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There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2...
Citations
... lacking vasculature and immune components typically composed of only a single layer or without the addition of any 3D ECM [10][11][12][13]. Pigs are the most commonly used animal model due to the physiological similarity of their skin to human skin [4,14,15], with mice and rats being used for initial testing, but lacking in their capability to replicate the thickness, complexity, and wound healing mechanisms of human skin [14]. Although porcine skin models provide the most complete and physiologic microenvironment to human skin, the dynamics and spatial kinetics of skin injury and wound healing cannot be easily studied without significant time and expense. ...
One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function in the skin and physiological transport properties. We created a 3D vascularized human skin equivalent (VHSE) with a dermal and epidermal layer, and compared keratinocyte differentiation (immunomarker staining), epidermal thickness (H&E staining), and barrier function (transepithelial electrical resistance (TEER) and dextran permeability) to a static, organotypic avascular HSE (AHSE). The VHSE had a significantly thicker epidermal layer and increased resistance, both an indication of increased barrier function, compared to the AHSE. The inclusion of keratin in our collagen hydrogel extracellular matrix (ECM) increased keratinocyte differentiation and barrier function, indicated by greater resistance and decreased permeability. Surprisingly, however, endothelial cells grown in a collagen/keratin extracellular environment showed increased cell growth and decreased vascular permeability, indicating a more confluent and tighter vessel compared to those grown in a pure collagen environment. The development of a novel VHSE, which incorporated physiological vasculature and a unique collagen/keratin ECM, improved barrier function, vessel development, and skin structure compared to a static AHSE model.
... It can be noticed that the THz-TDS measurements can predict the final result of the healing process with a higher ROC-AUC value of 93% compared to the diagnosis of the burn severity group with the average ROC-AUC value of 84.5% between the PT and FT burns. It has been indicated in the literature that the biopsies obtained in the first 24-hours post-burn period can underestimate the severity of the burns [85]. This can be either because of the burn wound progression over the inflammatory cascade of the tissue or the inability of the H&E staining to reveal the functional cell damage [85]. ...
... It has been indicated in the literature that the biopsies obtained in the first 24-hours post-burn period can underestimate the severity of the burns [85]. This can be either because of the burn wound progression over the inflammatory cascade of the tissue or the inability of the H&E staining to reveal the functional cell damage [85]. Further improvements might be obtained by using other biopsy staining methodologies. ...
The initial assessment of the depth of a burn injury during triage forms the basis for determination of the course of the clinical treatment plan. However, severe skin burns are highly dynamic and hard to predict. This results in a low accuracy rate of about 60 - 75% in the diagnosis of partial-thickness burns in the acute post-burn period. Terahertz time-domain spectroscopy (THz-TDS) has demonstrated a significant potential for non-invasive and timely estimation of the burn severity. Here, we describe a methodology for the measurement and numerical modeling of the dielectric permittivity of the in vivo porcine skin burns. We use the double Debye dielectric relaxation theory to model the permittivity of the burned tissue. We further investigate the origins of dielectric contrast between the burns of various severity, as determined histologically based on the percentage of the burned dermis, using the empirical Debye parameters. We demonstrate that the five parameters of the double Debye model can form an artificial neural network classification algorithm capable of automatic diagnosis of the severity of the burn injuries, and predicting its ultimate wound healing outcome by forecasting its re-epithelialization status in 28 days. Our results demonstrate that the Debye dielectric parameters provide a physics-based approach for the extraction of the biomedical diagnostic markers from the broadband THz pulses. This method can significantly boost dimensionality reduction of THz training data in artificial intelligence models and streamline machine learning algorithms.
... Burns with >90% depth of damage to the dermis are grouped as the FT burns. Although each burn site is labeled based on the histological assessment of one biopsy section, the scald and contact devices fabricated for the induction of the burn injuries are designed following the standardized approaches, 74,75 which have been demonstrated to result in highly consistent and fairly homogeneous burns. ...
