CN112075955B

CN112075955B - Method and device for measuring ultrasonic parameters of viscoelastic medium

Info

Publication number: CN112075955B
Application number: CN202010543160.6A
Authority: CN
Inventors: 洛朗·桑德兰; 斯蒂芬·奥迪尔
Original assignee: Echosens SA
Current assignee: Echosens SA
Priority date: 2019-06-14
Filing date: 2020-06-15
Publication date: 2024-03-19
Anticipated expiration: 2040-06-15
Also published as: KR20200143285A; ZA202003172B; CN112075955A; RU2020118865A; BR102020011526A2; AU2020203412A1; JP2020203078A

Abstract

A system and method for accumulating ultrasound attenuation data for detecting a disease or other condition. In one embodiment, an ultrasound system generates a number of imaging pulses during an imaging mode. Echo signals received from the imaging pulses are tested according to one or more quality metrics. Attenuation data from the echo signals, which passes the quality metrics, is accumulated and used to calculate tissue characteristics. In one embodiment, the tissue property is a CAP measurement related to fat mass in the liver.

Description

Method and device for measuring ultrasonic parameters of viscoelastic medium

Technical Field

The disclosed technology relates to ultrasound systems, and in particular, to systems and methods for measuring ultrasound attenuation in human or animal body tissue to detect liver steatosis and other medical conditions.

Background

Ultrasonic waves are a common tool for imaging internal body tissues of human and animal subjects due to their easy-to-use and non-ionizing properties. Ultrasound can also be used to quantify tissue characteristics to detect diseases and other medical conditions. One such example is the use of ultrasound in combination with shear waves to measure tissue stiffness in order to detect possible liver disease. The echo sense SA of paris, france (assignee of the present application) has been developed to quantify tissue stiffness using ultrasound by measuring the velocity of a mechanically induced shear wave transmitted through tissue. Another condition that can be detected by ultrasound is the amount of fat in the liver. It is well known that the amount of fat in the liver changes the attenuation of an ultrasound signal as it passes through tissue. Thus, measurement of ultrasound attenuation (also known as a controlled attenuation parameter or "CAP") is predictive of fatty liver disease such as liver steatosis.

Echo sens currently produces a system for non-invasively measuring CAP in a subject that uses the same probe used for vibration controlled transient elastography or "VCTE" to measure tissue stiffness. With respect to VCTE, the probe applies mechanical vibrations to the subject to induce a shear wave that travels through the tissue. Ultrasonic waves are then used to track the displacement induced by the propagation of the shear wave and then measure the velocity of the shear wave in relation to the stiffness of the tissue. To measure CAP, the attenuation of the ultrasonic signal used to track the velocity of the shear wave is measured. CAP measurements are considered valid when hardness measurements are considered valid. A detailed explanation of how such VCTE and CAP measurements can be implemented can be found in the following documents: sandrin et al, "Transient Elastography:a new non-invasive method for assessment of hepatic fibrosis (transient elastography: a novel non-invasive method of assessing liver fibrosis)" published on pages 1705-1713, 29, ultrasound in Medicine and Biology; m. Sasso et al, "The Controlled Attenuation Parameter (CAP) published in Clinical Research in Hepatology and Gastroenterology 2012): A novel tool for the non-invasive evaluation of steatosis using (controlled attenuation parameter (CAP)) use +.>New tools for non-invasive diagnosis of steatosis); m. Sasso et al, ultrasound in Medicine and Biology 2010, "Controlled Attenuation Parameter (CAP): A Novel VCTE ^TM Guided Ultrasonic Attenuation Measurement for the Evaluation of Hepatic Steatosis: preliminary Study and Validation in a Cohort of Patients with Chronic Liver Disease from Various Causes (controlled attenuation parameter (CAP)) novel VCTE for diagnosis of hepatic steatosis ^TM Guided ultrasonic attenuation measurement: preliminary study and validation of patient populations with chronic liver disease of various causes) "; and M.Sasso et al at Ultrasound in Medici"Liver steatosis assessed by controlled attenuation parameter (cap) measured with the xl probe of the Fibroscan: a pilot study assessing diagnostic accuracy (preliminary study by controlled attenuation parameters (cap) measured with the xl probe of Fibroscan: evaluating diagnostic accuracy)", published in ne and Biology 2015, which are incorporated herein by reference.

While CAPs measured according to prior methods exhibit statistically good performance (over 80% for steatosis grade diagnosis) in terms of area under ROC curve, CAP values are prone to high variability. For example, in a single patient, the measured CAP value may typically vary by about 40dB/m in the range from 100 to 400dB/m, which is detrimental to its applicability in clinical situations, especially for monitoring the patient's disease progression or regression.

Furthermore, these results depend on tissue homogeneity (i.e., no blood vessels or other tissue structures in the field of view) and may vary according to operator skill. Thus, there is a need for an improved system for more accurately measuring CAP in an object.

Disclosure of Invention

To at least partially address these problems of the state of the art, the disclosed technology is a system and method for measuring ultrasonic parameters based on the recording and automatic analysis of a large number of ultrasonic backscatter signals (e.g., echo signals) acquired during a longer period of time (at least 2 seconds, preferably at least 5 seconds, typically 20 seconds) to improve spatial averaging. Advantageously, these ultrasonic backscatter signals can be validated before being used to calculate ultrasonic parameters.

More particularly, the disclosed technology relates to a method for measuring an ultrasonic parameter of a viscoelastic medium, such as a human or animal body tissue sample, the method being performed with an ultrasonic system comprising: an ultrasonic transducer configured to transmit a series of ultrasonic beams (shots) and receive respective echo signals from a region of interest; and a processor programmed to generate one or more series of ultrasonic beams in a first mode of operation to measure attenuation of the ultrasonic signals in tissue, the method comprising:

Generating the one or more series of ultrasonic beams transmitted to the region of interest and receiving corresponding first mode echo signals from the region of interest, wherein the one or more series of ultrasonic beams are generated with an accumulation period of at least 2 seconds;

recording a first mode ultrasonic attenuation value associated with the received first mode echo signal, and

values of the ultrasonic parameters are calculated using the first mode ultrasonic attenuation values.

In particular, the series of ultrasound beams or the set of the series of ultrasound beams may comprise at least 10, preferably at least 20 ultrasound beams distributed over the period of time.

The above mentioned ultrasonic parameter means, for example, equivalent to the attenuation of an ultrasonic signal in a viscoelastic medium, such as a Controlled Attenuation Parameter (CAP).

The inventors have observed that the values of the ultrasonic parameters calculated using the ultrasonic attenuation values associated with the ultrasonic beams are more reproducible when they are generated for a longer period of at least 2 seconds than if the several successive ultrasonic beams were generated at a high rate for a period of only a fraction of a second.

The possible explanation for this surprising difference is as follows. A single echo signal backscattered by the medium contains a speckle-like component consisting of strong fluctuations (see, for example, echo signal 50 of fig. 1). For this and other reasons, the individual values of the ultrasound attenuation determined by such echo signals tend to have a high variability. And if the ultrasound beam emitted to detect the medium is generated with a high repetition rate only for a short period of time, the position of the ultrasound transducer, or the position of the organ/tissue to be characterized, does not change much from one ultrasound beam to another. Thus, in this case, the above-mentioned speckle-like component remains substantially the same from one echo signal to another echo signal. Thus, the different attenuation values determined by the different received echo signals are not independent of each other. These different values may even be substantially the same. Thus, considering such a set of values (e.g., by calculating an average of the values (or by another statistical analysis of the set of values)) does not significantly improve the accuracy or repeatability of the measurement of the ultrasound attenuation.

In contrast, if the ultrasonic beams emitted to detect the medium are generated over a period of time lasting a few seconds or more, the organ/tissue moves relative to the ultrasonic transducer during the period due to respiration and/or transducer displacement. Due to this relative displacement, the above-mentioned spot-like component changes during the period for detecting the medium. The different echo signals received by the system are at least partially de-correlated and the different values of the ultrasound attenuation determined by these different echo signals correspond to separate measurements to some extent. Calculating the average of these values thus yields a final ultrasonic attenuation value with improved accuracy and/or repeatability. Furthermore, the above mentioned displacements enable to smooth the potential inhomogeneities of the organ/tissue structure by spatial averaging over a wide area of the organ/tissue to be characterized.

The one or more series of ultrasonic beams that the processor is programmed to generate (when operating in the first mode) may include at least 10 (and preferably 20 or more) ultrasonic beams that are at least 0.05 seconds apart from each other. In other words, during the one or more series, the attenuation of ultrasound waves in the tissue is detected (sampled) successively at least 10 times, with a delay of at least 0.05 seconds between two of these samples (to benefit from the spatial averaging mentioned above). This may be achieved, for example, by generating these ultrasonic beams at a fairly low beam repetition rate of 20 hertz or less (and during a sufficiently long period of time). But this can also be achieved by generating the ultrasound beam at a higher beam repetition rate (e.g., a repetition rate of 100 or 200 hz) (and during a sufficiently long period of time). In fact, in the last case, the whole set of ultrasound beams generated comprises a number of ultrasound beams "well separated in time" (i.e. ultrasound beams separated from each other by at least 0.05 seconds) plus (due to the higher repetition rate) an additional (and to some extent redundant) ultrasound beam generated between two such "well separated in time" beams.

According to an optional feature of the above method, the series of ultrasonic beams are emitted with a beam repetition rate of 500 beams/sec, preferably 100 beams/sec, more preferably between 15 and 25 beams/sec. In particular, the ultrasonic beam is generated for a period of at least 20 seconds, and the repetition rate may be between 15 and 25 beams/second. The beam repetition rate may be higher than 5 beams/second (e.g., comprised between 5 and 200 beams/second), or even higher than 10 beams/second, throughout a series of ultrasonic beams.

At this repetition rate, there is sufficient time between two successive beams to move the organ/tissue relative to the ultrasound transducer. Thus, each beam effectively contributes to the improvement in accuracy/repeatability of the final value of ultrasonic attenuation described above. In contrast, if a series of ultrasound beams are transmitted at a high repetition rate (e.g., a few kilohertz), many of the transmitted beams do not contribute to the improvement in accuracy/repeatability described above, thus undesirably increasing the computational resources required to process the received echo signals and undesirably increasing the ultrasound radiation (which may be detrimental to the subject whose organ/tissue is being characterized, or to the practitioner performing the characterization). In addition, the above method can be implemented with high repetition rates (greater than 500 shots/second) even if it is not optimal, as long as a series of ultrasonic beams last for at least 2 seconds.

In an embodiment of the method provided above, the ultrasound system performing the method is an elastography system configured to generate shear waves in the region of interest, the processor being programmed to operate alternately in at least the first mode and the second mode, wherein in the second mode the processor is programmed to control the elastography system to generate shear waves in tissue and to generate a series of ultrasound beams to track how the tissue in the region of interest moves due to the shear waves. Thus, in this case, at least some of the ultrasonic beams used to measure the attenuation of the ultrasonic signal are emitted outside of a period of time when the processor is operating in the second mode. In this embodiment, the processor may be specifically programmed to operate alternately in a first mode, then in a second mode (to perform an elastographic measurement), then in the first mode (imaging mode), then again in the second mode, and so on (to perform another elastographic measurement). In this case, the above-described accumulation period of at least 2 seconds is a sum of respective periods during which the processor operates in the first mode. For example, if the processor is programmed to achieve 10 consecutive elastography measurements separated from each other by 0.5 second intervals, wherein the processor is operating in the first mode during the intervals, the sum of the respective periods of operation of the processor in the first mode will be 5 seconds (> 2 seconds). The processor may also be programmed to perform 10 consecutive elastography measurements separated from each other by 1 second intervals, wherein the processor operates in the first mode during the intervals. In this case, the sum of the respective periods of operation of the processor in the first mode will be 10 seconds; the beam repetition rate during these periods may be equal to 20 beams per second (thus the beams are separated from each other by 50 ms), resulting in 200 "first mode" ultrasound beams being obtained distributed over an accumulation period of 10 seconds, thus yielding a very accurate and reproducible ultrasound parameter determination.

