FR3140750A1 - Device for characterizing biological soft tissues - Google Patents

Abstract

Device for characterizing biological soft tissues, comprising: an impactor (10); a rod (20) having a proximal end (20a) forming an impact surface (21) and a distal end (20b) disposed in contact with the tissues (4); at least one force sensor (12) detecting the impaction force exerted at the impact surface (21) and providing a measurement signal representing the temporal variation of the impaction force during an impact; and a processing unit (30) of the measurement signal, connected to the sensor (12). The processing unit (30) calculates a first indicator representative of the stiffness of the tissues (4). This first indicator corresponds to the duration of a time window, the start of this time window being defined in relation to the first amplitude peak of the measurement signal and the end of this time window being defined in relation to the second amplitude peak of the measurement signal. (Figure 1)

Description

Device for characterizing biological soft tissues

The invention relates to a device and a method for the characterization of biological soft tissues. This device and this method can be used, in particular, for the characterization of the mechanical properties (rigidity, viscoelasticity, non-linearity) of biological soft tissues such as skin, muscles or any organ composed of soft tissues.

Background

Determining the mechanical properties of soft tissues is important in several medical fields such as dermatology, orthopedics (tendons), rheumatology, internal medicine or oncology, since the evaluation of these mechanical properties can then allow the diagnosis of various pathologies such as, for example, fibrosis. In addition, in the cosmetic field, determining the rigidity of the skin is of great interest in order to evaluate the performance of skin care.

Various devices for characterizing biological soft tissues based on different measuring principles are described below and in patent documents US 7556605 B2, US 10603013 B2 and EP 2658442 B1.

A known characterization device creates a negative pressure in a cavity so as to suck the skin into this cavity. After a defined time, the skin is released inside the cavity. The resistance of the skin to the negative pressure (firmness) and its ability to return to its original position (elasticity) are displayed as curves (penetration depth in mm/time unit) in real time during the measurement.

Another characterization method is to record the damped natural oscillation of soft biological tissues as an acceleration signal and simultaneously calculate tension state parameters, biomechanical properties, and viscoelastic properties. The damped natural oscillation is induced by a low-force, fast-release external mechanical impulse under constant preload.

Finally, elastography is a medical imaging technique that uses the speed of propagation of shear waves in soft tissues to measure their rigidity.

The invention aims to propose a new method for characterizing biological soft tissues using a simple and quick-to-use device.

General presentation

A device for characterizing biological soft tissues according to the invention comprises:
an impactor suitable for impacting an impact surface,
a rod having a proximal end forming the impact surface and a distal end adapted to be arranged in contact with the tissues, the rod being adapted to transmit to the tissues a force exerted by the impactor on the impact surface,
at least one force sensor capable of detecting the impact force exerted at the impact surface and of providing a measurement signal representing the temporal variation of the impact force during an impact, and
a measurement signal processing unit, connected to the sensor.

The processing unit is configured to calculate, from the temporal variation of the impaction force during the impact, a first indicator representative of the rigidity of the tissues. This first indicator corresponds to the duration of a time window, the start of this time window being defined relative to an instant corresponding to the first amplitude peak of the measurement signal and the end of this time window being defined relative to an instant corresponding to the second amplitude peak of the measurement signal.

In the present application, rigidity refers to the mechanical property characterized locally by the modulus of elasticity, or Young's modulus, expressed in Pascal. This mechanical property corresponds to elasticity in linear mode.

The proposed solution is based on the implementation of one or more force sensors delivering a measurement signal, the recording and analysis of this signal by the processing unit making it possible to determine an indicator revealing the rigidity of biological soft tissues. When several sensors are used, the signals respectively delivered by these sensors can be, for example, averaged or combined to obtain the measurement signal which will be analyzed and from which the indicator will be calculated. The electronic connection between the sensor and the processing unit can be wired or not.

In the present application, the term "impactor" refers to a percussion tool. In certain embodiments, the impactor comprises a striking head whose mass is between 3 and 50 g and, more particularly, between 5 and 20 g. Below 3 g, a loss of sensitivity is observed and it is more difficult to discriminate between the different tissues to be characterized. Above 50 g, in certain cases a disappearance of the second amplitude peak is observed linked to the absence of rebound of the rod during the impact. In addition, the greater the mass of the striking head, the greater the risk of damaging the tissues during the impact.

