Systems and related methods for characterizing organizations

Abstract

A system (1) for characterizing tissue comprises: a probe for transmitting continuous and periodic mechanical vibrations (PMV) to tissue (51) of a subject; an ultrasonic transmitter for transmitting a sequence of ultrasonic beams (80, 80', 80") and an ultrasonic receiver for receiving corresponding echo signals to track how the tissue moves due to the periodic mechanical vibrations transmitted 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 based on at least some of the echo signals and representing the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation. A method for characterizing tissue is also provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is related to PCT application PCT / EP2019 / 054656 filed on February 26, 2019 and PCT / EP2019 / 054658 filed on February 26, 2019, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The disclosed technology relates to non-invasive tissue characterization systems, and more particularly, to systems and methods for identifying homogeneous tissue, wherein tissue firmness or fat content can be non-invasively assessed. Background Art

[0004] It is well known that the stiffness of liver tissue is related to the degree of cirrhosis and other diseases, and the speed at which shear waves travel through a region of interest in a subject's liver is directly related to the stiffness of the liver. In practice, in soft tissue, the formula E = 3ρV s 2 From the tissue density (ρ) and shear wave velocity (V s ) to derive the hardness (Young's modulus). The density of soft tissue is close to 1000kg / m 3 . E is expressed in kPa, V s Expressed in meters per second (m / s).

[0005] In order to characterize the stiffness of the liver or other organs by shear wave velocity measurements, a technique called “harmonic elastography” has been developed, for example as described in “Probe Oscillation Shear Wave Elastography: Initial In Vivo Results in Liver” by DC Mellema et al. (published in IEEE Transactions on Medical Imaging, Vol. 37, No. 5, May 2018).

[0006] According to this technique, a transducer array for two-dimensional B-mode ultrasound imaging is placed in contact with the subject's body and vibrated at a low frequency, typically between 30 Hz and 100 Hz. An ultrasonic beam is then emitted to track how this low-frequency periodic vibration moves the subject's tissue. Thus, an instantaneous two-dimensional map (a 2D snapshot) is determined, which shows the tissue displacement 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 moment (see the aforementioned reference by D.C. Mellema et al.). Figure 9 a). The filtered 2D displacement map is then determined by complex spatial pattern filtering (Mellema et al. Figure 9 b or 8b). The inversion algorithm can then derive (from the 2D deformation map) a 2D map representing the values ​​of the shear wave velocity at different points distributed across the entire 2D cross section of the tissue (Mellema et al. Figure 8 c) Thus, using this technique, it is possible to derive a value for the shear wave velocity from the spatial information contained in the instantaneous two-dimensional displacement map.

[0007] However, implementing this method requires a rather complex multi-beam ultrasound device suitable for 2D ultrasound imaging. According to the research of Mellema et al., processing a single instantaneous 2D deformation map requires a lot of time, usually 3 vibration cycles. From a time perspective, such a long processing time makes it impossible to sample the entire vibration cycle at once (as in Mellema et al. Figure 3 More precisely, in the literature by Mellema et al., two ultrasonic beams are emitted (every 100 ms), and then two corresponding ultrasonic echo signals are collected and processed to calculate the displacement in the medium when the two ultrasonic beams are emitted. This process is then repeated 100 ms later, and so on (with a repetition rate of 10 Hz). Since a long processing time is required to calculate and analyze each two-dimensional deformation map, this process cannot be repeated at a higher repetition rate. Therefore, using this technique, it is not possible to sample the entire vibration cycle at once (because this would require a repetition rate higher than the mechanical vibration frequency (i.e., higher than 100 Hz)). Therefore, this harmonic elastography technique is capable of two-dimensional spatial imaging and focuses on the spatial characteristics of the deformation field, but has poor temporal resolution and is affected by tissue movement due to, for example, breathing or heartbeat.

[0008] Furthermore, shear wave velocity measurements using harmonic elastography are considered less reliable and accurate than those obtained using transient elastography, with harmonic elastography often providing overestimated velocity values. In practice, using harmonic elastography, periodic mechanical vibrations imparted to a subject propagate through the subject's tissue as a mixture of shear and compression waves (with propagation velocities much higher than either shear wave). These two components are difficult to separate due to the repetitive and continuous nature of the vibrations. Furthermore, harmonic elastography measurements can be biased by elastic wave reflections within the tissue, which can produce a stationary waveform (again, due to the repetitive and continuous nature of the vibrations).

[0009] As a result, thanks to its two-dimensional imaging capabilities, the aforementioned time-harmonic elastography technique provides valuable spatial information about the structure of the examined body part. However, the shear wave velocity values ​​it typically provides are not very accurate. The main reasons for this lack of accuracy are the combination of shear and compression waves, the influence of diffraction effects due to the large size of the vibration source, the influence of motion (such as breathing) (given that displacements are typically captured during a few cycles of vibration), and the fact that out-of-plane motion is not measured. These issues result in artifacts in the images that must be interpreted with extreme caution, especially when quantitative measurements are intended.

[0010] Therefore, transient elastography appears to be more suitable than time harmonic elastography for accurately measuring shear wave velocity in relatively large and homogeneous organs such as the liver or spleen.

[0011] 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 properties of this map), transient elastography focuses on the spatiotemporal tracking of the instantaneous mechanical impulse delivered to the tissue.

[0012] The well-known transient elastography system is manufactured and sold by Echosens SA in Paris, France. The system (an ultrasound-based elastography device used to measure the stiffness (or elasticity) and ultrasound attenuation of tissues and organs) enables operators to noninvasively measure the stiffness of the liver or other organs to assess the health of the organs.

[0013] use In the system, the operator brings the tip of a probe of relatively small diameter (typically between 5 and 10 mm) into contact with the subject's body and places it in front of the expected area of ​​the subject's liver. The operator then presses a button to cause the head of the probe to deliver a momentary low-frequency mechanical pulse to the subject (the spectrum of the pulse is typically at a center frequency between 10 and 500 Hz). The pulse generates elastic waves that propagate within the subject's body. The ultrasonic transducer is mounted on the head of the probe, in contact with the subject's body, and then transmits multiple ultrasound beams into the tissue at a high repetition rate of at least 2 kHz. The probe collects echo signals corresponding to the backscatter of the different ultrasound beams emitted to track the slight movement of the tissue caused by the passage of the elastic waves. Tracking is performed using a cross-correlation technique applied to continuous echo signals. The detected movement enables the synthesis of elastic wave propagation images showing tissue deformation according to depth d and according to time t (not according to two different spatial coordinates but at a given fixed moment to synthesize images showing tissue deformation). Figure 1 Such an elastic wave propagation image 105, sometimes referred to as an "elastogram", is shown.

[0014] In contrast to other elastography methods, The probe has an advantageous symmetrical design. The ultrasound transducer is a single-element transducer mounted on the vibrator axis. The axis of the ultrasound transducer coincides with the axis of the vibrator, which is why the displacements induced by the vibrations are largely longitudinal and therefore aligned with the axis of the ultrasound beam. In this case, displacement measurement is significantly improved, as off-axis displacements are difficult to measure using ultrasound. Other elastography devices, particularly harmonic imaging devices, are more complex. They use multi-element ultrasound transducers (typically linear or convex arrays) because they are designed to provide 2D or 3D maps of mechanical properties to locate heterogeneities. The symmetry of these systems is much more complex. Due to this design, the displacements induced by the vibrations are not aligned with the ultrasound beam. They require more computing time because they process significantly more data (several ultrasound lines) and use complex inversion algorithms to evaluate the 2D or 3D mechanical properties. In addition, they are very slow.

[0015] The mechanical pulse delivered by the probe tip generates both shear waves and compression waves. That is, the elastic wave described above is a combination of shear waves and compression waves. However, these two waves have very different propagation speeds, and thanks to the instantaneous nature of the mechanical excitation, they can be easily separated in time and identified in the elastic wave propagation image. For example, refer to Figure 1 , which shows an elastic wave propagation image 105. Figure 1 In FIG, the compression wave is identified by reference numeral 105C, while the much slower shear wave is identified by reference numeral 105S. Figure 1 Also shown is a region of interest (ROI), which is bounded by two dashed lines at 25 mm and 65 mm, corresponding to the depth of the liver below the patient's skin where the liver is typically located. This elastic wave propagation image can therefore be used to accurately determine the propagation velocity of the shear wave in the tissue to be characterized, from which the stiffness of the tissue can be derived. These stiffness results 106 are then provided to the operator, as shown in FIG. Figure 1 As shown, the figure shows the The display screen of the system shows different graphs 101 , 102 , 105 and indicators 103 , 106 , 107 to the operator.

[0016] The system also enables one to measure the attenuation of the ultrasound signal used to track shear waves, which is useful because ultrasound attenuation is correlated with the amount of fat in the liver (see Figure 1 , ultrasonic attenuation results 107).

[0017] although The technology works well, but sometimes it's difficult for the operator to know whether they've correctly positioned the probe in front of a homogeneous area of ​​liver tissue, or whether they've even aimed the probe at the liver at all. Ribs, blood vessels, fluid pockets (ascites), or other heterogeneous tissue artifacts in front of the liver (such as cysts or tumors in the liver tissue) can produce erroneous measurements of tissue stiffness and ultrasound attenuation. Additionally, the operator may believe they've aimed the probe at the liver when, in fact, it's too close to the lungs or other internal organs. As a result, the system may not obtain accurate measurements.

[0018] To help the operator find the appropriate probe position, The system is configured to continuously transmit ultrasound beams and collect corresponding echo signals while the operator finds the appropriate probe position. A-mode and TM-mode images are displayed and updated in real time to help the operator find the appropriate probe position. Figure 1 Examples of such an A-mode graph 101 and a TM-mode graph 102 are shown. The TM-mode graph represents continuously acquired ultrasonic echo signals after they have been processed. The processing of the ultrasonic echo signals includes, for example, envelope calculation and decimation. Figure 1 The TM mode diagram shown is a two-dimensional image in which each column represents one of the acquired, processed ultrasound echo signals. Each column represents an instantaneous one-dimensional image as a function of depth d, showing how ultrasound waves are backscattered by the subject's body part aligned with the probe. Successive acquired ultrasound echo signals are displayed side by side to illustrate how this one-dimensional image changes over time t (this change is caused by slight probe movement or organ movement caused by respiratory motion).

[0019] like Figure 1 and 2 As shown, the TM map can provide useful information about the positioning of the probe 3. In fact, when the probe axis x is aligned with a thick and homogeneous section of the liver 4, the TM map 402 generally looks like a stack of horizontal slices and has a uniform appearance in both the horizontal and vertical directions, as shown in FIG. Figure 4 In contrast, when the probe axis x approaches the edge of the liver 4, the TM pattern images 202, 302 are generally in the horizontal direction ( Figure 2 ) or vertically ( Figure 3 ) has a discontinuous appearance.

