U.S. patent application number 17/324775 was filed with the patent office on 2021-11-25 for non-invasive device for detecting liver damage.
The applicant listed for this patent is ECHOSENS. Invention is credited to Veronique MIETTE, Laurent SANDRIN, Magali SASSO.
Application Number | 20210361223 17/324775 |
Document ID | / |
Family ID | 1000005767582 |
Filed Date | 2021-11-25 |
United States Patent
Application |
20210361223 |
Kind Code |
A1 |
MIETTE; Veronique ; et
al. |
November 25, 2021 |
NON-INVASIVE DEVICE FOR DETECTING LIVER DAMAGE
Abstract
A device calculates a score reflecting a state of liver damage,
the calculating device being designed to calculate a score using
the following physical parameters: a parameter corresponding to
inflammation and/or fibrosis; and a parameter corresponding to
steatosis.
Inventors: |
MIETTE; Veronique;
(Villejuif, FR) ; SANDRIN; Laurent;
(Bourg-la-Reine, FR) ; SASSO; Magali; (Bellegarde,
FR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ECHOSENS |
Paris |
|
FR |
|
|
Family ID: |
1000005767582 |
Appl. No.: |
17/324775 |
Filed: |
May 19, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15579016 |
Dec 1, 2017 |
11039781 |
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PCT/EP2016/062392 |
Jun 1, 2016 |
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17324775 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/7275 20130101;
A61B 8/5223 20130101; A61B 5/4244 20130101; A61B 5/4842 20130101;
A61B 8/485 20130101; A61B 8/08 20130101; A61B 5/7264 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00; A61B 8/08 20060101 A61B008/08 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 2, 2015 |
FR |
1554995 |
Claims
1.-3. (canceled)
4. A system for calculating a score in a patient, said score being
a quantitative or semi-quantitative evaluation of liver damage of
alcoholic or non-alcoholic steatohepatitis type, said system
comprising: a) one or more measurement devices including one or
more ultrasound transducers and configured to carry out
measurements of a first physical parameter corresponding to liver
fibrosis, or liver inflammation, or both, and a second physical
parameter corresponding to liver steatosis; b) a calculating device
configured to receive values of said first and second physical
parameters measured by the one or more measurement devices and a
value of one or more biological parameters, the one or more
biological parameters including at least one transaminase (ASAT or
ALAT), said calculating device including one or more processors
configured to execute a sequence of instructions for determining a
score parameter, based on the values of the first and second
physical parameters and the one or more biological parameters,
representative of liver damage in said patient, c) a display device
including a screen, the display device configured to display the
score parameter determined by the calculating device, the score
parameter being displayed on said screen in the form of a numerical
value, a binary indicator, a probability or a risk, said score
parameter providing an estimate of NASH.
5. The system of claim 4, wherein the first physical parameter is
liver stiffness or liver elasticity and the second physical
parameter is ultrasonic attenuation or tissue viscosity.
6. The system of claim 4, wherein the one or more measurement
devices include an elastography apparatus, or an ultrasound scanner
or both.
7. The system of claim 4, wherein the one or more measurement
devices include an elastography apparatus that is configured to
carry out measurements of said first physical parameter and said
second physical parameter.
8. The system of claim 4, wherein the sequence of instructions
determine the score parameter according to a logistic regression, a
decision tree, a Bayes classifier, or a random forest
regression.
9. The system of claim 4, wherein the calculating device is
integrated in a device that includes the one or more measurement
devices and the display device.
10. The system of claim 4, wherein the calculating device is remote
from the one or more measurement devices.
11. The system of claim 4, wherein the calculating device is
adapted to communicate with the one or more measurement devices via
Ethernet or Wi-Fi link to receive said values of said first and
second physical parameters.
12. The system of claim 4, wherein the display device is part of a
computer that is remote from both the calculating device and the
one or more measurement devices.
