Noriko Tsuruoka

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.

Lactate and glucose measurement in subepidermal tissue using minimally invasive microperfusion needle

Knowing the concentrations of biological substances can help ascertain physiological and pathological states. In the present study, a minimally invasive microperfusion needle was developed for measuring the concentrations of biological substances in subepidermal tissue. The microperfusion needle has a flow channel with a perforated membrane through which biological substances from subepidermal tissue are extracted. Since this device uses a thin steel acupuncture needle as the base substrate, it has sufficient rigidity for insertion through the skin. The efficacy of the needle was examined by measuring lactate and glucose concentrations in mice. Lactate was injected intraperitoneally, and changes in lactate concentrations in subepidermal tissue over time were measured using the device. Lactate concentrations of blood were also measured as a reference. Lactate was successfully collected using the microperfusion needle, and the lactate concentration of perfused saline was significantly correlated with blood lactate concentration. Glucose solution was administered orally, and the glucose concentration of perfused saline was also correlated with blood glucose concentration. The newly developed microperfusion needle can be used for minimally invasive monitoring of the concentrations of biological substances.

Measurement of subcutaneous biological substances using thin metal needle with micro flow channel

Concentrations of biological substances are useful as indicators of physiological and pathological states. In order to monitor biological substances in daily life, we developed a minimally invasive needle type device with which biological substances are extracted through a microperfusion system inserted under the skin. The perfusion needle has a flow channel with perforated membrane through which biological substances from subepidermal tissue are extracted. The efficacy of the device was examined by measuring lactate concentration of exercising mice. Lactate was successfully collected from the back skin of the mice running on a treadmill using a fabricated microperfusion needle. Lactate concentration of perfused solution correlated with blood lactate concentration.

Brief effect of acupoint stimulation using focused ultrasound.

BACKGROUND Acupuncture is used worldwide in medical treatment. However, needle insertion damages the skin and patients sometimes feel pain. To avoid such drawbacks, an acupoint stimulation device using focused ultrasound has been developed. Ultrasound stimulation does not damage the skin like acupuncture does because ultrasound can deliver vibration energy to soft tissues noninvasively. OBJECTIVES The aim of this study was to clarify the effect of acupoint stimulation using focused ultrasound. SUBJECTS Fifty (50) healthy volunteers (40 males and 10 females) were included in this experiment. DESIGN Subjects were randomly assigned to two groups. LR-3 was stimulated bilaterally for 36 seconds by focused ultrasound and conventional acupuncture. Brachial artery blood flow volume was monitored by an ultrasound with an echo-tracking system. The hemodynamic parameters were measured before, during, and 30, 60, 180 seconds after stimulation. RESULTS During stimulation, the blood flow volume of the acupuncture stimulation group decreased significantly (p<0.05) compared with resting value, but that of the focused ultrasound stimulation group did not decrease. Blood flow volume of both groups increased gradually and showed significant increase at 180 seconds after stimulation (p<0.05). CONCLUSIONS Blood flow volume was increased significantly by both focused ultrasound stimulation and conventional acupuncture. Although a significant decrease of blood flow volume during acupuncture stimulation was observed, no such decrease was observed during ultrasound stimulation. Findings of the present study show that noninvasive stimulation of acupoints by focused ultrasound is as effective as conventional acupuncture in blood flow volume of the brachial artery.

Acupoint stimulation device using focused ultrasound

Acupuncture is used widely in oriental medicine. But it is difficult to stimulate continuously or intermittently in daily life with conventional acupuncture. An acupoint stimulation device using focused ultrasound has been developed. Because the device size is about 6 mm in diameter, it can be easily put on the skin during daily life. Appropriate stimulation intensity and pattern can be chosen by changing driving voltage and pattern. In this paper, we stimulated acupoints with this device and measured the blood flow volume of brachial artery. As a result, the blood flow volume increased significantly as well as acupuncture. Because the device stimulate acupoints with intactness of skin, advantages of this device is free from infection and fear and pain by insertion of acupuncture needles.

Application of Traditional Medical Ideas to Geriatric Syndrome

Background. Japan is a superaging society, with the percentage of persons aged >65 years increasing year after year. Traditional medicine (TM) for elderly has been practiced worldwide for thousands of years. Treatment methods for aspiration pneumonia, gait disorder, glaucoma, and bowel symptoms have been developed. The ideas of acupuncture, moxibustion, and herbal medicine have been implemented in modern medical settings, and medical devices using heat transfer engineering and nanotechnology have been developed. An ultrasound scanner can be used for the evaluation of effects and indications for these therapeutic measures. Objectives. To review published literature and our studies that evaluated medical treatments for the elderly on the basis of ideas of TM. Search Methods. We searched Pubmed, Scopus, and reference lists of relevant clinical trials. Authors’ Conclusions. Many studies were found. But there are insufficient data on the effects of traditional medical therapies and further research is needed. TM therapies vary widely and studies of these therapies that ascertain practical application are essential for the utilization of ideas of TM in modern medicine. Moreover, to verify practical application, a quantitative evaluation index is necessary. Nonetheless, modalities using ideas of TM may be promising treatments for some diseases in the elderly.