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New quantitative prognostic markers are needed for improved pancreatic ductal adenocarcinoma (PDAC) prognosis. Second harmonic generation microscopy has been used to show that collagen fiber alignment in PDAC is a negative prognostic factor. In this work, a series of PDAC and normal adjacent tissue (NAT) biopsies were imaged with spatial light interference microscopy (SLIM). Quantitative analysis performed on the biopsy SLIM images show that PDAC fiber structures have lower alignment per unit length, narrower width, and are longer than NAT controls. Importantly, fibrillar collagen in PDAC shows an inverse relationship between survival data and fiber width and length (p < 0.05).

Tissue biopsy evaluation in the clinic is in need of quantitative disease markers for diagnosis and, most importantly, prognosis. Among the new technologies, quantitative phase imaging (QPI) has demonstrated promise for histopathology because it reveals intrinsic tissue nanoarchitecture through the refractive index. However, a vast majority of past QPI investigations have relied on imaging unstained tissues, which disrupts the established specimen processing. Here we present color spatial light interference microscopy (cSLIM) as a new whole-slide imaging modality that performs interferometric imaging on stained tissue, with a color detector array. As a result, cSLIM yields in a single scan both the intrinsic tissue phase map and the standard color bright-field image, familiar to the pathologist. Our results on 196 breast cancer patients indicate that cSLIM can provide stain-independent prognostic information from the alignment of collagen fibers in the tumor microenvironment. The effects of staining on the tissue phase maps were corrected by a mathematical normalization. These characteristics are likely to reduce barriers to clinical translation for the new cSLIM technology.