CN112075955A

CN112075955A - Method and device for measuring ultrasonic parameters of viscoelastic medium

Info

Publication number: CN112075955A
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: 2020-12-15
Anticipated expiration: 2040-06-15
Also published as: KR20200143285A; JP2020203078A; BR102020011526A2; ZA202003172B; CN112075955B; RU2020118865A; AU2020203412A1

Abstract

A system and method for accumulating ultrasound attenuation data for use in 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 passing the quality metric are accumulated and used to calculate tissue properties. In one embodiment, the tissue characteristic is a CAP measurement correlated to the amount of fat 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

Ultrasound is a common tool used for imaging internal body tissues of human and animal subjects due to its ease of use and non-ionizing properties. Ultrasound can also be used to quantify tissue properties to detect diseases and other medical conditions. One such example is the combined use of ultrasound and shear waves to measure tissue stiffness in order to detect possible liver disease. Echosens SA (assignee of the present application) in paris, france has been developed to quantify tissue stiffness using ultrasound by measuring the velocity of mechanically induced shear waves transmitted through the tissue. Another condition that can be detected with 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 the ultrasound signal as it passes through the tissue. Thus, measurement of ultrasound attenuation (also known as controlled attenuation parameters or "CAP") is a prediction of fatty liver disease such as hepatic steatosis.

Echosens 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 VCTE, the probe applies mechanical vibrations to the subject to induce shear waves traveling through the tissue. The ultrasound 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 relative to the stiffness of the tissue. To measure the CAP, the attenuation of the ultrasonic signal used to track the velocity of the shear wave is measured. When the hardness measurement is considered valid, the CAP measurement is considered valid. A detailed explanation of how such VCTE and CAP measurements can be achieved can be found in the following literature: sandrin et al, "Transient elastomer mapping: a new non-invasive method for assessing fibrosis of liver (Transient Elastography: a novel non-invasive method for assessing liver fibrosis), published in Ultrasound in Medicine and Biology 2003, pp.29, 1705-1713; "The Controlled Authentication Parameter (CAP)" published by Sasso et al in Clinical Research in society and Gastroenterology 2012A novel tool for The non-innovative evaluation of surgery using

(controlled attenuation parameters (CAP): use

New tools for non-invasive diagnosis of steatosis) "; sass, mo et al, "Controlled engagement Parameter (CAP): A Novel VCTE, published by Ultrasound in Medicine and Biology 2010^TMGuided Ultrasonic characterization Measurement for the Evaluation of Liver Steatosis in advance Study and differentiation in a Coort of tissues with Chronic Liver Disease from tissues catalysts (controlled Attenuation parameters (CAP): New VCTE for diagnosis of Liver Steatosis^TMGuided ultrasonic attenuation measurements: preliminary studies and validation of patient populations with chronic liver disease of various causes) "; sasso et al, "Liver steatosis assessed by controlled attenuation parameters (cap) measured with the xl probe of the fibrous analysis (Liver steatosis assessed by using the xl probe of the fibrous analysis: preliminary study to assess diagnostic accuracy", published in Ultrasound in Medicine and Biology 2015, which are incorporated herein by reference.

While CAP measured according to prior methods statistically performs well in terms of the area under the ROC curve (over 80% for steatosis grade diagnosis), CAP values tend to have 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, in particular for monitoring the progression or regression of a disease in a patient.

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

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 ultrasound parameters based on the recording and automatic analysis of a large number of ultrasound backscatter signals (e.g., echo signals) acquired during a long period of time (at least 2 seconds, preferably at least 5 seconds, usually 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 ultrasonic parameters 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 ultrasound beams in a first mode of operation to measure attenuation of ultrasound signals in tissue, the method comprising:

generating the one or more series of ultrasound 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 ultrasound beams are generated with a cumulative time period of at least 2 seconds;

recording first-mode ultrasonic attenuation values associated with the received first-mode echo signals, an

Calculating values of the ultrasound parameters using the first mode ultrasound attenuation values.

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

The ultrasonic parameters mentioned above represent, 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 ultrasound parameters calculated using the ultrasound attenuation values associated with the ultrasound beams are more reproducible when the ultrasound beams are generated for a longer period of at least 2 seconds, compared to the case where several consecutive ultrasound beams are generated at a high rate for a period lasting only a fraction of a second.

A 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, e.g., echo signal 50 of fig. 1). For this and other reasons, the individual values of the attenuation of ultrasound waves determined from such echo signals are susceptible to high variability. And if the ultrasound beams emitted to probe the medium are generated only for a short period of time at a high repetition rate, the position of the ultrasound transducer, or of the organ/tissue to be characterized, does not change much from one ultrasound beam to another. Thus, in this case, the speckle-like component mentioned above remains substantially the same from one echo signal to another. 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, for example by calculating the average of these values (or by another statistical analysis of the set of values), does not significantly improve the accuracy or repeatability of the measurement of the ultrasonic attenuation.

In contrast, if the ultrasound beams emitted to probe the medium are generated over a period of time lasting a few seconds or more, the organ/tissue moves relative to the ultrasound transducer during that period due to respiration and/or transducer displacement. Due to this relative displacement, the spot-like component mentioned above changes during the period for detecting the medium. The different echo signals received by the system are at least partially decorrelated (decorrelated) and the different values of the ultrasound attenuation determined by these different echo signals correspond to a certain extent to independent measurements. 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 out potential inhomogeneities of the organ/tissue structure by spatial averaging over a wider area of the organ/tissue to be characterized.

The processor is programmed to generate (when operating in the first mode) the one or more series of ultrasound beams may comprise at least 10 (and preferably 20 or more) ultrasound beams separated from each other by at least 0.05 seconds. In other words, during the one or more series, the ultrasound attenuation in the tissue is detected (sampled) at least 10 times in succession, with a delay of at least 0.05 seconds between two of these samples (to benefit from the above-mentioned spatial averaging). This may be achieved, for example, by generating the ultrasonic beams at a relatively 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., 100 or 200 hertz repetition rate) (and during a sufficiently long period of time). In fact, in this last case, the whole set of ultrasound beams produced comprises several 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 produced between two such "well separated in time" beams.

According to an optional feature of the method, the series of ultrasound beams is transmitted at a beam repetition rate of 500 beams/second, preferably 100 beams/second, more preferably between 15 and 25 beams/second. In particular, the ultrasound 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 the 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 above-described improvement in the accuracy/repeatability of the final value of the ultrasonic attenuation. In contrast, if a series of ultrasound beams are transmitted at a high repetition rate (e.g., several kilohertz), many of the transmitted beams do not contribute to the accuracy/repeatability improvements described above, thus undesirably increasing the computational resources required to process the received echo signals and undesirably increasing the ultrasound radiation (which may be harmful to the subject whose organ/tissue is being characterized, or to the professional performing the characterization). In addition, even if it is not optimal, the above method can be implemented using a high repetition rate (higher than 500 shots/second) as long as a succession of ultrasound beams lasts at least 2 seconds.

