Lipid-Coated Ultrastable Microbubbles as a Contrast Agent in Neurosonography

Rh, Simon; Sy, Ho; D'Arrigo, Joseph; Wakefield, Andrew E.; Sg, Hamilton

doi:10.1097/00004424-199012000-00005

Cited by 36 publications

(15 citation statements)

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“…LCMs were prepared by admixing 25 mg of a powdered mixture of selected lipid surfactants with 100 ml of isotonic sodium chloride solution. The proprietary surfactant mixture used contains mostly glycerides and cholesterol esters [9,13]. Following removal of solid particulates, the microbubble suspension has a concentration of 520,000 to 550,000 microbubbles/ml in isotonic saline solution.…”

Section: Methodsmentioning

confidence: 99%

“…Following removal of solid particulates, the microbubble suspension has a concentration of 520,000 to 550,000 microbubbles/ml in isotonic saline solution. This microbubble suspension, Filmix, is stable in vitro for more than 6 months and in vivo for more than 24 hours [13].…”

Section: Methodsmentioning

confidence: 99%

“…These bubbles have the important quality of relative uniformity of size: The bubbles can be manufactured within a tight range of diameters; that is, more than 99% of the population has a diameter of less than 4.5 /J.m and all are less than 6 /J.m [ 11 ]. Furthermore, this liquid microbubble suspension (Filmix, CAY-CON, Farmington, CT; currently for laboratory animal use only) is stable in vitro for more than 6 months [12] and has an in vivo half-life of20 hours or more [13]. The uniformly small size of these synthetic microbubbles, and their extreme longevity in vivo, suggested that LCMs might be suitable for improving sonographic imaging of brain tumors.…”

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confidence: 99%

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Lipid‐Coated Uniform Microbubbles for Earlier Sonographic Detection of Brain Tumors

D'Arrigo

Simon²,

Ng³

1991

Journal of Neuroimaging

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Rapid technological improvements have fostered the continued clinical development of intraoperative neurosonology, despite the fact that no suitable contrast media have been available for ultrasound studies. Because they can be made of uniform size (99% are less than 4.5 mum in diameter) and are thought to cross disruptions in the tumor vessels, artificial lipid-coated microbubbles can fill this gap. Furthermore, these microbubbles are stable in vitro for at least 6 months, with an in vivo halflife of 20 hours or more. This study demonstrated that lipid-coated microbubbles injected intravascularly can intensify echoes from rat brain gliomas. Specifically, when this standardized microbubble contrast agent was injected intravenously daily in rats, the time to visual ultrasonic detection of developing brain tumors (C-6 gliomas) was 4.09 days (n = 11) after tumor inoculation, versus 6.67 days (n = 9) to detection without microbubble injection (Z = -3.71, p = 0.0004).

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Lipid‐Coated Uniform Microbubbles for Earlier Sonographic Detection of Brain Tumors

D'Arrigo

Simon²,

Ng³

1991

Journal of Neuroimaging

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“…Stabilization is achieved by encapsulating gas within shells comprised of protein [1, 2], protein plus sugar [3, 4] lipids [5–7], polymers [8, 9], or combinations of these materials. Stability is enhanced by producing MBs using heavier than air gasses [10], with fluorocarbon gasses such as octafluoropentane and n-decafluorobutane amongst those used most commonly.…”

Section: Introductionmentioning

confidence: 99%

Production of uniformly sized serum albumin and dextrose microbubbles

Borrelli

O’Brien

Bernock

et al. 2012

Ultrasonics Sonochemistry

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Uniformly-sized preparations with average microbubble (MB) diameters from 1 µm to 7 µm were produced reliably by sonicating decafluorobutane-saturated solutions of serum albumin and dextrose. Detailed protocols for producing and size-separating the MBs are presented, along with the effects that changing each production parameter (serum albumin concentration, sonication power, sonication time, etc.) had on MB size distribution and acoustic stability. These protocols can be used to produce MBs for experimental applications or serve as templates for developing new protocols that yield MBs with physical and acoustic properties better suited to specific applications. Size stability and ultrasonic performance quality control tests were developed to assure that successive MB preparations perform identically and to distinguish the physical and acoustic properties of identically sized MBs produced with different serum albumin-dextrose formulations and sonication parameters. MBs can be stored at 5°C for protracted periods (2 weeks to one year depending on formulation).

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“…Such MBs consist of a gaseous core stabilized by a shell comprised of lipids, proteins or polymers [1][2][3][4]. Currently, one intensely researched MB application is that of targeted vehicles.…”

Section: Introductionmentioning

confidence: 99%

Production approaches for microbubbles loaded with nanoparticles

Gauthier

Yin

Cheng

et al. 2013

2013 IEEE International Ultrasonics Symposium (IUS)

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A new production approach to make microbubbles (MBs) loaded with nanoparticles (NPs) (Protocol 1) was evaluated and compared with the more common procedure that was based on covalent linking of functionalized NPs (f-NPs) to MBs (Protocol 2). MBs were produced by sonicating bovine serum albumin (BSA) and dextrose solution. NPs consisted of Cy5-PLA conjugate. Protocol 1 involved incorporating the NPs into the BSA-dextrose solution before the sonication step. Protocol 2 involved mixing MBs and f-NPs, resulting from mixing the initial Cy5-PLA and PLA-PEG-COOH conjugates. For each protocol, unloaded MBs were produced as a reference. Two parameters were quantitatively analyzed using both analysis of variance (ANOVA) and t-test: diameter was estimated using a circle detection routine based on the Hough transform while the number density was estimated using a hemocytometer. Both parameters were evaluated for the NP-loaded MBs and unloaded MBs at 5 time points (2 hours to 5 days post MB fabrication). Protocols 1 and 2 resulted in significantly different loaded MBs: the more common approach of linking functionalized NPs to the MB surface (Protocol 2) was much more efficient than directly embedding NPs in the MB shell.

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Lipid-Coated Ultrastable Microbubbles as a Contrast Agent in Neurosonography

Cited by 36 publications

References 0 publications

Lipid‐Coated Uniform Microbubbles for Earlier Sonographic Detection of Brain Tumors

Lipid‐Coated Uniform Microbubbles for Earlier Sonographic Detection of Brain Tumors

Production of uniformly sized serum albumin and dextrose microbubbles

Production approaches for microbubbles loaded with nanoparticles

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