Thus, in contrast to prior art methods in which CAP measurements are performed during stiffness (VCTE) measurements, in the above-described embodiments, CAP measurements are performed using data or echo signals collected during imaging of an organ (e.g., liver) of a patient, that is, CAP measurements are performed while the processor is operating in the first mode, as opposed to CAP measurements being performed only during stiffness measurements of the organ/tissue. While measuring CAP during a hardness measurement is considered beneficial and reliable because the same data or echo signals collected from the same location on the liver are used to perform both CAP and hardness measurements (and thus it can be said that steatosis and fibrosis measurements are done at the same location on the patient's liver), the inventors have found that, in contrast, measuring CAP and hardness separately is greatly beneficial because these two parameters require different considerations to make an appropriate measurement. For example, oftenThe stiffness measurement requires a high frame rate (about 6000 Hz) during a short period (about 80 ms) in order to be able to track the shear wave and perform the stiffness measurement. In contrast, it was found that CAP measurements should be obtained over a long period of time to increase spatial averaging between the obtained ultrasound lines and reduce the variability of CAP values. When CAP values are measured simultaneously with hardness, these different considerations of CAP and hardness measurements are not fully considered. In practice, during a single stiffness measurement, the ultrasound line or echo signal is obtained at a high frame rate of 6000 beams/s during a period of 80 ms. The 480 ultrasound lines obtained during this 80ms period are highly correlated because the patient's organ (e.g., liver) does not move significantly during such a short period. As a result, the true contribution of 480 ultrasound lines or echo signals obtained during the hardness measurement to the CAP measurement is relatively poor. Even in use The probe does not move during the examination (an ultrasound-based elastography device for measuring the stiffness (or elasticity) and ultrasound attenuation of tissues and organs), and the liver itself moves due to respiratory movements, so that the stiffness measurements are done in different positions. The operator typically performs 10 measurements. The spatial averaging obtained from these 10 measurements was found to be suitable for hardness assessment, but may not be sufficient for CAP.

Furthermore, in contrast to conventional methods in which CAP measurements are performed only during hardness measurements, it is not intuitive to perform CAP measurements during imaging, as CAPs now use data or echo signals acquired from different locations in the liver, rather than data or echo signals used to make hardness measurements, to measure CAP. In fact, the patient's liver will necessarily move due to respiratory motion, regardless of whether the probe is moving during the examination of the patient's liver. As a result, data or echo signals acquired during imaging and data or echo signals acquired during stiffness measurements will be captured from different locations in the liver. Equally important is the fact that the skilled person will understand that during liver imaging (i.e. when the operator moves the probe over the liver of the patient to image it), many ultrasound lines or echo signals are acquired from locations in the abdomen of the patient instead of the liver. As a result, a number of ultrasound lines or echo signals are generated during liver imaging that cannot be used to determine CAP. In the disclosed technique, one or more quality criteria are used to exclude "bad" ultrasound lines or echo signals collected during imaging, as will be explained below.

The new system and method for performing CAP measurements enables a large number of ultrasound lines to be collected during a much longer period than conventional methods, which significantly improves the spatial averaging of acquired ultrasound lines and significantly reduces the variability of CAP values. Surprisingly, it was found that the variability of CAP values determined according to the disclosed techniques can be significantly reduced, for example by a factor of 4. It will be further appreciated that a significant increase in the determination of CAP values is not achieved at the expense of a loss of hardness measurement.

In some implementations, the shear wave may be generated by an actuator or by an acoustic speaker.

In some embodiments, ultrasound waves are emitted into the tissue of the subject at a relatively slow pulse repetition frequency, such as between 10-100 pulses/second and particularly at a rate of (20 +/-5) pulses/second. It is relevant to keep the rate low enough not to exceed the upper acoustic output power limit specified by the FDA of USA (2003). The ultrasonic echo signals received from the pulses are analyzed in the frequency domain to estimate the signal attenuation at the frequency. A plurality of attenuation measurements are collected over a period of time to produce CAP measurements. In some embodiments, the received ultrasound echo and attenuation measurements are compared to one or more quality metrics before being added to the measurement accumulation for producing CAP measurements. In some embodiments, the ultrasonic echo signals received and processed to generate the ultrasonic attenuation values are ultrasonic echo signals obtained when the elastography system is operating in a first mode, i.e. an imaging mode, rather than ultrasonic echo signals obtained when the elastography system is operating in a second mode, which corresponds to an ultrasonic echo signal in which a shear wave is generated and tracked to measure elasticity of the region of interest.

In some embodiments, the ultrasound system produces a display of "good" and "bad" first mode echo signals (i.e., echo signals received during the imaging mode or first mode of the elastography system) so that a user can visually determine whether they are aiming the ultrasound probe in a homogeneous tissue region. To measure CAP, a "good" echo signal is selected using one or more quality criteria. After a sufficient number of good attenuation values have been accumulated, the CAP measurement is calculated by the processor and displayed to the user. Further, a method according to the disclosed technology may include displaying a value of an ultrasonic parameter calculated using the first mode ultrasonic attenuation value.

In some embodiments, the CAP measurement is calculated using the first mode ultrasonic echo signal only if the signals are sufficiently decorrelated from previously received first mode echo signals. In other words, the system selects a different ultrasound line than the already captured ultrasound line. In some embodiments, the CAP measurement is calculated using the attenuation value from the received echo only if the attenuation value is within a predetermined range of values. The predetermined range may be, for example, a range of 100-500 db/m. It will be appreciated that a "good" ultrasound line may be selected first before a different ultrasound line is selected. Alternatively, a different ultrasound line may be selected first before a "good" ultrasound line is selected.

In some implementations, the system generates a histogram of attenuation values. The processor is programmed to fit a gaussian mixture or other bell-shaped distribution to the histogram to calculate the most likely CAP measurement from the received echo signals. Possible errors in the measurement can also be estimated from this gaussian or bell-shaped distribution.

In some embodiments, the value of the ultrasound parameter is calculated using the attenuation value from the received echo only when a coupling coefficient associated with the received echo, which represents a coupling force between the ultrasound transducer and the skin of the patient for which the viscoelastic medium characterization is performed, is considered to exceed a predetermined threshold.

It will be appreciated that the different embodiments presented above may be combined together according to all possible combinations of the techniques in accordance with the disclosed techniques.

The disclosed technology also relates to a method for measuring an ultrasonic parameter of a viscoelastic medium, such as a human or animal body tissue sample, the method being performed using an ultrasonic system comprising: an ultrasonic transducer configured to transmit a series of ultrasonic beams and receive respective echo signals from a region of interest; and a processor programmed to generate a series of ultrasonic beams in a first mode of operation to measure attenuation of ultrasonic signals in tissue, the method comprising:

Generating the series of ultrasonic beams transmitted to the region of interest and receiving corresponding first mode echo signals from the region of interest, wherein the series of ultrasonic beams are generated for a period of at least 2 seconds;

recording a first mode ultrasonic attenuation value associated with the received first mode echo signal; and

The disclosed technology also provides a system for measuring ultrasound attenuation in a region of interest in a tissue sample, comprising:

an ultrasonic transducer configured to transmit a series of ultrasonic beams and receive respective echo signals from the region of interest; and

a processor programmed to control the system to, in a first mode of operation:

generating one or more series of ultrasonic beams transmitted to the region of interest and receiving corresponding first mode echo signals from the region of interest, wherein the one or more series of ultrasonic beams are generated for an accumulation period of at least 2 seconds;

A value of ultrasound attenuation in the organ or tissue is calculated using the first mode ultrasound attenuation value.

Features of the different embodiments of the above method may also be applied to the system for measuring attenuation of ultrasound waves.

In particular, the processor may be programmed such that when it is operating in the first mode, the beams of the series of ultrasonic beams are emitted with a beam repetition rate of 500 beams/sec, preferably 100 beams/sec, more preferably between 15 and 25 beams/sec.

The system for measuring ultrasound attenuation may be an elastography system configured to generate a shear wave in the region of interest, the processor being programmed to operate alternately in at least a first mode and a second mode, wherein in the second mode the processor is programmed to control the elastography system to generate a shear wave in tissue and to generate a series of ultrasound beams to track how tissue in the region of interest is moved by the shear wave, the processor being programmed such that at least some of the ultrasound beams for measuring ultrasound signal attenuation are emitted outside a period of time that the processor is operating in the second mode.

The processor may also be programmed to determine a quality of an echo signal received from the ultrasonic beam obtained when the processor is operating in the first mode, and to determine an attenuation of the ultrasonic signal using the echo signal having a desired quality level. In particular, the processor may be programmed to determine the quality of the echo signals based on one or more of a correlation between successive echo signals and a comparison of the attenuation of the echo signals to a range of expected attenuation values.

an ultrasonic transducer configured to transmit a series of ultrasonic beams and receive respective echo signals from a region of interest; and

a processor programmed to control the system so that in a first mode of operation:

generating a series of ultrasonic beams transmitted to the region of interest and receiving respective first mode echo signals from the region of interest, wherein the series of ultrasonic beams are generated over a period of at least 2 seconds;

an ultrasound attenuation value in the organ or tissue is calculated using the first mode ultrasound attenuation value.

Drawings

Other features and advantages of the disclosed technology will become apparent from the following description, given by way of example and without limitation with reference to the accompanying drawings, in which:

FIG. 1 illustrates how ultrasound attenuation is estimated in the frequency domain in accordance with some implementations of the disclosed technology;

fig. 2 is a block diagram of a method of calculating CAP measurements in accordance with some implementations of the disclosed technology;

FIG. 3a illustrates a representation showing CAP measurements, a histogram of ultrasound attenuation values, TM mode ultrasound image data from a region of interest, and an indicator of whether the ultrasound attenuation data meets one or more quality criteria, in accordance with some implementations of the disclosed technology;

FIG. 3b illustrates a representation showing CAP measurements, attenuation measurement histograms, TM mode ultrasound image data from a region of interest, and an indicator of whether the ultrasound attenuation data meets one or more quality criteria, in accordance with some implementations of the disclosed technology;

FIG. 3c illustrates a representation showing a CAP measurement, a bimodal histogram of attenuation measurements, TM mode ultrasound image data from a region of interest, and an indicator of whether the ultrasound attenuation data meets one or more quality criteria, in accordance with some implementations of the disclosed technology;

FIG. 4 illustrates a timing diagram of a system for determining CAP measurements and VCTE tissue hardness measurements, according to some embodiments of the disclosed technology;

FIG. 5 is a representation of CAP measurements produced in accordance with some implementations of the disclosed technology;

FIG. 6 is a representation of a user interface showing both CAP and hardness measurements, in accordance with an embodiment of the disclosed technology;

7A-E show conventional CAP results and CAP results disclosed herein in a 113 patient population;

8A-B schematically illustrate spatial averaging of acquired ultrasound lines obtained according to a conventional method of measuring CAP (FIG. 8A) and according to a disclosed method of measuring CAP (FIG. 8B) in accordance with the disclosed technique; and

Fig. 9 is a block diagram of a system for generating CAP measurements in accordance with some implementations of the disclosed technology.

