Changes in the Collagen Structure of Thyroid Nodule Capsules Determined by Polarization-Resolved Second Harmonic Generation Microscopy

Thyroid carcinomas represent a challenging problem as their differentiation from the much more frequent benign pathologies can be sometimes difficult. Automatic diagnostic approaches that can differentiate between malignant and benign thyroid nodules would be of great benefit for addressing thyroid pathologies. In this study we have used polarization-resolved second harmonic generation microscopy to investigate collagen organization in the fibrillar capsules surrounding human thyroid nodules. We demonstrate that imaging the collagen capsules at different laser beam polarization angles and fitting the second harmonic generation intensity with a theoretical curve can yield information on the nonzero components of the second order susceptibility tensor and the orientation of the collagen fibres. We have used this approach to differentiate between capsules surrounding the thyroid follicular adenoma and papillary carcinoma nodules. These results indicate that polarization-resolved second harmonic generation microscopy can provide additional information about the collagenous capsule surrounding thyroid nodules, which may complement intensity-based quantitative second harmonic generation microscopy and eventually traditional histopathologic examination.