Ryusuke Nakamoto

Production of Local Acoustic Radiation Force to Constrain Direction of Microcapsules in Flow

We have ever reported our attempt to control the direction of microcapsules in flow by acoustic radiation force. However, the diameter of capsules was too large to be applied in vivo. Furthermore, the acoustic radiation force affected only the focal area because focused ultrasound was used. Thus, we have improved our experiment by using microcapsules as small as blood cells and introducing a plane wave of ultrasound. We prepared an artificial blood vessel including a Y-form bifurcation established in two observation areas. Then, we newly defined the induction index to evaluate the difference in capsule density in two downstream paths. As a result, the optimum angle of ultrasound emission to induct to the desired path was derived. The induction index increased in proportion to the central frequency of ultrasound, which is affected by the aggregation of capsules to receive more acoustic radiation force.

Effect of Existence of Red Blood Cells in Trapping Performance of Microbubbles by Acoustic Radiation Force

We have proposed a method to control microbubbles by making use of acoustic radiation force, which is generated with acoustic propagation, to correspond to therapeutic applications of ultrasound. By preventing bubbles from passing through the desired target area, the local concentration of bubbles can be enhanced. However, we have never experimentally confirmed this phenomenon under in vivo conditions or close to those. Thus, we carried out an experiment to evaluate the trapping performance of bubbles using a suspension of red blood cells (RBCs) and an artificial blood vessel. By defining the trapping index to evaluate the amount of trapped microbubbles, we have confirmed that the trapping performance was enhanced according to the concentration of RBCs and the sound pressure, but not according to the central frequency of ultrasound. The results indicate that the existence of RBCs near microbubbles contributed to the increase in the size of aggregations propelled against the vessel wall.

Active Path Selection of Fluid Microcapsules in Artificial Blood Vessel by Acoustic Radiation Force

Micrometer-sized microcapsules collapse upon exposure to ultrasound. Use of this phenomenon for a drug delivery system (DDS), not only for local delivery of medication but also for gene therapy, should be possible. However, enhancing the efficiency of medication is limited because capsules in suspension diffuse in the human body after injection, since the motion of capsules in blood flow cannot be controlled. To control the behavior of microcapsules, acoustic radiation force was introduced. We detected local changes in microcapsule density by producing acoustic radiation force in an artificial blood vessel. Furthermore, we theoretically estimated the conditions required for active path selection of capsules at a bifurcation point in the artificial blood vessel. We observed the difference in capsule density at both in the bifurcation point and in alternative paths downstream of the bifurcation point for different acoustic radiation forces. Comparing the experimental results with those obtained theoretically, the conditions for active path selection were calculated from the acoustic radiation force and fluid resistance of the capsules. The possibility of controlling capsule flow towards a specific point in a blood vessel was demonstrated.

Dependence of aggregate formation of microbubbles upon ultrasound condition and exposure time

We have previously reported our attempts to control microbubbles (microcapsules) behavior in flow by primary Bjerknes force to increase the local concentration of the bubbles at a diseased part. However, there was a limitation in efficiency to propel bubbles of μm-order size. Thus we consider that forming aggregates of bubbles is effective to be propelled before entering into an ultrasound field by making use of secondary Bjerknes force under continuous ultrasound exposure. In this study, we observed the phenomena of aggregates formation by confirming variation of diameter and density of aggregates under various conditions of ultrasound exposure. Then we elucidated frequency dependence of the size of aggregates of micro-bubbles.

Active control of microcapsules in artificial blood vessel by producing local acoustic radiation force

Micrometer-sized microcapsules collapse upon exposure to ultrasound. Use of this phenomenon for a drug delivery system (DDS), not only for local delivery of medication but also for gene therapy, should be possible. However, enhancing the efficiency of medication is limited because capsules in suspension diffuse in the human body after injection, since the motion of capsules in blood flow cannot be controlled. To control the behavior of microcapsules, acoustic radiation force was introduced. We detected local changes in microcapsule density by producing acoustic radiation force in an artificial blood vessel. Furthermore, we theoretically estimated the conditions required for active path selection of capsules at a bifurcation point in the artificial blood vessel. We observed the difference in capsule density at both in the bifurcation point and in alternative paths downstream of the bifurcation point for different the acoustic radiation forces. Also we confirmed the microcapsules are trapped against flow with the condition when the acoustic radiation force is more than fluid resistance of the capsules. The possibility of controlling capsule flow towards a specific point in a blood vessel was demonstrated.

