Terahertz Spectral Characterization of NIR Nanomaterials
Jillian P. Martin, M.E. Gkikas, C.S. Joseph and R.H. Giles
Biomedical Terahertz Technology Center, University of Massachusetts Lowell, MA, USA
Near-infrared responsive (NIR) nanomaterials are currently being developed for use in photothermal and photodynamic cancer treatment therapies. The NIR nanomaterials under investigation for such therapies include gold nanorods, gold nanoshells, lanthanide-doped nanomaterials, and graphene oxide. To date, researchers have shown that terahertz (THz) time-domain spectroscopy (TDS) can be used to track the concentration of gold nanorods. In this work, a THz-TDS system is utilized to investigate the terahertz spectral characteristics of various solutions of NIR nanomaterials.
Millimeter-wave technologies for the automotive industry are driving inexpensive source/receiver hardware solutions for a wide variety of applications. In order to accurately assess signature characteristics of various scenes, we tested the appropriateness of using an artificial torso in controlled environments and compared the results to data from live subjects. High-range resolution (HRR) backscatter Radar Cross Section (RCS) data from targets and in-scene calibration objects were obtained using a 75GHz transceiver with 8GHz bandwidth. Data was collected for both the artificial torso and live subjects at varying aspects in controlled environments – this included studying the RCS response at different illumination angles while calibrating the response using in-scene calibration targets. Comparing the HRR profiles has allowed UML/UMMS researchers to accurately assess and demonstrate the utilization of artificial constructs in scenes for testing the system response characteristics.
Transmission measurements of 11 different garments composed of different materials and different thickness under different conditions were measured. The setup consisted of a 100 Gigahertz camera system which used an IMPATT diode (66mW power output) as the source, a 32x32 image sensor array (1.5x1.5mm pixels, 1 nW/√Hz Noise Equivalent Power) focused with PTFE lens (50mm focal length). The camera system was configured for reflection imaging by placing the source emitter and imaging array at an off-axis angle and focused on a large flat mirrored surface. To simulate reflection of the emitted signal off human skin after transmission through the garments, we placed the garments over the mirrored surface. We then calculated the transmission loss, in terms of signal strength (amplitude), as the ratio of the recorded images with and without the garments. The materials and make-up of the garments were recorded, such as colors, accents, and thickness. To increase the realism of the data, we added several conditions for each garment transmission recording that included overlapping wrinkles and multiple garment layers. We were able to confirm transmission results reported from other research groups, but found that variations such as wrinkles and multiple layers can change the transmission ratios significantly.
Biomedical applications of terahertz (THz) radiation are appealing because THz radiation is nonionizing and has the demonstrated ability to detect intrinsic contrasts between cancerous and normal tissue. A linear polarization-sensitive detection technique for tumor margin delineation has already been demonstrated; however, utilization of a circular polarization-sensitive detection technique has yet to be explored at THz frequencies. A reflective, continuous-wave THz imaging system capable of illuminating a target sample at 584 GHz with either linearly or circularly polarized radiation, and capable of collecting both cross- and copolarized signals remitted from the target, is implemented. To demonstrate the system’s utility, a fresh ex vivo human skin tissue specimen containing nonmelanoma skin cancer was imaged. Both polarization-sensitive detection techniques showed contrast between tumor and normal skin tissue, although some differences in images were observed between the two techniques. Our results indicate that further investigation is required to explain the contrast mechanism, as well as to quantify the specificity and sensitivity of the circular polarization-sensitive detection technique.