Detailed Description

As will be discussed in more detail below, the disclosed technology relates to systems and methods for estimating tissue characteristics from measured attenuation of ultrasound signals transmitted in the body. In some embodiments, the tissue property is a CAP value indicative of the amount of fat present in the liver. Currently available from echoIn a system (an ultrasound-based elastography device for measuring the hardness (or elasticity) and ultrasound attenuation of tissues and organs), the system rapidly measures the hardness of the human or animal liver and the ultrasound attenuation caused by tissue properties in a non-invasive and reproducible manner.

In Vibration Controlled Transient Elastography (VCTE), a transient shear wave is generated by a vibrator, such as an electromechanical vibrator or acoustic speaker, placed adjacent to a medium to be characterized, such as on the skin in a liver region of a subject. The propagation of the shear wave is then tracked using a series of ultrasonic acquisitions (beams) generated by an ultrasonic transducer at a high repetition rate. Each ultrasound acquisition corresponds to at least one ultrasound transmission and reception. Each ultrasonic emission may be associated with the detection and instantaneous recording of echoes produced by reflective particles present in a defined depth range of the medium under analysis. The reflected ultrasonic signals are processed by cross-correlation or other signal pattern matching techniques to determine the movement of tissue as a function of time and the position of the medium caused by the propagation of the shear wave. Analysis of the motion enables determination of the velocity of the shear wave within the viscoelastic medium and thus the elasticity or stiffness of the tissue to be determined.

Currently availableIn the system, ultrasonic pulses for VCTE (VCTE is used and determines the velocity of the shear wave in the body) are analyzed to determine CAP measurements. The validation of CAP measurements is based on measurements of tissue hardness. If the tissue stiffness measurement is not valid, the corresponding ultrasound attenuation measurement is discarded. This is thus a post-verification. In other words, in the alternative,the system uses the results from the instantaneous elastography readings, i.e. at +.>Echo signals received during a second mode of operation of the system are used to verify the CAP measurement. These measurement techniques are described in patent applications FR 2949965 (published as u.s.2012190983) and FR 2978657 (published as u.s.2014249415), which are incorporated herein by reference.

Another problem with using the same ultrasonic signals as those used to detect shear wave velocity (VCTE acquisition) to determine CAP measurements is their high repetition rate or Pulse Repetition Frequency (PRF) and associated short acquisition duration. In some systems, the PRF of the ultrasonic pulse that tracks the shear wave is 6000 pulses/second and the acquisition lasts only 80ms, with the result that one stiffness measurement produces 480 ultrasonic lines or echo signals. Since the duration of the acquisition teaches that the organ is moving quite short due to respiration, heartbeat or the like, the return ultrasound signal is typically highly correlated and thus contains redundant data, which does not represent a large tissue area for ultrasound attenuation. Considering that a typical examination procedure consists of less than 10 effective hardness measurements, it can be estimated that the total number of acquired ultrasound lines or echo signals is high: the total number of ultrasound lines or echo signals is 4800 when each measurement corresponds to a set of 480 lines. However, the method is that Instead, each measurement lasts only 80ms, during which the ultrasound lines are hardly de-correlated. Thus, the true contribution of the 480 lines of a single group is quite low. Thus at presentIn the device settings, the duration of data acquisition for ultrasound attenuation is only 800ms, less than one second. Although at present->The number of ultrasonic lines obtained for CAP measurement in the device setting is large (4800), but note that the total acquisition time is short<1 second) and the actual number of ultrasound lines or echo signals contributing to CAP measurements is also quite small: 10 due to the decorrelation difference between the ultrasound lines acquired for one shear wave velocity measurement. The inventors have determined that a good determination of the attenuation of ultrasound waves requires a high spatial averaging, in which way a high spatial averaging may not be achieved. This high correlation and associated poor spatial averaging may facilitate measuring variability of ultrasonic parameters such as CAP.

Another possible cause of variability in the measured values is the presence of a varying area (heterogeneity) that alters the local measurement. In the case of a human or animal liver, this variability may be caused by the presence of veins or blood vessels in the region where the measurements are taken across.

To address these and other issues, the disclosed system processes ultrasonic or echo signals acquired at a lower rate over a much longer duration. In one embodiment, ultrasound waves are transmitted into the body to produce images of the tissue being examined, such as TM mode images and/or A mode images. This image is used by the operator to locate the region of interest in seconds, typically 10 seconds, which is undoubtedly much longer than 80ms for VCTE acquisition for detecting shear wave velocity. Ultrasound signals are transmitted into the body and reflected from the scatterers at a PRF selected such that the body can move over several acquisition periods. In one embodiment, the PRF is less than 100 beams/sec, and for example less than 50 beams/sec, such as (20 +/-5) beams/sec. The lower ultrasound beam rate compared to PRFs used for elastography allows the returned echo data to be less correlated, thus representing a larger sampling area as the probe and tissue move. By using a lower PRF associated with a longer acquisition duration, the disclosed system accumulates attenuation values over a long period of time, which significantly improves spatial averaging without increasing too much redundant ultrasound data and without increasing the average acoustic output power delivered to the patient.

The inventors have determined that measuring the attenuation of ultrasound waves in the time domain when calculating CAP measurements is not very accurate. To overcome this limitation, the system of the presently disclosed technology estimates attenuation by analyzing the received echo signals in the frequency domain. Fig. 1 illustrates one technique for determining ultrasound attenuation in accordance with the disclosed techniques. The ultrasonic signal 50 represents a line of received echo data. The return echo data for a period beginning at time 52 and extending to time 54 is digitized and analyzed, time 52 corresponding to the beginning of a desired region of interest (e.g., depth range), and time 54 representing the end of the region of interest. In the embodiment of fig. 1, the depth range extends from 20mm to 80mm, which corresponds to the subcutaneous depth range at the liver location. The period is subdivided into a number of smaller time segments or windows (a few microseconds, typically 5 mus), each corresponding to a portion of the depth range in the region of interest. In some embodiments, the windows may partially overlap, as shown in fig. 1. The digitized ultrasonic signal for each sub-period or window is converted into the frequency domain 60 using a Fast Fourier Transform (FFT) or other time-domain to frequency-domain transform. The result is a plot of the magnitude and depth of the frequency components present in the echo received at each time period.

The magnitude versus depth of the frequency components present in the echoes received at each time interval are plotted or stored in a non-transitory computer readable memory. In the example shown, line 62 represents the attenuation of the echo signal at 3.5MHz, which 3.5MHz corresponds to the frequency bandwidth used during the measurement of the attenuation of the ultrasound waves. The absorption slope α at 3.5MHz is determined and a best fit line 70, such as linear interpolation, is used to estimate the slope/attenuation at the frequency of the received ultrasonic echo signal. In the example shown, the frequency used is 3.5MHz. However, other bandwidth frequencies may be used depending on the transducer selected for the subject (e.g., pediatric, normal, obese subject, etc.). According to an embodiment of the invention, the slope measurement is a measurement of the CAP value. In other embodiments of the disclosed technology, measurements may be made at more than one frequency (e.g., a frequency other than 3.5 MHz) so that multiple slopes/attenuations may be determined to determine the CAP value.

Fig. 2 illustrates the basic steps of a method 100 for measuring ultrasonic parameters in accordance with some embodiments of the disclosed technology. Beginning at 102, the system generates a series of ultrasonic beams. These ultrasonic beams are emitted by an ultrasonic transducer placed close to the medium to be characterized. An ultrasonic signal propagating within a medium to be characterized is at least partially reflected by the medium being analyzed. The reflected ultrasonic echoes are digitized and stored in a computer readable memory. According to one practical way, the transmission and recording of the ultrasonic signals is performed using the same ultrasonic transducer. However, transducers having separate transmit and receive elements will be usable.

According to one practice, the ultrasonic beam is emitted at a repetition rate of less than 50Hz (e.g., equal to 20+/-5 Hz). Since the human eye typically captures 25 images per second, selecting a frequency of 20Hz is advantageous for real-time display of TM mode or A mode images. As mentioned above, this low repetition rate allows recording reflected ultrasound signals that are decorrelated from each other due to differences in acquisition time compared to respiratory motion velocity. At a repetition frequency of 20Hz, the ultrasonic signal is acquired every 50 ms. The breathing rate is typically between 12-50 cycles per minute, which translates to 1.2-5.0 seconds. Displacement of an organ, such as the liver, is typically a few centimeters and the velocity of liver motion due to respiration is typically on the order of 1 centimeter per second. Within 50ms the displacement will be 2mm, which is sufficient to de-correlate the ultrasound signal. The use of decorrelated ultrasonic signals improves the reliability of the measurement while reducing measurement errors.

At step 104, the method Accumulates (ACC) effective ultrasonic attenuation values. In some embodiments, each ultrasound line or echo signal is associated with a certain quality criterion. The quality criteria are used to automatically exclude ultrasound lines that do not meet some predetermined characteristics. Only the attenuation values associated with acceptable quality criteria are used to calculate the final CAP measurement. In some implementations, the quality criterion may be calculated based on a number of coefficients compared to one or more thresholds. In some embodiments, the coefficients may be used to select a sufficiently decorrelated ultrasound line or echo signal. The coefficients may be cross-correlation coefficients calculated from correlations between successive ultrasound lines previously acquired at different times.

In particular, the cross-correlation coefficient associated with the considered ultrasound line for assessing the quality of the ultrasound line may be a cross-correlation coefficient between all or a part of the ultrasound line and another ultrasound line received before it, such as the ultrasound line received just before the ultrasound line for which quality assessment is to be performed.

The cross-correlation coefficient between the considered ultrasound line and another previously received ultrasound line may be calculated by taking into account several "local" cross-correlation coefficients respectively associated with different portions of the considered ultrasound line (e.g. by averaging these different local cross-correlation coefficients). In this case, each of these local cross-correlation coefficients represents a correlation between the portion of the considered ultrasound line associated with that local cross-correlation coefficient and another ultrasound line received previously.

The cross-correlation coefficient is a number representing the degree of correlation, i.e. the degree of similarity between the two series of values or data under consideration, i.e. between the ultrasound line whose quality is to be evaluated and the preceding ultrasound line, or between parts of these ultrasound lines. The cross-correlation coefficients may be obtained by different algorithms, for example by cross-correlation "sliding dot product (slider dot product)" calculation ("sliding inner product (slider inner product)"), or by a least squares algorithm capable of evaluating the mismatch between the two series of values or data under consideration.

If the cross-correlation coefficient is above the predetermined threshold, the data is deemed too relevant and thus the attenuation value of the ultrasound line is not used to calculate the final CAP measurement. In practice, the predetermined threshold is set to 80% (80 percent) of the reference value corresponding to the fully correlated signal, so that attenuation values sufficiently independent of each other can be selected to be well suited for subsequent statistical filtering (such as averaging). In other words, when the cross-correlation coefficient associated with the echo signal is below 80% of the reference value, the signal may be considered to be sufficiently de-correlated and thus may be considered to calculate a final CAP measurement. For example, if the cross-correlation coefficient is the same as or multiplied by a proportionality coefficient between a portion of the considered ultrasound line and another previously received ultrasound line, the portion of the considered ultrasound line and the previously received ultrasound line may be considered to be completely correlated when the portion of the ultrasound line is found to be the same as or different from the position of the portion within the previously received ultrasound line. For example, when the cross-correlation coefficient is calculated by "sliding dot product" normalized correlation calculation, the reference value is equal to 1, and the predetermined threshold value is equal to 0.8.

