Increased resonant frequency of microslit filtered contrast agents

Abstract

Imaging using ultrasound contrast agents is highly dependent on the resonant frequency of the population. According to the Marmottant model, modern lipid coated agents have three regimes of resonant frequencies corresponding to the three regimes of bubble dynamics, the buckled, elastic, and ruptured states. The transition from buckled to elastic regime corresponds to the largest change in resonant frequency due to the addition of a second term inversely proportional to the bubbles’ radius. For a 1.75 μm bubble, this corresponds to a change from approximately 1.7 MHz, to approximately 5 MHz, leading to higher image resolution, and better separation between the fundamental and subharmonic components. Here we present a novel ultrathin silicon nitride membrane for this purpose. The membrane itself contains thousands of 1.75 × 50 μm slits and is housed in a centrifuge device. While the exact mechanism is unknown, bubbles that are forced across the membrane during centrifugation show a higher resonant frequency than their strictly size isolated counterparts. In addition, the centrifuged agent also had a lower subharmonic threshold compared to native and size isolated agents, independent of concentration. The possibility of tuning the device to precise frequencies for optimized imaging is also examined.