Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Quantitative polarization-sensitive super-resolution solid immersion microscopy reveals biological tissues' birefringence in the terahertz range.

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging.

Super-resolution THz endoscope based on a hollow-core sapphire waveguide and a solid immersion lens.

To address a challenging problem of super-resolution terahertz (THz) endoscopy, in this paper, an antiresonant hollow-core waveguide was coupled with a sapphire solid immersion lens (SIL), aimed at subwavelength confinement of guided mode. The waveguide is formed by a polytetrafluoroethylene (PTFE)-coated sapphire tube, the geometry of which was optimized to ensure high optical performance. SIL was judiciously designed, fabricated of bulk sapphire crystal, and then mounted at the output waveguide end. Study of the field intensity distributions at the shadow side of the waveguide-SIL system revealed the focal spot diameter of ≃0.2λ at the wavelength of λ = 500 µm. It agrees with numerical predictions, overcomes the Abbe diffraction limit, and justifies super-resolution capabilities of our endoscope.

Boosting photoconductive large-area THz emitter via optical light confinement behind a highly refractive sapphire-fiber lens.

We report on a sapphire-fiber-based lens that can be used to enhance the emitted THz power of a large-area photoconductive antenna (PCA). Using numerical simulations, we demonstrate that the lens provides a spatial redistribution of the photocarriers density in the PCA's gap. By optimizing the diameter of the sapphire-fiber, one could reach efficient confinement of the photocarriers in the vicinity of the PCA electrodes with a 10-µm gap size for a 220-µm-thick sapphire-fiber. This allows enhancing the coupling of the incident electromagnetic waves at the interface between the sapphire fiber and the semiconductor with the antenna terminals by ∼40 times for a single PCA element, as well as boosting the total efficiency of the large-area PCA-emitter up to ∼7-10 times. To validate our approach, we propose a step-by-step process that can be used for the precise and controllable placement of the sapphire-fiber on the surface of a single PCA.

Quantification of solid-phase chemical reactions using the temperature-dependent terahertz pulsed spectroscopy, sum rule, and Arrhenius theory: thermal decomposition of α-lactose monohydrate.

Transformations of the low-energy vibrational spectra are associated with structural changes in an analyte and closely related to the instability of weak chemical bounds. Terahertz (THz)/far-infrared optical spectroscopy is commonly used to probe such transformation, aimed at characterization of the underlying solid-phase chemical reactions in organic compounds. However, such studies usually provide quite qualitative information about the temperature- and time-dependent parameters of absorption peaks in dielectric spectra of an analyte. In this paper, an approach for quantitative analyses of the solid-phased chemical reactions based on the THz pulsed spectroscopy was developed. It involves studying an evolution of the sample optical properties, as a function of the analyte temperature and reaction time, and relies on the classical oscillator model, the sum rule, and the Arrhenius theory. The method allows one to determine the temperature-dependent reaction rate V1(T) and activation energy Ea. To demonstrate the practical utility of this method, it was applied to study α-lactose monohydrate during its temperature-induced molecular decomposition. Analysis of the measured THz spectra revealed the increase of the reaction rate in the range of V1 ≃ ~9 × 10-4-10-2 min-1, when the analyte temperature rises from 313 to 393 K, while the Arrhenius activation energy is Ea ≃ ~45.4 kJ/mol. Thanks to a large number of obtained physical and chemical parameters, the developed approach expands capabilities of THz spectroscopy in chemical physics, analytical chemistry, and pharmaceutical industry.

THz generation by two-color laser air plasma coupled to antiresonance hollow-core sapphire waveguides: THz-wave delivery and angular distribution management.

In this paper, hollow-core antiresonance sapphire waveguides were applied to guide the THz radiation emitted by the two-color laser air plasma, as well as to manage the THz source angular distribution. For this aim, three distinct waveguides were developed. Each of them is based on a cylindrical sapphire tube, either suspended in free space or coated by a polymer. The waveguides were first studied numerically, using the finite-difference eigenmode method, and experimentally, using the in-house THz pulsed spectrometer. The observed data uncovered the antiresonance regime of their operation, as well as their ability to guide broadband THz pulses over tens of centimeters with a high optical performance. The waveguides were then used to couple and guide (over the considerable distance) of THz radiation from the in-house two-color laser air plasma emitter, that exploits the mJ-energy-level femtosecond pulses of a Ti-sapphire laser. Small dispersion of a THz pulse and low-to-moderate propagation loss in the developed waveguide were observed, along with a considerable narrowing of the THz radiation angular distribution after passing the waveguide. Our findings revealed that such technologically-reliable hollow-core sapphire waveguides can boost the performance of laser air plasma-based THz emitters and make them more suitable for applications in the vigorously-explored THz sensing and exposure technologies.

Moisture adsorption by decellularized bovine pericardium collagen matrices studied by terahertz pulsed spectroscopy and solid immersion microscopy.

