The field of electronic skin has received considerable attention due to its extensive potential applications in areas including tactile sensing and health monitoring. With the development of electronic skin devices, electronic skin can be attached to the surface of human skin for long-term health monitoring, which makes comfort an essential factor that cannot be ignored in the design of electronic skin. Therefore, this paper proposes an assessment method for evaluating the comfort of electronic skin based on neurodynamic analysis. The holistic analysis framework encompasses the mechanical model of the skin, the modified Hodgkin-Huxley model for the transduction of stimuli, and the gate control theory for the modulation and perception of pain sensation. The complete process, from mechanical stimulus to the generation of pain perception, is demonstrated. Furthermore, the influence of different factors on pain perception is investigated. Sensation and comfort diagrams are provided to assess the mechanical comfort of electronic skin. The comfort assessment method proposed in this paper provides a theoretical basis when assessing the comfort of electronic skin.

This study presents a multilayer in vitro human skin platform to quantitatively relate predicted spatial time-temperature history with measured tissue injury response. This information is needed to elucidate high-temperature, short-duration burn injury kinetics and enables determination of relevant input parameters for computational models to facilitate treatment planning. Multilayer in vitro skin platforms were constructed using human dermal keratinocytes and fibroblasts embedded in collagen I hydrogels. After three seconds of contact with a 50-100 °C burn tip, ablation, cell death, apoptosis, and HSP70 expression were spatially measured using immunofluorescence confocal microscopy. Finite element modeling was performed using the measured thermal characteristics of skin platforms to determine the temperature distribution within platforms over time. The process coefficients for the Arrhenius thermal injury model describing tissue ablation and cell death were determined such that the predictions calculated from the time-temperature histories fit the experimental burn results. The activation energy for thermal collagen ablation and cell death was found to be significantly lower for short-duration, high-temperature burns than those found for long-duration, low-temperature burns. Analysis of results suggests that different injury mechanisms dominate at higher temperatures, necessitating burn research in the temperature ranges of interest and demonstrating the practicality of the proposed skin platform for this purpose.

Irreversible electroporation (IRE), also referred to as nonthermal pulsed field ablation (PFA), is an attractive focal ablation modality for solid tumors and cardiac tissue due to its ability to destroy aberrant cells with limited disruption of the underlying tissue architecture. Despite its nonthermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested as a potential means to limit thermal damage. However, several variables affect TM performance including the pulsing paradigm, electrode geometry, PCM composition, and chosen active cooling parameters, meaning direct comparisons between approaches are lacking. In this study, we developed a computational model of conventional bipolar and monopolar probes with solid, PCM-filled, or actively cooled cores to simulate clinical IRE treatments in pancreatic tissue. This approach reveals that probes with integrated PCM cores can be tuned to drastically limit thermal damage compared to existing solid probes. Furthermore, actively cooled probes provide additional control over thermal effects within the probe vicinity and can altogether abrogate thermal damage. In practice, such differences in performance must be weighed against the increased time, expense, and effort required for modified probes compared to existing solid probes.

High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay (d1)-negative phase-interpulse delay (d2) pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively.

We sought to determine whether modifications to the delays within H-FIRE bursts could yield a more desirable clinical outcome in terms of ablation volume versus extent of tissue excitation.

We used a modified spatially extended nonlinear node (SENN) nerve fiber model to evaluate excitation thresholds for H-FIRE bursts with varying delays. We then calculated non-thermal tissue ablation, thermal damage, and excitation in a clinically relevant numerical model.

Excitation thresholds were maximized by shortening d1, and extension of d2 up to 1,000 μs increased excitation thresholds by at least 60% versus symmetric bursts. In the ablation model, long interpulse delays lowered the effective frequency of burst waveforms, modulating field redistribution and reducing heat production. Finally, we demonstrate mathematically that variable delays allow for increased voltages and larger ablations with similar extents of excitation as symmetric waveforms.

Interphase and interpulse delays play a significant role in outcomes resulting from H-FIRE treatment.

Waveforms with short interphase delays (d1) and extended interpulse delays (d2) may improve therapeutic efficacy of H-FIRE as it emerges as a clinical tissue ablation modality.

