Label-free fluorescence lifetime imaging for real-time guidance of stereotactic biopsy: A feasibility study in brain cancer patients

Abstract Background Stereotactic needle biopsy is frequently indicated for diagnosis of malignant gliomas in initial management and at tumor recurrence. Current techniques have a sampling error of 24% and diagnostic errors of 10-30%. Fluorescence lifetime imaging (FLIm) distinguishes among types of brain tissue according to their intrinsic fluorescence properties. Intraprocedural FLIm has been implemented for biopsy guidance. Methods A FLIm imaging system (fiber optic probe; pulsed excitation: 355 nm; APD-based detection: 470/28 nm, 540/50 nm) linked to a stereotactic navigation platform was used to image tissue through the 10-mm side opening of a 1-mm diameter needle during MRI-directed stereotactic biopsy of five suspected malignant gliomas. As the biopsy needle advanced to its targets, FLIm data were continuously acquired and displayed in real-time. The data were analyzed by a classification model (trained with an independent dataset from 364 specimens from resection margins of 61 malignant gliomas), and displayed as probability of the needle’s tip lying within the targeted lesion. Predictions from FLIm were compared with biopsy histopathology. Results Differences in FLIm-derived parameters (intensity, lifetime, Laguerre coefficient) permitted distinguishing lesion (biopsy-confirmed) from uninvolved brain (not biopsy-confirmed) with 81% accuracy and an AUC of 88%. Differentiation was better for oligodendroglioma and astrocytoma than for non-enhancing glioblastoma and necrosis. Conclusions Incorporating FLIm with standard stereotactic biopsy needle and workflow could provide real-time guidance in selecting biopsy targets along the needle’s trajectory potentially improving diagnostic yield and safety. This approach may also aid biopsy of other body tissues and placement of brain probes treating functional disorders.