In this paper, terahertz (THz) pulsed spectroscopy and solid immersion microscopy were applied to study interactions between water vapor and tissue scaffolds-the decellularized bovine pericardium (DBP) collagen matrices, in intact form, cross-linked with the glutaraldehyde or treated by plasma. The water-absorbing properties of biomaterials are prognostic for future cell-mediated reactions of the recipient tissue with the scaffold. Complex dielectric permittivity of DBPs was measured in the 0.4-2.0 THz frequency range, while the samples were first dehydrated and then exposed to water vapor atmosphere with 80.0 ± 5.0% relative humidity. These THz dielectric measurements of DBPs and the results of their weighting allowed to estimate the adsorption time constants, an increase of tissue mass, as well as dispersion of these parameters. During the adsorption process, changes in the DBPs' dielectric permittivity feature an exponential character, with the typical time constant of =8-10 min, the transient process saturation at =30 min, and the tissue mass improvement by =1-3%. No statistically-relevant differences between the measured properties of the intact and treated DBPs were observed. Then, contact angles of wettability were measured for the considered DBPs using a recumbent drop method, while the observed results showed that treatments of DBP somewhat affects their surface energies, polarity, and hydrophilicity. Thus, our studies revealed that glutaraldehyde and plasma treatment overall impact the DBP-water interactions, but the resultant effects appear to be quite complex and comparable to the natural variability of the tissue properties. Such a variability was attributed to the natural heterogeneity of tissues, which was confirmed by the THz microscopy data. Our findings are important for further optimization of the scaffolds' preparation and treatment technologies. They pave the way for THz technology use as a non-invasive diagnosis tool in tissue engineering and regenerative medicine.

Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity.

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

Opal-based terahertz optical elements fabricated by self-assembly of porous SiO2 nanoparticles.

In this paper, we study artificial opals as a promising material platform for terahertz (THz) optics. Materials were synthesized using self-assembly of porous SiO2 nanoparticles and annealing at different temperatures to further tune their optical properties. Two distinct approaches for the fabrication of bulk THz optics from these novel materials were considered. First, THz cylindrical lenses of identical geometry but different refractive indices and focal lengths were produced using standard mechanical processing of opals, in order to highlight their compatibility with conventional technologies of bulk optics fabrication. Second, a THz axicone was made via direct sedimentation of aqueous colloidal suspension of SiO2 nanoparticles in the mold of geometry inverse to that of a desired optical shape, followed by annealing and polishing. The second approach has an advantage of being considerably less labor intensive, while capable of obtaining optical elements of complex geometries. Thus fabricated bulk THz optical elements were studied experimentally using continuous-wave THz imaging, and the results were compared with 2D and 3D numerical predictions based on the finite-difference time-domain and finite-element frequency-domain methods. Our findings highlight technological robustness of the developed THz optical material platform and, thus, open the door for creating a variety of bulk THz optical elements of complex shapes and widely-tunable optical performance.

Object-dependent spatial resolution of the reflection-mode terahertz solid immersion microscopy.

Terahertz (THz) solid immersion microscopy is a novel promising THz imaging modality that overcomes the Abbe diffraction limit. In our prior work, an original reflection-mode THz solid immersion microscope system with the resolution of 0.15λ (in free space) was demonstrated and used for imaging of soft biological tissues. In this paper, a numerical analysis, using the finite-difference time-domain technique, and an experimental study, using a set of objects with distinct refractive indexes, were performed in order to uncover, for the first time, the object-dependent spatial resolution of the THz solid immersion microscopy. Our findings revealed that the system resolution remains strongly sub-wavelength 0.15-0.4λ for the wide range of sample refractive indices n = 1.0-5.0 and absorption coefficients α = 0-400 cm-1 (by power). Considering these findings, two distinct regimes of the THz solid immersion microscopy were identified. First is the total internal reflection regime that takes place when the sample refractive index is relatively low, while the sub-wavelength resolution is enabled by both the evanescent and ordinary reflected waves at the interface between a high-refractive-index material and an imaged object. Second is the ordinary reflection regime that occurs when the sample refractive index is high enough, so that there is no more total internal reflection at the interface, while only the ordinary reflected waves inside a high-refractive-index material are responsible for the sub-wavelength resolution. The resultant conclusions are general and can be applied for analysis of solid immersion lenses operating in other spectral ranges, such as visible and infrared, given linear nature of the Maxwell's equations.

Terahertz dielectric spectroscopy of human brain gliomas and intact tissues ex vivo: double-Debye and double-overdamped-oscillator models of dielectric response.

