Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy

Abstract

The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8+/-0.3 ns) and 460 nm (lifetime=0.8+/-0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7+/-0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm; lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens.

Time-Resolved Fluorescence in Photodynamic Therapy

“…The potential fast data acquisition (e.g., ns laser pulses) thus provides a unique advantage for clinical applications [51]. For example, flexible fiber probes can be coupled to endoscopy systems for clinical surveillance [52][53][54][55][56]. Multiple time-resolved spectra can either be acquired by sequentially scanning in the spectral domain (e.g., via a monochromator) [57] or using a multiple fiber delay arrangement [58].…”

In vivo measurements of diffuse reflectance and time‐resolved autofluorescence emission spectra of basal cell carcinomas

“…Changes in the fluorescence properties of these molecules can report on altered metabolism, protein cross links, cell signalling and even disease state [15,[17][18][19]. In particular the fluorescence lifetime of endogenous fluorophores, which is relatively insensitive to fluorophore concentration and to signal attenuation by the sample, has been shown (both ex vivo and in vivo) to effectively differentiate between healthy and diseased tissue, for example in atherosclerotic plaques [20,21] and in various types of cancer [22][23][24][25][26][27][28][29][30][31]. Accordingly, there is significant interest in the development of instruments that can measure the autofluorescence properties of skin for clinical diagnosis, e.g.…”

Review of the potential of optical technologies for cancer diagnosis in neurosurgery: a step toward intraoperative neurophotonics

“…The system required a relatively long data acquisition time (∼30 s) to capture each tissue measurement, which would need to be shortened substantially for effective integration in clinical workflows. 79 Vasefi et al 80 recently reported on an improved TR-FS system with near real-time data acquisition and classification. In this study, tissue differentiation on larger tissue samples measured in vivo NC (n ¼ 10), WM (n ¼ 12), and GBM (n ¼ 13) with nine patients is described.…”