Generalized solution and estimation method for cooling performance of downscaled cryoprobe.

In cryosurgery, downscaling of cryoprobes is important to minimize surgical invasion. In this study, a set of analytical solutions to the freezing phenomenon around a cryoprobe in a dimensionless form is derived and the general trend is discussed to clarify the relationship between the freezing ability of a biological tissue and the cooling power of a cryoprobe. A one-dimensional axisymmetric model in the steady-state condition is considered. The relationship between the size of the frozen region, fluid temperature in the cryoprobe, and heat transfer coefficient on the wall of the cryoprobe in the dimensional form is derived under the condition mentioned above. The fluid temperature and heat transfer coefficient are eliminated from the solutions by introducing the steady-state cryoprobe surface temperature. This transformation indicates that the steady-state surface temperature directly affects the size of the frozen region and combination of fluid temperature and heat transfer coefficient occurs, which has the same cooling effect. The derived solutions are transformed into a dimensionless form using the characteristic length of bioheat transfer and normalizing the temperature distribution in an unfrozen tissue. The applicability of these analytical solutions is evaluated by comparing them with numerical simulation results from existing studies. The dimensionless solutions describe the general trend of the relationship between the frozen region and the cooling power of a cryoprobe, which is independent of the type of organ, fluid temperature, and heat transfer coefficient. Finally, the concept of freezing limit is established using the derived solutions. The freezing limit describes the minimum requirements to freeze a tissue, and it can be used as guideline to design future downscaled cryoprobes with a suitable cooling mechanism.

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.

Investigation of bimodal characteristics of the droplet size distribution in condensation spray.

To understand the generation process of airborne droplets during exhalation, this study investigates the mechanism of bimodal characteristics of the size distribution of droplets generated in a condensed spray flow. The phase change process in the condensed spray flow was estimated based on the droplet size distribution measured by a phase Doppler particle analyzer and the temperature distribution measured by a thermistor. On the central axis, the size distribution was unimodal in the spray interior. In contrast, bimodality of the size distribution at the outer edge of the spray flow was observed. At the edge of the spray flow, a large temperature gradient was formed. This indicates that condensation actively occurred at the outer edge. For the same reason as outlined above, condensation did not progress at the spray center because of the consumption of water vapor at the outer edge by the condensation, and the droplet diameter did not change significantly. Hence, owing to the difference in the local phase change process between the center and outer edge of the spray, large and small droplets can exist simultaneously in the middle region. As a result, the size distribution of the condensation spray is bimodal.

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.

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.

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.

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.

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.