Terahertz (THz) technology offers novel opportunities in the intraoperative neurodiagnosis. Recently, the significant progress was achieved in the study of brain gliomas and intact tissues, highlighting a potential for THz technology in the intraoperative delineation of tumor margins. However, a lack of physical models describing the THz dielectric permittivity of healthy and pathological brain tissues restrains the further progress in this field. In the present work, the ex vivo THz dielectric response of human brain tissues was analyzed using relaxation models of complex dielectric permittivity. Dielectric response of tissues was parametrized by a pair of the Debye relaxators and a pair of the overdamped-oscillators - namely, the double-Debye (DD) and double-overdamped-oscillator (DO) models. Both models accurately reproduce the experimental curves for the intact tissues and the WHO Grades I-IV gliomas. While the DD model is more common for THz biophotonics, the DO model is more physically rigorous, since it satisfies the sum rule. In this way, the DO model and the sum rule were, then, applied to estimate the content of water in intact tissues and gliomas ex vivo. The observed results agreed well with the earlier-reported data, justifying water as a main endogenous label of brain tumors in the THz range. The developed models can be used to describe completely the THz-wave - human brain tissues interactions in the frameworks of classical electrodynamics, being quite important for further research and developments in THz neurodiagnosis of tumors.

Capability of physically reasonable OCT-based differentiation between intact brain tissues, human brain gliomas of different WHO grades, and glioma model 101.8 from rats.

Optical coherence tomography (OCT) of the ex vivo rat and human brain tissue samples is performed. The set of samples comprises intact white and gray matter, as well as human brain gliomas of the World Health Organization (WHO) Grades I-IV and glioma model 101.8 from rats. Analysis of OCT signals is aimed at comparing the physically reasonable properties of tissues, and determining the attenuation coefficient, parameter related to effective refractive index, and their standard deviations. Data analysis is based on the linear discriminant analysis and estimation of their dispersion in a four-dimensional principal component space. The results demonstrate the distinct contrast between intact tissues and low-grade gliomas and moderate contrast between intact tissues and high-grade gliomas. Particularly, the mean values of attenuation coefficient are 7.56±0.91, 3.96±0.98, and 5.71±1.49 mm-1 for human white matter, glioma Grade I, and glioblastoma, respectively. The significant variability of optical properties of high Grades and essential differences between rat and human brain tissues are observed. The dispersion of properties enlarges with increase of the glioma WHO Grade, which can be attributed to the growing heterogeneity of pathological brain tissues. The results of this study reveal the advantages and drawbacks of OCT for the intraoperative diagnosis of brain gliomas and compare its abilities separately for different grades of malignancy. The perspective of OCT to differentiate low-grade gliomas is highlighted by the low performance of the existing intraoperational methods and instruments.

Proof of concept for continuously-tunable terahertz bandpass filter based on a gradient metal-hole array.

A continuously-tunable terahertz (THz) bandpass filter based on the resonant electromagnetic-wave transmission through a metal-hole array featuring a gradually changing period was developed and fabricated on a silicon substrate using optical lithography. A gradient geometry of the metal-hole array yields a wide tunability of the filter transmission, when operating with a focussed THz beam. The filter was studied numerically, using the finite element method, and experimentally, using the THz pulsed spectroscopy. We find that the central wavelength of the filter transmission band can be tuned in the wide range of λc = 400-800 µm with the relative bandwidth of Δλ/λc ≃ ~0.4. Finally, Kapton-based anti-reflection coating was applied to the filter flat side, in order to suppress an interference pattern in the filter transmission spectrum. We believe that the developed filter holds strong potential for multispectral THz imaging and sensing due to its conceptual simplicity and case of operation. Moreover, the presented filter concept can be translated to other spectral ranges, where appropriate technologies are available for the fabrication of gradient sub-wavelength metal-hole arrays.

Multimodal Optical Diagnostics of Glycated Biological Tissues.

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia accompanied by the disruption of carbohydrate, lipid, and proteins metabolism and development of long-term microvascular, macrovascular, and neuropathic changes. This review presents the results of spectroscopic studies on the glycation of tissues and cell proteins in organisms with naturally developing and model diabetes and in vitro glycated samples in a wide range of electromagnetic waves, from visible light to terahertz radiation. Experiments on the refractometric measurements of glycated and oxygenated hemoglobin in broad wavelength and temperature ranges using digital holographic microscopy and diffraction tomography are discussed, as well as possible application of these methods in the diabetes diagnostics. It is shown that the development and implementation of multimodal approaches based on a combination of phase diagnostics with other methods is another promising direction in the diabetes diagnostics. The possibilities of using optical clearing agents for monitoring the diffusion of substances in the glycated tissues and blood flow dynamics in the pancreas of animals with induced diabetes have also been analyzed.

Flame propagation in two-dimensional solids: Particle-resolved studies with complex plasmas.

Using two-dimensional (2D) complex plasmas as an experimental model system, particle-resolved studies of flame propagation in classical 2D solids are carried out. Combining experiments, theory, and molecular dynamics simulations, we demonstrate that the mode-coupling instability operating in 2D complex plasmas reveals all essential features of combustion, such as an activated heat release, two-zone structure of the self-similar temperature profile ("flame front"), as well as thermal expansion of the medium and temperature saturation behind the front. The presented results are of relevance for various fields ranging from combustion and thermochemistry, to chemical physics and synthesis of materials.