Seeing the Invisible—Ultrasound Molecular Imaging

Kosareva, Alexandra; Abou‐Elkacem, Lotfi; Chowdhury, Sayan Mullick; Lindner, Jonathan R.; Kaufmann, Beat A.

doi:10.1016/j.ultrasmedbio.2019.11.007

Cited by 38 publications

(28 citation statements)

References 151 publications

(213 reference statements)

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“…Ultrasound imaging can now use microbubbles and other contrast agents coated with specific targeting ligand molecules that bind selectively to the site of interest 14 . Thrombus‐targeted imaging technologies use ligands that are specific either for fibrin, 15 activated platelets expressing the integrin αIIbβ3, 16 or prothrombotic components such as factor XIIIa, 17 tissue factor, von Willebrand factor, or exposed collagen 14 . Noninvasive molecular imaging techniques targeting thrombus components have been used both in disease‐state animal models and in clinical applications.…”

Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

“…14 Thrombus-targeted imaging technologies use ligands that are specific either for fibrin, 15 activated platelets expressing the integrin αIIbβ3, 16 or prothrombotic components such as factor XIIIa, 17 tissue factor, von Willebrand factor, or exposed collagen. 14 To visualize flowing blood, blood cells, and thrombi, intravital molecular-based fluorescence imaging has been widely used in animal models of thrombosis. 19,20 Various blood components are labeled with different dyes and fluorescent antibodies followed by intravital epifluorescence or fluorescent confocal microscopy that allows time-lapse imaging to track formation and maturation of a thrombus.…”

Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

“…Traditional imaging techniques such as magnetic resonance imaging have also been improved by application of molecular imaging, involving the use of magnetic nanoparticles functionalized with highly specific vector molecules. Ultrasound imaging can now use microbubbles and other contrast agents coated with specific targeting ligand molecules that bind selectively to the site of interest 14 . Thrombus‐targeted imaging technologies use ligands that are specific either for fibrin, 15 activated platelets expressing the integrin αIIbβ3, 16 or prothrombotic components such as factor XIIIa, 17 tissue factor, von Willebrand factor, or exposed collagen 14 .…”

Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

See 2 more Smart Citations

Visualizing thrombosis to improve thrombus resolution

Weisel

Litvinov

2021

Research and Practice in Thrombosis and Haemostasis

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The severity, course, and outcomes of thrombosis are determined mainly by the size and location of the thrombus, but studying thrombus structure and composition has been an important but challenging task. The substantial progress in determination of thrombus morphology has become possible due to new intravital imaging methodologies in combination with mechanical thrombectomy, which allows extraction of a fresh thrombus from a patient followed by microscopy. Thrombi have been found to contain various structural forms of fibrin along with platelet aggregates, leukocytes, and red blood cells, many of which acquire a polyhedral shape (polyhedrocytes) as a result of intravital platelet‐driven contraction. The relative volume fractions of thrombus components and their structural forms vary substantially, depending on the clinical and pathogenic characteristics. This review summarizes recent research that describes quantitative and qualitative morphologic characteristics of arterial and venous thrombi that are relevant for the pathogenesis, prophylaxis, diagnosis, and treatment of thrombosis.

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Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

Section: Visualizing Thrombi In Vivo and Ex Vivomentioning

confidence: 99%

See 1 more Smart Citation

Visualizing thrombosis to improve thrombus resolution

Weisel

Litvinov

2021

Research and Practice in Thrombosis and Haemostasis

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“… 12 As contrast-imaging agents, in addition to anatomic imaging, NBs are used in imaging phenotypes at a cellular level, contributing to disease detection and assessment. 13 As delivery systems, NBs, by delivering chemical agents, genes and protein materials in a targeted manner, 14 , 15 enhance the treatment effect and prevent side effects. Their nanometer size facilitates their movement through the capillary endothelial cell gap to the tumor, thus causing enhanced permeability and retention (EPR) effect.…”

Section: Introductionmentioning

confidence: 99%

Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice

Tan¹,

Yang²,

Ma³

et al. 2021

IJN

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Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6. Materials and Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs. Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/ Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses. Conclusion:In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasoundmediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.

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“…Microbubbles are small gas bubbles (diameter 1-10 µm) that are clinically used as ultrasound contrast agents for non-invasive diagnostic imaging of blood perfusion [1]. Targeted microbubbles are employed for molecular imaging of inflammation, tumors, and cardiovascular disease [2]. Other types of microbubbles are being developed specifically for drug delivery [3].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles

et al. 2021

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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 acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.

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Seeing the Invisible—Ultrasound Molecular Imaging

Cited by 38 publications

References 151 publications

Visualizing thrombosis to improve thrombus resolution

Visualizing thrombosis to improve thrombus resolution

Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice

The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles

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