The impactor is, for example, shaped like a hammer and includes a handle topped with a striking head. However, other shapes could be considered as long as the impactor fulfills its percussion function.

The proposed device is of simple design. It therefore has the advantage of being less expensive and more robust than other known devices such as elastography devices. In addition, this device is easy to use since it is sufficient to impact the rod (i.e. tap the rod) with the impactor. It is therefore a common and simple gesture, within everyone's reach, when it is carried out manually. Alternatively, the movement of the impactor can be controlled automatically. A system for guiding the movement of the impactor and/or the rod can be envisaged without departing from the scope of the invention.

Furthermore, the proposed technology differs from existing technologies because it is based on the analysis of a one-time impact. In particular, the stiffness is measured from the duration of a time window between the initial impact, which results in a first amplitude peak in the measurement signal, and the rebound of the rod on the impactor, which results in a second amplitude peak. The inventors have demonstrated that the duration of this time window is correlated with the stiffness of the tissues and constitutes a reliable indicator.

In some embodiments, the processing unit is also configured to calculate, from the temporal variation of the impaction force during the impact, a second indicator representative of the viscoelasticity of the tissues. This second indicator corresponds to the ratio of the amplitude of the first peak to the amplitude of the second peak or to the ratio of the amplitude of the second peak to the amplitude of the third peak of the measurement signal. The inventors have demonstrated that this amplitude ratio was correlated with the viscoelasticity of the tissues and constituted a reliable indicator.

In some embodiments, the processing unit detects in the measurement signal the first amplitude peak and the amplitude peak following the first peak, the latter peak being considered as the second amplitude peak only if the measurement signal falls below a predetermined limit value between these two peaks (i.e. if the measurement signal falls below the limit value before rising above this value again to form the second peak). In particular, the limit value may be between 1 and 5% of the amplitude of the first peak. For example, the maximum amplitude peak following the first peak is considered as the second amplitude peak only if the measurement signal falls below a limit value equal to 5% of the amplitude of the first peak.

This precaution avoids measurement errors related to a phenomenon of splitting of the first peak, which has been observed in a small number of cases. During such a phenomenon, the two peaks obtained by splitting of the first peak are close to each other and the measurement signal does not have time to decrease significantly between these two peaks. Also, the solution consisting of checking that the measurement signal has sufficiently decreased before reaching the second amplitude peak, avoids wrongly considering the duplicate of the first peak as the second amplitude peak, and therefore avoids a measurement error on the indicator. Of course, other methods of analysis of the measurement signal could be considered to detect a splitting of the first peak and avoid measurement errors in such a case.

The invention also relates to a method for characterizing biological soft tissues, in which:
a characterization device as previously described is provided,
the distal end of the rod is placed in contact with the tissues,
an impact force is exerted with the impactor on the impact surface of the rod, and
The first indicator representing tissue stiffness is calculated using the processing unit.

In some implementation modes, the second indicator representing the viscoelasticity of the tissues is also calculated by means of the processing unit.

The advantages of such a method arise from the advantages of the device used. The device and the method of the invention can be used for an application in dermatology, oncology or myology since the measurement of the rigidity of the skin or of certain biological soft tissues can then make it possible to deduce the state of health of the tissues concerned or to detect certain diseases (cancer, hepatitis). Furthermore, they can be used in the cosmetic field where knowledge of the rigidity of the skin is useful for evaluating the effectiveness of a cosmetic product.

The distal end of the rod can be placed in contact with tissues in a non-invasive manner, i.e. without requiring injury to the body. This is the case, in particular, when the distal end of the rod is placed on the skin.

On the contrary, the distal end of the rod can be placed in contact with the tissues, in an invasive manner, that is to say after injury to the organism, in order to instantly and in vivo evaluate the rigidity of certain internal biological tissues. For example, the device can be used during a surgical procedure, in order to quantitatively evaluate the rigidity of the soft tissues of an organ or a muscle.

In some embodiments, the device further comprises a plurality of weights of different masses, each weight being adapted to be arranged in contact with the tissues so as to exert a prestress on the tissues, each weight being crossed by an opening of a size large enough to allow the rod to pass so that the distal end of the rod is in contact with the tissues when the weight exerts a prestress on the tissues.

