SYSTEMS AND ASSOCIATED METHODS FOR CHARACTERIZING TISSUES - Patent application

Abstract

To provide a system for discriminating a tissue, and a method for the system.SOLUTION: A system for characterizing a tissue includes: a probe that delivers a continuous and periodic mechanical vibration (PMV) to a tissue of a subject; an ultrasound emitter that emits a sequence (80, 80', 80'') of ultrasound shots and an ultrasound receiver that receives corresponding echo signals to track how the tissue is moved by the periodic mechanical vibration delivered to the tissue; and a control module programmed to provide homogeneity information (808, 808', 808'') to an operator of the system, the homogeneity information being determined from at least some of the echo signals and being representative of the ability of the tissue to transmit elastic waves and of the homogeneity of the tissue with respect to the propagation of elastic waves.SELECTED DRAWING: Figure 9

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is related to PCT application No. PCT / EP2019 / 054656, filed February 26, 2019, and PCT application No. PCT / EP2019 / 054658, filed February 26, 2019, which are incorporated by reference in their entireties.

[0002] The disclosed technology relates to non-invasive tissue characterization systems, and in particular to systems and methods for identifying homogenous tissues in which tissue hardness or fat content can be non-invasively assessed. [Background technology]

[0003] It is well known that liver tissue stiffness correlates with the degree of cirrhosis and other diseases, and that the speed at which shear waves travel through a region of interest in a subject's liver is directly related to liver stiffness. Indeed, in soft tissues, the tissue density (ρ) and shear wave velocity (V s ) from the equation E=3ρV s 2 The hardness (Young's modulus) can be estimated using the formula: The density of soft tissue is 1000 kg / m 3 E is in kilopascals, V is s is expressed in meters per second (m / s).

[0004] To characterize the stiffness of the liver or other organs by shear wave velocity measurements, a technique called "harmonic elastography" has been developed, described for example in the document "Probe Oscillation Shear Wave Elastography: Initial In Vivo Results in Liver" by DC Mellema et al., published in IEEE Transactions on Medical Imaging, volume 37, issue 5, May 2018.

[0005] According to this technique, an array transducer for two-dimensional B-mode ultrasound imaging is placed in contact with the subject's body and vibrated at a low frequency, typically comprised between 30 Hz and 100 Hz. Then, ultrasound shots are emitted in order to track how the subject's tissue is moved by this low-frequency periodic vibration. In this way, an instantaneous two-dimensional map (a kind of 2D snapshot) is determined, which shows the tissue displacements caused by the low-frequency periodic vibration at different points distributed on a two-dimensional cross-section of the subject's tissue at the same time (see Fig. 9a in the above-mentioned document by D.C. Mellema et al.). Then, a filtered two-dimensional displacement map is determined by a complex spatial mode filtering process (Fig. 9b or Fig. 8b in Mellema et al.). Then, an inversion algorithm allows the derivation (from the two-dimensional deformation map) of a two-dimensional map representing the values ​​of the shear wave velocity at different points distributed on the whole two-dimensional cross-section of the tissue (Fig. 8c in Mellema et al.). Thus, in this technique, the values ​​of the shear wave velocity are derived from the spatial information contained in the instantaneous two-dimensional displacement map.

[0006] However, implementing such a method requires very complex multi-beam ultrasound devices suitable for 2D ultrasound imaging. Also, according to Mellema et al., the processing of a single instantaneous 2D deformation map requires a lot of time, typically three vibration periods. This long processing time precludes sampling an entire vibration period at once, from a time perspective (as described in the capture of Figure 3 of Mellema et al.). More precisely, in Mellema, two ultrasound shots are emitted twice (100 ms each), then two corresponding ultrasound echo signals are acquired and processed to calculate the displacement of the medium when the two ultrasound shots were emitted. This procedure is then repeated 100 ms later, etc. (at a repetition rate of 10 Hertz). Due to the long processing time required to calculate and analyze each 2D deformation map, this procedure cannot be repeated at a higher repetition rate. Therefore, with this technique, it is not possible to sample an entire vibration period at once (as this would require a repetition rate higher than the frequency of the mechanical vibration, i.e., higher than 100 Hertz). Thus, although this harmonic elastography technique allows for two-dimensional spatial imaging and focuses on the spatial characteristics of the deformation field, it has poor temporal resolution and is affected by tissue motion due to, for example, breathing or heart beating.

[0007] Moreover, measurements of shear wave velocity by harmonic elastography are considered less reliable and accurate than those by transient elastography, and harmonic elastography usually provides overestimated velocity values. Indeed, in harmonic elastography, the periodic mechanical vibrations transmitted to the subject travel in the subject's tissues as elastic waves that mix shear and compression waves (whose propagation speed is much faster than that of shear waves), and these two components are hardly separable due to the repetitive and continuous nature of the vibrations. Harmonic elastography measurements can also be distorted by reflections of elastic waves in the tissue, which can create stationary wave patterns (again, due to the repetitive and continuous nature of the vibrations).

[0008] As a result, the time-harmonic elastography technique described above provides valuable spatial information about the structure of the subject's body part under examination due to its two-dimensional imaging capability. However, it generally provides less accurate shear wave velocity values. The main reasons for this lack of accuracy are the mixing of shear and compression waves, the influence of diffraction effects due to the large size of the vibration source, and the influence of motions such as respiratory motions and out-of-plane motions that are not measured when the displacements are usually captured during several vibration cycles. These issues introduce artifacts into the images, which need to be interpreted with great care, especially when quantitative measurements are to be provided.

[0009] Thus, the transient elastography technique appears to be more suitable than the time-harmonic elastography technique for accurately measuring shear wave velocity in very large and homogeneous organs such as the liver and spleen.

[0010] Transient elastography is based on a different approach than the harmonic elastography technique described above: instead of recording an instantaneous two-dimensional map of tissue deformation (and deriving shear wave velocity values ​​from the spatial characteristics of this map), transient elastography focuses on the spatiotemporal tracking of transient mechanical pulses transmitted to the tissue.

[0011] A well-known transient elastography system is the FIBROSCAN® system (ultrasound-based elastography device for measuring stiffness (or elasticity) and ultrasound attenuation of tissues and organs), manufactured and sold by Echosens SA, Paris, France, which allows operators to non-invasively measure stiffness of the liver and other organs to assess organ health.

[0012] In the FIBROSCAN® system, the operator places the tip of a probe with a rather small diameter (usually comprised between 5 and 10 mm) in contact with the subject's body in front of the expected area of ​​the subject's liver. The operator then presses a button, causing the head of the probe to transmit a transient low-frequency mechanical pulse (the spectrum of this pulse is usually centered on frequencies comprised between 10 and 500 Hz) to the subject. This pulse generates an elastic wave that travels inside the subject's body. An ultrasound transducer attached to the head of the probe and in contact with the subject's body then sends multiple ultrasound shots into the tissue at a high repetition rate of at least 2 kilohertz. Echo signals corresponding to the backscattering of the various emitted ultrasound shots are acquired by the probe in order to track the slight movements of the tissue caused by the passing elastic waves. This tracking is performed using correlation techniques applied to successive echo signals. The detected movements make it possible to synthesize an elastic wave propagation image that shows the tissue deformation both as a function of depth d and as a function of time t (instead of synthesizing an image that shows the tissue deformation as a function of two different spatial coordinates but at a given fixed instant in time). FIG. 1 shows such an elastic wave propagation image 105, sometimes referred to as an "elastogram."

[0013] In contrast to other elastography methods, the FIBROSCAN® probe uses a favorable symmetrical design. The ultrasound transducer is a single-element transducer mounted on the axis of the vibrator. The axis of the ultrasound transducer coincides with the axis of the vibrator, so the displacements induced by the vibrations are mainly longitudinal and therefore aligned with the axis of the ultrasound beam. Displacement measurements are significantly improved in such conditions, since it is much more difficult to measure off-axis displacements using ultrasound. Other elastography devices, especially harmonic devices, are more complex. They use multiple element ultrasound transducers (usually linear or convex arrays) with the aim of providing a map of mechanical properties in 2D or 3D to localize heterogeneities. The symmetry of these systems is much more complex. The displacements induced by the vibrations are not aligned with the ultrasound beam by design. They require longer calculation times to process more data (multiple ultrasound lines) and use advanced inversion algorithms to evaluate the mechanical properties in 2D or 3D. Moreover, they operate very slowly.

[0014] The mechanical pulse transmitted by the head of the FIBROSCAN® probe generates both shear and compression waves. In other words, the elastic waves described above are a mix of shear and compression waves. However, these two waves have very different propagation velocities and, thanks to the transient nature of the mechanical excitation, can be easily separated in time and identified in the elastic wave propagation image. For example, see FIG. 1, which shows an elastic wave propagation image 105. In FIG. 1, the compression wave is identified by reference 105C and the much slower shear wave is identified by reference 105S. Also shown in FIG. 1 are two dashed regions of interest (ROIs) at 25 mm and 65 mm, which correspond to the depths below the patient's skin where the liver is usually located. This elastic wave propagation image can therefore be used to accurately determine the shear wave propagation velocity in the tissue to be characterized, from which the stiffness of this tissue can be derived. These hardness results 106 are then provided to the operator, as depicted in FIG. 1, which shows different graphs 101, 102, 105 and indicators 103, 106, 107 displayed to the operator by the display screen of the FIBROSCAN® system.

[0015] The FIBROSCAN® system also makes it possible to measure the attenuation of the ultrasound signal used to track the shear waves, which is useful because ultrasound attenuation correlates with the fat content of the liver (see Figure 1, ultrasound attenuation results 107).

[0016] Although the FIBROSCAN® technology works well, it can be difficult for the operator to know if he / she has correctly positioned the probe in front of an area of ​​homogenous liver tissue, or even if he / she is aiming the probe at the liver. Other artifacts of non-homogeneous tissue, such as ribs, blood vessels, fluid pockets (ascites) in front of the liver, or cysts or tumors in liver tissue, can cause erroneous measurements of both tissue stiffness and ultrasound attenuation. In addition, the operator may believe he / she is aiming the probe at the liver when in fact the probe is too close to the lungs or other internal organs. As a result, the system may not obtain accurate measurements.

[0017] To help the operator find a suitable probe position, the FIBROSCAN® system is configured to continuously transmit ultrasound shots and acquire corresponding echo signals while the operator is searching for a suitable probe position. A-mode and TM-mode graphs are displayed and refreshed in real time to help the operator find a suitable probe position. FIG. 1 shows an example of such an A-mode graph 101 and a TM-mode graph 102. The TM-mode graph represents the subsequently acquired ultrasound echo signals after they have been processed. The processing of the ultrasound echo signals includes, for example, envelope calculation and decimation. The TM-mode graph shown in FIG. 1 is a two-dimensional image, with each column representing one of the acquired and processed ultrasound echo signals. Each column represents an instantaneous one-dimensional image showing how a part of the subject's body located in alignment with the probe backscatters ultrasound waves according to a depth d. The successive acquired ultrasound echo signals are displayed side-by-side to show the evolution of this one-dimensional image over time t (the evolution is caused by slight movements of the probe or organ movements caused by respiratory movements).

