渡會 展之, 桝田 晃司, 中元 隆介, 江田 廉

Nobuyuki WATARAI, Kohji MASUDA, Ryusuke NAKAMOTO, Ren KODA

東京農工大学大学院生物システム応用科学府

Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology

キーワード : microbubble, aggregation, Bjerknes force, aritificial blood vessel, bifurcation

目的：微小気泡を用いた低侵襲治療法として，超音波照射による温熱効果及び非温熱効果を利用した手法が開発検討されているが，微小気泡は生体内では血流と共に拡散するため，これまでは血流に任せる以外に送達手段が無く，投入効率と副作用の問題があった．対象と方法：本論文では微小気泡の動態を制御するため，複数の超音波音源と単純な形状の分岐を有する模擬血管を用いて，微小気泡の流路選択性能を向上させる方法について検討した．超音波が微小気泡に及ぼす作用力には，伝搬方向への推進力となるprimary Bjerknes forceと，気泡同士が結合した凝集体を形成する引力となるsecondary Bjerknes forceがあるが，前者では流路の分岐形状に対する音波照射角度等の，後者では凝集体のサイズとその飽和時間に必要な音波のパラメータをそれぞれ導出した．これらの両方を同一空間に発生させ，凝集体の形成後に目的の経路に誘導する実験を行った．結果：凝集体を形成しない場合に比べて，凝集体を押し出した場合の誘導率が1.3‐5.5倍向上することを確認した．凝集体の非形成時には中心周波数5 MHzの音波が最も推進力が得られた一方，凝集体形成時には中心周波数が2 MHzで誘導率が最も高くなることを確認した．結論：以上のことより，凝集体自体が一個の微小気泡であると見なした場合のサイズから導出される共振周波数に近いことが推測された．

Purpose: Although minimally invasive treatment methods based on the thermal and non-thermal effects of ultrasound on microbubbles are being reported, a problematic side effect arises because microbubbles are carried in the flow of the bloodstream. To get around this problem, we developed a method to control the behavior of microbubbles in flow by using an artificial blood vessel with multiple transducers to produce ultrasonic plane waves. Materials and Methods: Microbubbules are propelled in flow by a primary Bjerknes force, a physical phenomenon in which an acoustic wave moves an obstacle in its direction of propagation. These bubbles also aggregate when they enter an ultrasound field because of secondary Bjerknes forces that attract or repel neighboring microbubbles. We thus consider forming bubble aggregations to be an effective way to propel the bubbles before they enter an ultrasound field to receive greater primary Bjerknes force. We have investigated the phenomenon of bubble aggregations and observed variation in diameter and density of aggregations under various conditions of ultrasound exposure. Results: When ultrasound was emitted to cause aggregation, the induction index, which indicates the number of microbubbles induced to the desired path in an artificial blood vessel bifurcation, was confirmed to improve by a factor of 1.3 to 5.5 times greater than the index without forming aggregation. The maximum induction index with aggregation was found to be a central frequency of 2 MHz, where a central frequency of 5 MHz was most effective without aggregation. Conclusion: If a bubble aggregation can be regarded as one large bubble, its propulsion would require less primary Bjerknes force. For further development, we plan to realize active control of bubble aggregations in vivo.