Tumor-associated collagen signatures. (a)-(c) Example of TACS-1. A region of locally dense collagen (a) near (40 μm 'above') a small tumor region (b) that is within the globally increased collagen region surrounding tumors, resulting from increased SHG (collagen) signal intensity; (c) three-dimensional surface plot of intensity showing an approximately three-fold signal increase at TACS-1. (d), (e) Example of TACS-2, showing straightened (taut) collagen fibers stretched around and constraining an expanded epithelial tumor volume. At regions of TACS-2, quantitative analysis  of fiber angles relative to the tumor boundary shows a distribution of fibers around 0° that correlates to non-invading regions of tumor cells. (f) Example of TACS-3, showing radially aligned collagen fibers, reorganized by tumor cells, at regions of tumor cell invasion. At regions of TACS-3, quantitative analysis  of fiber angles relative to the tumor boundary shows a distribution of fibers around 90° that correlates with local invasion of tumor cells.