In an embodiment of the method that has been 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 a second mode, wherein in the second mode the processor is programmed to control the elastography system 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. Thus, in this case, at least some of the ultrasound beams used to measure the attenuation of the ultrasound 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 the first mode, then in the second mode (to perform an elastography measurement), then in the first mode (imaging mode), then again in the second mode, and so on (to perform another elastography measurement). In this case, the aforementioned accumulation period of at least 2 seconds is the sum of the respective periods in which the processor operates in the first mode. For example, if the processor is programmed to implement 10 consecutive elastography measurements separated from each other by an interval of 0.5 seconds, during which the processor operates in the first mode, the sum of the individual periods during which the processor operates 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 during which the processor operates in the first mode. In this case, the sum of the periods during which the processor operates in the first mode will be 10 seconds; the beam repetition rate during these periods may be equal to 20 beams per second (so the beams are 50ms apart from each other), resulting in 200 "first mode" ultrasound beams distributed over a cumulative 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, only in the organ/tissuePerforming the CAP measurement during the hardness measurement is reversed, the CAP measurement is performed while the processor is operating in the first mode. Although it is considered beneficial and reliable to measure CAP during hardness measurements 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 the steatosis and fibrosis measurements can be said to be 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 the two parameters require different considerations to make the appropriate measurements. For example, conventional hardness measurements require a high frame rate (about 6000Hz) during a short period (about 80ms) in order to be able to track shear waves and perform hardness measurements. 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 to reduce variability in CAP values. These different considerations for making the CAP and hardness measurements are not fully taken into account when the CAP value is measured simultaneously with the hardness. In practice, during a single hardness measurement, an ultrasonic line or echo signal is obtained at a high frame rate of 6000 beams/s over 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 the 480 ultrasonic lines or echo signals obtained during the hardness measurement to the CAP measurement is relatively poor. Even when in use

(ultrasound-based elastography device for measuring stiffness (or elasticity) and ultrasound attenuation of tissues and organs) the probe is not moved during the examination, the liver itself is also moved by the breathing motion, and the stiffness measurement is done in a different position. 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, performing CAP measurements during imaging is not intuitive, as opposed to performing CAP measurements only during hardness measurements as in conventional methods, because CAP now measures CAP using data or echo signals acquired from different locations in the liver, rather than data or echo signals used to make hardness measurements. In fact, regardless of whether the probe is moved during the examination of the patient's liver, the patient's liver will necessarily move due to the breathing motion. As a result, the data or echo signals acquired during imaging and the data or echo signals acquired during stiffness measurement will be captured from different locations in the liver. Equally important is the fact that the skilled person will understand that during imaging of the liver (i.e. when the operator moves the probe over the patient's liver to image it), many ultrasound lines or echo signals are acquired from locations in the patient's abdomen other than the liver. As a result, many ultrasound lines or echo signals are generated during imaging of the liver 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 over a much longer period of time than conventional methods, which significantly improves the spatial averaging of the acquired ultrasound lines and significantly reduces the variability of the CAP values. Surprisingly, it was found that the variability of CAP values determined according to the disclosed technique can be significantly reduced, for example by a factor of 4. It will be further appreciated that a significant increase in the determination of the CAP value is not achieved at the expense of hardness measurement.

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

In some embodiments, the 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 USA's FDA (2003). The ultrasonic echo signals received from the pulses are analyzed in the frequency domain to estimate the signal attenuation at frequency. A plurality of attenuation measurements are collected over a period of time to generate a CAP measurement. 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 used to generate the CAP measurement. In some embodiments, the ultrasound echo signals received and processed to produce ultrasound attenuation values are ultrasound echo signals obtained when the elastography system is operating in a first mode, i.e., imaging mode, rather than ultrasound echo signals obtained when the elastography system is operating in a second mode corresponding to where shear waves are produced and tracked to measure elasticity of a region of interest.

In some embodiments, the ultrasound system generates 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 the 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. When a sufficient number of good attenuation values have been accumulated, a CAP measurement is calculated by the processor and displayed to the user. Further, a method according to the disclosed technology may include displaying values of the ultrasound parameters calculated using the first mode ultrasound attenuation values.

In some embodiments, the CAP measurement is calculated using the first mode ultrasound echo signals only if these signals are sufficiently decorrelated from previously received first mode echo signals. In other words, the system selects ultrasound lines that are different from the ultrasound lines that have been captured. In some embodiments, the CAP measurement is calculated using attenuation values from the received echoes only if the attenuation values are within a predetermined range of values. The predetermined range may be, for example, a range of 100-500 db/m. It will be understood 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 embodiments, the system generates a histogram of the 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 measure 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 attenuation values from the received echoes is considered to be taken into account only if a coupling coefficient associated with the received echoes, which coupling coefficient represents a coupling force between the ultrasound transducer and the skin of the patient for which viscoelastic medium characterization is performed, is considered to exceed a predetermined threshold value.

It will be appreciated that the different embodiments presented above may be combined according to all possible combinations of techniques, according to the disclosed technology.

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 ultrasound transducer configured to transmit a series of ultrasound beams and receive respective echo signals from a region of interest; and a processor programmed to generate a series of ultrasound beams in a first mode of operation to measure attenuation of ultrasound signals in tissue, the method comprising:

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

recording first mode ultrasonic attenuation values associated with the received first mode echo signals; and

The disclosed technology also provides a system for measuring ultrasonic 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 ultrasound 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 ultrasound beams are generated for a cumulative period of at least 2 seconds;

calculating a value of ultrasound attenuation in the organ or tissue using the first mode ultrasound attenuation values.

The features of the different embodiments of the method described above are also applicable to this system for measuring the attenuation of ultrasound waves.

In particular, the processor may be programmed such that when it operates in the first mode, the beam of the series of ultrasound beams is emitted at a beam repetition rate of 500 beams/second, preferably 100 beams/second, more preferably between 15 and 25 beams/second.

The system for measuring ultrasound attenuation may be an elastography system configured to generate shear waves in a 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 shear waves in tissue and to generate a succession of ultrasound beams to track how tissue in the region of interest is moved by the shear waves, the processor being programmed such that at least some of the ultrasound beams used to measure ultrasound signal attenuation are emitted outside of a period of time during which 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 ultrasound beam obtained when the processor is operating in the first mode, and determine an attenuation of the ultrasound signal using the echo signal having the desired level of quality. In particular, the processor may be programmed to determine the quality of the echo signal based on one or more of a correlation between successive echo signals and a comparison of an attenuation of the echo signal to an expected range of attenuation values.

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

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

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

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

Drawings

Other features and benefits 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 ultrasonic attenuation is estimated in the frequency domain, in accordance with some embodiments of the disclosed technology;

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

FIG. 3a illustrates a representation of a CAP measurement, 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 embodiments of the disclosed technique;

FIG. 3b illustrates a representation showing a CAP measurement, an attenuation measurement histogram, 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 embodiments of the disclosed technology;

FIG. 3c illustrates a representation of 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 embodiments of the disclosed technique;

FIG. 4 illustrates a timing diagram of a system for determining CAP and VCTE tissue stiffness measurements, in accordance with some embodiments of the disclosed technology;

FIG. 5 is a representation of CAP measurements generated in accordance with some embodiments 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;

FIGS. 7a-e show conventional CAP results and CAP results disclosed herein in a population of 113 patients;

8A-B schematically illustrate spatial averaging of acquired ultrasound lines obtained according to a conventional method of measuring CAP (FIG. 8A) and according to the 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 embodiments 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 properties from measured attenuation of ultrasound signals transmitted in the body. In some embodiments, the tissue characteristic is a CAP value indicative of the amount of fat present in the liver. Currently available from Echosens

In a system (ultrasound-based elastography device for measuring stiffness (or elasticity) and ultrasound attenuation of tissues and organs), the system rapidly measures the stiffness of a human or animal liver and ultrasound attenuation caused by tissue properties in a non-invasive and reproducible manner.