Terahertz (THz) imaging is emerging as a robust platform for a myriad of applications in the fields of security, health, astronomy and material science. The terahertz regime with wavelengths spanning from microns to millimeters is a potentially safe and noninvasive medical imaging modality for detecting cancers. Endoscopic imaging systems provide high flexibility in examining the interior surfaces of an organ or tissue. Researchers have been working on the development of THz endoscopes with photoconductive antennas, which necessarily operate under high voltage, and require at least two channels to measure the reflected signal from the specimen. This manuscript provides the design and imperative steps involved in the development of a single-channel terahertz endoscopic system. The continuous-wave terahertz imaging system utilizes a single flexible terahertz waveguide channel to transmit and collect the back reflected intrinsic terahertz signal from the sample and is capable of operation in both transmission and reflection modalities. To determine the feasibility of using a terahertz endoscope for cancer detection, the co- and cross-polarized terahertz remittance from human colonic tissue specimens were collected at 584 GHz frequency. The two dimensional terahertz images obtained using polarization specific detection exhibited intrinsic contrast between cancerous and normal regions of fresh colorectal tissue. The level of contrast observed using endoscopic imaging correlates well with the contrast levels observed in the free space ex vivo terahertz reflectance studies of human colonic tissue. The prototype device developed in this study represents a significant step towards clinical endoscopic application of THz technology for in vivo colon cancer screening.
Colorectal cancer is the third most commonly diagnosed cancer in the world. The current standard of care for colorectal cancer is the conventional colonoscopy, which relies exclusively on the Physician’s experience. Continuous wave terahertz (THz) imaging has the potential to offer a safe, noninvasive medical imaging modality for detecting cancers. The current study demonstrates the design and development of a prototype terahertz endoscopic system based on flexible metal-coated terahertz waveguides. A CO2 pumped Far-Infrared molecular gas laser operating at 584 GHz frequency was used for illuminating the tissue, while the reflected signals were detected using liquid Helium cooled silicon bolometer. The continuous-wave terahertz imaging system utilizes a single waveguide channel to transmit the radiation and collect the back reflected intrinsic terahertz signal from the sample and is capable of operation in both transmission and reflection modalities. The two dimensional reflectance images obtained using a prototype terahertz endoscopic system showed intrinsic contrast between cancerous and normal regions of the colorectal tissue, thereby demonstrating the potential impact of terahertz imaging for in vivo cancer detection.
We demonstrate the design and development of an innovative single-channel terahertz (THz) prototype endoscopic imaging system based on flexible metal-coated THz waveguides and a polarization specific detection technique. The continuous-wave (CW) THz imaging system utilizes a single channel to transmit and collect the reflected intrinsic THz signal from the sample. Since the prototype system relies on a flexible waveguide assembly that is small enough in diameter, it can be readily integrated with a conventional optical endoscope. This study aims to show the feasibility of waveguide enabled THz imaging. We image various objects in transmission and reflection modes. We also image normal and cancerous colonic tissues in reflectance mode using a polarization specific imaging technique. The resulting cross-polarized THz reflectance images showed contrast between normal and cancerous colonic tissues at 584 GHz. The level of contrast observed using endoscopic imaging correlates well with contrast levels observed in ex vivo THz reflectance studies of colon cancer. This indicates that the single-channel flexible waveguide-based THz endoscope presented here represents a significant step forward in clinical endoscopic application of THz technology to aid in in vivo cancer screening.
Continuous wave terahertz (THz) imaging has the potential to offer a safe, noninvasive medical imaging modality for delineating colorectal cancer. The terahertz reflectance measurements of fresh 3 – 5 mm thick human colonic excisions were acquired using a continuous-wave polarization imaging technique. A CO2 optically pumped Far- Infrared molecular gas laser operating at 584 GHz was used to illuminate the colon tissue, while the reflected signals were detected using a liquid Helium cooled silicon bolometer. Both co-polarized and cross-polarized remittance from the samples was collected using wire grid polarizers in the experiment. The experimental analysis of 2D images obtained from THz reflection polarization imaging techniques showed intrinsic contrast between cancerous and normal regions based on increased reflection from the tumor. Also, the study demonstrates that the cross-polarized terahertz images not only correlates better with the histology, but also provide consistent relative reflectance difference values between normal and cancerous regions for all the measured specimens.