13. A method for calculating a score in a patient, said score being
a quantitative or semi-quantitative evaluation of liver damage of
alcoholic or non-alcoholic steatohepatitis type, the method
comprising: a) carrying out measurements of a first physical
parameter corresponding to liver fibrosis, or liver inflammation,
or both, and a second physical parameter corresponding to liver
steatosis with one or more measurement devices that include one or
more ultrasound transducers; b) calculating, with a calculating
device, a score parameter representative of liver damage in said
patient, the score parameter being based on values of the first and
second physical parameters and one or more biological parameters,
the calculating device configured to receive values of said first
and second physical parameters measured by the one or more
measurement devices and a value of the one or more biological
parameters, the one or more biological parameters including at
least one transaminase (ASAT or ALAT), said calculating device
including one or more microprocessors configured to execute a
sequence of instructions for determining the score parameter, and
c) displaying on a screen of a display device the score parameter
in the form of a numerical value, a binary indicator, a probability
or a risk, said score parameter providing an estimate of NASH.
14. The method of claim 13, wherein the first physical parameter is
liver stiffness or liver elasticity and the second physical
parameter is ultrasonic attenuation or tissue viscosity.
15. The method of claim 13, wherein the one or more measurement
devices include an elastography apparatus, or an ultrasound scanner
or both.
16. The method of claim 13, wherein the one or more measurement
devices include an elastography apparatus that is configured to
carry out measurements of said first physical parameter and said
second physical parameter.
17. The method of claim 13, wherein the sequence of instructions
determine the score parameter according to a logistic regression, a
decision tree, a Bayes classifier, or a random forest
regression.
18. The method of claim 13, wherein the calculating device is
integrated in a device that includes the one or more measurement
devices and the display device.
19. The method of claim 13, wherein the calculating device is
remote from the one or more measurement devices.
20. The method of claim 13, wherein the calculating device is
adapted to communicate with the one or more measurement devices via
Ethernet or Wi-Fi link to receive said values of said first and
second physical parameters.
21. The method of claim 13, wherein the display device is part of a
computer that is remote from both the calculating device and the
one or more measurement devices.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of U.S. application Ser. No.
15/579,016, filed Dec. 1, 2017, which is the U.S. National Stage of
PCT/EP2016/062392, filed Jun. 1, 2016, which in turn claims
priority to French Patent Application No. 1554995, filed Jun. 2,
2015, the entire contents of all applications are incorporated
herein by reference in their entireties.
TECHNICAL FIELD
[0002] The invention relates to a non-invasive device for detecting
liver damage using ultrasonic waves and shear waves. Said device
may be used for humans and animals and is for example intended for
the detection of liver damage of ASH (Alcoholic SteatoHepatitis) or
NASH (Non-Alcoholic SteatoHepatitis) type. The invention also
pertains to a score reflecting liver damage.
PRIOR ART
[0003] Normally, chronic liver tissue diseases cause liver damage
such as fibrosis. Fibrosis is a process of fibrous healing of liver
tissue resulting from inflammation. The initially asymptomatic
fibrosis may evolve into cirrhosis. The elasticity of liver tissue
constitutes a marker of liver fibrosis. In order to measure and
quantify the elasticity of liver tissue, it is known to use pulse
elastography, as described, for example, in the patent application
number FR 2843290.
[0004] This document describes an embodiment of a device according
to the prior at. This device is composed of a probe provided with a
vibration generator generating a low frequency elastic wave in a
tissue, for example by vibration, and analysing the propagation of
this low frequency elastic wave by means of high frequency
ultrasonic waves transmitted and received by an ultrasonic
transducer. The measurements obtained via this device make it
possible to quantify the elasticity of liver tissue. This device
also makes it possible to quantify the ultrasonic attenuation of
tissues, as described, for example, in the patent application
number FR 2949965. The quantification of ultrasonic attenuation in
the liver corresponds to the amount of steatosis.
[0005] On the other hand, in humans certain diseases, for example
NASH, are not necessarily linked only to the sole amount of
fibrosis or to the sole amount of steatosis, and may for example
associate steatosis type damage (presence of fat in the liver) and
inflammation with or without fibrosis. Consequently, the stage of
NASH or the evolution towards NASH cannot be diagnosed using a
single parameter.
