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Akihiro Kuwahata,1,* Muneer Ahmed,2,* Kohei Saeki,3 Shinichi Chikaki,1 Miki Kaneko,1 Wenqi Qiu,1 Zonghao Xin,1 Shinji Yamaguchi,3 Akiko Kaneko,1 Michael Douek,2 Moriaki Kusakabe,3,4 Masaki Sekino1 1Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; 2Division of Cancer Studies, King’s College London, Guy’s Hospital Campus, Great Maze Pond, London, UK; 3Graduate School of Agriculture and Life Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; 4Matrix Cell Research Institute Inc., Ibaraki, Japan *These authors contributed equally to this work Background: Sentinel node biopsy using radioisotope and blue dye remains a gold standard for axillary staging in breast cancer patients with low axillary burden. However, limitations in the use of radioisotopes have resulted in emergence of novel techniques. This is the first in vivo study to assess the feasibility of combining the two most common novel techniques of using a magnetic tracer and indocyanine green (ICG) fluorescence.Materials and methods: A total of 48 mice were divided into eight groups. Groups 1 and 2, the co-localization groups, received an injection of magnetic tracers (Resovist® and Sienna+®, respectively) and ICG fluorescence; distilled water was used as the solvent of ICG. Groups 3 and 4, the diluted injection groups, received an injection of magnetic tracers (Resovist and Sienna+, respectively) and saline for dilution. Groups 5, 6, and 7, the control groups, received magnetic tracer (Resovist, Sienna+) and ICG alone, respectively. Fluorescent intensity assessment and iron quantification of excised popliteal lymph nodes were performed. Group 1', a co-localization group, received an injection of magnetic tracers (Resovist) and ICG' fluorescence: saline was used as the solvent for ICG.Results: Lymphatic uptake of all tracers was confined to the popliteal nodes only, with co-localization confirmed in all cases and no significant difference in fluorescent intensity or iron content of ex vivo nodes between the groups (except for Group 1'). There was no impact of dilution on the iron content in the diluted Sienna+ group, but it significantly enhanced Resovist uptake (P=0.005). In addition, there was a significant difference in iron content (P=0.003) in Group 1'.Conclusion: The combination of a magnetic tracer (Resovist or Sienna+) and ICG fluorescence is feasible for sentinel node biopsy and will potentially allow for precise transcutaneous node identification, in addition to accurate intraoperative assessment. This radioisotope-free “combined technique” warrants further assessment within a clinical trial. Keywords: sentinel node biopsy, combined technique, fluorescence dye, magnetic nanoparticles, dilutional effect

We present a novel method for estimating the magnetic field that can generate the desired magnetic force to move magnetic nanoparticles in a region of interest. The magnetic field is expanded using vector spherical harmonics, and the optimal multipole moments are estimated. The multipole moments are included in quadratic form because the magnetic force is defined as the product of the magnetic field and its gradient. We transform the system of quadratic equations into a rank-one-matrix estimation problem to construct a convex numerical algorithm based on a well-established proximal operation. The proposed method was validated using numerical simulations and can be used to design magnetic force patterns that cannot be generated using a simple coil pair. [ABSTRACT FROM AUTHOR]

The finite-difference method is used for solving the diffusion equation of nuclear magnetization in discrete space and time. The purpose of this study was to obtain the time step [DELTA]t and the spatial step [DELTA]x, which minimize computational errors in simulation. We evaluated the difference between a discrete solution and an explicit solution that had been derived from the magnetization diffusion equation. The results revealed the existence of [DELTA]x, which minimizes computational errors. The spatial step [DELTA]x and computational errors increased as the time step [DELTA]t increased. The results should be useful for efficiently carrying out diffusion simulations within given time limitations for computation. Index Terms--Computational errors, diffusion, finite difference methods, magnetic resonance imaging, water molecules.

