KR20210012970A - System for characterizing tissue and associated method - Google Patents

Abstract

A system (1) for characterizing a tissue comprises: a probe which delivers a continuous and periodic mechanical vibration (PMV) to a tissue of a subject; an ultrasound emitter which emits a sequence of ultrasound shots (80, 80′, 80″) and an ultrasound receiver which receives corresponding echo signals to track how the tissue is moved by the PMV delivered to the tissue; and a control module programmed to provide homogeneity information (808, 808′, 808″) to an operator of the system, wherein the homogeneity information is determined from at least a part of the echo signals and representative of the ability of the tissue to transmit elastic waves and of the homogeneity of the tissue with respect to the propagation of the elastic waves. In addition, a method for characterizing a tissue is provided. According to the present invention, the system (1) for characterizing a tissue has enhanced guide performance.

Description

Tissue characterization system and method thereof TECHNICAL FIELD [SYSTEM FOR CHARACTERIZING TISSUE AND ASSOCIATED Method]

Cross-reference to related applications

This application relates to PCT application PCT/EP2019/054656 filed on February 26, 2019, and PCT application PCT/EP2019/054658 filed on February 26, 2019, these applications are incorporated herein by reference in their entirety do.

The disclosed technology relates to a non-invasive tissue characterization system, in particular a system for identifying homogeneous tissues for which tissue stiffness or fat content can be assessed non-invasively and methods for such systems.

It is well known that liver tissue stiffness is correlated with the degree of cirrhosis and other diseases, and that the rate at which shear waves travel through the region of interest in the subject's liver is directly related to liver stiffness. In fact, the rigidity (Young's modulus) in the soft tissue may be derived using the equation E = 3ρV _s ² in tissue density (ρ) and the shear wave velocity (V _s). The density of soft tissue is close to 1000 kg/m ³ . E is expressed in kilopascals and V _s is expressed in meters per second (m/s).

To characterize liver or other organ stiffness by shear wave velocity measurements, for example, D.C., published in IEEE Transactions on Medical Imaging, volume 37, issue 5, May 2018. A technique called "harmonic elastography" described in Mellema et al., "Probe Oscillation Shear Wave Elastography: Initial In Vivo Results in Liver" has been developed.

According to this technique, an array transducer for two-dimensional B-mode ultrasound imaging is placed in contact with a subject's body and is vibrated at a low frequency typically included between 30 Hz and 100 Hz. Thereafter, an ultrasonic shot is emitted to track how the subject's tissue moves by this low-frequency periodic vibration. This determines an instantaneous two-dimensional map (a kind of 2D snapshot) representing tissue displacement caused by low frequency periodic oscillations at different points distributed over a two-dimensional section of the subject's tissue and at the same moment ( 9A of the above-cited document by DC Mellema et al.). The filtered two-dimensional displacement map is then determined by complex spatial mode filtering (FIGS. 9B or 8B of Mellema et al.). Thereafter, the inverse algorithm makes it possible to derive a two-dimensional map representing the shear wave velocity values at different points distributed over the entire two-dimensional section of the tissue (from the two-dimensional deformation map) (Fig. 8c of Mellema et al. ). With this technique, the shear wave velocity value is thus derived from the spatial information contained in the instantaneous two-dimensional displacement map.

However, to implement such a method, a very complex multi-beam ultrasound device suitable for two-dimensional ultrasound imaging is required. According to Mellema et al., processing of a single instantaneous two-dimensional warp map takes a lot of time, typically three vibration cycles. This long processing time (as described in the capture of Fig. 3 by Mellema et al.) avoids sampling the entire oscillation period all at once in terms of time. More precisely, in Mellema, two ultrasound shots of a couple (every 100 ms) are emitted, after which two corresponding ultrasound echo signals are acquired and processed to determine the displacement in the medium when two ultrasound shots of a couple are emitted. Calculate. Thereafter, this procedure is repeated (with a repetition rate of 10 Hertz), for example after 100 ms. Because the processing time required to compute and analyze each two-dimensional deformation map is long, this procedure cannot be repeated with a higher iteration rate. So, using this technique, the entire oscillation period cannot be sampled all at once (since it requires a repetition rate higher than the frequency of the machine oscillation, i.e. higher than 100 hertz). So, this harmonic acoustic imaging technique enables two-dimensional spatial imaging and focuses on the spatial properties of the deformation field, but the temporal resolution is poor and affected by tissue motion, e.g. due to respiration or heartbeat. Receive.

Shear wave velocity measurements by harmonic seismic imaging are considered to be less reliable and less accurate than instantaneous seismic imaging, and harmonic seismic imaging generally provides over-estimated velocity values. In fact, as a harmonic acoustic image, the periodic mechanical vibration transmitted to the subject is a mixed shear wave and a compressed wave (the propagation speed of the compressed wave is much faster than the propagation speed of the shear wave), and these two components move within the subject's tissues. Due to its repetitive and continuous nature, it can hardly be separated. And harmonic seismic image measurements can also be distorted by seismic reflections inside the tissue, resulting in a static wave pattern (again, due to the repetitive and continuous nature of vibrations).

As a result, the above-described time-harmonic acoustic imaging technology provides valuable spatial information about the structure of a subject's body part under examination due to its two-dimensional imaging capability. However, this usually gives very inaccurate shear wave velocity values. The main reasons for this lack of accuracy take into account the combination of shear and compression waves, the influence of the diffraction effect due to the large size of the vibration source, and the displacement is typically captured during several vibration cycles and unmeasured out of plane motion. This is the effect of exercise such as breathing exercise. This problem leads to artifacts in the image that must be interpreted with great care, especially when quantitative measurements are provided.

As such, the instantaneous elastic imaging technique seems to be more suitable than the time-harmonic elastic technique to accurately measure the shear wave velocity in a fairly large and homogeneous organ such as the liver or spleen.

Instantaneous elasticity imaging is based on a different approach from the harmonic elasticity imaging technique presented above. Rather than recording an instantaneous two-dimensional map of tissue deformation (and deriving shear wave velocity values from the spatial properties of this map), instantaneous elastic imaging focuses on the spatio-temporal tracking of instantaneous mechanical pulses transmitted to the tissue. Are fitting.

A well-known instantaneous elastic imaging system is the FIBROSCAN® system (an ultrasound-based elastic imaging device for measuring the stiffness (or elasticity) and ultrasound attenuation of tissues and organs) produced and marketed by Echosens SA in Paris, France. Or other organ stiffness can be measured non-invasively to assess organ health.

With the FIBROSCAN® system, the operator places the tip of the probe of a somewhat smaller diameter (typically included between 5 and 10 mm) in contact with the subject's body in front of the subject's expected area of the liver. The operator then presses a button to cause the probe head to deliver an instantaneous low frequency mechanical pulse to the subject (the spectrum of this pulse is centered on a frequency typically contained between 10 and 500 Hertz). This pulse generates an acoustic wave that moves in the subject's body. The ultrasonic transducer mounted on the probe head in contact with the subject's body then sends multiple ultrasound shots to the tissue with a high repetition rate of at least 2 kilohertz. Echo signals corresponding to the backscattering of the emitted different ultrasound shots are acquired by the probe to track the slight movement of the tissue caused by the passing acoustic waves. Tracking is performed using a correlation technique applied to a continuous echo signal. The detected motion is a function of both tissue deformation as a function of depth (d) and as a function of time (t) (as a function of two different spatial coordinates, but instead of synthesizing an image representing tissue deformation at a given fixed moment). It makes it possible to synthesize the seismic wave propagation image that represents. 1 shows such an elastic wave propagation image 105, sometimes referred to as an “elastogram”.

Unlike other elastic imaging methods, the FIBROSCAN® probe uses an advantageous symmetric design. The ultrasonic transducer is a single element transducer mounted on the axis of the vibrator. The axis of the ultrasonic transducer coincides with the axis of the vibrator, which is why the displacement induced by the vibration is mainly longitudinal and therefore aligned with the axis of the ultrasonic beam. Displacement measurements are significantly improved under such conditions because out-of-axis displacement is very difficult to measure using ultrasound. Other acoustic imaging devices, especially harmonic devices, are more complex. They use multiple element ultrasonic transducers (typically liners or convex arrays) as they aim to provide a map of mechanical properties in 2D or 3D to find heterogeneity. The symmetry of these systems is much more complex. The displacement induced by vibration is not aligned with the ultrasonic beam(s) by design. They process much more data (multiple ultrasound lines) and require more computation time when evaluating the mechanical properties of 2D or 3D using sophisticated inverse algorithms. Moreover, they are very slow in motion.

Mechanical pulses delivered by the FIBROSCAN® probe head generate both shear and compression waves. In other words, the acoustic waves mentioned above combine shear waves and compression waves. However, these two waves have very different propagation velocities, and due to the instantaneous nature of the mechanical excitation, they can be easily separated over time and identified in the seismic propagation image. For example, referring to FIG. 1, this figure shows an acoustic wave propagation image 105. In Fig. 1, compressed waves are identified by reference numeral 105C, while very slow shear waves are identified by reference numeral 105S. In addition, as shown in Fig. 1, there are regions of interest (ROI) enclosed by two broken lines at 25 mm and 65 mm, which correspond to the depth under the patient's skin where the liver is normally located. This seismic propagation image can thereby be used to accurately determine the propagation velocity of shear waves in the tissue to be characterized, from which the stiffness of this tissue can be derived. Thereafter, this stiffness result 106 is the operator as shown in Fig. 1 showing the different graphs 101, 102, 105 and indicators 103, 106, 107 displayed to the operator by the display screen of the FIBROSCAN® system. Is provided to.

The FIBROSCAN® system can also measure the attenuation of the ultrasonic signal used to track the shear wave, which is useful because the ultrasonic attenuation correlates with the amount of fat content in the liver (see Figure 1, ultrasonic attenuation results (107)).

The FIBROSCAN® technology works well, but it is sometimes difficult for the operator to know if the probe has been correctly positioned in front of an area of the allogeneic hepatic tissue or if the probe is aiming at least a little towards the liver. Ribs in front of the liver, blood vessels, fluid sacs (ascites), or other artifacts of non-aligned tissue such as cysts or tumors of liver tissue can produce erroneous measurements of both tissue stiffness and ultrasound attenuation. Additionally, the operator may actually assume that the probe is aiming at the liver when it is too close to the lungs or other internal organs. As a result, the system may not be able to obtain accurate measurements.

