Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the lef...Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.展开更多
The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and pro...The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and properties,it has resulted in the development of various particle sizes and shapes of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials.This has led to the extension of the uses of the materials to photocatalysis,drug delivery,and CT image contrast agents.Accordingly,these applications have been compiled and discussed in depth in this review.The potential of these materials in the above applications has started to attract significant attention.Moreover,the compilation of in-vitro toxicity studies from the literature was also discussed to facilitate the biocompatibility of the developed Gd(OH)_(3)nanomaterials.However,despite the rapid progress of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials,there are still knowledge gaps in certain areas.Therefore,this review provides insights into the recent development of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials to aid in accelerating novel developments.展开更多
Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical...Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.展开更多
Contrast agents have transformed the field of medical imaging,significantly enhancing the visualisation of internal structures and improving diagnostic accuracy across X-rays,computed tomography,magnetic resonance ima...Contrast agents have transformed the field of medical imaging,significantly enhancing the visualisation of internal structures and improving diagnostic accuracy across X-rays,computed tomography,magnetic resonance imaging(MRI),and ultrasound.This review explores the historical development,physicochemical properties,and mechanisms of action of iodinated,gadolinium-based,barium sulfate,microbubble,and nanoparticle contrast agents.It highlights key advancements,including the transition from high-osmolar to low-and iso-osmolar iodinated agents,the integration of gado-linium in MRI,and the innovative use of microbubbles and nanoparticles.The review critically examines the safety profiles and adverse reactions of these contrast agents,categorising them into hypersensitivity and physiological reactions.It outlines risk factors,common misconceptions,and management strategies for adverse reactions,emphasising the importance of personalised approaches in clinical practice.Additionally,it delves into broader implications,including ethical considerations,environmental impact,and global accessibility of contrast media.The review also discusses technological advancements such as targeted contrast agents and the integration of artificial intelligence to optimise contrast dosage.By synthesising current knowledge and emerging trends,this review underscores the pivotal role of contrast agents in advancing medical imaging.It aims to equip clinicians,researchers,and policymakers with a thorough understanding to enhance diagnostic efficacy,ensure patient safety,and address ethical and environmental challenges,thereby informing future innovations and regulatory frameworks to promote equitable access to advanced imaging technologies globally.展开更多
Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This arti...Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.展开更多
Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modi...Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.展开更多
It is greatly desired to develop novel gadolinium-based contrast agents(GBCAs)as improved platforms for magnetic resonance imaging(MRI).Herein,we report the syntheses of a series of nonionic cyclenbased GBCAs by preci...It is greatly desired to develop novel gadolinium-based contrast agents(GBCAs)as improved platforms for magnetic resonance imaging(MRI).Herein,we report the syntheses of a series of nonionic cyclenbased GBCAs by precisely tuning carboxylate group on DO3A-pyridine scaffold.[Gd-DO3A-4cp]is isolated which adopts an octadentate coordination mode with a free carboxylate group at 4-position of pyridine.It shows the r_(1)relaxivity of 5.8(mmol/L)^(-1)s^(-1)(3 T,25℃),which is 75%higher than 3.3(mmol/L)^(-1)s^(-1)of the clinic used[Gd-DOTA].The possible mechanisms behind the enhanced relaxivity are investigated and proposed by structure-property relationship studies.After validation of low cytotoxicity and considerable kinetic inertness,in-vivo studies are further examined,demonstrating its good MRI performance,biodistribution as well as the way of excretion.展开更多
Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents su...Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions.However,the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage.The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired.The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions.In order to maximize lesion detection and characterization,novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles,nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent.In this review,the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed.Furthermore,liver target nanovectors aimed at improving the diagnostic accuracy of liver MRI by targeting additional features of focal liver lesions were highlighted.展开更多
Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment...Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound(US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents(UCAs)an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles(SPIOs), Cu S nanoparticles, DNA, si RNA, gold nanoparticles(GNPs), gold nanorods(GNRs), gold nanoshell(GNS), graphene oxides(GOs), polypyrrole(PPy) nanocapsules, Prussian blue(PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.展开更多
