Beyond Confounders: Addressing Source of Measurement Variability and Error in Shear Wave Elastography

Liver Diseases Clinical Trial

Official title:

Beyond Confounders: Addressing Source of Measurement Variability and Error in Shear Wave Elastography

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03342560
• Other study ID #: 2017P000940
• Status: Completed
• Phase: N/A
• Start date: June 29, 2017
• Est. completion date: August 30, 2018

Study information

• Verified date: October 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 effect of deviations from guidelines(less number of measurements and measurements during active breath)

Description:

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.

The objective of this study is to compare the variation in elastography values and study the factors that might cause these variations.

The proposed investigation is a cross-sectional study using ultrasound elastography. 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; Both operators will perform;

• Median Elastograpy (10 measurements) on regular and variable map at a depth(in the area between 2cm from capsule and 6.5cm from skin)

• Median SWE value with active/free breath(10measurements)

• Median SWE value with less number of acquisitions(3measurements)

These measurements will be collected in subgroups using specific systems. In second visit, all measurements will be repeated with the same operators.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 30, 2018
• Est. primary completion date: August 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Diseases
• Liver Fibrosis

Intervention

Device:
• Sonographic SWE measurements with 4 different ultrasound systems
Sonographic Shear wave elastography will be performed to quantify liver fibrosis

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Canon Medical Systems, Radiological Society of North America, Siemens Medical Solutions

Country where clinical trial is conducted

United States, 

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Deviations From Suggested Guidelines- Any Effect on Agreement	We collected guideline suggested shear wave elastography measurements from 20 patients. Guidelines suggest collecting 1) 10 measurements, 2) Asking patient to hold breath during the measurements. As a deviation from guideline suggestions, we collected measurements during free breath movements without asking patient to hold breath. As a deviation from the guideline suggestions, fewer number of measurements (3 measurements) were collected with asking the patient to hold breath during the measurements. All measurements were collected using one type of ultrasound system. All measurements were collected by 2 operators in 2 visits.	Visit 1 and Visit 2, an average of 2.5 hours for each visit
Primary	Interoperator and Intraoperator Agreement in m/s and kPA Units	In 20 patients we collected 10 shear wave elastography measurements in m/s and kPA units. Using one of the available ultrasound systems, 2 operators collected these measurements in 2 visits. Theoretically, m/s to kPA conversion can be made using an equation. However, some systems provide opportunity to get data in both units. Although algebraically m/s and kPA can be converted to each other, we found some minor differences in terms of inter-operator and intra-operator agreement.	Visit 1 and Visit 2, an average of 2.5 hours for each visit