Patent Description:
In neuroscience, a number of devices have been developed to better understand brain activity.

Usually, the developed device involves several imaging modalities allowing each to acquire a specific parameter of brain activity. Among the imaging modalities, it can be cited functional magnetic resonance imaging (also named after the acronym fMRI) related to the BOLD effect, the optical imaging (such as optical absorption imaging, acousto-optical imaging, photoacoustical imaging), functional ultrasound imaging (also named fUltrasound) and electroencephalogram.

Documents <CIT>, <CIT>, <CIT> and <CIT> illustrate that, in various field of medicine, systems have been developed to image an area. As a specific example, document <CIT> is relative to a system devoted to a patient's breast.

Nevertheless, these documents illustrate systems which are relative to area wherein the events are reproducible. These systems are thus not applicable for the brain because it is not anymore the case for the brain.

Indeed, the above-mentioned imaging modalities operate independently and cannot be achieved on the same animal at the same time to the same functional event. Therefore, in practice, the experiments on the "almost the same" functional event are repeated and then all parameters independently acquired are treated during a post-processing method. For example, it is difficult to achieve on the same animal an fMRI imaging, coupled with a photoacoustical imaging. But the knowledge of the parameters accessible to such imaging modalities at the same time is crucial to understanding specific diseases, such as epilepsy where knowledge of functional brain activity measured by fMRI coupled with blood oxygenation level measured by an optical imaging system is extremely interesting.

The invention aims at facilitating the imaging on the same subject.

To this end, the present specification describes a detecting apparatus according to claim <NUM>.

Thanks to the invention, it becomes possible to image several locations on the same subject in a very easy way.

Indeed, such detecting apparatus is reconfigurable, which enables to modify the position of the sensor without modifying the position of the position device.

In addition, such detecting apparatus can be used for different experiences.

Moreover, such detecting apparatus can be useful in the cases of biological phenomena difficult to reproduce.

Notably, when the detecting apparatus comprises several sensors, several imaging modalities operating independently can be achieved on the same animal at the same time to the same functional event.

According to further aspects of the invention which are advantageous but not compulsory, the detecting apparatus might incorporate one or several of the features of claims <NUM> to <NUM>, taken in any technically admissible combination.

The specification also relates to a kit according to claim <NUM>.

The invention will be better understood on the basis of the following description which is given in correspondence with the annexed figures and as an illustrative example, without restricting the object of the invention. In the annexed figures:.

A subject <NUM> and a detecting apparatus <NUM> are illustrated on <FIG>.

More generally, the subject <NUM> is an animal for which at least one specific area is to be analyzed.

The specific area to be analyzed depends, for instance, of the kind of biological problem that is to be studied.

As an illustration, when the biological problem is memory, the area is a specific area of the hippocampus.

For the remainder of the specification, for illustrative purpose only, it is considered that the mouse suffers from epilepsy and that the areas to be analyzed are areas of the brain.

For this, the subject <NUM> has a head <NUM>, the detecting apparatus <NUM> being maintained on the head of the subject <NUM>.

The detecting apparatus <NUM> is an apparatus adapted to detect at least one physical value in the areas of the brain of the subject <NUM>.

The detecting apparatus <NUM> comprises a positioning device <NUM>, three sensors <NUM>, <NUM>, <NUM> and three spacers <NUM>, <NUM>, <NUM>.

The positioning device <NUM> illustrated in the example of <FIG> is a frame with a periphery <NUM> and intersecting bars <NUM>.

According to the example illustrated, the frame has a polygonal shape delimited by sides.

As an example, the polygonal shape is a square. Each side has the same length.

For an animal considered as small, such as a rat or a mouse, the length of a side is equal to the length of the brain of the animal. For instance, the length is <NUM> centimeter when the subject <NUM> is a mouse or the length is <NUM> centimeters when the subject <NUM> is a rat.

For an animal considered as big, such as a human, the length of a side is equal to a portion of the length of the brain of the animal. For instance, the length of the side is inferior to <NUM> centimeters.

More generally, the length of a side is equal to the minimum of the length of the brain of the animal and <NUM> centimeters.

For the specific case of <FIG>, each side has a length inferior or equal to <NUM> centimeters (cm).

The intersecting bars <NUM> constitute a grid.

The number of bars <NUM> is superior or equal to <NUM>.

