Priyamvada Tewari

A Review of Tissue Substitutes for Ultrasound Imaging

The characterization and calibration of ultrasound imaging systems requires tissue-mimicking phantoms with known acoustic properties, dimensions and internal features. Tissue phantoms are available commercially for a range of medical applications. However, commercial phantoms may not be suitable in ultrasound system design or for evaluation of novel imaging techniques. It is often desirable to have the ability to tailor acoustic properties and phantom configurations for specific applications. A multitude of tissue-mimicking materials and phantoms are described in the literature that have been created using a variety of materials and preparation techniques and that have modeled a range of biological systems. This paper reviews ultrasound tissue-mimicking materials and phantom fabrication techniques that have been developed over the past four decades, and describes the benefits and disadvantages of the processes. Both soft tissue and hard tissue substitutes are explored.

THz Medical Imaging: in vivo Hydration Sensing

The application of THz to medical imaging is experiencing a surge in both interest and federal funding. A brief overview of the field is provided along with promising and emerging applications and ongoing research. THz imaging phenomenology is discussed and tradeoffs are identified. A THz medical imaging system, operating at ~525 GHz center frequency with ~125 GHz of response normalized bandwidth is introduced and details regarding principles of operation are provided. Two promising medical applications of THz imaging are presented: skin burns and cornea. For burns, images of second degree, partial thickness burns were obtained in rat models in vivo over an 8 hour period. These images clearly show the formation and progression of edema in and around the burn wound area. For cornea, experimental data measuring the hydration of ex vivo porcine cornea under drying is presented demonstrating utility in ophthalmologic applications.

Terahertz sensing in corneal tissues.

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.

In vivo terahertz imaging of rat skin burns

A reflective, pulsed terahertz (THz) imaging system was used to acquire high-resolution (d(10-90)/λ~1.925) images of deep, partial thickness burns in a live rat. The rats 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.

Assessment of corneal hydration sensing in the terahertz band: in vivo results at 100 GHz

Abstract. 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 sensing of corneal hydration

An indicator of ocular health is the hydrodyanmics of the cornea. Many corneal disorders deteriorate sight as they upset the normal hydrodynamics of the cornea. The mechanisms include the loss of endothelial pump function of corneal dystophies, swelling and immune response of corneal graft rejection, and inflammation and edema, which accompany trauma, burn, and irritation events. Due to high sensitivity to changes of water content in materials, a reflective terahertz (300 GHz and 3 THz) imaging system could be an ideal tool to measure the hydration level of the cornea. This paper presents the application of THz technology to visualize the hydration content across ex vivo porcine corneas. The corneas, with a thickness variation from 470 - 940 µm, were successfully imaged using a reflective pulsed THz imaging system, with a maximum SNR of 50 dB. To our knowledge, no prior studies have reported on the use of THz in measuring hydration in corneal tissues or other ocular tissues. These preliminary findings indicate that THz can be used to accurately sense hydration levels in the cornea using a pulsed, reflective THz imaging system.

Active THz medical imaging using broadband direct detection

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 outlooks discussed.

THz imaging studies of painted samples to guide cultural heritage investigations at the Enkleistra of St. Neophytos inPaphos, Cyprus

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.

Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

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.

Advances in biomedical imaging using THz technology with applications to burn-wound assessment

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.