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Objective: Contrast-enhanced ultrasound (CEUS) presents distinct advantages in diagnostic echography. Utilizing microbubbles (MBs) as conventional contrast agents enhances vascular visualization and organ perfusion, facilitating real-time, non-invasive procedures. There is a current tendency to replace traditional polydisperse MBs with novel monodisperse formulations in an attempt to optimize contrast enhancement and guarantee consistent behavior and reliable imaging outcomes. This study investigates the contrast enhancement achieved using various-sized monodisperse MBs and their influence on non-linear imaging artifacts observed in traditional CEUS.
Methods: To explore the differences between monodisperse and polydisperse populations without excessive experimentation, numerical simulations are employed for delivering precise, objective and expeditious results. The iterative non-linear contrast source (INCS) method has previously demonstrated efficacy when simulating ultrasound propagation in large populations in which each bubble has individual properties and several orders of multiple scattering are significant. Therefore, this method is employed to realistically simulate both monodisperse and polydisperse MBs.
Results: Our findings in CEUS imaging indicate that scattering from resonant monodisperse MBs is 11.8 dB stronger than scattering from polydisperse MBs. Furthermore, the amplitude of non-linear imaging artifacts downstream of the monodisperse population is 19.4 dB stronger compared with polydisperse suspension.
Conclusion: Investigating the impact of multiple scattering on polydisperse populations compared with various monodisperse suspensions has revealed that monodisperse MBs are more effective contrast agents, especially when at resonance. Despite the strong signal-to-noise ratio of monodisperse populations, imaging artifacts caused by non-linear wave propagation are also enhanced, resulting in further mis-classification of MBs as tissue.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2024.11.002 | DOI Listing |
Sci Rep
April 2025
Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Ultrasound (US)-mediated delivery is considered relatively safe and achieves tissue-specific targeting by simply adjusting the application site of the physical energy. Moreover, combining US with micro- or nanobubbles (MBs or NBs), which serve as US contrast agents, enhances the delivery of drugs, genes, and nucleic acids which also functioning as a tool for US. The performance of US-responsive MBs and NBs, including their therapeutic outcomes, is influenced by the bubble manufacturing methods.
View Article and Find Full Text PDFUltrason Sonochem
January 2025
Toronto Metropolitan University, 350 Victoria Street, Toronto, Ontario, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital and Toronto Metropolitan University, 209 Victoria St, Toronto, Ontario, Canada.
This study presents an experimental investigation of the influence of MB concentration on the resonance frequency of lipid-coated microbubbles (MBs). Expanding on theoretical models and numerical simulations from previous research, this work experimentally investigates the effect of MB size on the rate of resonance frequency increase with concentration, a phenomenon observed across MBs with two different lipid compositions: propylene glycol (PG) and propylene glycol and glycerol (PGG). Employing a custom-designed ultrasound attenuation measurement setup, we measured the frequency-dependent attenuation of MBs, isolating MBs based on size to generate distinct monodisperse sub-populations for analysis.
View Article and Find Full Text PDFUltrasound Med Biol
March 2025
Section of Medical Imaging, Department of Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands; Section of Biomedical Engineering, Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: m.d.verweij@
Objective: Contrast-enhanced ultrasound (CEUS) presents distinct advantages in diagnostic echography. Utilizing microbubbles (MBs) as conventional contrast agents enhances vascular visualization and organ perfusion, facilitating real-time, non-invasive procedures. There is a current tendency to replace traditional polydisperse MBs with novel monodisperse formulations in an attempt to optimize contrast enhancement and guarantee consistent behavior and reliable imaging outcomes.
View Article and Find Full Text PDFUltrasound Med Biol
March 2024
Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, Dallas, TX, USA; Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: Caroline.Lux@ut
Objective: We have previously determined that direct formulation of a phospholipid-based perfluorobutane (PFB) emulsion using high-pressure homogenization produces monodispersed PFB nanodroplets (NDs) with relatively few non-PFB-filled NDs. In this article, we describe a simpler strategy to reproducibly formulate highly concentrated superheated PFB NDs using a probe sonicator, a more widely available tool.
Methods: Similar to the homogenization technique, sonicating at low power a solution of phospholipids with condensed PFB at -10°C consistently yields NDs with an encapsulation efficiency close to 100% and very few non-PFB-filled particles.
Langmuir
December 2023
Department of Physics, Toronto Metropolitan University, Toronto M5B 2K3, Ontario, Canada.
The acoustic response of microbubbles (MBs) depends on their resonance frequency, which is dependent on the MB size and shell properties. Monodisperse MBs with tunable shell properties are thus desirable for optimizing and controlling the MB behavior in acoustics applications. By utilizing a novel microfluidic method that uses lipid concentration to control MB shrinkage, we generated monodisperse MBs of four different initial diameters at three lipid concentrations (5.
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