CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Stage of PCT/EP2019/054658, filed Feb. 26, 2019, which in turn claims priority to French patent application number 1851821 filed Mar. 2, 2018. The content of these applications are incorporated herein by reference in their entireties.

TECHNICAL FIELD

The invention belongs to the field of elastography for determining the viscoelastic properties of a viscoelastic medium having an ultrasonic signal after ultrasonic illumination. The invention firstly relates to a hybrid elastography method including a harmonic elastography step and a transient elastography step. The invention secondly relates to a probe for the implementation of the hybrid elastography method. The invention thirdly relates to a hybrid elastography device. The hybrid elastography method according to the invention is particularly suited for determining the properties of a viscoelastic medium such as a human or animal liver.

PRIOR ART

Transient elastography (also called pulse elastography) is one of the best known and efficient methods for determining the elasticity of a viscoelastic medium. For example, transient elastography is commonly used to determine the elasticity of the liver in humans or animals.

In transient elastography a pulse shear wave is generated and its propagation velocity within the viscoelastic medium of interest is measured. The propagation velocity of the shear wave next makes it possible to compute the Young's modulus of the medium and thus to measure its elasticity.

Several techniques exist for implementing transient elastography.

For example, the Applicant has developed and commercialised a vibration controlled transient elastography (VCTE) technique. The device implementing this technique, called Fibroscan®, is capable of measuring the elasticity of the human liver in a rapid, non-invasive and reproducible manner. In such a transient elastography device, the shear wave is generated by a vibrator placed in contact with the medium to characterise. The propagation of the shear wave is next monitored using a series of ultrasonic acquisitions realised by an ultrasonic transducer with high repetition rate. Each ultrasonic acquisition corresponds to at least one ultrasonic emission. Each ultrasonic emission may be associated with the detection and the recording on the go of the echoes generated by the reflective particles present in the studied medium for a defined range of depths. The reflected ultrasonic signals are processed by correlation to work back to the movements of the tissue generated by the propagation of the shear wave as a function of time and the position in the medium. The study of these movements makes it possible to work back to the propagation velocity of the shear wave within the viscoelastic medium, and thus to the elasticity of the tissues, as is explained in the document “Transient Elastography: a new non-invasive method for assessment of hepatic fibrosis” of L. Sandrin et al., published in Ultrasound in Medicine and Biology, Vol. 29, pages 1705-1713, 2003.

The VCTE technique is particularly advantageous because it makes it possible to separate in time the propagation of the shear wave and the propagation of the compression waves generated at the same time as the shear wave, the two types of waves having very different propagation velocities. The compression wave propagates at around 1500 m/s, it may be considered as infinitely rapid compared to the shear wave of which the propagation velocity is typically comprised between 1 and 10 m/s. Indeed, such a separation is important because the presence of compression waves at the same time as the shear wave introduces a systematic error into the measurement of the propagation velocity of the shear wave.

One of the main limitations of the VCTE technique is the difficulty of validating the positioning of the probe before carrying out the elasticity measurement and thus the triggering of a mechanical pulse. Indeed an incorrect positioning of the probe may result in an imperfect propagation of the shear wave or even the absence of shear wave. For example, the propagation of the shear wave may be perturbed by the presence of rebounds linked to the proximity of edges of the studied organ or not propagate at all in the presence of a liquid interface between the probe and the studied medium. It is in fact known that shear waves do not surmount liquid barriers; this is in particular the case in the presence of ascites in the abdomen. The measurement of the resulting elasticity would thus be invalid.

Today it is possible to use ultrasounds to guide the positioning of the vibrator for transient elastography. For example, it is possible to use ultrasonic imaging or a targeting tool such as that described in the patent application EP2739211 A1. However, these solutions are not satisfactory because they do not make it possible to predict directly an incorrect propagation of the shear wave linked for example to an incorrect positioning of the probe or to the presence of a liquid interface.

Among the other transient elastography techniques, it is possible to cite those based on the generation of a shear wave by radiation force or “Acoustic Radiation Force Impulse”—ARFI. This technique is for example described in the document “Acoustic Radiation Force Impulse Imaging: Ex-vivo and in-vivo demonstration of transient shear wave propagation” of K. Nightingale et al. published in IEEE Biomedical Imaging, 2002.

