Thu T. A. Nguyen

Three-dimensional phantoms for curvature correction in spatial frequency domain imaging

The sensitivity to surface profile of non-contact optical imaging, such as spatial frequency domain imaging, may lead to incorrect measurements of optical properties and consequently erroneous extrapolation of physiological parameters of interest. Previous correction methods have focused on calibration-based, model-based, and computation-based approached. We propose an experimental method to correct the effect of surface profile on spectral images. Three-dimensional (3D) phantoms were built with acrylonitrile butadiene styrene (ABS) plastic using an accurate 3D imaging and an emergent 3D printing technique. In this study, our method was utilized for the correction of optical properties (absorption coefficient μa and reduced scattering coefficient μs′) of objects obtained with a spatial frequency domain imaging system. The correction method was verified on three objects with simple to complex shapes. Incorrect optical properties due to surface with minimum 4 mm variation in height and 80 degree in slope were detected and improved, particularly for the absorption coefficients. The 3D phantom-based correction method is applicable for a wide range of purposes. The advantages and drawbacks of the 3D phantom-based correction methods are discussed in details.

Novel application of a spatial frequency domain imaging system to determine signature spectral differences between infected and noninfected burn wounds.

Complications of infection can increase burn-related morbidity and mortality. Early detection of burn wound infection could lead to more precise and effective treatment, reducing systemic complications and the need for long-term, broad-spectrum intravenous antibiotics. Quantitative cultures from biopsies are the accepted standard to determine infection. However, this methodology can take days to yield results and is invasive. This investigation focuses on the use of noninvasive imaging to determine the infection status of burn wounds in a controlled in vivo model. Full-thickness burn wounds were created on the dorsum of adult male rats (n = 6). Twenty-four hours after burn wound creation, wounds in the “Infected” group were inoculated with a vehicle containing 1 × 108 colony forming unit Staphylococcus aureus. “Control” group animals received vehicle alone. Subsequently, the wounds were imaged daily for a total of 10 days and the differences of skin optical properties were assessed using spatial frequency domain imaging at 16 different wavelengths from 500 to 700 nm. Regions of interest on the resulting images were selected and averaged at each time point. Statistically significant differences in average absorption and reduced scattering coefficients (&mgr;a and &mgr;s′) at 620 and 700 nm were observed between the two groups (P < .05). Differential optical properties were most evident by day 4 and persisted throughout the time course. Differential signature changes in optical properties are evident in infected burn wounds. This novel application of spatial frequency domain imaging may prove to be a valuable adjunct to burn wound assessment. Further work will be aimed at determining dose–response relationships and prokaryotic species differences.

Examination of local and systemic in vivo responses to electrical injury using an electrical burn delivery system

Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2–20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity.

Monitoring the impact of pressure on the assessment of skin perfusion and oxygenation using a novel pressure device

Skin perfusion and oxygenation is easily disrupted by imposed pressure. Fiber optics probes, particularly those spectroscopy or Doppler based, may relay misleading information about tissue microcirculation dynamics depending on external forces on the sensor. Such forces could be caused by something as simple as tape used to secure the fiber probe to the test subject, or as in our studies by the full weight of a patient with spinal cord injury (SCI) sitting on the probe. We are conducting a study on patients with SCI conducting pressure relief maneuvers in their wheelchairs. This study aims to provide experimental evidence of the optimal timing between pressure relief maneuvers. We have devised a wireless pressure-controlling device; a pressure sensor positioned on a compression aluminum plate reads the imposed pressure in real time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the sample. This apparatus was used to monitor the effect of increasing values of pressure on spectroscopic fiber probes built to monitor tissue oxygenation and Doppler probes used to assess tissue perfusion.

Skin microvascular and metabolic response to pressure relief maneuvers in people with spinal cord injury

Clinician’s recommendations on wheelchair pressure reliefs in the context of the high prevalence of pressure ulcers that occur in people with spinal cord injury is not supported by strong experimental evidence. Some data indicates that altered tissue perfusion and oxygenation occurring under pressure loads, such as during sitting, induce various pathophysiologic changes that may lead to pressure ulcers. Pressure causes a cascade of responses, including initial tissue hypoxia, which leads to ischemia, vascular leakage, tissue acidification, compensatory angiogenesis, thrombosis, and hyperemia, all of which may lead to tissue damage. We have developed an advanced skin sensor that allows measurement of oxygenation in addition to perfusion, and can be safely used during sitting. The sensor consists of a set of fiber optics probes, spectroscopic and Laser Doppler techniques that are used to obtain parameters of interest. The overriding goal of this project is to develop the evidence base for clinical recommendations on pressure reliefs. In this paper we will illustrate the experimental apparatus as well as some preliminary results of a small clinical trial conducted at the National Rehabilitation Hospital.