Such a device is used as follows:
a first weight is placed in contact with the tissues so as to exert a pre-stress on the tissues,
the rod is passed through the opening of the first weight so that the distal end of the rod comes into contact with the tissues when the first weight exerts a preload on the tissues,
an impact force is exerted with the impactor on the impact surface of the rod,
we calculate by means of the processing unit, a first value of the first indicator representative of the rigidity of the prestressed tissues,
the previous steps are repeated with at least a second weight having a mass different from that of the first weight so as to calculate at least a second value of the first indicator representative of the rigidity of the prestressed tissues,
we calculate by means of the processing unit, a linear regression model which estimates a linear relationship between the value of the first indicator and the mass of the weights, and
a third indicator representative of the non-linear behavior of the tissues is calculated, the third indicator corresponding to the slope coefficient of the regression line.

The inventors demonstrated that the slope of the regression line was correlated with the non-linear behavior of tissues and was a reliable indicator.

The above-mentioned features and advantages, as well as others, will become apparent from the following detailed description of exemplary embodiments of the proposed device and method. This detailed description refers to the attached drawings.

The attached drawings are schematic and are not necessarily to scale; they are intended primarily to illustrate the principles of the invention. In these drawings, from one figure (Fig) to another, identical elements (or parts of elements) are identified by the same reference signs.
This figure is a schematic representation of an example of a characterization device comprising a rod and an impactor equipped with a force sensor.
This figure is a graphical representation of an example signal obtained using the force sensor during an impact.
This figure is a graphical representation of the evolution of the sensitivity of the first indicator to the stiffness of the material.
This figure is a graphical representation of the evolution of the first indicator as a function of the prestress mass, for different samples.
This figure is a partial schematic representation of an example prestress weight.

Detailed description

Particular embodiments of the proposed device are described in detail below, with reference to the example shown in the accompanying drawings. These embodiments illustrate the characteristics and advantages of the invention. It is however recalled that the invention is not limited either to these embodiments or to the example shown.

There represents an example of a device for characterizing biological soft tissues. The tissues in question may be, for example, skin tissue, muscle tissue or any organ composed of soft tissues such as the breast, prostate, liver, etc. The device comprises a percussion tool, or impactor 10, a rod 20, a sensor 12 and a processing unit 30.

In some embodiments, as in the example shown, the impactor 10 is of the hammer type and comprises a handle 13 surmounted by a striking head 11.

The rod 20 has a proximal end 20a forming an impact surface 21 which the user strikes with the impactor 10, the striking head 11 then exerting a force F1 represented by an arrow on the rod 20.

The rod 20 has a distal end 20b forming a contact surface 22 adapted to be arranged against the tissues 4 to be characterized. The contact surface 22 can be between 0.5 mm2 and 12 cm2. Below 0.5 mm2, the stresses at the contact surface 22 are very significant and there is a risk of damaging, in particular piercing, the tissues 4 during the impact. In addition, the stressed tissue area is not deep enough. Beyond 12 cm2, the stressed tissue area is too large for most of the applications envisaged because the axial resolution is too poor. In certain embodiments, the contact surface 22 is a surface of revolution, in particular a circular flat surface or a hemispherical surface. This makes it possible to minimize the stress concentrations due to the angular parts likely to reduce the reproducibility of the measurement.

The rod 20 is made, for example, of metallic, polymer or composite material and, more generally, of a rigid material, non or slightly viscoelastic, having a linear behavior law in the field of use, so as to transmit to the tissues 4, without damping or modification, the force F1 exerted by the impactor 10.

The force sensor can be located either on the impact surface 21 of the rod 20 or on the striking face of the impactor 10. In the example shown, the sensor 12 is located on the striking face of the striking head 11.

When using the device, the user grasps the rod 20 with one hand and the handle 13 of the impactor 10 with the other hand. He then strikes the impact surface 21 with the striking head 11 of the impactor. The force F1 generated by the impactor 10 is transmitted to the tissues 4 via the rod 20.

The force sensor 12 is capable of detecting the impact force exerted at the impact surface 21 and of providing a measurement signal representing the temporal variation of the impact force during an impact. An example of a force sensor of this type is described in patent document EP 2923677 B1. It is, for example, a strain gauge sensor, or strain gauge, or an accelerometer or a piezoelectric sensor. The force sensor is connected according to an appropriate assembly to the processing unit 30, via a wireless connection (i.e. by radio waves) or a wired connection.