Another transient elastography technique is described in the document “Supersonic Shear Imaging: A new technique for soft tissue elasticity mapping” of J. Bercoff et al., published in IEEE Transactions on Utrasonics, Ferroelectrics, and Frequency Control, 2004. According to this technique, the shear waves are generated by radiation force by focusing an ultrasonic beam at different points in the medium, which makes it possible to obtain shear waves having a flat wave front.

However, none of these transient elastography techniques provides a simple and complete solution to the problem of positioning the probe in order to obtain a measurement of elasticity that is valid in a certain manner.

So-called harmonic elastography techniques also exist. These techniques are based on the application of a continuous vibration having a frequency comprised between 30 Hz and 100 Hz. The elastic waves created within the medium are quasi-stationary waves, superimpositions of shear waves and compression waves.

Among existing harmonic elastography techniques, it is possible to cite:The so-called “Magnetic Resonance Elastography” or MRE technique in which magnetic resonance imaging is used to view the quasi-stationary waves generated in the medium; this technique is described in the document “Magnetic resonance elastography by direct visualization of propagating acoustic strain waves” of R. Muthupillai et al., published in Science 269, 1995. This technique is guided by MRI;The so-called Sono Elastography technique described for example in the document “A pulsed doppler ultrasonic system for making noninvasive measurements of the mechanical properties of soft tissues” of T. Krouskop, published in Journal of Rehabilitation Research and Development, 24, 1987. This technique is guided by echographic imaging;The so-called “Time Harmonic Elastography” technique described for example in the document “In vivo time-harmonic multifrequency elastography of the human liver” of H. Tzschatzsch et al., published in Phys. Med. Biol., 59, 2004. This technique is guided by echographic imaging.

Even if these techniques do not require creating a pulse shear wave which propagates in the medium to characterise, they have certain difficulties.

For example, in harmonic elastography, it is impossible to separate the shear waves and the compression waves which are created at the same time in the medium to characterise. The quasi-stationary elastic wave created within the medium to characterise is thus a superimposition of quasi-stationary shear and compression waves. Since the velocity of the shear waves is much lower than the velocity of the compression waves, the velocity of the vibration really observed does not correspond to the velocity of a shear wave. It is thus necessary to take into account the effect of the propagation of the compression waves before being able to measure the propagation velocity of the shear waves. To do so, it is necessary to record complex data and to compute displacements in the three directions of space x, y, z.

The only harmonic elastography technique presently capable of carrying out such a correction is the MRE technique. However, this technique requires a magnetic resonance imaging device, very complex and expensive, and thus much more difficult to implement than the VCTE technique.

Furthermore, these techniques are guided by traditional methods of echographic imaging or magnetic resonance imaging type. They thus require considerable expertise of the operator, which is not favourable to widespread dissemination of the technology.

Furthermore, the harmonic elastography technique may be used to guide treatment methods. It involves for example treating tumours located by the harmonic elastography technique by means of hyperthermia type methods.

Technical Problem

Harmonic or transient elastography techniques rely on a guiding of the measurement using a traditional imaging technique (echographic imaging or magnetic resonance imaging) which requires considerable expertise of the operator and does not ensure optimal localisation of the tissue to characterise as regards the propagation of the shear waves. The result is the impossibility of predicting the validity of the elastography measurement that is going to be carried out. Finally, these techniques are not suited to an implementation with devices of small size and that are easy to use.

SUMMARY OF THE INVENTION

To resolve at least partially these problems, the present invention describes a novel elastography technique which will be called in the remainder of this document hybrid elastography.

To this end the invention firstly relates to a hybrid elastography method including the following steps:application, using a first vibrator comprised in a probe in contact with a viscoelastic medium, of a continuous low frequency vibration and generation, using an ultrasonic transducer in contact with the viscoelastic medium, of a first series of ultrasonic acquisitions, said first series of ultrasonic acquisitions including groups of ultrasonic acquisitions, the groups of ultrasonic acquisitions being generated with a first repetition rate, each group of ultrasonic acquisitions including at least one acquisition, the continuous vibration generating an elastic wave within the viscoelastic medium;application, using a second vibrator comprised in the probe in contact with a viscoelastic medium, of a low frequency pulse and generation, using the ultrasonic transducer, of a second series of ultrasonic acquisitions, the ultrasonic acquisitions composing the second series being generated with a second repetition rate, the low frequency pulse generating a transient shear wave propagating within the viscoelastic medium.

