Terahertz Spectroscopic Imaging Research Articles

Direct generation of a terahertz vector beam from a ZnTe crystal excited by a focused circular polarized pulse.

A vector beam is a type of topological beam in which the polarization direction of light rotates around a singularity on the wavefront. This paper proposes a method to generate a vector beam by tightly focusing a pump beam in the crystalline direction such that the second-order nonlinear optical effect is forbidden. The directional dependence of the effective nonlinearity in zincblende crystals, such as ZnTe, was analytically investigated. Two types of nonlinear polarization singularities were found in [111] and [100] directions. Their polarization topological charge ℓ was +1 and -1, respectively. To experimentally demonstrate the proposed method, a (111) cut ZnTe crystal was selected as the nonlinear crystal. The polarization state of the generated terahertz (THz) beams was measured with a custom-built THz spectroscopic polarization imaging system. Radially polarized distributions were observed within the entire generated spectral region. Such a broadband feature of the generated vector beam is likely due to the topological nature of the focused pump beam, where the wavevectors are winding once about the optical axis. This simple method for generating THz vector beams will accelerate its applications.

Studying Oral Tissue via Real-Time High-Resolution Terahertz Spectroscopic Imaging

Terahertz (THz) waves are extremely sensitive to water content and biological composition (proteins, genes, and metabolites), which are the key regulator of cancer development. Hence, the application of THz spectroscopy and imaging is promising in the field of biomedicine, especially in cancer diagnosis. Currently, the diagnosis of cancer patients (including tumor borders, tumor stage, etc.) mainly rely on optical microscope observation of pathological slices. The preparation of the slices is complicated and time consuming, and the microscopic field of view is small, which cannot effectively guide the precise removal of the tumor during the operation in time. To solve this problem, a label-free real-time high-resolution near-field THz spectroscopy imaging technique was developed. In this study, we successfully apply this technique to the oral tissue. Compared with conventional point-by-point scanning terahertz time-domain spectroscopy imaging, this technique can exhibit a real-time imaging rate (as high as 20 frames/s at 512 \ifmmode\times\else\texttimes\fi{} 1024 pixels) and a field of view approximately 5 mm in diameter with a spatial resolution up to \ensuremath{\lambda}/10 at 1 THz in near-field condition. The experimental results show that the terahertz spectroscopic imaging in this paper can clearly detect and identify not only biological tissues with different components, but also normal and cancerous tissues, as well as tissues with the same composition but different slice directions. This work lays an experimental foundation for the application of THz spectroscopy imaging to rapid label-free intraoperative diagnosis, and it provides a basis for promoting the wide application of THz technology in the biomedical field.

Supervised machine learning for automatic classification of in vivo scald and contact\xa0burn injuries using the terahertz Portable Handheld Spectral Reflection (PHASR) Scanner

We present an automatic classification strategy for early and accurate assessment of burn injuries using terahertz (THz) time-domain spectroscopic imaging. Burn injuries of different severity grades, representing superficial partial-thickness (SPT), deep partial-thickness (DPT), and full-thickness (FT) wounds, were created by a standardized porcine scald model. THz spectroscopic imaging was performed using our new fiber-coupled Portable HAndheld Spectral Reflection Scanner, incorporating a telecentric beam steering configuration and an f-theta scanning lens. ASynchronous Optical Sampling in a dual-fiber-laser THz spectrometer with 100 MHz repetition rate enabled high-speed spectroscopic measurements. Given twenty-four different samples composed of ten scald and ten contact burns and four healthy samples, supervised machine learning algorithms using THz-TDS spectra achieved areas under the receiver operating characteristic curves of 0.88, 0.93, and 0.93 when differentiating between SPT, DPT, and FT burns, respectively, as determined by independent histological assessments. These results show the potential utility of our new broadband THz PHASR Scanner for early and accurate triage of burn injuries.