[0020] Properly positioning the probe based on the TM map remains very difficult and requires proper operator training. Furthermore, as will be appreciated by those skilled in the art, improper probe positioning may result in inappropriate measurements and incorrect diagnosis of the patient's condition.

[0021] Although providing some information about the probe position, ultrasound signals displayed in TM mode or A-mode plots cannot predict shear wave propagation. In some cases, these plots may appear appropriate, as if the conditions are suitable for transient elastography measurements, when in fact no shear waves are able to propagate. This may occur in the presence of a liquid insert (see Figure 6 TM mode diagram 602), air insert (see Figure 6 TM mode diagram 602 '), narrow intercostal spaces, etc. In addition, although blood vessels may not be observed on the ultrasound signal due to being isoechoic, they may interfere with shear wave propagation. Figure 6 A TM mode image 602'" is shown acquired in the presence of an isoechoic vessel, wherein the vessel remains invisible (the location of the vessel is indicated by an arrow).

[0022] Using ultrasound data for guidance is not sufficient because it cannot predict shear wave propagation, as ultrasound and elasticity are not sensitive to the same conditions. A good ultrasound signal does not always result in good shear wave propagation. Some elements that affect shear wave propagation do not affect ultrasound propagation. Examples of isoechoic areas include blood vessels, cysts, fluid with particles, and hard or soft tumors.

[0023] Due to the limitations of conventional TM image guidance, the operator often fails to find the appropriate probe position on their first attempt to position the probe. In practice, it has been shown that the operator often must trigger the transient elastography measurement multiple times, testing different positions through trial and error, before finding the right position and recording an elastic wave propagation image suitable for characterizing liver stiffness. This is very time-consuming, and the operator must hold the probe still before triggering the transient elastography measurement. As those skilled in the art will appreciate, such attempts can be unpleasant for the patient being examined, as the patient is subjected to a small mechanical shock each time the operator takes a measurement. Furthermore, such attempts can prevent the operator from finding the right position, thereby increasing the failure rate.

[0024] Therefore, it is desirable to develop a system for characterizing tissue that is suitable for accurately characterizing the viscoelastic properties of the tissue and that is compatible with the above-mentioned The system has improved guidance capabilities compared to the previous one. Summary of the Invention

[0025] To address at least some of the above issues, the disclosed technology is directed to a system for identifying homogenous tissue in a subject or patient. Upon detecting an area of ​​homogenous tissue, an operator may initiate measurement of tissue stiffness and / or determination of ultrasound parameters.

[0026] In some embodiments, the system comprises:

[0027] a probe that is positioned against the subject's body and includes a vibrator that transmits mechanical vibrations to the subject's tissue;

[0028] an ultrasonic transmitter configured to transmit a sequence of ultrasonic beams, and an ultrasonic receiver configured to receive corresponding echo signals; and

[0029] A control module is programmed to cause the system to perform the following steps:

[0030] a) delivering continuous and periodic mechanical vibrations to tissue of a subject, the periodic mechanical vibrations comprising the same vibration pattern repeated multiple times sequentially over time;

[0031] b) transmitting a sequence of ultrasonic beams using an ultrasonic transmitter and acquiring corresponding echo signals received by an ultrasonic receiver to track how the tissue moves through the periodic mechanical vibrations imparted to the tissue;

[0032] c) providing homogeneity information to an operator of the system, the homogeneity information being determined based on at least some of the echo signals acquired in step b), the homogeneity information representing the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation.

[0033] The control module is programmed so that steps b) and c) are performed a plurality of times in succession by the system.

[0034] The homogeneity information obtained by tracking how periodic mechanical vibrations propagate through the tissue constitutes very effective guidance information that can help the operator quickly and easily find a suitable probe position in front of a thick and homogeneous section of the organ to be characterized.

[0035] It should be understood that two-dimensional elastic wave velocity maps, such as those described in the literature by Mellema et al. (or, for example, in 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), do not constitute information about the ability of tissue to propagate elastic waves or the homogeneity of the tissue with respect to elastic wave propagation. In fact, such maps do not actually provide information about wave propagation, as they only represent an instantaneous snapshot of the examined organ.

[0036] In an embodiment of the disclosed technology, the homogeneity information provided by the system indicates whether the space-time characteristics of the tissue deformation caused by the above-mentioned periodic mechanical vibration are the space-time characteristics of the wave propagating in the homogeneous medium (the deformation in question is tracked by the echo signal collected in step b).

[0037] like Figure 14 、 16 , 17 and 18, the spatiotemporal characteristics of the deformation of the tissue relative to the propagation of the elastic wave through the tissue, i.e., characteristics that represent the variation of the deformation both as a function of time and as a function of at least one spatial coordinate (thus truly representing the propagation mode of the elastic wave), reveal in a very direct and easy to understand way the more or less homogeneous nature of the tissue. For example, such spatiotemporal characteristics may include data representing the variation in the phase delay of the periodic deformation of the tissue over the depth. Figure 14 As shown in FIG, when the tissue is homogeneous, the phase delay changes substantially linearly with depth, which is easy for the operator to identify. The above-mentioned space-time characteristics may also include data representing tissue deformation as a function of depth d and as a function of time t. Figure 16 and 18 As shown in (graph 188a), when the tissue is homogeneous, the graph representing tissue deformation as a function of depth and as a function of time includes substantially linear stripes that are easily identified by the operator as diagonal.

[0038] like Figure 18 As shown in Figure 3, the propagation mode of this periodic elastic wave is more sensitive to the structure and elastic properties of the tissue than the TM pattern.

[0039] Figure 18 The last three columns of the table show TM mode images 182c, 182d, 182e, elastic wave propagation images 188c, 188d, 188e acquired in periodic mode (periodic elastic wave propagation images), and elastic wave propagation images 185c, 185d, 185e acquired in transient mode for three different cases, one of which corresponds to the probe position close to the edge of the liver (column c) and the other two are cases of liquid insertion (column d) or air insertion (column e). Figure 18As can be seen, in these cases, the TM mode images appear to be suitable for transient elastography measurements (as in column a), but are actually not suitable (see transient elastography images 185c, 185d, 185e). That is, TM mode imaging cannot distinguish between appropriate and inappropriate probe positions because it cannot accurately detect whether the probe is located close to the edge of the liver or whether air or fluid is inserted between the probe and the target organ. In sharp contrast, the noisy periodic elastic wave propagation images 188c, 188d, 188e include a large number of irregular fragments, as opposed to one or a few diagonal stripes in the case of smooth (substantially linear) edges. Therefore, the periodic elastic wave propagation images 188c, 188d, 188e directly show the appropriate probe positioning for transient elastography measurements. In addition, in the elastic wave propagation images acquired in the periodic mode, it is easy to detect (see Figure 18 182b) and even the presence of small and isoechoic vessels (see Figure 18 Graph 188b).

[0040] As will be understood by those skilled in the art, a periodic elastic wave propagation image having diagonal stripes (substantially uniform and / or having smooth edges), such as Figure 18 As shown in image 188a, it is a direct indication that the probe is correctly positioned and in a suitable position for transient elastography measurement (see Figure 18 Instantaneous elastic wave propagation image 185a).

[0041] It has been found that, in practice, the homogeneity information that is constantly updated and provided to the operator usually enables the operator, even an untrained one, to find the right probe position the first time.

[0042] Furthermore, the periodic mechanical vibrations imparted to the subject are less uncomfortable than short, transient mechanical pulses, which the operator would otherwise repeatedly trigger until they find the proper probe position. Furthermore, the vibration amplitude required for periodic elastic wave monitoring is significantly smaller than that required for transient elastography measurements. Furthermore, the continuous nature of the mechanical excitation used to guide the operator in the disclosed system enables continuous guidance.

[0043] A single-beam (single-transducer) ultrasound system without 2D or 3D imaging capabilities can be used to achieve space-time monitoring of deformations caused by periodic mechanical vibrations transmitted to the subject. In fact, from a space-time point of view, the propagation of monitoring waves can be achieved by monitoring tissue deformation as a function of time and only one spatial dimension (i.e., depth). That is, two-dimensional sampling of deformation can be used for space-time monitoring, one dimension is time and the other dimension is depth, rather than using two sampling dimensions that are both spatial dimensions (depth and lateral displacement, such as in the literature of Mellema et al.). As will be understood by those skilled in the art, the use of a single-beam ultrasound system instead of a 2D imaging ultrasound system enables people to quickly process the acquired echo signals, which are single-dimensional from a spatial perspective. This allows an increase in the time sampling rate for tracking the elastic deformation of the tissue. Therefore, the elastic deformation of the tissue is monitored with a higher time resolution than the harmonic elastography method of the prior art.

[0044] Furthermore, the high temporal sampling rate allows one to sample the same cycle, or at least a major part of the same cycle, of the periodic deformation of the tissue all at once. This is very interesting compared to techniques like stroboscopic observations, where the periodic deformation of the tissue is sampled in small parts, sampling a small part of the cycle (e.g. a single moment), then a small part of the subsequent cycle, and so on, to reconstruct a posterior image showing the entire vibration cycle (similar to Figure 13 In fact, using stroboscopic techniques, the delay time required to obtain a new fully refreshed image showing the entire vibration cycle is much longer than if the same cycle is sampled once at a high sampling rate (in Figure 13 In the example, the delay time is about four times the time of the same period of a single sampling. More importantly, the time images obtained by stroboscopic sampling are often corrupted by spurious effects and noise, especially due to tissue displacement caused by breathing or slight displacement of the probe. In addition, the time resolution of the propagation image obtained by stroboscopic sampling is usually less than the time resolution of the same period of a single sampling (e.g., Figure 13 The time resolution of the propagation images 131 to 134 is better than the time resolution of the propagation image 130).

[0045] As will be appreciated by those skilled in the art, a graph showing periodic deformation of tissue in a spatiotemporal manner as a function of depth and time (e.g., Figure 18This is very surprising when compared to prior art harmonic elastography techniques such as those of Mellema et al. or Tzschatzsch et al., where the graphs representing the instantaneous deformation of the tissue as a function of two spatial coordinates are barely understandable (see, for example, Millena et al. Figure 9 a or Tzschatzsch et al. Figure 3 a), and complex post-processing is required to obtain information useful to the operator (such as 2D shear wave velocity maps).

[0046] In summary, the system for characterizing tissue according to the disclosed technology has very good guidance capabilities, allowing the operator to quickly and easily find areas of homogeneous tissue suitable for performing transient elastography measurements or determining ultrasound parameters relative to the propagation of ultrasound waves within the tissue.