In the specific example of <FIG>, ten horizontal bars <NUM> and ten vertical bars <NUM> are illustrated.

Accordingly, ten rows and ten columns can be defined with the periphery <NUM>.

In the remainder of the specification, the rows are labeled L with a number so that each row is labeled L1, L2, L3, L4, L5, L6, L7, L8, L9 or L10.

Similarly, in the remainder of the specification, the columns are labeled C with a number so that each column is labeled C1, C2, C3, C4, C5, C6, C7, C8, C9 or C10.

In addition, the words "up" and "down" on the one hand and "left" and "right" on the other hand are defined with reference respectively to the rows L1, L2, L3, L4, L5, L6, L7, L8, L9, L10 and to the columns C1, C2, C3, C4, C5, C6, C7, C8, C9, C10.

It will be consider that the less high the number associated to the row L1, L2, L3, L4, L5, L6, L7, L8, L9, L10 is the upper the row L1, L2, L3, L4, L5, L6, L7, L8, L9, L10 is. In other words, the first row L1 is above the second row L2 while the second row L2 is below the first row L1. Similarly, the first column C1 is on the left of the second column C2 while the second column C2 is on the right of the first column C1.

The intersecting bars <NUM> are delimitating compartments <NUM> which are defined for the positioning device <NUM>.

In the illustrated example, the positioning device defines a number of compartments <NUM> which is equal to <NUM>.

More generally, the positioning device <NUM> defines a number of compartments <NUM> which is superior or equal to <NUM>.

Each compartment <NUM> is adapted to hold a sensor.

Each compartment <NUM> is located at a predetermined location.

In the illustrated example, the predetermined locations are defined with reference to the periphery <NUM>.

For instance, each compartment <NUM> can be linked in a one-to-one manner to two coordinates: one row coordinate and one column coordinate. As an example, the compartment <NUM> belonging to the first row L1 and the first column C1 is a neighbor for the compartment <NUM> belonging to the first row L1 and the second column C2, the compartment <NUM> belonging to the second row L2 and the first column C1 and the compartment <NUM> belonging to the second row L2 and the second column C2.

In such specific case, the compartments <NUM> are arranged in a lattice. Such lattice is a regular lattice.

In addition, the spatial distance between two adjacent predetermined locations is inferior or equal to <NUM>.

Preferably, the spatial distance between two adjacent predetermined locations is inferior or equal to <NUM>.

For instance, for each compartment <NUM>, a center is defined. The predetermined location of a compartment <NUM> then corresponds to the center of the considered compartment <NUM>. In such context, the spatial distance between two predetermined locations is defined as the distance between the corresponding centers.

Furthermore, the positioning device <NUM> comprises a holder.

The positioning device is adapted to be maintained on the head <NUM> of the subject <NUM> using the holder.

This means that the holder is adapted to be fixed on the skull of the subject <NUM>.

The first sensor <NUM> is an ultrasound transducer adapted to produce ultrasound waves.

According to a specific example, the first sensor <NUM> is a high frequency ultrasound transducer. In such case, the first sensor <NUM> is a linear array adapted to operate at a frequency around <NUM> (MegaHertz).

The first sensor <NUM> is used mainly to detect cerebral blood volume and flow through Doppler sequences or contrast agents.

The first sensor <NUM> is located on the second column C2 and on the ninth row L9.

More precisely, the first sensor <NUM> is located on the upper part on the right of the compartment <NUM> belonging to the second column C2 and the ninth row L9.

The second sensor <NUM> is an accelerometer.

An accelerometer is adapted to measure proper acceleration of the animal. The accelerometer can be used to detect the state of the animal. The state of the animal is, for instance sleeping, running or eating. The knowledge of such state is, for example, useful for behavorial studies.

The second sensor <NUM> is located on the second column C2 and on the sixth row L6.

More precisely, the second sensor <NUM> is located on the right of the compartment <NUM> belonging to the second column C2 and the sixth row L6.

The third sensor <NUM> is adapted to measure electrical signals.

For instance, the third sensor <NUM> is a voltmeter.

According to other embodiments, the third sensor <NUM> is a surface electrode, an implanted electrode or an array of such electrodes.

The third sensor <NUM> is located on the second column C2 and on the third row L3.

More precisely, the third sensor <NUM> is located on the upper part on the right of the compartment <NUM> belonging to the second column C2 and the third row L3.

