Theoretical and Experimental Characterisation of Magnetic Microbubbles

Mulvana, Helen; Eckersley, Robert J.; Tang, Meng‐Xing; Pankhurst, Quentin A.; Stride, Eleanor

doi:10.1016/j.ultrasmedbio.2012.01.027

Cited by 32 publications

(27 citation statements)

References 37 publications

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“…The microbubble fabrication protocol enabled the size distribution and concentration of the microbubbles to be kept consistent throughout the experiments. The quantity of magnetic nanoparticles encapsulated within each bubble, however, was much more difficult to control; and this would have affected both their ability to be retained by a magnetic field and their acoustic response [ 39 ]. It was clear when observing a population of magnetic microbubbles exposed to a magnetic field under an optical microscope that there was considerable variation in response (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Magnetic targeting of microbubbles against physiologically relevant flow conditions

et al. 2015

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The localization of microbubbles to a treatment site has been shown to be essential to their effectiveness in therapeutic applications such as targeted drug delivery and gene therapy. A variety of different strategies for achieving localization has been investigated, including biochemical targeting, acoustic radiation force, and the incorporation of superparamagnetic nanoparticles into microbubbles to enable their manipulation using an externally applied magnetic field. The third of these strategies has the advantage of concentrating microbubbles in a target region without exposing them to ultrasound, and can be used in conjunction with biochemical targeting to achieve greater specificity. Magnetic microbubbles have been shown to be effective for therapeutic delivery in vitro and in vivo. Whether this technique can be successfully applied in humans however remains an open question. The aim of this study was to determine the range of flow conditions under which targeting could be achieved. In vitro results indicate that magnetic microbubbles can be retained using clinically acceptable magnetic fields, for both the high shear rates (approx. 104 s−1) found in human arterioles and capillaries, and the high flow rates (approx. 3.5 ml s−1) of human arteries. The potential for human in vivo microbubble retention was further demonstrated using a perfused porcine liver model.

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Section: Discussionmentioning

confidence: 99%

Magnetic targeting of microbubbles against physiologically relevant flow conditions

et al. 2015

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“…However, the measure is equally relevant to therapeutic ultrasound in which echogenicity and treatment depth are of similar importance. Several groups have used this approach to make comparisons across microbubble formulations [26], [27]; however, it is not clear why it has not been more widely adopted.…”

Section: B Methods Of Standardizing Results For Comparison Across Rementioning

confidence: 99%

Characterization of Contrast Agent Microbubbles for Ultrasound Imaging and Therapy Research

Mulvana

Browning

Luan

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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The high efficiency with which gas microbubbles can scatter ultrasound compared with the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years, their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound and in particular these recent developments have amplified the need to characterize and fully understand microbubble behavior. The aim in doing so is to more fully exploit their utility for both diagnostic imaging and potential future therapeutic applications. This paper presents the key characteristics of microbubbles that determine their efficacy in diagnostic and therapeutic applications and the corresponding techniques for their measurement. In each case, we have presented information regarding the methods available and their respective strengths and limitations, with the aim of presenting information relevant to the selection of appropriate characterization methods. First, we examine methods for determining the physical properties of microbubble suspensions and then techniques for acoustic characterization of both suspensions and single microbubbles. The next section covers characterization of microbubbles as therapeutic agents, including as drug carriers for which detailed understanding of their surface characteristics and drug loading capacity is required. Finally, we discuss the attempts that have been made to allow comparison across the methods employed by various groups to characterize and describe their microbubble suspensions and promote wider discussion and comparison of microbubble behavior.

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“…This work proposes the use of microbubbles (MB) labelled with SPIONS (SPION-MBs) in conjunction with MMUS to generate larger tissue displacements capable of improving sensitivity of the technique which we refer to as contrast enhanced magneto-motive ultrasound (CE-MMUS). SPION-MBs have previously been developed and demonstrated for use in targeted drug delivery [5] and targeted imaging, as they can be guided to a desired location with the use of a permanent magnet [6], and this background magnetic field has been found to enhance MB cavitation amplitudes [7,8]. MB have already been demonstrated as an effective contrast agent for the lymph system via intra-dermal injection [9].…”

Section: Introductionmentioning

confidence: 99%

Contrast-enhanced magnetomotive ultrasound imaging (CE-MMUS) for colorectal cancer staging: Assessment of sensitivity and resolution to detect alterations in tissue stiffness

Sjöstrand

Evertsson

Thring

et al. 2019

2019 IEEE International Ultrasonics Symposium (IUS)

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A key challenge in the treatment of colorectal cancer is identification of the sentinel draining lymph node. Magnetomotive ultrasound, MMUS, has identified lymph nodes in rat models: superparamagnetic iron oxide nanoparticles (SPIONs) accumulated in the lymph are forced to oscillate by an external magnetic field; the resulting axial displacement is recovered allowing structure delineation with potential to indicate alterations in tissue stiffness, but it is limited by small vibration amplitudes. We propose CE-MMUS using SPION loaded microbubbles (SPION-MBs) to enhance sensitivity, reduce toxicity, and offer additional diagnostic or perfusion information. Laser doppler vibrometry measurements was performed on SPION containing tissue mimicking material during magnetic excitation. These measurements show a vibration amplitude of 279 ± 113 µm in a material with Young's modulus of 24.3 ± 2.8 kPa, while the displacements were substantially larger, 426 ± 9 µm, in the softer material, with a Young's modulus of 9.6 ± 0.8 kPa. Magnetic field measurement data was used to calibrate finite element modelling of both MMUS and CE-MMUS. SPION-MBs were shown to be capable of inducing larger tissue displacements under a given magnetic field than SPIONs alone, leading to axial displacements of up to 2.3x larger. A doubling in tissue stiffness (as may occur in cancer) reduces the vibration amplitude. Thus, there is potential for CE-MMUS to achieve improved stiffness sensitivity. Our aim is to define the potential contribution of CE-MMUS in colorectal cancer diagnosis and surgical guidance.

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Theoretical and Experimental Characterisation of Magnetic Microbubbles

Cited by 32 publications

References 37 publications

Magnetic targeting of microbubbles against physiologically relevant flow conditions

Magnetic targeting of microbubbles against physiologically relevant flow conditions

Characterization of Contrast Agent Microbubbles for Ultrasound Imaging and Therapy Research

Contrast-enhanced magnetomotive ultrasound imaging (CE-MMUS) for colorectal cancer staging: Assessment of sensitivity and resolution to detect alterations in tissue stiffness

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