Assessment of the Pathophysiology of Injured Tissue With an In Vivo Electrical Injury Model

Tissue destruction from electrical injury is devastating and hard to treat. Unfortunately, the pathophysiology of electrical trauma is still not well understood. We have developed a suite of tools aimed at investigating damage due to high voltage shock on the skin using a rat model. Electrical injuries were created with a custom made high-tension shock system and a spectroscopic system, based on spatial frequency domain imaging, was used to determine optical properties of electrically injured tissues. The extrapolated values of absorption and scattering coefficients at six different wavelengths were then utilized to monitor parameters of interest such as tissue oxygen saturation, methemoglobin volume fraction, and hemoglobin volume fraction at four time intervals post injury. An FLIR thermal camera was used to record skin temperature during the electrical shock. Finally, a laser Doppler imaging apparatus was used to assess tissue perfusion. In this paper, the results of experiments conducted on a rat model and discussions on the systemic changes in tissue optical properties before and after electrical shock are presented. A reduction in tissue oxygen saturation postinjury is observed as well as an increase in methemoglobin. Tissue perfusion increases immediately after the delivery of the electrical shock.

Modeling of skin cooling, blood flow, and optical properties in wounds created by electrical shock

High voltage electrical injuries may lead to irreversible tissue damage or even death. Research on tissue injury following high voltage shock is needed and may yield stage-appropriate therapy to reduce amputation rate. One of the mechanisms by which electricity damages tissue is through Joule heating, with subsequent protein denaturation. Previous studies have shown that blood flow had a significant effect on the cooling rate of heated subcutaneous tissue. To assess the thermal damage in tissue, this study focused on monitoring changes of temperature and optical properties of skin next to high voltage wounds. The burns were created between left fore limb and right hind limb extremities of adult male Sprague-Dawley rats by a 1000VDC delivery shock system. A thermal camera was utilized to record temperature variation during the exposure. The experimental results were then validated using a thermal-electric finite element model (FEM).

Construction of a digital and physical mouse model aimed at the study of electrical shock

Optical methods have been used to investigate electrical injury on animal models such as live mice, rats, and rabbits. Here we introduce a completely digital phantom of a mouse, with the aim of investigating electrical injury through spectroscopic imaging techniques. The basis of our phantom is a three-dimensional digital mouse reconstructed from co-registered computed tomographic images and cryosection by a different group. Image processing algorithms were applied to make the model suitable to Finite Element Analysis of thermal and electrical transport. Our digital model is capable of simulating temperature, voltage, current changes along the animal body during and after electrical shocks.

Better evaluation of electric shock injuries

Electrical injuries have a variety of causes but are most common in the workplace where typical injuring voltages are 1–10kV. Such injuries are devastating at and beyond the point of contact. Contact points are often completely carbonized, with both tissue and bone removed, and necrosis (death of tissue) can spread well beyond the main site of injury. Damage to cutaneous tissues depends on the site of impact, the strength of the field, and the exposure time. At present, the extent of electrical injury is often diagnosed by visual and tactile inspection. If we could develop direct, non-invasive diagnostics for tissue close to the entry and exit sites of electrical injury, clinicians would have important additional information when selecting an operative strategy. Various imaging techniques have been used to evaluate soft tissue injury.1 Magnetic resonance imaging (MRI) is a valuable tool for visualizing the extent of deep tissue damage and guiding surgical procedures. Furthermore, functional MRI can be used to monitor the physiological behavior of an organ system, but, unfortunately, this technique is very costly. Thermography has been used to assess burn depth in correlation to temperature, but its susceptibility to ambient temperature and time of injury restrict its suitability for real clinical use. Ultrasound can distinguish between necrotic and viable tissue—heat damaged tissue has significantly different acoustic impedance compared to healthy tissue—but has the disadvantage of requiring contact with the patient. Finally, laser doppler imaging (LDI) can be a useful and non-invasive tool for evaluating burn wounds by measuring blood perfusion (flow through the wound). We combined off-the-shelf imaging tools (laser doppler, thermal imagers) and custom-made devices (our spectral imaging system, see Figure 1) to determine tissue viability after electrical injury. First, hemoglobin volume fraction combined with an assessment of blood motility is useful to determine the presence Figure 1. Our electrical burn imaging system, consisting of a laser doppler imager (LDI), a spatial frequency domain imaging (SFDI) system, and an IR camera.

Correction of shape-induced artifacts in spectroscopic imaging of biological media

Imaging spectroscopy results are often biased by the surface structure of the imaged object. A combination of software and experimental tools has been designed to study and minimize this effect