To help the operator find the proper probe position, the FIBROSCAN® system is configured to continuously transmit ultrasound shots and acquire the corresponding echo signal while the operator searches for the appropriate probe position. A-mode and TM-mode graphs are displayed and updated in real time to help the operator find the proper probe position. 1 shows an example of such an A-mode graph 101 and TM-mode graph 102. The TM-mode graph represents an ultrasonic echo signal continuously acquired after the ultrasonic echo signal is processed. Processing of the ultrasonic echo signal includes, for example, envelope calculation and decimation. The TM-mode graph shown in FIG. 1 is a two-dimensional image representing one of the processed ultrasonic echo signals from which each column is acquired. Each row represents an instantaneous one-dimensional image as a function of depth (d) showing how the subject's body part aligned with the probe and positioned backscatters the ultrasonic wave. The acquired continuous ultrasonic echo signals are displayed side by side to show the evolution over time (t) of this one-dimensional image (this evolution is caused by slight probe movement or long-term movement due to breathing movement).

As shown in Figs. 1 and 2, the TM-graph can provide useful information regarding the positioning of the probe (3). In fact, when the probe axis (x) is aligned with the thick homogeneous portion of the liver (4), the TM-graph 402 generally looks like a stack of thin horizontal sheets, both horizontally and vertically as shown in FIG. It has a homogeneous aspect. In contrast, when the probe axis (x) is close to the edge of the liver (4), the TM-mode graphs 202, 302 often have a discontinuous aspect of either horizontal (FIG. 2) or vertical (FIG. 3).

Still, proper positioning of the probe based on the TM-graph is quite difficult and requires adequate training of the operator. Moreover, as one of ordinary skill in the art will appreciate, improper probe positioning can lead to improper measurement and inaccurate diagnosis of the patient condition.

The ultrasound signal displayed in the TM-mode or A-mode graph provides some information about the probe position but does not predict shear wave propagation. In some situations these graphs may seem appropriate, as the conditions are suitable for instantaneous elastic image measurements, but in reality no shear wave can propagate. This can occur when there is a liquid inclusion (see TM-mode graph 602 in FIG. 6), air inclusion (see TM-mode graph 602' in FIG. 6), a narrow intercostal space, and the like. Moreover, since the ultrasound signal is isoechoic, the blood vessel may not be observed on the ultrasound signal, but it may interfere with the propagation of the shear wave. FIG. 6 shows a TM-mode graph 602 ″'obtained when there is a dorsal vessel in which the vessel remains invisible (the location of this vessel is identified by an arrow).

As ultrasound and elasticity are not sensitive to the same conditions, guidance using ultrasound data is not sufficient because propagation of shear waves cannot be predicted. A good ultrasonic signal does not always result in good shear wave propagation. Some factors affecting shear wave propagation do not affect ultrasonic propagation. This is the case in the back of the nose, which can be blood vessels, cysts, fluid with particles, or a stiff or soft tumor.

Due to the limitations of conventional TM-graph guidance, operators generally do not find a suitable probe position in the first attempt to position the probe. In fact, it has been shown that operators often have to trigger instantaneous elastic image measurements several times while testing different locations by trial and error, before finding a suitable location and recording a suitable seismic propagation image to characterize liver stiffness. This takes a lot of time for the operator to still and firmly fix the probe before triggering the momentary elastic image measurement. As one of ordinary skill in the art will appreciate, such an attempt can be offensive to the patient under examination as the patient receives a small mechanical punch each time the operator performs a measurement. In addition, such attempts can prevent the operator from finding a suitable location, thereby increasing the job failure rate.

Thereby, it is desirable to develop a tissue characterization system, suitable for the precise characterization of the viscoelastic properties of such tissues and with improved guiding capabilities compared to the FIBROSCAN® system described above.

In order to address at least some of the above mentioned problems, the disclosed technology relates to a system for identifying allogeneic tissue in a subject or patient. Upon detecting an area of the allogeneic tissue, the operator may initiate measurement of tissue stiffness and/or determination of ultrasound parameters.

In some embodiments, the system:

A probe fixed to the subject's body and including a vibrator for transmitting mechanical vibration to the subject's tissue;

An ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive a corresponding echo signal; And

And a control module programmed to cause the system to execute the next step,

a) delivering continuous and periodic mechanical vibrations to the tissue of the subject, the periodic mechanical vibrations comprising the same vibration pattern repeated several times in succession over time;

b) emitting a sequence of ultrasonic shots by an ultrasonic emitter, acquiring a corresponding echo signal received by an ultrasonic receiver, and accumulating a method of moving the tissue by periodic mechanical vibrations transmitted to the tissue;

c) providing homogeneity information to the operator of the system-the homogeneity information is determined from at least some of the echo signals obtained in step b), and the homogeneity information is the ability of the tissue to transmit the acoustic wave and the Denotes the homogeneity of an organization for propagation.

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

Homogeneity information obtained by tracing how periodic mechanical vibrations travel through the tissue constitutes a highly efficient guidance information that helps the operator quickly and easily locate the appropriate probe positioned in front of the thick homologous portion of the organ to be characterized.

As will be appreciated, the "In vivo time-harmonic ultrasound elastography of the human brain detects acute cerebral stiffness changes induced by H. Tzschatzsch, published by Mellema et al. Two-dimensional seismic velocity maps such as those described in the document "intracranial pressure variations") do not constitute homogeneity information representing the tissue's ability to propagate seismic waves and its homogeneity to the propagation of seismic waves. In fact, such maps do not provide information about wave propagation, as these maps only represent instantaneous snapshots of the organ under examination.

In an embodiment according to the disclosed technology, the homogeneity information provided by the system indicates whether the spatiotemporal characteristic of the deformation of the tissue caused by the periodic mechanical vibration mentioned above is that of a wave traveling in the homogeneous medium (obtained in step b). The corresponding transformation is tracked by the generated echo signal)

14, 16, 17 and 18, the spatio-temporal properties of tissue deformation for propagation of elastic waves through the tissue, i.e., both as a function of time and as a function of at least one spatial coordinate. The characteristics (and thus the way the seismic waves actually propagate) reveal the somewhat homogeneous nature of the tissue in a very simple and easy-to-understand way. Such spatio-temporal properties may include data indicative of a change in the depth of the phase delay of a periodic deformation of the tissue, for example. As shown in Fig. 14, this phase delay changes substantially linearly with depth when the tissue is homogeneous, which is easy for the operator to discern. The above-mentioned spatiotemporal properties may also include data representing both the deformation of the tissue as a function of depth (d) and as a function of time (t). As shown in Figures 16 and 18 (Graph 188a), the graphs representing the deformation of the tissue as a function of depth and as a function of time comprise diagonal, substantially linear stripes, which, when the tissue is homogeneous, are Can be easily identified.

The manner in which such periodic acoustic waves propagate is much more sensitive to the structure of the tissue and its elastic properties than the TM-mode graph, as shown in FIG. 18.

The last three columns of the table in Fig. 18 are TM-mode graphs (182c, 182d, 182e), seismic propagation images (188c, 188d, 188e) acquired in periodic mode (periodic seismic propagation graph) and instantaneous Shows the seismic propagation images acquired in modes (185c, 185d, 185e), one corresponding to the probe position close to the edge of the liver (column c), and the other two liquid (column d) or air intercalation (column e) It is a situation to have. As can be seen in Fig. 18, in this situation, the TM-mode graph appears to be suitable for instantaneous elastic image measurement (such as column a), but in reality it is not (temporal elastic image images 185c, 185d, 185e)). In other words, TM-mode imaging cannot accurately detect whether the probe is located close to the edge of the liver, or whether there is air or liquid intervening between the probe and the target organ, so that proper probe positioning and improper probe positioning. There is no distinction between selections. In striking contrast, the noisy periodic seismic propagation images 188c, 188d, 188e contain numerous irregular fragments as opposed to one or several diagonal stripes with smooth (substantially linear) edges. As a result, the periodic seismic propagation images 188c, 188d, 188e immediately show the selection of a probe position suitable for instantaneous elastic image measurement. Moreover, the presence of small isoechoic blood vessels that are not visible in the ultrasound signal (see graph 182b in FIG. 18) can be easily detected in the seismic propagation image acquired in the periodic mode (see graph 188b in FIG. 18).

As one of ordinary skill in the art will appreciate, a periodic acoustic wave propagation image having a diagonal stripe with a substantially uniform and/or smooth edge, such as image 188a of FIG. It immediately indicates that it is suitable for image measurement (see instantaneous acoustic wave propagation image 185a in Fig. 18).

As has been found, in fact, the homogeneity information that is continuously updated and provided to the operator more often allows the operator, even an untrained one, to correctly find a suitable profile position in the first place.

In addition, the periodic mechanical vibrations transmitted to the subject during the examination are less unpleasant to the subject than the short, instantaneous mechanical pulses repeatedly triggered by the operator until the operator (he/she) finds a suitable probe position. Anything above the vibration amplitude required for seismic monitoring is significantly smaller than that required to achieve instantaneous seismic measurements. Additionally, the continuous nature of mechanical excitation used in the system of the disclosed technology to guide the operator enables continuous guidance.

Spatiotemporal monitoring of the deformation caused by periodic mechanical vibrations delivered to the subject can be achieved using a single-beam (single transducer) ultrasound system without 2D or 3D imaging capabilities. In practice, monitoring the propagation of waves from a spatiotemporal perspective can be achieved by monitoring tissue deformation as a function of time and only as a function of one spatial order (ie, depth). In other words, instead of using two sampling orders, which are both spatial orders (depth and lateral shifts as in Mellema et al.), instead of using a variant of two-dimensional sampling, one order is time and the other is depth. Can be done. As one of ordinary skill in the art will appreciate, using a single beam ultrasound system instead of a 2D imaging ultrasound system can quickly process the acquired echo signal, which is a single dimension from a spatial point of view. This allows to increase the temporal sampling rate at which the elastic deformation of the tissue is tracked. Thereby, the elastic deformation of the tissue is monitored with a higher temporal resolution than the harmonic acoustic imaging method in the prior art.

In addition, a high temporal sampling rate can sample the same period of periodic transformation of the tissue, or at least a major portion of the same period, all at once. This means that the periodic deformation of the tissue is sampled by a small portion, a small portion of the period (e.g., a single moment) is sampled, and then a small portion of the subsequent period, etc. 130)), which is very interesting when compared to a stroboscope-like technique that reconstructs the image post-hoc. In fact, with the stroboscope technique, the delay time required to obtain a completely updated new image showing the entire oscillation period is much longer than when the same period is sampled all at once at a high sampling rate (in the example of Fig. 13, the delay time is the same period. Is roughly 4 times longer than when all sampled at once). More importantly, the temporal images obtained with stroboscope sampling are often damaged by spurious effects and noise, especially due to tissue displacement caused by respiration or slight displacement of the probe. Moreover, the temporal resolution of the radio wave image obtained by stroboscope sampling is generally smaller than when the same period is all sampled at once (e.g., the temporal resolution of the radio wave images 131 to 134 in FIG. 13 is the radio wave image 130). Better than the temporal resolution of).

