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

当胰腺不能分泌足以消化的酶和液体时，就会发生外分泌胰腺功能不全(EPI)。急性复发性(ARP)和慢性胰腺炎(CP)在儿童中得到越来越多的认识，并且是EPI的一个日益重要的原因。EPI导致吸收不良，可能导致儿童营养不良和生长障碍。如果EPI能够被识别甚至预测，它的有害影响可以通过胰酶替代来逆转。 公认的CP诊断标准依赖于主观的影像表现，而主观的影像表现受到观察者之间的分歧的限制，而准确的、非侵入性的EPI诊断是具有挑战性的，如果不是不可能的话。目前诊断EPI需要以麻醉下内窥镜检查(EPFTs)的形式进行侵入性测试。因此，对儿童胰腺健康和功能的有效、非侵入性测量的需求尚未得到满足。包括MR胰腺功能测试(MR-PFTs)、胰腺实质体积和实质信号标测在内的定量MRI技术被认为是反映胰腺健康和功能的无创性指标。这项研究的总体目标是确定非侵入性、非对比、定量MRI测量与儿童胰腺健康和功能(包括由内窥镜PFTs[ePFTs]参考标准诊断的EPI)之间的关联。 我们建议测试多种非侵入性、非对比剂、定量MRI技术对儿童胰腺炎(急性胰腺炎到急性胰腺炎再到慢性胰腺炎)的识别和分期的能力。我们的中心假设是，正在研究的定量MRI技术将对胰腺健康变化具有诊断性能，允许检测EPI和量化胰腺炎的变化。 我们的初步研究表明，我们可以成功地将定量MRI技术应用于儿童，包括MR-PFT、体积成像和实质信号标测。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无创性地以极高的灵敏度识别外周静脉感染。这一应用的目的是：1)评估作为儿童胰腺健康指标的EPI的MRI标志物的诊断性能；2)开发胰腺定量MRI的处理流程；3)定义能够区分胰腺炎分期和识别早期CP的定量MRI标志物。 这项研究的成功完成将产生关于胰腺炎的非侵入性分期和外周感染诊断的独特的、有价值的数据。这项研究将产生方案和处理管道，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外周感染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.