Distinguishing IDH mutation status in gliomas using FTIR-ATR spectra of peripheral blood plasma indicating clear traces of protein amyloid aggregation.

BACKGROUND: Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate dehydrogenase (IDH) gene are strong predictors of treatment sensitivity and prognosis. In this study, we attempted to non-invasively diagnose glioma development and the presence of IDH mutations using multivariate analysis of the plasma mid-infrared absorption spectra for a comprehensive and sensitive view of changes in blood components associated with the disease and genetic mutations. These component changes are discussed in terms of absorption wavenumbers that contribute to differentiation. METHODS: Plasma samples were collected at our institutes from 84 patients with glioma (13 oligodendrogliomas, 17 IDH-mutant astrocytoma, 7 IDH wild-type diffuse glioma, and 47 glioblastomas) before treatment initiation and 72 healthy participants. FTIR-ATR spectra were obtained for each plasma sample, and PLS discriminant analysis was performed using the absorbance of each wavenumber in the fingerprint region of biomolecules as the explanatory variable. This data was used to distinguish patients with glioma from healthy participants and diagnose the presence of IDH mutations. RESULTS: The derived classification algorithm distinguished the patients with glioma from healthy participants with 83% accuracy (area under the curve (AUC) in receiver operating characteristic (ROC) = 0.908) and diagnosed the presence of IDH mutation with 75% accuracy (AUC = 0.752 in ROC) in cross-validation using 30% of the total test data. The characteristic changes in the absorption spectra suggest an increase in the ratio of ß-sheet structures in the conformational composition of blood proteins of patients with glioma. Furthermore, these changes were more pronounced in patients with IDH-mutant gliomas. CONCLUSIONS: The plasma infrared absorption spectra could be used to diagnose gliomas and the presence of IDH mutations in gliomas with a high degree of accuracy. The spectral shape of the protein absorption band showed that the ratio of ß-sheet structures in blood proteins was significantly higher in patients with glioma than in healthy participants, and protein aggregation was a distinct feature in patients with glioma with IDH mutations.

Mid-infrared photoacoustic spectroscopy based on ultrasound detection for blood component analysis.

For the non-invasive measurement of biological tissue, a piezoelectric photoacoustic spectroscopy (PZT-PAS) system that detects a single frequency of ultrasound induced by the irradiation of pulse-modulated mid-infrared laser light was developed. PA spectra of the optical phantom and biological samples were obtained, and the relationship between the PA signal intensity and optical absorbance in the fingerprint region (930-1,200 cm-1) was analyzed to estimate the optical absorbance. The resonance vibration of the induced ultrasound was utilized to further increase the signal strength for biological tissue measurement. Consequently, PA spectrum reflecting the absorption of components in biological tissues was obtained.

Vacuum Ultraviolet Absorption Spectroscopy Analysis of Breath Acetone Using a Hollow Optical Fiber Gas Cell.

Human breath is a biomarker of body fat metabolism and can be used to diagnose various diseases, such as diabetes. As such, in this paper, a vacuum ultraviolet (VUV) spectroscopy system is proposed to measure the acetone in exhaled human breath. A strong absorption acetone peak at 195 nm is detected using a simple system consisting of a deuterium lamp source, a hollow-core fiber gas cell, and a fiber-coupled compact spectrometer corresponding to the VUV region. The hollow-core fiber functions both as a long-path and an extremely small-volume gas cell; it enables us to sensitively measure the trace components of exhaled breath. For breath analysis, we apply multiple regression analysis using the absorption spectra of oxygen, water, and acetone standard gas as explanatory variables to quantitate the concentration of acetone in breath. Based on human breath, we apply the standard addition method to obtain the measurement accuracy. The results suggest that the standard deviation is 0.074 ppm for healthy human breath with an acetone concentration of around 0.8 ppm and a precision of 0.026 ppm. We also monitor body fat burn based on breath acetone and confirm that breath acetone increases after exercise because it is a volatile byproduct of lipolysis.

A Compact Mid-Infrared Spectroscopy System for Healthcare Applications Based on a Wavelength-Swept, Pulsed Quantum Cascade Laser.

