A novel technique to diagnose non-melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors.

The skin surface temperature reflects the physiological state of the human body. Quantitative methods of identification of skin cancers based on accurate measurement of effective thermal conductivity (ETC) are among the promising diagnostic tools for differentiating non-invasive and invasive melanomas before surgical treatment. To validate these findings, in this report, the diagnostic methods for invasive and non-invasive extramammary Paget's disease (EMPD) and squamous cell carcinoma (SCC) were further tested by measuring the absolute value of skin surface temperature and the ETC of the skin. In addition, to investigate the stromal factors that might affect ETC, immunohistochemical staining for LL37, periostin (POSTN), MMP12, and MMP28 was performed. The invasive SCC and EMPD group showed a relatively higher skin surface temperature compared to the in situ SCC group. The non-invasive EMPD and SCC group showed significantly lower values of ETC at lesions, whereas the invasive EMPD group showed significantly higher ETC values at lesions compared to healthy skin. Immunohistochemical staining showed that the percentage of LL37-producing cells was significantly increased in invasive EMPD and SCC compared to that in non-invasive EMPD and SCC. Moreover, Spearman's rank correlation test showed a significant inverse correlation between the percentage of MMP12-positive cells and increased levels of ETC-expressing areas in EMPD and SCC (r = -.5997). The present study suggested that differences in ETC could be a novel high-accuracy diagnostic technique for non-melanoma skin cancer, especially for detecting dermal invasion of SCC and EMPD.

High-speed phase-shifting interferometry using triangular prism for time-resolved temperature measurement.

This study proposes a high-speed phase-shifting interferometer with an original optical prism. This phase-shifting interferometer consists of a polarizing Mach-Zehnder interferometer, an original optical prism, a high-speed camera, and an image-processing unit for a three-step phase-shifting technique. The key aspect of the application of the phase-shifting technique to high-speed experiments is an original prism, which is designed and developed specifically for a high-speed phase-shifting technique. The arbaa prism splits an incident beam into four output beams with different information. The interferometer was applied for quantitative visualization of transient heat transfer. In order to test the optical system for measuring high-speed phenomena, the temperature during heat conduction was measured around a heated thin tungsten wire (diameter of 5 µm) in water. The visualization area is approximately 90 µm×210 µm, and the spatial resolution is 3.5 µm at 300,000 fps of the maximum temporal resolution with a high-speed camera. The temperature fields around the heated wire were determined by converting phase-shifted data using the inverse Abel transform. Finally, the measured temperature distribution was compared with numerical calculations to validate the proposed system; a good agreement was obtained.

24-gauge ultrafine cryoprobe with diameter of 550 µm and its cooling performance.

This paper describes the development of a novel cryoprobe with the same size as a 24-gauge injection needle and the evaluation of its cooling performance. This ultrafine cryoprobe was designed to reduce the invasiveness and extend application areas of cryosurgery. The ultrafine cryoprobe has a double-tube structure and consists of two stainless steel microtubes. The outer diameter of the cryoprobe is 550 µm, and the inner tube has a 70-µm inner diameter to depressurize the high-pressure refrigerant. By solving the bioheat transfer equation and considering freezing phenomena, the relationship between the size of the frozen region and the heat transfer coefficient of the refrigerant flow in an ultrafine cryoprobe was derived analytically. The results showed that the size of the frozen region is strongly affected by the heat transfer coefficient. A high heat transfer coefficient such as that of phase change heat transfer is required to generate a frozen region of sufficient size. In the experiment, trifluoromethane (HFC-23) was used as the refrigerant, and the cooling effects of the gas and liquid phase states at the inlet were evaluated. When the ultrafine cryoprobe was cooled using a liquid refrigerant, the surface temperature was approximately -50°C, and the temperature distribution on the surface was uniform for a thermally insulated condition. However, for the case with vaporized refrigerant, the temperature distribution was not uniform. Therefore, it was concluded that the cooling mechanism using liquid refrigerant was suitable for ultrafine cryoprobes. Furthermore, to simulate cryosurgery, a cooling experiment using hydrogel was conducted. The results showed that the surface temperature of the ultrafine cryoprobe reached -35°C and formed a frozen region with a radius of 4 mm in 4 min. These results indicate that the ultrafine cryoprobe can be applied in actual cryosurgeries for small affected areas.