As one of ordinary skill in the art will appreciate, graphs showing periodic deformation of tissue in a spatiotemporal manner (such as that of FIG. 18) as a function of depth and time are easy to understand as is. This means that graphs representing instantaneous deformations of tissue (as a function of two spatial coordinates) are hardly understandable (see, for example, Fig. 9A of Millena et al., or Fig. 3A of Tzschatzsch et al.), (such as a 2D shear wave velocity map). ) Compared to prior art harmonic acoustic imaging techniques such as Mellema et al. or Tzschatzsch et al., which require complex post-processing to obtain useful information to the operator, it was quite surprising.

In summary, the system for characterizing tissues according to the disclosed technology has very good guiding capabilities, allows the operator to quickly and easily find areas of the homogeneous tissue, is suitable for instantaneous elastic imaging measurements, or for ultrasonic wave propagation within tissues. Allows determination of ultrasonic parameters.

To benefit from these guiding capabilities, in embodiments of systems that characterize tissue according to the disclosed techniques, the control module of the system is further programmed to determine at least one physical property of the tissue, including one of the following: :

Ultrasonic parameters for ultrasonic wave propagation within the tissue attenuation value;

Mechanical properties of tissue related to shear wave propagation determined by instantaneous elastic imaging.

Ultrasound parameters are either Broadband Ultrasound Attenuation (BUA, usually expressed in dB/cm/MHz), attenuation measured at a specific frequency (dB/cm), or Controlled Attenuation Parameter (CAP). ), including ultrasonic attenuation parameters that reflect ultrasonic attenuation in the tissue. However, this is not limited as additional parameters may be determined in other embodiments.

The mechanical properties of the tissue associated with shear wave propagation may be quantities related to tissue stiffness, such as the propagation velocity of the shear wave (V _s ), the shear modulus of the tissue, or the Young's modulus of the tissue (E). This may be a quantity related to the attenuation of low frequency shear waves in the tissue, such as viscosity.

As will be appreciated, the system for determining the mechanical properties by instantaneous elastic imaging, in which the propagation of periodic seismic waves is preliminarily monitored to find homogeneous tissue, is somehow initially configured for instantaneous elastic imaging, and very different, even instantaneous. Seismic imaging technology (which aims to separate compressed and shear waves) and harmonic seismic imaging technology of the prior art (focusing on the almost pure spatial characteristics of the deformation field, helping the operator to properly position the probe) It is a further modified system to implement the guidance technology presented above, as opposed to).

In an embodiment according to the disclosed technology, the control module exhibits periodic deformation of the tissue from at least some of the echo signals obtained in step b), at different depths within the tissue, and at different moments of periodic mechanical vibrations transmitted to the tissue. It is programmed to determine the data.

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

A graph showing a change over the depth of at least one temporal characteristic of a temporal, periodic change of tissue deformation; or

An indication specifying whether the characteristic changes with depth as if the tissue was homogeneous over a given depth range.

The graph can display:

-Change in deformation over time as a function of depth;

-Phase delay of periodic deformation of tissue as a function of depth;

-The amplitude of the envelope of this periodic deformation as a function of depth.

In an embodiment, the above-mentioned graph represents the deformation of the tissue at different depths within the tissue and at different moments of cyclic mechanical vibration transmitted to the tissue, wherein the graph shows the pixel row index represents the depth and the pixel column index represents the time. A two-dimensional image performed or vice versa, with each pixel having a pixel value representing the deformation of the tissue in depth and time associated with the pixel being considered.

In an embodiment, the above-mentioned indication is a graph representing the deformation of the tissue at different depths within the tissue, and at different moments of cyclic mechanical vibration transmitted to the tissue, where the pixel row index represents the depth and the pixel column index is It is a two-dimensional image that represents time and vice versa, and specifies whether each pixel has a pixel value representing the deformation of the tissue in depth and time associated with the pixel being considered) is composed of diagonal stripes across the depth range. .

In embodiments, the system includes manual adjustment controls, such as cursors, sliders, buttons or knobs, that allow the operator to manually adjust the amplitude of periodic mechanical vibrations. This is useful when the amplitude of periodic deformation of the tissue caused by periodic mechanical vibration transmitted to the tissue is too low or too high. The system may include an amplitude indicator for displaying information to the operator regarding the amplitude of periodic deformation of the tissue.

In an embodiment, the system is configured to automatically adjust (ie, without requiring operator action) the amplitude of periodic mechanical vibrations based on the amplitude of the resulting periodic deformation of the tissue. More precisely, the system increases the amplitude of periodic mechanical vibrations when the amplitude of the resulting cyclical deformation of the tissue is too low (below a given threshold), and when the amplitude of the resulting cyclical deformation of the tissue is too high (another When the amplitude threshold is exceeded) it may be configured to reduce the amplitude of periodic mechanical vibrations.

In an embodiment, the system is configured to adjust the amplitude of the instantaneous mechanical pulse delivered to the subject to measure the mechanical properties of the tissue associated with shear wave propagation by instantaneous elastic imaging, based on the amplitude selected for the periodic mechanical vibration. . In this case, in addition to the different advantages presented above, the preliminary characteristics of the tissue by the periodic elastic imaging makes it possible to determine the amplitude of the instantaneous mechanical pulse suitable for performing the subsequent instantaneous elastic imaging measurement.

As will be appreciated, in accordance with the disclosed technology, the different embodiments presented above may be combined together in all technically possible combinations.

Optionally, the non-limiting features of the system characterizing the tissue presented above are defined according to the disclosed technology, by claims 3-7 and 10-18, as submitted.

The disclosed technology also provides a method of tissue characterization performed by a system comprising:

A probe fixed to the subject's skin and including a vibrator for transmitting mechanical vibration to the subject's tissue;

An ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive a corresponding echo signal; And

A control module programmed to cause the system to execute the next step of the method

a) delivering continuous and periodic mechanical vibrations to the tissue of the subject, the periodic mechanical vibrations comprising the same vibration pattern repeated several times in succession over time;

b) emitting a sequence of ultrasonic shots by an ultrasonic emitter, acquiring a corresponding echo signal received by an ultrasonic receiver, and tracking how the tissue is moved by periodic mechanical vibrations transmitted to the tissue;

c) providing homogeneity information to the operator of the system-the homogeneity information is determined from at least some of the echo signals obtained in step b), and the homogeneity information is the ability of the tissue to transmit the acoustic wave and the Indicates organizational homogeneity to propagation;

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

The features of the different embodiments of the systems described above can also be applied to this method of characterizing tissue.

1 shows different graphs and indicators displayed to the operator by the display screen of the FIBROSCAN® system;
Figures 2-4 show different TM-mode graphs displayed to the operator for different positions of the probe of FIBROSCAN® relative to the organ to be characterized;
5 shows a TM-mode graph obtained when the probe of FIBROSCAN® is well positioned (where its axis is centered on the organ to be characterized);
Figure 6 shows different TMs obtained in situations in which the probe will not be properly positioned (its axis is close to the edge of the organ to be characterized), or in the presence of liquid, air or vascular intercalation that is not suitable for proper mechanical characterization of the organ. -Show the mode graph;
7 is a block diagram of a tissue characterization system in accordance with some embodiments of the disclosed technology;
8 is a flow diagram of a method for tissue characterization in accordance with some embodiments of the disclosed technology;
9 is a sequence of ultrasonic shots emitted to track continuous and periodic mechanical vibrations transmitted to a subject's tissues, tissue deformation caused by these vibrations, and acoustic wave propagation obtained therefrom, according to some embodiments of the disclosed technology. Shows the image;
10 illustrates another way of emitting a sequence of ultrasound shots to track continuous and periodic mechanical vibrations delivered to the subject's tissues, and the deformation of the tissues caused by these vibrations, in accordance with some embodiments of the disclosed technology. Show;
11 is a still another way of emitting a sequence of ultrasound shots to track continuous and periodic mechanical vibrations delivered to the subject's tissue, the deformation of the tissue caused by this vibration, in accordance with some embodiments of the disclosed technology, and It shows the periodic acoustic wave propagation image obtained therefrom;
12 illustrates how the periodic acoustic wave propagation image of FIG. 11 can be momentarily aligned for operator viewing, in accordance with some embodiments of the disclosed technology;
13 shows between a low sampling rate, stroboscopic like method for tracking periodic deformation of tissue and a high sampling rate method for tracking periodic deformation of such tissue, according to some embodiments of the disclosed technology. Showing differences, wherein the same period of tissue deformation in the differences is monitored all at once as a whole;
14 illustrates the determination of a phase delay of an acoustic wave at a specific depth of tissue, in accordance with some embodiments of the disclosed technology;
15 illustrates different graphs and indicators displayed to an operator by a system characterizing tissue, in accordance with some embodiments of the disclosed technology;
16 and 17 show exemplary seismic propagation images from homogeneous and non-homogeneous tissues, respectively, in accordance with some embodiments of the disclosed technology;
18 shows exemplary TM-graphs, periodic seismic propagation images, and instantaneous seismic propagation images provided to the operator, in accordance with some embodiments of the disclosed technology, these graphs and images in a number of different situations and probe locations. Is obtained.

7 is a block diagram of a tissue characterizing ultrasound system 1, configured to detect allogeneic tissue. This system (1) includes:

-A probe 10 comprising a vibrator 12 held against the body of the subject 50 and configured to transmit mechanical vibrations to the tissue 51 of the subject;

-An ultrasonic emitter configured to emit a sequence of ultrasonic shots, and an ultrasonic receiver configured to receive a corresponding echo signal to track how the subject's tissue is moved by such mechanical vibrations;

-A control module 20 that controls the probe 10 and processes the data acquired by the ultrasonic receiver.

The expression “tissue” is understood to mean a body part of subject 50 (human or animal). This expression does not necessarily designate an entire organ or a single organ. The tissue 51 to which the mechanical vibration is transmitted and the tissue deformation is tracked by the ultrasonic shot is a part of the subject's body located near the probe 20, along the axis z of the probe.

The system 1 determines homogeneity information indicating whether the tissue 51 is homogeneous and whether the tissue can transmit an elastic wave, in particular a shear wave using periodic elastic imaging technology, and transfers this information to the operator interface 30. Is configured to provide to the operator.

Homogeneity information constitutes guiding information that helps the operator position and align the probe 20 to the organ to be characterized, such as the liver or spleen. Once the probe 20 is properly positioned due to this guiding information, one or several physical properties of the tissue can be determined to characterize this organ, for example using instantaneous elastic imaging.