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

Is currently available

In the system, the ultrasound pulses for VCTE (VCTE is used to determine the velocity of the shear wave in the body) are analyzed to determine CAP measurements. Validation of CAP measurements is based on measurements of tissue stiffness. If the tissue hardness measurement is not valid, the corresponding ultrasound attenuation measurement is discarded. This is therefore a post-verification. In other words,

the system uses results from instantaneous elastography readings, i.e. in

The echo signals received during the second mode of operation of the system to validate 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 ultrasound signals as those detecting 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, shear is trackedThe PRF of the ultrasonic pulses of waves is 6000 pulses/second and the acquisition lasts only 80ms, with the result that one hardness measurement yields 480 ultrasonic lines or echo signals. Since the duration of the acquisition teaches that the organ is moving relatively short due to respiration, heartbeat, or the like, the return ultrasound signals are typically highly correlated and therefore contain redundant data, which does not represent a large tissue area for ultrasound attenuation. Considering that a typical examination procedure consists of less than 10 valid hardness measurements, it can be estimated that the total number of acquired ultrasound lines or echo signals is high: when each measurement corresponds to a set of 480 lines, the total number of ultrasonic lines or echo signals is 4800. However, each measurement lasts only 80ms, during which the ultrasound line is hardly decorrelated. Thus, the true contribution of a single set of 480 lines is quite low. Thus at present

In the device setting, the duration of the data acquisition for the ultrasound attenuation is only 800ms, less than one second. Although at the present time

The number of ultrasound lines acquired for CAP measurements in the device setup is large (-4800), but not only the total acquisition time is noted to be short (4800)<1 second) and the actual number of ultrasonic lines or echo signals contributing to the CAP measurement is also quite small: 10, which is caused by 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 the ultrasound waves requires high spatial averaging, which may not be possible with this method. This high correlation and associated poor spatial averaging may facilitate measuring variability of ultrasound parameters, such as CAP.

Another possible cause of variability in the measured values is the presence of varying regions that alter the local measurement (heterogeneity). 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 traversed to make the measurements.

To address these and other problems, the disclosed system processes ultrasound signals 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 an image of the tissue being examined, such as a TM mode image and/or an A mode image. This image is used by the operator to locate the region of interest in seconds, typically 10 seconds, which is certainly much longer than 80ms for VCTE acquisition for detecting shear wave velocity. Ultrasound signals are transmitted into the body and reflected from scatterers at a PRF selected so 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 beamrate compared to the PRF used for elastography allows the return echo data to be more uncorrelated, 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 adding too much redundant ultrasound data and without increasing the average acoustic output power delivered to the patient.

The inventors have determined that measuring the ultrasonic attenuation in the time domain when calculating the CAP measurement is not very accurate. To overcome this limitation, the system of the disclosed technique estimates the attenuation by analyzing the received echo signal in the frequency domain. FIG. 1 illustrates one technique for determining ultrasonic attenuation in accordance with the disclosed technique. 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 start of the 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 time period is subdivided into a number of smaller time segments or windows (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 ultrasound signals for each sub-period or window are converted into the frequency domain 60 using a Fast Fourier Transform (FFT) or other time-to-frequency domain transform. The result is a plot of the magnitude of the frequency components present in the echoes received at each time interval versus depth.

The magnitude versus depth of the frequency components present in the echoes received at each time interval is mapped 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 ultrasonic attenuation. The absorption slope a at 3.5MHz is determined and a best fit line 70, such as a 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 3.5 MHz. However, other bandwidth frequencies may be used depending on the transducer selected for the subject (e.g., pediatric, normal, obese, 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 ultrasonic transducers placed close to the medium to be characterized. The ultrasonic signal propagating in the medium to be characterized is at least partially reflected by the medium to be analyzed. The reflected ultrasonic echoes are digitized and stored in a computer readable memory. According to one practice, the transmission and recording of the ultrasonic signal is performed using the same ultrasonic transducer. However, a transducer with separate transmit and receive elements would be used.

According to one practice, the ultrasound beam is transmitted 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, the low repetition rate allows to record reflected ultrasound signals that are decorrelated from each other due to differences in acquisition time compared to the speed of respiratory motion. Ultrasound signals are acquired every 50ms at a repetition rate of 20 Hz. The breathing rate is typically between 12 and 50 cycles per minute, which translates to 1.2 to 5.0 seconds. The displacement of an organ, such as the liver, is typically a few centimeters and the speed of movement of the liver due to breathing is typically of the order of 1 centimeter per second. Within 50ms the displacement will be 2mm, which is sufficient to decorrelate the ultrasonic signals. The use of decorrelated ultrasonic signals improves the reliability of the measurement while reducing measurement errors.

At step 104, the method Accumulates (ACC) valid ultrasound attenuation values. In some embodiments, each ultrasound line or echo signal is associated with a certain quality criterion. The quality criterion is used to automatically exclude ultrasound lines that do not meet some predetermined characteristic. Only attenuation values associated with acceptable quality criteria are used to calculate the final CAP measurement. In some embodiments, 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 sufficiently decorrelated ultrasound lines or echo signals. The coefficients may be cross-correlation coefficients calculated from the correlation between successive ultrasound lines previously acquired at different times.

In particular, the cross-correlation coefficient associated with the ultrasound line under consideration for assessing the quality of the ultrasound line may be the cross-correlation coefficient between all or part of the ultrasound line and another ultrasound line received before it (such as the ultrasound line received immediately before the ultrasound line for which the quality assessment is to be made).

The cross-correlation coefficient between the considered ultrasound line and the previously received further ultrasound line may be calculated by considering several "local" cross-correlation coefficients respectively associated with different parts 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 part of the considered ultrasound line associated with that local cross-correlation coefficient and another previously received ultrasound line.

The cross-correlation coefficient is a number representing the degree of correlation, i.e. the similarity between the values or data of the two series 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 can be obtained by different algorithms, for example by cross-correlation "sliding dot product" calculation ("sliding 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 a predetermined threshold, the data is considered too correlated and the attenuation values of the ultrasound line are not used to calculate the final CAP measurement. In practice, setting the predetermined threshold to correspond to 80% (80 percent) of the reference value of the fully correlated signal enables the attenuation values to be selected sufficiently independent of each other 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 above reference value, the signal may be considered sufficiently de-correlated and may thus be considered for calculating the final CAP measurement. For example, if the cross-correlation coefficient is a cross-correlation coefficient between a portion of the ultrasound line under consideration and another previously received ultrasound line, then the portion of the ultrasound line under consideration and the previously received ultrasound line may be considered to be fully correlated when the portion of the ultrasound line under consideration is found to be the same as or multiplied by a scaling coefficient within the previously received ultrasound line (at a location within the previously received ultrasound line which may be different from the location of the portion within the ultrasound line whose quality is to be evaluated). For example, when the cross-correlation coefficient is calculated by a "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 ultrasound lines that exhibit good characteristics, such as no vessel wall boundaries on the ultrasound lines. This coefficient may be referred to as a quality coefficient. The coefficients may be, for example, measurements applied to linear regression of the ultrasound line (R)²) And (4) the coefficient. In some embodiments, a coefficient may be used to select ultrasound lines having attenuation values in a desired range, such as in the 100-400dB/m range. In this case, attenuation values outside the expected range are disregarded, since they are considered outliers. In a particular embodiment of the invention, at least two quality criteria are used: first a first quality criterion is used to select sufficiently decorrelated ultrasound lines or echo signals and then a second quality criterion is used to select ultrasound lines or echo signals having attenuation values lying in the expected range, or vice versa. However, this is not limiting and other predetermined quality criteria may be used in other embodiments of the invention to automatically exclude ultrasound lines or echo signals that do not meet some predetermined characteristics. For example, in one embodiment, the quality criterion comprises a cross-correlation criterion, and the processing of the received first mode echo signals comprises associating 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 ones of the received first mode echo signals that are sufficiently decorrelated. Cross-correlation coefficients may be calculated based on the received first mode echo signals and previously received first mode echo signals, which may include from a first through nth previously received first mode echo signals.