Recent progress of the preparation and applications of superparamagnetic iron oxide（SPIO） clusters as magnetic resonance imaging（MRI） probes is reviewed with regard to their applications in labeling and tracking c...Recent progress of the preparation and applications of superparamagnetic iron oxide（SPIO） clusters as magnetic resonance imaging（MRI） probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles（NPs）, especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs＇ size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer（Lb L） capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin（T2） relaxivity and convenience for further functionalization.展开更多
This study examined the effect of P85 （a pluronic block copolymer） and microbubble （MB） ultrasound contrast agents under ultrasound irradiation on gene transfection and expression. The pEGFP plasmids that can enco...This study examined the effect of P85 （a pluronic block copolymer） and microbubble （MB） ultrasound contrast agents under ultrasound irradiation on gene transfection and expression. The pEGFP plasmids that can encode enhanced green fluorescent protein （pEGFP） served as a report gene and were mixed with different concentrations of MB/0.05% （w/v） P85. Then the plasmids were transfected into human hepatoma G2 （HepG2） cells. The HepG2 cells treated with MB/P85 or without treatment were exposed to ultrasound （US parameters： 1 MHz, 1.0 W/cm2, 20 s, 20% duty cycle）. Twenty-four hours later, the transfection efficiency was assessed by fluorescence microscopy and fluo-rescence activated cell sorting （FACS） analysis. The cell viability was evaluated by Trypan blue exclusion test. The results showed that the gene transfection efficiency in HepG2 cells under ultrasound irradiation was significantly higher than that without ultrasound irradiation. HepG2 cells in the MB or P85 group in the absence of ultrasound expressed less amount of green fluorescent protein. The expression efficiency reached （22.14±3.06）% and the survival rate was as high as （55.73±3.32）% in the 30% MB plus P85 group. It was concluded that MB and P85 in the presence of ultrasound can enhance gene transfection and expression.展开更多
Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast ag...Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions. However, the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage. The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired. The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions. In order to maximize lesion detection and characterization, novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles, nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent. In this review, the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed. Furthermore, liver target nanovectors aimed at improving the diagnostic accuracy of liver MR1 by tar~etin~ additional features of focal liver lesions were highlighted.展开更多
Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are expose...Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.展开更多
Magnetic resonance imaging(MRI)has become an indispensable diagnostic modality in clinical medicine owing to its superior spatial resolution and deep tissue penetration,particularly when contrast agents are exploited....Magnetic resonance imaging(MRI)has become an indispensable diagnostic modality in clinical medicine owing to its superior spatial resolution and deep tissue penetration,particularly when contrast agents are exploited.Current clinical protocols predominantly utilize mononuclear gadolinium(Ⅲ)complexes as contrast agents.Recently,coordination clusters composed of multi-nuclear paramagnetic metal ions(such as Gd^(3+),Mn^(2+),and Fe^(3+))have demonstrated promisingly higher relaxation rates as MRI contrast agents and adaptable stability in various solutions,offering promising medical application prospects.This mini-review mainly highlights such advancements,focusing on the influence of ligand selection and structural design on the relaxation rates of metal clusters as MRI contrast agents.展开更多
Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This s...Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This study presents a chiral strategy for developing high-performance polymeric gadoliniumbased CAs,PAA-EOB-GdA and PAA-EOB-GdB,tailored for enhanced vascular and tumor imaging.Notably,PAA-EOB-GdA,a chiral Gd-DOTA derivative integrated with sodium poly(acrylic acid)(PAA),benefits from the optimized water exchange rate of chiral Gd(Ⅲ)complex and the polymer effect of PAA,exhibiting exceptionally high relaxivity(r1=37.87 mM^(-1) s^(-1),11.9-fold of clinical Gd-DOTA)and showed remarkable imaging efficacy in magnetic resonance angiography(MRA)with low-dose administration(0.05 mmol kg^(-1))and an extended imaging duration.Its performance in tumor imaging was also impressive,maintaining superior enhancement values compared to Gd-DOTA.These characteristics feature PAA-EOB-GdA as a promising candidate for clinical diagnosis in both vascular and tumor imaging applications.展开更多
