WO2014033588A1

WO2014033588A1 - Stimulation and response monitoring in functional magnetic resonance imaging

Info

Publication number: WO2014033588A1
Application number: PCT/IB2013/056757
Authority: WO
Inventors: Sirel KARAKAS; Hakki Muammer KARAKAS
Original assignee: Norometrika Medikal Tip Teknolojileri Saglik Yazilim Donanim Ve Danismanlik Sanayi Ve Ticaret Limited Sirketi
Priority date: 2012-09-03
Filing date: 2013-08-20
Publication date: 2014-03-06

Abstract

The present invention relates to medical devices and stimulation methods that are used in producing brain activations on the basis of which neuro-cognitive evaluations are made in functional magnetic resonance imaging. A brain stimulation method and system are provided for use in making neuro-cognitive evaluations in functional MRI, and for this, for producing activations using standard tasks under routine clinical conditions and for recording the behavioural responses and brain activations.

Description

STIMULATION AND RESPONSE MONITORING IN FUNCTIONAL MAGNETIC RESONANCE IMAGING

Field of the Invention

The present invention relates to medical devices and methods for the magnetic resonance imaging (MRI) that produces stimulation leading to brain activation on the basis of which neurocognitive assessments can be made for.

Background of the Invention

In the present day, there are stimulation methods for visual, auditory and electrical stimuli for stimulating the patient undergoing magnetic resonance imaging (MRI). By analyzing the activations produced in the brain in response to these stimuli, and the behavioral responses of the patient to them, neuro-cognitive evaluations and diagnosis is made.

The method that we developed includes various software and hardware for stimulating the patient, obtaining patient responses, storing and analyzing these responses and monitoring the brain activity in magnetic resonance imaging.

Devices and the software that are presently used for stimulating and recording brain activation in the MR environment have mainly been designed with research laboratories in mind. In these products, the various hardware parts are not included in an integrative fashion. These devices and software also have very complex controls, are not suitable for use in routine clinic conditions (hospital environment) and medical diagnosis, have high costs and are ergonomically insufficient. The United States patent document no. US2002103428, an application in the state of the art, discloses an invention comprising a logic unit that allows the simultaneous measurement of brain activities and user decisions (behaviors) and enables the manipulation of stimulus presentation through an integrated evaluation of information,

The United States patent document no. US2007299359, another application in the art, discloses a triggering device which simultaneously sends an auditory signal to the user and a triggering signal to the analysis device. The device is developed for the detection of brainstem disorders.

The United States patent document no. 2010194389, another application in the state of the art, discloses a method for presenting moving pictures to the user and, when a movement is made in response to these pictures, for simultaneously mapping the relevant muscular activity and brain activity. The method is developed for analyzing the control of the brain over muscular movements.

Summary of the Invention

The objective of the invention is to develop stimulation methods for neuro- cognitive investigations in functional MRI. The methods allow the observation of the brain activity which is produced by standard stimulation methods under the routine clinical conditions of magnetic resonance imaging.

Another objective of the invention is to provide an integrated system of devices for functional magnetic resonance imaging that is easy to use and does not include complex controls.

Detailed Description of the Invention The brain stimulation method for functional MRI developed to fulfill the objectives of the present invention is illustrated in the accompanying figures, in which: Figure 1 is a schematic view of the system.

Figure 2 is the side view of the response pad.

Figure 3 is the flow chart of the method.

The components shown in the figures are each given reference numerals follows:

Functional magnetic resonance imaging

Control unit

21. Touch screen

22. Animation database

23. Imaging database

24. Response database

MRI scanner

31. Rear projection stimulus screen

32. Mirror

33. Triggering unit

Image Presentation Unit

41. Projector

42. MR compatible monitor

Response pad

51. Protrusions, indentations and slants

52. Buttons

Carrying cart with wheels

61. First holder

62. Second holder

63. Uninterrupted power supply 100. Method

The inventive functional MRI system (1) essentially comprises of:

- at least one control unit (2) which is adapted for controlling initiation and change of visual, auditory and sensory-motor tasks that are used for stimulating the brain.