In this document, the expression “elastic wave” refers to an ultrasonic shot or echo signal whose center frequency is typically higher than 0.1 MHz, or even higher than 1 MHz (while such an ultrasonic wave also propagates through the tissue, However, at very high frequencies they produce some kind of elastic deformation, which is not designated as "elastic waves" in this document), low frequency mechanical waves or tissue deformations, i.e. mechanical waves whose center frequency is less than 500 hertz, or even less than 100 hertz. Or tissue modification.

To provide homogeneity information, the control module 20 is more accurately programmed so that the system 1 for characterizing the tissue performs the following steps:

a) delivering a continuous and periodic mechanical vibration PMV to the tissue 51 of the subject 50, wherein the periodic mechanical vibration comprises the same vibration pattern (VP) repeated several times in succession over time (e.g. For example, see Fig. 9);

b) The ultrasonic emitter 11 emits one sequence of ultrasonic shots (same sequence 80, 80', 80'' in Fig. 9) and how the tissue 51 is transmitted to the tissue by a periodic mechanical vibration PMV. Acquiring a corresponding echo signal received by the ultrasonic receiver 11 to track whether it is moving;

c) providing the above-mentioned homogeneity information to the operator 40 of the system, wherein the homogeneity information is determined from at least some of the echo signals obtained in step b).

The control module 20 is programmed to repeatedly execute steps b) and c) continuously (ie, without interruption) until the operator 40 presses the control button 13 and triggers a momentary elastic image measurement. Thereby, the homogeneity information provided to the operator 40 is continuously updated, which helps the operator to locate the appropriate probe.

The system 1 may be configured to determine the homogeneity information mentioned above to more accurately indicate whether the tissue 51 is homogeneous for a given depth range or region of interest. This depth range is, for example, the depth range in which the subject's liver is expected to extend if the probe 20 is properly positioned. This depth range may extend, for example, from 25 millimeters deep to 65 millimeters deep under the subject's skin (the liver is usually located at these depths), or from 35 millimeters to 75 millimeters deep. This depth range defines, within the tissue 51, the region of interest (ROI) of the tissue to be characterized (in FIG. 15, this region of interest extends between two horizontal dashed lines).

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

Ultrasonic parameters for ultrasonic wave propagation within tissue values, for example ultrasonic attenuation values such as BUA, CAP and/or attenuation measured at a specific frequency;

The propagation rate of the shear wave (V _s ), the shear modulus of the tissue, the Young's modulus (E) of the tissue, or the viscosity of the tissue at low frequencies (i.e. 500 Hertz or less) are related to shear wave propagation determined by instantaneous elastic imaging. Mechanical properties of the tissue.

More precisely, system (1) of Fig. 7 determines the mechanical properties of the tissue, related to shear wave propagation, for tissues with a Young's modulus contained between 1 and 100 kilopascals (suitable for studying liver or spleen stiffness). Can be configured to System 1 may also be configured to determine an ultrasonic attenuation value in tissue where the CAP value is between 50 and 500 dB/m.

The structure of the system 1 of Fig. 7 is now described in more detail. Thereafter, a method of characterizing the tissue according to some embodiments of the disclosed technology that is shown in FIG. 8 and that may be implemented by the system (1) of FIG. 7 will be presented, furthermore exemplary results obtained by this system or method Will be presented (see Figures 15-18).

As already defined, the probe 20 of the system 1 of FIG. 7 includes a vibrator 12, such as an electromechanical vibrator or acoustic speaker, to transmit mechanical vibrations to the tissue 51 of the subject. Such mechanical vibration may be transmitted to the tissue as a force applied by the tip of the probe on the subject's body, the displacement of a part of the subject's body upon contact with the tip, or a combination thereof, exerted by the tip.

In the system 1 of FIG. 7, the vibrator 12 is rotationally symmetric about the vibrator axis, and the vibrator axis coincides with the probe axis z. When the vibrator 12 vibrates, the vibrator induces a displacement mainly in the longitudinal direction parallel to its axis.

In the system 1 of Fig. 7, the ultrasonic emitter and the ultrasonic receiver are composed of the same ultrasonic transducer 11 (for example a piezoelectric transducer). This ultrasonic transducer 11 is rotationally symmetric about the transducer axis and emits an ultrasonic beam about this axis. The transducer axis coincides with the axis of the vibrator. The ultrasonic transducer 11 has, for example, a circular section, the axis of the vibrator passing through the center of this 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 a part of the probe that will be positioned upon contact with the subject's body. The tip is relatively small; Its contact surface is usually less than 1 square centimeter. The tip may have a diameter of less than 1 centimeter, or less than 8 or even 5 millimeters.

The probe 10 includes a control button 13 or a manual trigger such as a dial. The system 1 is configured to achieve instantaneous elastic image measurements when the manual trigger 13 is actuated.

The probe may include manual adjustment controls such as cursors, sliders, buttons, or knobs to manually adjust the amplitude of periodic mechanical vibrations, the amplitude of momentary mechanical pulses, or both.

The system may be configured to automatically adjust the amplitude of the periodic mechanical vibrations (in harmonic elastic images) and/or the amplitude of the transient mechanical pulses (in momentary elasticity). The system can be configured to automatically adjust the amplitude of the instantaneous mechanical pulses based on the amplitude of the periodic mechanical oscillations adjusted in advance.

It will be appreciated that in other embodiments in accordance with the disclosed technology, the ultrasonic emitter and receiver may be composed of two separate transducers instead of the same. Additionally, the probe may include an additional vibrator such as an electromechanical vibrator, an acoustic speaker or an electric motor provided with an eccentric cam. This additional vibrator can be configured to induce vibrations that are rotationally symmetric about the z axis, or at least parallel to the z axis in the same manner as the vibrator 12 described above. In such an embodiment, the system may be configured to generate momentary mechanical vibrations by vibrator 12, while generating periodic mechanical vibrations by additional vibrators.

The system 1 of FIG. 7 also includes a control module 21, an ultrasonic front end 22 with an ultrasonic transmitter module 27 and an ultrasonic receiver module 29, and a motion-actuated servo controller for controlling the vibrator 12. It includes a central unit 20, including 23. Both the ultrasonic front end 22 and the motion actuation servo controller 23 are connected to the control module 21 (i.e., they can receive commands from the control module 21 or send data thereto).

The motion actuation servo controller 23 includes an electrical circuit configured to generate an electrical signal suitable for driving the vibrator 12 when directed by the control module 21. This electrical circuit may comprise a current amplifier, or another type of amplifier.

The ultrasonic front end 22 alternatively comprises a switch 28 for transmitting and receiving ultrasonic signals. The ultrasonic transmitter module 27 of this front end 22 is an electric ultrasonic signal suitable for driving the ultrasonic transducer 11 when indicated by the control module 21 (e.g., see step b for further description below). And an electrical circuit configured to generate a sequence of ultrasound shots). This electrical circuit may comprise an amplifier and a digital-to-analog converter (DAC), for example an 8 to 16 bit DAC with a 10 to 1000 mega-sample rate per second. The ultrasonic receiver module 29 is an electrical circuit configured to obtain an electrical ultrasonic signal (echo signal) that is previously received by the ultrasonic transducer 11 (and transmitted to the ultrasonic receiver module 29 through the switch 28) Includes. The electrical circuit of the ultrasonic receiver module 29 may comprise a tension amplifier, a filter and an analog-to-digital converter (ADC), for example an 8 to 16 bit ADC with a 10 to 1000 mega-sample rate per second.

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

As shown in Fig. 7, the control module 21 more specifically includes:

Processor 24, for example a general purpose processor;

Signal processing circuitry 26, for example an FPGA (FPGA coprocessor), DSP or another programmable circuit; And

A physical non-instantaneous memory module comprising 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. (25).

The control module 21 may be in the form of an FPGA carrier board, for example. The processor 24 can be embedded within (e.g., within an FPGA) or outside of the signal processing circuit 26 (e.g.: away from the FPGA, then the FPGA can be Offload the processor 24 by executing special signal processing tasks). The signal processing circuit 26 is configured to process the echo signal received by the transducer (when digitized by the ultrasonic receiver module 29).

As already mentioned, the control module 21 is programmed such that the system 1 executes the steps a), b) and c) presented above. The control module 21, when executed by the control module 21, is programmed so that the system includes instructions that cause the control module 21 to do the following:

Controlling the motion actuation servo control 23 to drive the vibrator 12 to transmit periodic mechanical vibrations to the tissue (step a));

It controls the ultrasonic front end 22 to drive the ultrasonic transducer 11 and accordingly emits a sequence of ultrasonic shots to track how the tissue is moving by periodic mechanical vibrations, and the ultrasonic receiver module 29 Acquire a signal (step b));

From at least some of the echo signals thus obtained, determine the ability of the tissue to transmit an elastic wave, i.e., the ability to propagate the elastic wave through it, and homogeneity information representing the homogeneity of the tissue to the propagation of the elastic wave, and this information, Providing to the operator, for example by sending it to the operator interface 30 (step c)).

Instructions that cause the control module 21 to control the system 1 to execute any given steps, in particular steps a), b) and c), are stored in the non-volatile memory 250 in mechanical form. Executable instructions or code instructions, or in the form of electrical (reconfigurable) connections between the gates of the circuit, or a combination thereof, are physically embedded in programmable circuit 26. The instructions that the control module 21 executes to control the system 1 to execute any given step, in particular steps a), b) and c), is a non-volatile memory in the form of mechanically executable instructions or code instructions. Stored in 250, or physically embedded in programmable circuit 26, in the form of electrical (reconfigurable) connections between the gates of this circuit, or combinations thereof.

In step c) the control module 21 can be more specifically programmed to:

c0) From the echo signal obtained in step b), data representing the deformation of the tissue 51 are obtained at different depths (d) within the tissue and at different moments (t1, t2, t3) of periodic mechanical vibrations transmitted to the tissue. Decide; And

c1) Homogeneity information is determined from the data representing the deformation of the tissue 51 determined in step c0).

Step c0) can be performed using a correlation technique or another pattern matching algorithm to determine how a part of the tissue 51 moves under the influence of an elastic wave passing through the tissue (the elastic wave is transmitted by the system). Caused by mechanical vibration). For example, tissue in a small zone of the region of interest may move slightly away from the transducer 11 and then slightly towards the transducer 11 as the spatial period of the acoustic wave passes through this zone. Step c0) is typically executed by the programmable circuit 26 to offload the processor 24.

The control module 21 can, inter alia, be further programmed to execute the different steps of the method for the system 1 to characterize the tissue shown in FIG. 8.

As shown in FIG. 7, the tissue characterization system 1 includes the operator interface 30 mentioned above. Still, in other embodiments in accordance with the disclosed technology, the operator interface may be distinct from the tissue characterization system. The operator interface can be embedded, for example, in a smartphone or computer that communicates with the organization characterization system. In such a case, in order to provide the homogeneity information to the operator, the control module 21 transmits this information to the external operator interface by the communication module of the organization characterization system. The communication module may be an electrical circuit configured to exchange data using a wired or wireless link, for example according to USB, Firewire, Bluetooth, 6LoWPAN, ZigBee, Z-Wave or Sigfox protocols.