Measurement of Soret and Fickian diffusion coefficients by orthogonal phase-shifting interferometry and its application to protein aqueous solutions.

We have developed a method to measure thermodiffusion and Fickian diffusion in transparent binary solutions. The measuring instrument consists of two orthogonally aligned phase-shifting interferometers coupled with a single rotating polarizer. This high-resolution interferometer, initially developed to measure isothermal diffusion coefficients in liquid systems [J. F. Torres, A. Komiya, E. Shoji, J. Okajima, and S. Maruyama, Opt. Lasers Eng. 50, 1287 (2012)], was modified to measure transient concentration profiles in binary solutions subject to a linear temperature gradient. A convectionless thermodiffusion field was created in a binary solution sample that is placed inside a Soret cell. This cell consists of a parallelepiped cavity with a horizontal cross-section area of 10 × 20 mm(2), a variable height of 1-2 mm, and transparent lateral walls. The small height of the cell reduces the volume of the sample, shortens the measurement time, and increases the hydrodynamic stability of the system. An additional free diffusion experiment with the same optical apparatus provides the so-called contrast factors that relate the unwrapped phase and concentration gradients, i.e., the measurement technique is independent and robust. The Soret coefficient is determined from the concentration and temperature differences between the upper and lower boundaries measured by the interferometer and thermocouples, respectively. The Fickian diffusion coefficient is obtained by fitting a numerical solution to the experimental concentration profile. The method is validated through the measurement of thermodiffusion in the well-known liquid pairs of ethanol-water (ethanol 39.12 wt.%) and isobutylbenzene-dodecane (50.0 wt.%). The obtained coefficients agree with the literature values within 5.0%. Finally, the developed technique is applied to visualize biomolecular thermophoresis. Two protein aqueous solutions at 3 mg∕ml were used as samples: aprotinin (6.5 kDa)-water and lysozyme (14.3 kDa)-water. It was found that the former protein molecules are thermophilic and the latter thermophobic. In contrast to previously reported methods, this technique is suitable for both short time and negative Soret coefficient measurements.

Development and clinical application of a precise temperature-control device as an alternate for conventional moxibustion therapy.

Moxibustion therapy has been used in East Asian medicine for more than a thousand years. However, there are some problems associated with this therapy in clinical practice. These problems include lack of control over the treatment temperature, emission of smoke, and uneven temperature distribution over the treatment region. In order to resolve these problems, we developed a precise temperature-control device for use as an alternate for conventional moxibustion therapy. In this paper, we describe the treatment of a single patient with paralytic ileus that was treated with moxibustion. We also describe an evaluation of temperature distribution on the skin surface after moxibustion therapy, the development of a heat-transfer control device (HTCD), an evaluation of the HTCD, and the clinical effects of treatment using the HTCD. The HTCD we developed can heat the skin of the treatment region uniformly, and its effect may be equivalent to conventional moxibustion, without the emission of smoke and smell. This device can be used to treat ileus, abdominal pain, and coldness of abdomen in place of conventional moxibustion in modern hospitals.

Analysis of airborne sputum droplets flow dynamic behaviors under different ambient conditions and aerosol size effects.

The coronavirus (COVID-19) is becoming more threatening with the emergence of new mutations. New virus transmission and infection processes remain challenging and re-examinations of proper protection methods are urgently needed. From fluid dynamic viewpoint, the transmission of virus-carrying droplets and aerosols is one key to understanding the virus-transmission mechanisms. This study shows virus transmission by incorporating flow-evaporation model into the Navier-Stokes equation to describe the group of airborne sputum droplets exhaled under Rosin-Rammler distribution. Solid components and humidity field evolution are incorporated in describing droplet and ambient conditions. The numerical model is solved by an inhouse code using advection-diffusion equation for the temperature field and the humidity field, discretized by applying the total-variation diminishing Runge-Kutta method. The results of this study are presented in detail to show the different trends under various ambient conditions and to reveal the major viral-transmission routes as a function of droplet size.

Changes of blood flow volume in the superior mesenteric artery and brachial artery with abdominal thermal stimulation.

