Edema, or tissue swelling, is a characteristic component of the tissue response to cutaneous injury and, therefore, a potentially useful diagnostic target for assessing wound severity and viability in vivo. Currently, there is no widely available pre-clinical or clinical technique that can identify the extent and distribution of tissue water content (TWC), the primary indicator of edema, early and accurately. We have previously shown that reflective terahertz (THz) imaging can rapidly and non-invasively generate native, pathology-specific contrast in superficial tissue based on hypothesized variations in TWC. TWC-based contrast and the sensing depth of THz imaging, however, have yet to be verified with a well-established TWC-sensing technique. Moreover, early and repeatable visualization of TWC in pre-clinical wound models may further support THz imaging as an emerging diagnostic tool in patients sustaining severe burns, surgical trauma, or other conditions leading to tissue edema.
This work details the iterative development, characterization, and pre-clinical testing of THz TWC imaging in phantom, ex vivo, and in vivo wound models for early wound and tissue viability assessment. First, the sensitivity of a novel, reflective THz system to variation in water concentration was calibrated through the use of gelatin phantoms for quantitative comparison of THz imagery of targets. Second, the ability of reflective THz imaging to track TWC changes was correlated with depth-resolved magnetic resonance imaging (MRI) in both an ex vivo porcine burn model and in vivo, burn-induced model of edema in rats. This work offers the first in vivo correlative assessment of mobile TWC as a major contributor to THz imaging contrast. Third, improved THz imaging methodologies were developed and implemented in vivo to acquire reproducible THz-TWC maps of burn wounds and interpret these results in the context of burn edema pathophysiology. These advancements included 1) an image registration method to reliably compare THz-TWC measurements with histological wound outcome; 2) a reproducible contact-burn induction technique; and 3) the use of multiple dielectric windows. Finally, the first in vivo pilot study was performed to investigate the utility of reflective THz TWC imaging for early assessment of tissue flap viability, the most significant determinant of tissue survival in reconstructive surgery. Collectively, these results demonstrate important implications of THz imaging in edema monitoring of wounds and skin evaluation and the potential use of this technology as an augmentation to the standard clinical assessment of superficial tissue.