With the system of Fig. 7, the homogeneity information determined by the control module 21 is, for example, the display screen 31 of the operator interface 30 in the form of graphs 808, 809 and indicators 810 of Fig. 15 Provided to the operator by The operator interface 30 also includes a light emitting diode or other light emitting device 14, arranged on the probe 10 to visually indicate to the operator 40 whether the tissue is homogeneous by a change in color or luminosity of the emitted light. ) Can be included.

In some embodiments where the system is a pocket system, the operator interface includes the light emitting device described above, but does not include a display screen.

In yet another embodiment, the operator interface includes a speaker for indicating to the operator whether the tissue is homogeneous by an audible signal. Such homogeneity information may also be provided to the operator by haptic indications such as a change in amplitude or type of mechanical vibration.

The central unit 20 and the probe 10 are shown as separate parts in FIG. 7, but all or part of the modules 21, 22, 23 of the central unit 20 presented above may be disposed within the probe.

It will be appreciated that many variations may be made in the system for characterizing the tissues presented above without departing from the scope of the disclosed technology. For example, some electrical functionality may be distributed within the central unit differently than described above. For example, the DAC and ADC may be located in the control unit instead of the ultrasonic transmitter and receiver module. Some of the modules 23-29 may be merged or distributed together. In addition, the control unit may include only one processor, instead of one processor and signal processing unit. Alternatively, the control unit may include a greater number of processing units than in FIG. 7.

A flow diagram of a method for characterizing tissue in accordance with some embodiments of the disclosed technology is shown in FIG. 8. As already mentioned, the control module 21 of the system 1 of FIG. 7 can be programmed so that the system 1 executes this method.

The method includes the following main steps: S0, allogeneic tissue detection, S1, measurement of tissue stiffness by instantaneous elastic imaging and S2, providing an ultrasonic attenuation value to the operator. In step S0, the system 1 delivers continuous periodic mechanical vibration to the subject to test tissue homogeneity and provides the above-mentioned homogeneity information to the operator 40. This information is continuously updated so that operators can test the location of different probes by monitoring tissue homogeneity in real time. If the homogeneity information indicates that the tissue 51 under examination is homogeneous, the operator 40 activates a manual trigger (eg: the operator presses the control button 13). After that, the execution of step S0 is stopped and the execution of steps S1 and S2 is started. When the tissue stiffness measurement is made in step S1, execution of step S0 is restarted so that the operator can confirm that the probe is still positioned in front of the allograft tissue. The alternating process between the release of continuous periodic mechanical vibrations (for homogeneity evaluation) and the measurement of tissue stiffness by instantaneous elastic imaging can be continued until the required number of tissue stiffness measurements are obtained.

Now steps S0, S1 and S2 are described in more detail in turn.

Step S0: allogeneic tissue detection

As shown in Fig. 8, step (S0) includes steps a), b) and c) presented above. Step (S0) begins with step a), during which the control module 21 controls the vibrator 12 (via the motion actuation servo control 23), so that the vibrator 12 (51) to deliver continuous and periodic mechanical vibration PMV. These periodic mechanical oscillation PMVs are all transmitted continuously along step S0 (which all continues along step S0). When the emission of this periodic mechanical vibration PMV begins, the control module executes step b), during which the control module controls the ultrasonic transducer 11 (via the ultrasonic transmitter module 27), thereby It emits a shot to track how the tissue moves by periodic mechanical vibrations, and acquires a corresponding echo signal (via the ultrasonic receiver module 29). Then, in step c), the control module determines the homogeneity information from the echo signal obtained in step b) and then provides it to the operator. Thereafter, the control module executes steps b) and c) again and provides the operator with new updated homogeneity information while the periodic mechanical vibration PMV is continuously transmitted. Thereby, the set steps comprising steps b) and c) are continuously executed several times in succession until step S0 is stopped by the operator actuating the manual trigger mentioned above. For example, in the case of Fig. 9, the set of steps comprising steps b) and c) is repeated every 50 milliseconds (at a repetition rate of 20 Hertz). So, in this case, if (for example) it takes 3 seconds for the operator to find a suitable probe position and activate the manual trigger, then step (S0) will last approximately 3 seconds, and the set steps including steps b) and c) Will be repeated approximately 60 times.

In the embodiment of Figure 8, the set steps comprising steps b) and c) are in real time, i.e. with a repetition rate of 10 hertz or more, or even 20 hertz or more, and a delay of less than 1 second, or even less than 0.1 seconds or less than 0.03 seconds. It runs with time. The delay time is the time interval between the start of the emission of the ultrasonic shot sequence in step b) and the moment when updated homogeneity information determined from the echo signal obtained in step b) is provided to the operator.

In the method of Fig. 8, step c) includes sub-steps c0) and c1) described above. In step c0), the control module collects data representing the deformation of the tissue 51 from the echo signal obtained in step b), at different depths (d) within the tissue, and at different moments of periodic mechanical vibration transmitted to the tissue (t1 , t2, t3). In step c1), the homogeneity information provided to the operator is the deformation of the tissue caused by periodic mechanical vibrations as a function of time (t) and as a function of depth (d) (this deformation was determined in step c0). Graphs 808 of FIGS. 9 and 15, graphs 168 and 178 of FIGS. 16 and 17, or graphs 188a-188e of FIG. 18, showing both.

Steps a), b) and c) are now described in more detail.

In step a) , the periodic mechanical vibrations transmitted to the tissue have a fundamental frequency, i.e., a fundamental frequency contained between 10 hertz and 200 hertz. More specifically, it may have a fundamental frequency included in 10 Hertz to 60 Hertz. Such a frequency value is advantageous for deep penetration of vibrations in the tissue, but is still fast enough to determine the updated homogeneity information with an update rate of 10 Hertz or more, thereby enabling real-time monitoring of tissue homogeneity. The periodic mechanical oscillation PMV can have a fundamental frequency of 40 Hertz (and thus a 25 millisecond period), as in FIGS. 9 and 10, or 25 Hertz (and thus a 40 millisecond period), as in FIG. 9, 10, and 11, the periodic mechanical vibration PMV is a sinusoidal vibration. Still, other periodic waveforms such as triangular waveforms can be used. Periodic mechanical vibration (PMV) is continuous in that it contains the same vibration pattern (VP) (here a sine wave period) repeated several times in succession, one immediately after the other, over time. Each new instance of the vibration pattern starts immediately after the previous one and there is no delay in between. The vibration pattern is repeated at the repetition rate, which is the aforementioned fundamental frequency. As already mentioned, the periodic mechanical vibrations all continue continuously along step S0. So, the periodic mechanical vibration usually lasts more than 1 second. A portion of the subject tissue 51 that comes into contact with the probe 20 vibrates with an amplitude typically contained between 0.1 and 2 millimeters as a result of periodic mechanical vibrations transmitted by the probe.

In step b) , the control module 21 instructs the ultrasonic transmitter module 27 to generate a sequence of ultrasonic electrical pulses converted by the ultrasonic transducer 11, and accordingly, a sequence named ultrasonic shot. By emitting short ultrasonic pulses of, it tracks, or in other words, seeks to see how the tissue 51 is moved by a periodic mechanical vibration PMV. 9 shows ultrasound shots 81, 82, ... of a representative sequence 80. The center frequency of each ultrasound shot is included, for example, between 1 and 5 megahertz. The duration of each shot, for example 100 microseconds, is typically less than one millisecond. In step b), the control module 20 also obtains a sequence of corresponding echo signals received by the ultrasonic transducer 11. Each echo signal corresponds to an ultrasonic shot emitted by the transducer in that the echo signal is an ultrasonic wave backscattered by the tissue in response to the emission of the considered ultrasonic shot (or at least exhibiting this backscattered wave). do. Each echo signal represents the backscattering property of the tissue as a function of depth (d) within the tissue (each moment within one of these short echo signals is an ultrasonic wave between the transducer and a point located at the considered depth). Since the round trip time of s is directly dependent on its depth, it corresponds to a given depth of tissue).

As already mentioned, these successive echo signals are obtained to compare with each other, for example using correlation techniques or another pattern matching algorithm, so that a portion of the tissue 51 under the influence of an acoustic wave passing through the tissue. Determine how it moves (this determination is done in step c)). Thereby, in order to prevent non-correlation between the two echo signals acquired successively, the ultrasound shot is emitted at a pulse repetition rate of 500 hertz or more, or even 1 kilohertz or more in step b) (actually, such Non-correlation can occur due to the total tissue displacement caused by respiration, e.g. when the duration between two consecutive shots is too long). Typically, the pulse repetition rate is included between 1 kilohertz and 10 kilohertz (depending on the control module calculation capacity). So, within a sequence of ultrasound shots emitted in step b), the duration between any shot and the immediately following shot is less than 2 milliseconds, or even less than 1 millisecond.

In the method of Figure 8, the sequence of ultrasonic shots emitted in step b) is at least 1/2 or more, or even at least 3/4 or more of the same period of periodic mechanical vibration PMV delivered to the tissue (e.g., Over the entire period). And this sequence includes at least 10, or even 50, ultrasound shots per periodic mechanical vibration period. As a result, in this case, the same period of the periodic mechanical oscillation PMV, or at least a major part of the same period, are all sampled entirely at once by the shot sequence emitted in step b). As already explained, this can monitor the propagation of periodic elastic deformation much better than sampling methods such as stroboscopes.

In step b), the control module may in particular control the ultrasonic transmitter module 27, thereby generating a sequence of ultrasonic shots as shown in Figs. 9, 10 or 11.

In the example of FIGS. 9 and 10, the ultrasonic shot sequence 80 emitted in step b) continues more accurately over a period of periodic mechanical vibration PMV. In these examples, the ultrasonic shot repetition rate is equal to 2 kilohertz. Therefore, the ultrasonic shot sequence contains 50 shots per period of periodic mechanical vibration (in these examples, the frequency of periodic mechanical vibration is equal to 40 Hertz).

In the example of Fig. 11, the sequence of ultrasound shots emitted in step b) continues over one or more periods. The ultrasonic shot repetition rate may also be equal to 2 kilohertz, which corresponds to 80 shots per period (in this case, the frequency of the periodic mechanical vibration equals 25 hertz).

The ultrasonic shots 80, 80', 80'' of the sequence emitted in step b) can be emitted in a synchronized manner with respect to periodic mechanical vibrations, which is the result of periodic mechanical vibrations (PMV) transmitted to the tissue 51. Within the cycle, it starts from the same instantaneous io for each execution of step b). As shown in Fig. 9, this makes it possible to obtain a stable propagation graph 808n with no rolling (time shift) effect from one execution of steps b) and c) to another.

