• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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    • 专利摘要:
    Info-optical system for the monitoring of the movement of laboratory rodents. The present invention consists of an info-optical system designed to monitor the movements of laboratory rodents in experiments carried out in labyrinths such as open-field, t-maze and morris water maze and in training wheels of the voluntary or motorized type. The system locates, tracks and records the trajectory described over time by one or several infrared light sources fixed to the skin of the laboratory animal; this allows the determination of a set of variables such as: movement time, inaction time, frequency in different areas of the enclosure, shape of the path, length of the traveled path, instantaneous speed, average speed, maximum speed, acceleration and other magnitudes physical derivatives of these. Therefore, it allows an automatic monitoring of the movements of laboratory rodents, replacing the human operator. This system can be applied simultaneously in up to 6 instruments of training or experimentation of as many laboratory rodents. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2596879A1
    申请号:ES201600601
    申请日:2016-07-12
    公开日:2017-01-12
    发明作者:José Ángel TOVAL SÁNCHEZ；Aurelio Arenas Dalla-Vecchia；José Ambrosio TOVAL ÁLVAREZ；Daniel ESCRIBANO MARTÍNEZ；José Luis FERRÁN；Miroljub POPOVIC POPOVIC
    申请人:Universidad de Murcia；
    IPC主号:
    专利说明:

    DESCRIPTION

    Info-optical system for monitoring the movement of laboratory rodents.

    Object of the invention 5

    The present invention consists of an info-optical system designed to monitor the movements, mainly, of laboratory rodents (mice, rats, hamsters, guinea pigs, etc.). This information will allow analyzing their displacement or positioning that will in many cases lead to specific conclusions about their behavior in the course of physical training sessions, or during specific experiments carried out in enclosures specially designed for it. The system tracks and records the trajectory of the laboratory animal's movement by capturing and storing the successive Cartesian coordinates of its position obtained in time periods of 5 ms. The processing of the series of coordinates and the instants of 15 time relative to those positions, allows the determination of parameters of interest, such as: frequency of positions in different areas of the enclosure, total distance traveled, described angles, instantaneous speeds, speeds means, maximum speeds, idle time. and other parameters derived from these.
     twenty
    This system can be applied in different experimental designs that include behavioral tests of different nature carried out with laboratory rodents (specific labyrinths, T-Maze, Morris water Maze, Open-Field, etc); or to assess the behavior of rodents, mainly in terms of the spatial position during the execution of physical activity (voluntary wheels. motorized wheels. on treadmills or in water tanks).

    Technical sector

    This system is part of the electronic instrumentation sector applied to experimentation with laboratory rodents and the study of their behavior during their physical activity.

    Background of the Invention and prior art
     35
    Rodent model research is applied in many situations such as: biological process studies, development of pharmaceutical products, disease diagnosis and prevention, therapy evaluation, biological safety assessment tests, etc. Many of these experiments require the evaluation and analysis of the animal's behavior, particularly when they are used in investigations that have immediate or long-term repercussions on the functioning of the central nervous system. Aspects ranging from the study of the normal functioning of brain structures, to the evaluation of the effect of certain drugs or the consequence that a genetic modification could have (covering very wide fields ranging from comparative neurobiology, experimental embryology, neurology, psychology, pharmacology or physiology among others). To evaluate these behaviors, for example, in certain aspects related to memory and learning, it is usually important to know in detail the rodent's spatial position over time. For this, different instruments such as mazes are used for the study of memory and learning (Open-Field, Morris water Maze, T-Maze), or 50 instruments for the study of physical activity (treadmill, voluntary wheel or wheel
    motor) The latter case is effective in assessing the rodent's response to physical activity and generating models that predict what the most likely response in time to a physical activity protocol will be.

    For the evaluation and recording of rodent behavior in this type of 5 instruments, human observation has traditionally been used by manual on-site registration, or with the filming of videos for later analysis by a human operator. The automation of animal behavior monitoring in this type of experiments reduces possible biases due to human failures and facilitates the reproducibility of the experiments. 10

    Currently, there are some strategies that allow automatic monitoring. In the case of experiments in labyrinths, camera monitoring is one of the most powerful techniques in the field of animal behavior analysis, thanks to its accuracy and constant monitoring. It consists of the use of infrared or high resolution cameras, together with a motion capture software that processes the data obtained. One of the exponents of this technique is Ethovision XT10, developed by the American company Noldus, composed of a computer program and cameras that are purchased separately. Ethovision software is dedicated to the zenith analysis of rodents in labyrinths and has a high economic cost, even in its 20 basic version.

