Gas vesicles are a unique class of gas-filled protein nanostructures which are commonly found in cyanobacteria and Halobacterium. The gas vesicles may scatter sound waves and generate harmonic signals, which enabled them to have the potential to become a novel ultrasound contrast agent. However, the current hypertonic cracking method for isolating gas vesicles contains tedious operational procedures and is of low yield, thus not suitable for large-scale application. To overcome these technical challenges, we developed a rapid and efficient method for isolating gas vesicles from Microcystis. The new H₂O₂-based method increased the yield by three times and shortened the operation time from 24 hours to 7 hours. The H₂O₂ method is not only suitable for isolation of gas vesicles from laboratory-cultured Microcystis, but also suitable for colonial Microcystis covered with gelatinous sheath. The gas vesicles isolated by H₂O₂ method showed good performance in ultrasound contrast imaging. In conclusion, this new method shows great potential for large-scale application due to its high efficiency and wide adaptability, and provides technical support for developing gas vesicles into a biosynthetic ultrasonic contrast agent.
Contrast Media ; Cyanobacteria ; Hydrogen Peroxide ; Microcystis ; Proteins/chemistry*

OBJECTIVETo prepare a phospholipid-coated microbubble loaded with hydrogen sulfide (HSMB) and evaluate its physicochemical and acoustic properties.

METHODSHydrogen sulfide and perfluoropropane were mixed at the ratios of 4:0, 3:1, 2:2, 1:3, and 0:4 to prepare hydrogen sulfide-loaded microbubbles (termed HSMB4:0, HSMB3:1, HSMB2:2, HSMB1:3, and HSMB0:4, respectively). The microbubble concentration and diameter were investigated and their stability were evaluated. The optimal ratio of hydrogen sulfide and perfluoropropane was determined according to the changes of microbubble concentration. The changes of dissolved hydrogen sulfide and concentration of the microbubbles were investigated after exposure to ultrasound, and their acoustic enhancement effects in the myocardium and kidney were observed after intravenous injection in rats.

RESULTSHSMBs were milky in color and spherical in shape without aggregations. The concentrations of HSMB4:0 and HSMB3:1 were lower than that of HSMB2:2 and decreased with time. HSMB2:2, HSMB1:3 and HSMB0:4 showed comparable concentrations and were stable within 72 h. After exposure to ultrasound, the concentration of HSMB2:2 decreased while the dissolved hydrogen sulfide increased significantly. Intravenous injection of HSMB2:2 produced a satisfactory contrast-enhancing effect in the myocardium and kidney of rats.

CONCLUSIONHSMB prepared with the hydrogen sulfide to perfluoropropane ratio of 2:2 has excellent contrast-enhancing effect and is capable of carrying and releasing hydrogen sulfide upon ultrasound exposure to potentially allow visual site-specific delivery of hydrogen sulfide.

Animals ; Contrast Media ; chemistry ; Fluorocarbons ; chemistry ; Heart ; Hydrogen Sulfide ; chemistry ; Kidney ; Microbubbles ; Phospholipids ; chemistry ; Rats ; Ultrasonics

Objective:Gliomas are the most common neoplasm of the central nervous system (CNS); however, traditional imaging techniques do not show the boundaries of tumors well. Some researchers have found a new therapeutic mode to combine nanoparticles, which are nanosized particles with various properties for specific therapeutic purposes, and stem cells for tracing gliomas. This review provides an introduction of the basic understanding and clinical applications of the combination of stem cells and nanoparticles as a contrast agent for glioma imaging.

Data SourcesStudies published in English up to and including 2017 were extracted from the PubMed database with the selected key words of "stem cell," "glioma," "nanoparticles," "MRI," "nuclear imaging," and "Fluorescence imaging."

Study Selection:The selection of studies focused on both preclinical studies and basic studies of tracking glioma with nanoparticle-labeled stem cells.

Results:Studies have demonstrated successful labeling of stem cells with multiple types of nanoparticles. These labeled stem cells efficiently migrated to gliomas of varies models and produced signals sensitively captured by different imaging modalities.

ConclusionThe use of nanoparticle-labeled stem cells is a promising imaging platform for the tracking and treatment of gliomas.

Animals ; Contrast Media ; chemistry ; Glioma ; diagnostic imaging ; Humans ; Nanoparticles ; chemistry ; Stem Cells ; chemistry

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field.
Angiography ; Arteries/anatomy & histology ; Contrast Media/*chemistry ; Gadolinium DTPA/*chemistry ; Humans ; Liver/*radiography ; *Magnetic Resonance Imaging

OBJECTIVETo prepare an ultrasound microbubble contrast agent using PLLA-PEG-PLLA copolymer as the shell material, and test their acoustic characteristics in vitro.

METHODSPLLA-PEG-PLLA tri-block co-polymers were synthesized by ring-opening polymerization. Microbubbles were prepared by using double emulsion technique. Light microscope and scanning electron microscope were applied to observe the morphology of the microbubbles. Their size distribution was analyzed using MASTERSIZER 2000. The acoustic characteristics of microbubbles were tested by using color Doppler Ultrasonography.