Qualitative detection of amino acids in a mixture with terahertz spectroscopic imaging

Terahertz time-domain spectroscopy (THz-TDS) is widely used in non-destructive testing and chemical identification due to the wide spectrum, low photon energy, distinctive absorption spectra, and higher intensity than other thermal radiators. Here, we propose a method to detect amino acids from a mixture at room temperature and in humid air. A THz-TDS spectrometer scans tablets of amino acid mixtures laid out on a polyethylene plate in transmission mode. The resulting spectroscopic imaging is then converted to probability maps (chemical maps), where the region containing the expected amino acid has higher pixel values, by a matrix manipulation with the matrix of absorption spectra. This approach is substantially resistant to air humidity and scattering caused by uneven grain sizes and is applicable to substances without strong absorption features. A classifier based on LeNet-5 is built to identify the subsection of the chemical map containing the expected substance, and the prediction reaches 100% accuracy for the testing dataset. The results of the classifier are compared with those of a support vector machine, whose accuracy is much lower due to its inferior ability to recognize complex patterns. The proposed method will enable us to qualitatively detect a component from an unknown mixture in a single measurement and will be useful for bio-molecule detection in real-life scenarios.

Application of Machine Learning to Terahertz Spectroscopic Imaging of Reagents Hidden By Thick Shielding Materials

We achieved high identification accuracy of reagents hidden by thick shielding materials, by combining injection-seeded terahertz (THz) wave parametric generator measurements and machine learning analysis. The analysis performance of three methods, support vector machine (SVM), k-nearest neighbor, and random forest, was compared in an attempt to identify the optimal approach. SVM proved to be the best model. Conventional systems could only identify reagents through premeasured shields; however, incorporation of machine learning allowed us to identify the reagents through shielding materials that had not been premeasured. Moreover, spectroscopic imaging of the reagents revealed the distribution pattern of the reagents, even through thick shielding materials that attenuated THz frequencies such that they were close to the noise level.

Non-destructive quality control detection of endogenous contaminations in walnuts using terahertz spectroscopic imaging

The precise detection of foreign bodies in food is significant for guaranteeing food safety and quality. Terahertz (THz) spectroscopic imaging is a rapidly evolving technique with the advantages of non-destructive, non-ionization, and spectral fingerprinting characteristics, so it has attracted a lot of attention in the food industry. In this paper, the possibility of THz spectroscopic imaging in the detection of endogenous contaminations in a complex food matrix was explored. We first tried to detect endogenous foreign bodies in walnuts though comparing the typical absorption spectra of kernels and shells with different concentrations. The spectral classification could be realized by principal component analysis with an accuracy higher than 95%, which proved the feasibility of distinguishing shells from kernels, and then, THz imaging was applied to locate shells and kernels in tablets. The results of this study showed that THz spectroscopic imaging could discriminate shell contaminations from walnut kernels.

A Comprehensive Review on Food Applications of Terahertz Spectroscopy and Imaging.

Food product safety is a public health concern. Most of the food safety analytical and detection methods are expensive, labor intensive, and time consuming. A safe, rapid, reliable, and nondestructive detection method is needed to assure consumers that food products are safe to consume. Terahertz (THz) radiation, which has properties of both microwave and infrared, can penetrate and interact with many commonly used materials. Owing to the technological developments in sources and detectors, THz spectroscopic imaging has transitioned from a laboratory-scale technique into a versatile imaging tool with many practical applications. In recent years, THz imaging has been shown to have great potential as an emerging nondestructive tool for food inspection. THz spectroscopy provides qualitative and quantitative information about food samples. The main applications of THz in food industries include detection of moisture, foreign bodies, inspection, and quality control. Other applications of THz technology in the food industry include detection of harmful compounds, antibiotics, and microorganisms. THz spectroscopy is a great tool for characterization of carbohydrates, amino acids, fatty acids, and vitamins. Despite its potential applications, THz technology has some limitations, such as limited penetration, scattering effect, limited sensitivity, and low limit of detection. THz technology is still expensive, and there is no available THz database library for food compounds. The scanning speed needs to be improved in the future generations of THz systems. Although many technological aspects need to be improved, THz technology has already been established in the food industry as a powerful tool with great detection and quantification ability. This paper reviews various applications of THz spectroscopy and imaging in the food industry.