In such a case, the absolute time (to, to', to'') at which the ultrasonic shot sequence begins is different from one execution of step b) to another. However, the time at which the sequence starts with respect to the start of the cycle of periodic mechanical oscillations is the same for each execution of step b) (more precisely, the time at which the sequence begins, but the closest to this start time is the The time with respect to the start of the cycle-ie with the start of the instance of the vibration pattern closest to this start time, is the same for each execution of step b).

In the case of Figs. 9 and 10, for example, for each execution of step b), the ultrasonic shot of the sequence starts almost at the beginning of the period of periodic mechanical vibrations as the vibration increases as it passes through zero ( The ultrasonic shot can also start a given fixed delay time after a period of periodic oscillation has begun).

Due to this synchronization, the propagation graph (inferred from the shot emitted in step b)) representing both the deformation of the tissue as a function of depth and as a function of time for each new run of steps b) and c) is a periodic machine. It starts from the same moment io within the cycle of vibration (displayed continuously to the operator as different propagation graphs 808, 808', 808' in Fig. 9). This keeps this graph stable from one run to another and is temporally aligned instead of rolling. Due to this stabilization, it is easier for the operator to understand the graph (since deformation monitoring is not hindered by time rolling, graph movement). This allows the operator to more easily determine whether the probe is positioned in front of the allograft tissue, in situations suitable for measuring the physical parameters of the tissue.

Step b) can be repeated at a rate such that each new sequence of ultrasound shots is emitted immediately after another shot, without interruption between them, as in FIG. 10. In the example of Fig. 10, hereby, a sequence of ultrasonic shots is emitted for each period of periodic mechanical oscillation PMV (to track tissue deformation). Step b) is also slower when the control module 21 has a more limited processing speed, e.g., by emitting a sequence of ultrasonic shots every two periods of the periodic mechanical vibration PMV, as in the case of FIG. It can be repeated at a rate. In the case of Fig. 9, before the next sequence of ultrasound shots is emitted, after each emission of one sequence of ultrasound shots, the operator is provided with a new updated version of homogeneity information. In other words, in this case, the execution of step c) is completed before the new execution of step b).

In step b), as shown in Fig. 11, a sequence of ultrasound shots (110, 110', 110'') can also start from the moment (io, io', io''), which is the tissue 51 Within the cycle of the periodic mechanical vibration PMV transmitted to, from one execution of step b) to another is different. In such a case, in step c), if a raw propagation graph, such as graph 118, 118 or 118'' of Fig. 11, is provided to the operator, the operator will have the disturbance rolling mentioned above when this raw graph is updated. In other words, the time-shifting effect will be recognized ("raw propagation graph" is understood to mean a graph representing both tissue deformation as a function of time and depth, the deformation being displayed over time in the order in which it was sampled; i.e. , In such a raw graph, the time coordinate is the actual time the deformation was measured).

So, in this case, in order to prevent such a rolling effect, the deformation data determined from the echo signal is temporally rearranged before being displayed, as in the graphs 118a, 118a', 118a'' of Fig. 12, the periodic mechanical vibration It is post-processed (in step c) in the form of a re-aligned propagation graph all starting from the same fixed moment within a cycle of. In other words, the re-aligned propagation graph provided to the operator in step c), within the period of periodic mechanical vibration transmitted to the tissue, is the same reference moment (i _R) whenever the graph is updated based on the newly determined deformation data. Starts from ). Temporal re-alignment can be achieved as follows: the transformation data obtained during the time (actual, absolute measurement time) preceding the reference instant (i _R ) is as schematically shown in FIG. 12, (ultrasonic shot sequence As measured immediately after), from a temporal point of view, it is moved as a block to be placed at the end of the transformation data. The reference moment (i _R ) is the beginning of this vibration pattern at a given fixed moment within the vibration pattern VP repeated several times in succession, for example, when the vibration increases as it passes through zero. This re-alignment technique significantly stabilizes the display of the propagation graph from a temporal point of view. However, the re-aligned propagation graph obtained in this way contains discontinuities at the junction with the cut-and-paste block of temporally shifted data (this discontinuity is the graph 118a of FIG. , 118a', 118a''). As in Figs. 9 and 10, it will be appreciated that the propagation graph obtained by directly synchronizing the emission of an ultrasonic shot sequence with periodic mechanical vibrations does not contain such discontinuities.

Step c) .

As already mentioned, in step c0), the control module 21 uses a correlation technique or another pattern matching algorithm to compare successive ultrasound echo signals, for different depths within the tissue, and to the tissue. At different moments of periodic mechanical vibration, the deformation data indicative of the tissue deformation are determined.

The term transformation is widely considered in this document. This includes any movement parameters such as displacement, velocity, strain, strain, strain rate, and any mathematical transformations applied to these parameters.

In step c1), the homogeneity information is determined from the transformation data determined in step c0). Homogeneity information may include one of the following:

Propagation graphs such as propagation graphs (808, 168, 178, ...) presented above;

A graph showing the phase delay φ of periodic deformation of the tissue as a function of depth (d), as in graph 809 of FIG. 15;

A graph showing the amplitude (Amp) of the envelope of periodic deformation of the tissue as a function of depth d, as in graph 811 of FIG. 15;

Homogeneity indicator (810).

15 shows an example of elements that can be displayed to an operator by the operator interface screen 31 to provide homogeneity information. In the case of Fig. 15, the homogeneity information includes all the elements listed above. Still, in other embodiments, the homogeneity information may include only one or only some of these elements. These different factors, and how to determine them, are now described in more detail.

At different depths within the tissue, and at different moments of periodic mechanical vibration, the propagation graph representing the deformation of the tissue may be a two-dimensional image 808 synthesized by the control module 21, wherein the pixel row index of the image is Depth (d) and its pixel column index represents time (t) (or vice versa), with each pixel having a pixel value representing the deformation of the tissue at the depth and time associated with the pixel being considered. The pixel value representing the deformation value at the considered viewpoint and instant may be a luminance value as shown in FIG. 15 (the pixel luminance is all higher than the logarithmic deformation value), or a color value (such as a hue value), or a combination thereof.

As already mentioned, when the tissue is homogeneous and suitable for seismic propagation (no air or liquid intervening), such periodic seismic propagation image 808 is composed of one or more diagonal stripes. This stripe is diagonal in that it is tilted in the t-d coordinate system. Their propensity is due to the propagation time of periodic seismic waves from the subject's skin to the considered depth. Thus, the slope of these stripes somehow represents the speed at which these elastic waves propagate in the tissue.

As detailed above with reference to FIGS. 16-18 (see section presenting a summary of the disclosed techniques), such a propagation graph allows the operator to easily determine whether the tissue is homogeneous and suitable for seismic propagation.

When the tissue 51 is homogeneous and suitable for seismic propagation (e.g., there is no air or liquid intervening between the probe and the target tissue), the phase delay φ is as shown by the graph 809 in FIG. Likewise, it varies substantially linearly over the depth.

The phase delay (φ) can be expressed as a duration or as an angle (degrees or radians). At a given depth (d), the phase lag (φ) is the out-of-phase between the periodic deformation of the tissue at that depth and the reference periodic vibration, such as cyclic mechanical vibration transmitted to the tissue, or the periodic deformation of the tissue in the upper part of the tissue. (dephasing). The control module 21 can be programmed to determine the phase delay φ from the frequency-domain representation of the modified data as shown in FIG. 14. In that case, at a certain depth, a measure of the deformation of the tissue over time 141 (using a Fourier transform or another time domain versus frequency domain transform) is transformed into a frequency-domain representation of this change 142. This frequency-domain representation shows the peak at frequency (fq), which is the fundamental frequency of periodic mechanical vibrations transmitted to the tissue. The value of the Fourier transform 142 of the transformation at this particular frequency fq is a complex number whose factor is the phase delay φ (in radians). After that, the phase delay (φ) can be converted to time before being plotted against the depth (d). The linear curve fit 144 can be superimposed on the phase delay graph 143 obtained in this way, so that the operator can more easily evaluate the tissue homogeneity (by checking that the phase delay does not deviate significantly from the linear change).

At a given depth (d), the amplitude (Amp) of the change in tissue deformation over time (i.e. the amplitude of the envelope of this change) can be determined in the same way as the phase delay, for example the peak frequency (fq) instead of the phase. ) Can be determined by considering the amplitude of the Fourier transform. The amplitude (Amp) can also be determined using another kind of amplitude envelope estimation or detection technique.

When tissue 51 is homogeneous and suitable for seismic propagation, the amplitude (Amp) is expected to vary with depth (d) according to a given theoretical model, for example proportional to 1/d ⁿ , where n is It is an integer contained in 1 to 3. In this way, by allowing the operator to easily check whether the amplitude (Amp) varies with depth, the amplitude (Amp) can be plotted against depth using a log-linear scale. Indeed, when such a scale is used, the graph representing the change in amplitude with depth is linear, which can be easily evaluated from a visual point of view if the amplitude changes proportionally to 1/d ⁿ .

Homogeneity indicator 810 is, for example, in the form of a binary indicator such as green/red or green/black, or in the form of a needle dial, a percentage value or a level bar (such as a progress bar type) in a more gradual manner. Can be displayed.

Homogeneity indicator 810 specifies whether the tissue 51 is homogeneous, more precisely homogeneous for a given depth range mentioned above, and suitable for propagation of acoustic waves. Homogeneity indicator 810 may define this information in an all-or-nothing manner in a binary manner, or in a more progressive manner as a continuous value.

For example, when the homogeneity indicator provides this information in a binary manner, it is homogeneous, has no air or liquid inclusions or intervenings, is sufficiently large (at least 10 cm wide and 10 cm deep), and 1 to 100 kilopascals. When the tip of the probe is positioned in contact with the surface of a phantom (which is a test sample made of a synthetic viscoelastic material) having a Young's modulus contained in (or, alternatively contained in 5 to 75 kilopascals), the indicator It is defined as homogeneous and suitable for the propagation of seismic waves (eg turning green). If the phantom is not homogeneous (e.g., including a hard bead), or contains a water layer several centimeters below its surface, the indicator indicates that the medium is not homogeneous or is not suitable for propagation of seismic waves (e.g. For example, it turns black).

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

The control module 21 also processes the periodic acoustic wave propagation image 808 to determine the homogeneity indicator by detecting the edge or average line of such a stripe, and this edge or line is substantially linear over a range of depth of interest. It can be programmed to determine by means of a linear curve fit whether it has a slope included in the possible values of a given interval and/or. The substantial linearity of this line or edge can be assessed based on custom quality parameters such as coefficients of determination (R ² ), standard deviations, or other tools that provide appropriateness between the fit line and the tight linear change with depth. The control module can be programmed to determine that this line or edge is substantially linear, for example when the coefficient of determination R ² is greater than or equal to 0.8 or even greater than or equal to 0.9. The homogeneity indicator may be determined to be equal to or proportional to this custom quality parameter.