[0047] To benefit from these guidance capabilities, in an embodiment of a system for characterizing tissue according to the disclosed technology, a control module of the system is further programmed to determine physical properties of the tissue including at least one of the following:

[0048] Ultrasound parameters relative to ultrasound wave propagation within tissue attenuation values;

[0049] Mechanical properties of tissue related to shear wave propagation determined by transient elastography.

[0050] Ultrasound parameters include, for example, ultrasound attenuation parameters that reflect ultrasound attenuation in tissue, such as broadband ultrasound attenuation (BUA, typically expressed in dB / cm / MHz), attenuation measured at a specific frequency (expressed in dB / cm), or controlled attenuation parameter (CAP). However, this is not limiting, and additional parameters may be determined in other embodiments.

[0051] The mechanical properties of the tissue that are relevant to shear wave propagation can be quantities related to tissue stiffness, such as the shear wave propagation velocity V s , the shear modulus of the tissue or the Young's modulus E of the tissue. It may also be a quantity related to the attenuation of low-frequency shear waves in the tissue, such as viscosity.

[0052] It will be appreciated that a system for determining mechanical properties by transient elastography, in which the propagation of periodic elastic waves is initially monitored to detect homogeneous tissue, a system originally configured in a certain manner for transient elastography and further modified to implement the above-mentioned guidance technique, is very different from and even opposite to transient elastography (which aims to separate compression waves and shear waves) and prior art harmonic elastography (which focuses on the almost purely spatial characteristics of the deformation field and is not intended to help the operator correctly place the probe).

[0053] In an embodiment according to the disclosed technology, the control module is programmed to determine data representing periodic deformation of the tissue at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue based on at least some of the echo signals acquired in step b).

[0054] In an embodiment according to the disclosed technology, the homogeneity information includes one of the following:

[0055] a graph representing the variation with depth of at least one temporal characteristic of the temporal periodic variation of tissue deformation; or

[0056] An indication that specifies whether the property varies with depth as if the tissue were homogeneous within a given depth range.

[0057] The above graph can be expressed as follows:

[0058] - Variation of deformation over time as a function of depth;

[0059] - Phase delay of the periodic deformation of the tissue as a function of depth;

[0060] - The amplitude of the envelope of the periodic deformation as a function of depth.

[0061] In one embodiment, the above-mentioned curve graph represents tissue deformation at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue, and the curve graph is a two-dimensional image whose pixel row index represents depth and whose pixel column index represents time, or conversely, each pixel has a pixel value representing tissue deformation at the depth and time associated with the pixel in question.

[0062] In one embodiment, the indication specifies whether a graph is composed of diagonal stripes within the depth range, the graph representing tissue deformation at different depths within the tissue and at different moments of periodic mechanical vibrations imparted to the tissue, the graph being a two-dimensional image whose pixel row indices represent depth and whose pixel column indices represent time, or conversely, each pixel having a pixel value representing tissue deformation at the depth and time associated with the pixel under consideration.

[0063] In one embodiment, the system includes a manual adjustment control, such as a cursor, slider, button, or knob, that enables an operator to manually adjust the amplitude of the periodic mechanical vibration. This is useful in situations where the amplitude of the cyclic deformation of the tissue caused by the periodic mechanical vibration imparted to the tissue is too low or too high. The system can include an amplitude indicator for displaying information about the amplitude of the cyclic deformation of the tissue to the operator.

[0064] In one embodiment, the system is configured to automatically (i.e., without operator action) adjust the amplitude of the periodic mechanical vibration based on the amplitude of the generated periodic deformation of the tissue. More precisely, the system can be configured to increase the amplitude of the periodic mechanical vibration when the amplitude of the generated periodic 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 generated periodic deformation of the tissue is too high (above another amplitude threshold).

[0065] In one embodiment, the system is configured to adjust the amplitude of a transient mechanical pulse delivered to a subject based on the amplitude selected for the periodic mechanical vibration to measure mechanical properties of the tissue associated with shear wave propagation via transient elastography. In this case, preliminary tissue characterization via periodic elastography, in addition to the various advantages described above, can also determine the amplitude of the transient mechanical pulse suitable for subsequent transient elastography measurements.

[0066] It should be understood that, according to the disclosed technology, the different embodiments described above may be combined together according to all technically possible combinations.

[0067] Optionally, in accordance with the disclosed technology, optional non-limiting features of the above-presented system for characterizing tissue are defined by claims 3 to 7 and 10 to 18 as filed.

[0068] The disclosed technology also provides a method for characterizing tissue, the method being performed by a system comprising:

[0069] a probe that is positioned against the subject's body and includes a vibrator that transmits mechanical vibrations to the subject's tissue;

[0070] an ultrasonic transmitter configured to transmit a sequence of ultrasonic beams, and an ultrasonic receiver configured to receive corresponding echo signals; and

[0071] A control module programmed to cause the system to perform the following method steps:

[0072] a) delivering continuous and periodic mechanical vibrations to tissue of a subject, the periodic mechanical vibrations comprising the same vibration pattern repeated multiple times sequentially over time;

[0073] b) transmitting a sequence of ultrasonic beams using an ultrasonic transmitter and acquiring corresponding echo signals received by an ultrasonic receiver to track how the tissue moves through the periodic mechanical vibrations imparted to the tissue;

[0074] c) providing homogeneity information to an operator of the system, the homogeneity information being determined based on at least some of the echo signals acquired in step b), the homogeneity information representing the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation.

[0075] The control module is programmed so that steps b) and c) are performed a plurality of times in succession by the system.

[0076] Features of the different embodiments of the system described above may also be applied to the method for characterizing tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0077] Figure 1 Shown by The system's display screen shows different graphs and indicators to the operator;

[0078] Figure 2-4 Different TM mode diagrams are shown to show the operator Different positions of the probe relative to the organ to be characterized;

[0079] Figure 5 Shown TM pattern image obtained when the probe is correctly placed (with its axis centered on the organ to be characterized);

[0080] Figure 6 shows different TM pattern images acquired when the probe is not correctly positioned (its axis is close to the edge of the organ to be characterized) or in the presence of liquid, air or vascular insertions that are not suitable for proper mechanical characterization of the organ;

[0081] Figure 7 is a block diagram of a system for characterizing an organization according to some embodiments of the disclosed technology;

[0082] Figure 8 is a flow chart of a method for characterizing tissue according to some embodiments of the disclosed technology;

[0083] Figure 9 Continuous and periodic mechanical vibrations delivered to tissue of a subject, a sequence of ultrasound beams transmitted to track deformation of the tissue caused by the vibrations, and elastic wave propagation images obtained therefrom according to some embodiments of the disclosed technology are shown;

[0084] Figure 10shows another way of transmitting a sequence of ultrasound beams to track deformation of the tissue caused by the vibrations, in accordance with some embodiments of the disclosed technology;

[0085] Figure 11 Shown are continuous and periodic mechanical vibrations delivered to tissue of a subject, yet another way of transmitting a sequence of ultrasound beams to track deformation of the tissue caused by the vibrations, and the resulting periodic elastic wave propagation images according to some embodiments of the disclosed technology;

[0086] Figure 12 Shows some embodiments according to the disclosed technology Figure 11 How can the periodic elastic wave propagation images be aligned in time for operator viewing?

[0087] Figure 13 illustrates the difference between a low sampling rate, stroboscopic-like approach for tracking periodic deformation of tissue according to some embodiments of the disclosed technology and a high sampling rate approach for tracking such periodic deformation of tissue, in which the deformation of the tissue is monitored in its entirety at once;

[0088] Figure 14 shows the phase delay of an elastic wave at a specific depth in tissue determined according to some embodiments of the disclosed technology;

[0089] Figure 15 shows various graphs and indicators displayed to an operator by a system for characterizing tissue according to some embodiments of the disclosed technology;

[0090] Figure 16 and Figure 17 shows illustrative elastic wave propagation images from homogeneous tissue and inhomogeneous tissue, respectively, according to some embodiments of the disclosed technology;

[0091] Figure 18 Illustrative TM maps, periodic elastic wave propagation images, and transient elastic wave propagation images provided to an operator are shown, obtained under a number of different circumstances and probe positions, in accordance with some embodiments of the disclosed technology. DETAILED DESCRIPTION

[0092] Figure 7 FIG. 1 is a block diagram of an ultrasound system 1 for characterizing tissue, the ultrasound system being configured to detect homogenous tissue. The system 1 comprises:

[0093] a probe 10 placed against the body of a subject 50 and comprising a vibrator 12 adapted to transmit mechanical vibrations to the subject's tissue 51 ;

[0094] - an ultrasound transmitter configured to transmit a sequence of ultrasound beams, and an ultrasound receiver configured to receive corresponding echo signals to track how the subject's tissue moves due to such mechanical vibrations;

[0095] A control module 20 for controlling the probe 10 and processing the data collected by the ultrasound receiver.

[0096] The term "tissue" should be understood to refer to a portion of the body of a subject 50 (human or animal). This term does not necessarily refer to an entire organ or a single organ. The tissue 51 to which the mechanical vibrations are transmitted and whose deformation is tracked by the ultrasound beam is a portion of the subject's body located near the probe 20 along the probe's axis z.

[0097] The system 1 is configured to determine whether the tissue 51 is homogeneous and whether the tissue 51 can transmit elastic waves (particularly shear waves) using periodic elastography techniques, and provide this information to the operator via the operator interface 30 .

[0098] The homogeneity information constitutes guidance information that helps the operator position and aim the probe 20 at the organ to be characterized (e.g., the liver or spleen). Once the probe 20 is properly positioned thanks to this guidance information, one or more physical properties of the tissue can be determined to characterize the organ, for example, using transient elastography.

[0099] In this document, the expression "elastic waves" is understood to refer to low-frequency mechanical waves or tissue deformations, i.e., mechanical waves or tissue deformations having a center frequency of less than 500 Hz, or even less than 100 Hz, as opposed to ultrasound beams or echo signals, which typically have a center frequency above 0.1 MHz or even above 1 MHz (such ultrasound waves also generate certain kinds of elastic deformations when propagating through tissue, but at a much higher frequency, and are not designated as "elastic waves" in this document).

[0100] In order to provide homogeneity information, the control module 20 is more precisely programmed to cause the system 1 for characterizing tissue to perform the following steps:

[0101] a) delivering to the tissue 51 of the subject 50 a continuous and periodic mechanical vibration PMV comprising the same vibration pattern VP repeated multiple times in succession over time (see, for example, Figure 9 );

[0102] b) using the ultrasonic transmitter 11 to transmit an ultrasonic beam sequence (e.g. Figure 9 and collecting corresponding echo signals received by the ultrasound receiver 11 to track how the tissue 51 moves by the periodic mechanical vibrations PMV transmitted to the tissue;

[0103] c) providing the above-mentioned homogeneity information to an operator 40 of the system, the homogeneity information being determined based on at least some of the echo signals acquired in step b).