In traditional Chinese medicine, moxibustion is a local thermal therapy that is used for several conditions. Quantifying the effects of moxibustion therapy has been difficult because the treatment temperature depends on the physician's experience, and the temperature distribution in the target area is not uniform. This prospective observational study aims to quantify the effect of local thermal stimulation to the abdomen. We developed a heat transfer control device (HTCD) for local thermal stimulation. Twenty-four healthy subjects were enrolled and they underwent abdominal thermal stimulation to the para-umbilical region with the device for 20 min. Blood flow volume in the superior mesenteric artery (SMA) and brachial artery (BA), the heart rate and the blood pressure were measured at rest, 15 min after starting thermal stimulation and 10, 20, 30 and 40 min after completing thermal stimulation. Blood flow parameters were measured by high-resolution ultrasound. In the SMA, blood flow volume was significantly increased during thermal stimulation (P < .01), as well as at 10 min (P < .01) and 20 min (P < .05) after stimulation. In the BA, blood flow volume decreased at 40 min after stimulation (P < .01). In conclusion we could quantify the effect of local thermal stimulation with an HTCD and high-resolution ultrasound. Thermal stimulation of the para-umbilical region increased blood flow in the SMA 20 min after stimulation in healthy subjects.

Evaporation flow characteristics of airborne sputum droplets with solid fraction: Effects of humidity field evolutions.

The continuance of the COVID-19 pandemic largely depends on the spread of virus-carrying aerosols in ambient air. The mechanism of virus transmission and infection remains under intense investigation. In this study, an evaporation flow model of airborne sputum droplets is proposed which considers the evolution effects of the humidity field under different particle distributions and solid/salt fraction interactions. The incompressible Navier-Stokes equations characterize a stream of airflow jets, and the convection-diffusion-evaporation process is used to account for the inhomogeneous humidity field caused by the respiratory tract. Momentum equations for droplet dynamics which involve the effects of drag, gravity, and Brownian motion on sputum droplets are introduced to quantify the transport of droplets in a humidity field. The Lattice Boltzmann method is used to track the evolution of the aerosol in space and time under different ambient temperature and relative humidity conditions. The results of the simulation demonstrate that airborne humidity accelerates the evaporation rate of droplet, while supersaturated humid air forms a vapor mass in front of the respiratory tract. Despite the short lifespan of this phenomenon, it significantly hinders the evaporation of the droplets. Besides, the droplet vortex dynamics in a humidity field are sensitive to the droplet size.

Numerical Simulation of Effects of Bioheat Transfer Characteristics of Malignant Melanoma on Thermal Conductivity Measurements.

In our previous study, we successfully detected a difference in the effective thermal conductivity between an invasive melanoma lesion and healthy skin, through clinical experiments conducted on melanoma patients. We found that the effective thermal conductivity of the lesions correlated with the tumor thickness, suggesting that it may be correlated with the prognostic risk of melanoma. However, the bioheat transfer mechanisms of the correlation remained unknown. The aim of this study was to numerically investigate the effects of the bioheat transfer characteristics of malignant melanoma on thermal conductivity measurements and explore the cause of the difference in the effective thermal conductivity between lesions and healthy skin. We used two different bioheat transfer models, the Pennes model and local thermal nonequilibrium model, and investigated the cause of the aforementioned differences by varying the bioheat transfer parameters associated with the thermophysical properties and blood flow of a tumor. The calculation results indicated that the contribution of the blood flow can be dominant in a measurement comprising the use of a guard-heated thermistor probe. Therefore, we found that it is necessary to take into consideration the contribution of the convective term to the effective thermal conductivity of the lesion in order to explain the clinical data of a Stage IV invasive melanoma.

Development and estimation of a novel cryoprobe utilizing the Peltier effect for precise and safe cryosurgery.