In some embodiments, a coefficient may be used to select an ultrasound line that exhibits good characteristics, such as not having vessel wall boundaries on the ultrasound line. This coefficient may be referred to as a quality coefficient. The coefficients may be, for example, measurements (R ² ) Coefficients. In some implementations, a coefficient may be used to select ultrasound lines having attenuation values in the desired range, such as in the range of 100-400 dB/m. In this case, attenuation values outside the expected range are disregarded because they are considered as outliers. In a particular embodiment of the invention, at least two quality criteria are used: a first quality criterion is first used to select a sufficiently decorrelated ultrasound line or echo signal, and a second quality criterion is then used to select an ultrasound line or echo signal having an attenuation value lying in the desired range, or vice versa. However, this is not limiting and predetermined other masses may be used in other embodiments of the inventionCriteria to automatically exclude ultrasound lines or echo signals that do not meet some predetermined characteristic. For example, in one embodiment, the quality criteria comprises a cross-correlation criteria and the processing of the received first mode echo signals comprises correlating each of the received first mode echo signals with a cross-correlation coefficient and selecting each of the received first mode echo signals having a cross-correlation coefficient exceeding a predetermined threshold to determine substantially de-correlated ones of the received first mode echo signals. The cross-correlation coefficient may be calculated based on the received first mode echo signal and a previously received first mode echo signal, which may include first through nth previously received first mode echo signals.

Alternatively, instead of analyzing the received first mode echo signals along with the previously received first mode echo signals to determine cross-correlation coefficients and cross-correlation criteria, each echo signal may be analyzed separately and individually to determine whether the echo signals meet a number of predetermined characteristics (e.g., signal strength, profile … … of the echo signals) corresponding to quality criteria. Further, the one or more quality criteria may include an attenuation criteria defined by a predetermined range of ultrasonic attenuation values, and the processing includes selecting each of the first mode ultrasonic attenuation values to be within the predetermined range. In an embodiment, two or more quality criteria may be used to select the received first mode echo signal to determine the CAP value.

According to one practice, at step 106 (CALC), the processor is programmed to analyze a number of effective attenuation values to calculate a CAP measurement. The number of effective attenuation values is the number of attenuation values that meet the quality criterion. In some embodiments, the system accumulates at least a predetermined number of effective attenuation values prior to displaying the CAP measurement, the displayed values being calculated from the accumulated effective attenuation values. The effective attenuation is selected using one or more of the quality criteria described above. The predetermined number of effective attenuation values may be selected to be between 100 and 10000. It may also be associated with an equivalent acquisition duration range, such as 5 to 500 seconds, which corresponds to a range of 100 to 10000 decay values at a rate of 20 Hz. The same acquisition duration range will correspond to a range of 1000 to 100000 attenuation values at a rate of 200 Hz. In some embodiments, once a sufficient number of effective attenuation measurements are obtained, the processor creates and analyzes a histogram of the accumulated effective ultrasonic attenuation values. In this case, each bar of the histogram represents the number of received ultrasonic echo signals having a given ultrasonic attenuation value. As will be explained in detail below, the histogram is analyzed to determine peaks (e.g., values of most common attenuations) and other statistics about the histogram, such as standard deviation. Such analysis may be performed by computing a gaussian distribution to fit the histogram. The fit may be performed in a unimodal or multimodal manner (gaussian mixture).

According to one practice, the CAP measurement is the median or average of the effective attenuation values.

According to one practice, the CAP measurement is a weighted average of the attenuation values. Each attenuation value is associated with a coefficient for weighting the attenuation value according to its importance.

According to one practice, the CAP measurement is associated with a scatter indicator, which may be a quarter bit distance (interquartile range) (iqr=q3-Q1) or standard deviation of the set of effective attenuation values.

Once the attenuation data is analyzed, the method displays a CAP measurement (DSP) calculated from the number of accumulated effective ultrasonic attenuation values at 108. When the organ to be measured is heterogeneous, the use of multimodal modes can be used to display several CAP measurements to the user.

Advantageously, the display at 108 is determined by the processor from the number of accumulated effective ultrasound attenuation values in real time (i.e., during the imaging mode of the medium), which enables the operator to verify the status of the inspection process. When used in conjunction with shear wave velocity measurements, the display may be updated only when the stiffness measurements are performed so as not to change the currentThe mode of operation of the device.

According to one practical approach, the instrument class indicator displayed to the operator graphically displays the number of representations (number of effective ultrasonic attenuation values, percentage compared to the target, numerical indicator, acquisition duration in seconds, etc.) of effective ultrasonic attenuation values selected to ensure a high quality measurement for calculating the CAP measurement. The greater the number of attenuation values used, the more reliable the CAP value will be. The instrument class indicator may indicate whether the number of effective ultrasonic attenuation values is less than or greater than a desired number.

Figures 3a-c illustrate how one embodiment of the system collects ultrasound signals and calculates CAP measurements. Figures 3a-c show data obtained on a human patient. As shown in fig. 3a, an ultrasound image is generated from the received ultrasound echo data. In some implementations, the echo data is a-line data (e.g., data received along a single linear path in the direction of interest). Multiple a signals are shown side by side to produce a TM mode image 150 showing how the tissue on a single line moves over time (horizontal axis). The TM mode image 150 represents ultrasound lines or echo signals received over time during operation of the elastography system in the first and second modes. The ultrasound line is plotted as a function of time in seconds. In TM mode image 150, imaging of the medium continues for more than 50 seconds. A region of interest (ROI) is also represented in the TM mode image 150, bounded by two dashed lines at 25mm and 65mm, and corresponding to a depth under the patient's skin where the liver is typically located. The TM mode image 150 also schematically shows the time t at which the operator activates the elastography device to generate a shear wave _3a1 、t _3a2 、t _3a3 、t _3a4 、t _3a5 、t _3a6 、t _3a7 、t _3a8 、t _3a9 、t _3a10 、t _3a11 、t _3a12 And t _3a13 . At each of these moments, the elastography system was operated in a second mode (i.e. a stiffness measurement mode) for a duration of 80 ms. Thus, fig. 3a shows the received ultrasound echoes when the elastography system is operated in the first and second mode (i.e. imaging mode and stiffness measurement mode). However, the received ultrasound echo associated with the second mode (represented in the TM mode image 150) is hardly visible in the image 150, because it is as above-explained The second mode is released for 80ms (i.e. at time t _3a1 、t _3a2 、t _3a3 、t _3a4 、t _3a5 、t _3a6 、t _3a7 、t _3a8 、t _3a9 、t _3a10 、t _3a11 、t _3a12 And t _3a13 The duration of the first mode is 80 ms) which is small compared to the total duration of 50 seconds. In speech, at time t _3a1 、t _3a2 、t _3a3 、t _3a4 、t _3a5 、t _3a6 、t _3a7 、t _3a8 、t _3a9 、t _3a10 、t _3a11 、t _3a12 And t _3a13 Each 80ms period corresponding to the second mode at the beginning includes 480 ultrasound lines that are almost invisible in the image 150 (due to image resolution). In contrast, the ultrasound lines acquired during the first imaging mode are more visible because they are acquired every 50 ms.

Below the TM mode image 150 are two charts 152, 154. The chart 154 represents calculated attenuation values for the corresponding a-lines in the TM mode image 150 directly above, which are stored in a computer readable memory. In some embodiments, if the attenuation data is "good", the data is marked or otherwise tagged in memory, which in some embodiments means that the attenuation data is within a predefined guard band and the echo data used to calculate the attenuation values meets correlation requirements. Attenuation values outside the guard bands or echo data that do not meet correlation requirements are marked as "bad" data. Graph 152 shows a record of the values of good and bad decay data. The good data corresponds to ultrasound lines meeting predefined one or more quality criteria discussed herein above. For example, in fig. 3a, two quality criteria have been used: a first quality criterion to determine a sufficiently decorrelated ultrasound line and a second quality criterion to determine an ultrasound line having an attenuation value within a predetermined range (e.g. 100-400 dB/m) or an extension range (50-500 dB/m). In the illustrated embodiment, the chart 152 includes a number of dark segments that mark bad data that does not meet the quality criteria (i.e., the ultrasound line is rejected by either the first quality criteria or the second quality criteria, or both the first and second quality criteria). The chart 152 also includes a number of white segments that mark areas of "good" ultrasound signal data that meet the quality criteria (i.e., the ultrasound lines meet both the first and second quality criteria). If all of the ultrasound signal data is "good," the entire display 152 will not have dark sections. It will be appreciated that other indicia, such as shading, cross hatching, etc., other than color may be used to mark good and bad attenuation data. It will be appreciated that the display map 152 may not be displayed to the operator. If the chart 152 is to be read only by the processor, the chart may be encoded, such as by storing a logical "1" for each good attenuation/echo signal line (good quality standard) or a logical "0" for each bad attenuation/echo signal line (bad quality standard). By analyzing the chart 152, the processor can determine if the probe is pointing to a good point in the liver to measure the CAP value and can facilitate the user to change the orientation of the probe if desired.

The graph 154 of fig. 3 also shows (a) conventionally, i.e., during shear wave tracking or elastic measurement, the CAP attenuation values obtained (identified as "current CAP attenuation values" in fig. 3a and shown as large dark dots) and (b) the CAP attenuation values obtained (identified as "selected published CAP attenuation values" in fig. 3a and shown as small black dots) according to an embodiment, i.e., outside of the shear wave tracking or elastic measurement period. As can be seen in graph 154, each large dark circle corresponds to time t _3a1 、t _3a2 、t _3a3 、t _3a4 、t _3a5 、t _3a6 、t _3a7 、t _3a8 、t _3a9 、t _3a10 、t _3a11 、t _3a12 And t _3a13 . The conventional CAP decay value varies significantly over time in graph 154. In the graph 154, the set comprising all CAP attenuation values obtained from all received echo signals prior to selection based on quality criteria is illustrated as a continuous line (in other words, the set comprises all unfiltered, obtained raw CAP attenuation values).

In an embodiment, supplemental criteria may be used to select the ultrasound line with respect to the coupling between the ultrasound transducer and the skin surface. This coupling may be represented by the level of applied force applied to the skin by the probe. In fact, good coupling between the ultrasound transducer and the skin surface is desirable. Ultrasound lines acquired using only minimal applied force may be included for calculation. A minimum applied force of 1 newton may be used. For example, the one or more quality criteria include a coupling criterion that represents a coupling force between the ultrasound transducer and the skin of the patient for which the viscoelastic medium is to be characterized, the coupling criterion being defined by a predetermined range of coupling coefficient values (e.g., force values). The received first mode echo signals are processed by associating each of the received first mode echo signals with a coupling coefficient and selecting each of the first mode echo signals having a coupling coefficient exceeding a predetermined threshold.

A processor in the ultrasound system is programmed to analyze the good attenuation data captured by the system. For example, a processor may execute computer readable instructions stored in a non-transitory memory of the disclosed system to process the ultrasound lines and determine whether the ultrasound lines pass quality criteria, such as the first and second quality criteria in fig. 3 a. Once the number of accumulated "good" decay data values exceeds some desired minimum, the processor calculates a histogram 155 of those values. In one embodiment, the minimum number of good values is recommended to be set to 400 or 20 seconds that are capable of receiving good echo signals at 20 beams/second. These data need not be acquired continuously. That is, some good ultrasound data may be interspersed with bad ultrasound data. More data than the minimum required can be used to increase the accuracy of the calculated histogram. It will be appreciated that other values of the required minimum number of good attenuation values may be used. In some embodiments, the minimum number may be set by the system or may be set by the user. Different types of probes may have different minima. For example, pediatric probes for children may require a smaller number of good data than probes for obese patients and the like.

