A Fast, Robust Method for Quantitative Assessment of Collagen Fibril Architecture from Transmission Electron Micrographs

Collagen is the most abundant protein in mammals; it exhibits a hierarchical organization and provides structural support to a wide range of soft tissues, including blood vessels. The architecture of collagen fibrils dictates vascular stiffness and strength, and changes therein can contribute to disease progression. While transmission electron microscopy (TEM) is routinely used to examine collagen fibrils under normal and pathological conditions, computational tools that enable fast and minimally subjective quantitative assessment remain lacking. In the present study, we describe a novel semi-automated image processing and statistical modeling pipeline for segmenting individual collagen fibrils from TEM images and quantifying key metrics of interest, including fibril cross-sectional area and aspect ratio. For validation, we show first-of-their-kind illustrative results for adventitial collagen in the thoracic aorta from three different mouse models.