Multi-parametric quantitative MRI for assessment of pancreas health in children

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Exocrine pancreatic insufficiency (EPI) occurs when the pancreas is unable to secrete enzymes and fluids adequate for digestion. Acute recurrent (ARP) and chronic pancreatitis (CP) are increasingly recognized in children and are an increasingly important cause of EPI. EPI results in malabsorption which can lead to malnutrition and growth failure in children. If EPI can be recognized or even predicted, its deleterious effects can be reversed with pancreatic enzyme replacement. Accepted diagnostic criteria for CP rely on subjective imaging findings which are limited by interobserver disagreement and accurate, non-invasive diagnosis of EPI is challenging, if not impossible. Currently diagnosis of EPI requires invasive testing in the form of endoscopy under anesthesia (ePFTs). Thus, there is an unmet need for validated, non-invasive measures of pancreatic health and function in children. Quantitative MRI techniques, including MR pancreatic function testing (MR-PFTs), pancreas parenchymal volume, and parenchymal signal mapping are showing promise as non-invasive markers of pancreatic health and function. The overall aim of this study is to define associations between non-invasive, non-contrast, quantitative MRI measures and established measures of pancreas health and function (including EPI diagnosed by a reference standard of endoscopic PFTs [ePFTs]) in children. We propose to test multiple non-invasive, non-contrast, quantitative MRI techniques for their ability to identify EPI and stage pancreatitis (acute pancreatitis to ARP to CP) in children. Our central hypothesis is that the quantitative MRI techniques under study will have diagnostic performance for changes in pancreatic health, allowing detection of EPI and quantification of changes of pancreatitis. Our preliminary studies show that we can successfully apply quantitative MRI techniques, inclusive of MR-PFTs, volumetric imaging, and parenchymal signal mapping in children. We have defined normal values for these MRI measures with preliminary data suggesting that threshold values derived from normal children can non-invasively identify EPI with excellent sensitivity. This application aims to: 1) Evaluate the diagnostic performance of MRI markers for EPI as an indicator of pancreas health in children, 2) Develop processing pipelines for quantitative MRI of the pancreas, and 3) Define quantitative MRI markers that can distinguish stages of pancreatitis and identify early CP. The successful completion of this study will generate unique, valuable data regarding non-invasive staging of pancreatitis and diagnosis of EPI. This study will generate protocols and processing pipelines to facilitate future clinical decision making and research use of MRI as a non-invasive test for EPI and pancreatic disease. Data from this study will set the stage for future studies of non-invasive imaging of pancreatitis and EPI in children.