New quasiperiodic structures in nematic liquid crystals.

Liquid crystal molecules tend to align with each other, often forming regions of opposite alignment that meet at a boundary-topological defects. These often offer information on configuration of the liquid crystal molecules with competing constraints on their order. Here, we experimentally demonstrate a mechanism to generate topological defects in the form of spatially oscillatory domain walls in nematic liquid crystals. We initially orient the molecules perpendicular to the substrate (i.e. homeotropic alignment) and when a horizontal electric field is applied, domain walls that change their shape with time emerge. These walls form at low frequencies of the applied electric field and remain stable as the frequency increases. If the initial biasing field is at larger frequencies (kHz regime), the domain walls still form, but are not oscillatory. We develop a general theory to predict the three-dimensional liquid crystal director evolution in any two-dimensional varying field. This theory gives the time dependence for the domain walls and confirms that both the oscillatory and straight walls are stable.

Magnetic particle based MRI thermometry at 0.2 T and 3 T.

This study provides insight into the advantages and disadvantages of using ferrite particles embedded in agar gel phantoms as MRI temperature indicators for low-magnetic field scanners. We compare the temperature-dependent intensity of MR images at low-field (0.2 T) to those at high-field (3.0 T). Due to a shorter T1 relaxation time at low-fields, MRI scanners operating at 0.2 T can use shorter repetition times and achieve a significant T2⁎ weighting, resulting in strong temperature-dependent changes of MR image brightness in short acquisition times. Although the signal-to-noise ratio for MR images at 0.2 T MR is much lower than at 3.0 T, it is sufficient to achieve a temperature measurement uncertainty of about ±1.0 °C at 37 °C for a 90 µg/mL concentration of magnetic particles.

On the optimization of imaging parameters for magnetic resonance imaging thermometry using magnetic microparticles.

Magnetic Resonance Imaging thermometry is an extremely useful technique which allows one to determine, noninvasively, the temperature deep in the tissue in two or three dimensions. Many methods of MR thermometry have been developed, including those that rely on the intrinsic MR properties of tissue and those which depend on the addition of contrast agents injected into the tissue to create temperature dependent MR images. One such method is to introduce magnetic particles whose magnetization's temperature dependence influences the MR properties of the surrounding tissue and obtain temperature from calibrated intensity changes of T2* weighted MR images. One limitation of this method is the temperature resolution which is determined by the rate of change of the magnetization with temperature. One can change the MR response either through varying the particles properties or finding the MR scan parameters which maximize the image contrast due to T2* weighting of images. In this work we calculate the MR signal strength, using known values of T1 and T2* relaxation times for agarose gel phantoms with embedded magnetic particles, and compared this with the temperature dependent intensity of experimental MR images. We seek to optimize the change in signal intensity with temperature by varying the selectable MR scanner parameters: echo time, repetition time, and flip angle. Based on comparison with experimental data we find that the change in signal with temperature can be significantly increased (by as much as 100%) through the appropriate choice of MR scan parameters.

Measurement of sub-zero temperatures in MRI using T1 temperature sensitive soft silicone materials: Applications for MRI-guided cryosurgery.

PURPOSE: One standard method, proton resonance frequency shift, for measuring temperature using magnetic resonance imaging (MRI), in MRI-guided surgeries, fails completely below the freezing point of water. Because of this, we have developed a new methodology for monitoring temperature with MRI below freezing. The purpose of this paper is to show that a strong temperature dependence of the nuclear relaxation time T1 in soft silicone polymers can lead to temperature-dependent changes of MRI intensity acquired with T1 weighting. We propose the use of silicone filaments inserted in tissue for measuring temperature during MRI-guided cryoablations. METHODS: The temperature dependence of T1 in bio-compatible soft silicone polymers was measured using nuclear magnetic resonance spectroscopy and MRI. Phantoms, made of bulk silicone materials and put in an MRI-compatible thermal container with dry ice, allowed temperature measurements ranging from -60°C to + 20°C. T1 -weighted gradient echo images of the phantoms were acquired at spatially uniform temperatures and with a gradient in temperature to determine the efficacy of using these materials as temperature indicators in MRI. Ex vivo experiments on silicone rods, 4 mm in diameter, inserted in animal tissue were conducted to assess the practical feasibility of the method. RESULTS: Measurements of nuclear relaxation times of protons in soft silicone polymers show a monotonic, nearly linear, change with temperature (R2  > 0.98) and have a significant correlation with temperature (Pearson's r > 0.99, p < 0.01). Similarly, the intensity of the MR images in these materials, taken with a gradient echo sequence, are also temperature dependent. There is again a monotonic change in MRI intensity that correlates well with the measured temperature (Pearson's r < -0.98 and p < 0.01). The MRI experiments show that a temperature change of 3°C can be resolved in a distance of about 2.5 mm. Based on MRI images and external sensor calibrations for a sample with a gradient in temperature, temperature maps with 3°C isotherms are created for a bulk phantom. Experiments demonstrate that these changes in MRI intensity with temperature can also be seen in 4 mm silicone rods embedded in ex vivo animal tissue. CONCLUSIONS: We have developed a new method for measuring temperature in MRI that potentially could be used during MRI-guided cryoablation operations, reducing both procedure time and cost, and making these surgeries safer.