The control module 21 also determines whether the phase delay (φ) varies substantially linearly with depth over the depth range of interest and/or has a slope included in the possible values of a given interval, thereby displaying the homogeneity indicator. Can be programmed to determine. This determination can be made by linear curve fitting, as described above.

The control module 21 also determines whether the phase delay (φ) varies substantially linearly with depth over the depth range of interest and/or has a slope included in the possible values of a given interval, thereby displaying the homogeneity indicator. Can be programmed to determine. This determination can be made by linear curve fitting, as described above.

The control module 21 can also be programmed to determine the homogeneity indicator by determining whether the amplitude (Amp) varies with depth according to a given model, in particular whether the amplitude (Amp) is proportional to 1/d ⁿ . have. This determination can be made with a curve fit. The fact that the amplitude (Amp) varies with depth according to the model can be assessed on the basis of the change in amplitude to depth and on the basis of custom quality parameters such as the coefficient of determination (R ² ), which provides a fit between the models. The homogeneity indicator can be determined as being equal to or proportional to this custom quality parameter.

The control module 21 also determines different intermediary homogeneity indicators based on the different criteria described above (so, from a periodic acoustic wave propagation image 808, from a change in phase delay, or from a change in amplitude (Amp)). Determined), then can be programmed to determine the final homogeneity indicators based on these different intermediary homogeneity indicators, for example by averaging these intermediary homogeneity indicators.

The control module 21 can also be programmed to estimate, in step c1), a preliminary value of the mechanical properties of the tissue associated with shear wave propagation, such as Young's modulus, or a range of values over which this mechanical property can be found. have. This value or range of values is determined from data representing the periodic deformation of the tissue determined in step c0). Thereafter, this value or range of values is provided to the operator, for example by a display screen of the operator interface 30.

To this end, the control module 21 provides a preliminary estimate of the propagation speed of the shear wave in the tissue, from the slope of the diagonal stripe of the periodic acoustic wave propagation image 808 described above, or of the phase delay φ with respect to the depth (d). It can be derived from the slope of the line 404 representing the change. The control module 21 can then determine a preliminary estimate of the Young's modulus from this value of the propagation speed of the shear wave. As mentioned at the outset, the value of the propagation velocity of the shear wave determined in this way is generally less accurate than the value determined by instantaneous elastic imaging (due to compression and shear wave superposition, inter alia). However, it is still useful to be provided with such a preliminary value, or range of values, from which the actual value of the Young's modulus (or other mechanical property of the tissue) can be found.

Step S1: momentary On the elastic image Tissue stiffness measurement

In step (S1), in order to determine the mechanical properties of the tissue 51 related to the shear wave propagation by the instantaneous elastic image (e.g.: shear modulus, Young's modulus E, shear wave velocity, ...), the control module 21 Is programmed to cause the system to perform the following steps:

d) stopping the continuous and periodic mechanical vibration PMV, after which instantaneous low-frequency mechanical pulses are delivered to the subject's tissue;

e) while the low frequency mechanical pulse travels through the tissue 51, emitting a sequence of ultrasonic shots by the ultrasonic emitter 11 and acquiring the corresponding echo signal received by the ultrasonic receiver 11

f) determining the mechanical properties of the tissue associated with shear wave propagation from at least some of the echo signals obtained in step f).

In step f) the control module 21 can be more specifically programmed for:

f0) from the echo signal obtained in step e), at different depths within the tissue, and at different times after the low frequency mechanical pulse is delivered to the tissue, determine data indicative of the instantaneous deformation of the tissue; And

f1) From the data representing the instantaneous deformation of the tissue determined in step f0), determine the mechanical properties of the tissue related to shear wave propagation.

In step d), the control module 21 controls the vibrator 12 (via the motion-actuated servo controller 23), delivering instantaneous mechanical pulses with a duration of less than 0.2 seconds to the tissue (pulse Duration is understood to mean a time lap where the pulse amplitude is less than 1/10 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 located below 500 hertz, or even below 100 hertz. 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.

In step e), the control module 21 controls the ultrasonic transducer 11 (via the ultrasonic transmitter module 27) to emit an ultrasonic shot sequence at a pulse repetition rate of 2 kilohertz or more. The emitted ultrasound shot is similar to the ultrasound shot emitted in step b) of step S0. However, they are released with a higher pulse repetition rate, since step (S1) is not only for visualizing and monitoring tissue homogeneity, but for accurately measuring the mechanical properties of the tissue.

For example, an instantaneous mechanical pulse can last for 20 or 40 milliseconds, the ultrasonic shot of the sequence lasts for 80 milliseconds, and the ultrasonic shot is emitted at a pulse repetition rate of 6 kilohertz, whereby this 80 milliseconds As a function of depth at the 480 different successive moments distributed over a second period (starting when the release of a momentary mechanical pulse begins), it makes it possible to track the deformation of the tissue. In other words, in this case, the instantaneous acoustic wave propagation image 805 will contain 480 rows.

In step f0), the data indicative of the instantaneous deformation of the tissue is obtained by comparing the echo signals obtained in step e) with each other, such as in step c0) of step (S0), a correlation-related technique or another panton matching. It is determined using an algorithm.

In step f1), the mechanical properties of the tissue associated with shear wave propagation are determined by techniques known in the art.

Control module 21, in step f1), as a function of depth and as a function of time, an instantaneous acoustic wave, such as image 805 in FIG. 15, showing both the deformation of the tissue caused by the instantaneous mechanical pulse. To provide a radio image, it can be programmed, so that the operator can visually check the quality of the instantaneous elastic image measurement.

The control module 21 may also be programmed to provide the operator with values of the mechanical properties of the tissue, for example once determined in the form of the rigid results display 106 shown in FIG. 1.

Step S2: To the operator Provides ultrasonic attenuation value

In step S2, the control module 12 provides the operator 40 with the value of the ultrasonic attenuation parameter mentioned above, for example by displaying this value on the screen 31 of the operator interface (e.g. For example: in the form of the attenuation result display 107 of FIG. 1).

The ultrasonic attenuation parameter is determined by the control module 21 from some or all of the echo signals obtained in step b) of step S0, more precisely during the last execution of step b), just before So stop. This calculation can be achieved in step S0 or only when executing step S2, i.e. when the operator activates a manual trigger.

It can be noted that a number of variations can be made in the method for characterizing the tissues presented above without departing from the scope of the disclosed technology.

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

In addition, the transition from step (S0) to step (S1 and/or S2) can be triggered automatically by the control module itself, when the homogeneity indicator described above indicates that the tissue under examination is homogeneous and suitable for seismic propagation. have.

The method may also comprise only step (S0), wherein the step of providing the ultrasonic attenuation parameter to the operator is carried out within step (S0), regardless of the more or less homogeneous nature of the tissue under examination. Still, in such case, the control module can be programmed to determine a quality factor associated with the ultrasonic attenuation parameter, which quality factor is all high when the tissue is homogeneous to the propagation of periodic mechanical vibrations transmitted to the tissue. This quality factor can be determined on the basis of the aforementioned homogeneity indicator, for example as being equal to or proportional to the value of this indicator.

The different actions performed during the method can be organized stepwise according to a distribution different from that presented above (in particular, the method may thereby comprise more steps or sub-steps).

The disclosed technology also provides a non-transitory computer-readable medium comprising a computer program comprising machine-executable instructions, wherein the machine-executable instructions are executed by a control module of the system to cause the control module to execute the next step. And the system,

A probe held with respect to the subject's body and comprising a vibrator to transmit mechanical vibrations to the subject's tissue,

An ultrasonic emitter configured to emit a sequence of ultrasonic shots, and

And an ultrasonic receiver configured to receive the corresponding echo signal,

The above steps are:

a) controlling the probe to transmit continuous and periodic mechanical vibration to the tissue of the subject;

b) controlling the ultrasonic emitter to emit a sequence of ultrasonic shots, and by acquiring a corresponding echo signal received by the ultrasonic receiver, tracking how the tissue is moved by periodic mechanical vibrations transmitted to the tissue;

c) providing homogeneity information to the operator of the system-the homogeneity information is determined from at least some of the echo signals obtained in step b), and the homogeneity information is the ability of the tissue to transmit the acoustic wave and the Including; indicating organizational homogeneity with respect to propagation;

Steps b) and c) are continuously executed several times in succession.

Embodiments of the claimed subject matter and operations or steps described herein (e.g., elements of central unit 20 in Fig. 7) may be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, The structures disclosed in and their structural equivalents, or combinations of one or more of them, may be implemented. Embodiments of the claimed subject matter described herein are one or more computer programs, i.e., one or more modules of computer program instructions executed by a data processing device or encoded on a computer storage medium to control the operation of the data processing device. Can be implemented.

The computer storage medium may be, or be included in, a computer-readable storage device, a computer-readable storage substrate, a random or serial access memory array or device, or a combination of one or more of these. Furthermore, the computer storage medium is not a radio wave signal, but the computer storage medium may be a source or destination of computer program instructions encoded with an artificially generated radio signal. Computer storage media may also be, or be included in, one or more individual physical components or media (eg, multiple CDs, disks or other storage devices). The operations described herein 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.

The term "control module" refers to any data processing data including, for example, a microprocessor, digital signal processor (DSP), computer, system on a chip, or multiple systems, or a combination of the foregoing. Includes types of devices, devices and machines. The control module may include a special purpose logic circuit unit (as in the case of FIG. 1), for example, an FPGA or an application-specific integrated circuit (ASIC).

A computer program (also known as a program, software, software application, script or code) can be written in any form of programming language, including compiled or interpreted language, declarative or procedural language, and can be used as a standalone program or computing. It can be distributed in any form, including modules, components, subroutines, objects, or other units suitable for use in the environment. A computer program can correspond to a file in a file system, but it is not necessarily so. A program is a part of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), a single file or multiple control files dedicated to that program (e.g., one or more modules, sub -Can be stored in a file that stores a part of a program or code). The computer program can be distributed to run on one computer, or on a number of computers located at one site or distributed across multiple sites and interconnected by a communication network.

The processes and logic flows described herein may 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 process and logic flow can also be performed as special purpose logic circuitry, for example, field programmable gate array (FPGA) or application-specific integrated circuit (ASIC) and the device can also be implemented.