DESCRIPTION OF THE INVENTION
[0006] The present invention aims to resolve at least one of the
aforesaid drawbacks of the prior art. To do so, the invention
proposes a non-invasive device for detecting liver damage taking
into account different parameters. The invention also proposes a
score reflecting a type of liver damage.
[0007] To this end, one aspect of the invention relates to a device
for calculating a score for humans or animals, said score being a
quantitative or semi-quantitative evaluation of liver damage of
alcoholic or non-alcoholic steatohepatitis type, said calculating
device being constructed and arranged to calculate a score using
the following at least physical or even biological parameters:
[0008] a parameter corresponding to inflammation and/or fibrosis,
[0009] a parameter corresponding to steatosis.
[0010] This embodiment particularly has the advantage of enabling
early detection of certain types of liver damage, such as for
example NASH, NASH being able to correspond to inflammation,
fibrosis and steatosis. On the other hand, NAFLD (Non-Alcoholic
Fatty Liver Disease) simply corresponds to steatosis. Thanks to the
score, it is thus possible to differentiate patients suffering from
a NAFLD type disease from patients suffering from a NASH type
disease.
[0011] In one non-limiting embodiment of the device according to
the invention, the score is a quantitative or semi-quantitative
evaluation (for example, binary indicator) of liver damage of
alcoholic or non-alcoholic steatohepatitis type.
[0012] In one non-limiting embodiment of the calculating device
according to the invention, the calculating device is integrated
in: [0013] an ultrasound scanner, or [0014] a device constructed
and arranged to measure at least liver elasticity.
[0015] In one non-limiting embodiment, the device according to the
invention is constructed and arranged to deliver the score
concurrently with the measured physical parameters. In other words,
the ultrasound scanner or the device constructed and arranged to
measure at least liver elasticity measures physical parameters and
the device according to the invention calculates the score while
taking into account at least the measured physical parameters.
[0016] In one non-limiting embodiment of the calculating device
according to the invention, the calculating device is constructed
and arranged to communicate with: [0017] a remote ultrasound
scanner, or [0018] a remote device constructed and arranged to
measure at least liver elasticity.
[0019] In one non-limiting embodiment of the device according to
the invention, the parameter corresponding to fibrosis is
elasticity.
[0020] In one non-limiting embodiment of the device according to
the invention, the parameter corresponding to steatosis is a
measurement of the attenuation of ultrasonic waves, for example the
parameter called CAP as described in the article Sasso, M., et al.
(2010). "Controlled attenuation parameter (CAP): a novel VCTE
guided ultrasonic attenuation measurement for the evaluation of
hepatic steatosis: preliminary study and validation in a cohort of
patients with chronic liver disease from various causes."
Ultrasound Med Biol 36(11): 1825-1835.
[0021] In one non-limiting embodiment of the device according to
the invention, the parameter corresponding to steatosis is a
measurement of liver tissue viscosity.
[0022] In one non-limiting embodiment of the device according to
the invention, the calculating device is constructed and arranged
to calculate a score using at least one additional parameter
corresponding to inflammatory activity. For example, this parameter
may be the transaminase value, ALAT, ASAT, GGT, liver elasticity or
liver viscosity.
[0023] In one non-limiting embodiment of the device according to
the invention, the calculating device is constructed and arranged
to calculate a score using at least one additional parameter
corresponding to metabolic syndrome.
[0024] In one non-limiting embodiment of the device according to
the invention, the calculating device is constructed and arranged
to calculate a score using at least one additional parameter of
anthropomorphic type.
[0025] In one non-limiting embodiment of the device according to
the invention, the calculating device is constructed and arranged
to calculate a score using at least one additional parameter of
biological type. The at least one biological parameter may for
example be selected from the following parameters: transaminases
(ASAT, ALAT), GGT, PAL, serum iron, ferritin, transferrin
saturation, adipokine (for example, adiponectin, leptin, resistin),
cytokine (for example, TNFa, IL6, I1_1-(3), HDL cholesterol,
glycaemia, insulinemia, bilirubin, a2macroglobulin, haptoglobin,
apolipoprotein A1, CK18, triglycerides, adiponectin, urea, genetic
polymorphism (for example: PNPLA3, TM6SF2 polymorphism), CRP and/or
leptin.
