Quantitative analysis of collagen remodeling in pancreatic lesions using computationally translated collagen images derived from brightfield microscopy images

The changes in stromal collagen play a crucial role during the pathogenesis and progression of pancreatic intraepithelial neoplasm (PanIN) to pancreatic ductal adenocarcinoma (PDAC) while misdiagnosis of PanIN is common because of the resemblance to chronic pancreatitis (CP) in its symptoms and subsequent evaluations similarities. To visualize fibrillar collagen in tissues, second harmonic generation microscopy is now utilized as a gold standard in various stromal-based research analyses. However, a technical approach that can perform a quantitative analysis of fibrillar collagen directly on standard slides stained with H&E can (i) discard the need for specialized and costly equipment or labels, (ii) further supplement the conventional histopathological insights and, (iii) potentially be integrated within the framework of standard histopathology workflow. In this study, the whole-core brightfield H&E-stained images of pancreatic tissues were translated computationally into the new collagen images. Subsequently, collagen characteristics of PDAC, PanIN, CP, and normal pancreatic tissues (control) were extracted and compared. The highest alignment (p < 0.01, R2 = 0.2594) was observed in PDAC cores in comparison to the remaining three groups, while the lowest fiber density (p < 0.0001, R2 = 0.3569) was observed in case of normal tissue cores. Moreover, the collagen area and fiber length had shown higher area under curve (0.83 and 0.81, respectively) in discriminating neoplastic and non-neoplastic tissues based on their receiver operating characteristics. The study demonstrated that the computationally generated collagen images can provide a quantitative assessment of collagen remodeling in pancreatic lesions. The cross-modality image synthesis may further lead towards better histopathological and tissue microenvironment insights without the need of specialized imaging equipment or labels.