It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50-400 mJ/pixel) from a CO₂ AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

A computational model was developed to better understand the impact of elevated skin temperatures on transdermal drug delivery and dermal clearance. A simultaneous heat and mass transport model with emphasis on transdermal delivery system (TDS) applications was developed to address transient and steady-state temperature effects on dermal absorption. The model was tested using representative data from nicotine TDS applied to human skin either in vitro or in vivo. The approximately 2-fold increase of nicotine absorption with a 10°C increase in skin surface temperature was consistent with a 50-65 kJ/mol activation energy for diffusion in the stratum corneum, with this layer serving as the primary barrier for nicotine absorption. Incorporation of a dermal clearance component into the model revealed efficient removal of nicotine via the dermal capillaries at both normal and elevated temperatures. Two-compartment pharmacokinetic simulations yielded systemic drug concentrations consistent with the human pharmacokinetic data. Both in vitro skin permeation and in vivo pharmacokinetics of nicotine delivered from a marketed TDS under normal and elevated temperatures can be satisfactorily described by a simultaneous heat and mass transfer computational model incorporating realistic skin barrier properties and dermal clearance components.

Purpose: This study evaluates the effects of various pulsing paradigms, on the irreversible electroporation (IRE) lesion, induced electric current, and temperature changes using a perfused porcine liver model. Materials and methods: A 4-monopolar electrode array delivered IRE therapy varying the pulse length and inter-pulse delay to six porcine mechanically perfused livers. Pulse paradigms included six forms of cycled pulsing schemes and the conventional pulsing scheme. Finite element models provided further insight into the effects of cycled pulsing on the temperature and thermal injury distribution. Results: 'Single pulse cycle with no interpulse delay' deposited maximum average energy (2.34 ± 0.35 kJ) and produced the largest ratio of thermally damaged tissue area and IRE ablation area from all other pulse schemes (18.22%  ±  8.11, p < .0001 all pairwise comparisons). These compared favorably to the conventional algorithm (2.09 ± 0.37 kJ, 3.49%  ±  2.20, p < .0001, all comparisons). Though no statistical significance was found between groups, the '5 pulse cycle, 0 s delay' pulse paradigm produced the largest average IRE ablation cross sectional area (11.81 ± 1.97 cm²), while conventional paradigm yielded an average of 8.90 ± 0.91 cm². Finite element modeling indicated a '10 pulse cycle, 10 s delay' generated the least thermal tissue damage and '1 pulse cycle, 0 s delay' pulse cycle sequence the most (0.47 vs. 3.76 cm²), over a lengthier treatment time (16.5 vs. 6.67 minutes). Conclusions: Subdividing IRE pulses and adding delays throughout the treatment can reduce white tissue coagulation and electric current, while maintaining IRE treatment sizes.

Understanding the impact of thermally and mechanically loading biological tissue to supraphysiological levels is becoming of increasing importance as complex multiphysical tissue-device interactions increase. The ability to conduct accurate, patient specific computer simulations would provide surgeons with valuable insight into the physical processes occurring within the tissue as it is heated or cooled. Several studies have modeled tissue as porous media, yet fully coupled thermoporomechanics (TPM) models are limited. Therefore, this study introduces a small deformation theory of modeling the TPM occurring within biological tissue. Next, the model is used to simulate the mass, momentum, and energy balance occurring within an artery wall when heated by a tissue fusion device and compared to experimental values. Though limited by its small strain assumption, the model predicted final tissue temperature and water content within one standard deviation of experimental data for seven of seven simulations. Additionally, the model showed the ability to predict the final displacement of the tissue to within 15% of experimental results. These results promote potential design of novel medical devices and more accurate simulations allowing for scientists and surgeons to quickly, yet accurately, assess the effects of surgical procedures as well as provide a first step toward a fully coupled large deformation TPM finite element (FE) model.

Thermal injury to skin and subcutaneous tissue is common in both civilian and combat scenarios. Understanding the change in tissue morphologies and properties and the underlying mechanisms of thermal injury are of vital importance to clinical determination of the degree of burn and treatment approach. This review aims at summarizing the research involving experimental and numerical studies of skin and subcutaneous tissue subjected to thermal injury. The review consists of two parts. The first part deals with experimental studies including burn protocols and prevailing imaging approaches. The second part deals with existing numerical models for burns of tissue and related computational simulations. Based on this review, we conclude that though there is literature contributing to the knowledge of the pathology and pathogenesis of tissue burn, there is scant quantitative information regarding changes in tissue properties including mechanical, thermal, electrical and optical properties as a result of burns that are linked to altered tissue morphology.

