Diagnosis of meningioma by time-resolved fluorescence spectroscopy.

We investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor specimens and delineation of tumor from surrounding normal tissue. Tissue autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the intensity decay profiles are recorded in the 370 to 500 nm spectral range with a fast digitizer (0.2 ns resolution). Experiments are conducted on excised specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site are used for tissue characterization. A linear discriminant analysis algorithm is used for tissue classification. Our results reveal that meningioma is characterized by unique fluorescence characteristics that enable discrimination of tumor from normal tissue with high sensitivity (>89%) and specificity (100%). The accuracy of classification is found to increase (92.8% cases in the training set and 91.8% in the cross-validated set correctly classified) when parameters from both the spectral and the time domain are used for discrimination. Our findings establish the feasibility of using TR-LIFS as a tool for the identification of meningiomas and enables further development of real-time diagnostic tools for analyzing surgical tissue specimens of meningioma or other brain tumors.

[1]  E. Sevick-Muraca,et al.  Quantitative optical spectroscopy for tissue diagnosis. , 1996, Annual review of physical chemistry.

[2]  Javier A. Jo,et al.  Fluorescence Lifetime Spectroscopy of Glioblastoma Multiforme¶ , 2004, Photochemistry and photobiology.

[3]  Qiyin Fang,et al.  Fast model-free deconvolution of fluorescence decay for analysis of biological systems. , 2004, Journal of biomedical optics.

[4]  R. Cubeddu,et al.  Time-resolved fluorescence imaging in biology and medicine , 2002 .

[5]  Qiyin Fang,et al.  Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm. , 2004, Applied optics.

[6]  David G. Gadian,et al.  Proton MR Spectroscopy of Intracranial Tumours: In Vivo and In Vitro Studies , 1990, Journal of computer assisted tomography.

[7]  S. L. Jacques,et al.  Diagnostic potential of laser-induced autofluorescence emission in brain tissue. , 1997, Journal of Korean medical science.

[8]  Qiyin Fang,et al.  Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics. , 2004, The Review of scientific instruments.

[9]  R. Martuza,et al.  Laser-induced fluorescence: experimental intraoperative delineation of tumor resection margins. , 1992, Journal of neurosurgery.

[10]  T. Yamashima,et al.  An ultrastructural and immunohistochemical study of extracellular matrix in meningiomas. , 1990, Histology and histopathology.

[11]  Webster K. Cavenee,et al.  Pathology and genetics of tumours of the nervous system. , 2000 .

[12]  Mark S. Greenberg,et al.  Handbook of Neurosurgery , 1993 .

[13]  H. Schneckenburger,et al.  Fluorescence decay kinetics and imaging of NAD(P)H and flavins as metabolic indicators , 1992 .

[14]  J. Lakowicz.  Principles of fluorescence spectroscopy , 1983 .

[15]  L. Sobin,et al.  World Health Organization classification of tumors , 2000, Cancer.

[16]  M W Berns,et al.  Time-resolved and steady-state fluorescence measurements of beta-nicotinamide adenine dinucleotide-alcohol dehydrogenase complex during UVA exposure. , 1997, Journal of photochemistry and photobiology. B, Biology.

[17]  A R Tate,et al.  Towards a method for automated classification of 1H MRS spectra from brain tumours , 1998, NMR in biomedicine.

[18]  V. Marmarelis.  Identification of nonlinear biological systems using laguerre expansions of kernels , 1993, Annals of Biomedical Engineering.

[19]  Anita Mahadevan-Jansen,et al.  In Vivo Brain Tumor Demarcation Using Optical Spectroscopy¶ , 2001, Photochemistry and photobiology.

[20]  Laura Marcu,et al.  Time-resolved fluorescence spectroscopy of human brain tumors , 2002, SPIE BiOS.

[21]  H. Ng,et al.  Expression of epithelial and extracellular matrix protein markers in meningiomas , 1993, Histopathology.

[22]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.

[23]  J. Aubin.  Autofluorescence of viable cultured mammalian cells. , 1979, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[24]  M Motamedi,et al.  Brain tumor demarcation using optical spectroscopy; an in vitro study. , 2000, Journal of biomedical optics.

[25]  Giovanni Bottiroli,et al.  Diagnostic Potential of Autofluorescence for an Assisted Intraoperative Delineation of Glioblastoma Resection Margins¶ , 2003, Photochemistry and photobiology.

[26]  Laura Marcu,et al.  Time-Resolved Laser-Induced Fluorescence Spectroscopy for Staging Atherosclerotic Lesions , 2003 .

[27]  V. Monnier,et al.  Isolation, purification and partial characterization of novel fluorophores from aging human insoluble collagen-rich tissue. , 1989, Connective tissue research.

[28]  Verlick Sf.  Fluorescence spectra and polarization of glyceraldehyde-3-phosphate and lactic dehydrogenase coenzyme complexes. , 1958 .

[29]  W S Grundfest,et al.  Discrimination of Human Coronary Artery Atherosclerotic Lipid-Rich Lesions by Time-Resolved Laser-Induced Fluorescence Spectroscopy , 2001, Arteriosclerosis, thrombosis, and vascular biology.