[0104] The control module 20 is programmed to continuously (i.e., uninterruptedly) repeat steps b) and c) until the operator 40 presses the control button 13 and triggers the transient elastography measurement. Therefore, the homogeneity information provided to the operator 40 is constantly updated, which helps the operator find the appropriate probe position.

[0105] The system 1 can be configured to determine the above homogeneity information so that it more accurately indicates whether the tissue 51 is homogeneous within a given depth range or region of interest. For example, the depth range refers to the depth range within which the subject's liver is expected to extend if the probe 20 is properly placed. The depth range can, for example, extend between a depth of 25 mm and a depth of 65 mm below the subject's skin (where the liver is typically located) or between a depth of 35 mm and a depth of 75 mm. The depth range defines a region of interest (ROI) within the tissue 51 where the tissue is to be characterized. Figure 15 In the example, the region of interest extends between the two horizontal dashed lines).

[0106] The control module 20 is also programmed to determine at least one physical property of the tissue 51 so that the organ of interest can be characterized once the probe 10 is properly positioned. The physical property may include:

[0107] Ultrasonic parameters relative to ultrasound wave propagation within tissue, such as ultrasound attenuation values, such as BUA, CAP, and / or attenuation measured at a specific frequency;

[0108] Mechanical properties of tissue related to shear wave propagation, such as the shear wave propagation velocity V, determined by transient elastography s , shear modulus of the tissue, Young's modulus E of the tissue, or viscosity of the tissue at low frequencies (below 500 Hz).

[0109] More precisely, Figure 7 The system 1 can be configured to determine mechanical properties of tissue related to shear wave propagation for tissues with a Young's modulus between 1 and 100 kilopascals (suitable for studying liver or spleen stiffness). The system 1 can also be configured to determine ultrasound attenuation values ​​in tissues with a CAP value between 50 and 500 dB / m.

[0110] We will now describe in more detail Figure 7 The structure of system 1. Then, we will show Figure 8 The method for characterizing tissue according to some embodiments of the disclosed technology shown can be performed by Figure 7 1 and exemplary results obtained by the system or method (see Figures 15 to 18 ).

[0111] As already pointed out, Figure 7 The probe 20 of the system 1 includes a vibrator 12, such as an electromechanical vibrator or an acoustic speaker, to transmit mechanical vibrations to the subject's tissue 51. The mechanical vibrations can be transmitted to the tissue as a force exerted on the subject's body by the tip of the probe, as a displacement of a portion of the subject's body exerted by the tip when in contact with the probe, or as a combination of the above.

[0112] exist Figure 7 In the system 1 of FIG. 1 , the vibrator 12 is rotationally symmetric about a vibrator axis coinciding with the probe axis z. When the vibrator 12 vibrates, it induces a predominantly longitudinal displacement parallel to its axis.

[0113] exist Figure 7 In the system 1, the ultrasound transmitter and the ultrasound receiver are composed of the same ultrasonic transducer 11 (for example, a piezoelectric transducer). The ultrasonic transducer 11 is rotationally symmetrical around the transducer axis and emits an ultrasonic beam centered on the axis. The transducer axis coincides with the axis of the vibrator. The ultrasonic transducer 11 has, for example, a circular cross-section, with the axis of the vibrator passing through the center of the cross-section. In this system, the transducer 11 is part of the probe 10. It is mounted between the vibrator 12 and the tip of the probe. The tip of the probe is the part of the probe that is to be placed in contact with the subject's body. The tip is relatively small: its contact surface is typically less than 1 square centimeter. The diameter of the tip can be less than 1 centimeter, or less than 8 or even 5 millimeters.

[0114] The probe 10 includes a manual trigger, such as a control button 13 or a dial. The system 1 is configured to achieve transient elastography measurements when the manual trigger 13 is manipulated.

[0115] The probe may include manual adjustment controls, such as cursors, sliders, buttons, or knobs, for manually adjusting the amplitude of the periodic mechanical vibrations, the amplitude of the transient mechanical pulses, or both.

[0116] The system can 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 can be configured to automatically adjust the amplitude of the transient mechanical pulse based on a previously adjusted amplitude of the periodic mechanical vibration.

[0117] It should be understood that in other embodiments of the disclosed technology, the ultrasound transmitter and receiver can be composed of two different transducers rather than the same transducer. In addition, the probe can include an additional vibrator, such as an electromechanical vibrator, an acoustic speaker, or an electric motor with an eccentric cam. This additional vibrator can be rotationally symmetric about the z-axis in the same manner as the vibrator 12 described above, or at least be configured to induce vibration parallel to the z-axis. In such an embodiment, the system can be configured so that the additional vibrator generates periodic mechanical vibrations, and the vibrator 12 generates transient mechanical vibrations.

[0118] Figure 7 The system 1 further comprises a central unit 20 comprising a control module 21, an ultrasonic front end 22 having an ultrasonic transmitter module 27 and an ultrasonic receiver module 29, and a motion-actuated servo controller 23 for controlling 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 the control module 21 or send data to the control module 21).

[0119] The motion-actuated servo controller 23 includes circuitry configured to generate electrical signals suitable for driving the vibrator 12 when directed by the control module 21. The circuitry may include a current amplifier or other type of amplifier.

[0120] The ultrasonic front end 22 includes a switch 28 for alternately generating and receiving ultrasonic signals. The ultrasonic transmitter module 27 of the front end 22 includes a circuit that is configured to generate an electrical ultrasonic signal suitable for driving the ultrasonic transducer 11 (e.g., an ultrasonic beam sequence further described below with reference to step b) when instructed by the control module 21. The circuit may include an amplifier and a digital-to-analog converter (DAC), such as an 8- to 16-bit DAC with a rate of 10 to 1000 megasamples / second. The ultrasonic receiver module 29 includes a circuit configured to acquire an electrical ultrasonic signal (echo signal) previously received by the ultrasonic transducer 11 (and generated to the ultrasonic receiver module 29 via the switch 28). The circuit of the ultrasonic receiver module 29 may include a tension amplifier, a filter, and an analog-to-digital converter (ADC), such as an 8- to 16-bit ADC with a rate of 10 to 1000 megasamples / second.

[0121] The control module 21 is a device or system that includes circuitry for processing data, such as a microprocessor coupled to a non-volatile memory that includes machine-executable instructions and / or a programmable microcircuit, such as an FPGA (field programmable gate array) or a DSP (digital signal processor).

[0122] like Figure 7 As shown, the control module 21 more specifically includes:

[0123] a processor 24, such as a general-purpose processor;

[0124] Signal processing circuit 26, such as FPGA (FPGA coprocessor), DSP or other programmable circuit; and

[0125] The physical non-transitory memory module 25 comprises a non-volatile memory 250 for storing machine executable instructions to be executed by the processor 24 and, optionally, a RAM memory 251 for storing signal data and instructions during system operation.

[0126] The control module 21 may be in the form of an FPGA carrier board, for example. The processor 24 may be embedded within the signal processing circuit 26 (e.g., within the FPGA), or may be external to the circuit (e.g., external to the FPGA, which then performs certain signal processing tasks, such as echo signal cross-correlation calculations, to relieve the burden on the processor 24). The signal processing circuit 26 is configured to process the echo signals received by the transducer (once digitized by the ultrasound receiver module 29).

[0127] As described above, the control module 21 is programmed to cause the system 1 to perform steps a), b) and c) above. The control module 21 is programmed to cause the system to perform these steps because it contains instructions that, when executed by the control module 21, enable the control module 21 to:

[0128] Controlling the motion actuator servo controller 23 to drive the vibrator 12 to transmit periodic mechanical vibrations to the tissue (step a));

[0129] Controlling the ultrasonic front end 22 so that it drives the ultrasonic transducer 11, which in turn emits a sequence of ultrasonic beams to track how the tissue moves through periodic mechanical vibrations, and causes the ultrasonic receiver module 29 to collect corresponding echo signals (step b));

[0130] Based on at least some of the echo signals thus acquired, homogeneity information is determined, which represents the ability of the tissue to transmit elastic waves, i.e., its ability to allow elastic waves to propagate through it, and the homogeneity of the tissue relative to the propagation of elastic waves, and this information is provided to the operator, for example by transmitting it to the operator interface 30 (step c)).

[0131] The execution of the instructions causes the control module 21 to control the system 1 so that it performs any given step, in particular steps a), b) and c), which instructions are 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 the circuit, or a combination of the above.

[0132] The control module 21 may be more specifically programmed to perform in step c):

[0133] c0) determining data representing deformation of the tissue 51 at different depths d in the tissue and at different times t1, t2, t3 of the periodic mechanical vibrations imparted to the tissue based on the echo signals acquired in step b); and

[0134] c1) Determining homogeneity information from the data representing the deformation of the tissue 51 determined in step c0).

[0135] Step c0) can be performed using a cross-correlation technique or another pattern matching algorithm to determine how portions of tissue 51 move under the influence of elastic waves (generated by the periodic mechanical vibrations imparted by the system) passing through tissue 51. For example, as the spatial period of the elastic waves passes through a small region of interest, the tissue in that region may move slightly away from transducer 11 and then slightly toward transducer 11. Step c0) is typically performed by programmable circuitry 26 to reduce the burden on processor 24.

[0136] The control module 21 can be further programmed to cause the system 1 to perform Figure 8 The different steps of the method for characterizing the tissue are represented in, etc.

[0137] like Figure 7 As shown, the system 1 for characterizing tissue includes the operator interface 30 described above. Furthermore, in other embodiments of the disclosed technology, the operator interface may be distinct from the system for characterizing tissue. The operator interface may, for example, be embedded in a smartphone or a computer that communicates with the system for characterizing tissue. In this case, to provide homogeneity information to the operator, the control module 21 transmits this information to the external operator interface via a communication module of the system for characterizing tissue. The communication module may be a circuit configured to exchange data using a wired or wireless link, for example, according to the USB, FireWire, Bluetooth, 6LoWPAN, ZigBee, Z-Wave, or Sigfox protocols.

[0138] use Figure 7 The system displays the homogeneity information determined by the control module 21 through the display screen 31 of the operator interface 30, for example, Figure 15 The operator interface 30 may further include a light emitting diode or other light emitting device 14 disposed on the probe 10 for visually indicating to the operator 40 whether the tissue is homogeneous by changing the color or intensity of the light emitted.

[0139] In some embodiments, according to the embodiment, the system is a pocket-sized system, and the operator interface includes the above-mentioned light emitting device, but does not include a display screen.

[0140] In another embodiment, the operator interface includes a speaker for indicating to the operator whether the tissue is homogeneous by an auditory signal.Such homogeneity information can also be provided to the operator by a tactile indication (e.g., a change in the type or amplitude of mechanical vibration).