The processing unit 30 comprises, for example, a microcontroller. The processing unit 30 may be housed in an external housing or be integrated into the impactor 10. Alternatively, the processing unit 30 may be formed of separate elements such as a microcomputer connected to a data acquisition module itself connected to the sensor 12. The sampling frequency of the processing unit 30 is at least 50 kHz.

During each impact, the sensor 12 measures the impact force exerted at the impact surface 21 and provides a measurement signal representing the temporal variation of this force during the impact. The impact is considered to begin from the moment when the impactor 10 and the rod 20 come into contact and lasts for a certain period of time after this moment. In any event, this period of time is less than 50 ms. An example of a signal provided by the sensor 12 is shown in FIG. and described below. The inventors have demonstrated that such a signal carries information on the stiffness of the tissues. In particular, the inventors have succeeded in determining, from the collected measurement signal, an indicator representative of the stiffness of the tissues, as explained below.

There is a graph schematically representing an example of a signal obtained using the force sensor 12 during an impact. The time t in seconds (s) is plotted on the abscissa, the force F measured by the sensor 12, in Newtons (N), is plotted on the ordinate. The impact is plotted at time t = 0. The first amplitude peak P1 appears almost instantaneously (i.e. less than a millisecond later) at time t1. The amplitude A1 of the first peak P1 reflects the force F1 exerted by the impactor 10 on the rod 20.

The second peak of amplitude P2 appears a few milliseconds after the first peak P1, at time t2. The amplitude A2 of the second peak P2 reflects the force F2 exerted during the first rebound of the rod 20 on the impactor 10. This force F2 is represented by an arrow on the .

The successive rebounds of the rod 20 on the impactor 10 lead to the appearance of other amplitude peaks after the second peak P2. Only the third peak P3, which appears at time t3, is represented on the . The amplitude A3 of the third peak P3 reflects the force exerted during the second rebound of the rod 20 on the impactor 10.

The inventors have highlighted the fact that the duration (t2 - t1) between the first two peaks P1 and P2, was a reliable and relevant IN1 indicator for evaluating the stiffness of tissues 4.

They also highlighted that the A1/A2 ratio of the A1 amplitude of the first peak P1 to the A2 amplitude of the second peak P2 or the A2/A3 ratio of the A2 amplitude of the second peak P2 to the A3 amplitude of the third peak P3 of the measurement signal was a reliable and relevant IN2 indicator for assessing tissue viscoelasticity 4.

In particular, tests were carried out on samples made from agar-agar, a powerful natural gelling agent whose action is perceptible in aqueous solution from a very low mass concentration. Such samples are test phantoms reproducing the properties of biological soft tissues, widely used in the field of research. In order to be able to compare different stiffnesses, the mass concentration of agar-agar is between 1% and 5%, which corresponds to elastic moduli in the stiffness range of biological soft tissues, namely between approximately 1.5 kPa and 400 kPa. For example, healthy breast tissues have an elastic modulus between 12 and 72 kPa and cancerous breast tissues have an elastic modulus between 56 and 450 kPa.

These tests were carried out with an impactor 10 having a striking head 11 weighing 5 g and a circular contact surface in the form of a disc of 1 mm in diameter. The sensor 12 was a piezoelectric sensor. The sampling frequency of the processing unit 30 was approximately 100 kHz, in this case 102 kHz.

In order to evaluate the reproducibility of the measurement by the sensor 12 and the processing of the associated measurement signal, ten impacts were carried out on the same agar-agar sample and ten measurements were made, i.e. one measurement per impact. For each impact, the first indicator IN1 corresponding to the duration of the time window (t2-t1) between the first two amplitude peaks P1, P2, was calculated. The means and standard deviations were compared for samples of different rigidity obtained by varying the mass concentration of agar-agar. The results are presented in Table 1 below.

Concentration
in agar-agar 1% 2% 3% 4% 5% IN1 (ms) 9,929 6,679 5,500 4,993 4,528 Standard deviation (ms) 0.494 0.236 0.083 0.128 0.114 Error (%) 4.9% 3.5% 1.5% 2.5% 2.5%

The results show good reproducibility of the measurement with an error on the IN1 indicator of less than 5% on all agar-agar concentrations. It is also noted that the measurement is all the more precise as the agar-agar concentration, and therefore the rigidity of the sample, is high.