[0018] As shown in Figures 1 and 2, the TM graph provides useful information regarding the positioning of the probe 3. Indeed, when the probe axis x is aligned with a thick homogenous part of the liver 4, the TM graph 402 typically looks like a stack of thin horizontal sheets, with a homogenous appearance in both the horizontal and vertical directions, as shown in Figure 4. In contrast, when the probe axis x is close to the edge of the liver 4, the TM mode graphs 202, 302 often have discontinuous appearance in either the horizontal (Figure 2) or vertical (Figure 3) directions.

[0019] Nevertheless, proper positioning of the probe based on the TM graph remains very difficult and requires proper training of the operator. Moreover, as will be appreciated by those skilled in the art, improper probe positioning can lead to improper measurement and inaccurate diagnosis of the patient's condition.

[0020] The ultrasound signal displayed in the TM or A-mode graphs provides some information about the position of the probe, but does not predict shear wave propagation. In some cases, these graphs may look appropriate, as if the conditions are suitable for transient elastography measurements, but shear waves cannot actually propagate. This can occur when there is intervening liquid (see TM mode graph 602 in FIG. 6), intervening air (see TM mode graph 602' in FIG. 6), narrow intercostal spaces, etc. Furthermore, blood vessels may not be visible in the ultrasound signal because they are isoechoic, but they may interfere with shear wave propagation. FIG. 6 shows a TM mode graph 602''' acquired in the presence of an isoechoic vessel, which remains invisible (the location of this vessel is identified by an arrow).

[0021] Since ultrasound and elasticity are not sensitive to the same conditions, guidance using ultrasound data is not good because it cannot predict shear wave propagation. A good ultrasound signal does not always result in good shear wave propagation. Some factors that affect shear wave propagation do not affect ultrasound propagation. This is the case for isoechoic parts such as blood vessels, cysts, liquids containing particles, hard or soft tumors, etc.

[0022] Due to the limitations of conventional TM graph guidance, operators usually do not find the proper probe location on the first attempt to position the probe. In practice, the operator often needs to trigger the transient elastography measurement several times to test various positions by trial and error before finding the proper position and recording an elastic wave propagation image suitable for characterizing liver stiffness. This is made even more time consuming by the operator having to hold the probe still and steady before triggering the transient elastography measurement. As will be appreciated by those skilled in the art, such attempts can be uncomfortable for the patient under test, as the patient receives a small mechanical punch each time the operator takes a measurement. Moreover, such attempts can discourage the operator from finding the proper position, thus increasing the failure rate.

[0023] It is therefore desirable to develop a system for characterizing tissue that is suitable for accurate characterization of the viscoelastic properties of this tissue and has improved guiding capabilities compared to the FIBROSCAN(R) system described above. [Prior art documents] [Non-patent literature]

[0024] [Non-Patent Document 1] DCMellema et al., “Probe Oscillation Shear Wave Elastography: Initial In Vivo Results in Liver,” IEEE Transactions on Medical Imaging, volume 37, issue 5, May 2018 [Non-Patent Document 2] H. Tzschatzsch et al., "In vivo time-harmonic ultrasound elastography of the human brain detects acute cerebral stiffness changes induced by intracranial pressure variations," Scientific Reports, Vol. 8, Article No. 17888, 2018 Summary of the Invention [Means for solving the problem]

[0025] To address at least some of the above problems, the disclosed technology is directed to a system for identifying homogenous tissue in a subject or patient. Once an area of ​​homogenous tissue is detected, an operator can begin measuring the stiffness and / or determining ultrasound parameters of the tissue.

[0026] In some embodiments, the system: a probe held against the subject's body and including a vibrator for transmitting mechanical vibrations to tissue of the subject; an ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive corresponding echo signals; a control module; The control module performs the following steps on the system: a) transmitting continuous periodic mechanical vibrations to tissue of a subject; b) emitting a sequence of ultrasound shots by an ultrasound emitter and acquiring corresponding echo signals received by an ultrasound receiver in order to track how the tissue is moved by the periodic mechanical vibrations transmitted to the tissue; c) providing the homogeneity information to an operator of the system. It is programmed to execute Periodic mechanical vibration consists of the same vibration pattern being repeated several times in succession over time. Homogeneity information is determined from at least some of the echo signals acquired in step b), the homogeneity information being representative of the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with regard to the propagation of elastic waves.

[0027] The control module is programmed such that steps b) and c) are executed consecutively by the system several times in succession.

[0028] The homogeneity information obtained by tracking how the periodic mechanical vibrations progress through the tissue constitutes very efficient guiding information helping the operator to quickly and easily find the appropriate probe position to be placed in front of the thick and homogeneous part of the organ to be characterized.

[0029] It will be understood that two-dimensional elastic wave velocity maps such as those described in Mellema et al. (or for example in the document "In vivo time-harmonic ultrasound elastography of the human brain detects acute cerebral stiffness changes induced by intracranial pressure variations" by H. Tzschatzsch et al., published in Scientific Reports, Vol. 8, Article No. 17888, 2018) do not constitute homogeneity information describing the ability of the tissue to propagate elastic waves and the homogeneity of the tissue with regard to the propagation of elastic waves. Indeed, such maps do not actually provide any information about the propagation of the waves, since these maps only represent a momentary snapshot of the organ under examination.

[0030] In an embodiment of the disclosed technology, the homogeneity information provided by the system indicates whether the spatiotemporal characteristics of the tissue deformation caused by the periodic mechanical vibrations are those of a wave traveling in a homogeneous medium (the deformation in question being tracked by the echo signal acquired in step b).

[0031] As shown in Fig. 14, Fig. 16, Fig. 17 and Fig. 18, the spatiotemporal characteristics of the tissue deformation with respect to the propagation of elastic waves through the tissue, i.e. the characteristics representing the variation of this deformation both as a function of time and as a function of at least one spatial coordinate (and therefore actually representing the manner in which the elastic waves propagate), reveal the more or less homogeneous nature of the tissue in a very simple and easy to understand manner. Such spatiotemporal characteristics may for example include data representing the variation with depth of the phase delay of the periodic deformation of the tissue. As shown in Fig. 14, when the tissue is homogeneous, this phase delay varies substantially linearly with depth, which is easily identifiable for the operator. Said spatiotemporal characteristics may also include data representing the deformation of the tissue both as a function of depth d and as a function of time t. As shown in Fig. 16 and Fig. 18 (graph 188a), the graphs representing the deformation of the tissue as a function of depth and as a function of time consist of oblique substantially linear stripes that can be easily identified by the operator when the tissue is homogeneous.

[0032] As shown in Figure 18, the propagation mode of such periodic elastic waves is much more sensitive to the structure of the tissue and its elastic properties than the TM mode graph.

[0033] The last three columns of the table in Fig. 18 show TM mode graphs 182c, 182d, 182e, elastic wave propagation images 188c, 188d, 188e acquired in periodic mode (periodic elastic wave propagation graphs), and elastic wave propagation images 185c, 185d, 185e acquired in transient mode for three different situations, one corresponding to a probe position close to the edge of the liver (column c) and the other two being situations with liquid (column d) or air intervening (column e). As shown in Fig. 18, in these situations, the TM mode graphs appear as if the situation is appropriate for transient elastography measurements (as in column a), but in fact it is not (see transient elastography images 185c, 185d, 185e). In other words, TM mode imaging does not distinguish between proper and improper probe positioning, since it cannot accurately detect whether the probe is placed near the edge of the liver or whether air or liquid is interposed between the probe and the targeted organ. In sharp contrast, the noisy periodic elastic wave propagation images 188c, 188d, 188e comprise a large number of irregular fragments, as opposed to one or several diagonal stripes with smooth (substantially linear) edges. Thus, the periodic elastic wave propagation images 188c, 188d, 188e immediately indicate proper probe positioning for transient elastography measurements. Moreover, the presence of even smaller and isoechoic blood vessels (see graph 182b in FIG. 18), which are not visible in the ultrasound signal, can be easily detected in the elastic wave propagation images acquired in periodic mode (see graph 188b in FIG. 18).

[0034] As will be appreciated by those skilled in the art, a periodic elastic wave propagation image having diagonal stripes with substantially uniform and / or smooth edges, such as image 188a in FIG. 18, immediately indicates that the probe is properly positioned and that the conditions are appropriate for transient elastography measurements (see transient elastic wave propagation image 185a in FIG. 18).

[0035] In fact, it has been found that the continuously refreshed homogeneity information provided to the operator in most cases allows the operator to find the proper probe position on the first try, even if he or she is untrained.

[0036] Furthermore, the periodic mechanical vibrations transmitted to the subject under test are less uncomfortable than short transient mechanical pulses that would otherwise be repeatedly triggered by the operator until a suitable probe position is found, and even less uncomfortable than the vibration amplitudes required for periodic elastic wave monitoring, which are significantly smaller than those required to achieve transient elastography measurements. In addition, the continuous nature of the mechanical excitation employed to guide the operator in the systems of the disclosed technology allows for continuous guidance.

[0037] Spatiotemporal monitoring of deformation caused by periodic mechanical vibrations transmitted to a subject can be realized using a single-beam (single-transducer) ultrasound system without 2D or 3D imaging capabilities. Indeed, monitoring wave propagation from a spatiotemporal perspective can be realized by monitoring tissue deformation as a function of time and only one spatial dimension (i.e., depth). In other words, spatiotemporal monitoring can be continued using two-dimensional sampling of deformation, one dimension being time and the other being depth, instead of using two sampling dimensions that are both spatial dimensions (depth and lateral shift as in Mellema et al.). As will be appreciated by those skilled in the art, using a single-beam ultrasound system instead of a 2D imaging ultrasound system allows for rapid processing of acquired echo signals that are one-dimensional from a spatial perspective. This allows for an increase in the temporal sampling rate at which elastic deformation of tissue is tracked, and thus, elastic deformation of tissue is monitored with a higher temporal resolution than prior art harmonic elastography methods.

[0038] Moreover, the high temporal sampling rate allows the same period of the periodic deformation of the tissue, or at least a major part of the same period, to be sampled in its entirety at once. This is very interesting in comparison with techniques such as stroboscope, in which the periodic deformation of the tissue is sampled in small portions, sampling a small part of the period (for example a single instant), then a small part of the subsequent period, etc., to reconstruct an image a posteriori (such as the propagating image 130 in FIG. 13) showing the entire oscillation period. In fact, with the stroboscope technique, the delay time required to obtain a new completely refreshed image showing the entire oscillation period is much longer than if the same period were sampled all at once with a high sampling rate (in the example of FIG. 13, the delay time is about four times longer than if the same period were sampled all at once). More importantly, the temporal images obtained by stroboscopic sampling are often corrupted by spurious effects and noise, especially due to tissue displacements caused by breathing, or even small displacements of the probe. Furthermore, the temporal resolution of propagation images obtained by stroboscopic sampling will generally be smaller than when the same period is sampled all at once (e.g., the temporal resolution of propagation images 131 to 134 in FIG. 13 is better than the temporal resolution of propagation image 130).

