Monodisperse versus Polydisperse Ultrasound Contrast Agents: In Vivo Sensitivity and safety in Rat and Pig

Helbert, Alexandre; Gaud, Emmanuel; Segers, Tim; Botteron, Catherine; Frinking, Peter; Jeannot, Victor

doi:10.1016/j.ultrasmedbio.2020.07.031

Cited by 38 publications

(36 citation statements)

References 87 publications

(97 reference statements)

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“…Currently, commercial, clinically approved microbubbles are polydisperse. However, recent papers show that monodisperse microbubbles have a more uniform acoustic response and an increased imaging sensitivity ( Segers et al, 2018 ; Helbert et al, 2020 ), which will also improve the reproducibility and controllability of USMB therapy.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

et al. 2021

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Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.

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Section: Discussionmentioning

confidence: 99%

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

et al. 2021

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“…This suboptimal match between ultrasound spectral content and bubble size distribution motivates the development and use of monodisperse microbubbles. The increased sensitivity of monodisperse bubbles with respect to polydisperse ones has first been demonstrated for molecular imaging using low bubble concentrations [7] and later for contrast imaging in vitro [8] and in vivo [9]. In particular, Segers et al [8] report sensitivity increase by two and three orders of magnitude for the fundamental and second harmonic, respectively.…”

Section: Introductionmentioning

confidence: 99%

Time-resolved velocity and pressure field quantification in a flow-focusing device for ultrafast microbubble production

et al. 2021

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Flow-focusing devices have gained great interest in the past decade, due to their capability to produce monodisperse microbubbles for diagnostic and therapeutic medical ultrasound applications. However, up-scaling production to industrial scale requires a paradigm shift from single chip operation to highly parallelized systems. Parallelization gives rise to fluidic interactions between nozzles that, in turn, may lead to a decreased monodispersity. Here we study the velocity and pressure field fluctuations in a single flow-focusing nozzle during bubble production. We experimentally quantify the velocity field inside the nozzle at 100 ns time resolution, and a numerical model provides insight into both the oscillatory velocity and pressure fields. Our results demonstrate that, at the length scale of the flow-focusing channel, the velocity oscillations propagate at fluid dynamical timescale (order of μs) whereas the dominant pressure oscillations are linked to the bubble pinch-off and propagate at a much faster timescale (order of ns).

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“…Since these monodisperse microbubbles can guarantee a more consistent microbubble behaviour they could make cavitation-based therapies much more predictable and efficient. Helbert, et al showed that the use of monodisperse microbubbles in rats and guinea pigs resulted in an imaging sensitivity (mean echo power per injected bubble) that was at least 10 and 15 times higher in rats and pigs, respectively, compared to the polydisperse control [391]. These findings imply that the use of monodisperse microbubbles is promising for diagnostic but also therapeutic applications.…”

Section: Monodisperse Microbubblesmentioning

confidence: 99%

Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

Deprez

Lajoinie

Engelen

et al. 2021

Advanced Drug Delivery Reviews

128

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Monodisperse versus Polydisperse Ultrasound Contrast Agents: In Vivo Sensitivity and safety in Rat and Pig

Cited by 38 publications

References 87 publications

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

Time-resolved velocity and pressure field quantification in a flow-focusing device for ultrafast microbubble production

Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

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