Optical Imaging of Magnetic Particle Cluster Oscillation and Rotation in Glycerol.

Magnetic particles have been evaluated for their biomedical applications as a drug delivery system to treat asthma and other lung diseases. In this study, ferromagnetic barium hexaferrite (BaFe12O19) and iron oxide (Fe3O4) particles were suspended in water or glycerol, as glycerol can be 1000 times more viscous than water. The particle concentration was 2.50 mg/mL for BaFe12O19 particle clusters and 1.00 mg/mL for Fe3O4 particle clusters. The magnetic particle cluster cross-sectional area ranged from 15 to 1000 µµm2, and the particle cluster diameter ranged from 5 to 45 µµm. The magnetic particle clusters were exposed to oscillating or rotating magnetic fields and imaged with an optical microscope. The oscillation frequency of the applied magnetic fields, which was created by homemade wire spools inserted into an optical microscope, ranged from 10 to 180 Hz. The magnetic field magnitudes varied from 0.25 to 9 mT. The minimum magnetic field required for particle cluster rotation or oscillation in glycerol was experimentally measured at different frequencies. The results are in qualitative agreement with a simplified model for single-domain magnetic particles, with an average deviation from the model of 1.7 ± 1.3. The observed difference may be accounted for by the fact that our simplified model does not include effects on particle cluster motion caused by randomly oriented domains in multi-domain magnetic particle clusters, irregular particle cluster size, or magnetic anisotropy, among other effects.

Fast Switching Dual-Frequency Nematic Liquid Crystal Tunable Filters.

We develop tunable optical filters with dual-frequency nematic liquid crystal optical retarders to enable fast switching between the passed wavelengths. The filters are composed of a series of two liquid crystal optical retarders. We select the specific thicknesses of the liquid crystal retarders and use individual biasing schemes to continuously tune the wavelength and bandwidth of the filter. This enables fine-tuned filter switching speeds of filter operation in the ms regime. We present theoretical predictions and experimental results for the electro-optical filter characterization as well as an example application for our filter in total internal reflection fluorescence microscopy. We find that our filter switching speeds can be as short as a few ms, an order of magnitude improvement over typical mechanical filter wheel switching speeds. The quality of our fluorescence images is similar to those obtained by conventional filters.

Exploration of Fermi-Pasta-Ulam Behavior in a Magnetic System.

We study nonlinear spin motion in one-dimensional magnetic chains. We find significant differences from the classic Fermi-Pasta-Ulam (FPU) problem examining nonlinear elastic motion in a chain. We find that FPU behavior, the transfer of energy among low order eigenmodes, does not occur in magnetic systems with only exchange and external fields, but does exist if a uniaxial anisotropy is also present. The FPU behavior may be altered or turned off through the magnitude and orientation of an external magnetic field. A realistic micromagnetic model shows such behavior could be measurable.

Spin Wave Power Flow and Caustics in Ultrathin Ferromagnets with the Dzyaloshinskii-Moriya Interaction.

The Dzyaloshinskii-Moriya interaction in ultrathin ferromagnets can result in nonreciprocal propagation of spin waves. We examine theoretically how spin wave power flow is influenced by this interaction. We show that the combination of the dipole-dipole and Dzyaloshinskii-Moriya interactions can result in unidirectional caustic beams in the Damon-Eshbach geometry. Morever, self-generated interface patterns can also be induced from a point-source excitation.