[0141] Despite Figure 7 The central unit 20 and the probe 10 are shown as separate parts, but all or part of the modules 21, 22, 23 of the central unit 20 may be arranged in the probe.

[0142] It will be appreciated that many variations may be made in the above described system for characterizing tissue without departing from the scope of the disclosed technology. For example, the distribution of some electrical functions within the central unit may differ from that described above. For example, the DAC and ADC may be located in the control unit rather than in the ultrasound transmitter and receiver modules. Some of the modules 23 to 29 may be combined or distributed. Furthermore, the control unit may include only a processor rather than a processor and signal processing unit. Alternatively, the control unit may include more than one processor. Figure 7 More processing units in the .

[0143] exist Figure 8 A flow chart of a method for characterizing tissue according to some embodiments of the disclosed technology is shown in FIG. As already mentioned, Figure 7 The control module 21 of the system 1 may be programmed to cause the system 1 to perform the method.

[0144] The method includes the following main steps: S0, detecting homogeneous tissue, S1, measuring tissue stiffness by transient elastography, and S2, providing an ultrasonic attenuation value to an operator. In step S0, system 1 transmits continuous periodic mechanical vibrations to a subject to test tissue homogeneity and provides the homogeneity information to operator 40. This information is continuously updated, allowing the operator to monitor tissue homogeneity in real time to test different probe positions. Once the homogeneity information indicates that the examined tissue 51 is homogeneous, operator 40 manipulates a manual trigger (e.g., the operator presses control button 13). Then, execution of step S0 is stopped and execution of steps S1 and S2 is resumed. Once the tissue stiffness measurement is performed in step S1, execution of step S0 is restarted so that the operator can ensure that the probe is still positioned in front of the homogeneous tissue. The alternating process between the emission of continuous periodic mechanical vibrations (for homogeneity assessment) and the measurement of tissue stiffness by transient elastography can be performed in a timed manner until the desired number of tissue stiffness measurements are obtained.

[0145] Now, steps S0 , S1 and S2 are described in more detail one by one.

[0146] Step S0: Detection of homogenized tissue

[0147] like Figure 8 As shown, step S0 includes the above steps a), b) and c). Step S0 starts from step a), during which the control module 21 (via the motion actuation servo controller 23) controls the vibrator 12 so that the vibrator 12 transmits continuous and periodic mechanical vibrations PMV to the tissue 51 of the subject 50. The periodic mechanical vibrations PMV are continuously transmitted in step S0 (always continuing in step S0). Once the transmission of the periodic mechanical vibrations PMV begins, the control module executes step b), during which the control module controls (via the ultrasonic transmitter module 27) the ultrasonic transducer 11 so that it transmits a sequence of ultrasonic beams to track how the tissue moves due to the periodic mechanical vibrations, and collects corresponding echo signals (via the ultrasonic receiver module 29). Then, in step c), the control module determines homogeneity information based on the echo signals collected in step b), and then provides it to the operator. Then, while continuously transmitting the periodic mechanical vibrations PMV, the control module executes steps b) and c) again to provide the operator with new and updated homogeneity information. Therefore, a set of steps including steps b) and c) is continuously performed a plurality of times in succession until step S0 is stopped by the operator manipulating the above-mentioned manual trigger. Figure 9 In this case, the set of steps including steps b) and c) is repeated every 50 milliseconds (repetition rate is 20 Hz). Therefore, in this case, if (for example) the operator takes 3 seconds to find a suitable probe position and actuate the manual trigger, step S0 will last about 3 seconds, and the set of steps including steps b) and c) will be repeated about 60 times.

[0148] exist Figure 8 In an embodiment, the set of steps including steps b) and c) is performed in real time, i.e., with a repetition rate higher than or equal to 10 Hz, or even higher than or equal to 20 Hz, and a delay time lower than or equal to 1 second, or even lower than or equal to 0.1 second, or lower than 0.03 second. The delay time is the time interval between the start of the emission of the ultrasound beam sequence in step b) and the provision of updated homogeneity information determined based on the echo signals acquired in step b) to the operator.

[0149] exist Figure 8In the method, step c) includes the above-mentioned sub-steps c0) and c1). In step c0), the control module determines data representing the deformation of the tissue 51 at different times t1, t2, and t3 of the periodic mechanical vibration transmitted to the tissue based on the echo signals collected in step b). In step c1), the homogeneity information provided to the operator includes a curve graph representing the tissue deformation caused by the periodic mechanical vibration as a function of both time t and depth d (the deformation determined in step c0), similar to Figure 9 and 15 The curve graph 808, Figure 16 and 17 Graphs 168 and 178 or Figure 18 Graphs 188a to 188e.

[0150] Steps a), b) and c) will now be described in more detail.

[0151] exist Step a) In the present invention, the periodic mechanical vibration transmitted to the tissue has a fundamental frequency, i.e., a fundamental frequency, comprised between 10 Hz and 200 Hz. Its fundamental frequency can be more specifically between 10 Hz and 60 Hz. Such a frequency value facilitates deep penetration of the vibration into the tissue, while still being fast enough to determine updated homogeneity information at a refresh rate greater than or equal to 10 Hz, thereby enabling real-time monitoring of tissue homogeneity. The periodic mechanical vibration PMV can, for example, have a fundamental frequency of 40 Hz (and therefore a period of 25 milliseconds), as shown in FIG. Figure 9 and 10 or with a fundamental frequency of 25 Hz (and therefore a period of 40 ms), as Figure 11 As shown. Figure 9 、 10 As shown in Figures 1 and 11, the periodic mechanical vibration PMV is a sinusoidal vibration. In addition, other periodic waveforms, such as triangular waveforms, can be used. The periodic mechanical vibration PMV is continuous, wherein it includes the same vibration pattern VP (here a sine wave period) that is repeated multiple times in succession over time, one immediately following another. Each new instance of the vibration pattern starts immediately after the previous instance, and there is no delay in between. The vibration pattern is repeated at a repetition rate that is the above-mentioned basic frequency. As already mentioned, the periodic mechanical vibration continues continuously in step S0. Therefore, the periodic mechanical vibration typically lasts for 1 second or longer. Due to the periodic mechanical vibration transmitted by the probe, a portion of the subject's tissue 51 in contact with the probe 20 oscillates with an amplitude typically between 0.1 and 2 mm.

[0152] exist Step b), the control module 21 instructs the ultrasound transmitter module 27 to generate a sequence of ultrasonic electrical pulses, which are converted by the ultrasonic transducer 11, which in turn transmits a short sequence of ultrasonic pulses, called an ultrasound beam, to track, or in other words, detect how the tissue 51 moves through the periodic mechanical vibrations PMV. Figure 9 A representative sequence 80 of ultrasound beams 81, 82, ... is shown. The central frequency of each ultrasound beam is, for example, between 1 and 5 MHz. The duration of each transmission is typically less than one millisecond, for example equal to 100 microseconds. In step b), the control module 20 also acquires a corresponding sequence of echo signals received by the ultrasound transducer 11. Each echo signal corresponds to an ultrasound beam emitted by the transducer, wherein the echo signal is the ultrasound wave scattered back by the tissue in response to the ultrasound beam in question (or at least represents the backscattered wave). Each echo signal represents the backscattering properties of the tissue as a function of the depth d in the tissue (because the round-trip propagation time of the ultrasound wave between the transducer and a point at the depth in question depends directly on the depth, each instant in one of these short echo signals corresponds to a given depth in the tissue).

[0153] As already mentioned, these consecutive echo signals are acquired for comparison with one another, for example using a cross-correlation technique or another pattern matching algorithm, in order to determine how parts of the tissue 51 move under the influence of the elastic waves passing through the tissue (this determination is performed in step c)). Therefore, in order to prevent decorrelation between two consecutively acquired echo signals, the ultrasound beam is emitted in step b) with a pulse repetition rate greater than or equal to 500 Hz, or even greater than or equal to 1 kHz (in practice, such decorrelation can occur due to overall tissue displacement caused by breathing, for example, when the duration between two consecutive transmissions is too long). Typically, the pulse repetition frequency is between 1 kHz and 10 kHz (depending on the computing power of the control module). Therefore, in the sequence of ultrasound beams emitted in step b), the duration between any emission and the immediately subsequent emission is less than or equal to 2 milliseconds, or even less than or equal to 1 millisecond.

[0154] exist Figure 8 In the method, the sequence of ultrasonic beams emitted in step b) spans at least half, or even at least three-quarters (e.g., the entire cycle of the periodic mechanical vibration PMV) transmitted to the tissue. And the sequence includes at least 10, or even 50 ultrasonic beams in each cycle of the periodic mechanical vibration. As a result, in this case, the same cycle of the periodic mechanical vibration PMV, or at least the main part of the same cycle, is sampled as a whole once by the emission sequence emitted in step b). As already explained, this makes it possible to monitor the propagation of periodic elastic deformation much better than sampling methods such as stroboscopic observation.

[0155] In step b), the control module may specifically control the ultrasound transmitter module 27 to generate the following Figure 9 、 10 Or the ultrasound beam sequence shown in 11.

[0156] exist Figure 9 and Figure 10 In the examples shown, the sequence of ultrasound beams 80 emitted in step b) more precisely spans one period of the periodic mechanical vibration PMV. In these examples, the repetition rate of the ultrasound beams is equal to 2 kHz. Thus, the sequence of ultrasound beams includes 50 beams per period of the periodic mechanical vibration (in these examples, the frequency of the periodic mechanical vibration is equal to 40 Hz).

[0157] exist Figure 11 In the example of , the sequence of ultrasound beams emitted in step b) spans more than one period. The repetition rate of the ultrasound beams may also be equal to 2 kHz, corresponding to 80 beams per period (in this case, the frequency of the periodic mechanical vibration is equal to 25 Hz).

[0158] The sequence of ultrasound beams 80, 80', 80" emitted in step b) can be emitted in a synchronized manner with respect to the periodic mechanical vibration, starting at a time instant io within the period of the periodic mechanical vibration PMV delivered to the tissue 51, the time instant io being the same for each execution of step b). Figure 9 As shown, this enables obtaining a stable propagation graph 808n without rolling (time shift) effects from one execution of steps b) and c) to another.

[0159] In this case, the absolute times to, to', to" of the start of the ultrasonic beam sequence differ from one execution of step b) to another. However, the time at which the sequence starts relative to the start of the periodic mechanical vibration cycle is the same for each execution of step b) (more precisely, the time at which the sequence starts relative to the start point of the periodic mechanical vibration cycle closest to this start time (i.e. relative to the start point of the vibration pattern instance closest to this start time) is the same for each execution of step b)).