[0039] As will be appreciated by those skilled in the art, graphs showing the periodic deformation of tissue in a spatiotemporal manner (such as in FIG. 18) as a function of depth and time are easy to understand as they are. This is quite surprising in comparison to prior art harmonic elastography techniques, such as those of Mellema et al. or Tzschatzsch et al., where graphs showing the instantaneous deformation of tissue (as a function of two spatial coordinates) are barely understandable (see, for example, FIG. 9a in Millena et al. or FIG. 3a in Tzschatzsch et al.) and require complex post-processing to obtain information useful to the operator (such as a 2D shear wave velocity map).

[0040] In summary, according to the disclosed technology, a system for characterizing tissue has very good guidance capabilities, allowing an operator to quickly and easily find areas of homogeneous tissue suitable for transient elastography measurements or to determine ultrasound parameters for ultrasound propagation in tissue.

[0041] To benefit from these guiding features, in an embodiment of a system for characterizing tissue according to the disclosed technology, a control module of the system: Ultrasound parameters for tissue ultrasound propagation attenuation values; Mechanical properties of tissues in response to shear wave propagation as determined by transient elastography The method is further programmed to determine at least one physical property of the tissue, including one of:

[0042] Ultrasound parameters include, for example, broadband ultrasound attenuation (BUA, usually expressed in dB / cm / MHz), attenuation measured at a particular frequency (expressed in dB / cm), or an ultrasound attenuation parameter reflecting the ultrasound attenuation of tissue, such as a controlled attenuation parameter (CAP), however, this is not limiting as additional parameters can be determined in other embodiments.

[0043] The mechanical properties of tissue related to shear wave propagation are determined by the shear wave propagation velocity V s , the shear modulus of the tissue, or a quantity related to the stiffness of the tissue, such as the Young's modulus E of the tissue. It may also be a quantity related to low frequency shear wave attenuation in the tissue, such as viscosity.

[0044] It will be appreciated that a system for determining mechanical properties by transient elastography, in which the propagation of periodic elastic waves is previously monitored to find homogeneous tissue, is in some way initially configured for transient elastography and further modified to implement the above-mentioned guiding technique, but is very different, even contradictory, to transient elastography techniques (which aim to separate compressional and shear waves) and different from prior art harmonic elastography techniques (which focus almost purely on the spatial characteristics of the deformation field and are not intended to help the operator properly position the probe).

[0045] In an embodiment according to the disclosed technology, the control module is programmed to determine data representative of periodic deformation of the tissue at various depths within the tissue and at various times of the periodic mechanical vibration transmitted to the tissue from at least some of the echo signals acquired in step b).

[0046] In an embodiment according to the disclosed technology, the homogeneity information is: a graph of the time-dependent, cyclical variation of the deformation of the tissue, representing the variation of at least one time characteristic with respect to depth; or An indication of whether the characteristic changes with depth, as if the tissue were homogenous over a given depth range. It has one of the following:

[0047] The graph is: - Changes in deformation over time and with depth; - phase delay of cyclic deformation of tissue as a function of depth; - the amplitude of the envelope of this periodic deformation as a function of depth can be represented as follows.

[0048] In one embodiment, the above graph represents the deformation of the tissue at various depths within the tissue and at various times of the periodic mechanical vibration transmitted to the tissue, the graph being a two-dimensional image where the pixel row index represents the depth and the pixel column index represents the time or vice versa, and each pixel has a pixel value representing the deformation of the tissue at the depth and time associated with the pixel considered.

[0049] In one embodiment, the indication specifies whether a graph representing the deformation of the tissue at various depths within the tissue and at various times of the periodic mechanical vibration transmitted to the tissue consists of diagonal stripes across said depth range, the graph being a two-dimensional image in which the row index of a pixel represents the depth and the column index of a pixel represents the time or vice versa, and each pixel has a pixel value representing the deformation of the tissue at the depth and time associated with the pixel considered.

[0050] In one embodiment, the system includes a manual adjustment control, such as a cursor, slider, button, or knob, that allows an operator to manually adjust the amplitude of the periodic mechanical vibration. This is useful when the amplitude of the periodic deformation of the tissue caused by the periodic mechanical vibration transmitted to the tissue is too low or too high. The system may include an amplitude indicator to display information regarding the amplitude of the periodic deformation of the tissue to the operator.

[0051] In one embodiment, the system is configured to automatically (i.e., without requiring operator action) adjust the amplitude of the periodic mechanical vibration based on the amplitude of the resulting cyclic deformation of the tissue. More precisely, the system may be configured to increase the amplitude of the periodic mechanical vibration when the amplitude of the resulting cyclic deformation of the tissue is too low (below a given threshold) and to decrease the amplitude of the periodic mechanical vibration when the amplitude of the resulting cyclic deformation of the tissue is too high (above another amplitude threshold).

[0052] In one embodiment, the system is configured to adjust the amplitude of a transient mechanical pulse delivered to the subject for measuring tissue mechanical properties associated with shear wave propagation by transient elastography based on the amplitude selected for the periodic mechanical vibration, whereby preliminary characterization of tissue by periodic elastography, in addition to the various advantages discussed above, allows for the determination of a suitable transient mechanical pulse amplitude for subsequent continued transient elastography measurements.

[0053] It will be understood that in accordance with the disclosed technology, the various embodiments presented above can be combined together in all combinations that are technically possible.

[0054] Optional, non-limiting features of the system for characterizing tissue presented above, in accordance with the disclosed technology, are defined by claims 3 to 7 and claims 10 to 18 as filed.

[0055] The disclosed technology also provides a method for characterizing tissue, comprising: a probe for being held against the skin of the subject and comprising a vibrator for transmitting mechanical vibrations to tissue of the subject; an ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive corresponding echo signals; Control module and Continued by a system with The control module may include the following steps: a) transmitting continuous periodic mechanical vibrations to tissue of a subject; b) emitting a sequence of ultrasound shots by an ultrasound emitter and acquiring corresponding echo signals received by an ultrasound receiver in order to track how the tissue is moved by the periodic mechanical vibrations transmitted to the tissue; c) providing the homogeneity information to an operator of the system. wherein the periodic mechanical vibrations consist of the same vibration pattern repeated several times in succession over time; Homogeneity information is determined from at least some of the echo signals acquired in step b), the homogeneity information being representative of the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with regard to the propagation of the elastic waves; The control module is programmed such that steps b) and c) are executed by the system continuously and several times in succession. A method is also provided.

[0056] The features of the various embodiments of the system described above may also be applied to this method for characterizing tissue. [Brief description of the drawings]

[0057] [Figure 1] FIG. 1 shows various graphs and indicators displayed to an operator by the display screen of the FIBROSCAN® system. [Diagram 2] FIG. 1 shows a TM mode graph displayed to the operator regarding the position of the FIBROSCAN® probe relative to the organ being characterized. [Diagram 3] FIG. 1 shows a TM mode graph displayed to the operator regarding the position of the FIBROSCAN® probe relative to the organ being characterized. [Figure 4] FIG. 1 shows a TM mode graph displayed to the operator regarding the position of the FIBROSCAN® probe relative to the organ being characterized. [Diagram 5] FIG. 2 shows a graph of the TM mode acquired when the FIBROSCAN® probe is properly positioned and its axis is centered on the organ to be characterized. [Figure 6] FIG. 13 shows graphs of various TM modes acquired when the probe is not properly positioned and its axis is close to the edge of the organ to be characterized, or in situations where there is intervening liquid, air, or blood vessels that are not suitable for proper mechanical characterization of the organ. [Figure 7] FIG. 1 is a block diagram of a system for characterizing tissue in accordance with some embodiments of the disclosed technology. [Figure 8] 1 is a flowchart of a method for characterizing tissue in accordance with some embodiments of the disclosed technology. [Figure 9] 1 illustrates a continuous, periodic mechanical vibration transmitted to tissue of a subject, a sequence of ultrasound shots emitted to track the deformation of the tissue caused by the vibration, and an elastic wave propagation image obtained therefrom, in accordance with some embodiments of the disclosed technology. [Figure 10] 1A-1C show another approach to emitting a sequence of ultrasound shots to track continuous, periodic mechanical vibrations transmitted to tissue of a subject and the deformation of the tissue caused by the vibrations, in accordance with some embodiments of the disclosed technology. [Figure 11] 1 illustrates a continuous, periodic mechanical vibration transmitted to tissue of a subject, yet another approach of emitting a sequence of ultrasound shots to track the deformation of the tissue caused by the vibration, and a periodic elastic wave propagation image obtained therefrom, in accordance with some embodiments of the disclosed technology. [Figure 12] 12 illustrates how the periodic elastic wave propagation image of FIG. 11 can be aligned in time for viewing by an operator in accordance with some embodiments of the disclosed technology. [Figure 13] FIG. 1 illustrates the difference between a low sampling rate stroboscope-like method for tracking periodic deformations of tissue, in accordance with some embodiments of the disclosed technology, and a high sampling rate method for tracking such periodic deformations of tissue, in which the same period of tissue deformation is monitored all at once, as a whole. [Figure 14] 1A-1C illustrate phase delays of elastic waves at specific depths in tissue, as determined in accordance with some embodiments of the disclosed technology. [Figure 15]1A-1C illustrate various graphs and indicators displayed to an operator by a system for characterizing tissue in accordance with some embodiments of the disclosed technology. [Figure 16] 1A-1C show exemplary elastic wave propagation images from homogenous tissue, in accordance with some embodiments of the disclosed technology; [Figure 17] 1A-1C show exemplary elastic wave propagation images from non-homogeneous tissue, in accordance with some embodiments of the disclosed technology; [Figure 18] 1A-1C are diagrams illustrating exemplary TM graphs, periodic elastic wave propagation images, and transient elastic wave propagation images that are provided to an operator in accordance with some embodiments of the disclosed technology, the graphs and images being obtained in several different situations and probe positions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0058] 7 is a block diagram of an ultrasound system 1 for tissue characterization configured to detect homogenous tissue. The system 1 comprises: - a probe 10 comprising a vibrator 12 adapted to be held against the body of a subject 50 and to transmit mechanical vibrations to tissue 51 of the subject; - an ultrasound emitter configured to emit a sequence of ultrasound shots and an ultrasound receiver configured to receive corresponding echo signals in order to track how tissue of the subject is moved by such mechanical vibrations; a control module 20 that controls the probe 10 and processes the data acquired by the ultrasound receiver; Equipped with.

[0059] The expression "tissue" is understood to mean a part of the body of a subject 50 (either human or animal). This expression does not necessarily designate an entire organ or a single organ. The tissue 51 to which the mechanical vibrations are transmitted and whose deformations are tracked by the ultrasound shots is the part of the subject's body located near the probe 20 along the axis z of the probe.

[0060] The system 1 is configured to determine homogeneity information indicating whether the tissue 51 is homogeneous and whether it is capable of transmitting elastic waves, in particular shear waves, using cyclic elastography techniques, and to provide this information to an operator via the operator interface 30.

[0061] The homogeneity information constitutes guide information that helps the operator to position and align the probe 20 with the organ to be characterized, such as the liver or spleen. Once the probe 20 is properly positioned thanks to this guide information, one or several physical properties of the tissue can be determined to characterize this organ, for example using transient elastography.