Alternatively, instead of analyzing the received first pattern echo signals along with the previously received first pattern echo signals to determine the cross-correlation coefficients and the cross-correlation criteria, each echo signal may be analyzed separately and individually to determine whether the echo signals satisfy a number of predetermined characteristics (e.g., signal strength, echo signal profile … …) corresponding to the quality criteria. Further, the one or more quality criteria may include an attenuation criterion defined by a predetermined range of ultrasonic attenuation values, and the processing includes selecting each first-mode ultrasonic attenuation value within the predetermined range. In an embodiment, two or more quality criteria may be used to select the received first mode echo signals 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 valid attenuation values is the number of attenuation values that meet the quality criterion. In some embodiments, prior to displaying the CAP measurement, the system accumulates at least a predetermined number of effective attenuation values, 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 would correspond to a range of 1000 to 100000 decay 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 ultrasound attenuation values. In this case, each bar of the histogram represents the number of received ultrasound echo signals having a given ultrasound attenuation value. As will be explained in detail below, the histogram is analyzed to determine peaks (e.g., the values of the most common attenuations) and other statistics about the histogram, such as the standard deviation. Such analysis may be performed by calculating a gaussian distribution to fit a histogram. The fitting can be done 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 dispersion indicator, which may be an interquartile range (IQR-Q3-Q1) or standard deviation of the set of effective attenuation values.

Once the attenuation data is analyzed, the method displays, at 108, the CAP measurement (DSP) calculated from the number of accumulated valid ultrasound attenuation values. The use of multimodal approach can be used to show the user several CAP measurements when the organ to be measured is heterogeneous.

Advantageously, the display at 108 is determined by the processor in real time (i.e., during an imaging mode of the medium) from the number of accumulated valid ultrasound attenuation values, which enables an 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 stiffness measurements are performed, so as not to change the current

The mode of operation of the device.

According to one practice, the meter-type indicator displayed to the operator graphically displays a representation of the effective ultrasound attenuation values (number of effective ultrasound attenuation values, percentage compared to target, numerical indicator, acquisition duration in seconds, etc.) selected to ensure a high quality measurement for calculating the CAP measurement. The larger the number of attenuation values used, the more reliable the CAP value will be. The meter type 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 a CAP measurement. 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 embodiments, 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 displayed 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 the ultrasonic lines or echo signals received over time during operation of the elastography system in the first and second modes. The ultrasound lines are plotted as a function of time in seconds. In TM mode image 150, the imaging of the medium lasts more than 50 seconds. A region of interest (ROI) is also represented in the TM mode image 150, which is bounded by two dashed lines at 25mm and 65mm, and corresponds to a depth under the patient's skin where the liver is typically located. TM mode image 150 also schematically shows an operator actuating an elastography device to generate a cutTime t of wave change_3a1、t_3a2、t_3a3、t_3a4、t_3a5、t_3a6、t_3a7、t_3a8、t_3a9、t_3a10、t_3a11、t_3a12And t_3a13. At each of these moments, the elastography system operates in the second mode (i.e., the stiffness measurement mode) for a duration of 80 ms. Thus, figure 3a shows the received ultrasound echoes when the elastography system is operating in the first and second modes (i.e. imaging mode and hardness measurement mode). However, the received ultrasound echoes (represented in the TM mode image 150) associated with the second mode are hardly visible in the image 150, because the second mode lasts 80ms (i.e., at time t) as explained above_3a1、t_3a2、t_3a3、t_3a4、t_3a5、t_3a6、t_3a7、t_3a8、t_3a9、t_3a10、t_3a11、t_3a12And t_3a13The duration of the second mode of starting is 80ms) which is small compared to the total duration of 50 seconds. In other words, 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_3a12And t_3a13Each 80ms period corresponding to the second mode that begins includes 480 ultrasound lines that are almost invisible in the image 150 (due to image resolution). In contrast, 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

graphs

152, 154. Graph 154 represents the attenuation values calculated 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 tagged or otherwise marked 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 the correlation requirements. Attenuation values outside the guard band or echo data that do not meet the correlation requirements are marked as "bad" data. Graph 152 shows a record of the values of good and bad decay data. Good data corresponds to ultrasound lines that meet one or more of the predefined quality criteria discussed herein above. For example, in fig. 3a, two quality criteria have been used: a first quality criterion for determining sufficiently decorrelated ultrasound lines and a second quality criterion for determining ultrasound lines having attenuation values lying within a predetermined range (e.g. 100-400dB/m) or an extension range (50-500 dB/m). In the illustrated embodiment, the chart 152 includes a number of dark sections that mark bad data that does not meet the quality criteria (i.e., ultrasound lines are rejected by either the first quality criteria or the second quality criteria, or both the first and second quality criteria). The graph 152 also includes a number of white sections that mark areas of "good" ultrasound signal data that meet the quality criteria (i.e., the ultrasound line meets both the first and second quality criteria). If all of the ultrasonic signal data is "good," then the entire display map 152 will not have dark sections. It will be appreciated that other indicia besides color may be used to mark good and poor attenuation data, such as shading, cross-hatching, and the like. It will be appreciated that the display 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 criterion) or a logical "0" for each bad attenuation/echo signal line (bad quality criterion). By analyzing the chart 152, the processor can determine whether the probe is pointed at a good spot in the liver to measure the CAP value, and can facilitate the user in changing the orientation of the probe if desired.

The graph 154 of fig. 3 also shows (a) CAP attenuation values obtained conventionally, i.e., during shear wave tracking or elasticity measurement (identified as "current CAP attenuation values" in fig. 3a and shown as large dark circles) and (b) CAP attenuation values obtained according to an embodiment, i.e., outside of the shear wave tracking or elasticity measurement period (identified as "selected disclosed CAP attenuation values" in fig. 3 a)Minus "and shown as small black dots). 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_3a12And t_3a13. Conventional CAP attenuation values vary significantly over time in graph 154. In the graph 154, the set comprising all of the CAP attenuation values obtained from all of the received echo signals before selection based on the quality criterion is illustrated as a continuous line (in other words, the set comprises all of the unfiltered, obtained raw CAP attenuation values).

In an embodiment, the ultrasound line may be selected using a complementary criterion 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 desired. Ultrasound lines acquired using only minimal applied forces may be included for the calculations. A minimum applied force of 1 newton may be used. For example, the one or more quality criteria include a coupling criterion representing a coupling force between the ultrasound transducer and the skin of the patient for which viscoelastic medium characterization is to be performed, 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 first mode echo signal 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 ultrasound lines and determine whether these ultrasound lines pass a quality criterion, such as the first and second quality criteria in fig. 3 a. Once the number of accumulated "good" attenuation data values exceeds some desired minimum value, the processor computes a histogram 155 of these values. In one embodiment, the minimum number of good values is suggested to be set to 400 or 20 seconds 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 amount required may be used to increase the accuracy of the calculated histogram. It will be appreciated that other values of a desired 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 minimums. For example, pediatric probes for children may require a smaller minimum amount of good data than probes for obese patients and the like.