We have developed a novel cryoprobe for skin cryosurgery utilizing the Peltier effect. The four most important parameters for necrotizing tissue efficiently are the cooling rate, end temperature, hold time and thawing rate. In cryosurgery for small skin diseases such as flecks or early carcinoma, it is also important to control the thickness of the frozen region precisely to prevent necrotizing healthy tissue. To satisfy these exacting conditions, we have developed a novel cryoprobe to which a Peltier module was attached. The cryoprobe makes it possible to control heat transfer to skin surface precisely using a proportional-integral-derivative (PID) controller, and because it uses the Peltier effect, the cryoprobe does not need to move during the operation. We also developed a numerical simulation method that allows us to predict the frozen region and the temperature profile during cryosurgery. We tested the performance of our Peltier cryoprobe by cooling agar, and the results show that the cryoprobe has sufficient cooling performance for cryosurgery, because it can apply a cooling rate of more than 250 degrees C/min until the temperature reaches -40 degrees C. We also used a numerical simulation to reconstruct the supercooling phenomenon and examine the immediate progress of the frozen region with ice nucleation. The calculated frozen region was compared with the experimentally measured frozen region observed by an interferometer, and the calculation results showed good agreement. The results of numerical simulation confirmed that the frozen region could be predicted accurately with a margin of error as small as 150 microm during use of the cryoprobe in cryosurgery. The numerical simulation also showed that the cryoprobe can control freezing to a depth as shallow as 300 microm.

First-in-human clinical study of novel technique to diagnose malignant melanoma via thermal conductivity measurements.

Melanoma is an aggressive skin cancer that originates from melanocytes and, especially in the case of early-stage melanoma, is distributed adjacent to the epidermis and superficial dermis. Although early-stage melanoma can be distinguished from benign nevus via a dermoscopy, it is difficult to distinguish invasive melanoma in its early stages from in situ melanoma. Because invasive melanoma must undergo a sentinel lymph node biopsy to be diagnosed, a non-invasive method to detect the micro-invasion of early-stage melanoma is needed for dermato-oncologists. This paper proposes a novel quantitative melanoma identification method based on accurate measurements of thermal conductivity using a pen-shaped device. This method requires skin temperature data for one minute to determine the effective thermal conductivity of the skin, allowing it to distinguish melanoma lesions from healthy skin. Results suggest that effective thermal conductivity was negative for in situ melanoma. However, in accordance with tumour progression, effective thermal conductivity was larger in invasive melanoma. The proposed thermal conductivity measurement is a novel tool that detects the micro-invasion of melanoma.

A MEMS-Based Quad-Wavelength Hybrid Plasmonic-Pyroelectric Infrared Detector.

Spectrally selective detection is of crucial importance for diverse modern spectroscopic applications such as multi-wavelength pyrometry, non-dispersive infrared gas sensing, biomedical analysis, flame detection, and thermal imaging. This paper reports a quad-wavelength hybrid plasmonic-pyroelectric detector that exhibited spectrally selective infrared detection at four wavelengths-3.3, 3.7, 4.1, and 4.5 µm. The narrowband detection was achieved by coupling the incident infrared light to the resonant modes of the four different plasmonic perfect absorbers based on Al-disk-array placed on a Al2O3-Al bilayer. These absorbers were directly integrated on top of a zinc oxide thin film functioning as a pyroelectric transducer. The device was fabricated using micro-electromechanical system (MEMS) technology to optimize the spectral responsivity. The proposed detector operated at room temperature and exhibited a responsivity of approximately 100-140 mV/W with a full width at half maximum of about 0.9-1.2 µm. The wavelength tunability, high spectral resolution, compactness and robust MEMS-based platform of the hybrid device demonstrated a great advantage over conventional photodetectors with bandpass filters, and exhibited impressive possibilities for miniature multi-wavelength spectroscopic devices.

Artificial chameleon skin that controls spectral radiation: Development of Chameleon Cool Coating (C3).

Chameleons have a diagnostic thermal protection that enables them to live under various conditions. Our developed special radiative control therefore is inspired by the chameleon thermal protection ability by imitating its two superposed layers as two pigment particles in one coating layer. One particle imitates a chameleon superficial surface for color control (visible light), and another particle imitates a deep surface to reflect solar irradiation, especially in the near-infrared region. Optical modeling allows us to optimally design the particle size and volume fraction. Experimental evaluation shows that the desired spectral reflectance, i.e., low in the VIS region and high in NIR region, can be achieved. Comparison between the measured and calculated reflectances shows that control of the particle size and dispersion/aggregation of particle cloud is important in improving the thermal-protection performance of the coating. Using our developed coating, the interior temperature decreases and the cooling load is reduced while keeping the dark tone of the object.

