Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics.

Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-µm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 µm, with no bubbles >44 µm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.

The influence of acoustic transmit parameters on the destruction of contrast microbubbles in vitro.

In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz), acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (p < or = 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US.

PURPOSE: To determine if lymphatic channels and sentinel lymph nodes (SLNs) with and without metastases can be detected with lymphatic ultrasonography (US) after peritumoral injection of a US contrast agent and to determine if lymphatic US can be used to assess SLNs for the presence of metastatic infiltration. MATERIALS AND METHODS: Six swine with 17 melanomas were evaluated. Conventional gray-scale, color flow, and gray-scale phase-inversion harmonic US examinations were performed. A US contrast agent was administered in four sites around each melanoma (1-mL total dose). Lymphoscintigraphy was followed by injection of a blue dye and then dissection. SLNs identified at lymphatic US were characterized by two readers in consensus as normal or as having metastases; results were compared with histologic findings. Statistical analyses included the sign test and the kappa statistic. RESULTS: Lymphatic US depicted 28 SLNs, while lymphoscintigraphy depicted 27 "hot spots" suspected of representing SLNs (including two false-positive findings). Dissection after blue dye injection helped identify 31 SLNs. There were no false-positive US findings for SLN detection. Five of six nodes not seen with lymphoscintigraphy were detected with lymphatic US. The accuracy of SLN detection was 90% (28 of 31) for lymphatic US and 81% (25 of 31) for lymphoscintigraphy (P =.29). Lymphatic US correctly depicted metastases in 19 of 20 SLNs, and five of the eight normal SLNs were correctly characterized, with an accuracy of 86% (kappa = 0.62). CONCLUSION: Detection of SLNs with lymphatic US compared favorably with that at lymphoscintigraphy. Lymphatic US can depict metastases within the SLN, which was not possible with lymphoscintigraphy.