Terahertz (THz) detection has been proposed and applied to a variety of medical imaging applications in view of its
unrivaled hydration profiling capabilities. Variations in tissue dielectric function have been demonstrated at THz
frequencies to generate high contrast imagery of tissue, however, the source of image contrast remains to be verified
using a modality with a comparable sensing scheme. To investigate the primary contrast mechanism, a pilot
comparison study was performed in a burn wound rat model, widely known to create detectable gradients in tissue
hydration through both injured and surrounding tissue. Parallel T2 weighted multi slice multi echo (T2w MSME)
7T Magnetic Resonance (MR) scans and THz surface reflectance maps were acquired of a full thickness skin burn in
a rat model over a 5 hour time period. A comparison of uninjured and injured regions in the full thickness burn
demonstrates a 3-fold increase in average T2 relaxation times and a 15% increase in average THz reflectivity,
respectively. These results support the sensitivity and specificity of MRI for measuring in vivo burn tissue water
content and the use of this modality to verify and understand the hydration sensing capabilities of THz imaging for
acute assessments of the onset and evolution of diseases that affect the skin. A starting point for more sophisticated
in vivo studies, this preliminary analysis may be used in the future to explore how and to what extent the release of
unbound water affects imaging contrast in THz burn sensing.
Terahertz (THz) imaging is a relatively new non-destructive analytical technique that is transitioning from established application research areas such as defense and biomedicine to studies of cultural heritage artifacts. Our research adopts a THz medical imaging system, originally designed for in vivo tissue hydration sensing, to acquire high contrast imagery of painted plaster samples in order to assess the ability of the system to image the Byzantine wall paintings at the Enkleistra of St. Neophytos in Paphos, Cyprus. The original 12th century paintings show evidence of later painting phases overlapping earlier iconography. A thin layer of lead white (2PbCO3·Pb(OH)2) underlies, in parts, later wall paintings, concealing the original painting scheme beneath. Traditional imaging modalities have been unable to image the underlying iconography due to a combination of absorption and scattering. We aim to use THz imaging and novel optical design to probe beyond the visible surface and perform in situ analysis of iconography beneath the lead white layer. Imaging results of painted plaster mock-ups covered with a thin layer of lead white and/or chalk, as well as of a painted wooden panel with obscured writing, are presented, and from these images sufficient contrast for feature identification is demonstrated. Preliminary results from the analysis of these mock-ups confirmed the utility of this technique and its potential to image concealed original paintings in the Enkleistra of St. Neophytos. The results encourage analysis of THz scattering within paint and plaster materials to further improve spatial resolution and penetration depth in THz imaging systems.
This paper presents novel a first pass on the thorough analysis of THz optical designs intended for image acquisition of
burn wounds in animal models. Current THz medical imaging research typically employs and fixed source detector
architecture coupled by a train of off-axis parabolic mirrors. When used individually, parabolic mirrors have near
diffraction limited focusing properties, extremely low loss, and are dispersion free. However, when a combination or train
of multiple parabolic mirrors are utilized geometric errors can be generated early in the train and exacerbated as the beam
propagates to the detector. These errors manifest as significant increases in spot size, asymmetries about the optical axis
in beam irradiance and polarization, and the generation of cross polarization components. This work presents a novel
configuration of off-axis parabolic mirrors designed to maximize the practicality of beam alignment and image acquisition.
Quasi-physical optics simulations of the optical performance are described and significant perturbations in polarization
symmetry were observed. The configuration can be described as in between two canonical parabolic mirror configurations.
The performance of three different pairs of off-axis parabolic mirror pairs coupled to the novel configuration are presented
Terahertz (THz) hydration sensing continues to gain traction in the medical imaging community due to its unparalleled
sensitivity to tissue water content. Rapid and accurate detection of fluid shifts following induction of thermal skin burns
as well as remote corneal hydration sensing have been previously demonstrated in vivo using reflective, pulsed THz
imaging. The hydration contrast sensing capabilities of this technology were recently confirmed in a parallel 7 Tesla
Magnetic Resonance (MR) imaging study, in which burn areas are associated with increases in local mobile water
content. Successful clinical translation of THz sensing, however, still requires quantitative assessments of system
performance measurements, specifically hydration concentration sensitivity, with tissue substitutes. This research aims
to calibrate the sensitivity of a novel, reflective THz system to tissue water content through the use of hydration
phantoms for quantitative comparisons of THz hydration imagery.Gelatin phantoms were identified as an appropriate
tissue-mimicking model for reflective THz applications, and gel composition, comprising mixtures of water and protein,
was varied between 83% to 95% hydration, a physiologically relevant range. A comparison of four series of gelatin
phantom studies demonstrated a positive linear relationship between THz reflectivity and water concentration, with
statistically significant hydration sensitivities (p < .01) ranging between 0.0209 - 0.038% (reflectivity: %hydration). The
THz-phantom interaction is simulated with a three-layer model using the Transfer Matrix Method with agreement in
hydration trends. Having demonstrated the ability to accurately and noninvasively measure water content in tissue
equivalent targets with high sensitivity, reflective THz imaging is explored as a potential tool for early detection and
intervention of corneal pathologies.