- at least one touch screen (21) on which stimulus animations are controlled, behavioral responses given to the stimuli and the test process are monitored and managed,

- one or more databases (22) (23) (24) in the control unit (2), wherein stimulus animations, MR images and behavioral responses given to the stimuli and are stored,

at least one MRI scanner (3) or electroencephalography device for performing brain mapping,

- at least one rear-projection stimulus screen (31) and head-coil attached mirror (32) or at least one MR compatible monitor (42) by which the patient, whose MR imaging is done, can see the stimulating animations,

- At least one triggering unit (33) adapted for starting the stimulus animations in the control unit (2) when it receives a start command from the MR scanner at the initiation of imaging and for ending the stimulus animations from the control unit when the unit receives a stop command from the MR scanner at the termination of imaging,

- at least one projector (41) which sends the stimulus animation images to the stimulus screen (31) or one or monitor (42),

- at least one response pad (5) on which there are a plurality of buttons (52) that the patient uses during MR imaging for giving the behavioral responses that are specified in the task animations,

- at least one carrying cart (6) on which there is at least one first holder (61) to which the control unit (2) is connected and at least one second holder (62) to which the projector (41) is connected and an uninterrupted power supply (63). In the inventive functional magnetic resonance imaging system (1), the patient whose neuro-cognitive assessment will be performed and the MRI scanner are in the MR room (the room where magnetic fields and the radio waves exist). The patient holds one response pad (5) with the right or left hand, or holds two response pads (5) with both the right and left hands. Patient looks at the stimulating screen (31) via a mirror (32) or watches the MR compatible monitor (42). The carrier cart (6) on which there is the control unit (2) and the projector (41) is located in the MRI control room that is separate from the MRI scanner room since metallic and electronic devices is not permissible in the MRI room. The connections between the response pads (5) in the MRI room and the control unit (2) are made using cables with magnetic shielding and/or fiber optic cables. The connection between the triggering unit (33) at the MRI scanner (3) and the control unit (2) is also made using cables with magnetic shielding and/or fiber optic cables.

In the preferred embodiment of the invention, the control unit (2) is a medical class touch screen POS (Point of Service) or POC (Point of Care) type computer. The user selects and starts the stimulus animation to be shown to the patient using the computer's touch screen (21). The stimulus animations are stored in the animation database (22). In the preferred embodiment of the invention, the control unit is an industrial class computer. The user selects and starts the stimulus animation to be shown to the patient on the medical class touch screen (21) of the industrial class computer. The stimulus animations are stored in the animation database (22). The triggering unit (33) sends a command to the control unit (2) to start animation when MR imaging starts. The triggering unit (33) sends a command to the control unit (2) to terminate the animation when MR imaging ends. MR imaging is performed during the interval between the start and end of the stimulus animation; it is thus performed simultaneously with stimulation. In another embodiment of the invention, it is possible not to use the triggering unit (33) and to start and/or end the animation independently of the MRI scanner using the buttons (22) on the touch screen (21) of the control unit (2). In another embodiment of the invention, it is possible for the control unit (2) to end the animation at the end of a predetermined time interval. The projector (41), which is placed on the carrying cart (6) and is connected to the control unit (2), projects the image of the animation to the rear projection screen (31) and from there on to a mirror that is attached to the head coil. The lens system (long throw lens) used in the projector (41) provides a net image at the distance between the control unit in the control room and the screen in the MRI scanner room. In another embodiment of the invention, an MR-compatible monitor (LCD or TFT or LED or OLED or plasma screen) (42) which is connected to the control unit (2), projects the image of the animation directly to the patient in the MRI scanner room. The control unit (2) and the projector (41) are connected to the carrying cart (6) with the first holder (61) and the second holder (62), respectively. The holders (61), (62) are connected to connection points (not shown on the figures) on the carrying cart (6) by means of connection units (i.e. screw, clips etc). Similarly, the holders (61), (62) are connected to connection points (not shown on the figures) on the control unit (2) and the projector (41) by means of connection units. The second holder (62) has a mechanism whereby the projector (41) is moved in the 3- dimensional space. Thus, an integrated system (1), whose component parts are compiled and wherein all pieces can be carried all at once, is provided. In the preferred embodiment of the inventive system (1), holders (61), (62) are removable. Drawers are provided on the carrying cart (6) and these are used to store the control unit (2) and the projector (41) when they are not in use. Stimulus animation is provided through various tasks that the patient is required to perform. The different stimulus animations in the tasks produce different activations in the patient's brain. These activations are detected using the images that are provided from the MRI scanner (3) and they are stored in the data base (22-24) by DICOM 3.0 or at a higher level image standard. In some of the animations, the tasks are performed by pushing buttons (52) that are provided on the response pad (5). The behavioral responses given by the patient by pushing buttons (52) are stored in the response database (24). The information stored in the response database (24) is then analyzed. The design of the response pad (5) incorporates some features. Response pad has a plurality of buttons (52); the handle fits the palm; the protrusions, indentations and slants (51) at the bottom and sides of the handle allows the 4 fingers (index- middle-ring-little fingers) grasp the handle whereby the sliding of the response pad is prevented. The behavioral responses are obtained using two symmetrically designed response pads (5), the one designed for the right-handers is slanted to the right and the one designed for left-handers is slanted to the left. These features lead to a response pad which is more ergonomic and easy-to-use compared to the previous ones in the art. In a preferred embodiment of the invention, EEG (electroencephalography) device is used instead of the MRI scanner (3).