[0062] In this document, the expression "elastic waves" is understood to mean low-frequency mechanical waves or tissue deformations, i.e. mechanical waves or tissue deformations having a central frequency of less than 500 Hertz, or even less than 100 Hertz, in contrast to ultrasound shots or echo signals, which have a central frequency typically higher than 0.1 Megahertz, or even higher than 1 Megahertz (such ultrasound waves, while propagating in tissue, also produce certain elastic deformations at much higher frequencies, which are not specified as "elastic waves" in this document).

[0063] To provide homogeneity information, the control module 20 controls the system 1 for characterizing tissue to perform the following steps: a) transmitting a continuous periodic mechanical vibration PMV to tissue 51 of a subject 50; b) emitting a sequence of ultrasound shots (such as the sequence 80, 80', 80'' in FIG. 9) by the ultrasound emitter 11 and acquiring corresponding echo signals received by the ultrasound receiver 11 in order to track how the tissue 51 is moved by the periodic mechanical vibrations PMV transmitted to the tissue; c) providing said homogeneity information to an operator 40 of the system. More precisely, the periodic mechanical vibration is programmed to execute the periodic mechanical vibration consisting of the same vibration pattern VP repeated several times successively over time (see, for example, FIG. 9 ), Homogeneity information is determined from at least some of the echo signals acquired in step b).

[0064] The control module 20 is programmed to perform steps b) and c) repeatedly, continuously (i.e., without interruption), until the operator 40 triggers the transient elastography measurement by pressing the control button 13. Thus, the homogeneity information provided to the operator 40 is continuously refreshed, which helps the operator find the proper probe position.

[0065] The system 1 may be configured to determine said homogeneity information to indicate, more precisely, whether the tissue 51 is homogeneous over a given depth range or region of interest. This depth range is, for example, the depth range in which the subject's liver is expected to extend if the probe 20 is properly positioned. This depth range may, for example, extend between 25 and 65 millimeters deep below the subject's skin (where the liver is usually located), or between 35 and 75 millimeters deep. This depth range delimits, within the tissue 51, a region of interest ROI of the tissue to be characterized (in FIG. 15, this region of interest extends between two horizontal dashed lines).

[0066] The control module 20 is also programmed to determine at least one physical property of the tissue 51 so that, once the probe 10 is properly positioned, the organ of interest may be characterized. Ultrasound parameter values ​​for ultrasound propagation in tissue, for example ultrasound attenuation values ​​such as BUA, CAP and / or attenuation measured at specific frequencies; Shear wave propagation velocity V s, mechanical properties of tissue relevant to shear wave propagation, as determined by transient elastography, such as tissue shear modulus, tissue Young's modulus E, or tissue viscosity at low frequencies (i.e., less than 500 Hz) may include.

[0067] More precisely, system 1 of Fig. 7 can be configured to determine tissue mechanical properties related to shear wave propagation for tissues with Young's modulus comprised between 1 and 100 kilopascals (suitable for studying liver or spleen stiffness). System 1 may also be configured to determine ultrasound attenuation values ​​in tissues with CAP values ​​comprised between 50 dB / m and 500 dB / m.

[0068] Next, the structure of system 1 of Figure 7 will be described in more detail. Then, a method for characterizing tissue according to some embodiments of the disclosed technology, depicted in Figure 8 and which may be implemented by system 1 of Figure 7, will be presented along with exemplary results obtained by this system or method (see Figures 15 to 18).

[0069] As already indicated, the probe 20 of the system 1 of Fig. 7 comprises a vibrator 12, such as an electromechanical vibrator or an acoustic speaker, for transmitting mechanical vibrations to the subject's tissue 51. This mechanical vibration may be transmitted to the tissue as a force applied to the subject's body by the tip of the probe, as forced by the tip, as a displacement of a part of the subject's body upon contact with the tip, or a combination thereof.

[0070] In the system 1 of Figure 7, the vibrator 12 is rotationally symmetric about a vibrator axis that coincides with the probe axis z. As the vibrator 12 vibrates, it induces a predominantly longitudinal displacement parallel to its axis.

[0071] In the system 1 of FIG. 7, the ultrasound emitter and the ultrasound receiver are constituted by the same ultrasound transducer 11 (for example a piezoelectric transducer). This ultrasound transducer 11 is rotationally symmetric about the transducer axis and emits an ultrasound beam centered on this axis. The axis of the transducer coincides with the axis of the vibrator. The ultrasound transducer 11 has for example a circular cross section, the axis of the vibrator passing through the center of this cross section. In this system, the transducer 11 is part of a probe 10. It is mounted between a vibrator 12 and the tip of the probe. The tip of the probe is the part of the probe that is placed in contact with the subject's body. The tip is relatively small: its contact surface is usually less than one square centimeter. The tip may have a diameter smaller than one centimeter, or smaller than 8 or even smaller than 5 millimeters.

[0072] The probe 10 includes a manual trigger, such as a control button or dial 13. The system 1 is configured to provide a transient elastography measurement when the manual trigger 13 is actuated.

[0073] The probe may include manual adjustment controls, such as cursors, sliders, buttons, or knobs, for manually adjusting the amplitude of the periodic mechanical vibration, the amplitude of the transient mechanical pulse, or both.

[0074] The system may be configured to automatically adjust the amplitude of the periodic mechanical vibration (in harmonic elastography) and / or the amplitude of the transient mechanical pulse (in transient elastography). The system may be configured to automatically adjust the amplitude of the transient mechanical pulse based on a previously adjusted amplitude of the periodic mechanical vibration.

[0075] It will be appreciated that in other embodiments of the disclosed technology, the ultrasonic emitter and receiver may be constituted by two separate transducers rather than the same. Furthermore, the probe may comprise an additional vibrator, such as an electromechanical vibrator, an acoustic speaker, or an electric motor with an eccentric cam. This additional vibrator may be rotationally symmetric about the z-axis, as with the vibrator 12 described above, or may be configured to induce vibrations at least parallel to the z-axis. In such an embodiment, the system may be configured to generate transient mechanical vibrations by the vibrator 12, while generating periodic mechanical vibrations by the additional vibrator.

[0076] 7 also comprises a central unit 20 including a control module 21, an ultrasonic front end 22 with an ultrasonic transmitter module 27 and an ultrasonic receiver module 29, and a motion actuated servo controller 23 that controls the vibrator 12. The ultrasonic front end 22 and the motion actuated servo controller 23 are both connected to the control module 21 (i.e., they can receive instructions from or send data to the control module 21).

[0077] The motion actuated servo controller 23 comprises an electrical circuit configured to generate appropriate electrical signals to drive the vibrator 12 when commanded by the control module 21. The electrical circuit may comprise a current amplifier, or another type of amplifier.

[0078] The ultrasonic front end 22 comprises a switch 28 for alternately transmitting and receiving ultrasonic signals. The ultrasonic transmitter module 27 of this front end 22 comprises an electrical circuit configured to generate an electrical ultrasonic signal suitable for driving the ultrasonic transducer 11 when commanded by the control module 21 (such as a sequence of ultrasonic shots described further below with reference to step b). This electrical circuit may comprise an amplifier and a digital-to-analog converter (DAC), for example an 8- to 16-bit DAC with a rate of 10 to 1000 megasamples per second. The ultrasonic receiver module 29 comprises an electrical circuit configured to acquire an electrical ultrasonic signal (echo signal) previously received by the ultrasonic transducer 11 (and transmitted to the ultrasonic receiver module 29 via the switch 28). The electrical circuit of the ultrasonic receiver module 29 may comprise a tension amplifier, a filter and an analog-to-digital converter (ADC), for example an 8- to 16-bit ADC with a rate of 10 to 1000 megasamples per second.

[0079] The control module 21 is a device or system having electrical circuitry for processing data, such as a microprocessor connected to a non-volatile memory with machine-executable instructions, and / or a programmable microcircuit such as an FPGA (Field Programmable Gate Array) or a DSP (Digital Signal Processor).

[0080] As represented in FIG. 7, the control module 21 more specifically: For example, a processor 24 such as a general purpose processor; a signal processing circuit 26, such as, for example, an FPGA (FPGA co-processor), a DSP or other programmable circuit; a physical non-transitory memory module 25 comprising non-volatile memory 250 for storing machine-executable instructions executed by the processor 24, and optionally RAM memory 251 for storing signal data and instructions during system operation; Equipped with.

[0081] The control module 21 may, for example, be in the form of an FPGA carrier board. The processor 24 may be embedded either within the signal processing circuit 26 (e.g., within the FPGA) or outside this circuit (e.g., where the FPGA offloads the processor 24 by performing special signal processing tasks such as echo signal correlation calculations). The signal processing circuit 26 is configured to process the echo signals received by the transducer (once digitized by the ultrasound receiver module 29).

[0082] As already mentioned, the control module 21 is programmed to cause the system 1 to carry out steps a), b) and c) above. When executed by the control module 21, the control module 21 is programmed to: controlling the motion actuated servo control 23 to drive the vibrator 12 to transmit periodic mechanical vibrations to the tissue (step a); controlling the ultrasonic front end 22 so that it drives the ultrasonic transducer 11 to emit a sequence of ultrasonic shots and so that the ultrasonic receiver module 29 acquires corresponding echo signals in order to track how the tissue is moved by the periodic mechanical vibrations (step b)); determining from at least some of the echo signals thus acquired homogeneity information representative of the ability of the tissue to transmit elastic waves, i.e. to propagate elastic waves, and of the homogeneity of the tissue with regard to the propagation of elastic waves, and providing this information to an operator, for example by transmitting it to the operator interface 30 (step c)); The system is programmed to perform these steps, including instructions to:

[0083] The instructions, the execution of which causes the control module 21 to control the system 1 so that it performs any given step, in particular steps a), b) and c), are either stored in the non-volatile memory 250 in the form of machine-executable instructions or code instructions, or are physically embedded in the programmable circuit 26 in the form of electrical (reconfigurable) connections between the gates of this circuit, or a combination thereof.

[0084] More specifically, in step c), the control module 21: c0) determining from the echo signals acquired in step b) data representative of the deformation of the tissue 51 at various depths d within the tissue and at various times t1, t2, t3 of the periodic mechanical vibration transmitted to the tissue; c1) determining homogeneity information from the data representative of the deformation of the structure 51 determined in step c0), It can be programmed.

[0085] Step c0) may be performed using correlation techniques or another pattern matching algorithm to determine how a portion of tissue 51 moves under the influence of elastic waves (which are generated by periodic mechanical vibrations transmitted by the system) passing therethrough. For example, tissue within a small zone of the region of interest may move slightly away from and then slightly towards transducer 11 as a spatial period of elastic waves passes through this zone. Step c0) is typically performed by programmable circuitry 26 to offload processor 24.

[0086] The control module 21 may be further programmed to, among other things, cause the system 1 to execute various steps of the method for characterizing tissue depicted in FIG.