A mid-infrared spectroscopic system using a high-speed wavelength-swept and pulsed quantum cascade laser (QCL) for healthcare applications such as blood glucose measurement is proposed. We developed an attenuated total reflection measurement system comprising the QCL with a micro-electromechanical system (MEMS)-scanning grating, hollow optical fibers, and InAsSb detector and tested its feasibility for healthcare applications. A continuous spectrum was obtained by integrating comb-shaped spectra, the timing of which was slightly shifted. As this method does not require complex calculations, absorption spectra are obtained in real-time. We found that the signal-to-noise ratio of the obtained spectrum had been improved by increasing the number of spectra that were integrated into the spectrum calculation. Accordingly, we succeeded in measuring the absorption spectrum of a 0.1% aqueous glucose solution. Furthermore, the absorption spectra of human lips were measured, and it was shown that estimation of blood glucose levels were possible using a model equation derived using a partial least squares regression analysis of the measured absorption spectra. The spectroscopic system based on the QCL with MEMS-scanning grating has the advantages of compactness and low cost over conventional Fourier transform infrared-based systems and common spectroscopic systems with a tunable QCL that has a relatively large, movable grating.

Noninvasive glucose monitoring using mid-infrared absorption spectroscopy based on a few wavenumbers.

A method for performing noninvasive blood glucose measurements was developed. The method is based on mid-infrared absorption spectroscopy and uses only a few wavenumbers to measure blood glucose levels in vivo unconditionally. We found that the regression of blood glucose levels using only three wavenumbers, which were selected using a series cross-validation technique, realized accuracies comparable to those of cases in which a greater number of wavenumbers are used. In addition, we demonstrated the performance of this model through correlations among different types of data.

Hollow optical-fiber based infrared spectroscopy for measurement of blood glucose level by using multi-reflection prism.

A mid-infrared attenuated total reflection (ATR) spectroscopy system employing hollow optical fibers and a trapezoidal multi-reflection ATR prism has been developed to measure blood glucose levels. Using a multi-reflection prism brought about higher sensitivity, and the flat and wide contact surface of the prism resulted in higher measurement reproducibility. An analysis of in vivo measurements of human inner lip mucosa revealed clear signatures of glucose in the difference spectra between ones taken during the fasting state and ones taken after ingestion of glucose solutions. A calibration plot based on the absorption peak at 1155 cm(-1) that originates from the pyranose ring structure of glucose gave measurement errors less than 20%.

Infrared hollow optical fiber probes for reflectance spectral imaging.

Systems for infrared reflectance imaging are built with an FT-IR spectrometer, hollow optical fibers, and a high-speed infrared camera. To obtain reflectance images of biological samples, an optical fiber probe equipped with a light source at the distal end and a hybrid fiber probe composed of fibers for beam radiation and ones for image detection have been developed. By using these systems, reflectance spectral images of lipid painted on biomedical hard tissue, which provides reflectance of around 4%, are successfully acquired.

Blood glucose measurement by using hollow optical fiber-based attenuated total reflection probe.

A noninvasive glucose monitoring system based on mid-infrared, attenuated total reflection spectroscopy using a hollow optical fiber probe is developed. Owing to the flexible fiber probe, measurement of oral mucosa, where blood capillaries are near the skin surface, is possible. Blood glucose levels are measured by detecting the peak intensity of glucose absorption bands, and the experimental results showed that the reproducibility of the measurement is high enough for monitoring blood glucose.

Remote Fourier transform-infrared spectral imaging system with hollow-optical fiber bundle.

A spectral imaging system consisting of a Fourier transform-infrared spectrometer, a high-speed infrared camera, and a bundle of hollow-optical fibers transmitting infrared radiation images was constructed. Infrared transmission spectra were obtained by carefully processing multiple interferograms taken by high-speed photography. Infrared spectral images of a variety of samples captured by the system were measured. We successfully detected existence maps of the oil and fat of biological samples by mapping the transmission of specific wavelengths in the spectrum.

Hollow-fiber-based flexible probe for remote measurement of infrared attenuated total reflection.

A hollow optical-fiber probe for infrared attenuated total reflection (ATR) spectroscopy is developed. A newly designed ATR prism, optimized for use with hollow optical fibers, is proposed. Results from preliminary experiments show the potential uses of the probe in clinical applications. The probe is appropriate for in vivo applications because it is consists of only nontoxic and chemically durable materials.

Nontoxic and chemically stable hollow optical fiber probe for fourier transform infrared spectroscopy.

Remote spectroscopy systems based on hollow optical fiber probes are proposed and experimental results using a Fourier transform spectroscope are presented. A hollow optical-fiber probe with a silver and polymer inner coating is used to deliver incoherent light to a target and another separate hollow fiber is used to collect the reflected light. The reflectance spectra of teeth, skin, and oral mucosa were successfully measured with the probe even from surfaces with reflectances lower than 0.5%. The preliminary results obtained using attenuated total reflection spectroscopy are also presented. This remote infrared spectroscope is useful for endoscopic measurements inside the body because it is flexible, durable, nontoxic, and has the low transmission losses associated with hollow-fiber-based probes.