An in vivo study was conducted using a mouse tumor model, to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers. Tumors were grown using melanoma tumor cells (B16/F10) subcutaneously on the right flanks of mice (C57Bl/6J). Physiologically relevant concentrations (0 and 0.125%) of gNPs were directly injected into the tumors. Sonications at acoustic powers of 10 and 30 W were performed for a duration of 16 s inside a magnetic-resonance system. Temperature increases and lesion volumes were calculated and compared for procedures with and without gNPs. Histopathology study was conducted using a cleaved caspase 3 antibody and hematoxylin and eosin staining after removing the tumors from the mice. For an acoustic power of 30 W, end-of-sonication temperature increases of 25.4 ± 3.8 °C (0% gNP) and 42.2 ± 4.6 °C (0.125% gNP) were measured. Using cleaved caspase 3 antibody, it was observed that more than 1% of nuclei are affected in the case of 0.125% and 30 W but only 0.01% of nuclei are affected in the 0% case. For 30 W and a gNP concentration of 0.125%, a lesion volume of 0.33 ± 0.22 mm3 was obtained, while no lesion was observed without gNP's.

Carbon is the fourth most abundant element in the universe and is a versatile element to form advanced lightweight materials. In contrast, metals provide a different suite of properties including low cost, high conductivities, and scalability, while ceramics provide abrasion resistance and fire retardancy. An obstacle in materials science has been the inability to manufacture a material that integrates carbon materials and metals or ceramics together into a reproducible material whose properties can be customized to meet specific design requirements. One application is to produce electrically and thermally conductive nanotube hybrid sheet for use as performance fabrics and textiles. Thus, an area that will benefit from interdisciplinary research is developing a process to synthesize carbon nanotube hybrid materials. This chapter describes initial research into developing a continuous manufacturing process to integrate metal and ceramic nanoparticles (NPs) with carbon nanotubes (CNTs) and produce continuous materials (sheet, tapes, and yarn) whose properties can be customized based on the constituent metals.

Long procedure times and collateral damage remain challenges in high-intensity focused ultrasound (HIFU) medical procedures. Magnetic nanoparticles (mNPs) and gold nanoparticles (gNPs) have the potential to reduce the acoustic intensity and/or exposure time required in these procedures. In this research, we investigated relative advantages of using gNPs and mNPs during HIFU thermal-ablation procedures. Tissue-mimicking phantoms containing embedded thermocouples (TCs) and physiologically acceptable concentrations (0.0625% and 0.125%) of gNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 s. It was observed that when the concentration of gNPs was doubled from 0.0625% to 0.125%, the temperature rise increased by 80% for a power of 5.2 W. For a fixed concentration (0.0625%), the energy absorption was 1.7 times greater for mNPs than gNPs for a power of 5.2 W. Also, for the power of 14.5 W, the sonication time required to generate a lesion volume of 50 mm3 decreased by 1.4 times using mNPs, compared with gNPs, at a concentration of 0.0625%. We conclude that mNPs are more likely than gNPs to produce a thermal enhancement in HIFU ablation procedures.

PURPOSE:The purpose of this study is to evaluate the impact of external head cooling on alleviating the heat stress in the human body by analyzing the temperatures of the core body (Tc), blood (Tblood) and head (Th) during exercise conditions using 3D whole body model.DESIGN/METHODOLOGY/APPROACH:Computational study is conducted to comprehend the influence of external head cooling on Tc, Tblood and Th. The Pennes bioheat and energy balance equations formulated for the whole-body model are solved concurrently to obtain Tc, Tblood and Th for external head cooling values from 33 to 233 W/m2 Increased external head cooling of 404 W/m2 is used to compare the numerical and experimental Th data.FINDINGS:Significant reductions of 0.21°C and 0.38°C are observed in Th with external head cooling of 233 and 404 W/m2, respectively. However, for external head cooling of 233 W/m2, lesser reductions of 0.03°C and 0.06°C are found in Tc and Tblood, respectively. Computational results for external head cooling of 404 W/m2 show a difference of 15 per cent in Th compared to experimental values from literature.ORIGINALITY/VALUE:The development of stress because of heat generated within human body is major concern for athletes exercising at high intensities. This study provides an insight into the effectiveness of external head cooling in regulating the head and body temperatures during exercise conditions.

