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

胰腺外分泌功能不全（EPI）发生在胰腺不能分泌足够消化的酶和液体时。急性复发性胰腺炎（阿普）和慢性胰腺炎（CP）在儿童中越来越多地被认识到，并且是EPI的一个越来越重要的原因。EPI导致吸收不良，这可能导致儿童营养不良和生长障碍。如果EPI可以被识别甚至预测，其有害作用可以通过胰酶替代来逆转。 公认的CP诊断标准依赖于主观影像学检查结果，这些结果受到观察者之间分歧的限制，并且EPI的准确、无创诊断即使不是不可能的，也是具有挑战性的。目前EPI的诊断需要麻醉下内窥镜检查（ePFT）形式的侵入性测试。因此，对儿童胰腺健康和功能的经验证的非侵入性测量存在未满足的需求。定量MRI技术，包括MR胰腺功能检测（MR-PFT）、胰腺实质体积和实质信号标测，有望成为胰腺健康和功能的非侵入性标志物。本研究的总体目的是确定儿童非侵入性、非造影剂、定量MRI测量与胰腺健康和功能的既定测量（包括通过内镜PFT [ePFT]参考标准诊断的EPI）之间的相关性。 我们建议测试多种非侵入性，非对比，定量MRI技术的能力，以确定EPI和阶段胰腺炎（急性胰腺炎阿普CP）的儿童。我们的中心假设是，研究中的定量MRI技术将具有胰腺健康变化的诊断性能，允许检测EPI和定量胰腺炎的变化。 我们的初步研究表明，我们可以成功地应用定量MRI技术，包括MR-PFT，体积成像和实质信号映射在儿童。我们已经定义了这些MRI测量的正常值，初步数据表明，来自正常儿童的阈值可以非侵入性地识别EPI具有良好的灵敏度。本申请旨在：1）评价MRI标记物对EPI的诊断性能，作为儿童胰腺健康的指标，2）开发胰腺定量MRI的处理管道，3）定义可以区分胰腺炎阶段和识别早期CP的定量MRI标记物。 这项研究的成功完成将产生关于胰腺炎非侵入性分期和EPI诊断的独特的、有价值的数据。这项研究将产生协议和处理管道，以促进未来的临床决策和研究使用MRI作为EPI和胰腺疾病的非侵入性测试。这项研究的数据将为未来儿童胰腺炎和EPI的非侵入性成像研究奠定基础。

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.