In a second step, tests were carried out to compare the results obtained for samples of different concentrations and, thus, to assess whether the measurement has good sensitivity. To reduce the uncertainty related to sample preparation (uncertainty of the balance, quantity of water), three samples were made for the same agar-agar concentration. For each agar-agar concentration, the means and standard deviations are calculated on the basis of thirty tests, namely ten impacts on each of the three samples.

The evolution of the IN1 indicator as a function of the agar-agar concentration is presented on the graph of the . The concentration C in agar-agar, from 1% to 5%, is reported on the abscissa. The mean value of the IN1 indicator obtained for each concentration is reported on the ordinate. The standard deviation is represented by a vertical segment extending on either side of the mean value of the IN1 indicator.

These tests show that the measurement standard deviations are low compared to the variation of the IN1 indicator according to the stiffness of the samples. The proposed characterization method therefore makes it possible to discriminate between two samples of different stiffnesses based on the measurement of the IN1 indicator. In addition, the error in estimating the agar-agar concentration of the samples, and therefore their stiffness, is 0.17% agar-agar, which is equivalent to a variation in the elastic modulus of around 17 kPa. For comparison, measurements obtained by elastography-based methods are around 0.07% agar-agar according to the literature (see, for example, the publication of Hamhaber, U., et al, 2003, "Comparison of quantitative shear wave MR-elastography with mechanical compression tests", Magnetic Resonance in Medicine, 49(1), 71-7–. These tests confirm the ability of the proposed characterization method to reliably assess the stiffness of biological soft tissues, with good sensitivity.

Finally, tests were carried out to demonstrate the ability of the proposed characterization method to determine the nonlinearity of the constitutive law of biological soft tissues. For this, increasing prestresses were applied to the samples and the first indicator IN1 was calculated for each prestress.

To prestress the sample, a series of weights W was used. An example of weight W is shown in the . This weight W is crossed by an opening 42 of a size large enough to allow the rod 20 to pass through so that the distal end 20b of the rod 20 is in contact with the sample (imitating the tissues 4) when the weight W exerts a prestress on the sample. In the example of the , the weight has an annular shape and is crossed by the rod 20 at its center. Other shapes of weight could however be envisaged.

The underlying idea is to prestress the tissues (the sample) by applying a mass to them in order to perform a local measurement of the tissue behavior law at the corresponding stress.

To perform the tests, five weights W1 to W5 with respective masses of 10g, 20g, 30g, 40g and 50g were used to prestress the sample before and during impact. The tests were performed for samples with different agar-agar mass concentrations, namely 1%, 2%, 3%, 4% and 5%.

The results presented on the show, for each sample, a variation, in this case a decrease, of the indicator IN1 (in ms) as a function of the mass M (in g) of the weight W used for the prestressing.

By calculating, using the processing unit 30, for each sample, a linear regression model which estimates a linear relationship (i.e. which determines a regression line) between the value of the first indicator IN1 and the mass M, it is possible to determine the slope coefficient (i.e. the slope) of the regression line. The regression lines calculated for the five samples appear in dotted lines on the . This leading coefficient is used as a third indicator IN3 to evaluate the non-linear behavior of the tissues 4 to be characterized. It should be noted that on the graph of the , the ordinate at the origin corresponds to the indicator IN1 in the absence of prestress (M = 0 g) and therefore reflects the stiffness of the tissues in the absence of prestress.

The results of the show that the IN3 indicator (i.e. the slope of the lines) is non-zero and negative, regardless of the agar-agar concentration. Moreover, in absolute value, the IN3 indicator increases when the agar-agar concentration decreases. We also know that all five samples have a non-linear behavior law, this non-linearity being all the more significant as the agar-agar concentration is low. The IN3 indicator therefore correctly reflects the non-linearity of the samples.

These tests confirm the ability of the proposed characterization method to evaluate the non-linear nature of the behavior law of biological soft tissues, reliably and with good sensitivity.

The various features of the embodiments or examples described herein may be considered in isolation or combined with each other. When combined, these features may be as described above or differently, the invention not being limited to the specific combinations previously described. In particular, unless otherwise specified or technically incompatibility, a feature described in relation to one embodiment or example may be applied in an analogous manner to another embodiment or example.