Collateral damage and long sonication times occurring during high-intensity focused ultrasound (HIFU) ablation procedures limit clinical advancement. In this reserarch, we investigated whether the use of magnetic nano-particles (mNPs) can reduce the power required to ablate tissue or, for the same power, reduce the duration of the procedure. Tissue-mimicking phantoms containing embedded thermocouples and physiologically acceptable concentrations (0%, 0.0047%, and 0.047%) of mNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 seconds. Lesion volumes were determined for the phantoms with and without mNPs. It was found that with the 0.047% mNP concentration, the power required to obtain a lesion volume of 13 mm3 can be halved, and the time required to achieve a 21 mm3 lesion decreased by a factor of 5. We conclude that mNPs have the potential to reduce damage to healthy tissue, and reduce the procedure time, during tumor ablation using HIFU.

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.

In this combined experimental and theoretical research, magnetic nano-particle (mNP) mediated energy transfer due to high intensity-focused ultrasound (HIFU) sonication has been evaluated. HIFU sonications have been performed on phantoms containing three different volume percentages (0%, 0.0047%, and 0.047%) of mNPs embedded in a tissue mimicking material (TMM). A theoretical model has been developed to calculate the temperature rise in the phantoms during HIFU sonication. It is observed from theoretical calculation that the phonon layer at the interface of the mNPs and TMM dominates the attenuation for higher (0.047%) concentration. However, for a lower concentration (0.0047%) of mNPs, intrinsic absorption is the dominating mechanism. Attenuation due to the viscous drag becomes the dominating mechanism for larger size mNPs (>1000 nm). At a higher concentration (0.047%), it is observed from theoretical calculations that the temperature rise is 25% less for gold nano-particles (gNPs) when compared to mNPs. However, at lower concentrations (0.0047% and 0.002%), the difference in temperature rise for the mNPs and gNPs is less than 2%.