[0160] For example, in Figure 9 and Figure 10 In this case, for each execution of step b), the ultrasound beam sequence starts almost at the beginning of a cycle of the periodic mechanical vibration when the vibration passes through zero while increasing (the ultrasound beam sequence can also be started at a given fixed delay time after the beginning of a cycle of the periodic mechanical vibration).

[0161] Thanks to this synchronization, for each new execution of steps b) and c), the propagation map representing the deformation of the tissue as a function of depth and time (derived from the emission emitted in step b) starts from the same instant io within the cycle of the periodic mechanical vibration (similar to Figure 9 Different propagation graphs 808, 808', 808" of the image are displayed successively to the operator. Thus, the graph remains stable from one execution to another, aligned in time, rather than rolling. Thanks to this stability, the operator can more easily understand the graph (because deformation monitoring is not disturbed by temporary rolling or movement of the graph). Therefore, the operator can more easily determine whether the probe is placed in front of homogeneous tissue in a manner suitable for measuring physical parameters of the tissue.

[0162] Step b) may be repeated at a repetition rate such that each new sequence of ultrasound beams is emitted immediately after another without a break between them, e.g. Figure 10 As shown. Figure 10 In the example of , an ultrasound beam sequence is therefore emitted in each period of the periodic mechanical vibration PMV (to track tissue deformation). When the processing speed of the control module 21 is limited, such as Figure 9 In the case of , step b) can also be repeated at a lower repetition rate, for example by emitting a sequence of ultrasound beams every two periods of the periodic mechanical vibration PMV. Figure 9 In this case, after each transmission of an ultrasound beam sequence, a new updated version of the homogeneity information is provided to the operator before the next transmission of an ultrasound beam sequence. That is, in this case, the execution of step c) is completed before a new execution of step b).

[0163] In step b), the ultrasound beam sequence 110, 110', 110" may also start at moments io, io', io" within the period of the periodic mechanical vibration PMV delivered to the tissue 51, these moments being different from one execution of step b) to another, e.g. Figure 11 In this case, if Figure 11 If an original propagation map such as Figure 118, 118 or 118" is provided to the operator, then in step c), the operator will feel the scrolling, time-shifting effect of the above-mentioned interference when the original map is refreshed ("original propagation map" refers to a map showing tissue deformation as a function of both time and depth, which deformation is displayed over time in the sampling order; that is, in such an original map, the time coordinate is the actual time when the deformation was measured).

[0164] Therefore, in this case, in order to prevent this rolling effect, the deformation data determined from the echo signals are post-processed (in step c)) so as to be realigned in time before being displayed, so that the realigned propagation diagrams all start from the same fixed moment within the period of the periodic mechanical vibration, e.g. Figure 12 That is, the realigned propagation maps provided to the operator in step c) are from a reference instant i within the cycle of the periodic mechanical vibration delivered to the tissue. R At the beginning, the reference time i R The same is true each time the map is updated according to newly determined deformation data. The time realignment can be achieved as follows: From a temporal point of view, at the reference instant i R The deformation data obtained at the previous time (actual, absolute measurement time) are shifted as a block to be placed at the end of the deformation data (as if they were measured right after the end of the ultrasound beam sequence), as shown in Figure 12 As shown schematically in the reference time i R is a given fixed instant in a vibration pattern VP that is repeated a number of times in succession, for example the starting point of the vibration pattern when the vibration passes through zero while increasing. This realignment technique stabilizes the display of the propagation map well from a temporal point of view. Nevertheless, the realigned propagation map obtained in this way includes discontinuities at the boundaries with the cut and pasted data blocks that have been shifted in time (the discontinuities are at Figure 12 It should be understood that, as shown in the graphs 118a, 118a', 118a". Figure 9 and 10 As shown, the propagation diagram obtained by directly synchronizing the emission of the ultrasound beam sequence with the periodic mechanical vibration does not include such discontinuities.

[0165] Step c).

[0166] As already mentioned, in step c0), the control module 21 determines deformation data representing tissue deformation at different depths within the tissue and at different moments of the periodic mechanical vibrations imparted to the tissue by comparing successive ultrasound echo signals using a cross-correlation technique or other pattern matching algorithm.

[0167] The term deformation is considered in this document in a broad sense. It encompasses any motion parameter, such as displacement, velocity, deformation, deformation rate, deformation speed, and any mathematical transformation applied to these parameters.

[0168] In step c1), homogeneity information is determined based on the deformation data determined in step c0). The homogeneity information may include one of the following:

[0169] Propagation diagrams, similar to Figures 808, 168, 178, etc. presented above.

[0170] represents the phase delay of the periodic deformation of the tissue as a function of depth d A graph similar to Figure 15 Graph 809;

[0171] A graph representing the amplitude Amp of the envelope of the periodic deformation of the tissue as a function of the degree d is similar to Figure 15 Graph 811;

[0172] Homogeneity indicator 810 .

[0173] Figure 15 An example of elements that may be displayed to the operator via the operator interface screen 31 to provide him / her with homogeneity information is shown. Figure 15 In the case of , the homogeneity information includes all the elements listed above. In addition, in other embodiments, the homogeneity information may include only one or only some of these elements. These different elements and the way to determine them will now be described in more detail.

[0174] The propagation map representing the deformation of the tissue at different depths and different moments of periodic mechanical vibration within the tissue can 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), and each pixel has a pixel value representing the deformation of the tissue at the depth and time associated with the pixel under consideration. The pixel value representing the deformation value at the considered point and time can be a brightness value, such as Figure 15 As shown in (the brightness of pixels higher than the algebraic deformation value is high), it can also be a color value (such as a hue value) or a combination thereof.

[0175] As already mentioned, when the tissue is homogeneous and suitable for elastic wave propagation (no air or liquid inserts), such a periodic elastic wave propagation image 808 includes one or more diagonal stripes. These stripes are diagonal in the td coordinate system because they are tilted. Their tilt is due to the propagation time of the periodic elastic waves from the subject's skin to the depth of interest. The slope of these stripes therefore represents, to some extent, the speed at which these elastic waves propagate in the tissue.

[0176] As mentioned above Figures 16 to 18 As explained in detail (see the section presenting an overview of the disclosed technology), such a propagation map enables the operator to easily determine whether the tissue is homogeneous and suitable for elastic wave propagation.

[0177] When the tissue 51 is homogeneous and suitable for elastic wave propagation (eg, there is no air or liquid intervening between the probe and the target tissue), the phase delay It changes basically linearly over the entire depth, such as Figure 15 As shown in the curve graph 809.

[0178] Phase Delay It can be expressed as a duration or an angle (in degrees or radians). At a given depth d, the phase delay represents the phase shift between the periodic deformation of the tissue at that depth and a reference periodic oscillation (e.g., a periodic mechanical vibration transmitted to the tissue or a periodic deformation of the tissue in the upper part of the tissue). Figure 14 As shown, the control module 21 can be programmed to determine the phase delay based on the frequency domain representation of the deformation data. In this case, a measurement of the deformation of the tissue over time 141 at a particular depth is converted into a frequency domain representation of that variation 142 (using a Fourier transform or other time-to-frequency domain conversion). This frequency domain representation shows a peak at a frequency fq, which is the fundamental frequency of the periodic mechanical vibrations imparted to the tissue. The value 142 of the Fourier transform of the deformation at that particular frequency fq is a complex number whose argument is the phase delay (in radians). The phase can then be delayed before plotting against the depth d A linear curve fit 144 can be superimposed on the phase delay map 143 obtained in this way, allowing the operator to more easily assess tissue homogeneity (by checking that the phase delay does not deviate significantly from linear variation).

[0179] At a given depth d, the amplitude Amp of the time-varying tissue deformation (i.e., the amplitude of the envelope of this variation) can be determined in the same manner as the phase delay, but by, for example, considering the amplitude of the Fourier transform at the peak frequency fq rather than its phase. Alternatively, another amplitude envelope estimation or detection technique can be used to determine the amplitude Amp.

[0180] When the tissue 51 is homogeneous and suitable for elastic wave propagation, according to a given theoretical model, the amplitude Amp is expected to vary with depth d, for example as 1 / d n where n is an integer between 1 and 3. In order to enable the operator to easily check whether the amplitude Amp varies with depth in this way, the amplitude Amp can be plotted against depth using a log-linear scale. In fact, when such a scale is used, the graph representing the variation of the amplitude with depth is linear if the amplitude is proportional to 1 / d n If the values ​​change in proportion, they can be easily assessed from a visual perspective.

[0181] The homogeneity indicator 810 may be displayed as a binary indicator, such as a green / red or green / black indicator, or in a more progressive manner, such as a dial, a percentage value, or a horizontal bar (eg, a progress bar).

[0182] Homogeneity indicator 810 specifies whether tissue 51 is homogeneous, more specifically, whether it is homogeneous within the given depth range and suitable for elastic wave propagation. Homogeneity indicator 810 can specify this information as a continuous value in a binary, all-or-nothing manner, or in a more gradual manner.

[0183] By way of illustration, 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 (which is a test sample made of a synthetic viscoelastic material) that is homogeneous, free of air or liquid inclusions or inserts, is sufficiently large (at least 10 cm wide and 10 cm deep), and has a Young's modulus comprised between 1 and 100 kPa (or, alternatively, between 5 and 75 kPa), then the indicator specifies (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., includes hard beads), or includes a water layer several centimeters below its surface, then the indicator specifies (e.g., by turning black) that the medium is not homogeneous or unsuitable for the propagation of elastic waves.

[0184] The control module 21 can 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.

[0185] The control module 21 can also be programmed to determine a homogeneity indicator by processing the periodic elastic wave propagation image 808 to detect an edge or average line of such fringes, and determining by linear curve fitting whether the edge or line is substantially linear over the depth range of interest and / or has a slope included in a given interval of possible values. The substantially linear nature of the line or edge can be evaluated based on a fit quality parameter, such as a coefficient of determination R 2 , standard deviation or other means to give the appropriateness between the fitted line and a strictly linear variation in depth. The control module can be programmed, for example, to determine the coefficient R 2 The line or edge is determined to be substantially linear when it is higher than or equal to 0.8, or even higher than or equal to 0.9. The homogeneity indicator may be determined to be equal to the fit quality parameter, or to be proportional to the fit quality parameter.

[0186] The control module 21 can also be programmed to determine the phase delay The homogeneity indicator is determined by whether it varies substantially linearly with depth over the depth range of interest and / or has a slope included in a given interval of possible values. As described above, this determination can be made by linear curve fitting.

[0187] The control module 21 can also be programmed to determine the phase delay The homogeneity indicator is determined by whether it varies substantially linearly with depth over the depth range of interest and / or has a slope included in a given interval of possible values. As described above, this determination can be made by linear curve fitting.