Once the operator decides to end the examination, these values are fixed and the system delivers a final CAP value (or CAP values if there are multiple peaks) that is indicative of fat content. After the number of valid ultrasound values exceeds a predefined threshold, the inspection may be automatically ended.

Once the processor calculates the histogram of the calculated attenuation values, the processor analyzes the histogram 155. In some embodiments, the processor fits a gaussian curve to the histogram (unimodal or multimodal). Statistical measures such as mean and standard deviation may be determined by the processor from the fitted gaussian. Other statistical curve fits may also be performed. In some embodiments, knowing the gaussian for the histogram allows the histogram to shift mathematically, etc.

In the example shown in fig. 3a, it can be seen that the histogram comprises one main peak and one small second peak. Histograms of this type generally represent a relatively uniform attenuation in the tissue, wherein the fat deposition (steatosis) concentration in the liver is relatively constant throughout the region of interest.

From the histogram of decay data (plotted in light grey in fig. 3 a), CAP 156 (shown as published CAP in fig. 3 a) measurements are calculated and displayed. In one practice, the display of the disclosed system provides an average value of the measured CAP (here 195 dB/m) and a standard deviation of the CAP value (here +/-12 dB/m). For comparison, fig. 3a also shows that during the hardness measurement on the same patient (i.e. at time t _3a1 、t _3a2 、t _3a3 、t _3a4 、t _3a5 、t _3a6 、t _3a7 、t _3a8 、t _3a9 、t _3a10 、t _3a11 、t _3a12 And t _3a13 ) The measured CAP value 157 ("current CAP"), which corresponds to the CAP value measured according to conventional methods (whose histogram is plotted as dark gray). As can be seen in fig. 3a, the CAP value measured using conventional methods ("current CAP") provides an average value similar to one measurement according to the disclosed technology. However, the skilled artisan will appreciate that the standard deviation measured using the disclosed techniques has been significantly reduced, particularly by a factor of 5 in the present example. Accordingly, the technology of the present disclosureSurgery significantly improves the accuracy of the measured CAP values, which makes this parameter a very good option for tracking liver steatosis in clinical situations.

Fig. 3b shows a second ultrasound image 160 and graphs 162 and 164 of corresponding attenuation values associated with a second patient, according to an embodiment. Fig. 3b shows a diagram similar to the diagram shown in fig. 3 a. Fig. 3b also shows time t when the operator activates the elastography device to generate shear waves _3b1 、t _3b2 、t _3b3 、t _3b4 、t _3b5 、t _3b6 、t _3b7 、t _3b8 、t _3b9 And t _3b10 . Gaussian fitting 165 shows a single peak. Histograms of this type generally indicate a relatively uniform attenuation in the tissue, wherein the fat deposition (steatosis) concentration in the liver is relatively constant throughout the region of interest. From the histogram of decay data, CAP166 (shown in fig. 3b as the CAP disclosed herein) measurements are calculated and displayed. In one practice, the display of the system disclosed herein provides an average value of the measured CAP (here 220 dB/m) and a standard deviation of the CAP value (here +/-23 dB/m). For comparison, fig. 3b also shows that during the hardness measurement on the same patient (i.e. at time t _3b1 、t _3b2 、t _3b3 、t _3b4 、t _3b5 、t _3b6 、t _3b7 、t _3b8 、t _3b9 And t _3b10 ) The measured CAP value 167 ("current CAP"), which corresponds to the CAP value measured according to conventional methods.

Fig. 3c shows a third ultrasound image 170 and graphs 172 and 174 of corresponding attenuation values associated with a third patient, according to an embodiment. Fig. 3c shows a diagram similar to the diagram shown in fig. 3 a. FIG. 3b also shows 20 times t when the operator activates the elastography device to generate shear waves _3c1 -t _3c20 . The plot of attenuation values 174 shown in fig. 3c is classified as "good" for more attenuation values than the plot of attenuation values 154 shown in fig. 3 a. Graph 172 also contains fewer dark lines marking poor ultrasound data than graph 152 of fig. 3 a. The good attenuation values are accumulated and analyzed by the processor to calculate the histogram 175. In the illustration shownIn the example, the gaussian function fitted to the histogram 175 includes two distinct peaks. In such an example, the double peak may inform the user that there are two regions of different fat content (steatosis) in the region of interest or steatosis non-uniformity in the liver. From the histogram of decay data, CAP 176 (shown in fig. 3c as the CAP disclosed herein) measurements are calculated and displayed. In one practice, the display of the system disclosed herein provides an average value of the measured CAP (here 292 dB/m) and a standard deviation of the CAP value (here +/-26 dB/m). For comparison, fig. 3c also shows that during the hardness measurement on the same patient (i.e. at time t _3c1 -t _3c20 ) The measured CAP value 177 ("current CAP"), which corresponds to the CAP value measured according to conventional methods.

As in fig. 3a-b, it can be seen that the standard deviation measured using the disclosed technique has been significantly reduced, particularly by a factor of 1 in this example of fig. 3 c. Equally important is the fact that the presently disclosed technique for calculating CAP values can now inform the operator that there are areas of different fat content in the liver of the patient, as shown in fig. 3 c. Such information is difficult to obtain using conventional methods.

Once the histogram is analyzed, the processor calculates CAP values from the gaussian curve. In some embodiments, CAP measurements are determined from gaussian function fits, wherein:

σ _CAP is (i.e. of CAP) Gaussian standard deviation

μ _CAP Is (i.e. of CAP) Gaussian average

Att is the ultrasound attenuation

f (Att) is a Gaussian curve

A is a constant.

However, other formulas for calculating CAP measurements may also be used. Furthermore, those skilled in the art will appreciate that other peak fitting methods may also be used.

Fig. 4 illustrates a timing diagram according to which a system performing both VCTE and CAP measurements may operate. As mentioned above, the ultrasound system operates in an imaging mode (first mode), such as a TM mode, whereby the user can view tissue in the region of interest during period 200. The system transmits short bursts of ultrasound at a relatively low PRF, such as 20 beams/sec (e.g., 1-2 ultrasound cycles at a center frequency, such as 3.5MHz (or another center frequency depending on the probe). Attenuation data is collected from each return echo signal. PRFs close to 20Hz are advantageous to update the display in real time. Higher PRFs may be used, but it must be remembered that lowering the average acoustic output power represents an important benefit in terms of safety and supervision.

Once the user sees that the tissue is homogenous or no anomaly is noted in the returned echo data, the user can press a button on the probe to generate a shear wave pulse in the tissue of the subject. The system then tracks the velocity of the shear wave by transmitting ultrasonic pulses at a much higher PRF, such as 6000 beams/sec, during a period 202 of about 80 ms. Correlation between return echo signals at higher PRFs enables tracking of the shear wave and determination of the velocity of the shear wave in the tissue. Those skilled in the art will appreciate that shear wave velocity is related to the Young's modulus of the tissue (i.e., the stiffness of the tissue). The system then returns to the imaging mode at time period 204 and determines a new attenuation value from the ultrasound beam used in the imaging mode.

In one embodiment, the user usesThe device or similar system that measures stiffness and ultrasound attenuation performs a non-invasive assessment of the patient. The stiffness measurement is obtained from the median or average of several measurements that produce the instantaneous shear wave. Ultrasonic attenuation is obtained from an ultrasonic signal acquired outside of the time at which the shear wave measurement is made. As shown in fig. 4, the system alternates between a first mode in which ultrasound attenuation is calculated (period 200) and a second mode in which tissue stiffness is measured by tracking shear waves (period 202) until such time as all desired tissue stiffness measurements are obtained.

In some embodiments, in addition to the ultrasound signals or echo signals acquired during imaging mode periods 200, 204, … … (see fig. 4, which illustrates imaging mode period 200, imaging mode period 204, and subsequent imaging mode periods), ultrasound signals acquired during stiffness measurement 202 (and subsequent stiffness measurements) may also be used to calculate ultrasound attenuation. In other words, the CAP value may be determined using a combination of the ultrasonic signals acquired during the imaging mode periods 200, 204, … … and the ultrasonic signals acquired during the hardness measurement period 202 and/or a subsequent period. In this embodiment, the ultrasonic signals acquired during the hardness measurement may also be processed using one or more of the quality criteria described above. In other embodiments, not all ultrasound signals acquired during the imaging mode periods 200, 204, … … outside of the hardness measurements are processed to determine CAP values. This may be the case where the duration of the imaging mode is set to a value longer than 20 seconds. For example, in one embodiment, at least 70% of the ultrasound signals acquired during the imaging mode periods 200, 204, … … may be processed to determine the CAP value. In another embodiment, at least 80% of the ultrasound signals acquired during the imaging mode periods 200, 204, … … may be processed to determine the CAP value. In yet another embodiment, at least 90% of the ultrasound signals acquired during the imaging mode periods 200, 204, … … may be processed to determine the CAP value. In another embodiment, 100% of the ultrasound signals acquired during the imaging mode periods 200, 204, … … may be processed to determine the CAP value.

In some embodiments, the processor of the elastography system is programmed such that any ultrasound signals acquired during the first imaging mode period 200 prior to the first stiffness measurement 202 are not processed to determine the CAP value. Therefore, in fig. 4, the ultrasonic signals acquired during the first imaging mode period 200 are not considered; instead, the CAP value is determined using the ultrasound signals acquired during the second imaging mode period 204 and the subsequent imaging mode period that occur after the first hardness measurement period 202. Indeed, it may be desirable to not determine or exclude attenuation values associated with the first imaging mode period 200 occurring prior to the first hardness measurement 202, as it may be that the target organ (e.g., liver) may not have been properly located during the first imaging mode period 200. In another embodiment, at least 70% of the ultrasound signals acquired during the first imaging mode period 200 may be processed to determine the CAP value.

In some embodiments, the VCTE examination protocol requires the user to apply 10 shear waves to the patient, and the displayed stiffness is determined from the median of the 10 measurements. In some implementations, the CAP measurement is obtained from attenuation values obtained from all return echo signals occurring during the imaging mode between VCTE measurements. In other embodiments, attenuation values obtained during the course of several imaging periods are accumulated and used to calculate CAP measurements. For example, if 400 effective attenuation values are suggested for CAP measurements and PRF is 20 beams/second, the time required to accumulate the required number of attenuation values is at least 20 seconds and may be longer than the time of a single imaging period.