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

Once the processor calculates a 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 can be determined by the processor from the fitted gaussian curve. Other statistical curve fits may also be performed. In some embodiments, knowing the gaussian for the histogram allows the histogram to be mathematically shifted, etc.

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

From the histogram of the attenuation data (plotted in light gray in fig. 3 a), the 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 the average value of the measured CAP (here 195dB/m) and the standard deviation of the CAP value (here +/-12 dB/m). For comparison, fig. 3a also shows the hardness measurement period 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_3a12And t_3a13) A measured CAP value 157 ("current CAP") corresponding to a CAP value measured according to conventional methods (the histogram of which is plotted in dark grey). 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 technique. However, the skilled person will appreciate that the standard deviation measured using the techniques of the present disclosure has been significantly reduced, in particular by a factor of 5 in this example. Thus, the disclosed technique significantly improves the accuracy of the measured CAP value, which makes this parameter a very good option to follow liver steatosis in a clinical situation.

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 a time t at which the operator activates the elastography device to generate a shear wave_3b1、t_3b2、t_3b3、t_3b4、t_3b5、t_3b6、t_3b7、t_3b8、t_3b9And t_3b10. The gaussian fit 165 shows a single peak. This type of histogram generally indicates a relatively uniform attenuation in tissue, where the fat deposition (steatosis) concentration in the liver is relatively constant throughout the region of interest. From the histogram of the attenuation data, a CAP166 (shown in fig. 3b as a CAP as disclosed herein) measurement is calculated and displayed. In one practice, the display of the system disclosed herein provides the average of the measured CAP (here 220dB/m) and the standard deviation of the CAP value (here +/-23 dB/m). For comparison, fig. 3b also shows the hardness measurement period (i.e. at time t) on the same patient_3b1、t_3b2、t_3b3、t_3b4、t_3b5、t_3b6、t_3b7、t_3b8、t_3b9And t_3b10) Measured CAP value 167 ("current CAP") corresponding to the conventional partyMeasured CAP values.

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 at which the operator activates the elastography device to generate shear waves_3c1-t_3c20. Comparing the graph of attenuation values 174 shown in FIG. 3c with the graph of attenuation values 154 shown in FIG. 3a, more attenuation values are classified as "good". Graph 172 also contains fewer dark lines marking poor ultrasound data as compared to graph 152 of fig. 3 a. Good attenuation values are accumulated and analyzed by a processor to calculate a histogram 175. In the example shown, the gaussian function fitted to the histogram 175 includes two distinct peaks. In such an example, the dual peaks may inform the user that there are two regions of different fat content (steatosis) in the region of interest or that the steatosis is not uniform in the liver. From the histogram of the attenuation data, a CAP 176 (shown in fig. 3c as a CAP disclosed herein) measurement is calculated and displayed. In one practice, the display of the system disclosed herein provides the mean value of the measured CAP (here 292dB/m) and the standard deviation of the CAP value (here +/-26 dB/m). For comparison, fig. 3c also shows the hardness measurement period (i.e. at time t) on the same patient_3c1-t_3c20) A measured CAP value 177 ("current CAP") corresponding to a 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 disclosed technique for calculating CAP values can now inform the operator that there are regions of different fat content in the patient's liver, as shown in fig. 3 c. Such information is difficult to obtain using conventional methods.

Once the histogram is analyzed, the processor calculates the CAP value from the gaussian curve. In some embodiments, the CAP measurement is determined according to a gaussian function fitting, wherein:

σ_CAPis (i.e. of CAP) Gaussian standard deviation

μ_CAPIs a Gaussian average (i.e., of CAP)

Att is ultrasonic attenuation

f (att) is a Gaussian curve

A is a constant.

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

Fig. 4 shows 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 a user may view tissue in a region of interest during period 200. The system transmits short ultrasonic bursts at a relatively low PRF, such as 20 beams/second (e.g., 1-2 ultrasonic 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. A PRF close to 20Hz is advantageous to update the display in real time. Higher PRFs may be used, but it must be borne in mind that reducing the average acoustic output power represents a significant benefit in terms of safety and regulatory.

Once the user sees that the tissue is homogeneous or no abnormalities are noticed in the return 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 an ultrasound pulse at a much higher PRF, such as at 6000 beams/sec, during a period 202 of approximately 80 ms. The correlation between the return echo signals at higher PRFs enables tracking of the shear wave and determination of the shear wave velocity 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 new attenuation values from the ultrasound beam used in the imaging mode.

In one embodiment, use is made ofIs used by people

A device or similar system that measures stiffness and ultrasonic attenuation performs 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. The ultrasonic attenuation is obtained from ultrasonic signals acquired outside the time at which the shear wave measurement is made. As shown in FIG. 4, the system alternates between a first mode in which the attenuation of the ultrasound waves is calculated (period 200) and a second mode in which the stiffness of the tissue is measured by tracking the shear waves (period 202) until such time as all of the desired tissue stiffness measurements are obtained.

In some embodiments, in addition to the ultrasound signals or echo signals acquired during the

imaging mode periods

200, 204, … … (see fig. 4, which shows the imaging mode period 200, the imaging mode period 204, and subsequent imaging mode periods), the ultrasound signals acquired during the stiffness measurement 202 (and subsequent stiffness measurements) may also be used to calculate the ultrasound attenuation. In other words, the CAP value may be determined using a combination of the ultrasound signals acquired during the

imaging mode periods

200, 204, … … and the ultrasound signals acquired during the stiffness measurement period 202 and/or subsequent periods. In this embodiment, the ultrasonic signals acquired during 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 period

200, 204, … … outside of the stiffness measurement are processed to determine the CAP value. 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 period

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 period

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 period

200, 204, … … may be processed to determine the CAP value. In another embodiment, 100% of the ultrasound signals acquired during the

imaging mode period

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 signal acquired during the first imaging mode period 200 is not considered; instead, the CAP value is determined using the ultrasound signals acquired during the second imaging mode period 204 and subsequent imaging mode periods 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 stiffness 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 exam protocol requires the user to apply 10 shear waves to the patient, and the displayed stiffness is determined by the median of the 10 measurements. In some embodiments, 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 a CAP measurement. For example, if 400 effective attenuation values are proposed for CAP measurements and the 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 a representative display of tissue stiffness 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 for hardness measurements, such as IQR or quartile results or IQR/median ratio, which indicates the confidence with which the hardness measurements were 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 suggested minimum attenuation value number. In the illustrated example, the bar graph 230 shows 90%, indicating that only 90% of the minimum number of suggested attenuation measurements are used in the CAP value calculation. In some implementations, the bar graph 230 may exceed 100% if more than the required minimum number of attenuation values are accumulated. 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 may end the inspection upon reaching 10, which is in common with the operator using what is currently available

The operation of the system is consistent when hardness measurements are taken, for example the operator stops when 10 valid hardness measurements are obtained.

