flavin-adenine-dinucleotide and Colonic-Neoplasms

Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.

Topics: Adenomatous Polyposis Coli; Algorithms; Collagen; Colon; Colonic Neoplasms; Data Interpretation, Statistical; Flavin-Adenine Dinucleotide; Hemoglobins; Humans; Hyperplasia; NAD; Neoplasms; Sensitivity and Specificity; Spectrometry, Fluorescence; Time Factors

To investigate the autofluorescence spectroscopic differences in normal and adenomatous colonic tissues and to determine the optimal excitation wavelengths for subsequent study and clinical application.. Normal and adenomatous colonic tissues were obtained from patients during surgery. A FL/FS920 combined TCSPC spectrofluorimeter and a lifetime spectrometer system were used for fluorescence measurement. Fluorescence excitation wavelengths varying from 260 to 540 nm were used to induce the autofluorescence spectra, and the corresponding emission spectra were recorded from a range starting 20 nm above the excitation wavelength and extending to 800 nm. Emission spectra were assembled into a three-dimensional fluorescence spectroscopy and an excitation-emission matrix (EEM) to exploit endogenous fluorophores and diagnostic information. Then emission spectra of normal and adenomatous colonic tissues at certain excitation wavelengths were compared to determine the optimal excitation wavelengths for diagnosis of colonic cancer.. When compared to normal tissues, low NAD(P)H and FAD, but high amino acids and endogenous phorphyrins of protoporphyrin IX characterized the high-grade malignant colonic tissues. The optimal excitation wavelengths for diagnosis of colonic cancer were about 340, 380, 460, and 540 nm.. Significant differences in autofluorescence peaks and its intensities can be observed in normal and adenomatous colonic tissues. Autofluorescence EEMs are able to identify colonic tissues.

Topics: Amino Acids; Case-Control Studies; Colonic Neoplasms; Flavin-Adenine Dinucleotide; Fluorescence; Humans; Imaging, Three-Dimensional; NADP; Protoporphyrins; Spectrometry, Fluorescence

Laser-induced fluorescence (LIF) of colonic tissue was examined both in vitro and in vivo to assess the ability of the technique to distinguish neoplastic from hyperplastic and normal tissue and to relate the LIF spectra to specific constituents of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, 49 adenomatous polyps, and 7 adenocarcinomas were recorded both in vivo and in vitro. With 337-nm excitation, the fluorescence spectra all had peaks at 390 and 460 nm, believed to arise from collagen and NADH, and a minimum at 425 nm, consistent with absorption attributable to hemoglobin. The spectra of colonic tissue recorded both in vivo and in vitro are different, primarily in the NADH fluorescence component, which decays exponentially with time after resection. When normal colonic tissue is compared to hyperplastic or adenomatous polyps, the predominant changes in the fluorescence spectra are a decrease in collagen fluorescence and a slight increase in hemoglobin reabsorption. A multivariate linear regression (MVLR) analysis was used to distinguish neoplastic tissue from non-neoplastic tissue with a sensitivity, specificity, predictive value positive, and predictive value negative toward neoplastic tissue of 80%, 92%, 82%, and 91%, respectively. When the MVLR technique was used to distinguish neoplastic polyps from non-neoplastic polyps, values of 86%, 77%, 86%, and 77% respectively, were obtained. The data suggest that the LIF measurements sense changes in polyp morphology, rather than changes in fluorophores specific to polyps, and it is this change in morphology that leads indirectly to discrimination of polyps.

Topics: Adenocarcinoma; Adenoma; Aged; Algorithms; Biology; Collagen; Colon; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Equipment Design; Female; Flavin-Adenine Dinucleotide; Fluorescence; Humans; Hyperplasia; Lasers; Male; Multivariate Analysis; NAD; Pattern Recognition, Automated; Regression Analysis; Spectrum Analysis; Ultraviolet Rays