Purpose: To assess the ability to activate and image perfluorocarbon (PFC) nanodroplets in a tumor-mimicking environment using high-frequency ultrasound (US), demonstrating that PFC nanodroplets could be noninvasively used as high-contrast molecular contrast agents imaged with high-frequency US.
Methods: PFC nanodroplets are able to undergo a phase transition from a liquid nanodroplet to a gaseous microbubble upon exposure to clinical US pulses with sufficiently high mechanical index (MI). In order to activate the nanodroplets and image the subsequent microbubbles, a pulse sequence was designed for the Verasonics Vantage 128 system using the Kolos Medical L22-8v CMUT transducer (15-MHz center frequency) using linear B-mode and pulse-inversion contrast-enhanced imaging. In order to optimize the nanodroplet size and US frequency used, nanodroplets with multiple diameters (360, 285, 250, and 210 nm) were activated and imaged at both 12.5 and 21 MHz, and the contrast enhancement was analyzed via a comparison of matched ROIs from pre-and post-activation imaging data. Once the optimal nanodroplet size and US frequency were determined, nanodroplets were activated and imaged in a tissue-mimicking gelatin phantom (8% gelatin, 1.0% silica, 91% water) in order to determine the activation and contrast enhancement in an environment containing tissue-mimicking acoustic absorption, scattering and speckle.
Results: US pulse sequences were optimized on the Verasonics system to consistently activate the nanodroplets with sufficient MI and subsequently visualize them using both B-mode and pulse-inversion imaging. Nanodroplets of initial diameter 350 and 285 nm provided the best results, both at 12.5 MHz. Nanodroplets (285 nm) were successfully activated and visualized in a tissue-mimicking phantom with contrast enhancement of 19 dB.
Conclusion: The results of this study show that PFC nanodroplets can be activated and imaged within tissue-mimicking phantoms using high-frequency clinical US pulses. This work demonstrates the potential for future translation of targeted PFC nanodroplets into in vivo trials.
Not Applicable / None Entered.