In the illustrated embodiment, the display also includes a quality indicator 232. In this example, the quality indicator 232 shows the number 2/5, i.e., the displayed CAP measurement has a quality of 2 out of 5 possible. 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 with the number of good data required and with the number of gaussian peaks found in the histogram. The particular metric for measuring CAP quality may be determined based on a statistical analysis of the relationship of the generated CAP measurements and their corresponding histograms to the actual fat content in the subject's liver 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 an amplitude above a predetermined threshold, thereby informing the operator of the presence of regions of different fat content in the liver of the patient.

Fig. 6 represents another possible display on a user interface showing the operator the subject's tissue hardness value and CAP measurement. 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, a-line echo data in the 0.5 second range is averaged to smooth it. In some embodiments, the color of the box surrounding the a-line data indicates whether the quality criterion of the current ultrasound line is good or bad. In one embodiment, when the quality criterion is good, block 254 is shown with a green outline 256.

In the illustrated embodiment, the display 250 also includes an image 258, the 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 is applying a force in the desired range for tissue measurement. For a system that calculates 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 shear wave induced in the tissue. The elastic map 260 has conventional diagonal stripes that indicate how the shear wave traverses the tissue as a function of depth and time. Finally, the display 250 includes CAP 262 and tissue stiffness 264 measurements. In some embodiments, quality criteria for the measurements may also be shown, such as IQR or quartile results or STD standard deviation, which indicates the confidence that the hardness and CAP measurements were measured correctly.

Figures 7a-e show the performance of a conventional CAP (current CAP) and a CAP disclosed herein (CAP disclosed herein) in a population of 113 patients using the same device. The sequence of the imaging mode and the 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 ultrasonic signals acquired during the stiffness measurement (i.e., mode 202 in fig. 4), which corresponds to a conventional method for determining the CAP. In accordance with the disclosed technique, a published CAP (published CAP) is measured using ultrasound signals acquired exclusively during the

imaging modes

200, 204 shown in fig. 4. These patients were measured using both methods and the CAP results were compared to a reference method for assessing steatosis. Steatosis can be assessed by a pathologist according to a histological scoring system. As known in the art, steatosis is defined by the number of hepatocytes with fat accumulation: s0 (according to test)<5 or 10%), S1(5 or 10-33%), S2 (34-66%), S3 (3-32%) (C)>66%). See the following publications: sasso et al in Clinical research"The Controlled Authentication Parameter (CAP)" published in 2012 by ch in Hepatology and Gastroenterology, A novel tool for The non-innovative evaluation of stepathy using

(controlled attenuation parameters (CAP): use

New tools for non-invasive diagnosis of steatosis) "; "Controlled engagement Parameter (CAP): A Novel VCTE, published by Sasso et al in Ultrasound in Medicine and Biology 2010^TMGuided Ultrasonic characterization Measurement for the Evaluation of Liver Steatosis in advance Study and differentiation in a Coort of tissues with Chronic Liver Disease from tissues catalysts (controlled Attenuation parameters (CAP): New VCTE for diagnosis of Liver Steatosis^TMGuided ultrasonic attenuation measurements: preliminary studies 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 assessed by both quartile range (IQR) and standard deviation (sd). As can be seen in 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 increasing liver fat content (i.e., pdff)<5％、5<＝pdff<10% and pdff>10%). The width of each box indicates that it belongs to each group (i.e., pdff)<5％、5<＝pdff<10% and pdff>10%) of patients. As can be seen from fig. 7B, the CAP values measured according to the conventional methods and according to the methods of the disclosed technique increased with increasing liver fat content (corresponding to an increase in the pdff percentage). Thus, inThere is a good correlation between the CAP value and the measurement of liver fat content. Figure 7C shows the area under the ROC curve (AUROC) for liver steatosis diagnosed above 5% using MRI-PDFF as a reference. As for AUROC, the performance of the disclosed CAP (suloc ═ 0.900) is better than that of the conventional CAP (AUROC ═ 0.886). In other words, CAP values obtained according to the presently disclosed technology provide a more closely approximating pathologist-obtained diagnosis of steatosis than current CAP: the clinical performance of the methods disclosed herein for measuring CAP disclosed herein is better than conventional methods. This improvement is attributed 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 the published CAP method is very low: 1.3dB/m, which indicates that the two methods are equivalent. Figure 7E shows a scatter plot of CAP values obtained for 113 patients using conventional methods and methods of the disclosed technology. As can be seen in fig. 7E, a very good correlation was found between the conventional method for measuring current CAP and the method for measuring the disclosed CAP according to the presently disclosed technique. Thus, the disclosed average value of the CAP is the same as the average value of the current CAP. However, the variability of the CAP disclosed and the variability of current CAPs are different.

Figures 8A-B schematically illustrate spatial averaging of acquired ultrasound lines obtained based on a conventional method for measuring CAP (figure 8A) and based on a method for measuring a disclosed CAP according to the presently disclosed technology (figure 8B). Figures 8A-B illustrate a probe that transmits ultrasound signals and receives ultrasound echoes. The probe can be

A probe of the system. The probe is placed against the patient's skin. Figures 8A-B also illustrate the changing position of a target organ (e.g., liver) during acquisition of ultrasound line or echo signals. The displacement of an organ, such as the liver, due to respiratory motion is typically a few centimeters. The speed of movement of the liver caused by breathing is typically of the order of 1 cm per second.

In fig. 8A, ultrasonic lines or echo signals are acquired during hardness measurement. As explained above, during a single hardness 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 done at different locations of the organ. This is illustrated in fig. 8A, where each line schematically represents one stiffness measurement, which corresponds to an 80ms ultrasound line or echo signal acquisition. CAP measurements according to conventional methods are done with echo signals captured only from different locations as shown in fig. 8A, which results in poor spatial averaging of the acquired signals.

In contrast, in FIG. 8B, the ultrasound beam is transmitted at a repetition rate of less than 50Hz, e.g., equal to 20+/-5 Hz. As explained above, this low repetition rate allows the recording of reflected ultrasound signals that are decorrelated from each other due to differences in acquisition time compared to respiratory motion speed. Ultrasound signals are acquired every 50ms at a repetition rate of 20 Hz. The breathing rate is typically between 12 and 50 cycles per minute, which translates to 1.2 to 5.0 seconds. Within 50ms the displacement will be 2mm, which is sufficient to decorrelate the ultrasonic signals. The use of decorrelated ultrasonic signals improves the reliability of the measurement while reducing measurement errors. Furthermore, 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 a CAP measurement from ultrasound data in accordance with some embodiments of the disclosed technology. Elastography system 1000 generally includes probe 300, main module 400, and user interface 500. In some embodiments, the probe 300 is used to detect shear wave velocity and transmit and receive ultrasound waves to obtain ultrasound attenuation values for calculating CAP measurements. The probe 300 includes an ultrasonic transducer 302, a vibrator 370, and a memory 380. The ultrasonic transducer 302 in the probe tip is, for example, a single element transducer, but may also be a 1, 1.5 or 2 dimensional array. 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 measurement, 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, where they are filtered and digitized in the ultrasonic receiver module 407. The ultrasound transmitter module 406 is used to deliver ultrasound beams to tissue for imaging and for collecting attenuation data. A programmed processor 401 analyzes the received signal to calculate a CAP measurement from a histogram of the ultrasonic attenuation data. The

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 only transmit and receive ultrasound signals for calculating the CAP measurement. 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 figure 9 but lacks the 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 the ultrasonic signal and to control the ultrasonic receiver module to receive the echo signal. The ultrasonic signals received by the transducer are processed by the ultrasonic receiver module and stored in memory where they are filtered and digitized. The ultrasound transmitter module is used to deliver an ultrasound beam to the tissue and collect attenuation data. A programmed processor analyzes the received signal to calculate a CAP measurement from a histogram of the ultrasonic 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 equal to, for example, 20+/-5 Hz. As explained above, this low repetition rate allows recording of reflected ultrasound signals that are decorrelated from each other due to differences in acquisition time compared to respiratory motion speed. Furthermore, the machine executable instructions stored in the memory are specifically designed to control the ultrasonic receiver module to acquire the echo signal or the received ultrasonic line in a much longer period of time than the period of time used during the hardness measurement (i.e., about 80 ms). This improves 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 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 disclosed technology is adapted to collect attenuation data as it images tissue prior to allowing a user to perform VCTE examinations, which is used to calculate CAP measurements. The received ultrasound data and attenuation measurements are subjected to one or more quality tests before being included in the measurement group for calculating the CAP value.

