Compact point-detection fluorescence spectroscopy system for quantifying intrinsic fluorescence redox ratio in brain cancer diagnostics

Abstract

Abstract.We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs one compact cw diode laser (407 nm) to excite two primary endogenous fluorophores, reduced nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. The spectra were first analyzed using a spectral filtering modulation method developed previously to derive the intrinsic fluorescence redox ratio, which has the advantages of insensitivty to optical coupling and rapid data acquisition and analysis. This method represents a convenient and rapid alternative for achieving intrinsic fluorescence-based redox measurements as compared to those complicated model-based methods. It is worth noting that the method can also extract total hemoglobin concentration at the same time but only if the emission path length of fluorescence light, which depends on the illumination and collection geometry of the optical probe, is long enough so that the effect of absorption on fluorescence intensity due to hemoglobin is significant. Then a multivariate method was used to statistically classify normal tissues and tumors. Although the first method offers quantitative tissue metabolism information, the second method provides high overall classification accuracy. The two methods provide complementary capabilities for understanding cancer development and noninvasively diagnosing brain cancer. The results of our study suggest that this portable system can be potentially used to demarcate the elusive boundary between a brain tumor and the surrounding normal tissue during surgical resection. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Metabolic Imaging in the Study of Oncological Processes (Review)

“…It was shown on uterine neck epithelium samples that samples with dysplasia had decreased FAD/(NADH+FAD) redox ratio compared to normal epithelium [82]. Similar results were obtained on rat brain tumor ex vivo: FAD/ (NADH+FAD) redox ratio in the tumor was much lower than in the normal tissue, which suggested prevalence of glycolysis in tumor cells [83]. Supposedly, the difference in redox ratio values may be used for visualization of tumor boundaries during the operation [83].…”

Early Prediction of Skin Viability Using Visible Diffuse Reflectance Spectroscopy and Autofluorescence Spectroscopy

“…The redox ratio can be calculated using the autofluorescence intensities of two major fluorophores in tissues (i.e., reduced nicotinamide adenine dinucleotide and flavin adenine dinucleotide). It is commonly defined by the following equation 16 :…”

“…9 Visible light spectroscopy has also been used to characterize tissue viability by measuring tissue oxygenation and total hemoglobin concentration. 10,11 Fluorescence spectroscopy using exogenous 12 and endogenous fluorophores [13][14][15][16] to measure the metabolic rate of tissue has also been reported in recent years. Diffuse reflectance spectroscopy and autofluorescence spectroscopy provide complementary information about tissue status and have shown excellent potential for assessing tissue viability separately; however, to the best of our knowledge, their simultaneous use to characterize the skin flap metabolism and their respective accuracies in flap viability assessment have not been studied.…”

Fiber based in-vivo imaging of epithelial FAD fluorescence: experiments and simulations

“…Single point fluorescence measurements have been used to discriminate diseased and non diseased tissues [14][15][16]. Although, these point measurement techniques has the ability to diagnose malignancies, the results may lead to false positive findings due to the insufficiency of data.…”