Computer simulation for postmortem cooling processes in the outer ear.

INTRODUCTION: A simulation using a computer model was undertaken to investigate postmortem cooling patterns in the outer ear. METHODS: Cooling patterns were analyzed using a 3-dimensional head model built from brain CT images of a volunteer. The simulation was verified with a case subject under constant environmental conditions to obtain an appropriate heat transmission coefficient. RESULTS: The cooling pattern of the head model agreed with that of the case subject when the heat transmission coefficient was 6W/m(2) degrees C, and it could be approximated to a single exponential curve. DISCUSSION: This is the first simulative study to show the postmortem cooling pattern of the head of an adult human. Our head model will prove useful to predict the cooling patterns of not only the outer ear but also of the entirety of the head.

Treatment of tumor in lymph nodes using near-infrared laser light-activated thermosensitive liposome-encapsulated doxorubicin and gold nanorods.

Tumor metastasis to lymph nodes is an important contributory factor for cancer-related deaths despite recent developments in cancer therapy. In this study, we demonstrate that tumor in the proper axillary lymph node (PALN) of the mouse can be treated by the application of external laser light to trigger the unloading of doxorubicin (DOX) encapsulated in thermosensitive liposomes (TSLs) administered together with gold nanorods (GNRs). GNRs + DOX-TSLs were injected into a mouse lymph node containing cancer cells (malignant fibrous histiocytoma-like cells) and intranodal DOX release was activated using near-infrared (NIR) laser irradiation. The temperature changes arising from the laser-irradiated GNRs triggered the release of DOX from the TSLs. A greater degree of inhibition of tumor growth was found in the co-therapy group compared to the other groups. The treatment effect was achieved by a combination of chemotherapy and NIR-activated hyperthermia. In vivo bioluminescence imaging and histological analysis confirmed tumor necrosis in response to combined treatment. This work presents a theranostic approach with excellent treatment results that has the potential to be developed into an alternative to surgery for the treatment of breast cancer metastasis.

A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy.

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.

Transition from multiplicity to singularity of steady natural convection in a tilted cubical enclosure.

The transition from the complex Rayleigh-Bénard convection to the simple heated-from-the-sides configuration in a cubical cavity filled with a Newtonian fluid is numerically studied. The cavity is tilted by an angle θ around its lower horizontal edge and is heated and cooled from two opposite tilted sides. We first analyze the effect of a marginal inclination angle on quasi-Rayleigh-Bénard convection (θ≈0∘), which is a realistic physical approximation to the ideal Rayleigh-Bénard convection. We then yield the critical angles where multiple solutions that were initially found for θ≈0∘ disappear, eventually resulting in the single steady roll solution found in the heated-from-the-sides configuration (θ=90∘). We confirm the existence of critical angles during the transition θ:0∘→90∘, and we demonstrate that such angles are a consequence of either singularities or collisions of bifurcation points in the Rayleigh-number-θ parameter space. We finally derive the most important critical angles corresponding to any Newtonian fluid of Prandtl number greater than that of air.

Artificial myocardium with an artificial baroreflex system using nano technology.

Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".

Thermal relaxation and critical instability of near-critical fluid microchannel flow.

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light.

Lymph node dissection for regional nodal metastasis is a primary option, but is invasive and associated with adverse effects. The development of non-invasive therapeutic methods in preclinical experiments using mice has been restricted by the small lymph node size and the limited techniques available for non-invasive monitoring of lymph node metastasis. Here, we show that photothermal therapy (PTT) using gold nanorods (GNRs) and near-infrared (NIR) laser light shows potential as a non-invasive treatment for tumors in the proper axillary lymph nodes (proper-ALNs) of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes (up to 13mm in diameter, similar in size to human lymph nodes). Tumor cells were inoculated into the proper-ALNs to develop a model of metastatic lesions, and any anti-tumor effects of therapy were assessed. We found that GNRs accumulated in the tumor in the proper-ALNs 24h after tail vein injection, and that irradiation with NIR laser light elevated tumor temperature. Furthermore, combining local or systemic delivery of GNRs with NIR irradiation suppressed tumor growth more than irradiation alone. We propose that PTT with GNRs and NIR laser light can serve as a new therapeutic method for lymph node metastasis, as an alternative to lymph node dissection.