In a preferred embodiment of the invention, animations sent to the patient over the projector (41) or the monitor (42) and the behavioral responses given by the patient are monitored on the touch screen (21) in real time. A method (100) enabling the production of activations in the brain through MR imaging, to record and store both these activations and the behavioral responses for later analysis is comprised of the following steps:

- teaching the patient the tasks that he/she is required to perform during the animations shown (101),

- placing the patient in the MRI scanner (3) (102),

- choosing, from the touch screen (21) the animations and sounds with which visual acuity of the patient, ability to distinguish colors and ability to hear sounds of different frequencies are tested (103),

- using the touch screen (21), adjusting the loudness of the sound to a level that the patient finds audible (104),

- using the touch screen (21), choosing from the animation data base the stimulus animation of predetermined duration that will be used for the patient (22) (105),

- upon the advent of MR imaging, the simultaneous initiation of the animations by a signal from the triggering unit (33), or the initiation of animations by pressing a button on the stimulus screen (106),

- sending the animation from the projector (41) to the mirror (32) over the stimulus screen (31) or sending the animation directly over the monitor (42) (107),

- throughout the animations, patient performs the tasks. For this, patient either responds behaviorally by using the response pads (5) or responds covertly (108),

- MRI scanner (3) performs brain imaging throughout the animations (109), - The behavioral responses that are made using the response pads (5) are stored in the response database (24). The brain activations that are produced during task performance where responding occurs through the response pads or responding occurs covertly are both stored in the imaging database (23) (1 10),

- when functional MRI ends, the triggering unit (33) ends the animation or animation is terminated with a button on the touch screen (21) or the animation spontaneously ends at the end of a predetermined time interval (H I),

- analyses of the behavioral responses and the brain activation images that have been stored in the relevant databases (22) (1 12).

In the brain stimulation method (100), the patient is taught the animations and the tasks that he has to make on practice trials using the touch screen (21) (101). After the practice trials, the patient is taken to the MRI scanner room (102) and placed in the MRI scanner (3).

From the touch screen (21) in the control room, the animations and sounds with which visual acuity of the patient, the ability to distinguish colors, and to hear sounds in different frequencies will be tested are chosen (103). Using the touch screen (21), the sound level is adjusted to a level that the patient can easily hear 104). The animation to be shown to the patient is chosen over the touch screen (21) in the control room (105). With the initiation of MR imaging, the triggering unit (33) sends a command to the control unit (2) to start the animation. By this way, functional MRI and animations start simultaneously (106). In another embodiment of the invention, animation is started manually upon the advent of MR imaging by using the button on the touch screen (21) (106).

The animation is sent by the projector (41) to the mirror (32) over the rear projection stimulus screen (31) (107). In another embodiment of the invention, the animation is sent to the patient directly over the monitor (42) (107). As the patient watches the animations over the mirror (32) or over the monitor (42), he/she responds as taught using the buttons on the response pad (52) or responds covertly without using the response pad.

Activations are produced in the brain as the patient performs the tasks that he/she has been taught (108). MRI scanner (3) performs imaging throughout the duration of the animations. Accordingly, imaging of behavioral responding and imaging of the activated brain is provided (109). Brain activity signals that are obtained through MR imaging and behavioral responses that are obtained from the response pads are stored (1 10) in databases (23-24). When functional MR imaging ends, the triggering unit (33) sends a command to the control unit (2) and the unit terminates the production of the animations. Or, the animation is manually terminated by means of a button on the touch screen (21) when functional MRI ends. Or the animation is spontaneously terminated at the end of a predetermined time period (111). Thus, MR imaging is performed simultaneously with stimulation animations. As the last step, data stored in the databases (23) (24) are analyzed in order to make neuro-cognitive assessments (1 12).