High-intensity focused ultrasound (HIFU) is a medical procedure to locally heat and ablate malignant tumors. Characterization of the HIFU beam location during the ablation procedures is critical for both accurate prediction of induced hyperthermia and development of regulatory standards for clinical devices. An accurate beam location and the orientation of the transducer with respect to the tumors are essential for precise ablation. A small change in the radial location or tilt in the application of the HIFU can lead to ablation of healthy tissue and result in grave injury. In in vitro systems, difficulties arise in perfectly aligning the phantom with the transducer and small tilt angles cannot be completely avoided. Traditional methods of finding the focus location by ablating on the thermocouples (TCs) involve artifacts and can result in positioning errors.In vitro experiments on tissue mimicking material (TMM) with embedded TCs can be used as a preclinical method to characterize the HIFU beam and the corresponding thermal field. The preclinical testing is necessary to determine the amount of lesion and avoid any collateral damage to healthy tissues during HIFU in clinical settings. However, several sources of error arise when focusing the beam on the TC junction and measuring the focal temperature. Viscous-heating artifact is one such source of error associated with direct sonication of the TC junctions [1]. Positioning error is another source of inaccuracy in measuring the focal temperature by locating the beam atop TC junction [2]. Thus, a localization method was developed [3] to find the radial location of HIFU beam as well as focal temperature with minimized error (artifact) using remote TC measurements. However, determination of the tilt (θ) between the transducer and phantom has not been accounted for in our prior studies [3].In this research, a method to determine the focal position of HIFU beam in cylindrical coordinates (r, θ, z) is determined. Such determination has not been done before. Sonications were performed on a phantom containing TMM at five predetermined (prescribed) distances along a line perpendicular to the axis of the phantom. Focus location (r, θ, z) is calculated using an inverse algorithm [3] using these five sonications which were conducted away from the TCs.A cylindrical fixture with an inner diameter of 8 cm was developed. The fixture was embedded with an array of eight thin-wire (Chromega-Constantine) TCs, labeled T1–T8, with a diameter of 0.003 in., arranged in four separate layers (Fig. 1). A gelrite-based TMM was prepared according to the protocol of King et al. [4] and poured into the fixture. The sonication was performed using an H101 transducer (Sonic Concepts, Bothell, WA) with an operating frequency of 3.3 MHz having a diameter and focal length of 6.4 cm and 6.26 cm, respectively. A positioning system capable of adjusting any of the coordinates in discrete 0.025 mm increments was used to move the transducer. The transducer was activated in continuous-wave mode for a period of 30 s. The temperature on the full array was recorded using an OMB-DAQ-56 (Omega Engineering, Inc., Stamford, CT) data-acquisition system (Fig. 2) for the 30 s heating period, as well as 20 s of cooling period for a 20 W acoustic power.Direct determination of the exact position of the beam in relation to the cylindrical coordinates (r, θ, z) is cumbersome. In order to get the angular orientation (tilt) of the transducer with respect to the phantom, sonications were performed at five different locations along a line in x direction as shown in Fig. 3. Precise positioning of the beam location on a TC is challenging due to the presence of artifacts and a smaller beam size. Hence, measurements of beam location were made relative to an initial sonication location rather than at a TC location. Initial sonication was performed between T3 and T4 (L0). All the beam positions for subsequent sonications were measured relative to this initial location along the x-axis. Four additional sonications were executed (Fig. 3), at locations −0.25 mm (L1), +0.5 mm (L2), −0.75 mm (L3), and +1.0 mm (L4) along the x-axis of the positioning system.An inverse algorithm developed by Hariharan et al. [3] was employed to determine the radial position (r) of the beam focus within the TC array. In this method, temperature rise in the phantom is calculated numerically based on an initial assumption for the beam location. The optimization error metric between the experimentally measured temperature (Texp) and the computed temperature (Tnum) corresponding to the assumed beam location was calculated. The optimization algorithm refined the beam location by minimizing the error using the Nelder–Mead scheme. Using this inverse algorithm, a beam radial location (r) (derived location—L0′, L1′, L2′, L3′, and L4′) was calculated and compared with the expected focal locations measured by the positioning system (prescribed locations—L0, L1, L2, L3, and L4) for all the five locations to determine the tilt.Figure 4 shows the beam locations in relation to the radial distance obtained for the five locations along the x-axis. The derived locations were plotted against the prescribed locations to determine the tilt. Here, the prescribed (L0) and derived (L0′) are assumed to be at the same location to determine the relative position of other locations. For the acoustic power of 20 W, the average variation of the radial location (r) from the prescribed distances was less than 0.1 mm.The slope of the line fit obtained for the derived locations in Fig. 4 was used to calculate the angle between the line joining the prescribed locations and the line joining the derived locations. L0 is taken as the center or origin to calculate the angle between the two lines (prescribed and derived). As it can be observed from Fig. 3, the angle between the line along which the sonications were conducted (prescribed location) and the regression line joining the derived locations (tilted in z-direction) is the same as the angle between the phantom and the transducer. The calculated tilt was found to be ∼5 deg. Focus location along the axial direction (z) is calculated using the inverse algorithm which is free of TC-related artifacts. The location of the focus (z) in relation to T1–T2 layer was found to be 1 mm away toward the T3–T4 layer.The exact location of the focus and the orientation of the transducer with respect to the tumor or tissue that is being ablated are very critical as errors in location can result in damage to the healthy tissue. Accuracy of targeting location is also important in preclinical testing for successful development of the HIFU method for tumor ablation. Even small tilt angles between the transducer and phantom can result in shift in the area of ablation.This study shows a method to characterize the location of the focus with respect to the transducer. An inverse algorithm was used to find the beam location within the tissue phantom while the derived location was not affected by TC artifact. In addition, the method described here to determine the tilt helps in better locating the focus and, in turn, helps in ablating the tumors with improved accuracy. Small tilt angles (∼5 deg), which cannot be identified by bare eyes, can be determined; consequently, the measured tilt can be incorporated into calculating the actual area of ablation.This project was funded by NSF No. 1403356.

A rotating bioreactor for the cell/tissue culture should be operated to obtain sufficient nutrient transfer and avoid damage to the culture materials. Thus, the objective of the present study is to determine the appropriate suspension conditions for the bead/cell distribution and evaluate oxygen transport in the rotating wall vessel (RWV) bioreactor. A numerical analysis of the RWV bioreactor is conducted by incorporating the Eulerian–Eulerian multiphase and oxygen transport equations. The bead size and rotating speed are the control variables in the calculations. The present results show that the rotating speed for appropriate suspensions needs to be increased as the size of the bead/cell increases: 10 rpm for 200 µm; 12 rpm for 300 µm; 14 rpm for 400 µm; 18 rpm for 600 µm. As the rotating speed and the bead size increase from 10 rpm/200 µm to 18 rpm/600 µm, the mean oxygen concentration in the 80% midzone of the vessel is increased by ∼85% after 1‐h rotation due to the high convective flow for 18 rpm/600 µm case as compared to 10 rpm/200 µm case. The present results may serve as criteria to set the operating parameters for a RWV bioreactor, such as the size of beads and the rotating speed, according to the growth of cell aggregates. In addition, it might provide a design parameter for an advanced suspension bioreactor for 3‐D engineered cell and tissue cultures. Biotechnol. Bioeng. 2008;99: 99–107. © 2007 Wiley Periodicals, Inc.