Researchers have introduced a model-free optical biomarker to analyze collagen structures in human breast cancer samples, according to a peer-reviewed study published by Nature.
The method uses high-resolution polarization-resolved Second-Harmonic Generation (pSHG) imaging to identify aligned collagen bundles in histological tissue samples without relying on assumed symmetry models. The study introduces Polarization Asymmetry as a parameter to quantify collagen supramolecular organization. Researchers compared Polarization Asymmetry against the angular phase shift of pSHG intensity curves and a second-order susceptibility tensor component derived from fitting data to a trigonal symmetry model.
High values across all three metrics over a micrometric scale consistently detected the presence of aligned collagen bundles. The results indicate a correlation with the structural remodeling of the extracellular matrix at a sub-micrometric scale, which may influence tissue mechanical properties.
To confirm the approach, the authors validated the method on human corneal tissue due to its established collagen architecture and biomechanics. Alessandro Ruzza from the Fondazione Banca degli occhi del Veneto—Onlus provided the corneal tissues for this validation.
The authors include Raffaella Mercatelli, Giuseppe Massimo Bernava, Giuseppe Lombardo, Tiziana Triulzi, and Rosaria Orlandi, representing institutions such as the Institute for Biomedical Technologies, the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, and the European Laboratory for Non-linear Spectroscopy. The manuscript was received on December 22, 2025, accepted on July 14, 2026, and published on August 12, 2026.
