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

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*

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

To prepare AS1411 targeted nano-ultrasonic contrast agent with liquid core, and to evaluate its ability for ultrasonic contrast enhancement and targeting MCF-7 cell in vitro.
 Methods: The modified solvent evaporation, self-synthesized membrane material and perfluorobrominane (PFOB) was used to form nano-ultrasonic contrast agent with PFOB core (nanoparticles, NP); then N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS) catalysis was used to connect AS1411 to the surface of NP to prepare NP-AS1411. The transmission electron microscopy was chosen to check the morphology of NP-AS1411. The size, surface charge, encapsulation efficiency, biocompatibility, the contrast grey value and the stability of NP-AS1411 and NP were compared. Whether AS411 was attached to the surface of NP was checked by gel electrophoresis. Fluorescence microscopy and flow cytometry were performed to examine the targeting ability of AS1411.
 Results: NP-AS1411 was a shell-nuclear structure under the electron microscope. Its size was at (245.4±16.5) nm, which was larger than that of NP (P=0.05). There was no significant difference in surface charge and encapsulation efficiency between NP-AS1411 and NP (P>0.05). In the MTT experiment, the cell viability decreased significantly at high concentration of NP-AS411 (25 mg/mL) after incubation for 24 h compared with the control group (0 mg/mL ) (P<0.05). The contrast gray value of NP-AS1411 was at 86.1+ 6.7, which was significantly higher than that of deionized water (P<0.05), and equivalent to that of NP (P>0.05). The contrast grey value of AS1411-NP was 80.1±9.2 after keeping at room temperature for 24 h, which showed no obviously change comparing with that before the treatment (P>0.05). The size of NP-AS1411didn't change too (P>0.05). The results of gel electrophoresis demonstrated that the AS1411 connecting to the surface of NP was the most when the molar ratio of NP:AS1411 was at 40:1. Flow cytometry analysis confirmed that NP and NP-AS1411 were combined with MCF-7 cells separately but the fluorescence produced by the combination of NP-AS1411 and MCF-7 was more intense.
 Conclusion: The modified solvent evaporation and EDC/NHS catalysis could successfully prepare ultrasound contrast agents with aptamer-conjugated nanoparticles with liquid core. The targeted ultrasonic contrast agents with liquid core possess good ultrasonic contrast enhancement ability in vitro, stability and specificity as well.
Cell Survival ; Contrast Media ; chemical synthesis ; Fluorocarbons ; Humans ; MCF-7 Cells ; Microscopy, Electron, Scanning Transmission ; Nanoparticles ; chemistry ; ultrastructure ; Oligodeoxyribonucleotides ; chemical synthesis

Objective To investigate the value of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting different stages of liver fibrosis in rats.Methods Rat models of liver fibrosis were induced by carbon tetrachloride intraperitoneal injection for 4 - 12 weeks (n=45). The control group was applied with 0.9% saline (n=15). The MRI protocol contained both dynamic contrast-enhanced sequence (60 continuous scans within 3 minutes,including three pre-contrast measurements) and multiple hepatobiliary-phase acquisitions (every 5 minutes after contrast injection,60 minutes in total). METAVIR score was used to grade liver fibrosis:normal (F0),mild fibrosis (F1 - F2),and advanced fibrosis (F3 - F4). Liver perfusion parameters [transfer constant (K ),extravascular extracellular volume fraction (V),initial area under curve (iAUC),maximum relative enhancement (RE),and time of maximum RE (T)] as well as hepatobiliary-phase parameters [RE at different time point,the decrease of RE (RE=RE - RE),and elimination half-life of RE (T)] were measured and compared with ANOVA analysis and Spearman rank correlation.Results Thirty-one rats completed MRI exams and were then divided into normal (n=10),mild fibrosis (n=10),and advanced fibrosis (n=11) groups. K ,V and iAUC decreased as liver fibrosis progressed (r=-0.631,P=0.002;r=-0.503,P=0.017;r=-0.446,P=0.037). K and V showed significant differences among three groups(F=7.011,P=0.005;F=4.656,P=0.023). K and V were significantly lower in advanced fibrosis group than in normal group (P=0.001,P=0.009). There were statistical significant differences of T,T and RE among groups(F=6.633,P=0.005;F=5.493,P=0.010;F=5.343,P=0.014). Compared to normal and mild fibrosis groups,advanced fibrosis group had significantly longer T and T (P=0.005,P=0.004;P=0.008,P=0.008)and significantly lower RE(P=0.007,P=0.012).Conclusion Perfusion and multi-hepatobiliary-phase parameters such as K ,V,T, T and RE obtained from Gd-EOB-DTPA-enhanced MRI,may be valuable for detecting and staging liver fibrosis.
Animals ; Contrast Media ; chemistry ; Gadolinium DTPA ; chemistry ; Liver ; diagnostic imaging ; pathology ; Liver Cirrhosis ; diagnostic imaging ; Magnetic Resonance Imaging ; Rats