Objective:To perform a comprehensive physical-level assessment of 13 contrast agents,including those with potential applications in CT imaging,focusing on their radiation shielding characteristics and transport behavi...Objective:To perform a comprehensive physical-level assessment of 13 contrast agents,including those with potential applications in CT imaging,focusing on their radiation shielding characteristics and transport behaviorssuch as energy deposition,collision frequency,and attenuation performance-under low-energy X-ray conditions.Methods:A dual-method framework was adopted.Geant4 Monte Carlo simulations were used to construct an X-ray tube model and simulate contrast agent interactions in a breast-equivalent water phantom,enabling analysis of microscopic radiation transport parameters including energy deposition,track length,and collision frequency.In parallel,Phy-X/PSD software was used to calculate macroscopic attenuation indices,including the linear attenuation coefficient(LAC),mass attenuation coefficient(MAC),mean free path(MFP),half-value layer(HVL),and exposure buildup factor(EBF),over a wide photon energy range,Results:The study revealed a strong consistency between radiation shielding metrics and transport characteristics across the same energy ranges.For instance,iothalamate meglumine exhibited the highest energy deposition(0.08560 MeV),shortest MFP(1.13 cm),and highest collision frequency(5.24×10^(8)),indicating excellent attenuation potential in the low-energy CT range.Gadolinium-and iron-based agents,while traditionally used in MR imaging,showed distinctive and stable transport behavior at medium-to-high energies,suggesting promising utility in CT or dual-modality applications.Conclusions:These findings highlight the importance of integrating microscopic transport analysis with macroscopic shielding evaluation to fully characterize contrast agent performance.The study provides a validated theoretical foundation for contrast agent screening and optimization in X-ray imaging,and supports future research into clinical applicability and biological safety of emerging contrast materials.展开更多
Ultrasmall superparamagnetic iron oxide nanoparticles(usSPIONs)are promising alternatives to gadolinium‐based contrast agents for positive contrast enhancement in magnetic resonance imaging(MRI).Unlike larger SPIONs ...Ultrasmall superparamagnetic iron oxide nanoparticles(usSPIONs)are promising alternatives to gadolinium‐based contrast agents for positive contrast enhancement in magnetic resonance imaging(MRI).Unlike larger SPIONs that primarily function as T2/T2*negative contrast agents,usSPIONs with core diameters below 5 nm can effectively shorten T1 relaxation times,producing bright signals in T1‐weighted images.This distinct behavior stems from their unique magnetic properties,including single‐domain configurations,surface spin canting,and rapid Néel relaxation dynamics,which are particularly enhanced at low magnetic field strengths.The biocompatibility of iron oxide,efficient renal clearance pathways,and versatility for surface functionalization offer potential advantages over gadolinium‐based agents,especially regarding safety concerns related to nephrogenic systemic fibrosis and gadolinium deposition.These nanoparticles show particular promise for applications in lowfield MRI,vascular imaging,targeted molecular imaging,and theranostic platforms.Although challenges remain in optimizing synthesis methods for consistent production of monodisperse usSPIONs with tailored surface chemistry,ongoing research continues to advance their potential for clinical translation.This review explores the mechanisms,synthesis approaches,applications,and future perspectives of usSPIONs as positive contrast agents in MRI.展开更多
Magnetic resonance imaging(MRI)has revolutionized medical imaging diagnostics with the advantages of non-invasive nature,absence of ionizing radiation,unrestricted penetration depth,high-resolution imaging of soft tis...Magnetic resonance imaging(MRI)has revolutionized medical imaging diagnostics with the advantages of non-invasive nature,absence of ionizing radiation,unrestricted penetration depth,high-resolution imaging of soft tissues,organs and blood vessels,and multi-parameter and multi-sequence imaging.Contrast agents(CAs)are crucial for enhancing image quality,detecting molecular-level changes,and providing comprehensive diagnostic information in contrast enhanced MRI.However,the performance of clinical Gd-based CAs represents a limitation to the improvement of MRI sensitivity,specificity,and versatility,thereby impeding the achievement of satisfactory imaging outcomes.In recent years,the development of magnetic nanoparticle-based CAs has emerged as a promising avenue to enhance the capabilities of MRI.Here,we review the advances in magnetic nanoparticle-based MRI CAs,including blood pool CAs,biochemically-targeted CAs,stimulus-responsive CAs,and ultra-high field MRI CAs,as well as the use of CAs for cell labeling and tracking.Additionally,we offer insights into the future prospects and challenges associated with the integration of these nanoparticles into clinical practice.展开更多
In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed t...In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents （CAs） available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells （RBCs） as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.展开更多
Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approxima...Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.展开更多
文摘Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.
基金the FRC grant(UBD/RSCH/1.4/FICBF(b)/2023/059)received from Universiti Brunei Darussalam,Brunei Darussalam。
文摘The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and properties,it has resulted in the development of various particle sizes and shapes of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials.This has led to the extension of the uses of the materials to photocatalysis,drug delivery,and CT image contrast agents.Accordingly,these applications have been compiled and discussed in depth in this review.The potential of these materials in the above applications has started to attract significant attention.Moreover,the compilation of in-vitro toxicity studies from the literature was also discussed to facilitate the biocompatibility of the developed Gd(OH)_(3)nanomaterials.However,despite the rapid progress of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials,there are still knowledge gaps in certain areas.Therefore,this review provides insights into the recent development of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials to aid in accelerating novel developments.