We demonstrate a reflective, continuous-wave terahertz (THz) imaging system to acquire ex vivo images of fresh human colonic excisions. Reflection measurements of 5-mm-thick sections of colorectal tissues were obtained using a polarization-specific detection technique. Two-dimensional THz reflection images of both normal and cancerous colon tissues with a spatial resolution of 0.6 mm were acquired using an optically pumped far-infrared molecular gas laser. Good contrast has been observed between normal and tumorous tissues at 584 GHz frequency. The resulting THz reflection images compared with the tissue histology showed a correlation between cancerous region and increased reflection. We hypothesize that the imaging system and polarization techniques are capable of registering reflectance differences between cancerous and normal colon. However, further investigations are necessary to completely understand the source mechanism behind the contrast and confirm the hypothesis; if true, it likely represents the first continuous-wave THz reflection imaging technique to show sufficient contrast to identify colon tumor margins. Also, it may represent a significant step forward in clinical endoscopic application of THz technology to aid in in vivo colorectal cancer screening.
Continuous wave terahertz (THz) imaging has the potential to offer a safe, non-ionizing, and nondestructive medical imaging modality for delineating colorectal cancer. Fresh excisions of normal colon tissue were obtained from surgeries performed at the University of Massachusetts Medical School, Worcester. Reflection measurements of thick sections of colorectal tissues, mounted in an aluminum sample holder, were obtained for both fresh and formalin fixed tissues. The two-dimensional reflection images were acquired by using an optically pumped far-infrared molecular gas laser operating at 584 GHz with liquid Helium cooled silicon bolometer detector. Using polarizers in the experiment both co-polarized and cross-polarized remittance form the samples was collected. Analysis of the images showed the importance of understanding the effects of formalin fixation while determining reflectance level of tissue response. The resulting co- and cross-polarized images of both normal and formalin fixed tissues showed uniform terahertz response over the entire sample area. Initial measurements indicated a co-polarized reflectance of 16%, and a cross-polarized reflectance of 0.55% from fresh excisions of normal colonic tissues.
Nonmelanoma skin cancers are the most common form of cancer. Continuous wave terahertz imaging has the
potential to differentiate between nonmelanoma skin cancers and normal skin. Terahertz imaging is non-ionizing
and offers a high sensitivity to water content. Contrast between cancerous and normal tissue in transmission mode
has already been demonstrated using a continuous wave terahertz system. The aim of this experiment was to
implement a system that is capable of reflection modality imaging of nonmelanoma skin cancers. Fresh excisions of
skin cancer specimens were obtained from Mohs surgeries for this study. A CO2 optically pumped far-infrared
molecular gas laser was used for illuminating the tissue at 584 GHz. The reflected signal was detected using a liquid
Helium cooled Silicon bolometer. The terahertz images were compared with sample histology. The terahertz
reflection images exhibit some artifacts that can hamper the specificity. The beam waist at the sample plane was
measured to be 0.57 mm, and the system's signal-to-noise ratio was measured to be 65 dB.
Low-loss hollow flexible metal/dielectric coated polycarbonate waveguides have been designed and fabricated
for the maximal transmission of Terahertz radiation (THz). Attenuation characteristics of Terahertz radiation in Ag/Au
coated waveguides with bore diameters 4.1 mm, 3.2 mm, 2 mm were studied at 215 µm wavelength and the maximal
transmission was obtained by coupling the lowest loss TE11 mode from an optically pumped terahertz laser.
Transmission loss can be reduced substantially by adding a dielectric layer to the metal coated waveguide and by
coupling HE11 mode into it. Polystyrene (PS) was chosen to be the dielectric, due to its low extinction coefficient, which
enhances the transmission through the waveguide. A propagation loss of less than 1 dB/m was achieved with these
metal/dielectric coated waveguides.
