Ren Koda

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.

Experimental Study to Produce Multiple Focal Points of Acoustic Field for Active Path Selection of Microbubbles through Multi-bifurcation

We previously reported our attempt to propel microbubbles in a flow by a primary Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation. However, when ultrasound was emitted from the surface of the body, controlling bubbles in an against-flow was necessary. It is unpractical to use multiple transducers to produce the same number of focal points because single-element transducers cannot produce more than two focal points. In this study, we introduced a complex artificial blood vessel according to a capillary model and a two-dimensional (2D) array transducer to produce multiple focal points for the active control of microbubbles in an against-flow. From the results, about 15% more microbubbles were led to the desired path with multiple focal points of ultrasound relative to the no-emission case.

Experimental Study of Active Path Block in a Multi-Bifurcated Flow by Microbubble Aggregation

We previously reported our attempts at the active control of microbubble aggregations using acoustic radiation force, which propels microbubbles and adjusts the size of aggregations. However, because we used simple-shape artificial blood vessels, the behavior of aggregations in a small channel, e.g., the probability to obstruct the bloodstream, and the possibility of embolization, has not been predicted. Thus, we designed and fabricated a multi-bifurcated artificial blood vessel to apply to the production and active control of microbubble aggregations. Then, we introduced two kinds of ultrasound transducers for producing and propelling aggregations. First, we produced aggregations in a flow to measure their size and investigate their variation according to the emission duration of ultrasound. Then, we control the aggregations in an artificial blood vessel to verify their controllability. When ultrasound was stopped, the aggregations flaked off the vessel wall and flowed downstream, were propelled to the desired path, and finally were caught at a narrow path. We verified the same experiment under similar parameters to calculate the probability of realizing a path block. When the flow velocity was 20 mm/s, almost 50% of the aggregations were induced to flow through the desired path and a maximum probability of realizing a path block of 86% was achieved with the formation of aggregations.

Production and validation of acoustic field to enhance trapping efficiency of microbubbles by using a matrix array transducer

We have developed a new matrix array transducer for controlling the behavior of microbubbles, which is different from that for high-intensity focused ultrasound (HIFU) therapy, in order to emit continuous wave by designing an acoustic field including multiple focal points. In the experiment using a thin-channel model, a wider acoustic field has an advantage for trapping microbubbles. In the experiment using a straight-path model, we have confirmed that a higher concentration of acoustic energy does not result in more aggregates. The dispersion of acoustic energy is important because the trapping performance is affected by the relationship between the shape of the acoustic field and the concentration of the suspension.

Experimental study of active control of microbubbles in blood flow by forming their aggregations

We have experimented a method to control behavior of microbubbles in flow using an artificial blood vessel with multiple transducers to emit ultrasonic plane wave. Microbubbules are propelled in flow owing to a primary Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation. Also they form aggregation when they are put into an ultrasound field because of secondary Bjerknes force, which acts as attractive or repulsive factor among neighboring microbubbles. Thus we consider that forming bubble aggregations is effective to be propelled before entering into an ultrasound field to receive greater primary Bjerknes force. We have investigated the phenomenon of bubble aggregations and observed behavior of aggregations with and without red blood cells in artificial blood vessels under various conditions of ultrasound exposure. As the results, when microbubble aggregations were formed, the efficiency was improved more than the condition without forming aggregation. The existence of red blood cells near microbubbles contributed to the increase in the size of aggregations propelled against the vessel wall.

Quantitative measurement of acoustic radiation force on a thin catheter for use in endovascular therapy

In this study, the quantitative measurement of acoustic radiation force acting on a thin catheter has been carried out to develop endovascular therapy with microbubbles. First, it is elucidated that the force acting on a thin catheter made of perfluoroalkoxy (PFA) copolymer can be obtained from the cantilever equation in the effective range, where the displacement of the catheter divided by the cube of the length of the catheter is less than 1.0 × 10−5 mm−2. Next, on the basis of the cantilever theory, the force acting on the catheter (diameter 400 µm, material PFA) is measured to be 24 µN under the continuous ultrasound (frequency 2 MHz, sound pressure 300 kPa) irradiation. Furthermore, it is observed that the force depends on the ultrasound frequency. Finally, we conclude that the force is obtained under practical conditions for the realization of endovascular therapy and suggest that thin catheter navigation using ultrasound is fully promising.

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.

Observation of flow variation in capillaries of artificial blood vessel by producing microbubble aggregations

Microbubbles form their aggregations between the neighboring microbubbles by the effect of secondary Bjerknes force under ultrasound exposure. However, because of the difficulty to reproduce a capillary-mimicking artificial blood vessel, the behavior of aggregations in a capillary has not been predicted. Thus we prepared artificial blood vessels including a capillary model, which was made of poly(vinyl alcohol) (PVA) by grayscale lithography method, with minimum diameter of the path of 0.5 mm. By using this model we investigated the possibility of artificial embolization, where the microbubble aggregations might block entire vessels not to penetrate flow in downstream. Confirming that the sizes of flown aggregation were greater than the section area of the minimum path in the capillary model, we investigated the probability of path block in it. As the results we confirmed the probability increased in proportion to sound pressure and inversely to flow velocity. We are going to investigate with more kinds of parameters to enhance the possibility of artificial embolization.

Forming acoustic attraction force to concentrate microbubbles in flow using a matrix array transducer

We have reported our attempts for active path selection of microbubbles by acoustic radiation forces, where we have investigated to control microbubbles by forming multiple focal points of continuous wave using a matrix array transducer. However, because those focal points were located to sweep microbubbles along the slope of sound pressure, it was difficult to concentrate microbubbles against the direction of flow. To produce attractive force to concentrate microbubbles in flow, we formed time-shared acoustic field of two focal points with phase variation. We have succeeded to concentrate microbubbles in water flow utilizing two focal points with opposite phase, where streamline of microbubbles was clearly confirmed in a thin channel. Also we confirmed induction performance using an artificial blood vessel with Y-form bifurcation, where induction rate to a desired path was calculated and varied according to the emission pattern of the focal points in time-shared acoustic fields.

Shear Wave Imaging of Breast Tissue by Color Doppler Shear Wave Elastography

Shear wave elastography is a distinctive method to access the viscoelastic characteristic of the soft tissue that is difficult to obtain by other imaging modalities. This paper proposes a novel shear wave elastography [color Doppler shear wave imaging (CD SWI)] for breast tissue. Continuous shear wave is produced by a small lightweight actuator, which is attached to the tissue surface. Shear wave wavefront that propagates in tissue is reconstructed as a binary pattern that consists of zero and the maximum flow velocities on color flow image (CFI). Neither any modifications of the ultrasound color flow imaging instrument nor a high frame rate ultrasound imaging instrument is required to obtain the shear wave wavefront map. However, two conditions of shear wave displacement amplitude and shear wave frequency are needed to obtain the map. However, these conditions are not severe restrictions in breast imaging. This is because the minimum displacement amplitude is