[0026] In one non-limiting embodiment of the device according to
the invention, the calculating device is constructed and arranged
to communicate with a device for displaying the score. The score
may be displayed in the form of a numerical value, a binary
indicator, a probability or a risk. This embodiment particularly
has the advantage of enabling simplicity of interpretation of the
analysis of the score reflecting a calculated state of liver
damage.
[0027] One aspect of the invention also pertains to a score taking
into account the following physical or even biological parameters:
[0028] a parameter corresponding to inflammation and/or fibrosis,
and [0029] a parameter corresponding to steatosis.
[0030] In one non-limiting embodiment, the score takes into account
at least one parameter of inflammatory activity. The at least one
parameter of inflammatory activity may be selected from the
following parameters: the transaminase value, liver elasticity or
liver viscosity.
[0031] In one non-limiting embodiment, the score takes into account
at least one anthropomorphic parameter of weight, height, waist
circumference, hip circumference, chest girth type or a demographic
parameter of age and sex type.
[0032] In one non-limiting embodiment, the score takes into account
at least one biological parameter.
[0033] The at least one biological parameter may be selected from
the following parameters: transaminases (ASAT, ALAT), GGT, PAL,
serum iron, ferritin, transferrin saturation, adipokine (for
example, adiponectin, leptin, resistin) cytokine (for example,
TNFa, IL6, I1_1-(3), cholesterol, HDL cholesterol, glycaemia,
insulinemia, bilirubin, a2macroglobulin, haptoglobin,
apolipoprotein A1, CK18, triglycerides, adiponectin, urea, genetic
polymorphism (for example: PNPLA3, TM6SF2 polymorphism), CRP and/or
leptin.
[0034] The biological parameter may be a metabolomic parameter.
[0035] In one non-limiting embodiment, the score is calculated
using statistical modelling (also called statistical learning) of
the type logistic regression, decision trees, Bayes classifiers,
random forests, WMS, neural networks, discriminatory analysis,
etc.
BRIEF DESCRIPTION OF THE FIGURES
[0036] Other characteristics and advantages of the invention will
become clear from the description that is given thereof below, for
indicative purposes and in no way limiting, with reference:
[0037] to FIG. 1 illustrating, in a schematic manner, a first
exemplary embodiment of a device for calculating a score reflecting
a state of liver damage integrated in a device constructed and
arranged to measure liver elasticity,
[0038] to FIG. 2 illustrating, in a schematic manner, a second
exemplary embodiment of a device for calculating a score reflecting
a state of liver damage constructed and arranged to communicate
with a remote ultrasound scanner.
[0039] to FIG. 3 illustrating, in a schematic manner, a third
exemplary embodiment of a device for calculating a score reflecting
a state of liver damage constructed and arranged to communicate
with a remote ultrasound scanner.
DESCRIPTION OF THE INVENTION
[0040] FIG. 1 represents a device 100 for calculating a score
reflecting a state of liver damage integrated in a device 200
constructed and arranged to measure liver elasticity.
[0041] In this non-limiting embodiment, the device 200 comprises an
elastography probe 201 provided with an ultrasonic transducer 202
constructed and arranged to transmit and receive ultrasonic waves.
In this embodiment, the elastography probe 201 further comprises
means for generating a shear wave in the liver tissue. Said means
may be an electrodynamic actuator 203 constructed and arranged to
generate a low frequency wave. The device 200 is thus constructed
and arranged to measure physical parameters, for example parameters
which correspond to inflammation and/or fibrosis and parameters
which correspond to steatosis.
[0042] As an example, a parameter linked to fibrosis may be the
elasticity of the liver. This elasticity measurement constitutes a
marker of the pathological state of the liver tissue.
[0043] The parameter corresponding to steatosis may be a
measurement of the attenuation of ultrasonic waves in the liver
tissue. Liver steatosis is an accumulation of fat in the liver. The
measurement of the attenuation of the propagation of ultrasonic
waves thus makes it possible to quantify steatosis.
