Time-Resolved Laser Induced Fluorescence Spectroscopy (TRLIFS): A Tool for Intra-operative Diagnosis of Brain Tumors and Maximizing Extent of Surgical Resection

Abstract

Time-resolved laser induced fluorescence spectroscopy (TR-LIFS) can be used to differentiate various tissue types in vivo, based on the intrinsic fluorescent time-decay properties of these tissues. We have developed TR-LIFS as an intra-operative tool for the delineation of gliomas from normal brain, and established an algorithm for real-time differentiation of normal cortex, normal white matter, low grade gliomas, and high grade glioma. Forty two patients who were undergoing glioma (WHO grade I-IV) surgery were enrolled in the study. A TR-LIFS prototype apparatus (gated detection, fast digitizer) was used to induce in vivo fluorescence using a pulsed N2 laser (337 nm excitation, 0.7 ns pulse width) and to record the time-resolved spectrum (360–550 nm range, 10 nm interval). The sites of TR-LIFS measurement were biopsied, and histology confirmed by conventional pathology (H&E staining). Comparison of the parameters derived from the TR-LIFS data, including intensity values and time-resolved intensity decay features (average fluorescence lifetime and Laguerre coefficients values), were used for to define the most common TR-LIFS “signature” for each tissue type. Seventy one biopsy samples of tumor and normal brain were analyzed. A linear discriminant algorithm classified low-grade gliomas with 100% sensitivity and 98% specificity. High-grade glioma demonstrated a high degree of heterogeneity reducing the discrimination accuracy of these tumors to 47% sensitivity and 94% specificity. These results indicate the potential of TR-LIFS for real-time, non-invasive intra-operative diagnosis of brain tumors. Validation studies are underway. If these validation studies confirm the findings, TR-LIFS is likely to become a rapid, safe, and easy to use means to maximize extent of tumor resection while minimizing damage to surrounding normal tissues.