Medical and security sensing applications of Terahertz (THz) imaging are currently
being developed. As a result, there is a need to further investigate the effects of THz
radiation on biological systems. In this study, a 94 GHz mechanically tuned Gunn Oscillator
was used to irradiate Bacillus subtilis at 94 GHz. The bacteria were cultured in trypticase
soy broth (TSB) and placed in polystyrene 96 well plates. The samples where irradiated
during the exponential growth phase for 1, 2, and 24 hours. Both the experimental and
control plates were kept at room temperature (~25°C) and were monitored for the
duration of the experiment using thermocouples interfaced with a computer via Labview
software. By evaluating the absorption of each well at 600nm immediately before and after
irradiation, the population density within each well was assessed. Following this, the
metabolic activity of each well was measured after irradiation by adding tetrazolium dye,
XTT, to the wells and evaluating the absorption of each well at 490nm after 2 hours of
Continuous wave terahertz imaging has the potential for diagnosing and delineating skin cancers. While contrast has
been observed between cancerous and normal tissue at terahertz frequencies, the source mechanism behind this contrast
is not clearly understood.1Transmission measurements of 240μm thick sections of nonmelanoma skin cancer were taken
at two frequencies of 1.39 THz and 1.63 THz that lie within and outside the tryptophan absorption band, respectively.
Two CO2 pumped Far-Infrared molecular gas lasers were used for illuminating the tissue while the transmitted signals
were detected using a liquid Helium cooled Silicon bolometer. At both THz frequencies 2-dimensional THz transmission
images of nonmelanoma skin cancers were acquired with better than 0.5mm spatial resolution. The resulting images
were compared to the sample histology and showed a correlation between cancerous tissue and decreased transmission.
The results of the imaging experiments will be presented and discussed.
Continuous wave terahertz imaging has the potential to offer a safe, non-invasive medical imaging modality for detecting
different types of human cancers. The aim of this study was to identify intrinsic biomarkers for non-melanoma skin
cancer and their absorption frequencies. Knowledge of these frequencies is a prerequisite for the optimal development of
a continuous wave terahertz imaging system for detecting different types of skin cancers. The absorption characteristics
of skin constituents were studied between 20 and 100 cm-1 (0.6 THz - 3 THz). Terahertz radiation is highly absorbed by
water. Thus, the high water content of human tissue necessitates a reflection based imaging modality. To demonstrate a
reflection based, high resolution, terahertz imaging system, a prototype imaging system was constructed at 1.56 THz.
The system resolution was determined to be 0.5 mm and the system signal to noise ratio was found to be 70 dB. Data
from the terahertz spectroscopy experiments and reflection based terahertz images at 1.56 THz are presented.
A Terahertz imaging system intended to demonstrate identification of objects concealed under clothing was designed, assembled, and tested. The system design was based on a 2.5 m standoff distance, with a capability of visualizing a 0.5 m by 0.5 m scene at an image rate of 2 frames per second. The system optical design consisted of a 1.56 THz laser beam, which was raster swept by a dual torsion mirror scanner. The beam was focused onto the scan subject by a
stationary 50 cm-diameter focusing mirror. A heterodyne detection technique was used to down convert the backscattered signal. The system demonstrated a 1.5 cm spot resolution. Human subjects were scanned at a frame rate of 2 frames per second. Hidden metal objects were detected under a jacket worn by the human subject. A movie including data and video images was produced in 1.5 minutes scanning a human through 180° of azimuth angle at 0.7° increment.
In response to the growing interest in developing terahertz imaging systems for concealed weapons detection, the Submillimeter-Wave Technology Laboratory (STL) at the University of Massachusetts Lowell has produced full-body terahertz imagery using coherent active radar measurement techniques. The proof-of-principle results were readily obtained utilizing the compact radar range resources at STL. Two contrasting techniques were used to collect the imagery. Both methods made use of in-house transceivers, consisting of two ultra-stable far-infrared lasers, terahertz heterodyne detection systems, and terahertz anechoic chambers. The first technique involved full beam subject illumination with precision azimuth and elevation control to produce high resolution images via two axis Fourier transforms. Imagery collected in this manner is presented at 1.56THz and 350GHz. The second method utilized a focused spot, moved across the target subject in a high speed two dimensional raster pattern created by a large two-axis positioning mirror. The existing 1.56THz compact radar range was modified to project a focused illumination spot on the target subject several meters away, and receive the back-reflected intensity. The process was repeated across two dimensions, and the resultant image was assembled and displayed utilizing minimal on-the-fly processing. Imagery at 1.56THz of human subjects with concealed weapons are presented and discussed for this scan type.