A comprehensive numerical investigation of the potential influence of the bubble size and ultrasound focal pressure in drug delivery enhancement

Stable Bubble oscillations contribute to a range of bio-effects such as enhanced drug delivery and blood-brain barrier opening. The treatment outcome depends on the bubble oscillation characteristics and the number of bubbles present at the target. Higher concentrations result in more bubbles per unit length of the vessels and, therefore, more uniform effects. At higher bubble concentrations, however, the pre-focal attenuation increases. Moreover, above a concentration threshold, bubble-bubble interactions suppress bubble oscillations. To enhance the treatment outcome, thus, not only the bubble concentration and activity should be optimized, but also the problem of pre-focal attenuation should be tackled. Numerical results show that, using the pressure gradient of focused ultrasound transducers and by taking advantage of the pressure dependent attenuation of size isolated bubbles, pre-focal attenuation can be minimized. The optimal bubble size for maximum propagation depends on the focal pressure. When volume is matched, and at lower pressures, bigger bubbles exhibit stronger radial oscillations, scattered pressure, and microstreaming (RSM). Above a pressure threshold that depend on the bubble size, smaller bubbles exhibit stronger RSM compared to their bigger counterparts. The treatment outcome may be enhanced using an optimal set of size and pressures. These results are in qualitative agreement with experimental case studies using size isolated bubbles.