Most test methods use skin burn prediction to evaluate the thermal protective performance of clothing. In this paper, we reviewed different burn prediction methods used in clothing evaluation. The empirical criterion and the mathematical model were analyzed in detail as well as their relationship and limitations. Using an empirical criterion, the onset of skin burn is determined by the accumulated skin surface energy in certain periods. On the other hand, the mathematical model, which indicates denatured collagen, is more complex, which involves a heat transfer model and a burn model. Further studies should be conducted to examine the situations where the prediction methods are derived. New technologies may be used in the future to explore precise or suitable prediction methods for both flash fire tests and increasingly lower-intensity tests.

To date, heat conduction from heat sources to tissue has been estimated by complex mathematical modeling. In the present study, we developed an intuitive in vitro skin burn model that illustrates heat conduction patterns inside the skin. This was composed of tightly compressed thermal papers with compression frames. Heat flow through the model left a trace by changing the color of thermal papers. These were digitized and three-dimensionally reconstituted to reproduce the heat conduction patterns in the skin. For standardization, we validated K91HG-CE thermal paper using a printout test and bivariate correlation analysis. We measured the papers' physical properties and calculated the estimated depth of heat conduction using Fourier's equation. Through contact burns of 5, 10, 15, 20, and 30 seconds on porcine skin and our burn model using a heated brass comb, and comparing the burn wound and heat conduction trace, we validated our model. The heat conduction pattern correlation analysis (intraclass correlation coefficient: 0.846, p < 0.001) and the heat conduction depth correlation analysis (intraclass correlation coefficient: 0.93, p < 0.001) showed statistically significant high correlations between the porcine burn wound and our model. Our model showed good correlation with porcine skin burn injury and replicated its heat conduction patterns.

Thermal effects of laser irradiation on skin are investigated in this paper. The main purpose is to determine the damage level induced by a laser exposure. Potential burns induced by two lasers (wavelength 808nm and 1940nm) are studied and animal experimentations are performed. Several exposure durations and laser powers are tested. Based on previous works, a mathematical model dedicated to temperature prediction is proposed and finite-element method is implemented. This numerical predictive tool based on the bioheat equation takes into account heat losses due to the convection on skin surface, blood circulatory and also evaporation. Thermal behavior of each skin layer is also described considering distinct thermal and optical properties. Since the mathematical model is able to estimate damage levels, histological analyses were also carried through. It is confirmed that the mathematical model is an efficient predictive tool for estimation of damage caused by lasers and that thermal effects sharply depend on laser wavelength.

Irreversible electroporation (IRE) is a new minimally invasive technique to kill undesirable tissue in a non-thermal manner. In order to maximize the benefits from an IRE procedure, the pulse parameters and electrode configuration must be optimized to achieve complete coverage of the targeted tissue while preventing thermal damage due to excessive Joule heating.

We developed numerical simulations of typical protocols based on a previously published computed tomographic (CT) guided in vivo procedure. These models were adapted to assess the effects of temperature, electroporation, pulse duration, and repetition rate on the volumes of tissue undergoing IRE alone or in superposition with thermal damage.

Nine different combinations of voltage and pulse frequency were investigated, five of which resulted in IRE alone while four produced IRE in superposition with thermal damage.

The parametric study evaluated the influence of pulse frequency and applied voltage on treatment volumes, and refined a proposed method to delineate IRE from thermal damage. We confirm that determining an IRE treatment protocol requires incorporating all the physical effects of electroporation, and that these effects may have significant implications in treatment planning and outcome assessment. The goal of the manuscript is to provide the reader with the numerical methods to assess multiple-pulse electroporation treatment protocols in order to isolate IRE from thermal damage and capitalize on the benefits of a non-thermal mode of tissue ablation.

Intense but short electrical fields can increase the permeability of the cell membrane in a process referred to as electroporation. Reversible electroporation has become an important tool in biotechnology and medicine. The various applications of reversible electroporation require cells to survive the procedure, and therefore the occurrence of irreversible electroporation (IRE), following which cells die, is obviously undesirable. However, for the past few years, IRE has begun to emerge as an important minimally invasive nonthermal ablation technique in its own right as a method to treat tumors and arrhythmogenic regions in the heart. IRE had been studied primarily to define the upper limit of electrical parameters that induce reversible electroporation. Thus, the delineation of IRE from thermal damage due to Joule heating has not been thoroughly investigated. The goal of this study was to express the upper bound of IRE (onset of thermal damage) theoretically as a function of physical properties and electrical pulse parameters. Electrical pulses were applied to THP-1 human monocyte cells, and the percentage of irreversibly electroporated (dead) cells in the sample was quantified. We also determined the upper bound of IRE (onset of thermal damage) through a theoretical calculation that takes into account the physical properties of the sample and the electric pulse characteristics. Our experimental results were achieved below the theoretical curve for the onset of thermal damage. These results confirm that the region to induce IRE without thermal damage is substantial. We believe that our new theoretical analysis will allow researchers to optimize IRE parameters without inducing deleterious thermal effects.

