imaging biomarkers of pancreatic function and disease

Conditions: Pancreatitis; Diabetes Mellitus

Summary: this study seeks to understand the performance of mri to characterize pancreatitis and predict chronic complications (endocrine and exocrine) of pancreatitis. through multiple aims, the investigators will benchmark mri against relevant reference standards (e.g. endoscopic pancreatic function tests, laboratory data). the investigators will also characterize repeatability of the imaging findings and will work to develop methods to simplify and automate analysis of the mri images. research interventions depend on the aim(s) participants enroll in but include: endoscopic pancreatic function testing (added on to clinically indicated upper gi endoscopy), blood tests, stool tests, gene sequencing, and survey completion. all participants will undergo research mri examinations, a subset of which will include administration of intravenous secretin.

pancreatitis can be acute \[ap\], acute recurrent \[arp\] (defined as two discrete attacks with interval resolution), or chronic \[cp\]. adult studies show that up to 40% of patients develop abnormal glucose metabolism after a single attack of ap, with a 2.5x increased risk of diabetes. cp is defined, in part, by the presence of established endocrine (diabetes) or exocrine pancreatic insufficiency \[epi\]. currently, it is not possible to non-invasively diagnose or predict development of pancreatitis-related endocrine or exocrine insufficiency. the investigator's data has shown that cftr gene variants play a significant role in progression to diabetes post first attack ap. existing literature suggests that imaging findings such as decreased pancreas volume are associated with diabetes, but this has not been systematically studied in children. epi, defined as insufficient secretion of digestive enzymes and fluid by the pancreas, can have significant effects in childhood including malnutrition, osteoporosis, and growth failure. if diagnosed early, epi can be treated with pancreatic enzyme replacement, improving nutrition and stabilizing growth. unfortunately, diagnosing epi early and accurately is a challenge in children and it is currently not possible to predict progression to cp or development of epi. magnetic resonance imaging (mri) is a powerful, non-invasive technique, capable of characterizing pancreatic disease. quantitative non-contrast mri techniques are attractive as potential markers of pancreatic disease but they have not been validated for diagnosis or prediction of diabetes or epi in children and they have not been explored for staging of pediatric pancreatitis. the overall goals of this study are to: 1. define associations between non-invasive, quantitative mri measures and established measures of pancreas health and function including diabetes and epi in children 2. identify clinical, genetic and imaging-related factors that predict progression to diabetes in children with pancreatitis.

Eligibility criteria:
aim 1- patient group: inclusion criteria: * age 5 to \<21 years * scheduled for clinically-indicated gastrointestinal endoscopy * clinical diagnosis or suspicion of exocrine pancreatic insufficiency exclusion criteria: * complete fatty replacement of pancreas on prior imaging * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy control group: inclusion criteria: * age 5 to \<21 years * scheduled for clinically-indicated gastrointestinal endoscopy exclusion criteria: * sweat chloride \>60 mmol/l * clinical diagnosis of gastrointestinal pathology * clinical diagnosis or history of pancreatic disease * complete fatty replacement of pancreas on prior imaging * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy aim 2- acute pancreatitis group: inclusion criteria: * age 5 to \<21 years * clinically documented episode of acute pancreatitis exclusion criteria: * more than one episode of acute pancreatitis * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * pregnancy acute recurrent pancreatitis group: inclusion criteria: * age 5 to \<21 years * clinical diagnosis of acute recurrent pancreatitis exclusion criteria: * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * pregnancy pancreatitis-related diabetes group: inclusion criteria: * age 5 to \<21 years * clinical diagnosis of pancreatitis-related diabetes exclusion criteria: * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * pregnancy aim 3- control group: inclusion criteria: • age 5 to \<21 years exclusion criteria: * sweat chloride \>60 mmol/l * clinical diagnosis of gastrointestinal pathology * clinical diagnosis or history of pancreatic disease, including acute pancreatitis * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy acute pancreatitis group: inclusion criteria: * age 5 to \<21 years * clinically documented episode of acute pancreatitis exclusion criteria: * more than one episode of acute pancreatitis * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy acute recurrent pancreatitis group: inclusion criteria: * age 5 to \<21 years * clinical diagnosis of acute recurrent pancreatitis with no evidence of cp or epi exclusion criteria: * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy chronic pancreatitis group: inclusion criteria: * age 5 to \<21 years * clinical diagnosis of chronic pancreatitis exclusion criteria: * current acute pancreatitis or acute pancreatitis less than 30 days prior to research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy aim 4- inclusion criteria: * age 5 to \<21 years * completed research mri under aims 1 or 3 of this study exclusion criteria: * failed/unable to complete first research mri under aims 1 or 3 * episode of acute pancreatitis since first research mri * current acute pancreatitis * any gastrointestinal surgery or pancreas intervention (e.g. ercp) since first research mri * need for sedation for mri * contraindication to mri (implanted metal hardware) * allergy to secretin * pregnancy aim 5- inclusion criteria: • mri performed at cchmc exclusion criteria: * severe image artifact compromising image quality (judgement of study team) * age \>21 years

Keywords: mri