An Imaging-based Quantitative Biomarker Assay for NAFLD in Children

An Imaging-based Quantitative Biomarker Assay for Non-alcoholic Fatty Liver Disease (NAFLD) in Children: a Feasibility Study

This study will validate recently developed Magnetic Resonance Imaging (MRI) and Ultrasound (US) based methods for liver fat quantification in children with obesity and healthy range of body mass index (BMI).

Study Overview

• Status: Active, not recruiting
• Conditions: NAFLD; NASH
• Intervention / Treatment: Device: Magnetic Resonance Imaging (MRI); Device: Ultrasound (US)

Detailed Description

The severity of the obesity epidemic in the U.S., particularly in Wisconsin, is alarming, with overall overweight or obesity rates of 35% in children. [Fryar 2020,] Obesity is a major risk factor for several comorbidities, one of the most common being non-alcoholic fatty liver disease (NAFLD, also denoted steatotic liver disease). The inflammatory state known as non-alcoholic steatohepatitis (NASH) may lead to fibrosis and, if left untreated, can lead to cirrhosis, liver failure, and cancer. For these reasons, there is enormous interest in effective interventions for weight loss and reversing NAFLD. A central challenge in the development of new interventions is the need for accurate and precise biomarkers to evaluate hepatic steatosis in children.

This pilot study focuses on demonstrating the feasibility of MRI and US based liver fat quantification in children and addresses technical challenges that may limit the performance of the proposed techniques in the population of interest through the following aims:

• Aim 1: Determine the bias and precision (repeatability) of emerging free-breathing MRI-based liver fat quantification in children with obesity and controls using current breath-held methods as a reference.
• Aim 2: Determine the precision (repeatability and reproducibility) of US-based biomarkers of liver steatosis with a focus on the impact of body wall thickness on the precision of the biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Study Population

1. 12 Children ages 10 - 14 years with BMI in the >95th percentile for age and sex
2. 12 Children ages 10 - 14 years with BMI < 85th percentile and >5th percentile for age and sex.

Description

Inclusion Criteria:

1. Age: 10 - 14years old
2. BMI: Case subjects: BMI>95th percentile for age and sex Healthy BMI volunteers: 5th ≤ BMI < 85th percentile for age and sex

Exclusion Criteria:

1. Children with contraindications to MRI.
2. Children who did not fast (verbally confirmed by children or guardian)
3. Pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Average or low BMI; Children with BMI under the 85th percentile for age and sex	Device: Magnetic Resonance Imaging (MRI); MRI procedures will include a 20-25 minute exam with periodic breath holds. The imaging series will be conducted twice to assess repeatability.; Device: Ultrasound (US); In each ultrasound exam, each participant will be scanned by twice by the same sonographer to evaluate intra-operator variability (repeatability). Each exam will take approximately 60 minutes to complete.
Experimental: High BMI; Children with BMI in the 95th percentile or higher for age and sex	Device: Magnetic Resonance Imaging (MRI); MRI procedures will include a 20-25 minute exam with periodic breath holds. The imaging series will be conducted twice to assess repeatability.; Device: Ultrasound (US); In each ultrasound exam, each participant will be scanned by twice by the same sonographer to evaluate intra-operator variability (repeatability). Each exam will take approximately 60 minutes to complete.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Measured by the Number of Participants Who Successfully Complete the Interventions	Demonstrate the feasibility of MRI- and US-based liver fat quantification in children and address technical challenges that may limit the performance of the proposed techniques in the population of interest.	through study enrollment (up to approximately 14 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI: Bias reported as difference in mean error in Percent Liver Fat measured from free-breathing MRI method and reference breath-held MRI method	To validate and confirm the reliability of a recently developed free-breathing CSE-based PDFF mapping method in children with high and average/low BMI for age and sex, bias is reported. Bias is defined as the mean error in liver PDFF measurements between the new free-breathing MRI method and the reference breath-held MRI method, reported in percentage.	Research visit 1 (up to 14 months)
MRI: Precision measured by Test-Retest of Percent Liver Fat	To validate and confirm the reliability of a recently developed free-breathing CSE-based PDFF mapping method in children with high and average/low BMI for age and sex, precision will be assessed. Precision (test-retest repeatability) for each acquisition method and within each liver segment will be calculated through the coefficient of repeatability.	Research visit 1 (up to 14 months)
Quantitative US: Repeatability of US Measurements (same sonographer) - Attenuation Coefficient (dB/cm-MHz)	Biomarkers of liver steatosis are measured and analyzed for their repeatability by the same sonographer in the high and healthy BMI cohorts.	Research visit 1 (up to 14 months)
Quantitative US: Repeatability of US Measurements (same sonographer) - Backscatter Coefficient (1/cm*sr)	Biomarkers of liver steatosis are measured and analyzed for their repeatability by the same sonographer in the high and healthy BMI cohorts.	Research visit 1 (up to 14 months)
Quantitative US: Reproducibility of US Measurements (different sonographers) - Attenuation Coefficient (dB/cm-MHz)	Biomarkers of liver steatosis are measured and analyzed for their reproducibility between different sonographers in the healthy BMI cohort.	Research visit 1 (up to 14 months)
Quantitative US: Reproducibility of US Measurements (different sonographers) - Backscatter Coefficient (1/cm*sr)	Biomarkers of liver steatosis are measured and analyzed for their reproducibility between different sonographers in the healthy BMI cohort.	Research visit 1 (up to 14 months)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Diego Hernando, PhD, University of Wisconsin, Madison; Principal Investigator: Ivan Rosado-Mendez, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): June 20, 2025
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging; Ultrasonography
• Other Study ID Numbers: 2023-1494; A534800 (Other Identifier: UW Madison); Protocol Version 12/19/24 (Other Identifier: UW Madison)

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