... It has been indicated in the literature that the biopsies obtained in the first 24 h post-burn period can underestimate the severity of the burns. 75 This can be because of either the burn wound progression over the inflammatory cascade of the tissue or the inability of the H&E staining to reveal the functional cell damage. 75 Therefore, the re-epithelialization rate of the burns obtained three or four weeks postburn is a more reliable histological assessment to establish the ground truth of the burns requiring grafting or healing spontaneously. ...
... 75 This can be because of either the burn wound progression over the inflammatory cascade of the tissue or the inability of the H&E staining to reveal the functional cell damage. 75 Therefore, the re-epithelialization rate of the burns obtained three or four weeks postburn is a more reliable histological assessment to establish the ground truth of the burns requiring grafting or healing spontaneously. It also should be noted that predicting the wound healing outcome is a binary classification task. ...
SignificanceSevere burn injuries cause significant hypermetabolic alterations that are highly dynamic, hard to predict, and require acute and critical care. The clinical assessments of the severity of burn injuries are highly subjective and have consistently been reported to be inaccurate. Therefore, the utilization of other imaging modalities is crucial to reaching an objective and accurate burn assessment modality.AimWe describe a non-invasive technique using terahertz time-domain spectroscopy (THz-TDS) and the wavelet packet Shannon entropy to automatically estimate the burn depth and predict the wound healing outcome of thermal burn injuries.ApproachWe created 40 burn injuries of different severity grades in two porcine models using scald and contact methods of infliction. We used our THz portable handheld spectral reflection (PHASR) scanner to obtain the in vivo THz-TDS images. We used the energy to Shannon entropy ratio of the wavelet packet coefficients of the THz-TDS waveforms on day 0 to create supervised support vector machine (SVM) classification models. Histological assessments of the burn biopsies serve as the ground truth.ResultsWe achieved an accuracy rate of 94.7% in predicting the wound healing outcome, as determined by histological measurement of the re-epithelialization rate on day 28 post-burn induction, using the THz-TDS measurements obtained on day 0. Furthermore, we report the accuracy rates of 89%, 87.1%, and 87.6% in automatic diagnosis of the superficial partial-thickness, deep partial-thickness, and full-thickness burns, respectively, using a multiclass SVM model.Conclusions
The THz PHASR scanner promises a robust, high-speed, and accurate diagnostic modality to improve the clinical triage of burns and their management.
... The importance of this is simplifying the experimental work as dealing with animal tissue i.e. (porcine skin) make flexibility in testing new materials and predicting possible signatures of the skin with and without clothing layer. A motivation for using porcine skin tissue is that it is cost effective, easy to handle and use, accessible and available with no restrictions, and it has close properties to the human tissue [19,20]. ...
... The samples were taken from the back region of different animal. This region is chosen since it is free from hair follicle and sweat glands [19,20]. ...
... Researchers in [19,20] reported similarities in porcine skin and human skin in terms of skin structure and functionality of the skin. In this research we are going to investigate how close the signature of the porcine skin to human skin i.e. (the palm of the hand region). ...