Atherosclerosis is a leading cause of heart diseases and mortality around the world. Recently, cryoplasty has emerged as a potential alternative method to treat arterial atherosclerosis. Finite element heat transfer and mass transfer models are developed using ANSYS in this study. The model analyzes the heat transfer within the atherosclerotic plaque and arterial wall during the cryoplasty procedure. The model is useful in predicting the transient temperature through the diseased wall tissues. The results may be used to decide required treatment procedure to effectively freeze the plaque with minimal damage to the healthy arterial tissues. Finally, the model investigates the parameters that may effect temperature distribution within the tissues during the ablative procedure.

Numerical studies were performed to investigate bone cement polymerization, temperature history and thermal osteonecrosis in cemented hip replacements with finite element methods. In this paper, the effects of pre-cooling and pre-heating of the prosthesis and/or the cement prior to implantation were simulated. It was found that the cement polymerization initiated near the bone-cement interface and progressed toward the prosthesis when both the cement and prosthesis were initially at room temperature. When the prosthesis and/or cement were pre-cooled, a reduction of the peak temperature at the bone-cement interface resulted, and this may reduce thermal osteonecrosis. However, this also slowed the polymerization process, and may result in a weaker bone cement. If the prosthesis was significantly initially heated, bone cement polymerization reversed reaction direction, started from the cement-prosthesis interface and proceeded toward the bone. Such polymerization direction may reduce or eliminate the formation of voids at the cement-prosthesis interface. Numerical results also showed that pre-heating seemed unlikely to produce significant thermal damage to the bone. The method of pre-heating the prosthesis prior to implantation may decrease the likelihood of cement-prosthesis loosening and increase the life of total hip arthroplasty.

A one-dimensional multi-layer model is presented to characterise the skin burn process resulting from the application of a high temperature heat source to a skin surface. Transient temperatures were numerically calculated using a finite difference method to solve the Pennes bioheat equation. A damage function denoting the extent of burn injury was then calculated using the Arrhenius assumptions. The model was used to predict the effects of thermal physical properties and geometrical dimensions on the transient temperature and damage function distributions. The results show that the epidermis and dermis thicknesses significantly affect the temperature and burn injury distributions, while variations of the initial temperatures and the blood perfusion have little effect.

Part 2 of this paper presents an analysis of variance (ANOVA) for investigating the precedence of the various parameters, and the effects of varying these parameters, in assessment of burn injury resulting from the exposure of skin surface to heat sources. A one-dimensional model based on the finite difference method (FDM), as implemented in a spreadsheet software application, is applied to the assessment of burn injury. Henriques' theory of skin burns is used for determining the spatial and temporal extent of tissue damage. The ranks of the effects of various factors were obtained. It was found that the highest ranked factor is the initial tissue temperature followed by the thermal conductivity of the epidermal layer. The effect of blood perfusion rate is ranked much below the combinations of other factors. The results from the present numerical experiment agree well with the results obtained by Palla. Sensitivity analysis of the critical exposure levels was also carried out and results are discussed. In this study, the effects of the various parameters on injury threshold were investigated. Again, the results indicate that the four parameters: thermal conductivity of the epidermis and dermis, convective heat transfer coefficient and initial tissue temperature, have a pronounced influence on assessing the burn injury threshold. It was also found that fat thermal conductivity and blood perfusion rate have no obvious effect on injury threshold. A two-dimensional analysis was further conducted to determine the sensitivity of the predicted injury to the values of frequency factor, P, and apparent activation energy, deltaE, used in the models. Part 1 of this study details the development of the computer models based on the one- and two-dimensional bioheat equations.