OBJECTIVE: The aim of the study was to compare the diagnostic performances of F-18 sodium fluoride positron emission tomography/computed tomography (bone PET/CT) and bone scintigraphy (BS) for the detection of thyroid cancer bone metastasis. MATERIALS AND METHODS: We retrospectively enrolled 6 thyroid cancer patients (age = 44.7 ± 9.8 years, M:F = 1:5, papillary:follicular = 2:4) with suspected bone metastatic lesions in the whole body iodine scintigraphy or BS, who subsequently underwent bone PET/CT. Pathologic diagnosis was conducted for 4 lesions of 4 patients. RESULTS: Of the 17 suspected bone lesions, 10 were metastatic and 7 benign. Compared to BS, bone PET/CT exhibited superior sensitivity (10/10 = 100% vs. 2/10 = 20%, p = 0.008), and accuracy (14/17 = 82.4% vs. 7/17 = 41.2%, p < 0.025). The specificity (4/7 = 57.1%) of bone PET/CT was not significantly different from that of BS (5/7 = 71.4%, p > 0.05). CONCLUSION: Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.
Adult ; Bone Neoplasms/*radiography/secondary ; Bone and Bones/*radiography ; Contrast Media/*chemistry ; Female ; Fluorine Radioisotopes/chemistry ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Retrospective Studies ; Sodium Fluoride/*chemistry ; Thyroid Neoplasms/*pathology ; Tomography, X-Ray Computed ; Whole Body Imaging

OBJECTIVE: To evaluate the efficacy and safety of balloon-occluded retrograde transvenous obliteration (BRTO) with sodium tetradecyl sulfate (STS) liquid sclerotherapy of gastric varices. MATERIALS AND METHODS: Between February 2012 and August 2014, STS liquid sclerotherapy was performed in 17 consecutive patients (male:female = 8:9; mean age 58.6 years, range 44-86 years) with gastric varices. Retrograde venography was performed after occlusion of the gastrorenal shunt using a balloon catheter and embolization of collateral draining veins using coils or gelfoam pledgets, to evaluate the anatomy of the gastric varices. We prepared 2% liquid STS by mixing 3% STS and contrast media in a ratio of 2:1. A 2% STS solution was injected into the gastric varices until minimal filling of the afferent portal vein branch was observed (mean 19.9 mL, range 6-33 mL). Patients were followed up using computed tomography (CT) or endoscopy. RESULTS: Technical success was achieved in 16 of 17 patients (94.1%). The procedure failed in one patient because the shunt could not be occluded due to the large diameter of gastrorenal shunt. Complete obliteration of gastric varices was observed in 15 of 16 patients (93.8%) with follow-up CT or endoscopy. There was no rebleeding after the procedure. There was no procedure-related mortality. CONCLUSION: BRTO using STS liquid can be a safe and useful treatment option in patients with gastric varices.
Adult ; Aged ; Aged, 80 and over ; Balloon Occlusion ; Contrast Media/*chemistry ; Demography ; Embolization, Therapeutic ; Endoscopy, Digestive System ; Esophageal and Gastric Varices/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Portal Vein/radiography ; Sclerotherapy ; Sodium Tetradecyl Sulfate/*chemistry ; Tomography, X-Ray Computed

OBJECTIVETo compare agitated saline solution (AS) and the mixture of AS with blood (ASb) as the contrast agents in contrast transcranial Doppler (c-TCD) in the diagnosis of patent foramen ovale (PFO).

METHODSWe recruited 248 consecutive patients for c-TCD examination between November 2015 and January 2016, and the sequence of the use of AS (9 mL saline solution mixed with 1 mL air) and ASb (9 mL saline solution and a drop of the patient's blood mixed with 1 mL air) was determined by coin-tossing method. Before the examination, the contrast agent was injected with or without Valsalva maneuvers (VM), and the number of microbubbles within 25 s after the contrast agent injection and the time of first appearance of microbubbles were recorded by observing the TCD spectrum. Each injection was repeated twice and the interval between tests was at least 5 min. We classified PFO according to the number of microbubbles into negative (no microbubble), grade I (1-10 microbubbles), grade II (>10 microbubbles but no curtain), and grade III (with curtain).

RESULTSs The positivity rates in diagnosis with AS without VM, AS with VM, ASb without VM, and ASb with VM tests were 10.9%, 23.8%, 12.1% and 25.8%, respectively. AS with VM test had a higher positive rate than AS without VM test (23.8% vs 10.9%, P=0.001), and ASb with VM test had a higher positive rate than ASb without VM test (25.8% vs 12.1%, P=0.001). The positive rates were similar between ASb without VM and AS without VM test (12.1% vs 10.9%, P=0.250) and between ASb with VM test and AS with VM test (25.8% vs 23.8%, P=0.125).

CONCLUSIONVM can improve the positive rate of PFO diagnosis in c-TCD examination, and the positive rates are comparable between examinations using the contrast agents AS and ASb.

Contrast Media ; chemistry ; Foramen Ovale, Patent ; diagnostic imaging ; Microbubbles ; Sensitivity and Specificity ; Sodium Chloride ; Ultrasonography, Doppler, Transcranial ; Valsalva Maneuver

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

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