文摘Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.
文摘Contrast agents have transformed the field of medical imaging,significantly enhancing the visualisation of internal structures and improving diagnostic accuracy across X-rays,computed tomography,magnetic resonance imaging(MRI),and ultrasound.This review explores the historical development,physicochemical properties,and mechanisms of action of iodinated,gadolinium-based,barium sulfate,microbubble,and nanoparticle contrast agents.It highlights key advancements,including the transition from high-osmolar to low-and iso-osmolar iodinated agents,the integration of gado-linium in MRI,and the innovative use of microbubbles and nanoparticles.The review critically examines the safety profiles and adverse reactions of these contrast agents,categorising them into hypersensitivity and physiological reactions.It outlines risk factors,common misconceptions,and management strategies for adverse reactions,emphasising the importance of personalised approaches in clinical practice.Additionally,it delves into broader implications,including ethical considerations,environmental impact,and global accessibility of contrast media.The review also discusses technological advancements such as targeted contrast agents and the integration of artificial intelligence to optimise contrast dosage.By synthesising current knowledge and emerging trends,this review underscores the pivotal role of contrast agents in advancing medical imaging.It aims to equip clinicians,researchers,and policymakers with a thorough understanding to enhance diagnostic efficacy,ensure patient safety,and address ethical and environmental challenges,thereby informing future innovations and regulatory frameworks to promote equitable access to advanced imaging technologies globally.
基金the United Kingdom Department of Health, British Medical Research Council, Grant No. G99000178 and the United Kingdom National Health Service Research and Development Initiative
文摘Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.
基金financially supported by the National Natural Science Foundation of China(Nos.21374061,81371703 and 81501571)the Marie Curie International Incoming Fellowship of the EU+2 种基金the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning“Shu Guang”project supported by Shanghai Municipal Education CommissionShanghai Education Development Foundation
文摘Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.
基金financial support from National Natural Science Foundation of China(No.21971045)National Key Technologies R&D Program of China(No.2017YFA0205103)。
文摘It is greatly desired to develop novel gadolinium-based contrast agents(GBCAs)as improved platforms for magnetic resonance imaging(MRI).Herein,we report the syntheses of a series of nonionic cyclenbased GBCAs by precisely tuning carboxylate group on DO3A-pyridine scaffold.[Gd-DO3A-4cp]is isolated which adopts an octadentate coordination mode with a free carboxylate group at 4-position of pyridine.It shows the r_(1)relaxivity of 5.8(mmol/L)^(-1)s^(-1)(3 T,25℃),which is 75%higher than 3.3(mmol/L)^(-1)s^(-1)of the clinic used[Gd-DOTA].The possible mechanisms behind the enhanced relaxivity are investigated and proposed by structure-property relationship studies.After validation of low cytotoxicity and considerable kinetic inertness,in-vivo studies are further examined,demonstrating its good MRI performance,biodistribution as well as the way of excretion.
基金New Century Excellent Talents in University (Grant No.NCET-08-0334)Independent Innovation Foundation of Shandong University(IIFSDU,Grant No.2010JC019).
文摘Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions.However,the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage.The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired.The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions.In order to maximize lesion detection and characterization,novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles,nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent.In this review,the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed.Furthermore,liver target nanovectors aimed at improving the diagnostic accuracy of liver MRI by targeting additional features of focal liver lesions were highlighted.
基金financially supported by the National Natural Science Foundation of China(Grant No.81501585)the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20150348)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.15KJB310019)China Postdoctoral Science Foundation(Grant No.2015M570475 and 2016T90496)
文摘Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound(US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents(UCAs)an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles(SPIOs), Cu S nanoparticles, DNA, si RNA, gold nanoparticles(GNPs), gold nanorods(GNRs), gold nanoshell(GNS), graphene oxides(GOs), polypyrrole(PPy) nanocapsules, Prussian blue(PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.
基金Project supported by the National Key Basic Research Program of China(Grant No.2013CB933903)the National Natural Science Foundation of China(Grant Nos.20974065+2 种基金51173117and 50830107)the Scientific Research Start-up Fund of Kunming University of Science and Technology(Grant No.KKSY201305089)
文摘Recent progress of the preparation and applications of superparamagnetic iron oxide（SPIO） clusters as magnetic resonance imaging（MRI） probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles（NPs）, especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs＇ size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer（Lb L） capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin（T2） relaxivity and convenience for further functionalization.