Research in THz imaging is generally focused on three primary application areas: medical, security, and nondestructive
evaluation (NDE). While work in THz security imaging and personnel screening is populated by a number of different
active and passive system architectures, research in medical imaging in is generally performed with THz time-domain
systems. These systems typically employ photoconductive or electro-optic source/detector pairs and can acquire depth
resolved data or spectrally resolved pixels by synchronously sampling the electric field of the transmitted/reflected
waveform. While time-domain is a very powerful scientific technique, results reported in the literature suggest that
desired THz contrast in medical imaging may not require the volume of data accessible from time-resolved
measurements and that a simpler direct detection, active technique may be sufficient for specific applications. In this
talk we discuss an active direct detection reflectometer system architecture operating at a center frequency of ~ 525 GHz
that uses a photoconductive source and schottky diode detector. This design takes advantage or radar-like pulse
rectification and novel reflective optical design to achieve high target imaging contrast with significant potential for high
speed acquisition time. Results in spatially resolved hydration mapping of burn wounds are presented and future
Terahertz (THz) sensing has shown potential as a novel imaging modality in medical applications due to
its high water sensitivity. The design of medical THz sensing systems and their successful application to
in vivo settings has attracted recent interest to the field, and highlighted the need for improved
understanding of the interaction of THz waves with biological tissues. This paper explores the modeling
of composite materials which combine strongly-interacting water with weakly-interacting species such as
those that are common to biological tissues. The Bruggeman, Maxwell-Garnett, and power law effective
media models are introduced and discussed. A reflection-mode 100 GHz Gunn diode sensing system was
used to measure the reflectivity of solutions of water and dioxane as a function of relative concentration,
and the results were compared with the predictions of the Maxwell-Garnett, power law, and Bruggeman
mixing theories. The Maxwell-Garnett model fit poorly to experimental data on near-equal mixtures of
water and dioxane and improved when the concentration of water exceeded ~55% or was below ~15%.
The first-order power law model fit poorly to experimental data across the entire range except at nearpure
solutions. Power law models employing 1/2 and 1/3 terms improved goodness of fit, but did not
match the accuracy of the Bruggeman model. The Bruggeman provided the best fit to experimental data
model as compared to Maxwell-Garnett and the power models and accurately predicted the solution
reflectivity through the whole range of concentrations. This analysis suggests that the Bruggeman model
may offer improved accuracy over more conventional dielectric mixing models when developing
simulation tools for THz reflectometry of hydrated biological tissues.
Applications for terahertz (THz) medical imaging have proliferated over the past few years due to advancements in
source/detector technology and vigorous application development. While considerable effort has been applied to
improving source output power and detector sensitivity, significantly less work has been devoted to improving image
acquisition method and time. The majority of THz medical imaging systems in the literature typically acquire pixels by
translating the target of interest beneath a fixed illumination beam. While this single-pixel whiskbroom methodology is
appropriate for in vitro models, it is unsuitable for in vivo large animal and patient imaging due to practical constraints.
This paper presents a scanned beam imaging system based on prior work that enables for reduced image acquisition time
while allowing the source, target and detector to remain stationary. The system employs a spinning polygonal mirror and
a set of high-density polyethylene (HDPE) objective lenses, and operates at a center illumination frequency of 525GHz
with ~125GHz of 3dB bandwidth. The system achieves a focused beam diameter of 1.66mm and a large depth of field of
<25 mm. Images of characterization targets and ex vivo tissue samples are presented and compared to results obtained
with conventional fixed beam scanning systems.
Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to
changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration
mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns
and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and
full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration
gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism
of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast
generation to support the translation of this technology to clinical application. The hydration contrast sensing
capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H),
are well established and provide measures of mobile water content, lending MRI as a suitable method to validate
hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo
porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from
this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat
models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.
Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea's depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing.
A reflective, pulsed terahertz (THz) imaging system was used to acquire high-resolution (d10-90/λ ∼ 1.925) images of deep, partial thickness burns in a live rat. The rat's abdomen was burned with a brass brand heated to ∼ 220°C and pressed against the skin with contact pressure for ∼ 10 sec. The burn injury was imaged beneath a Mylar window every 15 to 30 min for up to 7 h. Initial images display an increase in local water concentration of the burned skin as evidenced by a marked increase in THz reflectivity, and this likely correlates to the post-injury inflammatory response. After ∼ 1 h the area of increased reflectivity consolidated to the region of skin that had direct contact with the brand. Additionally, a low reflecting ring of tissue could be observed surrounding the highly reflective burned tissue. We hypothesize that these regions of increased and decreased reflectivity correlate to the zones of coagulation and stasis that are the classic foundation of burn wound histopathology. While further investigations are necessary to confirm this hypothesis, if true, it likely represents the first in vivo THz images of these pathologic zones and may represent a significant step forward in clinical application of THz technology.
Terahertz (THz) hydration sensing and image has been a topic of increased interest recently due largely to improvements
in source and detector technology and the identification of applications where current hydration sensing techniques are
insufficient. THz medical imaging is an expanding field of research and tissue hydration plays a key role in the contrast
observed in THz tissue reflectance and absorbance maps. This paper outlines the most recent results in burn and corneal
imaging where hydration maps were used to assess tissue status. A 3 day study was carried out in rat models where a
THz imaging system was used to assess the severity and extent of burn throughout the first day of injury and at the 24,
48, and 72 hour time points. Marked difference in tissue reflectance were observed between the partial and full
thickness burns and image features were identified that may be used as diagnostic markers for burn severity. Companion
histological analysis performed on tissue excised on Day 3 confirms hypothesized burn severity. The results of these
preliminary animal trials suggest that THz imaging may be useful in burn wound assessment where current clinical
modalities have resolution and/or sensitivity insufficient for accurate diagnostics.
THz medical imaging has been a topic of increased interest recently due largely to improvements in source and detector
technology and the identification of suitable applications. One aspect of THz medical imaging research not often
adequately addressed is pixel acquisition rate and phenomenology. The majority of active THz imaging systems use
translation stages to raster scan a sample beneath a fixed THz beam. While these techniques have produced high
resolution images of characterization targets and animal models they do not scale well to human imaging where
clinicians are unwilling to place patients on large translation stages. This paper presents a scanned beam THz imaging
system that can acquire a 1 cm2 area with 1 mm2 pixels and a per-pixel SNR of 40 dB in less than 5 seconds. The system
translates a focused THz beam across a stationary target using a spinning polygonal mirror and HDPE objective lens.
The illumination is centered at 525 GHz with ~ 125 GHz of response normalized bandwidth and the component layout is
designed to optically co-locate the stationary source and detector ensuring normal incidence across a 50 mm × 50 mm
field of view at standoff of 190 mm. Component characterization and images of a test target are presented. These
results are some of the first ever reported for a short standoff, high resolution, scanned beam THz imaging system and
represent an important step forward for practical integration of THz medical imaging where fast image acquisition times
and stationary targets (patients) are requisite.
This work introduces the potential application of terahertz (THz) sensing to the field of ophthalmology, where it is uniquely suited due to its nonionizing photon energy and high sensitivity to water content. Reflective THz imaging and spectrometry data are reported on ex-vivo porcine corneas prepared with uniform water concentrations using polyethylene glycol (PEG) solutions. At 79% water concentration by mass, the measured reflectivity of the cornea was 20.4%, 14.7%, 11.7%, 9.6%, and 7.4% at 0.2, 0.4, 0.6, 0.8, and 1 THz, respectively. Comparison of nine corneas hydrated from 79.1% to 91.5% concentration by mass demonstrated an approximately linear relationship between THz reflectivity and water concentration, with a monotonically decreasing slope as the frequency increases. The THz-corneal tissue interaction is simulated with a Bruggeman model with excellent agreement. THz applications to corneal dystrophy, graft rejection, and refractive surgery are examined from the context of these measurements.
