DWI Metrics Differentiating Benign Intraductal Papillary Mucinous Neoplasms from Invasive Pancreatic Cancer: A Study in GEM Models.

Abstract

Simple SummaryIntraductal papillary mucinous neoplasms (IPMN) are common premalignant precursors to pancreatic ductal adenocarcinoma (PDAC). However, current guidelines for clinical management of IPMN are suboptimal and limited to information obtained through anatomical imaging and cytology of biopsy samples. Our results have suggested that diffusion-weighted MRI, an imaging method sensitive to tumor cell density, architecture, and microenvironment is able to differentiate mouse models of IPMN versus PDAC.KPC (KrasG12D:Trp53R172H:Pdx1-Cre) and CKS (KrasG12D:Smad4L/L:Ptf1a-Cre) mice are genetically engineered mouse (GEM) models that capture features of human pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN), respectively. We compared these autochthonous tumors using quantitative imaging metrics from diffusion-weighted MRI (DW-MRI) and dynamic contrast enhanced (DCE)-MRI in reference to quantitative histological metrics including cell density, fibrosis, and microvasculature density. Our results revealed distinct DW-MRI metrics between the KPC vs. CKS model (mimicking human PDAC vs. IPMN lesion): the apparent diffusion coefficient (ADC) of CKS tumors is significantly higher than that of KPC, with little overlap (mean ± SD vs. , ) despite intratumor and intertumor variability. Kurtosis index (KI) is also distinctively separated in the two models. DW imaging metrics are consistent with growth pattern, cell density, and the cystic nature of the CKS tumors. Coregistration of ex vivo ADC maps with H&E-stained sections allowed for regional comparison and showed a correlation between local cell density and ADC value. In conclusion, studies in GEM models demonstrate the potential utility of diffusion-weighted MRI metrics for distinguishing pancreatic cancer from benign pancreatic cysts such as IPMN.