The present study demonstrated the measurement of [Na.sub.e]/[Na.sub.i] in sciatic nerves by [sup.23]Na-MRS using [sup.23]Na frequency shift agent [Na.sup.4] HTmDOTP. Sciatic nerves from bull frogs were submerged into the 5 mM TmDOTP solution for 12 h before acquisition. MRS was performed on a Varian 4.7-T magnetic resonance spectrometer. To obtain the shift of [Na.sub.e]/[Na.sub.i] resonance, [sup.23]Na spectra were acquired from the whole sample with TR 50 ms and 800 averages. [Na.sub.e] and [Na.sub.i] signals were detected clearly in the spectra of TmDOTP solution-immerged nerve. Then, for evaluation of nerves viability, action potential of TmDOTP solution-immerged nerve was examined. TmDOTP had no effects on the generation of action potential. An increase of [Na.sub.e] signal/[Na.sub.i] signal was observed during the electrical stimulation, suggesting that this result reflected the direct changes in sodium ions permeability during the nerves excitation. Index Terms--Magnetic resonance spectroscopy, nerve excitation, sodium ion.

Repetitive pulsed magnetic stimulation (RPMS) is the use of pulsed magnetic fields to induce electric fields in the tissues by electromagnetic induction without the need for surgery or external electrodes. In the present study, the combination effect of RPMS and an anticancer agent was examined on human chronic myelogenous leukemia-derived cell line TCC-S using molecular target drug (selective tyrosine kinase inhibitor) imatinib mesylate (imatinib). The stimulus conditions were determined as follows: 0.1, 0.25, and 0.5 T, 25 pulses/s, 1000, 3000, and 6000 pulses/day. TCC-S cells were cultured with 100 nM imatinib and exposed to RPMS at 1 h, 12 h, 24 h, 36 h, 48 h, and 56 h after drug treatment. The significant combination effects of RPMS and imatinib occurred by the stimulus intensity and pulse dose depended manner. To clarify the effects of RPMS on human normal lymphocytes, PBMCs were also exposed to RPMS with or without imatinib. RPMS had no effect on the viability of PBMCs. These results indicate that RPMS possibly improve the effectiveness of anticancer agents. Index Terms--Anticancer agent, leukemia cells, repetitive pulsed magnetic stimulation.

We investigate the effects of repetitive magnetic stimulation on tumors and immune functions. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) is used in the experiments. Stimulus conditions are: peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1000 pulses/sample/day, and magnetically induced eddy currents in mice = 0.79-1.54 A/[m.sup.2]]. The sham group mice are placed in the same holders and exposed to the same noise produced during the stimulation. The tumor growth study shows a significant tumor weight decrease due to the application of magnetic stimulation (54% versus the sham group). An immunological assay is also performed to examine the effects of the magnetic stimulation on immune functions. An in vivo study, TNF-[alpha] and IL-2 productions in the spleen are measured after exposure of the magnetic stimulation three or seven times. TNF-[alpha] production significantly increases in the stimulated group (146%-164% versus the sham group). In an in vitro study, isolated spleen cells (lymphocytes) are exposed to the magnetic stimulation (25 pulses/s, 1000 pulses/sample, and eddy currents: 2.36-2.90 A/[m.sup.2]) and a proliferation assay is performed. The poliferation activity of the lymphocytes is up-regulated in the exposed samples. These results indicate that the immune functions might be activated by repetitive magnetic stimulation exposure, resulting in a tumor weight decrease. Index Terms--Eddy currents, immune system, pulsed magnetic stimulation.

A method is described for noninvasively evaluating the permeability of the cell membrane in the rat brain by using diffusion magnetic resonance imaging (MRI). This method is useful for noninvasively estimating the cell membrane permeability of biological tissues and it can be easily applied to human tissues.

Current distribution image of the rat brain using diffusion weighted magnetic resonance imaging is discussed. By comparing subtraction MRI maps of ADC of rat brain tissue, we showed that applied external electrical currents increase the ADC of rat brain tissue.