Improving the security screening requires good knowledge and understanding of human skin signatures. Our previous publications indicate that the signature of the human skin varies from person to person under a dry and wet state. Human skin is a very sensitive organ and not all material can be applied or attached directly to the skin. Therefore, it is an essential requirement to find a close surrogate i.e. (animal tissue) and characterise similarities in signature between human and animal skin. The importance of this is that it will allow us to investigate more easily signatures of the human skin under different materials and conditions. This paper investigates signatures for the human skin and ex-vivo porcine skin samples using the 90 GHz calibrated radiometer. The paper aims to compare and show similarities and differences in the signature between human and ex-vivo porcine skin samples for the first time using millimetric wave radiometry. To this end, water and different types of cream were applied to the palm of the hand and porcine skin samples namely: skin with water jel, skin with silver sulfadiazine cream, and skin with betadine cream. The reflectance of the skin was measured before and after the application, with and without the presence of a clothing layer. Reflectance measurements on human skin were applied on six participants in the palm of the hand region for comparison with reflectance measurements of porcine skin from six samples taken from the back region of different animals. Reflectance measurements for the palm of the hand skin show that the mean reflectance values for all six participants are: 0.458, 0.618, 0.578, 0.548, and 0.488 for normal skin, skin with water, skin with water jel, skin with silver sulfadiazine cream, and skin with betadine cream respectively. For porcine skin samples, the mean reflectance values for all six samples are: 0.438, 0.608, 0.598, 0.558, and 0.508 for normal skin, skin with water, skin with water jel, skin with silver sulfadiazine cream, and skin with betadine cream respectively. These measurements indicate the similarities between the palm of the human hand and the back region of swine. The measurements also show that the difference in the mean reflectance values between the palm of the hand region and porcine skin for all cases is ~0.02. After adding a clothing layer made of textiles on the palm of the hand skin and porcine skin samples; the reflectance measurements for the palm of the hand skin become 0.408, 0.545, 0.498, 0.488, and 0.458 for normal skin, skin with water, skin with water jel, skin with silver sulfadiazine cream, and skin with betadine cream respectively. For porcine skin samples the mean reflectance values are: 0.388, 0.518, 0.488,0.488, and 0.478 respectively. These measurements indicate that textiles are relatively transparent over the frequency band (80-100) GHz and the signature of the skin can be observed through clothing. The increased understanding of these measurements brings means research into the medical applications of millimetre wave imaging to assess wounds under dressings. More specifically, subjects bearing bandaged wounds could be screened more reliably using imagers. In addition to the security screening applications and anomalies detection.
... A digital hotplate illustrated in Figure 3a (type: LED digital hotplate magnetic stirrer, manufacturer: SciQuip Ltd., Wem, UK) with a temperature range of 280 • C was used to heat the porcine skin samples and to stabilize the skin surface temperature to~35 • C. This temperature was chosen since it is similar to the in vivo surface temperature of the porcine skin~35 • C as reported in [50,51]. The heat control metal plate (model number: SP2230-280H, manufacturer: SciQuip Ltd.) that is shown in Figure 3b consists of a temperature controller, thermocouple, and a square metal plate (50 mm × 50 mm). ...
This paper presents a feasibility study of using a passive millimeter-wave imaging
(PMMWI) system to assess burn wounds and the potential for monitoring the healing process under dressing materials, without their painful removal. Experimental images obtained from ex vivo porcine skin samples indicate that a ThruVision passive imager operating over the band 232–268 GHz can be used for diagnosing burns and for potentially monitoring the healing under dressing materials. Experimental images show that single and multiple burns are observed throughout dressing materials.
As the interaction of millimeter-wave (MMW) radiation with the human body is almost exclusively with the skin, the major outcomes of the research are that PMMWI is capable of discriminating burn-damaged skin from unburned skin, and these measurements can be made through bandages without the imager making any physical contact with the skin or the bandage. This highlights the opportunity that the healing of burn wounds can be assessed and monitored without the removal of dressing materials. The key innovation in this work is in detecting single and multiple burns under dressing materials in noncontact with the skin and without exposing the skin to any type of manmade radiation (i.e., passive sensing technology). These images represent the first demonstration of burns wound under dressing materials using a passive sensing imager.
... These example etiologies were chosen because they are clinically representative of many real-world burn injuries [1]. Furthermore, scald burns should provide relatively high inter-group homogeneity [59,60] and contact burns are well validated in the literature for large [61] and small burn injuries [62][63][64]. As shown in Fig. 1(a), the first method of burn induction was with a contact device, which was created using a square brass bar and a spring loaded tube to maintain constant pressure (2 kg / 6.25 cm 2 ). ...