Errors in measurements of 222Rn in methane and carbon dioxide using scintillation cells calibrated for 222Rn in air.

Scintillation cells are used typically for measuring the concentration of (222)Rn in air and are calibrated for that purpose. However, scintillation cells are sometimes used for measuring (222)Rn in natural gas or carbon dioxide. The counting efficiencies of scintillation cells for measurements of (222)Rn in these gases should be different from those for measuring (222)Rn in air because the ranges of alpha particles emitted by (222)Rn and its progeny are greater in methane and smaller in carbon dioxide than in air. If these effects are not taken into consideration, measurements of (222)Rn in natural gas will be biased high and in carbon dioxide will be biased low. The authors previously investigated the effects of barometric pressure on measurements of (222)Rn in air using scintillation cells. A modeling technique was used in a previous study to calculate theoretical errors that would result if atmospheric pressure were not considered. In the current study, the same modeling technique was used to calculate theoretical errors that would be made for measurements of (222)Rn in methane and carbon dioxide if the calibration for (222)Rn in air were used. Results are presented for four types of scintillation cells of varying geometries and for barometric pressures representative of four elevations ranging from sea level to 1,963 m (6,440 feet). These results indicate that the errors introduced by the ranges of the alpha particles in gases different from air can be significant. Depending on the type of cell and the local pressure, a measurement of (222)Rn in methane may be biased high by 2-7%, while a measurement of (222)Rn in CO2 may be biased low by 15-20% if the calibration for (222)Rn in air is used.

The formation of linear aggregates in magnetic hyperthermia: implications on specific absorption rate and magnetic anisotropy.

The design and application of magnetic nanoparticles for use as magnetic hyperthermia agents has garnered increasing interest over the past several years. When designing these systems, the fundamentals of particle design play a key role in the observed specific absorption rate (SAR). This includes the particle's core size, polymer brush length, and colloidal arrangement. While the role of particle core size on the observed SAR has been significantly reported, the role of the polymer brush length has not attracted as much attention. It has recently been reported that for some suspensions linear aggregates form in the presence of an applied external magnetic field, i.e. chains of magnetic particles. The formation of these chains may have the potential for a dramatic impact on the biomedical application of these materials, specifically the efficiency of the particles to transfer magnetic energy to the surrounding cells. In this study we demonstrate the dependence of SAR on magnetite nanoparticle core size and brush length as well as observe the formation of magnetically induced colloidal arrangements. Colloidally stable magnetic nanoparticles were demonstrated to form linear aggregates in an alternating magnetic field. The length and distribution of the aggregates were dependent upon the stabilizing polymer molecular weight. As the molecular weight of the stabilizing layer increased, the magnetic interparticle interactions decreased therefore limiting chain formation. In addition, theoretical calculations demonstrated that interparticle spacing has a significant impact on the magnetic behavior of these materials. This work has several implications for the design of nanoparticle and magnetic hyperthermia systems, while improving understanding of how colloidal arrangement affects SAR.

Cellular metabolism as a basis for immune privilege.

We hypothesize that the energy strategy of a cell is a key factor for determining how, or if, the immune system interacts with that cell. Cells have a limited number of metabolic states, in part, depending on the type of fuels the cell consumes. Cellular fuels include glucose (carbohydrates), lipids (fats), and proteins. We propose that the cell's ability to switch to, and efficiently use, fat for fuel confers immune privilege. Additionally, because uncoupling proteins are involved in the fat burning process and reportedly in protection from free radicals, we hypothesize that uncoupling proteins play an important role in immune privilege. Thus, changes in metabolism (caused by oxidative stresses, fuel availability, age, hormones, radiation, or drugs) will dictate and initiate changes in immune recognition and in the nature of the immune response. This has profound implications for controlling the symptoms of autoimmune diseases, for preventing graft rejection, and for targeting tumor cells for destruction.

The effects of chemotherapeutics on cellular metabolism and consequent immune recognition.

Awidely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death.

Characterization of a novel metabolic strategy used by drug-resistant tumor cells.

Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.