[0188] The control module 21 can also be programmed to determine whether the amplitude Amp varies with depth according to a given model, in particular whether the amplitude Amp is proportional to 1 / d n The homogeneity indicator is determined proportionally. This determination can be performed by curve fitting. The fact that the amplitude Amp varies with depth according to the model can be evaluated based on the fit quality parameter, such as the coefficient of determination R that gives the goodness of fit between the amplitude variation with depth and the model 2 The homogeneity indicator may be determined to be equal to, or proportional to, the fit quality parameter.

[0189] The control module 21 can also be programmed to determine different intermediate homogeneity indicators based on the different criteria mentioned above (thus, based on the periodic elastic wave propagation image 808, based on the change in phase delay or based on the change in amplitude Amp), and then determine the final homogeneity indicator based on these different intermediate homogeneity indicators, for example by averaging these intermediate homogeneity indicators.

[0190] The control module 21 can also be programmed to estimate, in step c1), an initial value of a mechanical property of the tissue relevant to shear wave propagation, such as its Young's modulus, or a range of values ​​within which such a mechanical property may be found. This value or range of values ​​is determined based on the data representing the cyclic deformation of the tissue determined in step c0). This value or range of values ​​is then provided to the operator, for example, via a display screen of the operator interface 30.

[0191] To this end, the control module 21 can determine the phase delay of the periodic elastic wave propagation image 808 by the slope of the diagonal stripes or by the phase delay of the periodic elastic wave propagation image 808. The slope of the line 404 of the variation at depth d is used to derive a preliminary estimate of the propagation velocity of the shear wave in the tissue. The control module 21 can then determine a preliminary estimate of the Young's modulus based on the value of the propagation velocity of the shear wave. As mentioned in the introduction, the value of the propagation velocity of the shear wave determined in this way is generally less accurate than the value determined by transient elastography (especially due to the superposition of compression and shear waves). However, it is still useful to provide the operator with such a preliminary value or range of values ​​in which the actual value of the Young's modulus (or other mechanical property of the tissue) may be found.

[0192] Step S1: Measuring tissue stiffness by transient elastography

[0193] In step S1 , in order to determine the mechanical properties of the tissue 51 (e.g., shear modulus, Young's modulus E, shear wave velocity, etc.) related to shear wave propagation by transient elastography, the control module 21 is programmed to cause the system 1 to perform the following steps:

[0194] d) stopping the continuous and periodic mechanical vibration (PMV) and then delivering a transient low-frequency mechanical pulse to the subject's tissue;

[0195] e) transmitting a sequence of ultrasound beams by means of the ultrasound transmitter 11 and acquiring corresponding echo signals received by the ultrasound receiver 11 while the low-frequency mechanical pulses travel through the tissue 51;

[0196] f) Determining said mechanical property of the tissue relevant to shear wave propagation based on at least some of the echo signals acquired in step f).

[0197] The control module 21 may be more specifically programmed so that, in step f):

[0198] f0) determining data representing instantaneous deformation of the tissue at different depths within the tissue and at different times after delivering the low-frequency mechanical pulse to the tissue based on the echo signals acquired in step e); and

[0199] f1) Determining mechanical properties of the tissue relevant to shear wave propagation based on the data representing the instantaneous deformation of the tissue determined in step f0).

[0200] In step d), the control module 21 controls the vibrator 12 (via the motion actuator servo controller 23) so that it delivers a transient mechanical pulse to the tissue, the duration of which is typically less than 0.2 seconds (the pulse duration is understood to mean the time interval, and furthermore, the pulse amplitude is less than one-tenth of the peak, maximum amplitude of the pulse). This mechanical pulse is a low-frequency pulse, in that its spectral content (its spectral density) is mostly below 500 Hz, or even below 100 Hz. The pulse duration is typically less than 10 / f, or even less than 2 / f, where f is the center frequency of the pulse spectrum.

[0201] In step e), the control module 21 can control the ultrasonic transducer 11 (via the ultrasonic transmitter module 27) to transmit a sequence of ultrasonic beams at a pulse repetition rate greater than or equal to 2 kHz. The transmitted ultrasonic beams are similar to the ultrasonic beams transmitted in step b) of step S0. However, they are transmitted at a higher pulse repetition rate because step S1 is used to accurately measure the mechanical properties of the tissue, rather than simply to visualize and monitor tissue homogeneity.

[0202] For example, the transient mechanical pulse may last 20 or 40 milliseconds, the ultrasound beam sequence may last 80 milliseconds, and the ultrasound beam may be emitted at a pulse repetition rate of 6 kHz, thereby enabling tracking of the deformation of the tissue as it varies with depth at 480 different consecutive moments distributed during the 80-millisecond period (which begins when the transient mechanical pulse begins to be emitted). That is, in this case, the transient elastic wave propagation image 805 will include 480 columns.

[0203] In step f0), data representing the temporal deformation of the tissue are determined by comparing the echo signals acquired in step e) with each other, for example using a cross-correlation technique or another pattern matching algorithm, as in step c0) of step S0.

[0204] In step f1 ), mechanical properties of the tissue relevant to shear wave propagation are determined according to techniques known in the art.

[0205] The control module 21 may be programmed to provide an instantaneous elastic wave propagation image in step f1), such as Figure 15 An image 805 representing the deformation of the tissue caused by the transient mechanical pulse both as a function of depth and as a function of time allows the operator to visually check the quality of the transient elastography measurement.

[0206] The control module 21 may also be programmed to provide the operator with the value of the mechanical property of the tissue once determined, e.g. Figure 1 The hardness results shown in the figure show a form of 106.

[0207] Step S2: Providing the ultrasonic attenuation value to the operator

[0208] In step S2, the control module 12 displays this value on the screen 31 of the operator interface (e.g., in Figure 1 The attenuation result display 107 is used to provide the operator 40 with the values ​​of the above-mentioned ultrasonic attenuation parameters.

[0209] The control module 21 determines the ultrasonic attenuation parameter based on some or all of the echo signals acquired in step b) of step S0, more precisely, during the last execution of step b) and just before S0 is stopped. This calculation can be performed in step S0 or only once step S2 is executed, that is, once the operator manipulates the manual trigger.

[0210] It will be noted that numerous variations may be made to the above-described method for characterizing tissue without departing from the scope of the disclosed technology.

[0211] For example, step S2 may be eliminated (the method then comprises steps S0 and S1 , but not S2). Similarly, step S1 may be eliminated.

[0212] Furthermore, when the above-mentioned homogeneity indicator indicates that the examined tissue is homogeneous and suitable for elastic wave propagation, the transition from step S0 to steps S1 and / or S2 may be automatically triggered by the control module itself.

[0213] The method may also include only step S0, in which the step of providing the ultrasound attenuation parameter to the operator is performed regardless of the greater or lesser homogeneity of the examined tissue. In this case, the control module may be programmed to determine a quality factor associated with the ultrasound attenuation parameter, which quality factor is always higher when the tissue is homogeneous with respect to the propagation of periodic mechanical vibrations imparted to the tissue. This quality factor may be determined based on the aforementioned homogeneity indicator, for example being equal to or proportional to the value of this indicator.

[0214] The different operations performed during the method may be organized in steps according to a distribution different from the one described above (in particular, the method may therefore comprise a higher number of steps or sub-steps).

[0215] The disclosed technology also provides a non-transitory computer-readable medium including a computer program, wherein the computer program includes machine-executable instructions, and the machine-executable instructions are executed by a control module of a system including

[0216] a probe that is positioned against the subject's body and includes a vibrator that transmits mechanical vibrations to the subject's tissue;

[0217] an ultrasound transmitter configured to transmit a sequence of ultrasound beams, and

[0218] an ultrasonic receiver configured to receive the corresponding echo signal;

[0219] Have the control module perform the following steps:

[0220] a) controlling the probe so that it transmits continuous and periodic mechanical vibrations to the tissue of the subject;

[0221] b) controlling the ultrasound transmitter so that it transmits a sequence of ultrasound beams and collects corresponding echo signals received by the ultrasound receiver to track how the tissue moves through the periodic mechanical vibrations imparted to the tissue;

[0222] c) providing homogeneity information to an operator of the system, the homogeneity information being determined based on at least some of the echo signals acquired in step b), the homogeneity information representing the ability of the tissue to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation.

[0223] Steps b) and c) are performed multiple times in succession.

[0224] The subject matter and implementation of operations or steps described in this specification (e.g., Figure 7 The components of the central unit 20 of the computer system 20 may be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in a combination of one or more thereof. The embodiments of the subject matter described in this specification may be implemented as one or more computer programs, i.e., one or more modules of computer program instructions, encoded on a computer storage medium for execution by a data processing apparatus or to control the operation of the data processing apparatus.

[0225] A computer storage medium may be, or may 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 of them. Furthermore, although a computer storage medium is not a propagated signal, a computer storage medium may be a source or destination of computer program instructions encoded in an artificially generated propagated signal. A computer storage medium may also be, or may be included in, one or more separate physical components or media (e.g., multiple CDs, disks, or other storage devices). The operations described in this specification may be implemented as operations performed by a data processing apparatus on data stored on one or more computer-readable storage devices or received from other sources.

[0226] The term "control module" includes all kinds of devices, equipment and machines for processing data, including, for example, a microprocessor, a digital signal processor (DSP), a computer, a system on a chip, or multiple devices of the foregoing, or a combination of the foregoing. A control module may include dedicated logic circuits (such as Figure 1 case), such as FPGA or ASIC (application-specific integrated circuit).

[0227] A computer program (also referred to as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages, and it can be deployed in any form, including as a standalone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program can, but need not, correspond to a file in a file system. A program can be stored in a portion 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 collaborative files (e.g., files that store one or more modules, subroutines, or code portions). A computer program can be deployed to execute on one computer, or on multiple computers that are located in one location or distributed in multiple locations and interconnected by a communication network.

[0228] The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform operations by operating on input data and generating output. The processes and logic flows can also be performed by special purpose logic circuitry, and the apparatus can also be implemented as special purpose logic circuitry, such as an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit).

[0229] Processors suitable for executing computer programs include, for example, general-purpose and special-purpose microprocessors, as well as any one or more processors of any type of digital computer. Typically, a processor will receive instructions and data from read-only memory or random access memory, or both. The essential elements of a computer are a processor for performing operations in accordance with instructions and one or more memory devices for storing instructions and data. Typically, a computer will also include one or more mass storage devices for storing data, such as magnetic, magneto-optical, or optical disks, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices. However, a computer need not have such devices. Devices suitable for storing computer program instructions and data include all forms of nonvolatile memory, media, and storage devices, including, for example, semiconductor memory devices such as EPROM, EEPROM, and flash memory devices; magnetic disks, such as 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 into, special-purpose logic circuitry.