According to one practice, the step of calculating CALC 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 mode of practice, the adjustment is made using a gaussian-type mathematical function. In other words, the step of calculating comprises the step of detecting one or more gaussian curves forming a histogram of accumulated significant values. The centre of each gaussian curve then corresponds to a value representative of the ultrasonic parameter of the viscoelastic medium to be characterized.

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

In some embodiments, a method according to the presently disclosed technology further includes the step of displaying one or more values representative of the ultrasound parameters. In some embodiments, the step of displaying is only performed when the number of accumulated effective ultrasound attenuation values is above a predetermined minimum threshold.

Advantageously, the use of a high number of cumulative valid ultrasound attenuation values enables statistical analysis of the data and minimizes the risk of system errors in measuring the ultrasound parameters.

According to one practice, only the most representative values are displayed if several gaussian curves are detected. 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 mode of practice, the most representative value corresponds to the region of the viscoelastic medium that has been insonified (insonified) for the longest time during the examination. In an embodiment, the value may be obtained in real-time, i.e. when the operator operates the disclosed system in the first/imaging mode. Alternatively, the value may be obtained when the operator stops the inspection. In yet another embodiment, the value is obtained upon an automatic stop of the inspection.

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

It is important to note that if the values of the ultrasound parameters are calculated from a small number of ultrasound attenuation values, the accuracy of the calculation is reduced. In this case, the accumulated effective attenuation values are distributed along an asymmetric curve with a large uncertainty about the mean value.

According to one practice, the predetermined minimum threshold value of the accumulated effective ultrasound attenuation values is equal to 400 effective ultrasound beams.

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

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 mode of practice, the method according to the disclosed technique further comprises the step of determining a measurement depth of the ultrasound parameters.

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

According to one practice, ultrasonic 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 inches. 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 mode of practice, a method according to the disclosed technique includes the step of displaying the measured depth. The measurement depth and the number of valid 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 ultrasonic 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 the calculation of values representing the ultrasound parameters. Gaussian curves are automatically detected in order to adjust the histogram. The center of the gaussian curve and its standard deviation correspond to the value representing the ultrasonic attenuation and the associated measurement error, respectively.

Advantageously, the result of the calculating step is only displayed when the number of accumulated valid ultrasound 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 is automatically stopped 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 in real time by an indicator. The adjustment result of the histogram is displayed only when the number of the accumulated effective ultrasonic attenuation values is higher than the minimum threshold value.

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 created from the acquired attenuation values includes two or more different peaks corresponding to two or more different regions of viscoelastic medium.

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 ultrasonic parameter values, each gaussian corresponds to a region of the viscoelastic medium.

Beneficially, methods according to the presently disclosed technology enable characterization of a non-uniform viscoelastic medium having several regions, where each region is characterized by a given representative ultrasonic attenuation value.

Further, the method enables to automatically detect the most representative region of the heterogeneous viscoelastic medium according to a predetermined criterion. For example, the method comprises the step of automatically selecting the portion of the histogram that corresponds 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 values of the gaussian curve.

Advantageously, the method according to the disclosed technique enables a reduction of the measurement errors associated with the values of the ultrasonic attenuation parameter, while increasing the reliability of the measurement method.

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

According to one mode of practice, the device according to the invention comprises:

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

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

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

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

According to one practice, the ultrasonic probe comprises a single ultrasonic transducer or a single original ultrasonic transducer with a diameter between 4 and 12 mm.

According to one practice, 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 practice, the display device includes a video display with a touch screen designed to receive instructions to modify parameters or 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 ultrasound parameter is displayed only if the number of good or valid ultrasound attenuation values is above a predetermined minimum threshold.

According to one mode of practice, the display device is designed to display an indicator that represents the number of active ultrasound beams.

According to one practice, the indicator is produced in the form of a meter which displays in real time the number of active ultrasound beams compared to 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 mode of practice, the ultrasound probe is a probe for transient elastography.

The processor is programmed or configured to analyze the histogram of the accumulated values and to estimate the parameter 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 presently disclosed technology is a method for measuring an ultrasonic parameter of a viscoelastic medium to be characterized, the method comprising the steps of:

emitting 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 representing an ultrasonic parameter of the viscoelastic medium are calculated using the accumulated effective ultrasonic attenuation values.

The expression "ultrasound beam" is understood to mean an ultrasound pulse emitted in the medium to be characterized. According to one mode of practice, the viscoelastic medium to be characterized is a human or animal liver.

The expression "recording the reflected ultrasonic signal" is understood to mean the instantaneous recording of the echo generated by the reflecting particles present in a defined depth range of the medium being analyzed.

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

The expression "ultrasonic attenuation" is understood to mean any parameter reflecting the ultrasonic attenuation: broadband Ultrasonic Attenuation (BUA) in dB/cm/MHz, attenuation measured at a specific frequency in dB/cm, Controlled Attenuation Parameters (CAP), and the like.

The expression "effective ultrasound attenuation value" is understood to mean an ultrasound attenuation value having a good quality standard. Examples of invalid ultrasonic attenuation values are negative ultrasonic attenuation values or attenuation values that are not within an expected range. An example of the null ultrasound attenuation value is an ultrasound attenuation value obtained from an ultrasound signal that exhibits characteristics of a blood vessel. For example, the validity criteria for ultrasonic signals are given by the Tool "live Targeting Tool" or LTT developed by the Applicant (see also the document "fluorescence of heterologous on ultrasound evolution for lid stimulation (CAP)^TM) Relevance of a liver confirmation tool ultrasoundics Symposium (IUS) (influence of heterogeneity on ultrasound attenuation for assessment of liver steatosis (CAP)^TM): liver guidance tool ultrasonic symposium (IUS)) ", 2013IEEE International).

In some embodiments, the expression "accumulated effective ultrasound attenuation values" is understood to mean that effective ultrasound attenuation values are recorded. According to one practice, the accumulation of these values is represented by a histogram of the effective ultrasound attenuation values.

In some embodiments, the expression "values representative of ultrasonic parameters" is understood to mean values representative of the viscoelastic medium that is insonified.

For example, if the ultrasonic wave parameter measured by the method is an ultrasonic wave attenuation parameter, the indicating value is a value of the ultrasonic wave attenuation parameter calculated using the accumulated effective ultrasonic wave attenuation value. According to one practice, the most representative value of the ultrasound parameters 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 in which the number of effective attenuation values is the highest. Alternatively, the value of the most representative ultrasound parameter is the value associated with a region of the medium for which the greatest number of good attenuation values have been recorded.