... This device has the capability of maintaining temperatures up to 160°C. As shown in Fig. 1(b), the second method of burn induction was using a standardized hot water scald device [60]. This device consisted of a stainless steel pipe with a hot water inlet and a vacuum outlet (Adafruit Industries, New York, NY, USA) to constantly cycle hot water through the device and onto the surface of the skin. ...
Thermal injuries can occur due to direct exposure to hot objects or liquids, flames, electricity, solar energy and several other sources. If the resulting injury is a deep partial thickness burn, the accuracy of a physician’s clinical assessment is as low as 50-76% in determining the healing outcome. In this study, we show that the Terahertz Portable Handheld Spectral Reflection (THz-PHASR) Scanner combined with a deep neural network classification algorithm can accurately differentiate between partial-, deep partial-, and full-thickness burns 1-hour post injury, regardless of the etiology, scanner geometry, or THz spectroscopy sampling method (ROC-AUC = 91%, 88%, and 86%, respectively). The neural network diagnostic method simplifies the classification process by directly using the pre-processed THz spectra and removing the need for any hyperspectral feature extraction. Our results show that deep learning methods based on THz time-domain spectroscopy (THz-TDS) measurements can be used to guide clinical treatment plans based on objective and accurate classification of burn injuries.
... [39] In addition to our prior reporting, [32] other groups have also observed that this model results in certain burn depth variability between the anatomical locations, as well as between the center and the edges of each burn. [39,40] This variability is because good contact between the skin and the heat source may be obstructed by skin surface heterogeneities and air pockets. [39,40] Here, we address this concern by inducing the burns with a scalding device that allows hot water to be in direct contact with the skin. ...
... [39,40] This variability is because good contact between the skin and the heat source may be obstructed by skin surface heterogeneities and air pockets. [39,40] Here, we address this concern by inducing the burns with a scalding device that allows hot water to be in direct contact with the skin. [40] Furthermore, our previous work using a fiber-coupled commercial THz setup in a porcine burn model was restricted to single-point spectroscopic measurements. ...
... [39,40] Here, we address this concern by inducing the burns with a scalding device that allows hot water to be in direct contact with the skin. [40] Furthermore, our previous work using a fiber-coupled commercial THz setup in a porcine burn model was restricted to single-point spectroscopic measurements. [32] Here, we have developed the first handheld, alignment-free, and easily deployable THz-TDSI scanner for diagnostic mapping of the burn severity in large mammals. ...
The accuracy of clinical assessment techniques in diagnosing partial-thickness burn injuries has remained as low as 50–76%. Depending on the burn depth and environmental factors in the wound, such as reactive oxygen species, inflammation, and autophagy, partial-thickness burns can heal spontaneously or require surgical intervention. Herein, it is demonstrated that terahertz time-domain spectral imaging (THz-TDSI) is a promising tool for in vivo quantitative assessment and monitoring of partial-thickness burn injuries in large animals. We used a novel handheld THz-TDSI scanner to characterize burn injuries in a porcine scald model with histopathological controls. Statistical analysis (n = 40) indicates that the THz-TDSI modality can accurately differentiate between partial-thickness and full-thickness burn injuries (1-way ANOVA, p < 0.05). THz-TDSI has the potential to improve burn care outcomes by helping surgeons in making objective decisions for early excision of the wound.
... Tissues with burn depth between 40% and 80% of dermal thickness formed the deep partial-thickness (DPT) group, and samples having larger than 80% dermal burn depth, including those with a damaged hypodermis, were grouped as the full-thickness (FT) category. It should be noted that our burn induction devices, which are designed and fabricated following the techniques demonstrated in 57,58 , result in highly consistent and fairly homogeneous burns over the same location. In addition, the 40% burn thickness range encompassed by each burn severity group is large enough to account for slight variations in the burn thickness over the same burn location. ...
