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

October 5, 2019 updated by: Anthony Samir, Massachusetts General Hospital

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 30 Patients with known liver biopsy results
Patients with chronic liver disease with known biopsy results
Device: Sonographic SWE measurements with 4 different ultrasound systems
Sonographic Shear wave elastography will be performed to quantify liver fibrosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Deviations From Suggested Guidelines- Any Effect on Agreement
Time Frame: Visit 1 and Visit 2, an average of 2.5 hours for each visit
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
Interoperator and Intraoperator Agreement in m/s and kPA Units
Time Frame: Visit 1 and Visit 2, an average of 2.5 hours for each visit
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Siemens Medical Solutions
Radiological Society of North America
Canon Medical Systems, USA

Investigators

  • Principal Investigator: Anthony E. Samir, MD, MPH, Associate Medical Director, Ultrasound Imaging Services

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 29, 2017

Primary Completion (ACTUAL)

August 14, 2018

Study Completion (ACTUAL)

August 30, 2018

Study Registration Dates

First Submitted

November 6, 2017

First Submitted That Met QC Criteria

November 13, 2017

First Posted (ACTUAL)

November 17, 2017

Study Record Updates

Last Update Posted (ACTUAL)

October 28, 2019

Last Update Submitted That Met QC Criteria

October 5, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P000940

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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