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.
KEYWORDS: Terahertz radiation, Magnetic resonance imaging, Tissues, Skin, In vivo imaging, Reflectivity, Visualization, Injuries, Medical imaging, Natural surfaces
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.
KEYWORDS: Skin, Terahertz radiation, Reflectivity, Tissues, Injuries, In vivo imaging, Abdomen, Millimeter wave imaging, Medical imaging, Imaging systems
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.
KEYWORDS: Ultrasonography, Brain, In vivo imaging, Acoustics, In vitro testing, Potassium, Modulation, Molecular mechanisms, Transducers, Chemical elements
Low intensity focused ultrasound (LIFU) is now being considered as a noninvasive brain therapy for clinical
applications. We maintain that LIFU can efficiently deliver energy from outside the skull to target specific brain regions,
effecting localized neuromodulation. However, the underlying molecular mechanisms that drive this LIFU-induced
neuromodulation are not well-defined due, in part, to our lack of understanding of how particular sets of LIFU delivery
parameters affect the outcome. To efficiently conduct multiple sweeps of different parameters and determine their
effects, we have developed an in-vitro system to study the effects of LIFU on different types of cells grown in culture.
Presently, we are evaluating how LIFU affects the ionic flux that may underlie neuronal excitation and inhibition
observed in-vivo. The results of our in-vitro studies will provide a rationale for selection of optimal LIFU parameter to be
used in subsequent in-vivo applications. Thus, a prototype ultrasound cell assay system has been developed to conduct
these studies, and is described in this work.
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.
This paper describes the method of using the finite-element analysis software, PZFlex, to direct the
design of a novel ultrasound imaging system which uses conformal transducer arrays. Current
challenges in ultrasound array technology, including 2D array processing, have motivated exploration
into new data acquisition and reconstruction techniques. Ultimately, these efforts encourage a broader
examination of the processes used to effectively validate new array configurations and image formation
procedures. Commercial software available today is capable of efficiently and accurately modeling
detailed operational aspects of customized arrays. Combining quality simulated data with prototyped
reconstruction techniques presents a valuable tool for testing novel schemes before committing more
costly resources. To investigate this practice, we modeled three 1D ultrasound arrays operating multistatically instead of by the conventional phased-array approach. They are: a simple linear array, a half-circle array with 180-degree coverage, and a full circular array for inward imaging. We present the process used to create unique array models in PZFlex, simulate operation and obtain data, and subsequently generate images by inputting data into a reconstruction algorithm in MATLAB. Further discussion describes the tested reconstruction algorithm and includes resulting images.
KEYWORDS: Ranging, Ultrasonography, Transducers, Acoustics, Signal to noise ratio, Signal processing, Signal detection, Fourier transforms, Signal attenuation, Receivers
This paper presents a method setup for high-frequency ultrasound ranging based on stepped frequency-modulated
continuous waves (FMCW), potentially capable of producing a higher signal-to-noise ratio (SNR) compared to
traditional pulse-echo signaling. In current ultrasound systems, the use of higher frequencies (10-20 MHz) to
enhance resolution lowers signal quality due to frequency-dependent attenuation. The proposed ultrasound
signaling format, step-FMCW, is well-known in the radar community, and features lower peak power, wider
dynamic range, lower noise figure and simpler electronics in comparison to pulse-echo systems.
In pulse-echo ultrasound ranging, distances are calculated using the transmit times between a pulse and its
subsequent echoes. In step-FMCW ultrasonic ranging, the phase and magnitude differences at stepped frequencies are used to sample the frequency domain. Thus, by taking the inverse Fourier transform, a comprehensive range profile is recovered that has increased immunity to noise over conventional ranging methods. Step-FMCW and pulse-echo waveforms were created using custom-built hardware consisting of an arbitrary waveform generator and dual-channel super heterodyne receiver, providing high SNR and in turn, accuracy in detection.
KEYWORDS: Transducers, Ultrasonography, Chemical elements, Silicon, Ferroelectric materials, Semiconducting wafers, Imaging arrays, Thin films, Deep reactive ion etching, Silicon films
This paper presents the fabrication of a conformal, ring-annular ultrasound imaging array. Two-dimensional
(2D) ultrasound scanning is possible with ring-annular array transducers in which a number of piezoelectric
elements are arranged in a circle. The 2D scanning technique can be realized through time delays, potentially
allowing for 3D imaging. Ring-annular array transducers have previously been shown to have increased
bandwidth, better signal-to-noise, and uniform scanning in space in contrast to 2D matrix arrays of an equal
number elements and aperture size. Conformal, ring-annular transducers have the ability to match the curvature
of body surfaces, and have the additional advantage that the flexible array elements can be mechanically focused
to provide enhanced focusing capabilities relative to rigid ring-annular arrays. The process developed for the
fabrication of conformal, ring-annular ultrasound array is presented. A microfabrication approach is used to
produce ring-annular arrays featuring flexible joints with high durability, and capable of scaling in size and
element architectures. The fabrication process yields a ring of piezoelectric transducer elements held together with polyimide, which is the basis of the flexible joints that enable conformal ultrasonography. The described fabrication process is used to produce a ring-annular array with a single ring containing piezoelectric elements, but the process can be extended to form arrays with multiple annular-rings of varying sizes. The transducer had a fundamental thickness-mode resonant frequency of 12 MHz, a 6 dB bandwidth of 23%, and an acoustic pulse width of 1.8 μs in water.
