The unique viscoelastic properties of tissues throughout the human body can be utilized in a variety of clinical applications. Palpation techniques, for instance, enable surgeons to distinguish malignancies in tissue composition during surgical procedures. Additionally, imaging devices have begun utilizing the viscoelastic properties of tissue to delineate tumor margins. Vibroacoustography (VA), a non-invasive, high resolution imaging modality, has the ability to detect sub-millimeter differences in tissue composition. VA images tissue using a low frequency acoustic radiation force, which perturbs the target and causes an acoustic response that is dependent on the target’s viscoelastic properties. Given the unique properties specific to human and animal tissues, there are far-reaching clinical applications of VA. To date, however, a comprehensive model that relates viscoelasticity to VA tissue response has yet to be developed. Utilizing tissue-mimicking phantoms (TMPs) and fresh ex vivo tissues, a mechanical stress relaxation model was developed to compare the viscoelastic properties of known and unknown specimens. This approach was conducted using the Hertz theory of contact mechanics. Fresh hepatic tissue was obtained from porcine subjects (n=10), while gelatin and agar TMPs (n=12) were fabricated from organic extracts. Each specimen’s elastic modulus (E), long term shear modulus (η), and time constant (τ) were found to be unique. Additionally, each specimen’s stress relaxation profiles were analyzed using Weichert-Maxwell viscoelastic modeling, and retained high precision (R2>0.9) among all samples.
Vibroacoustography (VA) is an imaging technology that utilizes the acoustic response of tissues to a localized, low frequency radiation force to generate a spatially resolved, high contrast image. Previous studies have demonstrated the utility of VA for tissue identification and margin delineation in cancer tissues. However, the relationship between specimen viscoelasticity and vibroacoustic emission remains to be fully quantified. This work utilizes the effects of variable acoustic wave profiles on unique tissue-mimicking phantoms (TMPs) to maximize VA signal power according to tissue mechanical properties, particularly elasticity. A micro-indentation method was utilized to provide measurements of the elastic modulus for each biological replica. An inverse relationship was found between elastic modulus (E) and VA signal amplitude among homogeneous TMPs. Additionally, the difference frequency (Δf ) required to reach maximum VA signal correlated with specimen elastic modulus. Peak signal diminished with increasing Δf among the polyvinyl alcohol specimen, suggesting an inefficient vibroacoustic response by the specimen beyond a threshold of resonant Δf. Comparison of these measurements may provide additional information to improve tissue modeling, system characterization, as well as insights into the unique tissue composition of tumors in head and neck cancer patients.
In the absence of an imaging technique that offers a highly dynamic range detection of malignant tissue intra-operatively, surgeons are often forced to excise excess healthy tissue to ensure clear margins of resection. Techniques that are currently used in the detection of tumor regions include palpation, optical coherence tomography (OCT) elastography, dye injections, and conventional ultrasound to pinpoint the affected area. However, these methods suffer from limitations such as minimal specificity, low contrast, and limited depth of penetration. Lack of specificity and low contrast result in the production of vague disease margins and fail to provide a reliable guidance tool for surgeons. The proposed work presents an alternative diagnostic technique, ultrasound-stimulated vibro-acoustography (USVA), which may potentially provide surgeons with detailed intra-operative imagery characterized by enhanced structural boundaries and well-defined borders based on the viscoelastic properties of tissues. We demonstrate selective imaging using ex vivo tissue samples of head and neck squamous cell carcinoma (HNSCC) with the presence of both malignant and normal areas. Spatially resolved maps of varying acoustic properties were generated and show good contrast between the areas of interest. While the results are promising, determining the precision and sensitivity of the USVA imaging system in identifying boundary regions as well as intensities of ex vivo tissue targets may provide additional information to non-invasively assess confined regions of diseased tissues from healthy areas.
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.
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.
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.
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 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.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.