There are no stimulation tasks that enable the analysis of brain functionality in efficient scope during basic and advanced cognitive functions. So, for example before a brain surgery, the state of the basic and advanced cognitive functions of the brain cannot be determined comprehensively. Mental and emotional disorders in neuro-psychiatry patients; learning and memory disorders of students cannot be analyzed comprehensively and problem areas cannot be detected. The stimulation tasks in the Brain Mapping Battery's section on basic cognitive functions trigger visual perception, auditory perception, body perception and motor responding. The Battery's section on basic cognitive functions thus shows the functionality of the visual, auditory and sensory-motor areas of the brain. The stimulation tasks in the Battery's section on advanced cognitive functions trigger the functions of language, working memory, learning and conflict resolution. The Battery's section on the advanced cognitive functions thus shows the functionality of Broca's area, Wernicke's area, prefrontal cortex, anterior cingulate and orbitofrontal cortex.

In an example of the brain stimulation method (100) applied to make comprehensive brain mapping; the animation consists of a 6-second preparation section followed by 8 blocks, 4 of which are task and 4 of which are rest blocks. Each block resides in the stimulation screen (31) for 18 seconds. The animation starts with the task instruction "LOOK AT THE PICTURE". The 1 -second black screen is followed by the task block. In the task block, two kinds of whole-screen (31) achromatic checkerboards are shown in alternation. Animation starts with the checkerboard with the black center; this is followed by the checkerboard with the white center. Each checkerboard resides on the screen for 66.9 milliseconds. Total number of checkerboards is 270. The task is to look at the checkerboards as the black parts turn into white and vice versa (101). The task blocks are followed by rest blocks. Rest blocks consist of a white plus (+) sign on a black screen. The task block-rest block pairs are shown 4 times and visual animation ends with a screen showing the script "END".

There are no stimulation tasks that enable the analysis of brain functionality in efficient scope during attention and inhibition. Accordingly, the problems and disorders and the quality and quantity thereof in Attention Deficit Hyperactivity Disorder (ADHD) patients; the attention and self-control disorders in students cannot be comprehensively analyzed.

The stimulation tasks in the ADHD Battery trigger focused attention, selective attention and sustained attention. The battery's section on attention enables the scanning of the state of the prefrontal lobe and parietal lobe of the brain. Stimulation tasks in the battery's section on inhibition-control triggers the abilities of inhibition of a potential response, inhibition of an ongoing response and inhibiting of an automatic behavior. The battery's section on inhibition enables the scanning of the state of the prefrontal lobes and the anterior cingulate cortex. In one example of the brain stimulation method (100) applied for mapping brain activations during attention and inhibition-control; a 3-second black screen and ae 2-second screen with the script "STARTING" on it is followed by a 3-second black screen. The stimuli are green and red flying saucers. These appear on the stimulus screen (31) with inter- stimulus intervals of 1.5 seconds and each stimulus resides on the screen for 0.2 seconds. The tasks are arranged in 4 blocks. In each block, there are 20 stimuli, 16 of which are green and 4 of which are red flying saucers. Accordingly, the total of 4 task blocks are composed of 80 stimuli, 64 of which are green and 16 of which are red flying saucers. The patient is asked to press the button of the response pad (52) at the 9:00 o'clock position with the thumb when the image is a green flying saucer and not to press any button (52) when the image is a red flying saucer. The task ends with "END" and "WELL- DONE, SUCCESSFUL" script.

There is not a well-controlled method which enables the sorting out the effects of post- traumatic stress disorder (PTSD) in the brain in FMRI. The stimulation tasks in the battery require covertly uttering the color of the objects, uttering the color of words by suppressing the automatic response of reading, and uttering the color of the words on the incident causing stress. By comparing the brain activations that these animations produce, effects specific to PTSD are detected.

In an example of the brain stimulating method (100) used to analyze the posttraumatic stress disorder; the animation is composed of a preparation screen of 3 seconds white screen followed by a 2.65-second "SAY THE COLORS COVERTLY" instruction screen. This is followed by a 19-seconds white screen with a black plus (+) sign on it. The task block that follows is made up of an image that stays on the screen for 35 seconds. The images are discs of four different colors. Task blocks are followed by 25-second rest blocks. Rest blocks are composed of a white plus (+) sign on a black screen. Unlike the preceding ones, the last (4^th) rest block is 40 seconds long. The task is to specify the color of the discs (101). Yellow is specified by pressing the response pad button (52) at the 12:00 o'clock position with the thumb; red by pressing the button (52) at 3:00 o'clock position; blue by pressing the button (52) at the 6 o'clock position; and green by pressing the button (52) at the 9 o'clock position. With the inventive brain stimulation method (100) for functional magnetic resonance imaging (1), a system and a method that can be used under routine clinic conditions and applied by the MR technician is provided. The system and method is not only for laboratory research and does not include complex controls. Within the framework of the foregoing basic concepts, it is possible to develop a wide variety of embodiments of the inventive brain stimulation method (100) for functional magnetic resonance imaging (1). The invention cannot be limited to the examples described herein; it is essentially as defined in the claims.