Each spacer <NUM>, <NUM>, <NUM> is removable.

By "removable", it is meant that each spacer <NUM>, <NUM>, <NUM> can be placed at a specific location and then moved to another location.

Each spacer <NUM>, <NUM>, <NUM> has predetermined dimensions.

The first spacer <NUM> has a parallelepiped shape, the first spacer <NUM> occupying half a column along one dimension and two rows according to the other dimension.

The second spacer <NUM> has a parallelepiped shape, the second spacer <NUM> occupying one column and a half along one dimension and ten rows according to the other dimension.

The third spacer <NUM> has a parallelepiped shape, the third spacer <NUM> occupying three columns along one dimension and two rows according to the other dimension.

Each spacer <NUM>, <NUM>, <NUM> is adapted for guiding the insertion of a sensor in a compartment <NUM>.

In the illustrated example of <FIG>, the first spacer <NUM> is on the right of the compartments <NUM> belonging respectively to the second column C2 and the fifth row L5 and to the second column C2 and the sixth row L6.

The first spacer <NUM> is adapted to guide the first sensor <NUM> and the second sensor <NUM>.

The second spacer <NUM> is situated on the first column C1 and on the left of the second column C2.

The second spacer <NUM> is adapted to guide each sensor <NUM>, <NUM> and <NUM>.

As can be seen on <FIG>, the third spacer <NUM> is on the compartments <NUM> belonging respectively to the third column C3 and the first row L1, to the third column C3 and the second row L2, to the fourth column C4 and the first row L1, to the fourth column C4 and the second row L2. The third spacer <NUM> is also located on the right of the compartments <NUM> belonging to the second column C2 and the first row L1 and to the second column C2 and the second row L2. The third spacer <NUM> is also located on the left of the compartments <NUM> belonging to the fifth column C5 and the first row L1 and to the fifth column C5 and the second row L2.

The third spacer <NUM> is adapted to guide the third sensor <NUM>.

The detecting apparatus <NUM> is reconfigurable as can be illustrated on the kit <NUM> for forming detecting apparatuses <NUM> which is illustrated on <FIG>.

The kit <NUM> comprises the positioning device <NUM>, a sensor bag <NUM> and a spacer bag <NUM>.

The sensor bag <NUM> comprises the first sensor <NUM>, the second sensor <NUM>, the third sensor <NUM> and a fourth sensor <NUM>.

According to this specific embodiment, the fourth sensor <NUM> is a temperature sensor.

Alternatively, the fourth sensor <NUM> is an optical sensor.

The spacer bag <NUM> comprises the three spacers <NUM>, <NUM> and <NUM>.

Operation of the kit <NUM> is now described in reference to an example of carrying out of a method for determining the locations of compartments <NUM> being adapted to hold a sensor.

The method comprises a step of providing physical quantities to measure.

For instance, it may be desired to measure the temperature, the blood flux, the proper acceleration and electric activity.

The method comprises a step of providing the area where each physical quantity is to be measured.

In the example illustrated, the area is a spatial zone of the brain of the subject <NUM>.

The method comprises a step of providing the kit <NUM>.

The method also comprises a step of providing the individual dimensions of each element <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> of the kit <NUM>.

For instance, for the first spacer <NUM>, the following data are provided: the first spacer <NUM> has a parallelepiped shape, the first spacer <NUM> occupying half a column along one dimension and two rows according to the other dimension.

The method also comprises a step of optimizing the locations of the compartments <NUM> to fulfill a predetermined criteria.

By way of an illustration, the optimizing step is performed by a series of iterations in an optimization program. The goal of this optimization program, starting from an initial configuration of the locations is to obtain a configuration of locations of the compartments <NUM> that confer to the detecting apparatus <NUM> a property that as much as possible fulfills the criteria.

For this, a cost function C representative of deviations of the detecting apparatus <NUM> from the ideal apparatus fulfilling the criteria is used.

The cost function C is a positive function that should be minimized during the step of optimizing.

In order to proceed with performing this minimization, it is sufficient to start from initial configuration of the locations and to use a calculation method that provides the ability to reduce by iterations the value of the cost function C.

As illustration, the calculation method used is a damped least squares method (often referred to by the English acronym DLS for "damped least-squares").

The configuration of locations of the compartments <NUM> are thus obtained after iterations of the optimization program.

