Correlation of Ultrasound Based Measurements of Liver Stiffness and Steatosis With MRI

• ClinicalTrials.gov Identifier: NCT03342703
• Recruitment Status: Unknown
• First Posted: November 17, 2017
• Last Update Posted: September 7, 2018
• Sponsor: Stanford University
• Information provided by (Responsible Party): Aya Kamaya, Stanford University

Study Description

Brief Summary:

The investigators will assess the ability of ultrasound (US) to measure liver stiffness (cirrhosis) and liver fat content (steatosis).

Condition or disease	Intervention/treatment
Liver Steatoses; Liver Cirrhosis	Diagnostic Test: Ultrasound

Detailed Description:

Non-invasive monitoring of liver fibrosis using magnetic resonance imaging (MRI) can help determine which patients will most benefit from interventional therapies to help reverse the condition. Similarly, quantitative assessment of liver fat content using MRI can assist physicians in identifying patients at risk for hepatic steatohepatitis.

Due to the widespread dissemination of US machines and their relative lower cost compared to other imaging modalities, e.g. MRI, the ability of US to assess these parameters widens diagnostic availability.

Patients who have undergone an MRI exam to assess liver stiffness (cirrhosis) and/or liver fat content (steatosis) will be asked to undergo an US exam to assess the same parameters. The cirrhosis and steatosis measurements obtained from both exams will be compared. If US-based measurements of liver stiffness and/or liver fat content are shown to be reproducible and accurate when compared to MRI values (will be used as the gold standard), US may become the first-line diagnostic test for these liver conditions.

Study Design

• Study Type: Observational
• Estimated Enrollment: 120 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Correlation of Ultrasound Based Measurements of Liver Stiffness and Steatosis With MRI
• Actual Study Start Date: November 4, 2016
• Estimated Primary Completion Date: August 1, 2020
• Estimated Study Completion Date: August 1, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Patients with Liver Fibrosis Measurement; Group1: Patients will undergo an Ultrasound to correlate fibrosis measurements obtained using standard-of-care MRI.	Diagnostic Test: Ultrasound; Patients will undergo a standard liver US protocol for approximately 15 minutes.; Other Names: US elastography; US fat quantification
Patients with Liver Steatosis Measurement; Group 2: Patients will undergo an Ultrasound to correlate steatosis measurements obtained using standard-of-care MRI.	Diagnostic Test: Ultrasound; Patients will undergo a standard liver US protocol for approximately 15 minutes.; Other Names: US elastography; US fat quantification

Outcome Measures

Primary Outcome Measures :

1. Discriminatory value (AUC) of US in assessing liver stiffness [ Time Frame: an estimated time of 30 minutes ]

   Discriminatory value (the ability of the test to diagnose disease from healthy) will be calculated using nonparametric receiver operating characteristic (ROC) curve analysis. Sensitivity (i.e. true positive rate: the ability of a test to correctly identify patients with the disease being investigated) is plotted on the y axis and 1-specificity (i.e. false positive rate: the test incorrectly identifies patients who do not have the disease being investigated as having the disease) will be plotted on the x-axis. Cutoff points of US liver stiffness values will be chosen to create the graph of sensitivity versus 1-Specificity, i.e. the ROC curve, and the area under the curve (AUC) is used to determine how well US discriminates patients with liver stiffness from patients without liver stiffness.

   The closer the AUC gets to 1, the more discriminatory the test. An AUC=0.5 is a test that is right 50% of the time, and is no better than flipping a coin.

2. Discriminatory value (AUC) of US in assessing liver fat content [ Time Frame: an estimated average of 30 minutes ]

   Discriminatory value (the ability of the test to diagnose disease from healthy) will be calculated using nonparametric receiver operating characteristic (ROC) curve analysis. Sensitivity (i.e. true positive rate: the ability of a test to correctly identify patients with the disease being investigated) is plotted on the y axis and 1-specificity (i.e. false positive rate: the test incorrectly identifies patients who do not have the disease being investigated as having the disease) will be plotted on the x-axis. Cutoff points of US liver fat content values will be chosen to create the graph of sensitivity versus 1-specificity, i.e. the ROC curve, and the area under the curve (AUC) is used to determine how well US discriminates patients with liver fat content from patients without liver fat content.

   The closer the AUC gets to 1, the more discriminatory the test. An AUC=0.5 is a test that is right 50% of the time, and is no better than flipping a coin.

Secondary Outcome Measures :

1. US Elastography Stiffness [ Time Frame: an estimated average of 30 minutes ]

   MRI tissue stiffness is reported in shear modulus (S), while US uses Young's modulus (Y). Since Y = 2*(1+m)*S, where m is the Poisson's ratio for the material, and since that ratio is between 0.49 and 0.50 for tissue, the US measurements should be three times that of the MRI ones. In particular, treating the MRI measurements as the reference, theory predicts a linear relationship:

   Y = 0 + 3*S

   which can be tested with a linear regression model. The most straightforward means is by calculating the expected Young's modulus values for US from the MR measurements, and regressing them on the observed US measurements.

   Both US and MRI values are given below.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Subjects who have or are scheduled to undergo a routine clinical MRI at Stanford that included assessment of liver stiffness or liver fat content will be identified using the radiology schedule.

Criteria

Inclusion Criteria:

1. participants who have a clinical indication for a standard of care MRI exam that included assessment of the liver
2. participant is at least 18 years of age

Exclusion Criteria:

1. Participants unable to take part in the decision making process on whether to consent to the trial
2. Patients with previous chemoembolization or other focal liver therapies to the liver (* NOTE: for liver transplant patients, this criterion is only applicable to the transplanted liver)

Contacts and Locations

Contacts

Contact: Andrea Otte; anotte@stanford.edu

Locations

United States, California

Stanford University Hospital; Recruiting

Stanford, California, United States, 94305

Contact: Andrea Otte anotte@stanford.edu

Sub-Investigator: Andreas Loening, MD

Principal Investigator: Aya Kamaya, MD

Stanford University; Recruiting

Stanford, California, United States, 94305

Contact: Andreas Loening, MD 650-725-4936 loening@stanford.edu

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Aya Kamaya, MD; Stanford University
• Principal Investigator: Andreas Loening, MD; Stanford University

More Information

• Responsible Party: Aya Kamaya, Associate Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT03342703
• Other Study ID Numbers: 38649
• First Posted: November 17, 2017
• Last Update Posted: September 7, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Liver Cirrhosis; Fatty Liver; Liver Diseases; Digestive System Diseases