[0087] As depicted in FIG. 7, the system 1 for characterizing tissue comprises the operator interface 30 described above. Moreover, in other embodiments according to the disclosed technology, the operator interface may be different from the system for characterizing tissue. The operator interface may be embedded in, for example, a smartphone or a computer that communicates with the system for characterizing tissue. In such a case, to provide the homogeneity information to the operator, the control module 21 transmits this information to the external operator interface by way of a communication module of the system for characterizing tissue. The communication module may be an electrical circuit configured to exchange data using a wired or wireless link, for example according to USB, Firewire, Bluetooth, 6LoWPAN, ZigBee, Z-Wave, or Sigfox protocols.

[0088] In the system of Figure 7, homogeneity information determined by the control module 21 is provided to the operator by the display screen 31 of the operator interface 30, for example in the form of graphs 808, 809 and indicator 810 of Figure 15. The operator interface 30 may also include a light emitting diode or other light emitting device 14 disposed on the probe 10 to visually indicate to the operator 40 whether the tissue is homogeneous by a change in color or intensity of emitted light.

[0089] According to some embodiments in which the system is a pocket system, the operator interface comprises the light emitting devices described above but does not comprise a display screen.

[0090] In yet another embodiment, the operator interface comprises a speaker for indicating to the operator via an audible signal whether the tissue is homogenous or not. Such homogeneity information may also be provided to the operator via tactile indications such as changes in the type or amplitude of mechanical vibrations.

[0091] Although the central unit 20 and the probe 10 are represented as separate parts in FIG. 7, all or some of the modules 21, 22, 23 of the central unit 20 presented above may be located within the probe.

[0092] It is understood that many variations can be made in the system for characterizing tissue presented above without departing from the scope of the disclosed technology. For example, some electrical functions can be distributed in the central unit differently than described above. As an example, the DAC and ADC can be placed in the control unit instead of the ultrasound transmitter module and the ultrasound receiver module. Some of the modules 23 to 29 can be merged together or distributed. Furthermore, the control unit may include only one processor instead of one processor and a signal processing unit. Alternatively, the control unit can include more processing units than in FIG. 7.

[0093] A flow chart of a method for characterizing tissue according to some embodiments of the disclosed technology is depicted in Figure 8. As previously mentioned, the control module 21 of the system 1 of Figure 7 can be programmed to cause the system 1 to perform this method.

[0094] The method includes the following main steps: S0, detecting homogeneous tissue; S1, measuring tissue stiffness by transient elastography; and S2, providing ultrasonic attenuation values ​​to an operator. In step S0, the system 1 transmits continuous periodic mechanical vibrations to the subject to test tissue homogeneity and provides said homogeneity information to the operator 40. This information is continuously refreshed so that the operator can monitor the tissue homogeneity in real time and test various probe positions. When the homogeneity information indicates that the tissue 51 under test is homogeneous, the operator 40 activates a manual trigger (e.g., the operator presses the control button 13). Then, execution of step S0 stops and execution of steps S1 and S2 starts. Once the tissue stiffness measurement is made in step S1, execution of step S0 resumes so that the operator can verify that the probe is still placed in front of the homogeneous tissue. The process of alternating between emitting continuous periodic mechanical vibrations (for homogeneity assessment) and measuring tissue stiffness by transient elastography can be continued until the required number of tissue stiffness measurements have been obtained.

[0095] Steps So, S1 and S2 will now be described in more detail in turn.

[0096] Step S0: Detecting homogeneous tissue As represented in FIG. 8, step So comprises the above steps a), b) and c). Step So starts with step a), during which the control module 21 controls (via the motion actuated servo control 23) the vibrator 12, which transmits a continuous periodic mechanical vibration PMV to the tissue 51 of the subject 50. This periodic mechanical vibration PMV is continuously transmitted (persistent throughout step S0) throughout step S0. Once the emission of this periodic mechanical vibration PMV begins, the control module executes step b), during which the control module controls the ultrasonic transducer 11 (via the ultrasonic transmitter module 27) to emit a sequence of ultrasonic shots and to acquire (via the ultrasonic receiver module 29) corresponding echo signals in order to track how the tissue is moved by the periodic mechanical vibration. Then, in step c), the control module determines homogeneity information from the echo signals acquired in step b) and then provides it to the operator. The control module then executes steps b) and c) again, but the periodic mechanical vibration PMV continues to be transmitted to provide the operator with new updated homogeneity information. Thus, the set of steps comprising steps b) and c) is executed successively several times until step S0 is stopped by the operator activating the manual trigger described above. For example, in the case of FIG. 9, the set of steps comprising steps b) and c) is repeated every 50 milliseconds (at a repetition rate of 20 Hertz). Thus, in this case, if the operator takes (for example) 3 seconds to find the appropriate probe location and activate the manual trigger, step So will last for about 3 seconds, and the set of steps comprising steps b) and c) will be repeated about 60 times.

[0097] In the embodiment of Figure 8, the set of steps including steps b) and c) is performed in real time, i.e. at a repetition rate of 10 Hertz or more, or even 20 Hertz or more, with a delay time of 1 second or less, or 0.1 seconds or less, or even less than 0.03 seconds. The delay time is the time interval between the start of the emission of the sequence of ultrasound shots in step b) and the moment that updated homogeneity information determined from the echo signals acquired in step b) is provided to the operator.

[0098] In the method of Fig. 8, step c) comprises the sub-steps c0) and c1) described above. In step c0), the control module determines from the echo signals acquired in step b) data representative of the deformation of the tissue 51 at various depths d in the tissue and at various time points t1, t2, t3 of the periodic mechanical vibration transmitted to the tissue. In step c1), the homogeneity information provided to the operator comprises a graph representing the deformation of the tissue caused by the periodic mechanical vibration (this deformation having been determined in step c0)), both as a function of time t and as a function of depth d, such as graphs 808 of Figs. 9 and 15, graphs 168, 178 of Figs. 16 and 17, or graphs 188a to 188e of Fig. 18.

[0099] Steps a), b) and c) will now be described in more detail.

[0100] In step a), the periodic mechanical vibration transmitted to the tissue has a base frequency, i.e. a fundamental frequency, comprised between 10 and 200 Hertz. It may have a base frequency comprised more specifically between 10 and 60 Hertz. Such a frequency value is preferred for deep penetration of the vibration in the tissue, but is fast enough to determine the homogeneity information updated at an update rate of 10 Hertz or more, thus allowing real-time monitoring of the homogeneity of the tissue. The periodic mechanical vibration PMV may have a base frequency of, for example, 40 Hertz (thus with a period of 25 milliseconds) as in Figs. 9 and 10, or 25 Hertz (thus with a period of 40 milliseconds) as in Fig. 11. As represented in Figs. 9, 10, and 11, the periodic mechanical vibration PMV is a sinusoidal vibration. Nevertheless, other periodic waveforms, such as triangular waveforms, may be adopted. The periodic mechanical vibration PMV is continuous in that it comprises the same vibration pattern VP (here a sinusoidal period) repeated cyclically one after the other and several times in succession over time. Each new instance of the vibration pattern starts immediately after the previous one, with no delay in between. The vibration pattern is repeated at a repetition rate, which is the base frequency mentioned above. As already mentioned, the periodic mechanical vibration continues continuously throughout step S0. Thus, the periodic mechanical vibration typically lasts for more than 1 second. The part of the subject's tissue 51 in contact with the probe 20 oscillates with an amplitude typically comprised between 0.1 and 2 millimeters as a result of the periodic mechanical vibration transmitted by the probe.

[0101] In step b), the control module 21 commands the ultrasonic transmitter module 27 to generate a sequence of ultrasonic electric pulses that are transduced by the ultrasonic transducer 11, which then emits a sequence of short ultrasonic pulses, called ultrasonic shots, to track, or in other words probe, how the tissue 51 is moved by the periodic mechanical vibration PMV. FIG. 9 shows a representative sequence 80 of ultrasonic shots 81, 82, .... The central frequency of each ultrasonic shot is comprised, for example, between 1 megahertz and 5 megahertz. The duration of each shot is, for example, equal to 100 microseconds, and is usually shorter than a millisecond. In step b), the control module 20 also acquires a sequence of corresponding echo signals received by the ultrasonic transducer 11. Each echo signal corresponds to an ultrasonic shot emitted by the transducer, in that each echo signal is (or at least represents) an ultrasonic wave backscattered by the tissue in response to the emission of the ultrasonic shot considered. Each echo signal represents the backscattering properties of the tissue as a function of depth d within the tissue (since each instant within one of these short echo signals corresponds to a given depth within the tissue, since the round-trip travel time of the ultrasound between the transducer and a point located at the depth under consideration depends directly on that depth).

[0102] As already mentioned, these successive echo signals are acquired for comparison with each other, for example using correlation techniques or another pattern matching algorithm, to determine how parts of the tissue 51 move under the effect of elastic waves passing through the tissue (this determination continues in step c)). Therefore, in order to prevent decorrelation between two subsequently acquired echo signals, in step b), ultrasound shots are emitted with a pulse repetition rate of 500 Hertz or even 1 kilohertz or more (indeed, such decorrelation can occur due to global tissue displacements caused by breathing, for example when the duration between two successive shots is too long). Typically, the pulse repetition rate is comprised between 1 kilohertz and 10 kilohertz (depending on the computational capacity of the control module). Thus, within the sequence of ultrasound shots emitted in step b), the duration between any shot and the shot immediately following it is less than 2 milliseconds, or even less than 1 millisecond.

[0103] In the method of Fig. 8, the sequence of ultrasound shots emitted in step b) extends over at least half, or even at least 3 / 4, of the same period (for example the entire period of the periodic mechanical vibration) of the periodic mechanical vibration PMV transmitted to the tissue, and the sequence comprises at least 10, or even 50 ultrasound shots per period of the periodic mechanical vibration. As a result, in this case, the same period of the periodic mechanical vibration PMV, or at least a major part of the same period, is sampled all at once as a whole by the sequence of shots emitted in step b). As already explained, this allows a better monitoring of the propagation of the periodic elastic deformation than with sampling methods such as stroboscopes.

[0104] In step b), the control module may in particular control the ultrasonic transmitter module 27 to generate a sequence of ultrasonic shots as represented in FIG. 9, FIG. 10 or FIG.

[0105] In the examples of Figures 9 and 10, the sequence 80 of ultrasonic shots emitted in step b) extends, more precisely, over one period of the periodic mechanical vibration PMV. In these examples, the repetition rate of the ultrasonic shots is equal to 2 kilohertz. The sequence of ultrasonic shots therefore comprises 50 shots per period of the periodic mechanical vibration (in these examples, the frequency of the periodic mechanical vibration is equal to 40 hertz).

[0106] In the example of figure 11, the sequence of ultrasound shots emitted in step b) extends over more than one period. The repetition rate of the ultrasound shots may be equal to 2 kilohertz, which corresponds to 80 shots per period (in this case the frequency of the periodic mechanical vibrations is equal to 25 hertz).

[0107] The sequence 80, 80', 80'' of ultrasound shots emitted in step b) can be emitted synchronously with respect to the periodic mechanical vibration, starting from a moment io that is the same for each execution of step b) within a cycle of the periodic mechanical vibration PMV transmitted to the tissue 51. As shown in FIG. 9, this makes it possible to obtain a stable propagation graph 808n without rolling (time shift) effects from one execution of steps b) and c) to the other.