FIG. 5 shows representative displays of tissue hardness measurements 220 (E in kilopascals) and ultrasonic attenuation 224 (CAP in dB/m) (with a standard deviation of 23 dB/m). FIG. 5 also shows quality criteria regarding the hardness measurement, such as an IQR or a quartile result or an IQR/median ratio, indicating the confidence that the hardness measurement was properly measured. In some embodiments, the display further includes a graph 230 showing a comparison of the number of "good" attenuation values used to calculate the CAP value to the recommended minimum attenuation value number. In the example shown, bar graph 230 shows 90%, indicating that only 90% of the minimum number of suggested attenuation measurements are used in CAP value calculation. In some embodiments, if more than the minimum required number of attenuation values are accumulated, the bar graph 230 may exceed 100%. In some embodiments, the bar graph may display a range of values from 0 to 10, where 0 means 0%, and 10 means 100%. By doing so, the operator can end the inspection when reaching 10, which is the same as the operator is using the current availabilityThe system operates consistently when taking hardness measurements, for example, the operator stops when 10 effective hardness measurements are obtained. />

In the illustrated embodiment, the display also includes a quality indicator 232. In this example, the quality indicator 232 shows a number of 2/5, i.e., the displayed CAP measurement has a quality of 2 out of the possible 5. However, other ratios may be used. In some embodiments, the quality indicator is calculated based on a comparison of the number of good data obtained to the number of good data required and to the number of gaussian peaks found in the histogram. The specific metric for measuring CAP quality may be determined based on a statistical analysis of the generated CAP measurements and their corresponding histogram versus actual fat content in the liver of the subject, as determined by MRI studies of the subject. In another embodiment, the display may be configured to display the presence of more than one gaussian peak (e.g. using the numbers "1", "2" … …) having a magnitude above a predetermined threshold, thereby informing the operator that there are areas of differing fat content in the patient's liver.

Fig. 6 shows another possible display on the user interface showing the tissue hardness value and CAP measurement of the subject to the operator. In the illustrated example, the display 250 includes a TM mode image 252 generated from the received echo signals. Block 254 includes a-line echo data. In one embodiment, the a-line echo data in the 0.5 second range is averaged to smooth it. In some implementations, the color of the box around the a-line data indicates whether the quality criteria of the current ultrasound line is good or bad. In one embodiment, block 254 is shown with a green outline 256 when the quality criteria is good.

In the illustrated embodiment, display 250 also includes an image 258, image 258 representing the amount of force applied to the probe tip in contact with the patient's skin. Some probes include a force sensor that generates a signal that is read by the processor and used to control the image 258 to show when the user applies a force in a desired range for tissue measurement. For systems that calculate both tissue stiffness and CAP measurements, the display includes an elasticity map (or shear wave propagation map) 260 showing the slope (e.g., velocity) of the induced shear wave in the tissue. The elastic plot 260 has conventional diagonal stripes that represent how the shear wave passes through tissue as a function of depth and time. Finally, the display 250 includes CAP 262 and tissue hardness 264 measurements. In some implementations, quality criteria for the measurement, such as IQR or quartile results or STD standard deviation, may also be shown, indicating the confidence that the hardness and CAP measurements were correctly measured.

Figures 7A-E show the performance of a conventional CAP (current CAP) and a CAP disclosed herein (CAP disclosed herein) in a 113 patient population using the same device. The order of imaging mode and hardness measurement mode shown in fig. 4 was applied to each of the 113 patients. Ten (10) VCTE measurements were performed for each patient. For each patient, a conventional CAP (current CAP) was measured using the ultrasound signals acquired during the hardness measurement (i.e., mode 202 in fig. 4), which corresponds to the conventional method for determining CAP. In accordance with the disclosed technology, a public CAP (public CAP) is measured using ultrasonic signals acquired exclusively during the imaging modes 200, 204 shown in fig. 4. These patients were measured using both methods and CAP results were compared to a reference method for assessing steatosis. Steatosis may be assessed by a pathologist according to a histological scoring system. As is known in the art, steatosis is defined by the number of hepatocytes with fat accumulation: s0 (according to test)<5 or 10 percent, S1 (5 or 10-33 percent), S2 (34-66 percent), S3%>66%). See the following publications: m. Sasso et al, "The Controlled Attenuation Parameter (CAP) published in Clinical Research in Hepatology and Gastroenterology 2012): A novel tool for the non-invasive evaluation of steatosis using (controlled attenuation parameter (CAP)) use +.>New tools for non-invasive diagnosis of steatosis); m. Sasso et al, ultrasound in Medicine and Biology 2010, "Controlled Attenuation Parameter (CAP): A Novel VCTE ^TM Guided Ultrasonic Attenuation Measurement for the Evaluation of Hepatic Steatosis:Preliminary Study and Validation in a Cohort of Patients with Chronic Liver Disease from Various Causes (controlled attenuation parameter (CAP)) novel VCTE for diagnosis of hepatic steatosis ^TM Guided ultrasonic attenuation measurement: preliminary study and validation of patient populations with chronic liver disease of various causes) ". Since liver biopsy is a non-invasive procedure, MRI-PDFF is used as a reference method for measuring liver fat. Such methods are well known in the art. Fig. 7A shows a comparison of the variability of each method. Conventional CAP variability (current CAP) was evaluated by both the quarter bit distance (IQR) and the standard deviation (sd). As can be seen from fig. 7A, the variability of the disclosed CAP is much better than that of the conventional CAP. In other words, CAP values obtained according to the disclosed techniques better track the progression or regression of the disease. Thus, the described techniques significantly improve the diagnosis of steatosis in the liver of a patient. Fig. 7B shows the dispersion of CAP measurements in 3 patient groups for both methods. These groups correspond to progressively increasing liver fat levels (i.e. pdff <5％、5<＝pdff<10% and pdff>=10%). The width of each box represents the width of the box belonging to each group (i.e., pdff<5％、5<＝pdff<10% and pdff>Number of patients =10%). As can be seen from fig. 7B, CAP values measured according to conventional methods and methods according to the disclosed technology increase as liver fat content (corresponding to an increase in the percentage of pdff) increases. Thus, there is a good correlation between CAP values and the measurement of liver fat content. Fig. 7C shows the area under ROC curve (AUROC) for liver steatosis diagnosed with higher than 5% using MRI-PDFF as reference. The performance of the disclosed CAP (suroc=0.900) is better than the conventional CAP (auroc=0.886) with respect to AUROC. In other words, CAP values obtained according to the disclosed technology provide a diagnosis of steatosis that is closer to pathologists than current CAPs: the clinical performance of the presently disclosed methods for measuring CAP as disclosed herein is better than conventional methods. This improvement is due to the reduced variability of the disclosed CAP. Fig. 7D shows a Bland-Altman plot comparing the two methods. The deviation between the conventional and disclosed CAP methods is very low: 1.3dB/m, which means that the two methods are equivalent. FIG. 7E shows a conventional method and present disclosureThe method of the open technology is directed to a scatter plot of CAP values obtained for 113 patients. As can be seen from fig. 7E, a very good correlation was found between the conventional method for measuring the current CAP and the method for measuring the disclosed CAP according to the presently disclosed technology. Thus, the average value of the disclosed CAP is the same as the average value of the current CAP. However, the variability of the disclosed CAP and the variability of the current CAP are different.

Fig. 8A-B schematically illustrate spatial averaging of acquired ultrasound lines obtained based on a conventional method for measuring CAP (fig. 8A) and based on a method for measuring the disclosed CAP (fig. 8B) in accordance with the disclosed technology. Fig. 8A-B illustrate probes that transmit ultrasonic signals and receive ultrasonic echoes. The probe may beA probe of the system. The probe is held against the skin of the patient. Fig. 8A-B also show the location of changes in a target organ (e.g., liver) during acquisition of ultrasound lines or echo signals. Displacement of an organ, such as the liver, due to respiratory motion is typically several centimeters. The liver movement velocity caused by respiration is typically of the order of 1 cm per second.

In fig. 8A, ultrasound lines or echo signals are acquired during the stiffness measurement. As explained above, during a single stiffness measurement, ultrasound lines or echo signals are acquired with a period of 80ms at a high frame rate of 6000 beams/s. Because the organ (e.g., liver) moves during the measurement, the stiffness measurements are made at different locations of the organ. This is shown in fig. 8A, where each line schematically represents one stiffness measurement, which corresponds to an 80ms ultrasound line or echo signal acquisition. CAP measurement according to the conventional method is done with echo signals captured only from the different locations shown in fig. 8A, which results in poor spatial averaging of the acquired signals.

In contrast, in FIG. 8B, the ultrasonic beam is emitted at a repetition rate of less than 50Hz, for example, equal to 20+/-5 Hz. As explained above, this low repetition rate allows recording reflected ultrasound signals that are decorrelated from each other due to the difference in acquisition time compared to respiratory motion velocity. At a repetition frequency of 20Hz, the ultrasonic signals are acquired every 50 ms. The breathing rate is typically between 12-50 cycles per minute, which translates to 1.2-5.0 seconds. Within 50ms the displacement will be 2mm, which is sufficient to de-correlate the ultrasound signal. The use of decorrelated ultrasonic signals improves the reliability of the measurement while reducing measurement errors. Further, since a high number of ultrasound lines (echo signals) are acquired over a long period of time (at least 5 seconds, typically 20 seconds), the echo signals or ultrasound lines are collected from a larger area than shown in fig. 8A, which significantly improves the spatial averaging of the acquired ultrasound lines.

Fig. 9 is a block diagram of an elastography system 1000 that calculates CAP measurements from ultrasound data, in accordance with some embodiments of the presently disclosed technology. The elastography system 1000 generally includes a probe 300, a main module 400, and a user interface 500. In some embodiments, the probe 300 is used to detect shear wave velocity and transmit and receive ultrasound to obtain ultrasound attenuation values for computing CAP measurements. The probe 300 includes an ultrasonic transducer 302, a vibrator 370, and a memory 380. The ultrasonic transducers 302 in the probe tip are, for example, single element transducers, but may also be 1, 1.5, or 2-dimensional arrays. The main module 400 includes a processor 401, a controller 402, a memory 403, a vibration controller 404, a transducer 405 for alternately transmitting and receiving ultrasonic signals, an ultrasonic transmitter module 406, and an ultrasonic receiver module 407. During operation of the system 1000, the processor 401 is configured to execute machine executable instructions stored in the memory 403 for instructing the controller 402 to control the vibration controller 404 to transmit shear waves during stiffness measurements, to control the ultrasonic transmitter module 406 to transmit ultrasonic signals, and to control the ultrasonic receiver module 407 to receive echo signals. The ultrasonic signals received by the transducer 302 are processed by the ultrasonic receiver module 407 and stored in the memory 403, and these ultrasonic signals are filtered and digitized in the ultrasonic receiver module 407. The ultrasound transmitter module 406 is used to deliver an ultrasound beam to tissue for imaging and for collecting attenuation data. The programmed processor 401 analyzes the received signal to calculate a CAP measurement from a histogram of the ultrasound attenuation data. Modules 401, 402, 403, 404, 405, 406, and 406 may have different circuit forms.

If the same probe is used for elastography, the probe 300 also includes an electromagnetic actuator 370 (vibrator), similar to an acoustic speaker with a voice coil, coupled to the probe tip to produce physical movement of the transducer tip to produce shear waves in the tissue. In the embodiment shown in fig. 9, the probe is used for both VCTE and CAP measurements. However, in some embodiments, the probe may be configured to transmit and receive only ultrasonic signals for calculating CAP measurements. In this case, the probe may not include an electromagnetic actuator.