The predetermined criteria to be considered at the step of optimizing is, for instance, that the ratio of signal to noise of each sensor <NUM>, <NUM>, <NUM> and <NUM> be strictly superior to a given value.

Alternatively, the predetermined criteria is the total dimensions and weight of the kit <NUM> when assembled. In other words, the predetermined criteria is the total dimensions and weight of the detecting apparatus <NUM> formed when assembling the kit <NUM>.

Then, with the configuration of locations of the compartments <NUM>, a new detecting apparatus <NUM> may be obtained.

<FIG> illustrates another example of detecting apparatus <NUM> that can be obtained.

The detecting apparatus <NUM> comprises the positioning device <NUM> and the four sensors <NUM>, <NUM>, <NUM> and <NUM>.

In this specific embodiment, the detecting apparatus <NUM> does not comprise any spacer.

The first sensor <NUM> is located on the fifth column C5 and on the second row L2.

More precisely, the first sensor <NUM> is located on the upper part on the left of the compartment <NUM> belonging to the fifth column C5 and on the second row L2.

The third sensor <NUM> is located on the first column C1 and on the sixth row L6.

More precisely, the third sensor <NUM> is located on the upper part on the right of the compartment <NUM> belonging to the first column C1 and on the sixth row L6.

The third sensor <NUM> is located on the first column C1 and on the second row L2.

More precisely, the third sensor <NUM> is located on the upper part on the left of the compartment <NUM> belonging to the first column C1 and on the second row L2.

The fourth sensor <NUM> is located on the tenth column C10 and on the sixth row L6.

More precisely, the fourth sensor <NUM> is located on the upper part on the right of the compartment <NUM> belonging to the tenth column C10 and on the sixth row L6.

It should be understood that multiple detecting apparatus <NUM> are obtainable with the kit <NUM>.

According to another embodiment, the detecting apparatus <NUM> comprises only two sensors.

In such case, preferably, the two sensors are adapted to measure different physical quantities.

Alternatively, more than one sensor is an ultrasound transducer.

In other word, it becomes possible to image several locations on the same subject <NUM> in a very easy way.

Indeed, the detecting apparatus <NUM> is reconfigurable, which enables to modify the position of the sensors <NUM>, <NUM>, <NUM> and <NUM> without modifying the position of the position device <NUM>.

In addition, such detecting apparatus <NUM> can be used for different experiences.

Moreover, such detecting apparatus <NUM> can be useful in the cases of biological phenomena difficult to reproduce.

For instance, thanks to such detecting apparatus <NUM>, several different physical quantities can be measured simultaneously on the same subject <NUM> when this subject <NUM> is facing an epilepsy crisis.

<FIG> illustrates other examples of detecting apparatuses that may be considered.

On <FIG>, a detecting apparatus <NUM> is illustrated.

The detecting apparatus <NUM> comprises a positioning device <NUM> which is a frame with a periphery <NUM>.

The detecting apparatus <NUM> comprises a first ultrasound probe <NUM> and a second ultrasound probe <NUM>.

The detecting apparatus <NUM> comprises removable spacers <NUM>, <NUM>, <NUM>, <NUM> and <NUM>.

The remarks made for an element with reference to <FIG> apply in a similar to the same element in the embodiment of <FIG>.

The detecting apparatus <NUM> combines both ultrasound probes <NUM> and <NUM> over different selected brain areas. For example, the sensors <NUM> and <NUM> are positioned using spacers <NUM>, <NUM>, <NUM>, <NUM> and <NUM>.

On <FIG>, another detecting apparatus <NUM> is illustrated.

The detecting apparatus <NUM> comprises a positioning device <NUM> which is a frame with a periphery <NUM> and a grid <NUM>.

The detecting apparatus <NUM> comprises an ultrasound probe <NUM> and an implanted electrode array <NUM>.

The detecting apparatus <NUM> also comprises rods <NUM> for positioning the sensors <NUM> and <NUM>.

The detecting apparatus <NUM> combines the ultrasound probe <NUM> and the implanted electrode array <NUM> in the context of epilepsy monitoring on awake rats. For example, the sensors <NUM> and <NUM> are positioned using the rods <NUM> on the grid <NUM>.

On <FIG>, another detecting apparatus <NUM> is schematically shown.