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

According to one practice, the ultrasound 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 decorrelated from each other in relation.

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

Advantageously, the statistical analysis of the accumulated effective ultrasound attenuation values enables an improved reliability and repeatability of the method of measuring ultrasound parameters.

According to one mode of practice, the step of calculating one or more values representative of the ultrasonic parameters of the viscoelastic medium is performed using a histogram representative of the accumulated effective ultrasonic attenuation values.

Due to the fact that there is a high number of ultrasound attenuation values that are decorrelated with respect to 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-type mathematical functions may be used to adjust the histogram of the accumulated effective ultrasound attenuation values. In this case, the maximum value of each gaussian curve corresponds to an attenuation value representing a 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 the 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 values of the ultrasound parameters.

Advantageously, the method according to the disclosed technique enables the automatic detection of the presence of different zones within the viscoelastic medium, each zone corresponding to a bell-shaped curve of a portion of a histogram describing the accumulated effective ultrasonic attenuation values. In other words, a histogram described by a single bell-shaped curve corresponds to a completely homogeneous medium.

Beneficially, a method according to the disclosed technique enables the measurement of several values of an ultrasonic attenuation parameter, where each value represents a different region of the insonified medium. In other words, the method according to the present technique enables the selection of the region characterized by the value of the ultrasound parameter with respect to the regions characterized by different values of the ultrasound parameter.

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

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

In some embodiments, a 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 comprises an indicator indicating a predetermined minimum threshold value for the cumulative valid value and/or an indicator recommending a predetermined threshold value for the cumulative valid value. In some embodiments, one or more values representing ultrasound parameters are calculated from a histogram representing the accumulated effective ultrasound attenuation values. In some embodiments, one or more values representing ultrasound parameters are calculated and automatically adjusted using a histogram representing accumulated effective ultrasound attenuation values. The automatic adjustment is performed using one or more gaussian-type mathematical functions. In some embodiments, the ultrasound parameter is an ultrasound attenuation parameter.

In some embodiments, the ultrasonic attenuation parameters at several different depths are calculated, and a method according to the present technique includes selecting the depth that best represents the medium to be characterized (or allowing the user to select that depth). In some embodiments, the method further comprises the step of displaying the measured depth of the ultrasound parameter. The succession of ultrasound beams is emitted with an emittance lower than 50Hz, for example lower than or equal to 20+/-5 Hz.

Embodiments of the subject matter and the operations described in this specification, such as the elements of block 400 of fig. 8, may 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 can be a source or destination of computer program instructions encoded in an artificially generated propagated signal. The computer storage medium may also be or be included in one or more separate physical components or media, such as 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 data 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 a chip, or a plurality of the above, or a combination of the above. The apparatus can comprise special purpose logic circuitry, e.g., 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. A 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 any 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. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, a mass storage device for storing data, e.g., magnetic, magneto-optical disks, or optical disks. However, the computer need not have these devices. Suitable means for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example: semiconductor memory devices such as EPROM, EEPROM, and flash memory devices; magnetic disks, such as internal hard disks or removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and 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, such as an LCD (liquid crystal display), LED (light emitting diode), or OLED (organic light emitting diode) screen, for displaying information to the user and a keyboard and a pointing device, such as a mouse or a trackball, by which the user can provide input to the computer. In some implementations, a touch screen can be used to display information and receive input from a user. Other types of devices may also be used to provide for interaction with the user; for example, feedback provided to the user can be any form of sensory feedback, such as visual feedback, auditory feedback, or tactile feedback; and input 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. Method for measuring an ultrasonic parameter of a viscoelastic medium to be characterized, the method being performed by an ultrasonic system (1000), the ultrasonic system (1000) comprising an ultrasonic transducer (302) and a processor (400), the ultrasonic transducer (302) being configured to emit a succession of ultrasonic beams and to receive a respective echo signal (50) from a region of interest (ROI), the processor being programmed to generate one or more succession of ultrasonic beams in a first mode of operation for measuring attenuation of the ultrasonic signal in tissue, the method comprising:

generating the one or more series of ultrasound beams transmitted to the region of interest (ROI), wherein the one or more series of ultrasound beams are generated over a cumulative period of at least 2 seconds, and receiving respective first mode echo signals (50) from the region of interest;

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

Calculating a value (156,166,176,224,262) of the ultrasound parameter using the first mode ultrasound attenuation value (a).

2. The method of claim 1, wherein when the processor is operating in the first mode, the beam of the one or more series of ultrasound beams is transmitted at a beam repetition rate of 500 beams/second, preferably 100 beams/second, more preferably between 15 and 25 beams/second.

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 succession of ultrasound beams to track how the tissue in the region of interest moves due to the shear waves.

4. The method of claim 3, wherein the values of the ultrasound parameters are calculated using only the first ultrasound attenuation values obtained when the processor is operating in the first mode.

5. The method of claim 3, further comprising the steps of:

recording second mode ultrasonic attenuation values associated with the received second mode echo signals when the processor is operating in the second mode;

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

calculating a value of the ultrasound parameter using the ultrasound attenuation values obtained from both the first mode ultrasound attenuation values and the second mode ultrasound attenuation values and having the predetermined quality level.

6. The method of any of claims 1 to 5, further comprising processing the first mode ultrasound attenuation values using one or more quality criteria to determine ultrasound attenuation values of the recorded first mode ultrasound attenuation values having a predetermined quality level, and wherein the values of the ultrasound parameters are calculated using the first mode ultrasound attenuation values having the predetermined quality level.

7. The method of claim 6, wherein the one or more quality criteria include cross-correlation criteria, and wherein the step of processing includes associating each of the received first pattern echo signals with a cross-correlation coefficient, and selecting each of the received first pattern echo signals having a cross-correlation coefficient that exceeds a predetermined threshold to determine ones of the received first pattern echo signals that are sufficiently decorrelated.

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

9. The method of any of claims 6 to 8, wherein the one or more quality criteria include an attenuation criterion 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 within the predetermined range.

10. The method as claimed in claim 9, wherein the predetermined range is 100 and 500 db/m.

11. The method according to any one of claims 6 to 10, wherein the one or more quality criteria comprise a coupling criterion indicative of a coupling force between the ultrasound transducer and the skin of the patient for viscoelastic medium characterization thereof, the coupling criterion being defined by a predetermined range of coupling coefficient values, and wherein the step of processing comprises 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 value.

12. The method of any of claims 6 to 11, 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 any of claims 6 to 12, further comprising the step of: accumulating the ultrasonic attenuation values having a predetermined quality level, wherein the value of the ultrasonic parameter is calculated only when the number of the ultrasonic attenuation values having a predetermined quality level reaches a predetermined threshold value.

14. The method of any one of claims 1 to 13, wherein the ultrasound parameter is a Controlled Attenuation Parameter (CAP).

15. The method of any of claims 1 to 14, further comprising displaying the value of the ultrasound parameter (224, 262).

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

an ultrasonic transducer (302), the ultrasonic transducer (302) configured to transmit a series of ultrasonic beams and 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 of operation:

generating one or more series of ultrasound 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 ultrasound beams are generated for a cumulative period of at least 2 seconds;

Calculating a value of ultrasonic attenuation (156,166,176,224,262) 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 shear waves in the tissue; and generating a series of ultrasound beams to track how the tissue in the region of interest moves due to the shear wave.