    However, the monitoring of rodent trainings on wheels, for example, is performed by lap count systems, which measures the number of turns performed by the rodent. This technique does not provide visual information, it only generates data of a total number of 25 turns and the frequency of the wheel, data that must be interpreted afterwards. This method does not allow knowing the rodent's spatial position preferences during the execution of the exercise, a key aspect in determining a possible long-term response. An example of this system is the one manufactured by the company Bioseb, BIO-ACTIVM-M, which measures the number of turns, the average angular speed, the maximum and minimum speed, among other variables. It can simultaneously monitor up to 64 wheels.

    On the other hand, regarding the trajectory tracking using infrared cameras, the use of the infrared camera of the Nintendo Wii 35 console control has been described in [ABELLÁN, F.J., ARENAS, A., NÚÑEZ, M.J. and VICTORIA, L., "The use of a Nintendo Wii relay control in physics experiments", Eur J Phys, 2013, Vol. 34, pages 1,277-1,286], which describes how to obtain the most important parameters in the study of different types of rectilinear, circular, parabolic movements, etc., of interest in physics laboratory experiments. 40

    Description of the invention

    The dynamic characterization of the physical activity developed by laboratory rodents can be carried out based on the measurement of the individual's position at specific moments of time, that is, in a synchronized manner, with a sampling rate high enough so that it can result a quasi continuous movement. In addition to obtaining detailed individual trajectory over time, from these two variables. position and time, by mathematical derivation, other variables of interest such as speed and acceleration are deduced. fifty
    The system presented here measures the position of one or more moving points, with a resolution of 0.1% of the full scale, within a range of variable dimensions and with a maximum sampling frequency of 200 Hz. It uses a Nintendo Wii console controller that contains a camera with a 940 nm infrared light filter and an embedded graphics processor, capable of locating one or more 5 bulbs (up to 4 bulbs) that emit infrared light, determines its geometric center and assigns a pair of Cartesian coordinates (xi, yi) to each of the geometric centers of the focus (s), all in a time of 5 ms. The field of view of the camera is a rectangular window of 1,024 pixels in the horizontal direction and 768 pixels in the vertical and the aperture angles of the lens are 35 ° and 25 ° respectively, so that at a greater distance from the camera , the greater the measures in units of length of the range of vision. Doing some trigonometric calculations, you can deduce the distance to which the objective of the camera must be placed to open the field to a given surface. For example, at a distance of about 1,500 mm the field of view of the camera is approximately 1,000 mm x 750 mm. That is to say. a focus of infrared light that moves 15 in a plane perpendicular to the axis of vision of the camera lens, located at 1,500 mm, can make a movement registered by the camera within a 1,000 mm x 750 mm rectangle, representing 1 mm Each pixel, approximately. Logically, in order to determine exactly the mm / pixel ratio, a previous calibration must be carried out that gives us the conversion of units in pixels to units in millimeters. twenty

    The communication that makes it possible to transfer data collected by the camera to a computer is the standard Bluetooth communication.

    To follow the movement of the laboratory animal during training phases, an element (or more than one) of light-reflecting material must be placed so that when it is illuminated by an infrared light source of 940 nm in length wave, can be "seen" by reflection by the camera of the control of the Wii and can follow the path of its movement.
     30
    In experiments with zenith observation, such as Open-Field and other labyrinths, there are observation and monitoring systems using infrared or high-speed cameras that send the images to a computer with a computer program that processes them. The technological advantage of the system of this invention is that a camera (that of the Wii console controller) is used that has an embedded graphics processor to calculate the position of the geometric center of the light object (in infrared) and sends only the coordinates of position from one to four points observed. which simplifies the process to be carried out later by the computer program and, therefore, the economic cost of the entire system, in fact the cost of a Wii remote is about € 30. This makes the system of this invention have a technological advantage to be used in monitoring with zenithal observation of the enclosure. In experiments with laboratory rodents in which voluntary or motorized wheels are used, currently, monitoring is not carried out with cameras but using lap-counting devices, which allow to extract limited information of the physical activity performed by the laboratory animal in said laboratory. device. The monitoring of exercises on 45 voluntary or motorized wheels by means of the system represented by this invention, presents a technological advantage by extracting a higher volume of information, which allows deeper analyzes of the physical activity and behavior of laboratory rodents. On the other hand, the predictive value of knowing the rodent's spatial position during the execution of the exercise program is fundamental.
    In monitoring systems with infrared cameras or high-speed cameras, such as the one described in the state of the art section, the recording of a single enclosure with a laboratory rodent is performed. In this invention, the computer program can be designed in a way that allows monitoring and data recording of up to 6 Wii controllers simultaneously in operation, over as many rodents 5 undergoing training, which constitutes a technological advantage.

