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.

Terahertz fiber link using dielectric silicon waveguide interface.

Nascent data-intensive emerging technologies are mandating low-loss, short-range interconnects, whereas existing interconnects suffer from high losses and low aggregate data throughput owing to a lack of efficient interfaces. Here, we report an efficient 22-Gbit/s terahertz fiber link using a tapered silicon interface that serves as a coupler between the dielectric waveguide and hollow core fiber. We investigated the fundamental optical properties of hollow-core fibers by considering fibers with 0.7-mm and 1-mm core diameters. We achieved a coupling efficiency of ∼ 60% with a 3-dB bandwidth of 150 GHz in the 0.3-THz band over a 10 cm fiber.

Mid-infrared laser heterodyne spectrometer by hollow optical fiber and its newly designed coupler.

We demonstrate a newly designed, to the best of our knowledge, hollow optical fiber coupler for a mid-infrared (IR) laser heterodyne spectrometer that mixes a targeted light source with local oscillator (LO) light. The hollow fiber achieves a high transmission efficiency ∼80-90%/m, not only for a coherent laser source but also for an incoherent blackbody source. The branching characteristics of the hollow optical fiber coupler are found to be strongly dependent on the curvature and length of the input port fiber, indicating that the branching ratio could be designed independently for each input port. Our laboratory measurements demonstrate that the branching ratio and transmittance of the coupler can be varied by coupling a flexible fiber to the input side owing to the excitation of higher-order modes. Using the hollow optical fiber coupler, a high-resolution emission spectrum of the quantum cascade laser at 10.3 µm for our C O 2 laser-based heterodyne spectrometer is successfully achieved. Using a C O 2 laser with a hollow fiber and a blackbody as a direct input signal in free space, we obtain the sensitivity performance of IR laser heterodyne spectrometer as 2000-3000 K of the system noise temperature. This suggests that the transmission of a coherent LO laser through a hollow optical fiber has almost the same sensitivity for the IR heterodyne detection as that without a fiber.

Analysis of Trace Metals in Human Hair by Laser-Induced Breakdown Spectroscopy with a Compact Microchip Laser.

A laser-induced breakdown spectroscopy (LIBS) system using a microchip laser for plasma generation is proposed for in-situ analysis of trace minerals in human hair. The LIBS system is more compact and less expensive than conventional LIBS systems, which use flashlamp-excited Q-switched Nd:YAG lasers. Focusing optics were optimized using a Galilean beam expander to compensate for the low emitted pulse energy of the microchip laser. Additionally, hundreds of generated LIBS spectra were accumulated to improve the signal-to-noise ratio of the measurement system, and argon gas was injected at the irradiation point to enhance plasma intensity. LIBS spectra of human hair in the UV to near IR regions were investigated. Relative mass concentrations of Ca, Mg, and Zn were analyzed in hairs obtained from five subjects using the intensity of C as a reference. The results coincide well with those measured via inductively coupled argon plasma mass spectrometry. The lowest detectable concentrations of the measured LIBS spectra were 9.0 ppm for Mg, 27 ppm for Zn, and 710 ppm for Ca. From these results, we find that the proposed LIBS system based on a microchip laser is feasible for the analysis of trace minerals in human hair.

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.

Infrared Hollow Optical Fiber Probe for Localized Carbon Dioxide Measurement in Respiratory Tracts.

A real-time gas monitoring system based on optical absorption spectroscopy is proposed for localized carbon dioxide (CO2) measurement in respiratory tracts. In this system, a small gas cell is attached to the end of a hollow optical fiber that delivers mid-infrared light with small transmission loss. The diameters of the fiber and the gas cell are smaller than 1.2 mm so that the probe can be inserted into a working channel of common bronchoscopes. The dimensions of the gas cell are designed based on absorption spectra of CO2 standard gases in the 4.2 µm wavelength region, which are measured using a Fourier-transform infrared spectrometer. A miniature gas cell that is comprised of a stainless-steel tube with slots for gas inlet and a micro-mirror is fabricated. A compact probing system with a quantum cascade laser (QCL) light source is built using a gas cell with a hollow optical fiber for monitoring CO2 concentration. Experimental results using human breaths show the feasibility of the system for in-situ measurement of localized CO2 concentration in human airways.

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.

Real-Time Analysis of Isoprene in Breath by Using Ultraviolet-Absorption Spectroscopy with a Hollow Optical Fiber Gas Cell.

