GaWRDenMap: a quantitative framework to study the local variation in cell-cell interactions in pancreatic disease subtypes.

Spatial pattern modelling concepts are being increasingly used in capturing disease heterogeneity. Quantification of heterogeneity in the tumor microenvironment is extremely important in pancreatic ductal adenocarcinoma (PDAC), which has been shown to co-occur with other pancreatic diseases and neoplasms with certain attributes that make visual discrimination difficult. In this paper, we propose the GaWRDenMap framework, that utilizes the concepts of geographically weighted regression (GWR) and a density function-based classification model, and apply it to a cohort of multiplex immunofluorescence images from patients belonging to six different pancreatic diseases. We used an internal cohort of 228 patients comprised of 34 Chronic Pancreatitis (CP), 71 PDAC, 70 intraductal papillary mucinous neoplasm (IPMN), 16 mucinous cystic neoplasm (MCN), 29 pancreatic intraductal neoplasia (PanIN) and 8 IPMN-associated PDAC patients. We utilized GWR to model the relationship between epithelial cells and immune cells on a spatial grid. The GWR model estimates were used to generate density signatures which were used in subsequent pairwise classification models to distinguish between any two pairs of disease groups. Image-level, as well as subject-level analysis, were performed. When applied to this dataset, our classification model showed significant discrimination ability in multiple pairwise comparisons, in comparison to commonly used abundance-based metrics, like the Morisita-Horn index. The model was able to best discriminate between CP and PDAC at both the subject- and image-levels. It was also able to reasonably discriminate between PDAC and IPMN. These results point to a potential difference in the spatial arrangement of epithelial and immune cells between CP, PDAC and IPMN, that could be of high diagnostic significance. Further validation on a more comprehensive dataset would be warranted.