Claims (12)

Device for characterizing biological soft tissues, comprising:
an impactor (10) adapted to impact an impact surface (21),
a rod (20) having a proximal end (20a) forming the impact surface (21) and a distal end (20b) adapted to be arranged in contact with the tissues (4), the rod (20) being adapted to transmit to the tissues (4) a force (F1) exerted by the impactor (10) on the impact surface (21),
at least one force sensor (12) capable of detecting the impact force exerted at the impact surface (21) and of providing a measurement signal representing the temporal variation of the impact force during an impact, and
a processing unit (30) of the measurement signal, connected to the sensor (12),
in which:
the processing unit (30) is configured to calculate, from the temporal variation of the impaction force during the impact, a first indicator (IN1) representative of the rigidity of the tissues, and
the first indicator (IN1) corresponds to the duration of a time window, the start of this time window being defined relative to an instant (t1) corresponding to the first amplitude peak (P1) of the measurement signal and the end of this time window being defined relative to an instant (t2) corresponding to the second amplitude peak (P2) of the measurement signal. Device according to claim 1, in which the processing unit (30) is also configured to calculate, from the temporal variation of the impaction force during the impact, a second indicator (IN2) representative of the viscoelasticity of the tissues, and
the second indicator (IN2) corresponds to the ratio (A1/A2) of the amplitude (A1) of the first peak (P1) to the amplitude (A2) of the second peak (P2) or to the ratio (A2/A3) of the amplitude (A2) of the second peak (P2) to the amplitude (A3) of the third peak (P3) of the measurement signal. Device according to claim 1 or 2, in which the impactor (10) comprises a striking head whose mass is between 3 and 50 g.
Device according to any one of claims 1 to 3, in which the impactor has the shape of a hammer and comprises a handle (13) surmounted by a striking head (11). Device according to any one of claims 1 to 4, in which the distal end of the rod forms a contact surface of between 0.5 mm2 and 12 cm2. Device according to any one of claims 1 to 5, in which the contact surface is a surface of revolution. Device according to any one of claims 1 to 6, further comprising a plurality of weights (W) of different masses, each weight (W) being adapted to be placed in contact with the tissues (4) so as to exert a prestress on the tissues (4), each weight (W) being crossed by an opening (42) of a size large enough to allow the rod (20) to pass through so that the distal end (20b) of the rod (20) is in contact with the tissues (4) when the weight (W) exerts a prestress on the tissues (4). Device according to any one of claims 1 to 7, in which the processing unit (30) is configured to detect in the measurement signal the first amplitude peak (P1) and the amplitude peak following the first peak (P1), the latter peak being considered as the second amplitude peak (P2) only if the amplitude of the signal becomes lower than a predetermined limit value between the two peaks. Device according to claim 8, in which the predetermined limit value is between 1 and 5% of the amplitude of the first peak (P1). Method for characterizing biological soft tissues (4), in which:
a device according to any one of claims 1 to 9 is provided,
the distal end (20b) of the rod is placed in contact with the tissues in a non-invasive manner,
an impact force is exerted with the impactor (10) on the impact surface (21) of the rod, and
the first indicator (IN1) representative of the stiffness of the tissues is calculated using the processing unit (30). Method according to claim 10, in which the second indicator (IN2) representative of the viscoelasticity of the tissues is further calculated by means of the processing unit (30). A method according to claim 10 or 11, wherein:
a device according to claim 7 is provided,
a first weight (W1) is placed in contact with the tissues (4) so as to exert a pre-stress on the tissues (4),
the rod (20) is passed through the opening (42) of the first weight (W1) so that the distal end (20b) of the rod (20) comes into contact with the tissues (4) when the first weight (W1) exerts a prestress on the tissues (4),
an impact force is exerted with the impactor (10) on the impact surface (21) of the rod (20),
a first value (V1) of the first indicator (IN1) representative of the rigidity of the pre-stressed tissues (4) is calculated by means of the processing unit (30),
the previous steps are repeated with at least a second weight (W2) having a mass different from that of the first weight (W1) so as to calculate at least a second value (V2) of the first indicator (IN1) representative of the rigidity of the prestressed tissues (4),
a linear regression model is calculated using the processing unit (30) which estimates a linear relationship between the value of the first indicator (IN1) and the mass of the weights (W1, W2), and
a third indicator (IN3) representative of the non-linear behavior of the tissues is calculated (4), the third indicator (IN3) corresponding to the slope coefficient of the regression line.