Aya Sato

Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser

In vivo two-photon microscopy has revealed vital information on neural activity for brain function, even in light of its limitation in imaging events at depths greater than several hundred micrometers from the brain surface. We developed a novel semiconductor-laser-based light source with a wavelength of 1030 nm that can generate pulses of 5-picosecond duration with 2-W output power, and a 20-MHz repetition rate. We also developed a system to secure the head of the mouse under an upright microscope stage that has a horizontal adjustment mechanism. We examined the penetration depth while imaging the H-Line mouse brain and demonstrated that our newly developed laser successfully images not only cortex pyramidal neurons spreading to all cortex layers at a superior signal-to-background ratio, but also images hippocampal CA1 neurons in a young adult mouse.

Lateral resolution enhancement of laser scanning microscopy by a higher-order radially polarized mode beam.

We demonstrate that the lateral resolution of confocal laser scanning microscopy is dramatically improved by a higher-order radially polarized (HRP) beam with six concentric rings. This beam was generated simply by inserting liquid crystal devices in front of an objective lens. An HRP beam visualized aggregated 0.17 μm beads individually and is also applicable to biological imaging. This method can extend the capability of conventional laser scanning microscopes without modification of the system, with the exception of the addition of the liquid crystal devices in the optical path.

Cyclical Tensile Force on Periodontal Ligament Cells Inhibits Osteoclastogenesis through OPG Induction

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

Nonlinear-microscopy optical-pulse sources based on mode-locked semiconductor lasers

We developed picosecond optical-pulse sources suitable for multiphoton microscopy based on mode-locked semiconductor lasers. Using external-cavity geometry, stable hybrid mode locking was achieved at a repetition rate of 500 MHz. Semiconductor optical amplifiers driven by synchronized electric pulses reached subharmonic optical-pulse repetition rates of 1-100 MHz. Two-stage Yb-doped fiber amplifiers produced optical pulses of 2 ps duration, with a peak power of a few kilowatts at a repetition rate of 10 MHz. These were employed successfully for nonlinear-optic bio-imaging using two-photon fluorescence, second-harmonic generation, and sum-frequency generation of synchronized two-color pulses.

All-optical phase modulations in a silicon wire waveguide at ultralow light levels

Cross-phase modulation(XPM) in a silicon wire waveguide at 1.55 μ m telecom band was studied down to ultralow light levels. In the low-power regime, we found that free-carrier dispersion as well as the optical Kerr effect contributes to the XPM. Possible mechanisms of the low-power XPM are discussed.

Oscillatory interlayer exchange coupling in epitaxial Co2MnSi∕Cr∕Co2MnSi trilayers

Interlayer exchange coupling (IEC) in trilayers, which consist of a full Heusler Co2MnSi (CMS) phase as ferromagnetic layers separated by a Cr spacer layer, has been investigated. The shape of magnetization loops shows unusual oscillatory behavior with the thickness of Cr. The oscillation period is about 3.3–3.5nm. The charecteristics of magnetization curves show that 90° coupling plays a dominant role in IEC between CMS layers. Moreover, the strength of 90° coupling turns out to be very high (up to −1.85ergs∕cm2) around the first oscillation peak.

Sub-5-ps optical pulse generation from a 1.55-µm distributed-feedback laser diode with nanosecond electric pulse excitation and spectral filtering

This paper reports generation of sub-5-ps Fourier-transform limited optical pulses from a 1.55-µm gain-switched single-mode distributed-feedback laser diode via nanosecond electric excitation and a simple spectral-filtering technique. Typical damped oscillations of the whole lasing spectrum were observed in the time-resolved waveform. Through a spectral-filtering technique, the initial relaxation oscillation pulse and the following components in the output pulse can be well separated, and the initial short pulse can be selectively extracted by filtering out the short-wavelength components in the spectrum. Short pulses generated by this simple method are expected to have wide potential applications comparable to mode-locking lasers.

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain

OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 μl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way ANOVA). The Vd of Gd-DTPA was also significantly larger in the UFD group than in the control group (p < 0.05, Student t-test). The volume of Gd-DTPA in the nonhuman primate used in this study was 1209.8 ± 193.6 mm(3). This volume was much larger than that achieved by conventional CED (568.6 ± 141.0 mm(3)). CONCLUSIONS The UFD system facilitated the distribution of EBD and Gd-DTPA more effectively than conventional CED. Lower frequency and higher applied voltage using resonance frequencies might be more effective to enlarge the Vd. The UFD system may provide a new treatment approach for CNS disorders.

Dynamics of short-pulse generation via spectral filtering from intensely excited gain-switched 1.55-μm distributed-feedback laser diodes

Picosecond-pulse-generation dynamics and pulse-width limiting factors via spectral filtering from intensely pulse-excited gain-switched 1.55-μm distributed-feedback laser diodes were studied. The spectral and temporal characteristics of the spectrally filtered pulses indicated that the short-wavelength component stems from the initial part of the gain-switched main pulse and has a nearly linear down-chirp of 5.2 ps/nm, whereas long-wavelength components include chirped pulse-lasing components and steady-state-lasing components. Rate-equation calculations with a model of linear change in refractive index with carrier density explained the major features of the experimental results. The analysis of the expected pulse widths with optimum spectral widths was also consistent with the experimental data.

A high-peak-power UV picosecond-pulse light source based on a gain-switched 1.55 μm laser diode and its application to time-resolved spectroscopy of blue-violet materials

We generated sub-kilowatt peak-power and 6-ps duration 390-nm optical pulses via the fourth harmonic generation of amplified optical output from a gain-switched 1.55-microm laser diode. We obtained a power-conversion-efficiency of 12% from 1.55-microm to 390-nm light, and subsequently applied the ultraviolet pulses to time-resolved spectroscopy of blue-violet luminescent materials, including a Coumarine dye solution and nitride semiconductor materials using single-photon and two-photon excitation schemes.