Abstract
.Significance: An effective contrast agent for concurrent multimodal photoacoustic (PA) and ultrasound (US) imaging must have both high optical absorption and high echogenicity. Integrating a highly absorbing dye into the lipid shell of gas core nanobubbles (NBs) adds PA contrast to existing US contrast agents but may impact agent ultrasonic response.Aim: We report on the development and ultrasonic characterization of lipid-shell stabilized NBs with integrated Sudan Black (SB) B dye in the shell as dual-modal PA-US contrast agents.Approach: Perfluoropropane NBs stabilized with a lipid shell including increasing concentrations of SB B dye were formulated by amalgamation (SBNBs). Physical properties of SBNBs were characterized using resonant mass measurement, transmission electron microscopy and pendant drop tensiometry. Concentrated bubble solutions were imaged for 8 min to assess signal decay. Diluted bubble solutions were stimulated by a focused transducer to determine the response of individual NBs to long cycle (30 cycle) US. For assessment of simultaneous multimodal contrast, bulk populations of SBNBs were imaged using a PA and US imaging platform.Results: We produced high agent yield () with a mean diameter of to 300 nm depending on SB loading. A 40% decrease in bubble yield was measured for solutions with 0.3 and SB. The addition of SB to the shell did not substantially affect NB size despite an increase in surface tension by up to . The bubble decay rate increased after prolonged exposure (8 min) by dyed bubbles in comparison to their undyed counterparts (2.5-fold). SB in bubble shells increased gas exchange across the shell for long cycle US. PA imaging of these agents showed an increase in power (up to 10 dB) with increasing dye.Conclusions: We added PA contrast function to NBs. The addition of SB increased gas exchange across the NB shell. This has important implications in their use as multimodal agents.
Highlights
Microvascular morphology is a hallmark of many diseases, including cancer.[1]
We showed that integration of the Sudan Black (SB) dye agent modifies the shell properties of US contrast agents by increasing lipid surface tension at the lipid-gas interface
Differences in surface tension correlated with decreased bubble stability, as shown from prolonged Sudan Black nanobubble (SBNB) exposure to US excitation
Summary
Microvascular morphology is a hallmark of many diseases, including cancer.[1]. Medical imaging modalities, such as photoacoustic (PA) and ultrasound (US) imaging, can effectively assess the Journal of Biomedical OpticsDownloaded From: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics on 02 Mar 2022 Terms of Use: https://www.spiedigitallibrary.org/terms-of-useJanuary 2022 Vol 27(1)Wegierak et al.: Effects of shell-integrated Sudan Black dye. . .morphology of microvasculature. Microvascular morphology is a hallmark of many diseases, including cancer.[1] Medical imaging modalities, such as photoacoustic (PA) and ultrasound (US) imaging, can effectively assess the Journal of Biomedical Optics. Downloaded From: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics on 02 Mar 2022 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use. Wegierak et al.: Effects of shell-integrated Sudan Black dye. In PA imaging, ultrasonic pressure waves are generated from the thermoelastic expansion of tissue chromophores after laser absorption. Present in the human body, hemoglobin in red blood cells is a strong light absorber and generates a relatively high PA signal.[1] On the other hand, US imaging utilizes acoustic waves that are generated by a transducer, transmitted through tissue, and reflected off boundaries of tissues that exhibit differences in acoustic impedance. PA-US multimodal imaging is a promising tool for early tumor detection and diagnosis
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