RESULTSMicrobubbles were well dispersed in water. Contrast enhancement was stronger and longer lasting at low mechanical index.

CONCLUSIONThe polymer-encapsulated microbubbles prepared by using double emulsion technique with PLLA-PEG-PLLA as the shell material can be used as an ultrasound contrast agent.

Contrast Media ; chemistry ; Drug Compounding ; Lactates ; chemistry ; Microbubbles ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Ultrasonography, Doppler, Color ; methods

Dendrimers are new macromolecules synthesized in recent years, which are of great interests in many fields where they have potential important applications because of their hyperbranched, well defined and monodisperse structures. In this paper, the unique structures, general synthesis routes and basic physical and chemical properties of dendrimers are introduced in brief, and the progress in the research of dendrimers in drug (gene) delivery, contrast agents, cancer therapy were reviewed, as well as the perspective in research and applications.
Contrast Media ; chemistry ; Dendrimers ; chemistry ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Gene Transfer Techniques ; Humans ; Polyamines

OBJECTIVETo evaluate the effect of a phospholipid-coated microbubble contrast agent for myocardium opacification in comparison with a albumin-coated microbubble contrast agent (Quanfuxian).

METHODSIn 10 dogs with single coronary artery stenosis involving the anterior descending branch or circumflex branch randomly received infusion of the two contrast agents through the femoral vein. The myocardial blood flow, heart rate and blood pressure were analyzed qualitatively and quantitatively. The concentration and the particle diameter of the two contrast agents were determined.

RESULTSThe concentration of the phospholipid-coated microbubbles was (1.06-/+0.22) x10(9)/ml, with a diameter of 3.04-/+0.34 microm, similar to the concentration and diameter of Quanfuxian ((1.31-/+0.33)x10(9)/ml and 2.88-/+0.58 microm, respectively, P>0.05). Both of the agents achieved grade three myocardium opacification, and produced no obvious effect on the heart rate and blood pressure. Quantitative analysis of myocardial opacification in terms of myocardial blood volume (A), blood velocity (beta), and blood flow (A x beta) revealed no significant difference between the two agents (P>0.05), and the parameters derived from the two agents showed good correlations (P<0.05, rA=0.809, r beta=0.932, rA.beta=0.925).

CONCLUSIONThe phospholipid-coated microbubble contrast agent shows good effect for myocardial opacification without significant difference from Quanfuxian. Both of the agents are good ultrasound contrast agents for quantitative analysis of myocardium blood flow.

Albumins ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Coronary Stenosis ; diagnostic imaging ; Dogs ; Echocardiography ; methods ; Female ; Male ; Microbubbles ; Phospholipids ; chemistry

OBJECTIVETo prepare microbubble, made of N-carboxymethyl chitosan, as ultrasound contrast agent and evaluate its characteristics and acoustic effects in vivo.

METHODSOil-Water-Oil multiple emulsion/solvent evaporation method was used to prepare the microbubble contrast agent. Both optical micrography and scanning electron micrography were performed to determine the bubble size and morphology. The acoustic effect of the N-carboxymethyl chitosan echo contrast agent was evaluated in vivo in rabbit. Liver echo images were recorded with ultrasound machine before and after intravenous bolus injecting 0.5 ml of the agent.

RESULTSThe novel N-carboxymethyl chitosan echo contrast agent was formulated as lyophilized product, with a mean diameter of 2-3 microm and a shell thickness of 250-300 nm. Its size is relatively uniform. The imaging effect was remarkably enhanced with the ultrasonic contrast agent when applied in rabbit livers.

CONCLUSIONIt is feasible to prepare excellent microbubble ultrasound contrast agent with N-carboxymethyl chitosan as membrane components.

Animals ; Chitin ; analogs & derivatives ; chemical synthesis ; chemistry ; Contrast Media ; Liver ; diagnostic imaging ; Microbubbles ; Rabbits ; Ultrasonics ; Ultrasonography

In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.
Humans ; Contrast Media/chemistry* ; Molecular Targeted Therapy ; Ultrasonography/methods* ; Diagnostic Imaging

OBJECTIVETo prepare polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent (UCA) and evaluate its effects in contrast imaging on normal rabbit's liver parenchyma.

METHODSPerfluorocarbon (PFC) -containing microbubble UCA (ST68-PFC) were prepared by sonication-based on surfactants (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polylysine (PLL) and alginate (Alg) by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in contrast imaging on normal rabbit's liver parenchyma were assessed.

RESULTSThe obtained microbubble UCA exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film-coated UCA effectively enhanced the imaging of rabbit's liver parenchyma.

CONCLUSIONSThe novel microbubble UCA obtained via layer-by-layer self-assembly, when enabling more functions, has no obvious difference in enhancement effects compared with the premodified microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for the attachment of targeting ligands to microbubbles, which allows the selective targeting of the microbubbles to desired sites.

Alginates ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Fluorocarbons ; chemistry ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Liver ; diagnostic imaging ; Microbubbles ; Polylysine ; chemistry ; Rabbits ; Ultrasonography