[0044] The device 100 for calculating a score reflecting a state of
liver damage is constructed and arranged to calculate a score using
a parameter corresponding to inflammation of liver tissue and/or a
parameter corresponding to fibrosis. In the example described,
these parameters are measured using the device 200 together with
the elastography probe 201 and received by the device 100.
[0045] In the example illustrated, the device 200 also comprises a
human-machine interface 204 constructed and arranged to enter
metabolic syndrome marker parameters used to calculate the
score.
[0046] Thus, an operator may enter, via the human-machine interface
204, metabolic syndrome marker parameters. Metabolic syndrome is
taken to mean the association of a series of health problems having
in common poor corporal metabolism, it is a grouping together of
risk factors more or less linked by a common origin, metabolic
targets or mechanisms. This group of parameters may thereby
comprise: HDL cholesterol, triglycerides, glycaemia, arterial
pressure, and/or the waist circumference.
[0047] This human-machine interface 204 is also constructed and
arranged to enter biological parameters used to calculate the
score. These biological parameters may be: transaminases (ALAT,
ASAT), GGT, PAL, serum iron, cholesterol, HDL cholesterol,
glycaemia, insulinemia, bilirubin, a2macroglobulin, haptoglobin,
apolipoprotein A1, CK18, triglycerides, adiponectin, and/or
leptin.
[0048] This human-machine interface 204 is also constructed and
arranged to enter demographic and anthropomorphic parameters used
to calculate the score. These demographic and anthropomorphic
parameters are for example formed by the age, the sex, the height,
the weight, the waist circumference, the hip circumference or the
chest girth of an individual.
[0049] As a function of these different parameters, the calculating
device 100 calculates a score using a logistic regression or any
other scoring method, for example of the type decision trees, Bayes
classifiers, random forests, wide margin separator (WMS) decision
trees, or instead neural networks.
[0050] To this end, the calculating device 100 may be formed by one
or more microprocessors constructed and arranged to execute
sequences of instructions enabling the implementation of the
aforesaid logistic regression or any other scoring method.
[0051] In the example illustrated of FIG. 1, the calculated score
is represented in the form of a binary indicator 205 equal to 1 and
displayed on a screen 206 of the device 200. This binary indicator
205 may be used to advise a patient to consult a specialist. For
example, when the indicator is equal to 1, the patient is diagnosed
as being at risk and requires a more detailed investigation or
additional examinations have to be carried out. In the embodiment
of FIG. 3, the screen 206 is positioned remotely from the
calculating device 100 and the device 200 that comprises the
elastography probe 201.
[0052] In contrast, when the indicator is equal to 0, the patient
does not need to consult a specialist. This indicator may also be
different, it may be implemented in the form of a value.
[0053] In this non-limiting embodiment, the measurements of
physical parameters, the input of other parameters, the calculation
of the score and the display of the score are carried out in the
device 200. Thus, this embodiment particularly has the advantage of
calculating in real time the score (in other words at the place
where the measurements of the physical parameters are carried out),
then displaying the score enabling rapidity of analysis.
[0054] In different non-limiting examples, the device 200 may be
formed by an ultrasound scanner, an MRI, or an MRI implementing
magnetic resonance elastography (MRE).
[0055] In one non-limiting embodiment illustrated in FIG. 2, the
device for calculating a score reflecting a state of liver damage
100 is constructed and arranged to communicate with a remote
ultrasound scanner 300. In other words, the calculating device 100
is remote vis-a-vis the ultrasound scanner 300. Thus, the
measurements are carried out on the ultrasound scanner 300 then
transmitted via a network link 140, for example an Ethernet or
Bluetooth or Wi-Fi type link, to the calculating device 100. It is
also possible to transmit other parameters, for example of
anthropomorphic or demographic type, to the calculating device 100
via a computer 400. Similarly, this computer 400 may communicate
with the calculating device 100 via an Ethernet or Wi-Fi link 150.
The calculating device 100 may be materialised by one or more
processors. Furthermore, the computer may be integrated in the
ultrasound scanner 300.
[0056] In this non-limiting embodiment, the score may be displayed
on the ultrasound scanner 300, on the computer 400 or both.
* * * * *