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.
This paper presents the use and evaluation of stepped frequency modulated continuous waves (FMCW) in a conformal
ultrasound array-based medical imaging system currently in development. Conventional medical ultrasound systems
featuring rigid transducer arrays are highly user-dependent and require manual rotation and translation to identify and
image landmarks. Conformal ultrasound arrays have a larger aperture that can follow the surface curvature of the body,
thereby enabling increased data capture without mechanical scanning. The complexity of image reconstruction in
conformal ultrasound necessitates the use of step-FMCW, since it directly captures the frequency space thereby enabling
image reconstruction techniques to operate directly on the data, greatly simplifying and allowing for real-time
performance. Further, FMCW is advantageous in general since it requires lower peak power and produces better
receiver noise characteristics than conventional pulse-echo signaling.
In the proposed stepped FMCW signaling, packets of acoustic waves at stepped frequencies are emitted from transducers
sequentially. Phase and magnitude information from each transmitter-receiver pair of the array are captured producing
the frequency space representation of the conventional A-scan data.
The results comprise of simulations and bistatic experimental data produced by the step-FMCW signaling method, and
obtained using a multistatic transducer array with a stationary metal target. In experimental verification using, the step-
FMCW signaling and processing method gave accurate target detection, thereby demonstrating its viability in a
conformal ultrasound array and imaging system.
Due to their increased angular coverage around body surfaces, conformal ultrasound transducers may potentially provide
increased signal acquisition relative to rigid medical ultrasound probes and eliminate the need for mechanical scanning.
This paper describes a novel, high efficiency, and robust conformal ultrasound transducer array based on a flexible
substrate of silicon islands joined together using polyimide joints. The array incorporated diced bulk lead zirconate
titanate (PZT) mounted atop the silicon islands as its piezoelectric material for its desirable electromechanical coupling
factor and high piezoelectric coefficients. Parylene thin films deposited over the array reinforced the bendable joints,
encapsulated the metal film interconnects, and formed, in conjunction with the silicon, an acoustical match between the
PZT and soft tissue. Eight element linear arrays were fabricated with a pitch of 3.5 mm, operating at a center frequency
of 12 MHz with a 6dB bandwidth of 27%. The robustness of the transducer was demonstrated by iterative bending
around a 1 cm diameter cylinder, and the durability of the electrical traces and the frequency performance was measured
using a vector network analyzer. This paper presents a robust, durable conformal ultrasound array with the versatility to
scale to enable new applications in diagnostic ultrasound imaging.
In this paper, we present the image reconstruction algorithm developed for a conformal ultrasound
array imaging system operating in the step frequency-modulated continuous wave (FMCW) mode. The
image formation procedure is based on a key relationship that establishes the equivalence between
pulse-echo and step FMCW modalities, and thus permits conversion between the data types. Prior step
FMCW simulation work could then be merged with pulse-echo data collected experimentally to achieve
full-scale synthesis between laboratory data and a structured theoretical framework. We describe how
an experimentally acquired pulse-echo waveform was extracted and incorporated into a step FMCW
imaging simulation to increase image accuracy and improve visualization of physical effects. With
knowledge of the transducer element positions in a multistatic configuration, image reconstruction was
achieved by mapping the complex range profiles over to a target region. Included in this paper are
images reconstructed after waveform synthesis, which feature transducer elements uniformly spaced
around a circular aperture imaging several enclosed targets with different bandwidths.
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.
Terahertz medical imaging has emerged as a promising new field because of its non-ionizing photon energy
and its acute sensitivity to water concentration. To better understand the primary contrast mechanism in
THz imaging of tissues, the reflectivity of varying water concentrations was measured. Using a pulsed THz
reflective imaging system, a 0.3 mm thin paper sample with varying water concentrations was probed and
from the measured data a noise equivalent delta water concentration (NEΔWC) of 0.054% was derived.
The system is based on a photoconductive pulsed source and time-gated waveguide-mounted Schottky
diode receiver. It operates at a center frequency of 500 GHz with 125 GHz of noise-equivalent bandwidth
and at a standoff of 4 cm, the imaging system achieved a spot size of 2.2 mm. The high water sensitivity of
this system was exploited to image burned porcine (pig) skin models in reflection using differences in
water content of burned and unburned skin as the contrast mechanism. The obtained images of the porcine
skin burns are a step towards the ability to quantify burn injuries using THz radiation.
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