Evaluation of cancer tissue morphology via THz spectroscopic imaging: Human lung and small intestine malignancies

We investigate the potential of terahertz spectroscopic imaging for assessment of malignant tissues in human lung and small intestine using a reflection-mode time-domain spectroscopy system spanning the 60 GHz–2 THz band. These two tissue groups are among the few that can be reached via an endoscopic sensor, thus potentially allowing for in-situ assessment of suspected tumors. As an initial study toward this goal, we characterized formalin-fixed and paraffin-embedded tissue blocks using a commercially-available reflection-mode time domain spectroscopy system. We verify that the measured THz responses of these tissue groups reveal key differences in their morphology, material density, and electrical properties. The spectroscopic characteristics in the THz band are contrasted with the histopathologic assessment of hematoxylin and eosin stained tissue slices to demonstrate the potential of THz spectroscopy for evaluating lung and small intestine malignancies. For both types of organ tissues, it is demonstrated that the THz images provide key discriminatory information such as tissue morphology, cancer margin, and necrotic areas in the tumor.

Spectroscopic Analysis of Melatonin in the Terahertz Frequency Range.

There is a need for fast and reliable quality and authenticity control tools of pharmaceutical ingredients. Among others, hormone containing drugs and foods are subject to scrutiny. In this study, terahertz (THz) spectroscopy and THz imaging are applied for the first time to analyze melatonin and its pharmaceutical product Circadin. Melatonin is a hormone found naturally in the human body, which is responsible for the regulation of sleep-wake cycles. In the THz frequency region between 1.5 THz and 4.5 THz, characteristic melatonin spectral features at 3.21 THz, and a weaker one at 4.20 THz, are observed allowing for a quantitative analysis within the final products. Spectroscopic THz imaging of different concentrations of Circadin and melatonin as an active pharmaceutical ingredient in prepared pellets is also performed, which permits spatial recognition of these different substances. These results indicate that THz spectroscopy and imaging can be an indispensable tool, complementing Raman and Fourier transform infrared spectroscopies, in order to provide quality control of dietary supplements and other pharmaceutical products.

Terahertz spectroscopic imaging with discriminant analysis for detecting foreign materials among sausages

The accurate and rapid detection of foreign materials in food products is essential for ensuring food safety and quality. Terahertz (THz) imaging is an emerging technology for non-destructive detection in food industrial with the advantages of non-ionization and spectroscopic fingerprinting. In this study, we have attempted to explore the effectiveness of THz spectroscopic imaging for foreign material detection in food with complicated compositions. The feasibility of locating contaminations in sausages were demonstrated through typical spectral comparison, spectral classification assisted by principal component analysis and discriminant analysis methods, and one-dimensional scanning spectral analysis. Our imaging results indicated THz spectroscopic imaging has the ability to locate metal contaminations in sausages no matter what part of sausages is as the food matrix. This study will provide new knowledge about foreign material detection in food with complicated compositions and a basis for parameters selection of continuous-wave THz imaging for contamination detection in this case.

Measuring water contents in animal organ tissues using terahertz spectroscopic imaging.

We investigated the water contents in several organ tissues such as the liver, spleen, kidney, and brain tissue of rats using the terahertz spectroscopic imaging technique. The water contents of the tissues were determined by using a simple equation containing the absorption coefficients of fresh and lyophilized tissues and water. We compared the measured water contents with the difference in mass of tissues before and after lyophilization. All results showed a good match except for the kidney, which has several Bowman's capsules.