[0108] In such a case, the absolute time to, to', to'' at which the sequence of ultrasound shots starts will be different for each execution of step b). However, the time at which the sequence starts relative to the start of a cycle of the periodic mechanical vibration is the same for each execution of step b) (more precisely, the time at which the sequence starts relative to the start of the cycle of the periodic mechanical vibration that is closest to this start time - i.e. relative to the start of the instance of the vibration pattern that is closest to this start time - is the same for each execution of step b).

[0109] For example, in the case of Figures 9 and 10, for each execution of step b), the sequence of ultrasonic shots starts approximately at the beginning of a period of the periodic mechanical vibration, when the vibration passes through zero while increasing (the sequence of ultrasonic shots can also start a given fixed delay time after the start of the period of the periodic mechanical vibration).

[0110] Thanks to this synchronization, for each new run of steps b) and c), the propagation graph representing the deformation of the tissue (estimated from the shots emitted in step b), both as a function of depth and as a function of time, starts from the same instant io in the cycle of the periodic mechanical vibration (like the various propagation graphs 808, 808', 808'' of FIG. 9, which are subsequently displayed to the operator). This graph therefore remains stable for each run and is aligned in time, instead of rolling. Thanks to this stabilization, the graph becomes easier for the operator to understand (since the monitoring of the deformation is not hindered by rolling in time or by shifts of the graph). The operator can therefore more easily determine whether the probe is placed in front of homogeneous tissue, in the right conditions to measure the physical parameters of the tissue.

[0111] Step b) may be repeated at a rate such that each new sequence of ultrasound shots is emitted one after the other without any break between them, as in FIG. 10. In the example of FIG. 10, a sequence of ultrasound shots is thus emitted (to track the deformation of the tissue) for each period of the periodic mechanical vibration PMV. Step b) may also be repeated at a slower rate, for example, by emitting a sequence of ultrasound shots every two periods of the periodic mechanical vibration PMV, as in FIG. 9, when the processing speed of the control module 21 is more limited. In the case of FIG. 9, after each sequence of ultrasound shots is emitted, a new updated version of the homogeneity information is provided to the operator before the next sequence of ultrasound shots is emitted. In other words, in this case, the execution of step c) is completed before a new execution of step b).

[0112] In step b), as represented in FIG. 11, the sequence 110, 110', 110'' of ultrasound shots may also start from different instants io, io', io'' for one execution of step b) within the cycle of the periodic mechanical vibration PMV transmitted to the tissue 51. In such a case, if a raw propagation graph like graphs 118, 118 or 118'' of FIG. 11 is provided to the operator in step c), the operator will notice the above-mentioned disturbance, rolling and time-shifting effects when this raw graph is updated ("raw propagation graph" is understood to mean a graph showing the deformation of the tissue as a function of both time and depth, the deformations being displayed over time in the sampled order; in other words, in such raw graphs, the time coordinate is the actual time at which the deformations were measured).

[0113] Therefore, in this case, in order to prevent such rolling effects, the deformation data determined from the echo signals are post-processed (in step c) in the form of realigned propagation graphs, such as graphs 118a, 118a', 118a'' of FIG. 12, which are all starting from the same, fixed instant within the cycle of the periodic mechanical vibration, in order to be realigned in time before being displayed. In other words, the realigned propagation graphs provided to the operator in step c) are aligned from a reference instant i, which is the same each time the graphs are updated based on newly determined deformation data within the period of the periodic mechanical vibration transmitted to the tissue. R Temporal realignment can be achieved as follows: starting from a reference time point i R The deformation data acquired for a time preceding the reference instant i (the actual absolute measurement time) are moved from the time point of view as a block placed at the end of the deformation data (as if it had been measured immediately after the end of the sequence of ultrasound shots). Ris a given fixed instant in the vibration pattern VP that is repeated several times in succession, for example the beginning of this vibration pattern when the vibration passes through zero with increasing frequency. This realignment technique provides a good stabilization of the representation of the propagation graph from a time point of view. However, the realigned propagation graph thus obtained comprises discontinuities at the junctions with the cut-and-paste blocks of time-shifted data (these discontinuities are identified by arrows in the graphs 118a, 118a', 118a'' of FIG. 12). It will be understood that a propagation graph obtained by directly synchronizing the emission of a sequence of ultrasound shots with a periodic mechanical vibration, as in FIGS. 9 and 10, does not comprise such discontinuities.

[0114] Step c) As already mentioned, in step c0), the control module 21 determines deformation data representative of the deformation of the tissue for different depths within the tissue and at different times of the periodic mechanical vibration transmitted to the tissue by comparing successive ultrasound echo signals using a correlation technique or another pattern matching algorithm.

[0115] In this document, the term deformation is considered in a broad sense, including any motion parameter such as displacement, velocity, deformation, deformation rate, deformation velocity, and any mathematical transformations applied to these parameters.

[0116] In step c1) homogeneity information is determined from the deformation data determined in step c0). The homogeneity information comprises: Propagation graphs such as 808, 168, 178 above; a graph representing the phase delay φ of the periodic deformation of the tissue as a function of depth d, such as graph 809 in FIG. 15; a graph representing the amplitude Amp of the envelope of the cyclic deformation of the tissue as a function of the depth d, such as graph 811 of FIG. 15; Homogeneity Indicator 810 The signal may include one of the following:

[0117] Figure 15 shows examples of elements that may be displayed to an operator by the operator interface screen 31 to provide the operator with homogeneity information. In the case of Figure 15, the homogeneity information comprises all of the elements described above. Additionally, in other embodiments, the homogeneity information may comprise only one or only some of these elements. These various elements and techniques for determining them will now be described in more detail.

[0118] A propagation graph representing the deformation of the tissue at various depths in the tissue and various times of the periodic mechanical vibration may be a two-dimensional image 808 synthesized by the control module 21, whose pixel row index represents the depth d and whose pixel column index represents the time t (or vice versa), with each pixel having a pixel value representing the deformation of the tissue at the depth and time associated with the considered pixel. The pixel value representing the deformation value at the considered point and instant may be a brightness as in FIG. 15 (where the brightness of the pixel is infinitesimally higher than the algebraic deformation value), a color value (such as a hue value), or a combination thereof.

[0119] As already mentioned, when the tissue is homogenous and suitable for elastic wave propagation (no air or liquid), such a periodic elastic wave propagation image 808 consists of one or more oblique stripes. These stripes are oblique in that they are inclined in the td coordinate system. Their slope depends on the propagation time of the periodic elastic waves from the subject's skin to the depth considered. Thus, the slope of these stripes somehow represents the speed at which these elastic waves propagate in the tissue.

[0120] As explained in detail above with reference to Figures 16 to 18 (see section providing an overview of the disclosed technology), such a propagation graph allows an operator to easily determine whether the tissue is homogenous and suitable for elastic wave propagation.

[0121] When the tissue 51 is homogeneous and suitable for elastic wave propagation (e.g., there is no air or liquid between the probe and the target tissue), the phase delay φ varies substantially linearly with depth, as shown by graph 809 in FIG. 15.

[0122] The phase delay φ may be expressed as a duration or an angle (in degrees or radians). At a given depth d, the phase delay φ represents the dephasing between the periodic deformation of the tissue at that depth and a reference periodic oscillation, such as the periodic mechanical vibration transmitted to the tissue or the periodic deformation of the tissue at the top of the tissue. The control module 21 may be programmed to determine the phase delay φ from a frequency domain representation of the deformation data, as represented in FIG. 14. In such a case, a measurement 141 of the deformation of the tissue over time at a particular depth is converted (using a Fourier transform or other time-domain to frequency-domain transform) into a frequency domain representation 142 of this change. This frequency domain representation exhibits a peak at a frequency fq, which is the base frequency of the periodic mechanical vibration transmitted to the tissue. The value 142 of the Fourier transform of the deformation at this particular frequency fq is a complex number whose argument is the phase delay φ (in radians). The phase delay φ is then converted to time and plotted against the depth d. A linear curve fitting 144 is superimposed on the phase delay graph 143 thus obtained to allow the operator to more easily assess the tissue homogeneity (by ensuring that the phase delay does not deviate significantly from a linear variation).

[0123] The amplitude Amp of the change over time of the tissue deformation at a given depth d (i.e. the amplitude of the envelope of this change) can be determined in the same manner as for the phase delay, but for example by considering the amplitude of the Fourier transform at the peak frequency fq instead of the phase. The amplitude Amp can be determined using other types of amplitude envelope estimation or detection techniques.

[0124] When the tissue 51 is homogeneous and suitable for elastic wave propagation, the amplitude Amp is, according to a given theoretical model, for example, 1 / d nwhere n is an integer between 1 and 3. To allow the operator to easily see whether the amplitude Amp varies with depth in this manner, the amplitude Amp can be plotted against depth using a log-linear scale. Indeed, when such a scale is used, the graph showing the change in amplitude with depth is linear, which means that the amplitude varies as a function of 1 / d n If the change is proportional to , it can be easily evaluated from a visual point of view.

[0125] The homogeneity indicator 810 may be displayed in the form of a binary indicator, such as green / red or green / black, or in a more graduated manner, for example, as a needle dial, a percentage value, or a level bar (such as a progress bar).

[0126] The homogeneity indicator 810 identifies whether the tissue 51 is homogeneous, or more precisely, homogeneous over the given depth range above and suitable for the propagation of elastic waves. The homogeneity indicator 810 may identify this information as a continuous value, either in a binary, all-or-nothing manner, or in a more graduated manner.

[0127] As an example, when the homogeneity indicator provides this information in a binary manner, if the tip of the probe is placed in contact with the surface of a phantom (i.e., a test sample made of a synthetic viscoelastic material) that is homogeneous without air or liquid inclusions or inclusions, is sufficiently large (at least 10 cm wide and 10 cm deep), and has a Young's modulus comprised between 1 and 100 kilopascals (or alternatively, between 5 and 75 kilopascals), the indicator will identify (e.g., by turning green) that the medium is homogeneous and suitable for the propagation of elastic waves, and if the phantom is not homogeneous (e.g., contains hard beads) or has a water layer several centimeters below its surface, the indicator will indicate (e.g., by turning black) that the medium is not homogeneous or not suitable for the propagation of elastic waves.

[0128] The control module 21 may be programmed to determine a homogeneity indicator by processing the periodic elastic wave propagation image 808 to detect the presence of one or more homogeneous diagonal stripes in the image. When such stripes are detected, the homogeneity indicator 810 indicates that the tissue 51 is homogeneous and suitable for elastic wave propagation, for example, by switching from black to green.