In another embodiment, the ultrasound system may be a system configured to perform CAP measurements but not configured to perform VCTE measurements. The ultrasound system of this embodiment is similar to the system of fig. 9 but lacks vibrator 370 and vibration controller 404. In this embodiment, the ultrasound system may include a probe having an ultrasound transducer, a main module, and a user interface. As in fig. 9, the main module may include a processor, a controller, a memory, a vibration controller, a transducer for alternately transmitting and receiving ultrasonic signals, an ultrasonic transmitter module, and an ultrasonic receiver module. During operation of the system, the processor is configured to execute machine-executable instructions stored in the memory for instructing the controller to control the ultrasonic transmitter module to transmit ultrasonic signals and the ultrasonic receiver module to receive echo signals. Ultrasonic signals received by the transducer are processed by an ultrasonic receiver module and stored in a memory, where they are filtered and digitized. The ultrasound transmitter module is used to deliver an ultrasound beam to tissue and collect attenuation data. The programmed processor analyzes the received signal to calculate a CAP measurement from a histogram of the ultrasound attenuation data. The machine-executable instructions stored in the memory are specifically designed to control the ultrasonic transmitter module to transmit ultrasonic signals at a repetition rate of less than 100Hz, such as 50Hz in one embodiment, and such as equal to 20+/-5 Hz. As explained above, this low repetition rate allows to record reflected ultrasound signals that are decorrelated from each other due to the difference in acquisition time compared to respiratory motion speed. Furthermore, the machine-executable instructions stored in the memory are specifically designed to control the ultrasound receiver module to acquire echo signals or accepted ultrasound lines in a period of time that is much longer than the period of time of use during hardness measurement (i.e., about 80 ms). This improves the spatial averaging of the acquired data. In one embodiment, the period of time is set to at least 5 seconds, and in one embodiment at least 10 seconds, and in another embodiment at least 20 seconds. For example, in an embodiment, the CAP measurement may be performed using echo signals acquired over a period of time of at least 30 seconds, or at least 45 seconds, or at least 1 minute and at most one or several minutes, such as at most 5 minutes, such as at most 4 minutes, such as at most 3 minutes, such as at most 2 minutes, such as at most 1 minute.

As described, it can be seen that the ultrasound system of the presently disclosed technology is adapted to collect attenuation data for use in calculating CAP measurements as it images tissue before allowing a user to perform a VCTE examination. The received ultrasound data and attenuation measurements undergo one or more quality tests before being included in a measurement group for calculating CAP values.

According to one practical approach, the calculating CALC step is performed using a histogram representing the accumulated effective ultrasound attenuation values. In this case, the histogram is automatically adjusted using one or more bell curves.

According to one practical approach, the adjustment is performed using a gaussian mathematical function. In other words, the step of calculating comprises the step of detecting one or more gaussian curves forming a histogram of the accumulated effective values. The center of each gaussian then corresponds to the value of the ultrasonic parameter representing the viscoelastic medium to be characterized.

Advantageously, the automatic detection of several bell curves comprising a histogram enables detection of different areas of the viscoelastic medium. In other words, the method according to the disclosed technology enables identification of regions of viscoelastic medium having different properties.

In some embodiments, the method according to the disclosed technology further comprises the step of displaying one or more values representing the ultrasonic parameter. In some embodiments, the step of displaying is only performed when the number of accumulated effective ultrasonic attenuation values is above a predetermined minimum threshold.

Advantageously, the use of a high number of accumulated effective ultrasonic attenuation values enables statistical analysis of the data and minimizes the risk of systematic errors in measuring ultrasonic parameters.

According to one practice, if several gaussian curves are detected, only the most representative values are displayed. In this case, the most representative value is automatically selected by the method, for example based on the detected properties of the different gaussian curves.

According to one practical way, the most representative value corresponds to the region of the viscoelastic medium that is insonified (insonified) for the longest time during the examination. In one embodiment, the value may be obtained in real time, i.e., as the operator operates the disclosed system in the first/imaging mode. Alternatively, the value may be obtained when the operator stops checking. In a further embodiment, the value is obtained at the time of automatic stop of the inspection.

According to one practice, the measurement error associated with the value representing the ultrasonic parameter is determined by the gaussian standard deviation fitted to the histogram of ultrasonic attenuation values.

It is important to note that if the value of the ultrasound parameter is calculated from a small number of ultrasound attenuation values, the accuracy of the calculation is reduced. In this case, the cumulative effective attenuation value is distributed along an asymmetric curve having a large uncertainty about the average value.

According to one practical approach, the predetermined minimum threshold value of the accumulated effective ultrasonic attenuation values is equal to 400 effective ultrasonic beams.

The value of the calculated ultrasonic attenuation parameter and the measurement error associated with the value may be communicated to an operator during the displaying step. For example, these values are displayed on a screen or an indicator.

Advantageously, the operator checks in real time for changes in the number of active ultrasound beams and can correct the positioning of the probe if necessary to reduce the duration of the examination or to improve the quality of the examination.

According to one practical manner, the method according to the disclosed technology further comprises the step of determining the measurement depth of the ultrasonic parameter.

According to one practice, the measurement depth is determined before the ultrasound is transmitted in a series of ultrasound beams. In this case, the operator may perform pre-positioning of the region of interest. According to one practical way, the measurement depth is kept constant throughout the duration of the ultrasonic parameter measurement.

According to one practice, ultrasound attenuation values are measured and accumulated for more than one (such as three) different depth ranges. These three depth ranges may be staggered by an amount such as 5mm or 1/4 inch. In this case, only the scale representing the accumulated effective attenuation value is displayed. At the end of the examination, the operator selects the depth range to be used. For example, the depth range may depend on the distance between the ultrasound probe and the outer wall of the medium to be characterized. For example, if the medium to be characterized is a human or animal liver, the depth range to be used is selected based on the distance between the ultrasound probe and the capsule of the liver.

According to one practice, a method according to the disclosed technology includes the step of displaying a measured depth. The measurement depth and the number of effective ultrasonic signals can be displayed simultaneously.

Alternatively, the ultrasonic parameters may be measured in three different depth ranges. At the end of the examination, a single depth will be used based on the distance between the ultrasound probe and the outer wall of the viscoelastic medium to be characterized.

During the calculation step, the histogram is adjusted using a gaussian curve, which enables calculation of a value representing the ultrasonic parameter. The gaussian curve is automatically detected in order to adjust the histogram. The center of the gaussian curve and its standard deviation correspond to the value representing the attenuation of the ultrasonic wave and the associated measurement error, respectively.

Advantageously, the result of the calculating step is displayed only if the number of accumulated effective ultrasonic attenuation values is above a predetermined minimum threshold. According to one practice, the minimum number of cumulative effective ultrasonic attenuation values is 400.

According to one practice, the inspection automatically stops when the number of accumulated effective ultrasonic attenuation values reaches a predetermined threshold, e.g., 400.

According to one practice, the number of accumulated effective ultrasonic attenuation values is represented by the indicator in real time. The result of the adjustment of the histogram is only displayed when the number of accumulated effective ultrasound attenuation values is above a minimum threshold.

According to one practice, the meter may also display a recommended value for the effective ultrasonic attenuation value.

As explained above, in some embodiments, the histogram established from the acquired attenuation values includes two or more distinct peaks corresponding to two or more distinct viscoelastic medium regions.

During the step of calculating the CAP measurement, the presence of two regions is automatically detected and the histogram is adjusted, for example using a suitable expectation maximization algorithm for the two gaussian curves. In the case where the two regions are characterized by two different ultrasound parameter values, each gaussian curve corresponds to one region of the viscoelastic medium.

Advantageously, methods according to the disclosed technology enable characterization of heterogeneous viscoelastic media having several regions, where each region is characterized by a given representative ultrasonic attenuation value.

Furthermore, the method enables the automatic detection of the most representative areas of the heterogeneous viscoelastic medium according to predetermined criteria. For example, the method comprises the step of automatically selecting the histogram portion corresponding to the region that has been swept for the longest time. In this case, the measurement error is calculated as the standard deviation of the value of the gaussian curve.

Advantageously, the method according to the disclosed technology enables reducing the measurement error associated with the value of the ultrasonic attenuation parameter while increasing the reliability of the measurement method.

Another aspect of the disclosed technology is an apparatus for implementing the method.

According to one practical form, the device according to the invention comprises:

an ultrasonic probe comprising an ultrasonic transducer for emitting a series of ultrasonic beams and for recording ultrasonic signals reflected by a medium to be characterized;

means, such as a digital signal processor or a programmed processor, configured to automatically accumulate effective attenuation values; and

Means, such as a digital signal processor or a programmed processor, configured to calculate one or more values of an ultrasonic parameter representative of the viscoelastic medium using the accumulated effective attenuation values.

The ultrasound probe may include one or more ultrasound transducers. The ultrasonic probe allows a series of ultrasonic beams to be emitted.

According to one practical form, the ultrasound probe comprises a single ultrasound transducer or a single-element ultrasound transducer having a diameter between 4 and 12 mm.

According to one practical form, the repetition rate of the ultrasound beam during the acquisition of the attenuation values is between 10Hz and 50 Hz.

According to one practice, the center frequency of the ultrasonic beam is between 1MHz and 10 MHz.

According to one practical form, the display device comprises a video display with a touch screen, which is designed to receive instructions to modify parameters or to initiate measurements. In other embodiments, the display may be a remote device (laptop, iPad, smartphone) connected to the system by a wired or wireless communication link to display data generated from the ultrasound beam.

In some embodiments, the value representing the ultrasonic parameter is displayed only when the number of good or effective ultrasonic attenuation values is above a predetermined minimum threshold.

According to one practical form, the display device is designed to display an indicator, which indicates the number of effective ultrasound beams.

According to one practical form, the indicator is produced in the form of a meter, which in fact displays a comparison of the number of effective ultrasonic beams with a predetermined threshold.

According to one practice, an indicator in the form of a meter displays a recommended effective ultrasonic attenuation value threshold.

According to one practical form, the ultrasound probe is a probe for transient elastography.

The processor is programmed or configured to analyze the histogram of the cumulative values and to estimate the parameters only when the analyzed signals are decorrelated from each other to increase the reliability of the measurement. The method according to the present technique also enables the selection of a region representing the viscoelastic medium to be characterized using an automatic analysis of a high number of good ultrasonic echo signals.

In some embodiments, one aspect of the disclosed technology is a method for measuring an ultrasonic parameter of a viscoelastic medium to be characterized, the method comprising the steps of:

transmitting a series of ultrasonic beams using an ultrasonic transducer and recording ultrasonic signals reflected by the medium to be characterized;

Automatically accumulating effective ultrasonic attenuation values, wherein the effective ultrasonic attenuation values are obtained from recorded reflected ultrasonic signals; and

One or more values of an ultrasonic parameter representative of the viscoelastic medium are calculated using the accumulated effective ultrasonic attenuation values.

The expression "ultrasonic beam" is understood to mean an ultrasonic pulse emitted in the medium to be characterized. According to one practical form, the viscoelastic medium to be characterized is the human or animal liver.

The expression "recording reflected ultrasonic signals" is understood to mean the instantaneous recording of echoes which result from reflective particles present in a defined depth range of the analyzed medium.

An example of an ultrasonic parameter measured by the method according to the invention is an ultrasonic attenuation parameter.

The expression "ultrasound attenuation" is understood to mean any parameter that reflects the attenuation of ultrasound: broadband ultrasonic attenuation (BUA in dB/cm/MHz), attenuation measured at a particular frequency (in dB/cm), controlled Attenuation Parameters (CAP), and the like.

Expression "effective ultrasoundThe "wave attenuation value" is understood to mean an ultrasonic attenuation value with a good quality standard. Examples of ineffective ultrasound attenuation values are negative (negative) ultrasound attenuation values or attenuation values that are not within the expected range. An example of an invalid ultrasound attenuation value is an ultrasound attenuation value obtained from an ultrasound signal that characterizes a blood vessel. For example, the validity criteria of an ultrasound signal are given by the applicant's developed tools "Liver Targeting Tool" or LTT (see also document "Influence of heterogeneities on ultrasound attenuation for liver steatosis evaluation (CAP ^TM ) Relevance of a liver guidance tool Ultrasonics Symposium (IUS) (effect of heterogeneity on ultrasound attenuation for liver steatosis assessment (CAP) ^TM ): liver guidance tool ultrasound seminar (IUS)) ",2013IEEE International.