    Description of the figures

    To complement the description of the invention and in order to help a better compression of its characteristics, according to a preferred example of practical implementation thereof, a set of drawings is attached as an integral part of the description, where, Illustrative and not limiting, the following is represented:

    FIG 1.- General view of the Open-Field enclosure monitored with the Wii remote. fifteen

    FIG 2.- General view of a training wheel monitored with the Wii remote.

    FIG 3.- View of a Wii remote with a LED bulb installed around its objective. twenty

    Reference List

    1. Wii console control.
     25
    2. Support.

    3. Objective

    4. Open Field Enclosure. 30

    5. Training wheel.

    6. LED spotlight.
     35
    7. Printed circuit board.

    8. Laboratory rodent.

    9. Piece of sheet of reflective material. 40

    Description of a preferred embodiment of the invention

    The operation of the info-optical system that was prepared for the monitoring of trajectories of a laboratory animal is illustrated in FIG 1, in zenith observation mode in an Open-Field exercise and in FIG 2 in horizontal observation mode In an exercise with training wheel. In both figures the control of the Wii 1 can be seen, held by a support 2 that keeps it fixed in space with its objective 3 oriented towards the Open-field enclosure 4, in one case, and towards the training wheel 5, in other. The Wii remote control camera, illustrated in FIG 3, can locate from 50 one to four infrared light emission sources that are in its field of
    view. A focus of infrared LEDs 6 mounted on a printed circuit board 7, which illuminate the field of view of the camera, was fixed on the camera lens. This printed circuit board was powered by a direct current source to polarize the LEDs and emit infrared light. The laboratory animal 8 has a sheet 9 of reflective material attached to its skin, in a place visible by the camera of the control 5 of the Wii. The Wii Remote sends, via Bluetooth communication, the position data to the computer with which it is tuned, at a sampling frequency set by a computer program installed in the computer. This frequency can be configured from the computer program between 0 Hz and 200 Hz maximum.
     10
    The computer receives, via Bluetooth wireless communication, the data of the Cartesian coordinates (X, Y) in pixels and based on a previously performed calibration, a computer program converts them into units of millimeters, records and processes the data of said coordinates and times and presents through physical tables and graphs the physical variables of interest: trajectories, frequencies of the positions in different areas of the enclosure, distance traveled, instantaneous speed, maximum speed, average speed, angular speed, linear and angular acceleration, etc. This allows qualitative and quantitative characterization of the movement and behavior of the laboratory animal under observation.
     twenty
    During the installation of the Wii remote in its support, a calibration process was carried out, with the help of the computer program, so that the information in pixels of the position coordinates is translated into units of millimeters.

    The sheet of reflective material that was attached to the skin of the laboratory animal reflects the infrared light 25 coming from the focus of LEDs located around the lens of the Wii remote's camera. The light is reflected by that sheet in the same direction with which it strikes it, allowing even a 50 ° inclination of the normal of said sheet with respect to the direction of the incident radiation, without ceasing to reflect the light in the same direction Where do you get it from. 30

    Since the field of vision is enlarged for planes further away from the objective of the Wii remote control camera, for larger surface scenarios, such as Open-Field with dimensions of 1 m x 1 m. The Wii remote control was placed about 170 cm from the reference plane of the Open-Field enclosure, while a size of the 35 sheet of the reflective material of about 3 cm2 was used. In the case of a smaller surface movement scenario, such as the training wheel of about 40 cm in diameter, the command was located about 70 cm away from the training wheel, while a sheet size of 1 cm2. Therefore, the size of said piece of reflective material can range between 1 cm 2 and 3 cm 2 of surface; However, the geometric shape of said sheet can be circular, oval, regular polygonal and even irregular with straight or curved sides, since the Pixar embedded graphics processor that has the Wii remote's camera calculates the geometric center of the reflective sheet and extract its Cartesian coordinates.
     Four. Five
    As the Wii console controller can simultaneously locate and capture the position coordinates of up to 4 points of infrared radiation, up to four pieces of aligned reflective sheet material were fixed on the animal's skin, which provided more data to the program to determine other parameters such as the direction in which it is oriented at all times, or the degree of stretching or contraction of the body of the laboratory animal.
    One way to achieve the reflection of infrared radiation similar to that provided by the sheets of reflective material is by using a liquid varnish reflecting the radiation. With this varnish a small surface region (similar in size to that of the reflective sheet) was painted on the skin of the laboratory rodent. Once dry this varnish has the desired light reflection properties. 5

