor cortex, there was little change in blood flow in response to the task, and the increase in blood flow in the primary somatosensory cortex had a longer latency than that in the primary motor cortex.

(4) The increase in blood flow associated with the clue stimulus found in the early stage of learning in the supplementary motor area was attenuated when the learning was established.

(5) Even when the separation task with delay was changed to a simple task without delay in one day, the increase in blood flow associated with the cues stimulated in the supplementary motor cortex gradually diminished and disappeared. .

As is clear from these figures, according to the present invention, the relationship between the blood flow velocity from the cerebral cortex, the relationship between sensory stimulation (input) or behavior (output) and local brain activity (internal state), and those We were able to observe the dynamic temporal changes of the interactions of the.

The present invention is not limited to the above embodiments, and various modifications can be made within the scope of the present invention, and these modifications are not excluded from the scope of the present invention.

[0041]

As described in detail above, according to the present invention, the following effects can be achieved.

(A) The functional imaging of the brain can be performed by directly monitoring the cerebral blood flow by applying the ultrasonic Doppler method.

(B) By using an ultrasonic imaging apparatus having an ultrasonic Doppler function to directly monitor the change in cerebral blood flow velocity, a higher time resolution than that of the conventional fMRI method or PET method is obtained. It is possible to obtain a brain function analysis system not only having high spatial resolution but also excellent in terms of cost, operability, and versatility.

[Brief description of drawings]

FIG. 1 is a schematic diagram of a brain function analysis system showing an embodiment of the present invention.

FIG. 2 is a diagram showing a signal waveform of each part of the brain function analysis system showing the embodiment of the present invention.

FIG. 3 is an L (left) -R (right) -B (both) in each movement region by the brain function analysis system showing the embodiment of the present invention.
It is a figure which shows the increase amount (Vmax) of the blood flow velocity with respect to the control period at the time of performing both (left, right) in a discrimination task.

FIG. 4 is an L (left) -R (right) -B (both) in each movement region according to the brain function analysis system showing the embodiment of the present invention.
It is a figure which shows the increase amount (Vmax) of the blood flow velocity with respect to the control period at the time of performing the same side (left) in a discrimination task.

[Explanation of symbols]

1 Monkey as a subject 2 Localization device 3 display panel 4 Input device (key switch) 5 Control computer (control PC) 6 Ultrasonic probe 7 Ultrasonic device 8 Brain function data analysis computer (analysis PC)

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Hironobu Tokuno             4-13-57 East, Kunitachi, Tokyo (72) Inventor Masahiko Takada             2-31-16 Kitamachi, Kokubunji, Tokyo (72) Inventor Atsushi Nanbu             Maison Bamboo 2-9-23 Wisteria, Kokubunji, Tokyo             Of which 101 F-term (reference) 4C017 AA11 AB10 AC23                 4C301 CC01 DD01 DD02 EE11 JB23                       JB29 KK02 KK12 KK16 KK22                 4C601 DD03 DE01 EE09 JB34 JB35                       JB36 JB45 JC25 KK02 KK18                       KK19 KK21 KK23 KK24

Claims (2)

[Claims] 1. (a) The skull is partially removed, the blood flow velocity in the cerebral microarteries is measured from the dura surface with an ultrasonic probe, and (b) the Doppler sound data is used with a time-frequency analyzer. (C) Trace the peak value of each of the waveformd phases, (d) Add the results of multiple trials, and (e) Calculate the rate of change of the peak value at rest and during activity. , (F) Color plotting the rate of blood flow change on the tomographic image based on the obtained data, and (g) three-dimensionally reconstructing the tomographic image using computer graphic software to obtain a functional image of the brain. A method for analyzing brain function applying the ultrasonic Doppler method, which is characterized in that 2. An (a) ultrasonic probe arranged in a craniotomy portion corresponding to the brain of the subject, (b) a localization device for restraining the subject in a predetermined position, and (c) the above. Means for giving an instruction to the subject, (d) an input means for outputting a signal in response to the instruction, and (e) a task control device for issuing an instruction to the subject and taking in a signal from the input means,
(F) an ultrasonic device that captures the output signal from the ultrasonic probe; and (g) a brain function data analyzer that captures the output signal from the ultrasonic device and the task event signal from the task control device. A brain function analysis system applying the ultrasonic Doppler method, which is characterized by being provided.