[0230] To provide for interaction with a user, embodiments of the subject matter described in this specification can be implemented on a computer having a display device (e.g., an LCD (liquid crystal display), LED (light emitting diode), or OLED (organic light emitting diode) monitor) for displaying information to the user, and a keyboard and pointing device (e.g., a mouse or trackball) that the user can use to provide input to the computer. In some embodiments, a touch screen can be used to display information and receive input from the user. Other types of devices can also be used to provide for interaction with the user; for example, feedback provided to the user can be any form of sensory feedback, such as visual feedback, auditory feedback, or tactile feedback; and input from the user can be received in any form, including sound, voice, or tactile input.

[0231] 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.

Claims

1. A system (1) for characterizing a tissue, comprising: a probe, positioned against the body of a subject (50) and comprising a vibrator (12) for transmitting mechanical vibrations to the tissue (51) of the subject; An ultrasonic transmitter (11) and an ultrasonic receiver (11), wherein the ultrasonic transmitter (11) is configured to transmit a sequence of ultrasonic beams (80, 80', 80", 110', 110") and the ultrasonic receiver (11) is configured to receive corresponding echo signals; and The control module (21) is programmed to cause the system (1) to perform the following steps: a) delivering continuous and periodic mechanical vibrations (PMV) to the tissue (51) of the subject, the periodic mechanical vibrations comprising the same vibration pattern (VP) repeated several times successively over time; b) transmitting a sequence of ultrasonic beams (80, 80', 80", 110', 110") using the ultrasonic transmitter (11) and collecting corresponding echo signals received by the ultrasonic receiver (11) to track how the tissue (51) moves due to the periodic mechanical vibrations (PMV) transmitted to the tissue; c) providing homogeneity information (808, 808', 808", 809, 810, 811, 118a', 118a") to an operator of the system (1), the homogeneity information being determined based on at least some of the echo signals acquired in step b), the homogeneity information being indicative of the ability of the tissue (51) to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation; The control module (21) is programmed so that Steps b) and c) are performed multiple times in succession by the system (1), and the sequence of ultrasound beams (80, 80', 80", 110', 110") emitted in step b) spans at least half of the same period (VP) of the periodic mechanical vibration (PMV) transmitted to the tissue, and each period of the mechanical vibration includes at least 10 ultrasound beams.

2. The system (1) according to claim 1, wherein The control module (21) is further programmed to determine that the tissue (51) comprises at least one of the following physical properties: an ultrasound parameter relative to ultrasound wave propagation within the tissue; Mechanical properties of the tissue related to shear wave propagation determined by transient elastography.

3. The system (1) according to claim 2, wherein The control module (21) is programmed to determine the mechanical properties of the tissue related to shear wave propagation by transient elastography. The control module (21) is also programmed to cause the system (1) to perform the following steps: d) stopping the continuous and periodic mechanical vibration (PMV) and then delivering a transient low-frequency mechanical pulse to the tissue of the subject (51); e) transmitting a sequence of ultrasound beams using the ultrasound transmitter (11) and acquiring corresponding echo signals received by the ultrasound receiver (11) while the low-frequency mechanical pulses travel through the tissue; f) Determining said mechanical properties of said tissue related to shear wave propagation based on at least some of said echo signals acquired in step e).

4. The system (1) according to claim 3, wherein The control module (21) is programmed to trigger the execution of steps d), e) and f) by: When an operator (40) of the system operates a manual trigger (13); or Automatically triggered when the homogeneity information (808, 808', 808", 809, 810, 811, 118a', 118a") indicates that the tissue is homogeneous with respect to the propagation of elastic waves.

5. System (1) according to claim 3 or 4, wherein The control module (21) is programmed so that in step e), the ultrasound beam is emitted at a pulse repetition rate higher than or equal to 2 kHz.

6. The system (1) according to claim 2, wherein The control module (21) is also programmed to determine the ultrasound parameter when the homogeneity information (808, 808', 808", 809, 810, 811, 118a', 118a") indicates that the tissue is homogeneous with respect to the propagation of the elastic wave, and wherein the ultrasound parameter is determined based on one or more echo signals of the echo signals acquired in step b).

7. The system (1) according to claim 2, wherein The control module (21) is programmed to determine the ultrasound parameter based on one or more echo signals among the echo signals collected in step b), and to determine a quality coefficient (R 2 ), when the tissue (51) is homogeneous with respect to the propagation of elastic waves, the mass coefficients are all high.

8. The system (1) according to claim 1, wherein The control module (21) is programmed to determine data representing periodic deformation of the tissue (51) at different depths (d) in the tissue and at different times (t) of the periodic mechanical vibrations (PMV) delivered to the tissue based on at least some of the echo signals acquired in step b), and wherein the homogeneity information comprises one of the following: a graph (808, 808', 808", 809, 811, 118a', 118a") representing a variation of at least one temporal characteristic of a temporal periodic variation of deformation of the tissue as a function of depth; or An indication (810) specifies whether the characteristic varies with depth (d) as if the tissue were homogeneous within a given depth range (ROI).

9. The system (1) according to claim 8, wherein: The graph (808, 808', 808", 118a', 118a") represents the deformation of the tissue (51) at different depths (d) within the tissue and at different moments (t) of periodic mechanical vibrations (PMV) imparted to the tissue, the graph being a two-dimensional image whose pixel row index represents depth and whose pixel column index represents time, or conversely, each pixel having a pixel value representing the deformation of the tissue at the depth and time associated with the pixel under consideration; or wherein The indication (810) specifies whether the graph (808, 808', 808", 809, 811, 118a', 118a") consists of diagonal stripes within the depth range (ROI), the graph representing the deformation of the tissue (51) at different depths (d) within the tissue and at different moments (t) of the periodic mechanical vibrations (PMV) transmitted to the tissue, the graph being a two-dimensional image whose pixel row indices represent depth and whose pixel column indices represent time, or conversely, each pixel having a pixel value representing the deformation of the tissue at the depth and time associated with the pixel under consideration.

10. System (1) according to claim 8 or 9, wherein The homogeneity information includes at least one of the following: Graph (809) showing the phase delay of the periodic deformation of the tissue (51) as a function of depth (d) or among them Instruction (810) specifying the phase delay of the periodic deformation of the tissue (51) Whether within the depth range (ROI) varies substantially linearly with depth (d).

11. The system (1) according to claim 1, wherein The control module (21) is programmed so that: The fundamental frequency of the periodic mechanical vibrations (PMV) delivered to the tissue (51) of the subject is between 10 Hz and 200 Hz, and In step b), the ultrasound beam is emitted at a pulse repetition rate higher than or equal to 500 Hz.

12. The system (1) according to claim 1, wherein The control module (21) is programmed to cause the system to execute a set of steps including steps b) and c) in real time.

13. The system (1) according to claim 1, wherein: The homogeneity information provided to the operator comprises graphs (808, 808', 808") representing deformation of the tissue (51) at different depths (d) within the tissue and at different moments (t) of the periodic mechanical vibrations imparted to the tissue, and wherein The control module (21) is programmed so that the emission of the ultrasound beam sequence (80, 80', 80") of step b) is synchronized with the periodic mechanical vibration (PMV), the ultrasound beam sequence starting from an instant (io) within the period (VP) of the periodic mechanical vibration transmitted to the tissue, the instant (io) being the same for each execution of step b).

14. The system (1) according to claim 1, wherein The homogeneity information provided to the operator in step c) comprises a graph representing the deformation of the tissue (51) both as a function of depth (d) and as a function of time (t), the graph being a graph of the deformation of the tissue (51) from instants (io, i) within a period (VP) of the periodic mechanical vibration (PMV) transmitted to the tissue. R ), each time the graph is updated based on newly determined deformation data, the instant (io, i R ) are the same.

15. The system (1) according to claim 1, wherein The vibrator (12) of the probe is rotationally symmetric around a vibrator axis (z), and the ultrasound transmitter and the ultrasound beam generator are constituted by the same ultrasound transducer (11) which is rotationally symmetric around a transducer axis coinciding with the vibrator axis (z).

16. The system (1) according to claim 1, wherein The control module (21) is programmed to: determining data representing periodic deformation of the tissue (51) at different depths (d) in the tissue and at different times (t) of the periodic mechanical vibrations imparted to the tissue based on at least some of the echo signals acquired in step b); as well as Based on the data, a value of a mechanical property of the tissue relevant to shear wave propagation is estimated, or a range of values ​​of a mechanical property of the tissue relevant to shear wave propagation is estimated in which the values ​​are likely to be found.

17. The system (1) according to claim 1: - further comprising a manually adjustable control for adjusting the amplitude of the periodic mechanical vibrations (PMV), the control module being further programmed to provide to the operator (40) information representing the amplitude of a periodic deformation of the tissue (51) caused by the periodic mechanical vibrations imparted to the tissue, the amplitude of the periodic deformation of the tissue being determined based on at least some of the echo signals acquired in step b), or -in, The control module (21) is programmed to automatically adjust the amplitude of the periodic mechanical vibrations (PMV) delivered to the subject (50) based on the amplitude of the periodic deformation of the tissue.

18. A method for characterizing a tissue, the method being performed using a system (1) comprising: a probe, positioned against the body of a subject (50) and comprising a vibrator (12) for transmitting mechanical vibrations to the tissue (51) of the subject; an ultrasonic transmitter (11) configured to transmit a sequence of ultrasonic beams (80, 80', 80", 110', 110") and an ultrasonic receiver (11) configured to receive corresponding echo signals; and A control module (21) is programmed to cause the system (1) to perform the following steps of the method: a) delivering continuous and periodic mechanical vibrations (PMV) to the tissue (51) of the subject, the periodic mechanical vibrations comprising the same vibration pattern (VP) repeated a plurality of times successively over time; b) transmitting a sequence of ultrasonic beams (80, 80', 80", 110', 110") using the ultrasonic transmitter (11) and collecting corresponding echo signals received by the ultrasonic receiver (11) to track how the tissue (51) moves through periodic mechanical vibrations (PMV) imparted to the tissue; c) providing homogeneity information (808, 808', 808", 809, 810, 811, 118a', 118a") to an operator of the system (1), the homogeneity information being determined based on at least some of the echo signals acquired in step b), the homogeneity information being indicative of the ability of the tissue (51) to transmit elastic waves and the homogeneity of the tissue with respect to elastic wave propagation; The control module (21) is programmed so that Steps b) and c) are performed multiple times in succession by the system (1), and The sequence of ultrasound beams (80, 80', 80", 110', 110") emitted in step b) spans at least more than half of the same period (VP) of the periodic mechanical vibration (PMV) delivered to the tissue, and each period of the mechanical vibration includes at least 10 ultrasound beams.

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