PROJECT SUMMARY/ABSTRACT One of the defined objectives of the consortium for the study of Chronic Pancreatitis (CP), Diabetes and Pancreatic Cancer is to propose studies evaluating non-invasive methods to detect and quantify pancreatic fibrosis. Characteristic features of CP may be absent on standard imaging studies. Preliminary data suggest that certain features on Magnetic Resonance Imaging (MRI) not currently used in clinical practice (T1 relaxation time, extracellular volume [ECV] fraction, T1-weighted gradient echo signal intensity ratio [SIR], diffusion-weighted imaging [DWI] and apparent diffusion coefficient [ADC]) are useful for the diagnosis of CP. However, limited data exist in normal subjects or those with definite CP. We hypothesize that MRI can serve as a valuable non- invasive tool to detect CP, even in the early stages of the disease. We propose the following specific aims (SA) to meet this objective, with all patients to be recruited from the consortium’s “PROCEED” study. SA#1: As the primary endpoint, we will evaluate the role of T1 relaxation properties of the pancreatic parenchyma on T1 mapping in the assessment of CP. This study will be the first to measure the normal T1 relaxation time of the pancreas in no pancreas disease controls. As secondary endpoints, we will evaluate T1-weighted gradient echo SIR, ECV fraction, arterio-venous enhancement ratio, ADC, MR elastography, volume/atrophy, pancreatic steatosis, ductal features (narrowing/stricture, dilation, filling defects, side branch dilation) and pancreatic exocrine output after secretin stimulation. This will be the first prospective study to evaluate ECV fraction, and the most comprehensive study performed in well-phenotyped groups of patients for pancreatic MR elastography and other imaging features. SA#2: We will combine the results from the primary and secondary endpoints to generate a composite scoring system. We will demonstrate that an increased number of features will correlate with a diagnosis of advanced or definite CP with higher sensitivityand specificity. Furthermore, we anticipate that cumulative MRI features may allow the diagnosis of early CP and serve as a surrogate marker for the quantification of pancreatic fibrosis. Lastly, as an exploratory aim, we will obtain pilot data in 60 patients with suspected CP, evaluating the same techniques, parameters, and endpoints as in SA#1 and #2. These data will allow for sample size calculation for a future larger study evaluating the role of MRI in suspected vs. definite CP. We propose that MRI may be used as a biomarker to assess disease progression, utilizing a subset of patients who undergo follow-up MR evaluation.