Quantifying Body Composition and Liver Disease in Children Using Free-Breathing MRI and MRE

Recruiting

• Conditions: NASH - Nonalcoholic Steatohepatitis; NAFLD
• Interventions: Diagnostic Test: Magnetic resonance imaging (MRI); Diagnostic Test: Magnetic resonance elastography (MRE); Device: Prototype MRE soft flexible passive transducer paddle

• Registration Number: NCT04591106
• Lead Sponsor: University of California, Los Angeles

Brief Summary

Magnetic resonance imaging (MRI) is used to measure liver fat content and fatty tissues in the body, and magnetic resonance elastography (MRE) is used to measure liver stiffness. The information from MRI and MRE are used to understand risk factors and diagnose liver diseases, such as fatty liver disease and liver fibrosis. However, current MRI and MRE scans need to be performed during a breath-hold, which may be challenging or impossible in children and infants. The goal of this research project is to develop and evaluate new free-breathing MRI and MRE technology to improve the comfort and diagnostic accuracy for children and infants.

Detailed Description

More than 13.7 million children in the U.S. are obese, and all are at high risk for non-alcoholic fatty liver disease (NAFLD), which can lead to fibrosis and progress to liver failure. NAFLD is the most common chronic pediatric liver disease and number one indication for liver transplant in young adults. Accurate assessments of visceral adipose tissue and hepatic fat and fibrosis are critical to the understanding, early diagnosis, and evaluation of new treatments for pediatric obesity and NAFLD. However, there is a lack of child-appropriate technologies to quantify visceral adipose tissue and hepatic fat and fibrosis. Conventional imaging techniques for body composition involve radiation and do not measure individual adipose tissue compartments. Although liver biopsy is the gold standard for diagnosis, this procedure is invasive, requires anesthesia and has complications. Moreover, biopsy findings can be non-specific and suffer from sampling bias and interpretation variability.

Magnetic resonance imaging and elastography (MRI and MRE) are promising non-invasive technologies. MRI quantifies visceral adipose tissue and hepatic fat. MRE quantifies hepatic fibrosis. MRI and MRE do not require ionizing radiation or biopsy. However, current MRI/MRE technology is not appropriate for most children and infants because it requires breath-holding to limit abdominal motion. In young children and infants, breath-holding is not possible. Even in children who can breath-hold, inconsistency and reduced capacity in breath-holding leads to long scan times, corrupted images, failed scans, and unreliable results. Although sedation can facilitate breath-holding, it is associated with negative side effects. As a result, current MRI/MRE technologies typically exclude many children.

To overcome these limitations, the research team created new free-breathing (FB) 3D stack-of-radial MRI technology to quantify visceral adipose tissue and hepatic fat in children and infants. The research team has also developed new 2D radial FB-MRE technology to quantify hepatic fibrosis in children. The objectives of this project are to further develop and evaluate FB-MRI/MRE. The research team will reduce FB-MRI/MRE scan times while maintaining high image quality, demonstrate a high level of accuracy and precision, validate FB-MRI/MRE results against biopsy, and test FB-MRI in a population that cannot breath-hold. The research team will leverage innovations in simultaneous multi-slice imaging, sparsity-constrained tensor image reconstruction, and self-navigation to investigate four aims:

Aim 1. Develop new radial FB-MRI/MRE technologies that quantify visceral adipose tissue and hepatic fat and fibrosis with rapid scan times (1-2 min) and minimal motion artifacts,

Aim 2. Measure the accuracy and precision of the new FB-MRI/MRE for quantifying these biomarkers,

Aim 3. Compare the FB-MRI/MRE biomarkers to liver biopsy in children with liver disease,

Aim 4. Test new FB-MRI technology in infants.

The innovative radial FB-MRI/MRE technology will reliably quantify body composition and liver disease in children and infants. In turn, FB-MRI/MRE will improve the early diagnosis, treatment monitoring, and understanding and management of pediatric obesity, NAFLD, and other liver diseases.

