Rapid Discrimination of High-Grade Prostate Cancer Using Label-Free Fluorescence Lifetime Measurements

Histologic evaluation of prostatic needle biopsies is essential for prostate cancer (PCa) diagnosis and treatment planning, yet tissue targeting remains suboptimal despite MRI-guided Bx procedures. This pilot study investigates the use of label-free Fluorescence Lifetime Imaging (FLIm) for real-time biopsy guidance. Using ex vivo specimens, we assess FLIm's preliminary efficacy in discriminating malignant from benign prostate tissue.

Twenty patients undergoing prostate biopsy were enrolled. FLIm measurements were performed immediately after sample collection using a custom fiber-optic probe. Optical parameters from 4 spectral bands associated with distinct endogenous fluorophores including structural proteins and metabolic cofactors (e.g. NADH, FAD) were extracted and labeled based on histological annotation. Data were analyzed to characterize tissue-type differences and train and evaluate a classifier to distinguish malignancy.

Separation between benign tissue and Gleason grade ≥4 PCa was achieved using just 2 of 56 FLIm-derived parameters. A Support Vector Machine classifier using all parameters achieved a ROC of 0.88 in identifying grade 4 PCa. A reduced lifetime value in the NADH-associate band, likely due to increased free NADH from upregulated glycolysis, supports the biochemical basis for optical differentiation.

FLIm shows significant potential for high-grade PCa identification. The single-fiber approach requires minimal modification for integration into current biopsy tools, supporting its feasibility for clinical translation.