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: 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, 2) Measure the accuracy and precision of the new FB-MRI/MRE for quantifying these biomarkers, 3) Compare the FB-MRI/MRE biomarkers to liver biopsy in children with liver disease, and 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.

Public Health Relevance

Childhood obesity and non-alcoholic fatty liver disease (NAFLD) are global health problems. This research project aims to develop, evaluate, validate, and test new rapid free-breathing abdominal magnetic resonance imaging and elastography (MRI and MRE) technologies that can accurately quantify body composition and liver fat and fibrosis in children of all ages without the need for ionizing radiation, sedation, breath holding, or liver biopsy. The novel free- breathing MRI and MRE technology can then be used to improve early diagnosis, test preventative strategies and therapeutics, and investigate the early beginnings of obesity, NAFLD, and other pediatric liver diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Clinical Translational Imaging Science Study Section (CTIS)
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Doo, Edward
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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