Beyond Confounders: Addressing Source of Measurement Variability and Error in Shear Wave Elastography
| Status: | Recruiting |
|---|---|
| Conditions: | Gastrointestinal, Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/25/2018 |
| Start Date: | June 29, 2017 |
| End Date: | August 30, 2018 |
| Contact: | Anthony E. Samir, MD, MPH |
| Email: | asamir@mgh.harvard.edu |
| Phone: | 617 643 2009 |
Chronic liver disease is a major problem in the general population and there is an unmet need
to diagnose(and screen) for liver disease with using noninvasive, cost-effective and
sensitive techniques.The investigators hypothesize that variation using ultrasound
elastography for the estimation of stage of liver fibrosis and steatosis in patients with
diffuse liver disease exists due to different methods of measurements, and/or different
systems. The proposed investigation is a cross-sectional study using ultrasound elastography
and fat quantification modalities. The investigators are planning to enroll 30 subjects 18
years old and older in whom diffuse liver disease is suspected, and who have undergone
non-focal liver biopsy in the past 6 months or are scheduled to undergo biopsy within 3
months of enrollment, as part of their routine clinical care. The investigators will use 4
different ultrasound devices with their shear wave elastography and speed of sound functions.
Specific aims;
- Compare shear wave elastography(SWE) measurements from different ultrasound systems;
using histopathology as reference standards.
- Assess intra-operator and inter-operator reliability by measuring variability in
elastography values by two operators on a single system.
- Determine the steatosis effect on liver disease, with using speed of sound(SoS) mode
- Determine the effect of deviations from guidelines(less number of measurements and
measurements during active breath)
to diagnose(and screen) for liver disease with using noninvasive, cost-effective and
sensitive techniques.The investigators hypothesize that variation using ultrasound
elastography for the estimation of stage of liver fibrosis and steatosis in patients with
diffuse liver disease exists due to different methods of measurements, and/or different
systems. The proposed investigation is a cross-sectional study using ultrasound elastography
and fat quantification modalities. The investigators are planning to enroll 30 subjects 18
years old and older in whom diffuse liver disease is suspected, and who have undergone
non-focal liver biopsy in the past 6 months or are scheduled to undergo biopsy within 3
months of enrollment, as part of their routine clinical care. The investigators will use 4
different ultrasound devices with their shear wave elastography and speed of sound functions.
Specific aims;
- Compare shear wave elastography(SWE) measurements from different ultrasound systems;
using histopathology as reference standards.
- Assess intra-operator and inter-operator reliability by measuring variability in
elastography values by two operators on a single system.
- Determine the steatosis effect on liver disease, with using speed of sound(SoS) mode
- Determine the effect of deviations from guidelines(less number of measurements and
measurements during active breath)
Liver disease and cirrhosis are important causes of morbidity and mortality in the United
States and are a major public health problem with 40,000 deaths and more than 1.4 billion
dollars spent on medical services. Hepatic fibrosis is the final common pathway for many
different liver insults and is known to be a dynamic process, which is reversible if
diagnosed early and treated. If untreated, fibrosis eventually progresses to cirrhosis, which
is irreversible. The diagnosis of fibrosis relies on liver biopsy (the gold standard)
however, is an invasive procedure with risks and sampling errors. Indirect biomarkers of
fibrogenesis can measure some of these components to determine categories of fibrosis, with a
sensitivity and specificity of 47% and 90% respectively.It is shown in the literature that,
fat content of liver is related with fibrosis development. Biopsy is accepted as the most
accurate technique to assess liver fat and fibrosis amount.
Fibrotic livers demonstrate increased stiffness, a property that can be measured using
technology named Ultrasound Elastography or sonoelastography (SWE). SWE is performed by
insonating the patient with a low energy, amplitude, and frequency shear wave created by a
vibrating probe. The propagated wave travels faster with increasing fibrosis: the stiffer the
tissue, the faster the shear wave propagates. A pulse-echo ultrasound acquisition allows
measurement of the wave velocity and the results are presented as kilopascals (kPa). Prior
reports have described sensitivity and specificity for liver fibrosis detection of 80% and
97% respectively for SWE. The benefits of SWE are that it is inexpensive, reproducible,
painless, rapid (< 10 min), easy to perform, and can be used for diagnosis, prognosis and
monitoring disease progression. Speed of sound measurement on liver, is demonstrated in
previous studies as a quantitative parameter to assess the lipid profile. However,
significant variations exist as a result of variation of systems, and scanning protocols.
The objective of this study is to compare this variation and study the factors that might
cause these variations.
The proposed investigation is a cross-sectional study using ultrasound elastography and fat
quantification modalities. The investigators are planning to enroll 30 subjects 18 years old
and older in whom diffuse liver disease is suspected, and who have undergone non-focal liver
biopsy in the past 6 months or are scheduled to undergo biopsy within 3 months of enrollment,
as part of their routine clinical care.
All subjects will be required to come to the MGH main campus for 2 study visits within 60
days of each other. In addition, subjects will need to fast for at least 4 hours prior to
study visits
There will be two visits in this study and maximum 60 days time frame between the visits is
anticipated. Two operators will perform the ultrasound examination. Reproducibility and
repeatability of the ultrasound devices will be estimated.
