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Miniaturized therapeutic systems for ultrasound-modulated drug delivery to the central and peripheral nervous system

Zhu, P. (author), Simón Grau, I. (author), Kokalari, I. (author), Kohane, Daniel S. (author), Rwei, A.Y. (author)

Ultrasound is a promising technology to address challenges in drug delivery, including limited drug penetration across physiological barriers and ineffective targeting. Here we provide an overview of the significant advances made in recent years in overcoming technical and pharmacological barriers using ultrasound-assisted drug delivery to...

review 2024

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Are monodisperse phospholipid-coated microbubbles “mono-acoustic?”

Spiekhout, Sander (author), van Elburg, Benjamin (author), Voorneveld, J.D. (author), de Jong, N. (author), Versluis, Michel (author), Bosch, Johannes G. (author), Segers, Tim (author)

Phospholipid-coated microbubbles with a uniform acoustic response are a promising avenue for functional ultrasound sensing. A uniform acoustic response requires both a monodisperse size distribution and uniform viscoelastic shell properties. Monodisperse microbubbles can be produced in a microfluidic flow focusing device. Here, we investigate...

journal article 2024

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Ultrasonic Characterization of Ibidi μ-Slide I Luer Channel Slides for Studies With Ultrasound Contrast Agents

Zangabad, Reza Pakdaman (author), Li, H. (author), Kouijzer, Joop J.P. (author), Langeveld, Simone A.G. (author), Beekers, Ines (author), Verweij, M.A. (author), de Jong, N. (author), Kooiman, Klazina (author)

Understanding and controlling the ultrasound contrast agent (UCA)'s response to an applied ultrasound pressure field are crucial when investigating ultrasound imaging sequences and therapeutic applications. The magnitude and frequency of the applied ultrasonic pressure waves affect the oscillatory response of the UCA. Therefore, it is...

journal article 2023

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Coupling Two Ultra-high-Speed Cameras to Elucidate Ultrasound Contrast-Mediated Imaging and Therapy

Li, H. (author), Li, X. (author), Collado Lara, G. (author), Lattwein, K.R. (author), Mastik, Frits (author), Beurskens, Robert (author), van der Steen, A.F.W. (author), Verweij, M.A. (author), de Jong, N. (author), Kooiman, Klazina (author)

Ultrasound contrast-mediated medical imaging and therapy both rely on the dynamics of micron- and nanometer-sized ultrasound cavitation nuclei, such as phospholipid-coated microbubbles and phase-change droplets. Ultrasound cavitation nuclei respond non-linearly to ultrasound on a nanosecond time scale that necessitates the use of ultra-high...

journal article 2023

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Higher Order Singular Value Decomposition Filter for Contrast Echocardiography

Wahyulaksana, G. (author), Wei, Luxi (author), Voorneveld, J.D. (author), Hekkert, Maaike Te Lintel (author), Strachinaru, Mihai (author), Duncker, Dirk J. (author), de Jong, N. (author), van der Steen, A.F.W. (author), Vos, H.J. (author)

Assessing the coronary circulation with contrast-enhanced echocardiography has high clinical relevance. However, it is not being routinely performed in clinical practice because the current clinical tools generally cannot provide adequate image quality. The contrast agent's visibility in the myocardium is generally poor, impaired by motion...

journal article 2023

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Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide

Lattwein, K.R. (author), Beekers, Inés (author), Kouijzer, Joop J.P. (author), Leon-Grooters, Mariël (author), Langeveld, Simone A.G. (author), van Rooij, Tom (author), van der Steen, A.F.W. (author), de Jong, N. (author), van Wamel, Willem J.B. (author), Kooiman, Klazina (author)

Bacteria encased in a biofilm poses significant challenges to successful treatment, since both the immune system and antibiotics are ineffective. Sonobactericide, which uses ultrasound and microbubbles, is a potential new strategy for increasing antimicrobial effectiveness or directly killing bacteria. Several studies suggest that...

journal article 2022

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Internalization of targeted microbubbles by endothelial cells and drug delivery by pores and tunnels

Beekers, Inés (author), Langeveld, Simone A.G. (author), Meijlink, Bram (author), van der Steen, A.F.W. (author), de Jong, N. (author), Verweij, M.D. (author), Kooiman, Klazina (author)

Ultrasound insonification of microbubbles can locally enhance drug delivery by increasing the cell membrane permeability. To aid development of a safe and effective therapeutic microbubble, more insight into the microbubble-cell interaction is needed. In this in vitro study we aimed to investigate the initial 3D morphology of the endothelial...

journal article 2022

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Theranostic Microbubbles with Homogeneous Ligand Distribution for Higher Binding Efficacy

Langeveld, Simone A.G. (author), Meijlink, Bram (author), Beekers, Inés (author), Olthof, Mark (author), van der Steen, A.F.W. (author), de Jong, N. (author), Kooiman, Klazina (author)

Phospholipid-coated targeted microbubbles are used for ultrasound molecular imaging and locally enhanced drug delivery, with the binding efficacy being an important trait. The use of organic solvent in microbubble production makes the difference between a heterogeneous or homogeneous ligand distribution. This study demonstrates the effect of...

journal article 2022

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The impact of lipid handling and phase distribution on the acoustic behavior of microbubbles

Langeveld, Simone A.G. (author), Beekers, Inés (author), Collado Lara, G. (author), van der Steen, A.F.W. (author), de Jong, N. (author), Kooiman, Klazina (author)

Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the...

journal article 2021

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Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms

Kouijzer, Joop J.P. (author), Lattwein, Kirby R. (author), Beekers, Inés (author), Langeveld, Simone A.G. (author), Leon-Grooters, Mariël (author), Strub, Jean Marc (author), Oliva, Estefania (author), de Jong, N. (author), van der Steen, A.F.W. (author)

Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as...

journal article 2021

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

de Maar, Josanne S. (author), Rousou, Charis (author), van Elburg, Benjamin (author), Vos, H.J. (author), Lajoinie, Guillaume P.R. (author), Bos, Clemens (author), Moonen, Chrit T.W. (author), Deckers, Roel (author)

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...

journal article 2021

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High Frame Rate Volumetric Imaging of Microbubbles Using a Sparse Array and Spatial Coherence Beamforming

Wei, Luxi (author), Wahyulaksana, G. (author), Meijlink, Bram (author), Ramalli, Alessandro (author), Noothout, E.C. (author), Verweij, M.D. (author), van der Steen, A.F.W. (author), de Jong, N. (author), Vos, H.J. (author)

Volumetric ultrasound imaging of blood flow with microbubbles enables a more complete visualization of the microvasculature. Sparse arrays are ideal candidates to perform volumetric imaging at reduced manufacturing complexity and cable count. However, due to the small number of transducer elements, sparse arrays often come with high clutter...

journal article 2021

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Opening of endothelial cell–cell contacts due to sonoporation

Beekers, D.I. (author), Vegter, Merel (author), Lattwein, Kirby R. (author), Mastik, Frits (author), Beurskens, Robert (author), van der Steen, A.F.W. (author), de Jong, N. (author), Verweij, M.D. (author), Kooiman, Klazina (author)

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell...

journal article 2020

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Acoustic trapping of microbubbles in complex environments and controlled payload release

Baresch, Diego (author), Garbin, V. (author)

Contactless manipulation of microparticles using acoustic waves holds promise for applications ranging from cell sorting to threedimensional (3D) printing and tissue engineering. However, the unique potential of acoustic trapping to be applied in biomedical settings remains largely untapped. In particular, the main advantage of acoustic...

journal article 2020

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High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles

Beekers, D.I. (author), Mastik, Frits (author), Beurskens, Robert (author), Tang, Phoei Ying (author), Vegter, Merel (author), van der Steen, A.F.W. (author), de Jong, N. (author), Verweij, M.D. (author), Kooiman, Klazina (author)

Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Ca_i ²⁺) is a key cellular regulator, unraveling the Ca_i ²⁺ fluctuations caused by an oscillating microbubble provides crucial...

journal article 2020

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Combined Confocal Microscope and Brandaris 128 Ultra-High-Speed Camera

Beekers, D.I. (author), Lattwein, Kirby R. (author), Kouijzer, Joop J.P. (author), Langeveld, Simone A.G. (author), Vegter, M. (author), Beurskens, Robert (author), Mastik, F. (author), Verduyn Lunel, Rogier (author), van der Steen, A.F.W. (author), de Jong, N. (author)

Controlling microbubble-mediated drug delivery requires the underlying biological and physical mechanisms to be unraveled. To image both microbubble oscillation upon ultrasound insonification and the resulting cellular response, we developed an optical imaging system that can achieve the necessary nanosecond temporal and nanometer spatial...

journal article 2019

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Local microbubble concentration by defocused volumetric shadowgraphy with a single camera

Cornel, W.A. (author), Westerweel, J. (author), Poelma, C. (author)

The challenge presented in this research is to determine the local volumetric bubble concentration (or void fraction) in the center of a microbubble cloud with limited optical access and without disturbing the flow. By applying defocused volumetric shadowgraphy to an aerated water column we were able to measure the characteristics of single...

conference paper 2018

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Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

van Rooij, Tom (author), Beekers, D.I. (author), Lattwein, Kirby R. (author), van der Steen, A.F.W. (author), de Jong, N. (author), Kooiman, Klazina (author)

One of the main challenges for ultrasound molecular imaging is acoustically distinguishing nonbound microbubbles from those bound to their molecular target. In this in vitro study, we compared two types of in-house produced targeted lipid-coated microbubbles, either consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, C16:0 (DPPC) or 1...

journal article 2017

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Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and in Vivo Evaluation

Daeichin, Verya (author), van Rooij, Tom (author), Skachkov, Ilya (author), Ergin, Bulent (author), Specht, Patricia A.C. (author), Lima, Alexandre (author), Ince, Can (author), Bosch, Johan G. (author), van der Steen, A.F.W. (author), de Jong, N. (author), Kooiman, Klazina (author)

Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is...

journal article 2017

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Laser-driven resonance of dye-doped oil-coated microbubbles: Experimental study

Lajoinie, Guillaume (author), Lee, Jeong Yu (author), Owen, Joshua (author), Kruizinga, P. (author), de Jong, N. (author), Van Soest, Gijs (author), Stride, Eleanor (author), Versluis, Michel (author)

Photoacoustic (PA) imaging offers several attractive features as a biomedical imaging modality, including excellent spatial resolution and functional information such as tissue oxygenation. A key limitation, however, is the contrast to noise ratio that can be obtained from tissue depths greater than 1-2 mm. Microbubbles coated with an...

journal article 2017