    From the positions in units of mm and the times in units of ms, measured by the system, the computer program determines the trajectory, the frequencies of the different locations. resting times, movement times, instantaneous speed, maximum speed, average speed, etc. of the laboratory rodent. 10

    In this embodiment of the invention, the computer program was designed in such a way that it allowed the monitoring and recording of data of up to 6 Wii controls simultaneously in operation, on as many rodents undergoing training. fifteen
    权利要求:
    Claims (13)
    [1]

    1. Info-optical system for tracking trajectories of spotlights of infrared light inscribed in a flat area, comprising:
     5
    - a remote control of the Nintendo Wii console (1) containing an infrared vision camera that locates 1, 2, 3, or 4 foci of infrared light and that assigns the two-dimensional Cartesian coordinates of its geometric centers within a rectangular frame of reference;
     10
    - a support (2) that keeps the Wii console in a fixed position in the space whose objective is oriented towards the training or experimentation instrument for laboratory rodents;
    - a spotlight of infrared LEDs (6); fifteen
    - pieces of sheet of reflective material (9) of infrared light with adhesive;
    - a computer with a Bluetooth communication system;
     twenty
    - a computer program installed on the computer that receives the information of the Cartesian coordinates and time, sent by the Wii console controller, registers, processes the data of said coordinates and presents the statistical and physical variables through tables and graphs: frequency of the positions, distance traveled, instantaneous speed, maximum speed, average speed, movement times, 25 rest times, acceleration, discrimination of trajectory types, to qualitatively and quantitatively characterize the displacement of the infrared light emitting foci.

    [2]
    2. Info-optical system according to claim 1, wherein a piece of infrared radiation reflective material with adhesive is fixed on the back of the laboratory rodent body 30 (8) so as to reflect the light from the infrared light source surrounding the lens of the Wii remote's camera.

    [3]
    3. Info-optical system according to the preceding claims, wherein two, three or four pieces of reflective material are fixed along the back of the laboratory animal 35 defining its specific orientation and its degree of stretching or contraction of its body.

    [4]
    4. Info-optical system according to the preceding claims, wherein the Wii control captures the coordinates of the positions of the geometric centers of the pieces of reflective material at a configurable sampling frequency between 1 Hz and 200 Hz.

    [5]
    5. Info-optical system according to the preceding claims, wherein the computer program transforms the information received in pixels of the coordinates of the positions of the geometric centers of the pieces of reflective material, in units of millimeters. Four. Five

    [6]
    6. Info-optical system according to the preceding claims, wherein the infrared light source is formed by a series of LEDs mounted on a printed circuit board
    (7) and arranged around the lens (3) of the Wii remote's camera.
     fifty
    [7]
    7. Info-optical system according to the preceding claims, wherein the area of the sheet of reflective material can have a different size, between 1 cm2 and 3 cm2.

    [8]
    8. Info-optical system according to the preceding claims, wherein the shape of the sheet of reflective material can be circular, oval, regular polygonal or irregular polygonal, 5 straight or curved sides, or irregular contour.

    [9]
    9. Info-optical system according to claims 1 to 6, wherein the reflective element consists of a layer of light reflective varnish, applied on an area of the laboratory rodent's skin. 10

    [10]
    10. Use of the info-optical system according to claims 1 to 9, for zenithal observation, monitoring and analysis of laboratory rodent behavior, in Open Field (4), T-Maze and Morris water Maze environments, as well as in other specific mazes. fifteen

    [11]
    11. Use of the info-optical system according to claims 1 to 9, for the observation, monitoring and analysis of the behavior of laboratory rodents on voluntary wheels (5) and on motorized wheels.
     twenty
    [12]
    12. Use of the info-optical system according to claims 1 to 9, to know the spatial position of the rodent in the training wheel during the exercise.

    [13]
    13. Use of the info-optical system according to the preceding claims, for simultaneous monitoring with 6 Wii console controls with overhead observation or 6 25 training wheels with horizontal observation, using a single computer with a single computer program.
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    ES2596879B1|2017-10-19|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2013170129A1|2012-05-10|2013-11-14|President And Fellows Of Harvard College|A system and method for automatically discovering, characterizing, classifying and semi-automatically labeling animal behavior and quantitative phenotyping of behaviors in animals|
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