We present an automatic classification strategy for early and accurate assessment of burn injuries using terahertz (THz) time-domain spectroscopic imaging. Burn injuries of different severity grades, representing superficial partial-thickness (SPT), deep partial-thickness (DPT), and full-thickness (FT) wounds, were created by a standardized porcine scald model. THz spectroscopic imaging was performed using our new fiber-coupled Portable HAndheld Spectral Reflection (PHASR) scanner, incorporating a telecentric beam steering configuration and an f-\theta scanning lens. ASynchronous Optical Sampling (ASOPS) in a dual-fiber-laser THz spectrometer with 100 MHz repetition rate enabled high-speed spectroscopic measurements. Given twenty-four different samples composed of ten scald and ten contact burns and four healthy samples, supervised machine learning algorithms using THz-TDS spectra achieved areas under the receiver operating characteristic (ROC) curves of 0.88, 0.93, and 0.93 when differentiating between SPT, DPT, and FT burns, respectively, as determined by independent histological assessments. These results show the potential utility of our new broadband THz PHASR scanner for early and accurate triage of burn injuries.
... These example etiologies were chosen because they are clinically representative of many real-world burn injuries [1]. Furthermore, scald burns should provide relatively high inter-group homogeneity [59,60] and contact burns are well validated in the literature for large [61] and small burn injuries [62][63][64]. As shown in Fig. 1(a), the first method of burn induction was with a contact device, which was created using a square brass bar and a spring loaded tube to maintain constant pressure (2 kg / 6.25 cm 2 ). ...
... This device has the capability of maintaining temperatures up to 160°C. As shown in Fig. 1(b), the second method of burn induction was using a standardized hot water scald device [60]. This device consisted of a stainless steel pipe with a hot water inlet and a vacuum outlet (Adafruit Industries, New York, NY, USA) to constantly cycle hot water through the device and onto the surface of the skin. ...
... We consider a stochastic model that describes the spatio-temporal diffusion of thermal energy in a heterogeneous, layered biological material. We are motivated by the experimental work of Andrews et al. [21][22][23][24] who consider heat conduction through living, layered porcine skin, shown in figure 1a. Andrews' experiments are performed by placing a constant temperature external heat source at the surface of the skin, at the top of the epidermis. ...
... Over time, thermal energy conducts across the epidermis and dermis, reaching the subdermal fat layer. Andrews et al. [21][22][23][24] measure this heat conduction process in real time by obliquely inserting a temperature probe at the base of the fat layer. For example, the data in figure 1b show the result of an experiment where a constant heat source at 50 • C is placed at the top of the skin, and the subdermal temperature is measured at intervals of 1 s at the base of the fat layer. ...
... These data suggest that the thermal disturbance at the surface of the layered skin takes approximately 14 s to affect the subdermal temperature. A key restriction of Andrews' experimental design is that the living tissues are relatively thin and the temperature probe can only be placed at a single location without destroying the integrity of the living tissue [21][22][23][24]. Given that Andrews' data take the form of a time series of temperature data recorded at the base of the fat layer, a key quantity of interest is to measure the duration of time required for the temperature at the base of the fat layer to respond to the thermal disturbance at the surface of the layered skin. ...
We compute profile likelihoods for a stochastic model of diffusive transport motivated by experimental observations of heat conduction in layered skin tissues. This process is modelled as a random walk in a layered one-dimensional material, where each layer has a distinct particle hopping rate. Particles are released at some location, and the duration of time taken for each particle to reach an absorbing boundary is recorded. To explore whether these data can be used to identify the hopping rates in each layer, we compute various profile likelihoods using two methods: first, an exact likelihood is evaluated using a relatively expensive Markov chain approach; and, second, we form an approximate likelihood by assuming the distribution of exit times is given by a Gamma distribution whose first two moments match the moments from the continuum limit description of the stochastic model. Using the exact and approximate likelihoods, we construct various profile likelihoods for a range of problems. In cases where parameter values are not identifiable, we make progress by re-interpreting those data with a reduced model with a smaller number of layers.