A breath analysis system based on ultraviolet-absorption spectroscopy was developed by using a hollow optical fiber as a gas cell for real-time monitoring of isoprene in breath. The hollow optical fiber functions as an ultra-small-volume gas cell with a long path. The measurement sensitivity of the system was evaluated by using nitric-oxide gas as a gas sample. The evaluation result showed that the developed system, using a laser-driven, high-intensity light source and a 3-m-long, aluminum-coated hollow optical fiber, could successfully measure nitric-oxide gas with a 50 ppb concentration. An absorption spectrum of a breath sample in the wavelength region of around 200-300 nm was measured, and the measured spectrum revealed the main absorbing components in breath as water vapor, isoprene, and ozone converted from oxygen by radiation of ultraviolet light. The concentration of isoprene in breath was estimated by multiple linear regression. The regression analysis results showed that the proposed analysis system enables real-time monitoring of isoprene during the exhaling of breath. Accordingly, it is suitable for measuring the circadian variation of isoprene.

Multi-element hollow-core anti-resonant fiber for infrared thermal imaging.

A bundle composed of 245 anti-resonant glass hollow optical fibers with a total diameter of 1 mm and fiber core diameter of 60 µm is fabricated for endoscopic infrared-thermal imaging. The bundle fiber shows low losses in the wavelength range of 3 to 4 µm owing to the anti-resonant effect of the thin glass wall. An image resolution of around 420 µm with a field-of-view of 3-mm diameter is obtained although crosstalk between adjacent fibers is observed. The experimental results of an imaging system using the fiber bundle with a half-ball lens at the distal end, which can be inserted into a working channel of endoscopes, are also shown.

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%.

Optical-fiber-based laser-induced breakdown spectroscopy for detection of early caries.

A laser-induced breakdown spectroscopy (LIBS) system targeting for the in vivo analysis of tooth enamel is described. The system is planned to enable real-time analysis of teeth during laser dental treatment by utilizing a hollow optical fiber that transmits both Q-switched Nd:YAG laser light for LIBS and infrared Er:YAG laser light for tooth ablation. The sensitivity of caries detection was substantially improved by expanding the spectral region under analysis to ultraviolet (UV) light and by focusing on emission peaks of Zn in the UV region. Subsequently, early caries were distinguished from healthy teeth with accuracy rates above 80% in vitro.

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.

All-optical photoacoustic imaging system using fiber ultrasound probe and hollow optical fiber bundle.

An all-optical 3D photoacoustic imaging probe that consists of an optical fiber probe for ultrasound detection and a bundle of hollow optical fibers for excitation of photoacoustic waves was developed. The fiber probe for ultrasound is based on a single-mode optical fiber with a thin polymer film attached to the output end surface that works as a Fabry Perot etalon. The input end of the hollow fiber bundle is aligned so that each fiber in the bundle is sequentially excited. A thin and flexible probe can be obtained because the probe system does not have a scanning mechanism at the distal end.

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.

Noninvasive subsurface analysis using multiple miniaturized Raman probes, part I: basic study of thin-layered transparent models of biomedical tissues.

This study describes a basic theory for reconstructing pure Raman signals of materials composing a multilayer sample from Raman spectra obtained using two types of miniaturized Raman probes. An illustrative example is demonstrated using a multilayer system of samples composed of the transparent plastics polymethylmethacrylate (PMMA) and polyethylene (PE) as a model of thin-layered biomedical tissues. When the same region of an object is measured using Raman probes with different focal properties, the Raman spectra provide different depth profile information depending on the level of light penetration. Thus, a detailed comparison of the spectra can provide an interesting opportunity to probe the differences between the layers. A simple analytic form is presented for reconstructing the pure Raman spectra of the embedded layer. The method applies an understanding of the Raman sampling volume in layered transparent materials to the interpretation of Raman spectra experimentally measured by multiple probes. The basic theory described here is necessary for the expansion of the technique to turbid media, such as biological samples, where light-scattering effects must be considered. The potential applications of the proposed method include material and catalyst subsurface probing through different embedded materials, such as assessment of silicon wafers, effective noninvasive screening for catalyst synthesis, and biomedical tissue research.

Synchronous radiation with Er:YAG and Ho:YAG lasers for efficient ablation of hard tissues.

Er:YAG and Ho:YAG laser beams were combined to irradiate hard tissues to achieve highly efficient ablation with low laser power. The delay time between pulses of the two lasers was controlled to irradiate alumina ceramic balls used as hard tissue models. With optimized delay time, the combined laser beam perforated the sample 40% deeper than independent radiation by either an Er:YAG or Ho:YAG laser. An ultra-high-speed camera and an infrared thermography camera were used to observe and investigate the ablation mechanisms.

Flexible hollow optical fiber bundle for infrared thermal imaging.

A flexible and coherent bundle of hollow optical fibers was fabricated for infrared thermal imaging. For acquisition of thermal images, differences in the transmission efficiency among the fibers were numerically compensated to obtain high temperature resolution of 1°C for measuring body temperature. In a lens system with 10-fold magnification and hollow fibers of 320-µm inner diameter, the spatial resolution is around 3 mm. The hollow-fiber bundle enables observation of the surface temperature of inner organs and blood flow of the surfaces when the bundle is introduced into the human body with an endoscope.