Time-resolved laser induced fluorescence spectroscopy (TRLIFS): A tool for intra-operative diagnosis of brain tumors andmaximizing 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 IIV) 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 potentia 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.