Skin burn injury and heat tolerance in man is a complex interaction of physical heat exchange processes and the potential for physiological adjustments. In recently developed one-dimensional finite difference and two-dimensional finite element bioheat transfer based numerical models of the skin, the prediction of the thermal efficacy of cooling treatment was evaluated. With the use of a standard Arrhenius model for damage rate, the extent of burn injury was computed from the transient temperature solution. Simulated isotherms results for current models were found to be consistent in both one- (experimental) and two-dimensional (analytical) data. The two-dimensional code provided some additional precision to previously published models. This was due to the mesh-independent grid which enabled more accurate numerical prediction of thermal and injury patterns as they developed during the injury process. Numerical data obtained in the current study suggest that non-thermal factors must be considered in the calculation of the efficacy of postburn cooling therapy. However, when dealing with living tissue, any numerical model can provide only an approximation to conditions in real exposures. Together with analysis of variance, the models were used for investigating the precedence of the various parameters and the effects of varying these parameters on assessment of burn injury resulting from exposure of skin surface to heat sources (Part 2).

The finite element method was used to analyze heat transfer within a section of the forearm while exposed to different ambient conditions and with different metabolic states. The three-dimensional model accounts for the different material properties of bone, muscle and blood and incorporates a single artery-vein pair for counter-current heat exchange. The geometry of the model was developed from anatomical cross-sectional images of the forearm. The model was used to determine the effects or rest vs. exercise, free vs. forced surface convection and 0 degrees C vs. -20 degrees C external temperatures. The results of the model were compared to experimental data and the model exhibits qualitatively correct behaviour. This model can be used to study hyperthermia, burns and cryogenic freezing of tissue.

This paper presents a robust finite element model (FEM) with multiple-layers of varying properties for investigation of burn effects on human skin during a burning process resulting from exposure of skin surface to a contact heat source and a hot moving fluid. Henriques' theory of skin burns is used in conjunction with two-dimensional Pennes bioheat transfer equation for determining the spatial and temporal extent of burn injury. The model developed is a two-dimensional axisymmetric model in cylindrical coordinates. The various tissue layers account for changing thermal properties with respect to skin anatomy. A finite element scheme that uses the backward Euler method is used to solve the problem. The injury processes of skin subsequent to the removal of the heat source (post-burn) will also be inspected. The mesh employed in this model consists of a high density of nodes and elements in which a thorough mesh convergence study was done. A comparison of the transient temperature field computed by this model against Diller's results using the FE technique with a comparatively coarse mesh of 125 elements and experimental data by Orgill et al. has been done in the present study. It concluded that improved accurate solutions have been performed using the robust model developed due to the achievement of a mesh-independent solution.

Intraluminal resistance to gas transport between the microcirculation and tissue was neglected for a half-century following the early work of Krogh. In recent years it has come to be understood that this neglect is seriously in error. This paper reviews the background for the long period of misdirection, and progress in placing the simulation of gas transport processes on a more accurate, quantitative basis.

Successful hyperthermia treatment of tumors requires understanding the attendant thermal processes in both diseased and healthy tissue. Accordingly, it is essential for developers and users of hyperthermia equipment to predict, measure and interpret correctly the tissue thermal and vascular response to heating. Modeling of heat transfer in living tissues is a means towards this end. Due to the complex morphology of living tissues, such modeling is a difficult task and some simplifying assumptions are needed. Some investigators have recently argued that Pennes' interpretation of the vascular contribution to heat transfer in perfused tissues fails to account for the actual thermal equilibration process between the flowing blood and the surrounding tissue and proposed new models, presumably based on a more realistic anatomy of the perfused tissue. The present review compares and contrasts several of the new bio-heat transfer models, emphasizing the problematics of their experimental validation, in the absence of measuring equipment capable of reliable evaluation of tissue properties and their variations that occur in the spatial scale of blood vessels with diameters less than about .2 mm. For the most part, the new models still lack sound experimental grounding, and in view of their inherent complexity, the best practical approach for modeling bio-heat transfer during hyperthermia may still be the Pennes model, providing its use is based on some insights gained from the studies described here. In such cases, these models should yield a more realistic description of tissue locations and/or thermal conditions for which the Pennes' model might not apply.

Analytic solutions to the time-dependent multiregion bioheat equation are evaluated numerically for cartesian and spherical models. Principle and alternate branch contributions to the solutions are examined. The calculations include a parametric investigation and analyses of temperature behaviour in idealised upper thigh and tumour models.

The role of optical properties in the distribution of laser light and the resulting thermodynamic processes in biological tissue is studied from a theoretical perspective. Light distribution is modeled by a discrete ordinate method and heat transfer and ablation is modeled by an immobilized finite element method. The effect of parametric variation of absorption, scattering anisotropicity on the dynamics of the ablation process is examined. The manifestation of higher than the ablation threshold temperature in the subsurface tissue is observed and discussed. Results indicate significant differences in the ablation behavior which may have important clinical implications.