基金supported by grants from National Natural Sciences Foundation of China(No.30970882)Natural Sciences Foundation of Hubei Province,China(No.2008CDB-148)
文摘This study examined the effect of P85 （a pluronic block copolymer） and microbubble （MB） ultrasound contrast agents under ultrasound irradiation on gene transfection and expression. The pEGFP plasmids that can encode enhanced green fluorescent protein （pEGFP） served as a report gene and were mixed with different concentrations of MB/0.05% （w/v） P85. Then the plasmids were transfected into human hepatoma G2 （HepG2） cells. The HepG2 cells treated with MB/P85 or without treatment were exposed to ultrasound （US parameters： 1 MHz, 1.0 W/cm2, 20 s, 20% duty cycle）. Twenty-four hours later, the transfection efficiency was assessed by fluorescence microscopy and fluo-rescence activated cell sorting （FACS） analysis. The cell viability was evaluated by Trypan blue exclusion test. The results showed that the gene transfection efficiency in HepG2 cells under ultrasound irradiation was significantly higher than that without ultrasound irradiation. HepG2 cells in the MB or P85 group in the absence of ultrasound expressed less amount of green fluorescent protein. The expression efficiency reached （22.14±3.06）% and the survival rate was as high as （55.73±3.32）% in the 30% MB plus P85 group. It was concluded that MB and P85 in the presence of ultrasound can enhance gene transfection and expression.
基金Foundation items： New Century Excellent lalents in University （Grant No. NCET-08-0334） and Independent Innovation Foundation of Shandong University （IIFSDU, Grant No. 2010JC019）.
文摘Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions. However, the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage. The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired. The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions. In order to maximize lesion detection and characterization, novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles, nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent. In this review, the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed. Furthermore, liver target nanovectors aimed at improving the diagnostic accuracy of liver MR1 by tar~etin~ additional features of focal liver lesions were highlighted.
文摘Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.
基金supported by the Medical-Engineering Cross Project of the First Affiliated Hospital of XJTU(QYJC02)Key Scientific and Technological Innovation Team of Shaanxi Province(No.2020TD-001)+3 种基金Natural Science Foundation of China(No.22375157)the Programme of Introducing Talents of Discipline to Universities(B23025)Key Laboratory Construction Program of Xi'an Municipal Bureau of Science and Technology,the Fundamental Research Funds for Central Universities(No.xtr052023002)“Scientists engineers”Team Building Project of Qin Chuang Yuan in Shaanxi Province of China(2022KXJ-088).
文摘Magnetic resonance imaging(MRI)has become an indispensable diagnostic modality in clinical medicine owing to its superior spatial resolution and deep tissue penetration,particularly when contrast agents are exploited.Current clinical protocols predominantly utilize mononuclear gadolinium(Ⅲ)complexes as contrast agents.Recently,coordination clusters composed of multi-nuclear paramagnetic metal ions(such as Gd^(3+),Mn^(2+),and Fe^(3+))have demonstrated promisingly higher relaxation rates as MRI contrast agents and adaptable stability in various solutions,offering promising medical application prospects.This mini-review mainly highlights such advancements,focusing on the influence of ligand selection and structural design on the relaxation rates of metal clusters as MRI contrast agents.
基金financially supported by the National Natural Science Foundation of China(Grants 22075281 and 22105201)Zhejiang Provincial Natural Science of Foundation of China(Grant LZ21B010001)+3 种基金The Scientific Research Fund of Hunan Provincial Education Department(Grant 24B0456)the Natural Science Foundation of Hunan Province(Grant 2025JJ50125)University of Chinese Academy of Science(Grant WIUCASQD2020008)Wenzhou high-level innovation team(Development and Application Team of Functional Liver Cancer-on-a-Chip).
文摘Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This study presents a chiral strategy for developing high-performance polymeric gadoliniumbased CAs,PAA-EOB-GdA and PAA-EOB-GdB,tailored for enhanced vascular and tumor imaging.Notably,PAA-EOB-GdA,a chiral Gd-DOTA derivative integrated with sodium poly(acrylic acid)(PAA),benefits from the optimized water exchange rate of chiral Gd(Ⅲ)complex and the polymer effect of PAA,exhibiting exceptionally high relaxivity(r1=37.87 mM^(-1) s^(-1),11.9-fold of clinical Gd-DOTA)and showed remarkable imaging efficacy in magnetic resonance angiography(MRA)with low-dose administration(0.05 mmol kg^(-1))and an extended imaging duration.Its performance in tumor imaging was also impressive,maintaining superior enhancement values compared to Gd-DOTA.These characteristics feature PAA-EOB-GdA as a promising candidate for clinical diagnosis in both vascular and tumor imaging applications.