Study Timeline

• Study First Submitted: 2020-10-13
• Study First Submitted QC: 2020-10-15
• Study First Posted: 2020-10-19
• Study Start: 2021-02-17
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-17
• Last Update Posted: 2023-11-21
• Primary Completion: 2024-10-15
• Study Completion: 2024-10-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

Not provided

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Exclusion Criteria

• contra-indications to MRI/MRE
• inability to perform breath-holding

Study 3 (Aim 4):

Inclusion criteria for the cohort of infants at risk for future obesity and NAFLD:

• 1 week-6 months of age
• greater than or equal to 35 weeks gestational age
• born to a mother with gestational diabetes and whose pre-pregnancy body mass index >=25 kg/m2
• mother must provide consent to participate in the study

Inclusion criteria for the healthy cohort:

• 1 week-6 months of age
• greater than or equal to 35 weeks gestational age
• appropriate for gestational age birth weight
• born to a mother with a pre-pregnancy body mass index <25 kg/m2 and without any major co-morbid conditions (gestational diabetes, pregnancy-induced hypertension, etc.)
• admitted to the newborn nursery after birth
• mother must provide consent to participate in the study

Exclusion criteria for both cohorts:

• known liver disease and/or infection, major congenital anomalies, inborn error of metabolism
• any contraindications for an MRI exam

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group 1	Magnetic resonance imaging (MRI)	50 healthy subjects and 50 subjects with NAFLD between ages of 6-17 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 1	Magnetic resonance elastography (MRE)	50 healthy subjects and 50 subjects with NAFLD between ages of 6-17 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 2	Magnetic resonance imaging (MRI)	60 subjects with Liver Disease and Fibrosis between ages of 1 month - 40 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 2	Magnetic resonance elastography (MRE)	60 subjects with Liver Disease and Fibrosis between ages of 1 month - 40 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 1	Prototype MRE soft flexible passive transducer paddle	50 healthy subjects and 50 subjects with NAFLD between ages of 6-17 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 2	Prototype MRE soft flexible passive transducer paddle	60 subjects with Liver Disease and Fibrosis between ages of 1 month - 40 years old. Each subject will receive 1 MRI/MRE exam. The MRE portion will be performed by placing a paddle on the belly that will produce gentle vibrations.
Group 3	Magnetic resonance imaging (MRI)	15 healthy infants between 1 week - 6 months old and their mothers; 15 at-risk infants (mother had gestational diabetes) between 1 week - 6 months old and their mothers. Each infant will receive 1 MRI scan.

Primary Outcome Measures

Name	Time	Method
Liver Proton Density Fat Fraction (PDFF) by MRI	4 years	Liver proton density fat fraction (PDFF; 0 to 100%) is an MRI based measurement of liver fat content. The liver PDFF measured by the new free-breathing MRI technique will be compared with standard breath-holding MRI in terms of the concordance correlation coefficient. The repeatability of liver PDFF will be measured in terms of the coefficient of variation between two scans. In addition, the diagnostic performance of MRI liver PDFF to detect liver fat will be validated against liver biopsy.
Abdominal Visceral Adipose Tissue (VAT) Volume by MRI	4 years	Visceral adipose tissue (VAT) volume (cm3) in the abdomen is an MRI based measurement of body composition. The VAT volume measured by the new free-breathing MRI technique will be compared with standard breath-holding MRI in terms of the concordance correlation coefficient. The repeatability of VAT volume will be measured in terms of the coefficient of variation between two scans.
Liver Tissue Stiffness by MRE	4 years	Liver tissue stiffness (kPa) measured by MRE correlates with liver fibrosis. The liver tissue stiffness measured by the new free-breathing MRE technique will be compared with standard breath-holding MRE in terms of the concordance correlation coefficient. The repeatability of liver tissue stiffness will be measured in terms of the coefficient of variation between two scans. In addition, the diagnostic performance of MRE liver tissue stiffness to detect liver fibrosis will be validated against liver biopsy.

Trial Locations

Locations (1)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States