Ultrasound examination including sonoelastography will be performed using four FDA-approved
ultrasound units; (1) Toshiba Aplio500, (2) Siemens S3000, (3) GE LOGIQ E9, (4) Fibroscan.
Both operators will perform;
1. Toshiba APLIO500
• Median Elastograpy (10 measurements) on regular and variable map at a depth(in the
sweet spot- 2cm from capsule and 6.5cm from skin)
2. Siemens S3000
• Median SWE value (10 measurements) at a depth(in the sweet spot- 2cm from capsule and
6.5cm from skin)
3. GE LOCIQ E9
- Median SWE value (10 measurements) at a depth(in the sweet spot- 2cm from capsule
and 6.5cm from skin) Median SWE value with active breath(10measurements) Median SWE
value with less number of acquisitions(3measurements)
- 20 B-mode image acquisitions using variable speed of sound inputs (1400m/sec to
1600m/sec at increments of 10 m/sec) will be obtained.
4. Fibroscan • 10 measurements will be made using the Fibroscans device.
In second visit, all measurements will be repeated with the same operators.
States and are a major public health problem with 40,000 deaths and more than 1.4 billion
dollars spent on medical services. Hepatic fibrosis is the final common pathway for many
different liver insults and is known to be a dynamic process, which is reversible if
diagnosed early and treated. If untreated, fibrosis eventually progresses to cirrhosis, which
is irreversible. The diagnosis of fibrosis relies on liver biopsy (the gold standard)
however, is an invasive procedure with risks and sampling errors. Indirect biomarkers of
fibrogenesis can measure some of these components to determine categories of fibrosis, with a
sensitivity and specificity of 47% and 90% respectively.It is shown in the literature that,
fat content of liver is related with fibrosis development. Biopsy is accepted as the most
accurate technique to assess liver fat and fibrosis amount.
Fibrotic livers demonstrate increased stiffness, a property that can be measured using
technology named Ultrasound Elastography or sonoelastography (SWE). SWE is performed by
insonating the patient with a low energy, amplitude, and frequency shear wave created by a
vibrating probe. The propagated wave travels faster with increasing fibrosis: the stiffer the
tissue, the faster the shear wave propagates. A pulse-echo ultrasound acquisition allows
measurement of the wave velocity and the results are presented as kilopascals (kPa). Prior
reports have described sensitivity and specificity for liver fibrosis detection of 80% and
97% respectively for SWE. The benefits of SWE are that it is inexpensive, reproducible,
painless, rapid (< 10 min), easy to perform, and can be used for diagnosis, prognosis and
monitoring disease progression. Speed of sound measurement on liver, is demonstrated in
previous studies as a quantitative parameter to assess the lipid profile. However,
significant variations exist as a result of variation of systems, and scanning protocols.
The objective of this study is to compare this variation and study the factors that might
cause these variations.
The proposed investigation is a cross-sectional study using ultrasound elastography and fat
quantification modalities. The investigators are planning to enroll 30 subjects 18 years old
and older in whom diffuse liver disease is suspected, and who have undergone non-focal liver
biopsy in the past 6 months or are scheduled to undergo biopsy within 3 months of enrollment,
as part of their routine clinical care.
All subjects will be required to come to the MGH main campus for 2 study visits within 60
days of each other. In addition, subjects will need to fast for at least 4 hours prior to
study visits
There will be two visits in this study and maximum 60 days time frame between the visits is
anticipated. Two operators will perform the ultrasound examination. Reproducibility and
repeatability of the ultrasound devices will be estimated.
Ultrasound examination including sonoelastography will be performed using four FDA-approved
ultrasound units; (1) Toshiba Aplio500, (2) Siemens S3000, (3) GE LOGIQ E9, (4) Fibroscan.
Both operators will perform;
1. Toshiba APLIO500
• Median Elastograpy (10 measurements) on regular and variable map at a depth(in the
sweet spot- 2cm from capsule and 6.5cm from skin)
2. Siemens S3000
• Median SWE value (10 measurements) at a depth(in the sweet spot- 2cm from capsule and
6.5cm from skin)
3. GE LOCIQ E9
- Median SWE value (10 measurements) at a depth(in the sweet spot- 2cm from capsule
and 6.5cm from skin) Median SWE value with active breath(10measurements) Median SWE
value with less number of acquisitions(3measurements)
- 20 B-mode image acquisitions using variable speed of sound inputs (1400m/sec to
1600m/sec at increments of 10 m/sec) will be obtained.
4. Fibroscan • 10 measurements will be made using the Fibroscans device.
In second visit, all measurements will be repeated with the same operators.
Inclusion Criteria:
- Adult Patients
- Men or Woman
- Suspected diffuse liver disease and have had a liver biopsy within the last 6 months
or are scheduled for a liver biopsy in the next 3 months.
- Consent to participate in the study
Exclusion Criteria:
- Pregnancy
- Acute illness/ cognitive impairment resulting in inability to cooperate with
ultrasound
- Patients that do not consent to ultrasound examination
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Anthony E. Samir, MD, MPH
Phone: 617-643-2009
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