Ultrasound microbubble contrast agents: Application to therapy for peripheral vascular disease

Hu, Yingguo; Zhu, Jiaan; Jiang, Ye-ging; Hu, Bing

doi:10.1007/s12325-009-0020-y

Cited by 31 publications

(14 citation statements)

References 54 publications

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“…SonoVue consists of microbubbles containing sulfur hexafluoride in a perfluorocarbon inactive gas (18). SonoVue and CNTs were both clearly echogenic (Fig.…”

Section: Resultsmentioning

confidence: 99%

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Delogu

Vidili

Venturelli

et al. 2012

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

144

102

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Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.

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“…SonoVue consists of microbubbles containing sulfur hexafluoride in a perfluorocarbon inactive gas (18). SonoVue and CNTs were both clearly echogenic (Fig.…”

Section: Resultsmentioning

confidence: 99%

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Delogu

Vidili

Venturelli

et al. 2012

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

144

102

View full text Add to dashboard Cite

show abstract

“…In the arena of disease targeting, the surfaces of microbubbles and nanobubbles have been conjugated with disease-targeting moieties, such as antibodies and peptides, for molecular imaging [19]. Targeted microbubbles with the size around several microns may circulate in blood stream and bind with the over-expressed endothelial biomarkers [20,21]. Targeted nanobubbles or nanoparticles with the size of hundred nanometers or less may penetrate the tumor endothelial barrier and bind with the over-expressed tissue biomarkers [22,23].…”

Section: Discussionmentioning

confidence: 99%

Targeted microbubbles for ultrasound mediated gene transfection and apoptosis induction in ovarian cancer cells

Chang

Guo

Sun

et al. 2013

Ultrasonics Sonochemistry

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Ultrasound-targeted microbubble destruction (UTMD) technique can be potentially used for non-viral delivery of gene therapy. Targeting wild-type p53 (wtp53) tumor suppressor gene may provide a clinically promising treatment for patients with ovarian cancer. However, UTMD mediated gene therapy typically uses non-targeted microbubbles with suboptimal gene transfection efficiency. We synthesized a targeted microbubble agent for UTMD mediated wtp53 gene therapy in ovarian cancer cells. Lipid micro-bubbles were conjugated with a Luteinizing Hormone–Releasing Hormone analog (LHRHa) via an avidin– biotin linkage to target the ovarian cancer A2780/DDP cells that express LHRH receptors. The microbubbles were mixed with the pEGFP-N1-wtp53 plasmid. Upon exposure to 1 MHz pulsed ultrasound beam (0.5 W/cm2) for 30 s, the wtp53 gene was transfected to the ovarian cancer cells. The transfection efficiency was (43.90 ± 6.19)%. The expression of wtp53 mRNA after transfection was (97.08 ± 12.18)%. The cell apoptosis rate after gene therapy was (39.67 ± 5.95)%. In comparison with the other treatment groups, ultrasound mediation of targeted microbubbles yielded higher transfection efficiency and higher cell apoptosis rate (p < 0.05). Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles will enhance the gene transfection efficiency in ovarian cancer cells.

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“…CEUS thus could be employed in other type of experimental SCI, such as compression, chronic SCI and even in clinical applications, which includes traumatic, iatrogenic SCI or spinal cord tumors during operation. Potential clinical application of contrast agents was shown in not only diagnostic but also therapeutic aspects [25]. Using CEUS combined with neuroprotective or therapeutic genes or drugs could be a new strategy for SCI.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury

Huang

Chen

et al. 2017

Oncotarget

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This study tried to quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute spinal cord perfusion after injury was detected by CEUS, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were obtained by autotracking contrast quantification (ACQ) software in the epicenter and adjacent regions of injury, respectively. Neurological and histological examinations were performed to confirm the severity of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord contusion, the injured spinal cord was hyperechoic on US, and intramedullary vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS hypoperfusion were found in the epicenter of injury, while hyperperfusion in its adjacent region. Quantitative analysis showed that peak intensity (PI) decreased in epicenters of injury but significantly increased in adjacent regions at all time points (p < 0.05). Functional evaluation demonstrated significant deterioration compared to pre-contusion (p < 0.05). Quantitative analysis with CEUS is a promising method for monitoring perfusion changes of spinal cord injury in overall views and real-time.

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Ultrasound microbubble contrast agents: Application to therapy for peripheral vascular disease

Cited by 31 publications

References 54 publications

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Targeted microbubbles for ultrasound mediated gene transfection and apoptosis induction in ovarian cancer cells

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury

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