According to one embodiment, the continuous vibration applied by the first vibrator is stopped before the application of the low frequency pulse by the second vibrator and the generation of the second series of ultrasonic acquisitions.

Hybrid elastography is taken to mean a method for implementing an elastography technique including at least one step of application of a continuous low frequency vibration and a step of application of a low frequency pulse. In other words, the hybrid elastography method according to the invention includes both a generation of a continuous vibration, which is characteristic of a harmonic elastography technique, and a generation of a low frequency pulse, which is characteristic of a transient elastography technique.

Thus the continuous low frequency vibration which is continuous and the low frequency pulse of which the duration is brief are distinguished. Typically the duration of the low frequency pulse is comprised between ½*tSWF and 20/tSWF, tSWF being the central frequency of the low frequency pulse.

Continuous low frequency vibration is taken to mean continuous reproduction of a wave form pattern. This pattern may for example be a perfect sinusoid; this is then known as monochromatic vibration. The vibration may also be constituted by the reproduction of an arbitrary pattern. According to one embodiment, the continuous vibration is interrupted during switching to low frequency pulse mode, to stop the measurement process or when the measurement conditions are no longer satisfactory. The measurement conditions being able to be for example a condition on the contact force with the studied medium. The central frequency of the continuous low frequency vibration is typically comprised between 5 and 500 Hz.

Elastic wave is taken to mean the superimposition of compression waves and shear waves.

Ultrasonic acquisition is taken to mean the emission of an ultrasonic shot. Said ultrasonic emission may be associated with the detection and the recording on the go of the echoes generated by the reflective particles present in the studied medium for a defined range of depths.

The first series of ultrasonic acquisitions is thus formed by a repetition of groups of acquisitions. A group of acquisitions includes at least one ultrasonic acquisition. The groups of acquisition are emitted or generated with a first repetition rate. The first repetition rate is also called inter-group repetition rate. The first repetition rate is typically comprised between 5 and 500 Hz.

When each group of acquisitions is formed by at least two ultrasonic acquisitions, the ultrasonic acquisitions forming a same group are emitted or generated with an intra-group repetition rate typically comprised between 500 Hz and 100 kHz.

Advantageously, the use of a first low repetition rate during the application of the continuous vibration makes it possible to measure the movements of the viscoelastic tissue while limiting the acoustic energy sent into the same tissue so as not to exceed the peak and average acoustic power limits.

The term displacement is considered in the wider sense in this document. It encompasses any movement parameter such as the displacement, the velocity, the deformation, the deformation rate, the velocity of deformation and any mathematical transformation applied to these parameters.

Low frequency pulse is taken to mean a pulse of which the central frequency is typically comprised between 5 and 500 Hz.

Second series of ultrasonic acquisitions is taken to mean a series of ultrasonic acquisitions emitted or generated with a repetition rate greater than 500 Hz and preferably comprised between 500 Hz and 100 kHz.

During the application of the continuous vibration, an elastic wave is generated within the viscoelastic medium.

The first series of ultrasonic acquisitions is used to study the propagation of the elastic wave within the viscoelastic medium. It is possible to detect the echoes or ultrasonic signals reflected by the viscoelastic medium and to compute, from these reflected ultrasonic signals, the displacements of the viscoelastic medium caused by the propagation of the elastic wave within the viscoelastic medium generated by the continuous vibration.

For example, it is possible to compute the displacements of the viscoelastic medium by applying a correlation technique to the ultrasonic acquisitions composing a same group of acquisitions of the first series of ultrasonic acquisitions.

It is then possible to measure the properties of the elastic wave within the medium and to compute in real time a positioning indicator from the measured properties. This indicator is displayed in real time to guide the operator. Examples of such properties are the amplitude and the phase of the elastic wave, measured as a function of the depth in the tissue to characterise. It is also possible to compute the phase velocity of the elastic wave. However, an elasticity value may be deduced from the phase velocity of the elastic wave but the latter differs from the elasticity value deduced with the pulse wave given the superimposition of shear waves and compression waves during the application of the continuous vibration.

In the remainder of this document “positioning indicator” and “real time positioning indicator” refer to the same real time positioning indicator.

Real time is taken to mean an indicator of which the display is regularly refreshed during the examination. In general, the refresh rate is around 20 Hz but may also be of the order of 1 Hz.