Recent advances in the applications of vibrational spectroscopic imaging and mapping to pharmaceutical formulations

Vibrational spectroscopic imaging and mapping approaches have continued in their development and applications for the analysis of pharmaceutical formulations. Obtaining spatially resolved chemical information about the distribution of different components within pharmaceutical formulations is integral for improving the understanding and quality of final drug products. This review aims to summarise some key advances of these technologies over recent years, primarily since 2010. An overview of FTIR, NIR, terahertz spectroscopic imaging and Raman mapping will be presented to give a perspective of the current state-of-the-art of these techniques for studying pharmaceutical samples. This will include their application to reveal spatial information of components that reveals molecular insight of polymorphic or structural changes, behaviour of formulations during dissolution experiments, uniformity of materials and detection of counterfeit products. Furthermore, new advancements will be presented that demonstrate the continuing novel applications of spectroscopic imaging and mapping, namely in FTIR spectroscopy, for studies of microfluidic devices. Whilst much of the recently developed work has been reported by academic groups, examples of the potential impacts of utilising these imaging and mapping technologies to support industrial applications have also been reviewed.

THz Spectroscopic Identification of Red Mineral Pigments in Ancient Chinese Artworks

Nondestructive analysis of historical objects is of significance for cultural heritage conservation. In this paper, terahertz time-domain spectroscopy (THz-TDS) was used to distinguish seven red mineral pigments used in ancient Chinese artworks. Two absorption features of natural minerals HgS and four highly resolved spectral features of mineral pigment Pb3O4 were observed and identified as their fingerprints in the range 0.2 to 3.0 THz, based on which the spatial distribution of individual chemical substances including cinnabar, vermilion, and red lead were clearly revealed at various frequencies using terahertz spectroscopy imaging. Moreover, a noncontact evaluation of thickness changing and dehydration of a wet painting was monitored by inferring time delay as well as signal amplitude of THz pulses transmitted through the painting. In order to demonstrate the feasibility of THz-TDS and THz imaging for authentic artworks detection, a complete set of THz analysis of two nineteenth century wall paintings discovered in the Fuchen Temple of the Forbidden City, Beijing, was performed and the results indicate that THz measurement techniques provide a noninvasive and nondestructive solution for the care, preservation, and restoration of cultural relics.

Real-time broadband terahertz spectroscopic imaging by using a high-sensitivity terahertz camera

Terahertz (THz) imaging has a strong potential for applications because many molecules have fingerprint spectra in this frequency region. Spectroscopic imaging in the THz region is a promising technique to fully exploit this characteristic. However, the performance of conventional techniques is restricted by the requirement of multidimensional scanning, which implies an image data acquisition time of several minutes. In this study, we propose and demonstrate a novel broadband THz spectroscopic imaging method that enables real-time image acquisition using a high-sensitivity THz camera. By exploiting the two-dimensionality of the detector, a broadband multi-channel spectrometer near 1 THz was constructed with a reflection type diffraction grating and a high-power THz source. To demonstrate the advantages of the developed technique, we performed molecule-specific imaging and high-speed acquisition of two-dimensional (2D) images. Two different sugar molecules (lactose and D-fructose) were identified with fingerprint spectra, and their distributions in one-dimensional space were obtained at a fast video rate (15 frames per second). Combined with the one-dimensional (1D) mechanical scanning of the sample, two-dimensional molecule-specific images can be obtained only in a few seconds. Our method can be applied in various important fields such as security and biomedicine.

THz Spectroscopic Imaging of Chemicals Using IS-TPG

In 2003, we demonstrated a non-destructive terahertz spectroscopic imaging of illicit drugs hidden in envelopes using a widely tunable THz-wave parametric source, though its dynamic range at that time was less than four orders. Recently, we have realized more than nine orders of dynamic range with an evolved injection seeded THz-wave spectrometer. Now we can detect drugs under much thicker obstacles than before. In this report, we introduce the result of THz spectroscopic imaging of chemicals under thick envelopes and related topics; Enhanced tuning range of is-TPG up to 5 THz and >90 dB dynamic range THz spectroscopic system.