Study to prevent the density of microcapsules from diffusing in blood vessel by local acoustic radiation force

We have already reported our attempt to constrain direction of microcapsules in flow owing to an acoustic radiation force. However, the diameter of capsules was too large not to be applied in vivo. Furthermore, acoustic radiation force affected only in focal area because focused ultrasound was used. Thus we have improved our experiment by using microcapsules as small as blood cells and introducing a plane wave of ultrasound. We prepared an artificial blood vessel including a Y-form bifurcation established two observation areas. Then we newly defined the induction index to evaluate the difference of capsule density in two paths of downstream. As the result, optimum angle of ultrasound emission to induce to desired path was derived. And the induction index increased in proportion to the central frequency of ultrasound, which is affected by forming aggregation of capsules to receive more radiation force.

Active path selection of fluid microcapsules by acoustic radiation force in the artificial blood vessel

Microcapsules of µm order collapse themselves after ultrasound emission. Recently, this technique attracts attention to apply to the gene delivery because virus vector is not necessary. However, it has been limitation to enhance the efficiency of medication because capsules suspension diffuses after the injection, where motion of capsules in blood flow cannot be controlled. To affect behavior of microcapsules, acoustic radiation force was introduced. Then we have detected the local change of microcapsules density by producing acoustic radiation force in the artificial blood vessel. Furthermore, we estimated theoretically condition for active path selection of capsules at the bifurcation in the artificial blood vessel. We observed the difference of density in capsules according to the acoustic radiation force and the produced point. Comparing the experimental results with theoretical equations, the condition for active path selection is calculated from acoustic radiation force and fluid resistance of capsules. It showed a possibility to control capsules direction and to lead to an objective point in blood vessel.

Evaluation of local density enhancement of microcapsules in artificial blood vessel during exposure to focused ultrasound

We have proposed a physical DDS (Drug Delivery System) which makes use of microcapsules of μm size, which may contain a specified drug and also are easily affected by ultrasound exposure near their resonant frequency, to release various kinds of medications. These capsules are easily detected and actuated by ultrasound. However, because of the diffusion of capsules after injection into human body, it was difficult to enhance the efficiency of drug delivery. Thus we have considered a method for controlling the density of capsules in flow which uses acoustic radiation force, which moves the capsules to balance flow resistance. We have experimented with trapping microcapsules or microbubbles in flow of an artificial blood vessel. We have evaluated the effect of radiation force by measuring the trapped area of capsules or bubbles for various frequencies, sound pressures, and exposure times of sinusoidal ultrasound. The trapped area of capsules or bubbles increased with sound pressure and exposure time, and decreased with frequency. From those results, we have derived optimal conditions for trapping the capsules or bubbles.We have proposed a physical DDS (Drug Delivery System) which makes use of microcapsules of μm size, which may contain a specified drug and also are easily affected by ultrasound exposure near their resonant frequency, to release various kinds of medications. These capsules are easily detected and actuated by ultrasound. However, because of the diffusion of capsules after injection into human body, it was difficult to enhance the efficiency of drug delivery. Thus we have considered a method for controlling the density of capsules in flow which uses acoustic radiation force, which moves the capsules to balance flow resistance. We have experimented with trapping microcapsules or microbubbles in flow of an artificial blood vessel. We have evaluated the effect of radiation force by measuring the trapped area of capsules or bubbles for various frequencies, sound pressures, and exposure times of sinusoidal ultrasound. The trapped area of capsules or bubbles increased with sound pressure and exposure time, and de...

Study to trap fluid microcapsules in artificial blood vessel by producing local acoustic radiation force

Microcapsules of μm order collapse themselves after ultrasound emission. Applying this technique as drug delivery system (DDS), not only local medication but also gene therapy method should be possible. However, it has been limitation to enhance the efficiency of medication because capsules suspension spreads in human body after the injection, where motion of capsules in blood flow cannot be controlled. To affect behavior of microcapsules, acoustic radiation force was introduced. We have observed the local aggregation of microcapsules by producing local acoustic radiation force in the artificial blood vessel. Then we estimated amount of trapped capsules by optical image processing. We confirmed fluid microcapsules of similar diameter with red blood cell were trapped in the middle of the path and by ultrasound of sinusoidal signal of 1 MHz. The condition to trap capsules was indicated by higher sound pressure and lower flow velocity.