Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

Abstract

Background: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US. Purpose: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical imaging. Methods: PNCAs with varied core compositions (i.e., mixtures of perfluoropentane [C5] and/or perfluorohexane [C6]) and two coating formulations (i.e., with and without cholesterol) were characterized and investigated for thermal/temporal stability and postactivation, nonlinear US contrast in phantom and in vivo environments. Through hydrophone measurements and nonlinear numerical modeling, MI was estimated for pulse sequences used for PNCA activation. Results: All PNCA compositions were characterized to have similar diameters (249-267 nm) and polydispersity (0.151-0.185) following fabrication. While PNCAs with majority C5 core composition showed higher levels of spontaneous signal (i.e., not due to US activation) in phantoms than C6-majority PNCAs, all compositions were stable during imaging experiments. When activating PNCAs with a 12.3-MHz US pulse (MI = 1.1), C6-core particles with cholesterol-free coatings (i.e., CF-C6-100 particles) generated a median contrast of 3.1, which was significantly higher (p < 0.001) than other formulations. Further, CF-C6-100 particles were activated in a murine model, generating US contrast ≥3.4. Conclusion: C6-core PNCAs can provide high-contrast US imaging with minimal nonspecific activation in phantom and in vivo environments.

Effect of Phase-Change Nanodroplets and Ultrasound on Blood–Brain Barrier Permeability In Vitro

“…PFP has a boiling point of 29 °C, while PFH has a boiling point of 56 °C. The PFC type did not affect the resulting average ND size, which appeared similar and in agreement with previous studies [21] (Figure 3).…”

“…In this study, we have formulated NDs with three different PFC cores: perfluoropentane (PFP), perfluorohexane (PFH), and a 1-1 mixture of PFP:PFH (1:1 volumetric ratio). PFP has a boiling point of 29 • C, while PFH has a boiling point of 56 • C. The PFC type did not affect the resulting average ND size, which appeared similar and in agreement with previous studies [21] (Figure 3).…”

Fast and Selective Super-Resolution Ultrasound In Vivo With Acoustically Activated Nanodroplets

“…Tissue motion, uneven and spatially varying attenuation and the image application e.g., difference between the desired frame rate for kidney or cardiac imaging further diminish the control over nanodroplet vaporization with fast-AWSALM, and to a lesser extent with ASWALM. Changing the lipid shell [36], [39], [40], using mono-sized nanodroplets [37] and implementing real-time feedback to automatically adjust ultrasound parameters based on the received signals should be able to further improve the reproducibility of fast-AWSALM. Heterogeneity in attenuation and local pressure might explain the uneven distribution of localization as seen in Figure 8.…”

Preparation of ultrasound contrast agents: The exploration of the structure-echogenicity relationship of contrast agents based on neural network model

“…Moreover, in this model, the PDI was the second most important factor affecting the contrast agent enhancement effect. Previous PDI-related studies, mostly for targeted applications of nanoparticles and microbubbles, described experiments with almost monodisperse particles (polydispersity index <0.2) ( 28 – 30 ). In our model, the enhancement effect was best when the PDI was 0.53 ± 0.19.…”