d detect PanIN. Materials and Methods DTI was explored for the detection and characterization of PanIN in genetically engineered mice (KC, KPC). Following in vivo DTI, ex vivo ultrahigh-field (16.4 T) MR microscopy using DTI, T2* was performed with histological validation. Sources of MR contrasts and histological features were investigated, including histological scoring for disease burden (lesion span) and severity (adjusted score). To test if findings in mice can be translated to humans, human pancreas specimens were imaged. Results DTI detected PanIN and pancreatic ductal adenocarcinoma in vivo (6 KPC, 4 KC, 6 controls) with high discriminative ability: fractional anisotropy (FA) and radial diffusivity with area under the curve = 0.983 (95% confidence interval: 0.932–1.000); mean diffusivity and axial diffusivity (AD) with area under the curve = 1 (95% confidence interval: 1.000–1.000). MR microscopy with histological correlation (20 KC/KPC; 5 controls) revealed that sources of MR contrasts likely arise from microarchitectural signatures: high FA, AD in fibrotic areas surrounding lesions, high diffusivities within cysts, and high T2* within lesions' stroma. The strongest histological correlations for lesion span and adjusted score were obtained with AD (R = 0.708, P < 0.001; R = 0.789, P < 0.001, respectively). Ex vivo observations in 5 human pancreases matched our findings in mice, revealing substantial contrast between PanIN and normal pancreas. Conclusions DTI and T2* are useful for detecting and characterizing PanIN in genetically engineered mice and in the human pancreas, especially with AD and FA. These are encouraging findings for future clinical applications of pancreatic imaging....