The detecting apparatus <NUM> comprises a positioning device <NUM> which is a frame. The frame is obtained by three-dimensional printing. Such technique is a specific example of rapid prototyping technique.

The detecting apparatus <NUM> further comprises two ultrasound probes <NUM>, <NUM>, one accelerometer <NUM> and one surface electrode <NUM>.

Each sensor <NUM>, <NUM>, <NUM> and <NUM> are embedded in the printed frame.

The detecting apparatus <NUM> is, for instance, usable in the context of functional connectivity and behavioral study in awake mice.

According to another example, each sensor <NUM>, <NUM>, <NUM> has a sensing portion and a mechanical portion adapted to maintain the sensing portion in position. In addition, for each sensor, the mechanical portion of one sensor <NUM>, <NUM>, <NUM> has a shape which is complementary to the shape of the mechanical portions of the other sensors <NUM>, <NUM>, <NUM>.

In other words, the cooperation between two mechanical portions of two different sensors <NUM>, <NUM>, <NUM> enables to maintain each sensing portion in position and to reduce the congestion.

For instance, each mechanical portion has a recess and a protusion, the shape of the protusion being complementary to the shape of the recess. Thus, the protusion of one mechanical portion can be inserted in the recess of the adjacent mechanical portion so as to enable the maintaining of each sensor <NUM>, <NUM>, <NUM>. In addition, in such example, the mechanical portion can be identical which results in an easier fabrication.

In such embodiment, each sensor <NUM>, <NUM>, <NUM> can be imbricated one in another.

According to a specific embodiment, one sensor <NUM> is an ultrasound transducer while one sensor <NUM> is a printed multielectrode electroencephalography (EEG) foil. The foil is positioned below the ultrasound transducer compartment, that is nearer to the area to be sensed.

In this case, the foil is proximal to the brain while the ultrasound transducer is distal to the brain. In such context, proximal and distal are defined with relation to the brain. In other words, a proximal element is nearer to the brain than a distal element.

According to another embodiment, one sensor <NUM> is an ultrasound transducer while one sensor <NUM> is one or multiple implantable electroencephalography (EEG) electrodes.

These electrodes are guided obliquely inside the brain. In addition, these electrodes are below the ultrasound transducer compartment, which means nearer to the area to be sensed.

In this case, the electrodes are proximal to the brain while the ultrasound transducer is distal to the brain. In such context, proximal and distal are defined with relation to the brain. In other words, a proximal element is nearer to the brain than a distal element.

The embodiments and alternative embodiments considered here-above can be combined to generate further embodiments of the invention.

In addition, the detecting apparatus <NUM> may be used for various uses.

According to the first use, the detecting apparatus <NUM> is adapted to image a specific plane of the mobile rat with an embedded camera.

A frame is implanted on a rat with screws and dental cement. The skull of the rat is rendered thinner or opened on a window.

In a first embodiment, the position of the frame is determined before thanks to an anatomical frame. Superficial veins of the brain or skull suture lines are examples of anatomical frame.

According to another embodiment, after putting the frame on the skull of the rat, the precise location of the frame is determined thanks to an anatomical frame, such as superficial veins of the brain as previously proposed.

According to still another embodiment, after putting the frame on the skull of the rat, the precise location of the frame is determined thanks to a specific sensor. This specific sensor has a known position with relation to the frame. Such known position can be obtained by using a compartment adapted to hold the sensor. In specific cases, the compartment is translated to obtain a more precise estimation of the position of the frame.

The area to be imaged is then determined. As an example, the determined area is the visual cortex.

The kind of additional sensor to be fixed and the associated location are chosen.

As an example, the additional sensor is a camera.

In variant, the additional sensor is an accelerometer or a microphone.

According to the case, the additional sensor is put on the compartment corresponding to the chosen associated location or the additional sensor is put in a removable case which is then positioned at the associated location.

If a removable case is used, the detecting apparatus <NUM> only comprises the additional sensor during the experiment which enables the rat to move relatively freely. The only constraint is that the rat moves with the frame.

In such first use, the detecting apparatus <NUM> has two sensors: a probe and a camera. The probe is positioned in a stereotactic way with relation to the brain of the rat. The position of the camera, and more generally the second sensor, is reconfigurable as well as the choice of the nature of the sensor. The position of the second sensor is determined by using the position of the first sensor. It should be noted that the position of the second sensor may be subjected to less strict constraints that the position of the first sensor in so far as the area to be imaged may be relatively large whereas the position of the first sensor is imposed a stereotactic way with relation to the brain of the rat.

