Second harmonic generation (SHG) imaging of cancer heterogeneity in ultrasound guided biopsies of prostate in men suspected with prostate cancer

Prostate cancer is a multifocal disease with characteristic heterogeneity and foci that can range from low grade indolent to aggressive disease. The latter is characterised by the well-established histopathological Gleason grading system used in the current clinical care. Nevertheless, a large discrepancy exists on initial biopsy and after the final radical prostatectomy. Moreover, there is no reliable imaging modality to study these foci, in particular at the level of the cells and surrounding matrix. Extracellular matrix (ECM) remodelling is significant in cancer progression with collagen as the dominant structural component providing mechanical strength and flexibility of tissue. In this study, the collagen assembly in prostate tissue was investigated with second harmonic generation (SHG) microscopy: malignant foci demonstrated a reticular pattern, with a typical collagen pattern for each Gleason score. The orientation of collagen for each biopsy was computed by applying a ratio of the anisotropic and isotropic collagen fibres. This value was found to be distinct for each Gleason score. The findings suggest that this approach can not only be used to detect prostate cancer, but also can act as a potential biomarker for cancer aggressiveness.