It is important to note that the continuous vibration is used to verify the positioning of the probe used for the hybrid elastography. As an example, the continuous vibration may be used to verify the presence of the hepatic parenchyma facing the probe. It is important to note that the continuous vibration is not used to replace the measurement carried out with the pulse; it completes this measurement. In other words, during the step of application of a continuous vibration, the indirect measurement of the viscoelastic properties of the medium is possible but not indispensable. This latter measurement is not physically identical to the elasticity in the sense of the Young's modulus but may be correlated with this value.

The application of a low frequency pulse generates a transient shear wave propagating within the viscoelastic medium to characterise. The monitoring of the propagation of the shear wave makes it possible to measure the viscoelastic properties of the tissue to characterise, for example the propagation velocity of the shear wave, the elasticity of the tissue, the shear modulus of the tissue or the Young's modulus of the tissue. Thanks to the method according to the invention, the measurement of the viscoelastic properties of the medium may be disregarded if the positioning of the probe is not satisfactory. In other words, it is possible to validate a priori the measurement of elasticity by using a positioning indicator obtained during the step of application of a continuous vibration.

Alternatively, the application of the low frequency pulse may be only triggered if the positioning of the probe has been validated beforehand during the harmonic elastography step.

The second series of ultrasonic acquisitions emitted or generated with a second repetition rate is used to study the propagation of the transient shear wave within the viscoelastic medium to characterise. It is possible to record the ultrasonic signals reflected by the viscoelastic medium and to compute from these reflected ultrasonic signals the displacements of the viscoelastic medium caused by the propagation of the shear wave. The measurement of the displacements generated in the viscoelastic medium by said propagation next makes it possible to work back to the propagation velocity of the shear wave and thus to the elasticity of the medium using the formula E=3ρVs2where E is the elasticity or Young's modulus, p the density and Vsthe shear velocity.

The hybrid elastography method according to the invention thus makes it possible to validate the positioning of the probe using a harmonic elastography technique and next to measure the viscoelastic properties of the medium to characterise by using a transient or pulse elastography technique. In particular, once the positioning of the probe has been validated, a measurement of the viscoelastic properties is carried out during the transient elastography step. This measurement provides a more precise value of the viscoelastic properties of the medium than with harmonic elastography because in pulse elastography the compression and shear waves are not superimposed, unlike what is observed in harmonic elastography.

In other words, the first step of harmonic elastography makes it possible to guide the positioning of the probe with regard to the tissue to characterise by providing to the operator an indicator predictive of the success of the measurement by pulse elastography. Once the positioning of the probe has been validated, it is possible to trigger an acquisition in transient elastography, the transient shear wave propagating correctly within the medium.

Advantageously, the hybrid elastography method according to the invention makes it possible to carry out a measurement of the viscoelastic properties of the tissue to characterise in a reliable and reproducible manner using a transient elastography technique, while positioning the probe in a simple and precise manner thanks to a harmonic elastography technique.

The hybrid elastography method according to the invention may also have one or more of the characteristics below, considered individually or according to all technically possible combinations thereof:The hybrid elastography method according to the invention further includes the following steps:determination, from the first series of ultrasonic acquisitions, of at least one property of the elastic wave within the viscoelastic medium;determination, from the second series of ultrasonic acquisitions, of at least one property of the transient shear wave and a property of the viscoelastic medium;the same vibrator is used to apply the continuous low frequency vibration and the low frequency pulse;a property of the elastic wave within the viscoelastic medium is used to compute a real time positioning indicator of the probe with respect to the viscoelastic medium to study;the method according to the invention further includes a step of displaying in real time the real time positioning indicator; the refresh rate of the display is for example greater than or equal to 5 Hz;the step of computation and the step of displaying the positioning indicator and its display are carried out concomitantly.the step of application of the low frequency pulse and generation of the second series of ultrasonic acquisitions is only triggered if the real time positioning indicator satisfies a predetermined condition;the step of application of the low frequency pulse and generation of the second series of ultrasonic acquisitions is triggered automatically on the basis of the value of the real time positioning indicator;the step of application of the low frequency pulse and generation of the second series of ultrasonic acquisitions is triggered automatically;the step of application of the continuous low frequency vibration is only triggered if the contact force between the vibrator and the viscoelastic medium is above a predetermined lower threshold;the step of application of the continuous low frequency vibration is only triggered if the contact force between the vibrator and the viscoelastic medium is comprised between a predetermined lower threshold and a predetermined upper threshold;the step of application of a low frequency pulse is only triggered if the contact force between the vibrator and the viscoelastic medium is above a predetermined lower threshold;the upper and lower contact force thresholds for the application of the continuous vibration are typically equal to respectively 1 N and 10 N;the upper and lower contact force thresholds for the application of the low frequency pulse are typically equal to respectively 4 N and 10 N;the frequency of the continuous low frequency vibration, cSWF, applied by the vibrator is comprised between 5 and 500 Hz;the amplitude of the continuous low frequency vibration applied by the vibrator is comprised between 10 μm and 5 mm;the first series of ultrasonic acquisitions is formed by a repetition of groups including at least two ultrasonic acquisitions having an intra-group repetition rate comprised between 500 Hz and 10 kHz and a first repetition rate comprised between 10 Hz and 10 kHz;the first repetition rate is lower than the continuous vibration frequency;the central frequency tSWF of the low frequency pulse is comprised between 10 Hz and 1000 Hz;the pulse duration is comprised between 1/(2*tSWF) and 20/tSWF, tSWF being the central frequency of the low frequency pulse;the repetition rate of the second series of ultrasonic shots is comprised between 500 Hz and 100 kHz;the amplitude of the low frequency pulse is comprised between 100 μm and 10 mm;the stopping of the continuous vibration of the vibrator and the application of the low frequency pulse are separated by a time interval, the time interval being able to be greater than or equal to 10 ms and preferably being comprised between 1 ms and 50 ms;the amplitude of the low frequency pulse is determined on the basis of the properties of the elastic wave created by the continuous vibration.