Spectroscopic Terahertz Imaging at Room Temperature Employing Microbolometer Terahertz Sensors and Its Application to the Study of Carcinoma Tissues.

A terahertz (THz) imaging system based on narrow band microbolometer sensors (NBMS) and a novel diffractive lens was developed for spectroscopic microscopy applications. The frequency response characteristics of the THz antenna-coupled NBMS were determined employing Fourier transform spectroscopy. The NBMS was found to be a very sensitive frequency selective sensor which was used to develop a compact all-electronic system for multispectral THz measurements. This system was successfully applied for principal components analysis of optically opaque packed samples. A thin diffractive lens with a numerical aperture of 0.62 was proposed for the reduction of system dimensions. The THz imaging system enhanced with novel optics was used to image for the first time non-neoplastic and neoplastic human colon tissues with close to wavelength-limited spatial resolution at 584 GHz frequency. The results demonstrated the new potential of compact RT THz imaging systems in the fields of spectroscopic analysis of materials and medical diagnostics.

Terahertz spectroscopic imaging and properties of gastrointestinal tract in a rat model.

We have investigated basic properties of normal gastrointestinal (GI) tract tissues, including glandular stomach (GS), fore stomach (FS), large intestine (LI), small intestine (SI), and esophagus (ESO), from a rat model using terahertz (THz) reflection imaging and spectroscopy. The THz images collected from stratified squamous epithelia (SSE) of FS and ESO show a lower peak-to-peak value compared to those from columnar epithelia (CE) of GS, LI, or SI because the SSE contains less water than CE. The refractive index and absorption coefficient of FS were less than those of GS or LI, both having values similar to those of water. Additionally, we report internal reflection THz signals from ESO, although we were unable to determine the exact interface for this internal reflection.

Observation of hydrofluoric acid burns on osseous tissues by means of terahertz spectroscopic imaging.

Terahertz technologies have gained great amount of attention for biomedical imaging and tissue analysis. In this study, we utilize terahertz imaging to study the effects of hydrofluoric acid on both compact bone tissue and cartilage. We compare the differences observed in the exposure for formalin fixed and raw, dried, tissue as well as those resulting from a change in hydrofluoric (HF) concentration. Measurements are performed with THz-TDS, and a variety of spectroscopic-based image reconstruction techniques are utilized to develop contrast in the features of interest.

Observation of Hydrofluoric Acid Burns on Osseous Tissues by Means of Terahertz Spectroscopic Imaging

Terahertz technologies have gained great amount of attention for biomedical imaging and tissue analysis. In this study, we utilize terahertz imaging to study the effects of hydrofluoric acid on both compact bone tissue and cartilage. We compare the differences observed in the exposure for formalin fixed and raw, dried, tissue as well as those resulting from a change in hydrofluoric (HF) concentration. Measurements are performed with THz-TDS, and a variety of spectroscopic-based image reconstruction techniques are utilized to develop contrast in the features of interest.

Chemical Mapping of Pharmaceutical Cocrystals Using Terahertz Spectroscopic Imaging

Terahertz (THz) spectroscopic imaging is a promising technique for distinguishing pharmaceuticals of similar molecular composition but differing crystal structures. Physicochemical properties, for instance bioavailability, are manipulated by altering a drug's crystal structure through methods such as cocrystallization. Cocrystals are molecular complexes having crystal structures different from those of their pure components. A technique for identifying the two-dimensional distribution of these alternate forms is required. Here we present the first demonstration of THz spectroscopic imaging of cocrystals. THz spectra of caffeine-oxalic acid cocrystal measured at low temperature exhibit sharp peaks, enabling us to visualize the cocrystal distribution in nonuniform tablets. The cocrystal distribution was clearly identified using THz spectroscopic data, and the cocrystal concentration was calculated with 0.3-1.3% w/w error from the known total concentration. From this result, THz spectroscopy allows quantitative chemical mapping of cocrystals and offers researchers and drug developers a new analytical tool.