THz and millimeter wave technology have shown the potential to become a valuable
medical imaging tool because of its sensitivity to water and safe, non-ionizing photon
energy. Using the high dielectric constant of water in these frequency bands, reflectionmode
THz sensing systems can be employed to measure water content in a target with
high sensitivity. This phenomenology may lead to the development of clinical systems to
measure the hydration state of biological targets. Such measurements may be useful in
fast and convenient diagnosis of conditions whose symptoms can be characterized by
changes in water concentration such as skin burns, dehydration, or chemical exposure. To
explore millimeter wave sensitivity to hydration, a reflectometry system is constructed to
make water concentration measurements at 100 GHz, and the minimum detectable water
concentration difference is measured. This system employs a 100 GHz Gunn diode
source and Golay cell detector to perform point reflectivity measurements of a wetted
polypropylene towel as it dries on a mass balance. A noise limited, minimum detectable
concentration difference of less than 0.5% by mass can be detected in water
concentrations ranging from 70% to 80%. This sensitivity is sufficient to detect hydration
changes caused by many diseases and pathologies and may be useful in the future as a
diagnostic tool for the assessment of burns and other surface pathologies.
This study describes terahertz (THz) imaging of hydration changes in physiological tissues with high water concentration sensitivity. A fast-scanning, pulsed THz imaging system (centered at 525 GHz; 125 GHz bandwidth) was utilized to acquire a 35 mm x 35 mm field-of-view with 0.5 mm x 0.5 mm pixels in less than two minutes. THz time-lapsed images were taken on three sample systems: (1) a simple binary system of water evaporating from a polypropylene towel, (2) the accumulation of fluid at the site of a sulfuric acid burn on ex vivo porcine skin, and (3) the evaporative dehydration of an ex vivo porcine cornea. The diffusion-regulating behavior of corneal tissue is elucidated, and the correlation of THz reflectivity with tissue hydration is measured using THz spectroscopy on four ex vivo corneas. We conclude that THz imaging can discern small differences in the distribution of water in physiological tissues and is a good candidate for burn and corneal imaging.
A reflective terahertz (THz) system has been under development for imaging and monitoring of skin hydration, and
through consideration of attenuation, scattering, spatial resolution and measurement of sensitivity, the frequency band
0.4 - 0.7 THz has been determined optimal for operation. THz, typically defined as the frequency range between 0.1-10
THz, has been proposed for skin hydration imaging and monitoring primarily due to being non-ionizing radiation and
highly sensitivity to water concentrations. While it is important to maximize measurement sensitivity to changes in water
concentration, the optimal operational frequency band must simultaneously minimize the scattering from the targets (i.e.
skin) and attenuation, as well as maximize the spatial resolution. In terms of atmospheric attenuation, from 0.4 to 1 THz,
there are broad absorption lines at 556 GHz and 750 GHz, and large transmission windows centered at 500, 650, and 870
GHz. Scattering of the energy reflected from skin was show, using modeling, that as the frequency increased there was a
considerable decrease in the power fraction reflected in the specular direction. For measurement sensitivity, it was
shown that a change in reflectivity per change in water volume at 100 GHz was nearly an order of magnitude higher at 1
THz. Finally, as should be expected, higher frequencies were better for spatial resolution. In consideration of the above
criteria, the motivation for using the 0.4-0.7 THz band will be presented as well as an overview the developed THz pulse
reflective imaging system for imaging of skin hydration.
Reflective terahertz (THz) imaging may potentially become a valuable tool in determining skin hydration due to its non-ionizing photon energy, high sensitivity to water concentration and ability to penetrate through clothing. The high absorption coefficient of water in the THz range is responsible for contrast between substances with lesser or higher degrees of water saturation. Water content, as well as collagen fiber arrangement, varies between different layers of skin. This study sought to determine whether the high THz absorption in water could be exploited to distinguish between these layers. Porcine skin specimens were sectioned into samples of increasing thickness, with the undersides corresponding to different layers in skin. The undersides of the samples were scanned using a THz imaging system operating at a center frequency of 0.5 THz with 0.125 THz of noise-equivalent bandwidth at a standoff of 4 cm and a spot size of 13 mm. Collagen solutions of varying hydrations were also prepared and raster scanned with the same system. The reflectivity of the deeper layers of skin was found to be higher than that of the upper layers, indicating that the deeper layers are more hydrated. The collagen solutions with higher hydration also had higher THz reflectivity. These results suggested that THz is able to distinguish between different layers of skin based on water content and the nature of its association with components in skin.