The present invention also relates to a probe for the implementation of the hybrid elastography method according to the invention. The probe according to the invention includes:A first vibrator configured to apply to the viscoelastic medium a continuous low frequency vibration, the continuous low frequency vibration generating an elastic wave within the viscoelastic medium;A second vibrator configured to apply to the viscoelastic medium a low frequency pulse generating a transient shear wave within the viscoelastic medium;An ultrasonic transducer configured to emit:a first series of ultrasonic acquisitions, said first series of ultrasonic acquisitions including groups of ultrasonic acquisitions, the groups of ultrasonic acquisitions being generated with a first repetition rate, each group of ultrasonic acquisitions including at least one acquisition;a second series of ultrasonic acquisitions, the ultrasonic acquisitions composing the second series being generated with a second repetition rate;

said probe being further configured to stop the application of the continuous vibration before the application of the low frequency pulse.

The probe according to the invention enables the implementation of the method according to the invention.

According to one embodiment, the probe according to the invention includes a single vibrator that is used both to apply a continuous vibration to the viscoelastic medium during the harmonic elastography step and to apply a low frequency pulse during the pulse elastography step.

The probe is configured so that the application of the low frequency pulse and the stopping of the continuous vibration are separated by a time interval comprised between 1 ms and 50 ms. Preferably the time interval is greater than or equal to 10 ms.

The ultrasonic transducer is used to send the first and the second series of ultrasonic acquisitions within the viscoelastic medium. The same ultrasonic transducer detects the reflected ultrasonic signals at each acquisition. The reflected ultrasonic signals are next processed to detect the displacements of the viscoelastic medium caused by the continuous low frequency vibration and the low frequency pulse.

The probe for hybrid elastography according to the invention may also have one or more of the characteristics below, considered individually or according to all technically possible combinations thereof:the vibrator is an electric motor or an audio reel or an electrodynamic actuator;the ultrasonic transducer is mounted on the axis of a vibrator;the hybrid elastography probe according to the invention further includes means for triggering the application of a low frequency pulse;the ultrasonic transducer is circular with a diameter comprised between 2 mm and 15 mm;the ultrasonic transducer has an operating frequency comprised between 1 MHz and 15 MHz;the ultrasonic transducer is a convex abdominal probe;the first and second vibrators are axisymmetric;at least one of the two vibrators is axisymmetric;at least one vibrator has the same axis of symmetry as the ultrasonic transducer;at least one vibrator has a ring shape and is arranged around the ultrasonic transducer;the probe further includes means for computing and displaying the real time positioning indicator.

The present invention also relates to a hybrid elastography device implementing the hybrid elastography method according to the invention.

Such a hybrid device according to the invention includes:A hybrid elastography probe according to the invention;A central unit connected to the probe and including at least computing means for processing the reflected ultrasonic signals, display means and control and/or input means.

According to one embodiment, the display means are used to display in real time the real time positioning indicator.