[0129] The control module 21 may also be programmed to determine a homogeneity indicator by processing the periodic elastic wave propagation image 808 to detect such stripe edges or mean lines, and determine by linear curve fitting whether the edges or lines are substantially linear over the depth range of interest and / or have a slope that is contained within a given interval of possible values. The substantially linear nature of the line or edge is determined by the coefficient of determination R 2 The fitting quality may be evaluated based on fitting quality parameters such as the mean square root of the fitted line, the standard deviation, or other tools that give the relevance between the fitted line and the strictly linear change with depth. The control module is based on the coefficient of determination R 2 It may be programmed to determine that the line or edge is substantially linear if, for example, t is greater than or equal to 0.8, or even greater than or equal to 0.9. The homogeneity indicator may be determined to be equal to or proportional to this fitting quality parameter.

[0130] The control module 21 may also be programmed to determine a homogeneity indicator by determining whether the phase delay φ varies substantially linearly with depth over the depth range of interest and / or has a slope that falls within a given interval of possible values, which may be followed by linear curve fitting as described above.

[0131] The control module 21 may also be programmed to determine a homogeneity indicator by determining whether the phase delay φ varies substantially linearly with depth over the depth range of interest and / or has a slope that falls within a given interval of possible values. This determination may be followed by linear curve fitting, as described above.

[0132] The control module 21 also determines whether the amplitude Amp varies with depth according to a given model, in particular whether the amplitude Amp varies with depth as a function of 1 / d n The model may be programmed to determine the homogeneity indicator by determining whether Amp is proportional to depth. This determination may be followed by curve fitting. According to this model, the fact that the amplitude Amp varies with depth is used to determine the coefficient of determination R, which gives the goodness of fit between the model and the variation of amplitude with depth. 2 The homogeneity indicator may be evaluated based on a fitting quality parameter such as: The homogeneity indicator is determined to be equal to or proportional to this fitting quality parameter.

[0133] The control module 21 may also be programmed to determine various intermediate homogeneity indicators based on the various criteria described above (thus determined either from the periodic elastic wave propagation image 808, from the change in phase delay, or from the change in amplitude Amp) and then determine a final homogeneity indicator based on these various intermediate homogeneity indicators, for example by averaging these intermediate homogeneity indicators.

[0134] The control module 21 may also be programmed in step c1) to estimate a preliminary value of a mechanical property of the tissue related to shear wave propagation, such as Young's modulus, or a range of values ​​where this mechanical property is likely to be found. This value or range of values ​​is determined from the data representative of the cyclic deformation of the tissue determined in step c0). This value or range of values ​​is then provided to the operator, for example by a display screen of the operator interface 30.

[0135] For this purpose, the control module 21 can derive a preliminary estimate of the shear wave propagation velocity in the tissue from the gradient of the diagonal stripes of the periodic elastic wave propagation image 808 described above, or from the gradient of the line 404 representing the change in phase delay φ with respect to depth d. The control module 21 can then determine a preliminary estimate of the Young's modulus from this value of the shear wave propagation velocity. As mentioned in the previous sentence, the value of the shear wave propagation velocity determined in this manner is usually less accurate than the value determined by transient elastography (due, among other things, to the superposition of compressional and shear waves). However, it is still useful to provide the operator with such a preliminary value, or a range of values ​​where the actual value of the Young's modulus (or other mechanical property of the tissue) is likely to be found.

[0136] Step S1: Measuring tissue stiffness by transient elastography In step S1, to determine by transient elastography the mechanical properties of tissue 51 associated with shear wave propagation (e.g., shear modulus, Young's modulus E, shear wave velocity, etc.), the control module 21 causes the system 1 to perform the following steps: d) ceasing the continuous periodic mechanical vibration PMV and then transmitting a transient low frequency mechanical pulse to the subject's tissue; e) emitting a sequence of ultrasound shots by the ultrasound emitter 11 while the low frequency mechanical pulse is traveling through the tissue 51 and acquiring corresponding echo signals received by the ultrasound receiver 11; f) determining said mechanical properties of tissue related to shear wave propagation from at least some of the echo signals acquired in step f). is programmed to execute the

[0137] The control module 21 in step f): f0) determining from the echo signals acquired in step e) data representative of the transient deformation of the tissue at various depths within the tissue and at various times after the low frequency mechanical pulse has been transmitted to the tissue; and f1) from the data representing the transient deformation of the tissue determined in step f0), to determine the mechanical properties of the tissue relevant to shear wave propagation. It can be programmed more specifically. In step d), the control module 21 controls (via the motion actuated servo controller 23) the vibrator 12 to transmit a transient mechanical pulse into the tissue, the duration of which is typically shorter than 0.2 seconds (pulse duration is understood to mean the time lap outside which the pulse amplitude is smaller than 1 / 10 of the maximum amplitude of the pulse peak). This mechanical pulse is a low-frequency pulse, in that its spectral content (its spectral density) is mostly located below 500 Hertz, or even below 100 Hertz. The pulse duration is typically shorter than 10 / f, or even shorter than 2 / f, where f is the central frequency of the pulse spectrum.

[0138] In step e), the control module 21 may control the ultrasonic transducer 11 (via the ultrasonic transmitter module 27) to emit a sequence of ultrasonic shots at a pulse repetition rate of 2 kilohertz or higher. The emitted ultrasonic shots are similar to those emitted in step b) of step S0. However, because step S1 is for precisely measuring the mechanical properties of the tissue as well as visualizing and monitoring the homogeneity of the tissue, the ultrasonic shots are emitted at a higher pulse repetition rate.

[0139] For example, the transient mechanical pulse may last 20 or 40 milliseconds, and the sequence of ultrasound shots last 80 milliseconds, the ultrasound shots being emitted at a pulse repetition rate of 6 kilohertz, making it possible to track the deformation of the tissue as a function of depth at 480 different successive instants distributed during this 80 millisecond period (starting when the emission of the transient mechanical pulse begins). In other words, in this case, the transient elastic wave propagation image 805 will comprise 480 columns.

[0140] In step f0), data representative of the transient deformation of the tissue is determined by comparing the echo signals acquired in step e) with each other, e.g. using correlation techniques or another pattern matching algorithm, as in step c0) of step S0.

[0141] In step f1), the mechanical properties of the tissue related to shear wave propagation are determined according to techniques known in the art.

[0142] The control module 21 may be programmed in step f1) to provide a transient elastic wave propagation image, such as image 805 of FIG. 15, depicting the tissue deformation caused by the transient mechanical pulse both as a function of depth and as a function of time, thereby allowing the operator to visually verify the quality of the transient elastography measurement.

[0143] The control module 21 may also be programmed to provide the value of the tissue mechanical property, once determined, to the operator, for example in the form of a hardness result display 106 shown in FIG.

[0144] Step S2: Providing an ultrasonic attenuation value to an operator In step S2, the control module 12 provides the values ​​of the above mentioned ultrasound attenuation parameters to the operator 40, for example by displaying the values ​​on the screen 31 of the operator interface (for example: in the form of the attenuation result display 107 of FIG. 1).

[0145] The ultrasound attenuation parameters are determined by the control module 21 in step b) of step S0, or more precisely from some or all of the echo signals acquired during the last execution of step b) just before So is stopped. This calculation can be realized either in step S0 or when executing step S2, i.e. when the operator activates the manual trigger.

[0146] It may be noted that many variations may be made in the methods for characterizing tissue presented above without departing from the scope of the disclosed technology.

[0147] For example, step S2 may be suppressed (the method then includes steps S0 and S1, but not S2). Similarly, step S1 may be suppressed.

[0148] Furthermore, the transition from step S0 to steps S1 and / or S2 may be triggered automatically by the control module itself when the homogeneity indicator described above indicates that the tissue under examination is homogeneous and suitable for elastic wave propagation.

[0149] The method includes only step S0, and the step of providing the operator with the ultrasound attenuation parameters is performed in step S0 regardless of the more or less homogeneous nature of the tissue under examination. Furthermore, in such a case, the control module may be programmed to determine a quality factor associated with the ultrasound attenuation parameters, the quality factor being higher when the tissue is homogeneous with respect to the propagation of the periodic mechanical vibrations transmitted to the tissue. The quality factor may be determined, for example, based on the homogeneity indicator described above, as being equal to or proportional to the value of this indicator.

[0150] The various operations performed during the methods may be organized into steps according to a different distribution to that presented above (and thus, in particular, the methods may comprise more steps or sub-steps).

[0151] The disclosed technology also provides a non-transitory computer-readable medium having a computer program with machine-executable instructions, a probe held against the subject's body and including a vibrator for transmitting mechanical vibrations to tissue of the subject; an ultrasonic emitter configured to emit a sequence of ultrasonic shots; an ultrasonic receiver configured to receive corresponding echo signals; The execution by the control module of the system includes causing the control module to perform the following steps: a) controlling a probe to deliver continuous, periodic mechanical vibrations to tissue of a subject; b) controlling an ultrasonic emitter to emit a sequence of ultrasonic shots and acquire corresponding echo signals received by an ultrasonic receiver in order to track how the tissue is moved by the periodic mechanical vibrations transmitted to the tissue; c) providing the homogeneity information to an operator of the system. Run the command, Homogeneity information is determined from at least some of the echo signals acquired in step b), the homogeneity information being representative of the ability of the tissue to transmit elastic waves and of the homogeneity of the tissue with regard to the propagation of the elastic waves; Steps b) and c) are carried out successively several times.

[0152] Embodiments of the subject matter and operations or steps described herein (e.g., elements of central unit 20 in FIG. 7) may be implemented in digital electronic circuitry, or computer software, firmware, or hardware including the structures disclosed herein and structural equivalents thereof, or one or more combinations thereof. Embodiments of the subject matter described herein may be implemented as one or more computer programs, i.e., one or more modules of computer program instructions, encoded in a computer storage medium for execution by or to control the operation of a data processing apparatus.

[0153] A computer storage medium can be or be included in a computer readable storage device, a computer readable storage substrate, a random or serial access memory array or device, or a combination of one or more thereof. Additionally, a computer storage medium is not a propagating signal, but a computer storage medium can be a source or destination of computer program instructions encoded in an artificially generated propagating signal. A computer storage medium can also be or be included in one or more separate physical components or media (e.g., multiple CDs, disks, or other storage devices). The operations described herein can be implemented as operations performed by a data processing apparatus on data stored in one or more computer readable storage devices or received from other sources.

[0154] The term "control module" encompasses any type of apparatus, device, and machine for processing data, including, by way of example, a microprocessor, a digital signal processor (DSP), a computer, a system on a chip, or a combination of two or more of these or the foregoing. A control module may include, for example, special purpose logic circuitry (as in FIG. 1), such as an FPGA or an ASIC (application specific integrated circuit).

[0155] A computer program (also known as a program, software, software application, script, or code) may be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages, and may be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program may be stored in part of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., a file that stores one or more modules, subprograms, or portions of code). A computer program may be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0156] The process and logic flows described herein may be performed by one or more programmable processors executing one or more computer programs to perform actions by operating on input data and generating output. The process and logic flows may also be performed by, and devices may be implemented as, special purpose logic circuitry, such as, for example, an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0157] Processors suitable for executing computer programs include, by way of example, both general purpose and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor receives instructions and data from a read-only memory or a random access memory, or both. The essential elements of a computer are a processor for performing actions in accordance with the instructions, and one or more memory devices for storing instructions and data. Generally, a computer also includes, or is operatively coupled to receive data from, or transfer data to, one or more mass storage devices for storing data, such as, for example, magnetic, magneto-optical, or optical disks. However, a computer need not have such devices. Devices suitable for storing computer program instructions and data include, by way of example, all forms of non-volatile memory, media, and memory devices, including, for example, semiconductor memory devices, such as, for example, EPROM, EEPROM, and flash memory devices, magnetic disks, such as, for example, internal hard disks or removable disks; magneto-optical disks, and CD-ROM and DVD-ROM disks. The processor and memory may be supplemented by or incorporated in special purpose logic circuitry.

