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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
Opioid Dependence is a Critical Public Health Crisis
Since 2003, deaths from drug overdose have increased in almost every county in the United States. This growing public health crisis has been routinelyreportedon over the last several years, and the federal government has very recently published the first national standards for prescription painkillers. In 2014, the death toll from overdoses related to prescription painkillers or heroin reached almost 29,000 – a 14% increase over the previous year. When combined with other forms of drug-overdose related deaths, the total impact is approaching that of the HIV epidemic in the late 1980s, according to the Center for Disease Control’s chief of mortality statistics.
Figure 1: Overdose deaths from painkillers or heroin, per 100,000 people. Source: New York Times
Luna is Developing Controlled Delivery Bandages
In order to address this critical public health concern, Luna Innovations, Massachusetts General Hospital’s Center for Translational Pain Research (Dr. Jianren Mao) and the University of Virginia’s Plastic Surgery Research Lab (Dr. Patrick Cottler) are developing a unique nanofiber-based dressing known as “TuneCoat™.” The dressing is designed to deliver combination pain therapy at the site of discomfort in order to substantially reduce the required opioid dose and eliminate the need for systemic (oral or intravenous) delivery. This localized delivery combined with lower drug doses will significantly reduce the chance of addiction and dependence. In addition, by administering lower, targeted, yet effective amounts of pain reliever in each treatment regimen, the developed TuneCoat™ dressings will be less susceptible to abuse and illegal trade than current prescription opioid form factors like pills.
The research, sponsored by the US Army Medical Research Acquisition Activity and funded by the Defense Health Program, is initially aimed at delivering known effective opioids in lower, controlled concentrations in a localized manner to provide pain relief to burn wounds. These active burn dressings can also be designed to protect the wound from infection, aid in healing, and to deliver both pain relievers and antimicrobials in the same bandage. Luna’s TuneCoat™ burn dressing is prepared using a unique electrospinning process, allowing drugs of different chemistry and function to have individually tuned release rates and concentrations. Luna has confirmed controlled drug release, and has recently demonstrated antimicrobial function of the dressings. Further, as demonstrated in the figure below, Luna’s dressings have the capability of delivering drugs with burst or zero-order (sustained) release. This allows different drug compounds to be delivered at different rates, and ensures rapid pain relief using the burst-delivery concept.
Though these dressings are being targeted to burn wound pain management in initial forms, Luna envisions broad acceptance for a variety of different indications such as peripheral neuropathy, postherpetic neuralgia, or other forms of chronic and debilitating pain. Luna’s dressings provide a desperately needed solution to a critical and growing public health crisis, and provide unique and practical solutions that can be directly integrated into standard practices of care.
Figure 2: (A) Cross-section of Luna’s TuneCoat™ dressing. These dressings are unique nanofiber mats capable of delivering different therapeutics simultaneously, with individually controlled release kinetics. As demonstrated in (B), different drug analogs show burst- and zero-order release kinetics from the same dressing.
The high contrast resolution afforded by terahertz (1 THz = 1012 Hz) imaging of physiologic tissue continues to drive explorations into the utility of THz technology for burn wound detection. Although we have previously reported the use of a novel, reflective THz imaging technology to sense spatiotemporal differences in reflectivity between partial and full thickness burn wounds, no evidence exists of a one-to-one correlation between structural damage observed in histological assessments of burn severity and THz signal. For example, varying burn induction methods may all result in a common burn wound severity, however, burn features observed in parallel THz imagery may not be identical. Successful clinical translation of THz technology as a comprehensive burn guidance tool, therefore, necessitates an understanding of THz signal and its relation to wound pathophysiology. In this work, longitudinal THz imagery was acquired with a quartz (n = 2.1, 500 μm) window of cutaneous wounds induced with the same brand geometry and contact pressure but varying contact times (5, 7, and 10 seconds) in in vivo, pre-clinical rat models (n=3) over a period of 3 days. Though all burn wounds were evaluated to be deep partial thickness with histology, THz contrasts observed for each burn contact time were intrinsically unique. This is the first preliminary in vivo evidence of a many-to-one relationship between changes in THz contrast and burn severity as ascertained by histology. Future large-scale studies are required to assess whether these observed changes in THz contrast may be interpreted as physiological changes occurring over time, morphometric changes related to anatomical change, or electromagnetic changes between dielectric substrate windows and the underlying tissue.
Optics Express, Vol. 22, Issue 10, pp. 11465-11475 (2014) http://dx.doi.org/10.1364/OE.22.011465
The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse’s ear skin with an average power of 260 mW/cm2 for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process.
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