According to the second use, two planes of the brain of a mobile rat are imaged with two ultrasound probes.

The areas to be imaged are then determined. As an example, the determined area can be the visual cortex and the olfactory bulb.

For this second use, it is assumed that several compartments are positioned in a stereotactic way with relation to the brain of the rat.

According to an embodiment, such compartments are not removable and are positioned with the frame.

According to another embodiment, the compartments are removable and are positioned by using one of the previous proposed methods for positioning the frame. As an example, the precise location of a compartment is determined thanks to a specific sensor.

The ultrasound probes are assembled in a transitory way with the compartments which correspond to the desired location.

This enables to cumulate several advantages.

On the one hand, the rat only holds the ultrasound probes during the experiment.

On the other hand, both the frame and the ultrasound probes are positioned in a stereotactic way with relation to the brain of the rat.

In other words, the use of the detecting apparatus <NUM> in such context really renders carrying out an in vivo experiment on the brain of a rat easier for the scientist, without loss of precision in the measurements to be achieved on the rat.

According to the third use, only one plane of the brain of a mobile mouse is imaged with a probe while enabling the simultaneous use of an array of surface EEG multielectrodes.

A frame is implanted on a mouse with screws and dental cement. The skin of the mouse is removed.

According to another embodiment, after putting the frame on the skull of the mouse, the precise location of the frame is determined thanks to an anatomical frame, such as superficial veins of the brain as previously proposed.

According to still another embodiment, after putting the frame on the skull of the mouse, the precise location of the frame is determined thanks to a specific sensor. This specific sensor has a known position with relation to the frame. Such known position can be obtained by using a compartment adapted to hold the sensor. In specific cases, the compartment is translated to obtain a more precise estimation of the position of the frame.

The area to be imaged is then determined. As an example, the determined area is the hippocampus. The ultrasound probe is assembled in a transitory way with the compartment which corresponds to the desired location.

For this third use, it is assumed that a second compartment adapted to receive an array of surface EEG multielectrodes such as printed foil is first positioned in a stereotactic way with relation to the brain of the mouse and then glued with a mix of EEG paste and glue to the skull.

According to an embodiment, such printed foil is positioned with the frame below the ultrasound probe compartment.

In variant, the additional sensor is an EEG electrode that is guided obliquely inside the brain below the ultrasound probe.

In this third use, the same advantages as detailed for the second use still apply.

In each use, it appears that the detecting apparatus <NUM> has two main interests which may be cumulated in the use.

The first interest is the fact that the detecting apparatus <NUM> is reconfigurable by construction which enables to change the detecting apparatus <NUM> easily for the scientist.

One advantage is that each additional sensor can be chosen and/or positioned according to the specific needs of the experiment.

One advantage resulting from such reconfigurability is that the weight applied on the skull of the rat is limited to the time of acquisition. The useful sensor(s) is only hold for a limited time.

The second interest is the fact that the detecting apparatus <NUM> is adapted for achieving brain imaging of a small animal, such as a rat.

Notably, the detecting apparatus <NUM> enables to ensure that several sensors are positioned in a stereotactic way with relation to the brain of the rat.

Claim 1:
Detecting apparatus (<NUM>) adapted to detect at least one physical value in areas of a brain of a subject (<NUM>), the detecting apparatus (<NUM>) comprising :
- at least two sensors (<NUM>, <NUM>, <NUM>, <NUM>), with at least one sensor (<NUM>) being an ultrasound transducer adapted to produce ultrasound waves, the ultrasound transducer being adapted to detect cerebral blood volume and flow through Doppler sequences or contrast agents, the detecting apparatus (<NUM>) comprising at least two sensors (<NUM>, <NUM>, <NUM>, <NUM>) adapted to measure different physical quantities, and
- a positioning device (<NUM>) defining several compartments (<NUM>), each compartment (<NUM>) being adapted to hold a sensor (<NUM>, <NUM>, <NUM>, <NUM>) and each compartment (<NUM>) being located at predetermined location, the positioning device (<NUM>) comprising a holder adapted to be fixed on the skull of a subject, the positioning device (<NUM>) being adapted to be maintained on the head of the subject using the holder,
the compartments (<NUM>) being removable cases.