In some embodiments, the expression "accumulating the effective ultrasonic attenuation values" is understood to mean recording the effective ultrasonic attenuation values. According to one practical approach, the accumulation of these values is represented by a histogram of effective ultrasonic attenuation values.

In some embodiments, the expression "a value representing an ultrasonic parameter" is understood to mean a value representing an insonified viscoelastic medium.

For example, if the ultrasonic parameter measured by the method is an ultrasonic attenuation parameter, the representative value is the value of the ultrasonic attenuation parameter calculated using the accumulated effective ultrasonic attenuation value. According to one practical approach, the most representative value of the ultrasound parameter is the value associated with the region of the medium that is insonified for the longest time during the examination, or the value associated with the region with the highest number of effective attenuation values. Alternatively, the most representative value of the ultrasound parameter is the value associated with a region of the medium for which the maximum number of good attenuation values have been recorded.

According to one practical way, the method according to the present technique comprises the step of displaying one or more values representative of the ultrasound attenuation parameter, wherein said displaying is only performed when the number of accumulated effective ultrasound attenuation values is above a predetermined minimum threshold. For example, the value of the ultrasound attenuation parameter is only displayed when the number of recorded effective ultrasound signals is higher than 100, for example higher than 200, such as 400 or more.

According to one practice, the ultrasonic beam is emitted at a repetition rate of less than 50Hz, for example equal to 20+/-5 Hz. When the viscoelastic medium is a human or animal organ, the difference between the breathing frequency and the repetition rate of the ultrasound beam enables recording of ultrasound signals that are decorrelated from each other in relation.

Advantageously, having a high number of effective attenuation values decorrelated from each other increases the likelihood that these values represent media that are insonified.

Advantageously, statistical analysis of the accumulated effective ultrasonic attenuation values enables to improve the reliability and repeatability of the method of measuring ultrasonic parameters.

According to one practical approach, the step of calculating one or more values representing the ultrasound parameters of the viscoelastic medium is performed using a histogram representing the accumulated effective ultrasound attenuation values.

Due to the fact that there are a high number of ultrasound attenuation values that are decorrelated from each other, the histogram may be described by one or more bell-shaped curves, such as gaussian curves.

According to one practice, one or more gaussian-like mathematical functions may be used to adjust the histogram of accumulated effective ultrasonic attenuation values. In this case, the maximum value of each gaussian corresponds to an attenuation value representing the region of the viscoelastic medium that is insonified.

According to one practice, the measurement error associated with the value representing the ultrasonic attenuation parameter is calculated as the standard deviation of a gaussian fitted to the effective ultrasonic attenuation value.

Advantageously, the statistical representation of the standard deviation is significant due to the high number of values, enabling accurate estimation of the measurement error associated with the value of the ultrasound parameter.

Advantageously, the method according to the disclosed technology enables automatic detection of the presence of different regions within a viscoelastic medium, wherein each region corresponds to a bell-shaped curve describing a portion of a histogram of cumulative effective ultrasonic attenuation values. In other words, the histogram depicted by a single bell-shaped curve corresponds to a completely uniform medium.

Advantageously, the method according to the disclosed technology enables measuring several values of an ultrasonic attenuation parameter, wherein each value represents a different region of the medium being insonified. In other words, the method according to the present technology enables selection of a region characterized by a value of an ultrasound parameter relative to a region characterized by a different value of the ultrasound parameter.

According to one practical way, the method according to the invention further comprises the step of automatically selecting the value of the ultrasonic parameter most representative of the medium to be insonified, when the histogram representing the cumulative effective ultrasonic attenuation values is described by several bell-shaped curves corresponding to different regions. The ultrasound parameter measurement method according to the present technique may also have one or more of the following characteristics considered alone or in all the possible combinations of techniques:

the method according to the disclosed technology further comprises the step of displaying one or more values of the ultrasonic parameter representative of the viscoelastic medium, wherein the displaying step is performed only when the number of accumulated effective ultrasonic attenuation values is above a predetermined minimum threshold.

In some embodiments, the method according to the present technology further comprises the step of displaying a meter indicating the number (or approximate number) of accumulated effective ultrasonic attenuation values. The meter includes an indicator that indicates a predetermined minimum threshold for the cumulative effective value and/or an indicator that recommends a predetermined threshold for the cumulative effective value. In some embodiments, one or more values representing the ultrasound parameters are calculated from a histogram representing the accumulated effective ultrasound attenuation values. In some embodiments, one or more values representing the ultrasound parameters are calculated and automatically adjusted using a histogram representing the accumulated effective ultrasound attenuation values. Automatic adjustment is performed using one or more gaussian-like mathematical functions. In some embodiments, the ultrasound parameter is an ultrasound attenuation parameter.

In some embodiments, ultrasound attenuation parameters are calculated at several different depths, and methods in accordance with the present technology include selecting a depth that best represents the medium to be characterized (or allowing a user to select the depth). In some embodiments, the method further comprises the step of displaying the measured depth of the ultrasonic parameter. The series of ultrasonic beams are emitted at an emissivity of less than 50Hz, for example less than or equal to 20+/-5 Hz.

Embodiments of the subject matter and the operations described in this specification (e.g., the elements of block 400 of fig. 8) can be implemented in digital electronic circuitry, or in computer software, firmware, or in hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Embodiments of the subject matter described in this specification can be implemented as one or more computer software, i.e., one or more modules of computer program instructions, encoded on a computer storage medium for execution by, or to control the operation of, data processing apparatus.

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

The term "programmed processor" encompasses all kinds of devices, apparatuses and machines for processing data, including by way of example a programmable processor, a Digital Signal Processor (DSP), a computer, a system-on-chip, or a plurality of the foregoing, or a combination of the foregoing. The apparatus may comprise dedicated logic circuits, such as an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

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

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

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

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

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

Claims

1. A method for measuring an ultrasound parameter of a viscoelastic medium to be characterized, the method being performed by an ultrasound system (1000), the ultrasound system (1000) comprising an ultrasound transducer (302) and a processor (400), the ultrasound transducer (302) being configured to transmit a series of ultrasound beams and to receive respective echo signals (50) from a region of interest (ROI), the processor being programmed to generate one or more series of ultrasound beams in a first mode to measure attenuation of the ultrasound signals in tissue, the method comprising:

Generating the one or more series of ultrasonic beams transmitted to the region of interest (ROI), and receiving respective first mode echo signals (50) from the region of interest, wherein the one or more series of ultrasonic beams are generated for an accumulation period of at least 2 seconds, wherein the tissue being measured moves relative to the ultrasonic transducer during the accumulation period;

recording a first mode ultrasonic attenuation value (alpha) associated with the received first mode echo signal, and

values (156,166,176,224,262) of the ultrasonic parameters are calculated using the first mode ultrasonic attenuation values (a).

2. The method of claim 1, wherein beams of the one or more series of ultrasonic beams are emitted at a beam repetition rate of between 15 and 25 beams/sec when the processor is operating in the first mode.

3. The method of claim 1 or claim 2, wherein the ultrasound system (1000) is an elastography system configured to generate shear waves in the region of interest (ROI), the processor being programmed to operate alternately in at least the first mode and a second mode, wherein in the second mode the processor (400) is programmed to control the elastography system (1000) to generate shear waves in the tissue and to generate a series of ultrasound beams to track how the tissue in the region of interest moves due to the shear waves.

4. A method as claimed in claim 3, wherein the value of the ultrasonic parameter is calculated using only the first mode ultrasonic attenuation value obtained when the processor is operating in the first mode.

5. A method as claimed in claim 3, further comprising the steps of:

recording a second mode ultrasonic attenuation value associated with a received second mode echo signal when the processor is operating in the second mode;

processing the second mode ultrasound attenuation values using the one or more quality criteria to determine ultrasound attenuation values of a predetermined quality level in the recorded second mode ultrasound attenuation values; and

the value of the ultrasonic parameter is calculated using the ultrasonic attenuation values obtained from both the first mode ultrasonic attenuation value and the second mode ultrasonic attenuation value and having the predetermined quality level.

6. The method of claim 1, further comprising processing the first mode ultrasonic attenuation values using one or more quality criteria to determine ultrasonic attenuation values of a predetermined quality level among the recorded first mode ultrasonic attenuation values, and wherein the value of the ultrasonic parameter is calculated using the first mode ultrasonic attenuation values of the predetermined quality level.

7. The method of claim 6, wherein the one or more quality criteria comprise a cross-correlation criteria, and wherein the step of processing comprises correlating each of the received first mode echo signals with a cross-correlation coefficient, and selecting each of the received first mode echo signals having a cross-correlation coefficient exceeding a predetermined threshold to determine a sufficiently decorrelated one of the received first mode echo signals.

8. The method of claim 7, wherein the cross-correlation coefficient is calculated based on one or more of the received one of the first mode echo signals and the previously received one of the first mode echo signals.

9. The method of claim 6, wherein the one or more quality criteria include an attenuation criteria defined by a predetermined range of ultrasound attenuation values, and wherein the step of processing includes selecting each of the first mode ultrasound attenuation values that are within the predetermined range.

10. The method of claim 9, wherein the predetermined range is 100-500db/m.

11. The method of claim 6, wherein the one or more quality criteria include a coupling criterion representing a coupling force between the ultrasound transducer and skin of a patient for which viscoelastic medium characterization is performed, the coupling criterion being defined by a predetermined range of coupling coefficient values, and wherein the step of processing includes associating each of the received first mode echo signals with a coupling coefficient and selecting each first mode echo signal having the coupling coefficient exceeding a predetermined threshold.

12. The method of claim 6, wherein the one or more quality criteria comprise a linear regression decision coefficient applied to the received first mode echo signal.

13. The method of claim 6, further comprising the step of: the ultrasound attenuation values having a predetermined quality level are accumulated, wherein the value of the ultrasound parameter is calculated only when the number of ultrasound attenuation values having a predetermined quality level reaches a predetermined threshold value.

14. The method of claim 1, wherein the ultrasonic parameter is a Controlled Attenuation Parameter (CAP).

15. The method of claim 1, further comprising displaying values (224, 262) of the ultrasonic parameter.

16. A system (1000) for measuring ultrasound attenuation in a region of interest (ROI) in a tissue sample, comprising:

-an ultrasound transducer (302), the ultrasound transducer (302) being configured to transmit a series of ultrasound beams and to receive respective echo signals (50) from the region of interest; and

a processor (400) programmed to control the system (1000) to, in a first mode:

generating one or more series of ultrasonic beams transmitted to the region of interest and receiving corresponding first mode echo signals (50) from the region of interest, wherein the one or more series of ultrasonic beams are generated for an accumulation period of at least 2 seconds, wherein the tissue being measured moves relative to the ultrasonic transducer during the accumulation period;

a value (156,166,176,224,262) of ultrasonic attenuation is calculated using the first mode ultrasonic attenuation value (α).

17. The system of claim 16, the system being an elastography system configured to generate shear waves in the region of interest (ROI), wherein the processor (400) is programmed to operate alternately in at least the first mode and a second mode, wherein in the second mode the processor is programmed to control the elastography system (1000) to perform: generating a shear wave in the tissue; and generating a series of ultrasonic beams to track how the tissue in the region of interest moves due to the shear wave.