James Garritano

THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10 × higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

THz and mm-Wave Sensing of Corneal Tissue Water Content: Electromagnetic Modeling and Analysis

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.

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.

Dynamic Optical Contrast Imaging: A Technique to Differentiate Parathyroid Tissue from Surrounding Tissues

The variable location and indistinct features of parathyroid glands can make their intraoperative identification challenging. Currently, there exists no routine use of localization methods during surgery. Dynamic optical contrast imaging (DOCI) leverages a novel realization of temporally dependent measurements of tissue autofluorescence that allows the acquisition of specific tissue properties. A prospective series of patients with primary hyperparathyroidism was examined. Parathyroid lesions and surrounding tissues were collected; fluorescence decay images were acquired via DOCI. Ex vivo samples (81 patients) were processed for histologic assessment. DOCI extracts relative fluorescence decay information in a surgically relevant field of view with a clinically accessible acquisition time <2 minutes. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology (P < .05). DOCI is capable of efficiently distinguishing parathyroid tissue from adjacent tissues. Such an intraoperative tool would be transformative, helping surgeons to identify lesions, preserve healthy tissue, and improve patient outcomes.

Dynamic optical contrast imaging as a novel modality for rapidly distinguishing head and neck squamous cell carcinoma from surrounding normal tissue.

Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patients prognosis depends heavily on complete tumor resection. Currently, the surgeons fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes.

Preliminary results of non-contact THz imaging of cornea.

This paper presents a novel THz optical design that allows the acquisition of THz reflectivity maps of in vivo cornea without the need for a field flattening window and preliminary imaging results of in vivo rabbit cornea. The system’s intended use is to sense small changes in corneal tissue water content (CTWC) that can be precursors for a host of diseases and pathologies. Unique beam optics allows the scanning of a curved surface at normal incidence while keeping the source detector and target stationary. Basic system design principles are discussed and image sets of spherical calibration targets and corneal phantom models are presented. The presented design will enable, for the first time, non-contact THz imaging of animal and human cornea.

Ex vivo viscoelastic characterization of head and neck tissue abnormalities using ultrasound-stimulated vibro-acoustography (USVA)

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.

Optical and system design for THz medical imaging using spatially resolved hydration mapping

Summary form only given. THz medical imaging has made significant advances in the years since the first results were published in the late 1990s. The field has benefited significantly from advances in source/detector technology, room temperature component operation, and extensive spectroscopic studies of the THz properties of tissue. Additionally, clinical translation of THz medical imaging technology in the US has been aided by the establishment of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) in 2000. While progress has been promising, wide scale clinical translation of THz technology has not yet materialized. In this talk we focus on receiver system design, optical system design, and diagnostic applications intended to maximize the rate of clinical acceptance of THz medical imaging technology. Receiver architectures and novel optical concepts will be presented that are implemented to trade away unused information for gains in image acquisition time, robustness to target clutter, and sensitivity to gradients in surface tissue water content. Following system discussions three applications will be presented: corneal hydration sensing, burn wound edema imaging, and explorations into the physiologic response of the body to histamine. Each of these applications benefit from spatially resolved hydration mapping; a capability enabled by THz imaging and not feasible with traditional medical imaging modalities. In vivo animal image results are presented.