Claims

A functional magnetic resonance imaging system (1) essentially comprising;

at least one MRI scanner (3) performing MR imaging,

at least one stimulus screen (31) by way of which the patient, whose MR imaging is done, can see the stimulating animations

at least one head-coil attached mirror (32) that the patient sees onto which animation images from the stimulus screen (31) are reflected,

at least one projector (41) which sends the stimulus animation images ultimately to the mirror (32),

at least one response pad (5) wherein there is a plurality of buttons (52) and wherein the patient uses the buttons (52) for giving the behavioral responses to the task animations during MR imaging,

at least one control unit (2) that is used in controlling the initiation of visual and auditory tasks and for changing between the tasks,

at least one touchscreen (2) where stimulus animations are controlled, the behavioral responses that are given to the stimuli and the testing process are monitored and managed

- at least one database (22), which is placed in the control unit (2), and wherein visual and/or audio stimulus animations, activation images and behavioral responses are stored,

at least one triggering unit (33) adapted to start the animations by sending a start command to the control unit (2) when functional MRI starts; and to terminate the animations by sending a terminate command to the control unit when MR imaging ends,

A functional MRI system (1) characterized by at least one carrying cart (6) with at least one first holder (61) to which the control unit (2) is connected and at least one second holder (62) to which the projector (41) is connected. A functional magnetic resonance imaging system (1) according to Claim 1, characterized in that the connection between control unit (2) and triggering unit (33) at the MRI scanner and the connection between the control unit (2) and the response pad (5) are made of cables with magnetic shielding or by fiber optic cables.

A functional magnetic resonance imaging system (1) according to any one of the preceding claims, characterized by a control unit (2) wherein there is a POS (Point of Service) or POC (Point of Care) type of computer (2), with a medical class touch screen; or control unit (2) wherein there is an industrial type computer.

A functional magnetic resonance imaging system (1) according to any one of the preceding claims characterized by a right hand response pad, the handle of which includes indentations, protrusions and slants (51) suitable for usage with the right-hand, is placed in the palm and is stabilized by the index-middle-ring-little fingers, has a plurality of embedded buttons that are placed according to positions on the clock-face (i.e. 03:00, 06:00, 09:00, 12:00 o'clock); a left-hand response pad, the handle of which includes indentations, protrusions and slants (51) suitable for usage with the left hand, is placed in the palm and is stabilized by the index-middle- ring-little fingers, and has a plurality of embedded buttons that are placed according to positions on the clock-face (i.e.03:00, 06:00, 09:00, 12:00 o'clock)

A functional magnetic resonance imaging system (1) according to any one of the preceding claims, characterized by a carrying cart (6) to which an uninterrupted power supply (63) is integrated.

A functional magnetic resonance imaging system (1) according to any one of the preceding claims, characterized by a the medical class carrying cart (6), on which there are drawers to hold the control unit (2) and the projector (41) when not in use.

7. An imaging system (1) according to any of the preceding claims, characterized by an EEG device instead of the MRI scanner (3).

8. A method (100), which enables the production of brain activations during MR imaging and the storage of these brain activations and the patient responses for ensuing analysis, comprising the steps of:

- placing the patient in the MRI scanner (3) (102),

- choosing, from the touch screen (21) the animations and sounds with which visual acuity of the patient, ability to distinguish colors, ability to hear sounds of different frequencies are tested (103),

- sending the animations from the projector (41) to the mirror (32) over the stimulus screen (31) or sending the animations directly over the monitor (42) (107),

- MRI scanner (3) performs brain imaging throughout the animations (109), - behavioral responses that are made using the response pads (5) are stored in the response database (24). The brain activations that are produced during task performance where responding occurs through the response pads or responding occurs covertly are both stored in the imaging database (23) (1 10),

- when functional MRI ends, the triggering unit (33) ends the animation or animation is terminated with a button on the touch screen (21) or the animation spontaneously ends at the end of a predetermined time interval

(H I),

9. A brain stimulation method (100) according to Claim 9, characterized in that an MR compatible LCD or TFT or LED or OLED or plasma monitor which is mounted on the MR head coil is used in the MRI scanner room in step 107.