Processors suitable for execution of computer programs include, by way of example, both general purpose microprocessors and special purpose microprocessors, and any one or more processors of any kind of digital computer. In general, the processor will receive instructions and data from read-only memory or random access memory or both. Essential elements of a computer are a processor for performing operations according to the instructions, and one or more memory devices for storing instructions and data. In general, the computer also includes one or more mass storage devices for storing data, e.g., magnetic, magneto-optical disks or optical disks, for receiving data from or transmitting the data, or both. Will be operatively coupled for. However, computers do not need such devices. Devices suitable for storing computer program instructions and data include, for example, semiconductor memory devices, for example all types of non-volatile memory, media and memory devices including EPROM, EEPROM and flash memory devices; Magnetic disks, such as internal hard disks or removable disks; Magneto-optical disk; And CD-ROM and DVD-ROM disks. The processor and memory may be supplemented by special purpose logic circuitry or may be integrated into the circuitry.

In order to provide interaction with a user, embodiments of the claimed subject matter described herein include display devices that display information to the user, such as LCD (liquid crystal display), LED (light emitting diode) or OLED (organic light emitting diode). ) A monitor, and a keyboard and pointing device through which the user can provide input to the computer, for example a mouse or trackball. In some implementations, a touch screen can be used to display information and receive input from a user. Other types of devices may be used to provide user interaction; For example, the feedback provided to the user may be any form of sensory feedback, such as visual feedback, auditory feedback or tactile feedback; In addition, input from the user may be received in any form including acoustic, voice, or tactile input.

From the foregoing, although specific embodiments of the present invention have been described herein for purposes of illustration, it will be appreciated that various modifications may be made without departing from the scope of the present invention.

Claims (22)

In the system that characterizes the organization,
A probe fixed to the subject's body and including a vibrator for transmitting mechanical vibration to the subject's tissue;
An ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive a corresponding echo signal; And
And a control module programmed to cause the system to execute the next step,
a) delivering continuous and periodic mechanical vibrations to the tissue of the subject, the periodic mechanical vibrations comprising the same vibration pattern repeated several times in succession over time;
b) emitting a sequence of ultrasonic shots by the ultrasonic emitter, acquiring a corresponding echo signal received by the ultrasonic receiver, and tracking how the tissue is moved by periodic mechanical vibrations transmitted to the tissue;
c) providing homogeneity information to the operator of the system-the homogeneity information is determined from at least some of the echo signals obtained in step b), and the homogeneity information is the ability of the tissue to transmit the acoustic wave and the Indicates organizational homogeneity to propagation;
Wherein the control module is programmed such that steps b) and c) are continuously executed by the system several times in succession. The method according to claim 1,
The control module:
Ultrasonic parameters for ultrasonic wave propagation in the tissue;
Mechanical properties of tissue related to shear wave propagation determined by instantaneous elastic imaging;
The tissue characterization system, further programmed to determine at least one physical property of the tissue comprising one of. The method according to claim 2,
The control module is programmed to determine the mechanical properties of the tissue related to shear wave propagation as an instantaneous elastic image,
The control module, wherein the system:
d) stopping the continuous and periodic mechanical vibration, and thereafter delivering an instantaneous low frequency mechanical pulse to the subject's tissue;
e) emitting a sequence of ultrasonic shots by the ultrasonic emitter while the low frequency mechanical pulse travels through the tissue and obtaining a corresponding echo signal received by the ultrasonic receiver;
f) determining a mechanical property of the tissue associated with shear wave propagation from at least some of the echo signals obtained in step e); the tissue characterization system further programmed to execute. The method of claim 3,
The control module:
When a manual trigger is actuated by the operator of the system; Or automatically, when the homogeneity information indicates that the tissue is homogeneous with respect to the propagation of periodic mechanical vibrations transmitted to the tissue, it is programmed to trigger the execution of steps d), e) and f). The method according to claim 2,
The control module is further programmed to determine the ultrasound parameter when the homogeneity information indicates that the tissue is homogeneous with respect to the propagation of the elastic wave, and the ultrasound parameter is at least one of the echo signals obtained in step b). As determined from the tissue characterization system. The method according to claim 2,
The control module is programmed to determine the ultrasound parameter from one or more of the echo signals obtained in step b), and to determine a quality factor associated with the ultrasound parameter,
Wherein both of the quality factors are higher than when the tissue is homogeneous for propagation of an acoustic wave. The method according to claim 1,
Said control module is programmed to determine data indicative of periodic deformation of the tissue from at least some of the echo signals obtained in step b), at different depths within the tissue, and at different moments of periodic mechanical vibrations transmitted to the tissue, The homogeneity information is:
A graph showing a change over the depth of at least one temporal characteristic of a temporal, periodic change of tissue deformation; or
An indication specifying whether the characteristic changes with depth as if the tissue was homogeneous over a given depth range;
Tissue characterization system comprising one of. The method of claim 7,
The graph represents the deformation of the tissue at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue, the graph being a two-dimensional, with pixel row index representing depth and pixel column index representing time and vice versa. Is an image, and each pixel has a pixel value representing the deformation of the tissue in depth and time associated with the pixel being considered; or
The indication specifies whether a graph representing the deformation of the tissue at different depths within the tissue and at different moments of cyclic mechanical vibration transmitted to the tissue is composed of diagonal stripes across the depth range, the graph having a pixel row index A tissue characterization system, wherein a two-dimensional image that represents depth and the pixel column index represents time and vice versa, each pixel has a pixel value representing a deformation of the tissue in depth and time associated with the pixel being considered. The method of claim 7,
The graph represents the phase delay of periodic deformation of tissue as a function of depth; or
Wherein the indication specifies whether the phase lag of periodic deformation of the tissue changes substantially linearly with depth over the depth range. The method according to claim 1,
The control module is programmed to include at least 10 ultrasonic shots per period of the mechanical vibration over at least half of the same period of periodic mechanical vibrations in which the ultrasonic shots of the sequence emitted in step b) are delivered to the tissue. Organizational characterization system. The method according to claim 1,
The control module:
The tissue characterization system, wherein the fundamental frequency of periodic mechanical vibrations delivered to the subject's tissue is contained between 10 and 200 hertz, and in step b), the ultrasound shot is programmed to be emitted at a pulse repetition rate of 500 hertz or more. The method of claim 3,
Wherein the control module is programmed to emit an ultrasonic shot at a pulse repetition rate of at least 2 kilohertz in step e). The method according to claim 1,
Wherein the control module is programmed to cause the system to execute a set of steps comprising steps b) and c) in real time. The method according to claim 1,
The homogeneity information provided to the operator includes a graph representing the deformation of the tissue at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue, and
The control module is programmed such that the emission of a sequence of ultrasonic shots in step b) is synchronized with periodic mechanical vibrations, and the ultrasonic shots in the sequence are transmitted to the tissue, within a cycle of periodic mechanical vibrations, at each execution of step b). Starting from the same moment for the organizational characterization system. The method according to claim 1,
The homogeneity information provided to the operator in step c) above includes a graph representing both the deformation of the tissue as a function of depth and as a function of time,
The graph, within a period of periodic mechanical vibration transmitted to the tissue, starts from the same moment each time the graph is updated based on newly determined deformation data. The method according to claim 1,
The vibrator of the probe is rotationally symmetric about a vibrator axis, the ultrasound emitter and the ultrasound transmitter are configured by the same ultrasound transducer, and the ultrasound transducer is rotationally symmetric about a transducer axis coinciding with the vibrator axis, Organizational characterization system. The method according to claim 1,
The control module:
From at least some of the echo signals obtained in step b), at different depths within the tissue and at different moments of periodic mechanical vibration transmitted to the tissue, to determine data indicative of periodic deformation of the tissue; And
Based on the data, the tissue characterization system is programmed to estimate a value of the mechanical property of the tissue associated with shear wave propagation, or a range of values over which the mechanical property of the tissue associated with shear wave propagation can be found. The method according to claim 1,
-Further comprising a manual adjustment control for adjusting the amplitude of the periodic mechanical vibration, the control module is further programmed to provide the operator with information indicative of the amplitude of the periodic deformation of the tissue caused by the periodic mechanical vibration transmitted to the tissue And the amplitude of the periodic deformation of the tissue is determined from at least some of the echo signals obtained in step b), or
-The control module is programmed to automatically adjust the amplitude of periodic mechanical vibration delivered to the subject based on the amplitude of the periodic deformation of the tissue. In the method of characterizing the tissue performed by the system,
The system is:
A probe fixed to the subject's skin and including a vibrator for transmitting mechanical vibration to the subject's tissue;
An ultrasonic emitter configured to emit a sequence of ultrasonic shots and an ultrasonic receiver configured to receive a corresponding echo signal; And
And a control module programmed to cause the system to execute the next step,
a) delivering continuous and periodic mechanical vibrations to the tissue of the subject, the periodic mechanical vibrations comprising the same vibration pattern repeated several times in succession over time;
b) emitting a sequence of ultrasonic shots by the ultrasonic emitter, acquiring a corresponding echo signal received by the ultrasonic receiver, and tracking how the tissue is moved by periodic mechanical vibrations transmitted to the tissue;
c) providing homogeneity information to the operator of the system-the homogeneity information is determined from at least some of the echo signals obtained in step b), and the homogeneity information is the ability of the tissue to transmit the acoustic wave and the Indicates organizational homogeneity to propagation;
Wherein the control module is programmed such that steps b) and c) are continuously executed by the system several times in succession. The method of claim 19,
Further comprising determining at least one physical attribute of the tissue, wherein the physical attribute is:
Ultrasonic parameters for ultrasonic wave propagation in tissue;
Mechanical properties of tissues related to shear wave propagation determined by instantaneous elastic imaging;
Tissue characterization method comprising one of. The method of claim 19,
From at least some of the echo signals obtained in step b), determining data indicative of periodic deformation of the tissue at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue,
The homogeneity information is:
A graph showing a change over the depth of at least one temporal characteristic of a temporal, periodic change of tissue deformation; or
An indication specifying whether the characteristic changes with depth as if the tissue was homogeneous over a given depth range;
A method for tissue characterization, comprising one of. The method of claim 21,
The graph represents the deformation of the tissue at different depths within the tissue and at different moments of periodic mechanical vibrations transmitted to the tissue, the graph being a two-dimensional, with pixel row index representing depth and pixel column index representing time and vice versa. Is an image, and each pixel has a pixel value representing the deformation of the tissue in depth and time associated with the pixel being considered; or
The indication specifies whether a graph representing the deformation of the tissue at different depths within the tissue and at different moments of cyclic mechanical vibration transmitted to the tissue is composed of diagonal stripes across the depth range, the graph having a pixel row index A method of tissue characterization, wherein a two-dimensional image representing depth and a pixel column index representing time or vice versa is performed, each pixel having a pixel value representing a deformation of the tissue at a depth and time associated with the pixel being considered.

Images