[0158] To provide interaction with a user, embodiments of the subject matter described herein may be implemented on a computer having a display device, such as, for example, an LCD (liquid crystal display), LED (light emitting diode), or OLED (organic light emitting diode) monitor, to display information to the user, and a keyboard and a pointing device, such as, for example, a mouse or trackball, through which the user can provide input to the computer. In some embodiments, a touch screen may be used to display information and receive input from the user. Other types of devices may also be used to provide interaction with the user. For example, feedback provided to the user may be any form of sensory feedback, such as, for example, visual feedback, auditory feedback, or tactile feedback, and input from the user may be received in any form, including acoustic, speech, or tactile input.

[0159] From the foregoing it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the scope of the invention. [Explanation of symbols]

[0160] 1 Ultrasound System 3, 10 Probe 4. Liver 11 Ultrasonic transducers, ultrasonic receivers, ultrasonic emitters 12. Vibrator 13 Manual trigger, control button 14 Light-emitting devices 20 Central Unit 21 Control Module 22 Ultrasonic Front End 23 Motion Actuated Servo Controller 24 processors 25 Memory Modules 26 Signal processing circuits, programmable circuits 27 Ultrasonic transmitter module 28 Switch 29 Ultrasonic Receiver Module 30 Operator Interface 31 Display screen, operator interface screen 40 Operator 50 subjects 51 Organization 80, 80', 80'' sequence of ultrasound shots 81, 82 Ultrasound shot 101 A mode graph 102, 602, 602', 602''' TM mode graph 103 Indicators 105 Elastic wave propagation image 105C Compression Wave 105S shear wave 106 Hardness Results, Indicators 107 Ultrasonic attenuation results, indicators 110, 110', 110'' Sequence of ultrasound shots, graph 141 Measurements 142 Frequency domain representation, Fourier transform values 143 Phase Delay Graph 144 Linear Curve Fitting 185a Transient elastic wave propagation image 250 Non-volatile memory 402 TM Graph 805 Transient Elastic Wave Propagation Image 808n Propagation Graph

Claims

1. 1. A system for characterizing tissue of a subject, comprising: a probe held against the subject's body and equipped with a vibrator; an ultrasonic emitter and an ultrasonic receiver; A control module, the system comprising: a) transmitting continuous periodic mechanical vibrations to tissue of a subject, the continuous periodic mechanical vibrations comprising a vibration pattern that is repeated several times successively over time; b) emitting a sequence of ultrasound shots by said ultrasound emitter and acquiring corresponding echo signals received by said ultrasound receiver in order to track how the tissue of the subject is moved by said continuous periodic mechanical vibrations transmitted to said tissue of the subject; c) providing homogeneity information to an operator of the system, said homogeneity information being determined from at least some of the echo signals acquired in step b), said homogeneity information being indicative of the ability of the subject's tissue to transmit elastic waves and the homogeneity of the subject's tissue with regard to the propagation of said elastic waves. and a control module programmed to execute the steps of: The control module includes: Steps b) and c) are performed by the system consecutively and several times in succession; and The system is programmed such that the sequence of ultrasound shots emitted in step b) spans at least half of one period of one of the vibration patterns and comprises at least 10 ultrasound shots emitted during each vibration pattern of the successive periodic mechanical vibrations.

2. The control module: a mechanical property of tissue of the subject, said mechanical property of tissue of the subject being associated with shear wave propagation; 13. The system of claim 1, further programmed to determine by transient elastography at least one physical property of the tissue comprising:

3. The control module configures the system with the steps of: d) ceasing the continuous periodic mechanical vibration and then transmitting a transient low frequency mechanical pulse to tissue of the subject; e) emitting a second sequence of ultrasound shots by the ultrasound emitter while the transient low frequency mechanical pulse is traveling through the subject's tissue and acquiring corresponding second echo signals received by the ultrasound receiver; f) determining said mechanical properties of tissue of the subject from at least some of said second echo signals acquired in step e). The system of claim 2 , further programmed to:

4. when a manual trigger is actuated by an operator of the system; or automatically when the homogeneity information indicates that the subject's tissue is homogeneous with respect to the propagation of the elastic waves; The system of claim 3 , wherein the control module is programmed to trigger the execution of steps d), e) and f).

5. 5. The system of claim 3 or 4, wherein the control module is programmed in step e) such that the second sequence of ultrasound shots is emitted at a pulse repetition rate of 2 kilohertz or greater.

6. 6. The system of claim 1, wherein the control module is further programmed to determine ultrasound parameters related to ultrasound propagation in tissue if the homogeneity information indicates that the subject's tissue is homogeneous with respect to the propagation of the elastic waves, the ultrasound parameters being determined from one or more of the echo signals acquired in step b).

7. 7. The system of claim 6, wherein the control module is programmed to determine the ultrasound parameters from one or more of the echo signals acquired in step b) and to determine a quality factor associated with the ultrasound parameters, the quality factor being higher when the subject's tissue is homogeneous with respect to the propagation of the elastic waves.

8. the control module is programmed to determine from at least some of the echo signals acquired in step b) data representative of periodic deformations of the subject's tissue at various depths within the subject's tissue and at various times of the continuous periodic mechanical vibration transmitted to the subject's tissue, the homogeneity information being calculated based on:

8. The system of claim 1, further comprising a graph representing the variation with depth of at least one time characteristic of the time-periodic variation of deformation of tissue of a subject.

9. 9. The system of claim 8, wherein the graph represents deformation of the subject's tissue at various depths within the subject's tissue and at various times of the continuous, periodic mechanical vibration transmitted to the subject's tissue, the graph being a two-dimensional image comprising a plurality of pixels, each pixel of the plurality of pixels being associated with a row index representing depth and a column index representing time, or vice versa, and each pixel of the plurality of pixels being associated with a pixel value representing the deformation of the subject's tissue at the depth and time associated with the pixel under consideration.

10. A system as described in any one of claims 1 to 7, wherein the control module is programmed to determine from at least some of the echo signals acquired in step b) data representative of periodic deformation of the subject's tissue at various depths within the subject's tissue and at various times of the continuous, periodic mechanical vibration transmitted to the subject's tissue, and the homogeneity information comprises a homogeneity indicator identifying whether at least one temporal characteristic of the temporal, periodic change in deformation of the subject's tissue varies with depth as if the subject's tissue were homogeneous over a given depth range.

11. The system described in claim 10, wherein the homogeneity indicator indicates whether a graph representing the variation of at least one temporal feature with respect to depth consists of diagonal stripes across the depth range.

12. The homogeneity information is a graph representing the phase delay of said periodic deformation of tissue of a subject as a function of depth; or a homogeneity indicator that identifies whether the phase delay of the periodic deformation of tissue of a subject varies substantially linearly with depth across the depth range; The system according to claim 8 , further comprising at least one of the following:

13. a base frequency of the continuous periodic mechanical vibration transmitted to the subject's tissue is comprised between 10 Hertz and 200 Hertz; In step b), the sequence of ultrasound shots is emitted at a pulse repetition rate of 500 Hz or greater.

13. A system according to any one of claims 1 to 12, wherein the control module is programmed.

14. 14. The system of claim 1, wherein the control module is programmed such that the system executes a set of steps including steps b) and c) in real time.

15. the homogeneity information provided to the operator comprises a graph representing deformation of the subject's tissue at various depths within the subject's tissue and at various times during the continuous, periodic mechanical vibration transmitted to the subject's tissue; 15. The system of claim 1, wherein the control module is programmed such that the emission of the sequence of ultrasound shots of step b) is synchronized with the continuous, periodic mechanical vibration, and the sequence of ultrasound shots of step b) begins at a moment within a cycle of the continuous, periodic mechanical vibration transmitted to the subject's tissue that is the same for each execution of step b).

16. 16. The system of claim 1, wherein the homogeneity information provided to the operator in step c) comprises a graph representing the deformation of the subject's tissue both as a function of depth and as a function of time, the graph starting from a moment that is the same each time the graph is updated based on newly determined deformation data within a period of the continuous, periodic mechanical vibration transmitted to the subject's tissue.

17. 17. A system according to any one of claims 1 to 16, wherein the vibrator of the probe is rotationally symmetric about a vibrator axis and the ultrasonic emitter and ultrasonic transmitter are constituted by the same ultrasonic transducer that is rotationally symmetric about a transducer axis coinciding with the vibrator axis.

18. determining from at least some of the echo signals acquired in step b) data representative of periodic deformations of the subject's tissue at different depths within the subject's tissue and at different times of the continuous periodic mechanical vibration transmitted to the subject's tissue, and estimating a value of a second mechanical property of the subject's tissue associated with shear wave propagation, or a range of values ​​in which the second mechanical property of the subject's tissue is likely to be found, based on the data.

18. The system of claim 1, wherein the control module is programmed to:

19. a manual adjustment control for adjusting the amplitude of the continuous periodic mechanical vibration, the control module being further programmed to provide an operator with information representative of the amplitude of the periodic deformation of the subject's tissue caused by the continuous periodic mechanical vibration transmitted to the subject's tissue, the amplitude of the periodic deformation of the subject's tissue being determined from at least some of the echo signals acquired in step b), or the control module is programmed to automatically adjust the amplitude of the continuous periodic mechanical vibrations transmitted to the subject based on the amplitude of periodic deformation of the subject's tissue; 19. A system according to any one of claims 1 to 18.

20. 1. A method for characterizing tissue of a subject, comprising: a probe held against the skin of the subject and comprising a vibrator; an ultrasonic emitter and an ultrasonic receiver; a control module; The control module controls the system to perform the following steps of a method: a) transmitting continuous periodic mechanical vibrations to tissue of a subject by a vibrator, said continuous periodic mechanical vibrations consisting of the same vibration pattern repeated several times successively over time; b) emitting a sequence of ultrasound shots by said ultrasound emitter and acquiring corresponding echo signals received by said ultrasound receiver in order to track how the tissue of the subject is moved by said continuous periodic mechanical vibrations transmitted to said tissue of the subject; c) providing homogeneity information to an operator of the system, said homogeneity information being determined from at least some of the echo signals acquired in step b), said homogeneity information being indicative of the ability of the subject's tissue to transmit elastic waves and the homogeneity of the subject's tissue with regard to the propagation of said elastic waves; It is programmed to execute The control module includes: Steps b) and c) are performed by the system consecutively and several times in succession; and The method of claim 1, wherein the sequence of ultrasound shots emitted in step b) is programmed to span at least half of one period of the vibration pattern and comprises at least 10 ultrasound shots emitted during each vibration pattern of the successive periodic mechanical vibrations.

Images