Abstract
Liquid perfluorocarbon-based nanodroplets are stable enough to be used in extravascular imaging, but provide limited contrast enhancement due to their small size, incompressible core, and small acoustic impedance mismatch with biological fluids. Here we show a novel approach to overcoming this limitation by using a heating–cooling cycle, which we will refer to as thermal modulation (TM), to induce echogenicity of otherwise stable but poorly echogenic nanodroplets without triggering a transient phase shift. We apply thermal modulation to high-boiling point tetradecafluorohexane (TDFH) nanodroplets stabilized with a bovine serum albumin (BSA) shell. BSA-TDFH nanodroplets with an average diameter under 300 nanometers showed an 11.9 ± 5.4 mean fold increase in echogenicity on the B-mode and a 13.9 ± 6.9 increase on the nonlinear contrast (NLC) mode after thermal modulation. Once activated, the particles maintained their enhanced echogenicity (p < 0.001) for at least 13 h while retaining their nanoscale size. Our data indicate that thermally modulated nanodroplets can potentially serve as theranostic agents or sensors for various applications of contrast-enhanced ultrasound.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
This study discovered that bovine serum albumin (BSA)-TDFH nanodroplets have a temperature-sensitive echogenic behavior that is independent of transient droplet vaporization, and we showed that thermal modulation could be used as a novel method to induce echogenicity to PFC nanodroplets
We showed that the echogenicity of TDFH nanodroplets was enhanced without a transient phase change of the liquid core by thermal modulation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ultrasound (US) is one of the most widely used clinical imaging modalities. It is used in cardiology and vascular imaging, urology, gynecology, obstetrics, as well as in general abdominal imaging [1]. US imaging is portable, non-ionizing, and has a high spatial and temporal resolution [2]. One limitation of ultrasound is its poor contrast resolution, which often makes the differentiation between the blood pool and adjacent soft tissues difficult
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