Renal Ultrafiltration Changes Induced by Focused US

Fischer, Krisztina; McDannold, Nathan; Zhang, Yongzhi; Kardos, Magdolna; Szabó, András; Szabó, Antal; Reusz, György; Jólesz, Ferenc A.

doi:10.1148/radiol.2532082100

Cited by 18 publications

(14 citation statements)

References 38 publications

(41 reference statements)

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“…There is data demonstrating that disruption of the blood-retinal [182] and blood-spinal cord [183] barriers can be disrupted by FUS, and that the glomerular function in the kidney can be enhanced, presumably through changes in the “blood-urine barrier” [184]. Also, using pressure amplitudes higher than are needed for FUS-induced BBB disruption, one can use microbubble-enhanced sonications for ablation [185], thrombolysis [186], or radiosensitization [187].…”

Section: Going Forwardmentioning

confidence: 99%

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Aryal

Arvanitis

Alexander

et al. 2014

Advanced Drug Delivery Reviews

355

237

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The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.

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Section: Going Forwardmentioning

confidence: 99%

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Aryal

Arvanitis

Alexander

et al. 2014

Advanced Drug Delivery Reviews

355

237

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“…(Arvanitis et al, 2011;Bazan-Peregrino et al, 2012;Bekeredjian et al, 2005;Choi et al, 2007;Hynynen et al, 2001), fragmentation of the microbubble can release encapsulated drugs for targeted release , and convection enhancement can facilitate molecular transport (Marmottant and Hilgenfeldt, 2003;Rifai et al, 2010). Other microbubble-mediated therapies include dissolution of thrombi through mechanical disruption (Datta et al, 2008;Datta et al, 2006), molecular delivery to cells through sonoporation (Deng et al, 2004), enhancement of renal ultrafiltration (Fischer et al, 2009), and blood clotting through hemostasis (Poliachik et al, 2001). Despite advances in the aforementioned techniques, both their biological and cavitation mechanisms remain poorly understood and are in a large part due to limitations in the ability to control and monitor cavitation dynamics generated.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure

Choi

Coussios

2012

The Journal of the Acoustical Society of America

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Ultrasound and microbubble-based therapies utilize cavitation to generate bioeffects, yet cavitation dynamics during individual pulses and across consecutive pulses remain poorly understood under physiologically relevant flow conditions. SonoVue(®) microbubbles were made to flow (fluid velocity: 10-40 mm/s) through a vessel in a tissue-mimicking material and were exposed to ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa, pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number of pulses: 10-250]. Radiated emissions were captured on a linear array, and passive acoustic mapping was used to spatiotemporally resolve cavitation events. At low PRPs, stable cavitation was maintained throughout several pulses, thus generating a steady rise in energy with low upstream spatial bias within the focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3 ± 1.3 ms of a pulse, followed by an energy reduction and high upstream bias. Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced predictable and consistent cavitation dynamics. Above the PRF(crit), energy generated was unpredictable and spatially biased. In conclusion, key parameters in microbubble-seeded flow conditions were matched with specific types, magnitudes, distributions, and durations of cavitation; this may help in understanding empirically observed in vivo phenomena and guide future pulse sequence designs.

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“…F ocused ultrasound (FUS) and microbubble-based drug delivery systems (DDSs) can increase the dose of an agent in a target volume and has potential in applications such as blood-brain barrier (BBB) disruption for the treatment of neurological diseases (1, 2), molecular and viral treatment of tumors (3), gene therapy for treating heart conditions (4), and enhancement of renal ultrafiltration (5). In each method, biologically inert and preformed microbubbles, with a lipid or polymer shell, a stabilized gas core, and a diameter less than 10 μm, are systemically administered and subsequently exposed to noninvasively delivered FUS pulses.…”

mentioning

confidence: 99%

Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles

Choi¹,

Selert²,

Vlachos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

137

141

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Focused ultrasound activation of systemically administered microbubbles is a noninvasive and localized drug delivery method that can increase vascular permeability to large molecular agents. Yet the range of acoustic parameters responsible for drug delivery remains unknown, and, thus, enhancing the delivery characteristics without compromising safety has proven to be difficult. We propose a new basis for ultrasonic pulse design in drug delivery through the blood-brain barrier (BBB) that uses principles of probability of occurrence and spatial distribution of cavitation in contrast to the conventionally applied magnitude of cavitation. The efficacy of using extremely short (2.3 μs) pulses was evaluated in 27 distinct acoustic parameter sets at low peak-rarefactional pressures (0.51 MPa or lower). The left hippocampus and lateral thalamus were noninvasively sonicated after administration of Definity microbubbles. Disruption of the BBB was confirmed by delivery of fluorescently tagged 3-, 10-, or 70-kDa dextrans. Under some conditions, dextrans were distributed homogeneously throughout the targeted region and accumulated at specific hippocampal landmarks and neuronal cells and axons. No histological damage was observed at the most effective parameter set. Our results have broadened the design space of parameters toward a wider safety window that may also increase vascular permeability. The study also uncovered a set of parameters that enhances the dose and distribution of molecular delivery, overcoming standard trade-offs in avoiding associated damage. Given the short pulses used similar to diagnostic ultrasound, new critical parameters were also elucidated to clearly separate therapeutic ultrasound from disruption-free diagnostic ultrasound.F ocused ultrasound (FUS) and microbubble-based drug delivery systems (DDSs) can increase the dose of an agent in a target volume and has potential in applications such as blood-brain barrier (BBB) disruption for the treatment of neurological diseases (1, 2), molecular and viral treatment of tumors (3), gene therapy for treating heart conditions (4), and enhancement of renal ultrafiltration (5). In each method, biologically inert and preformed microbubbles, with a lipid or polymer shell, a stabilized gas core, and a diameter less than 10 μm, are systemically administered and subsequently exposed to noninvasively delivered FUS pulses. Microbubbles within the target volume are "acoustically activated" in a complex range of behaviors known as acoustic cavitation. In stable cavitation, the microbubbles expand and contract with the acoustic pressure rarefaction and compression over several cycles (6). This activity has been associated with a range of bioeffects including displacement of the vessel wall through dilation and contractions (7,8). Large radial bubble expansions may induce inertial cavitation activity, which may lead to bubble collapse due to the inertia of the surrounding media and affect the vascular physiology (8). Each type and magnitude of cavitation activity results...

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Renal Ultrafiltration Changes Induced by Focused US

Abstract: Glomerular ultrafiltration and size selectivity can be temporarily modified with simultaneous application of US and microbubbles. This method could offer new opportunities for treatment of renal disease.

Cited by 18 publications

References 38 publications

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure

Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles

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