基金supported by the ITER Project of Ministry of Science and Technology(No.2022YFE03080002)China,Hunan Natural Science Foundation of China(No.2025JJ50048)+1 种基金the International Cooperation Base Project of Hunan Province of China(No.2018WK4009)the Key Laboratory of Magnetic Confinement Nuclear Fusion Research in Hengyang(No.2018KJ108),China。
文摘Objective:To perform a comprehensive physical-level assessment of 13 contrast agents,including those with potential applications in CT imaging,focusing on their radiation shielding characteristics and transport behaviorssuch as energy deposition,collision frequency,and attenuation performance-under low-energy X-ray conditions.Methods:A dual-method framework was adopted.Geant4 Monte Carlo simulations were used to construct an X-ray tube model and simulate contrast agent interactions in a breast-equivalent water phantom,enabling analysis of microscopic radiation transport parameters including energy deposition,track length,and collision frequency.In parallel,Phy-X/PSD software was used to calculate macroscopic attenuation indices,including the linear attenuation coefficient(LAC),mass attenuation coefficient(MAC),mean free path(MFP),half-value layer(HVL),and exposure buildup factor(EBF),over a wide photon energy range,Results:The study revealed a strong consistency between radiation shielding metrics and transport characteristics across the same energy ranges.For instance,iothalamate meglumine exhibited the highest energy deposition(0.08560 MeV),shortest MFP(1.13 cm),and highest collision frequency(5.24×10^(8)),indicating excellent attenuation potential in the low-energy CT range.Gadolinium-and iron-based agents,while traditionally used in MR imaging,showed distinctive and stable transport behavior at medium-to-high energies,suggesting promising utility in CT or dual-modality applications.Conclusions:These findings highlight the importance of integrating microscopic transport analysis with macroscopic shielding evaluation to fully characterize contrast agent performance.The study provides a validated theoretical foundation for contrast agent screening and optimization in X-ray imaging,and supports future research into clinical applicability and biological safety of emerging contrast materials.
文摘Ultrasmall superparamagnetic iron oxide nanoparticles(usSPIONs)are promising alternatives to gadolinium‐based contrast agents for positive contrast enhancement in magnetic resonance imaging(MRI).Unlike larger SPIONs that primarily function as T2/T2*negative contrast agents,usSPIONs with core diameters below 5 nm can effectively shorten T1 relaxation times,producing bright signals in T1‐weighted images.This distinct behavior stems from their unique magnetic properties,including single‐domain configurations,surface spin canting,and rapid Néel relaxation dynamics,which are particularly enhanced at low magnetic field strengths.The biocompatibility of iron oxide,efficient renal clearance pathways,and versatility for surface functionalization offer potential advantages over gadolinium‐based agents,especially regarding safety concerns related to nephrogenic systemic fibrosis and gadolinium deposition.These nanoparticles show particular promise for applications in lowfield MRI,vascular imaging,targeted molecular imaging,and theranostic platforms.Although challenges remain in optimizing synthesis methods for consistent production of monodisperse usSPIONs with tailored surface chemistry,ongoing research continues to advance their potential for clinical translation.This review explores the mechanisms,synthesis approaches,applications,and future perspectives of usSPIONs as positive contrast agents in MRI.
基金supported by the National Key R&D Program of China(Nos.2021YFA1201401 and 2021YFA1201402)the National Natural Science Foundation of China(Nos.82202306,82150301,82072063,and 31901003)+1 种基金the Guangdong Natural Science Foundation(No.2023A1515012508)the China Postdoctoral Science Foundation(Nos.2022M723700 and 2023T160776).
文摘Magnetic resonance imaging(MRI)has revolutionized medical imaging diagnostics with the advantages of non-invasive nature,absence of ionizing radiation,unrestricted penetration depth,high-resolution imaging of soft tissues,organs and blood vessels,and multi-parameter and multi-sequence imaging.Contrast agents(CAs)are crucial for enhancing image quality,detecting molecular-level changes,and providing comprehensive diagnostic information in contrast enhanced MRI.However,the performance of clinical Gd-based CAs represents a limitation to the improvement of MRI sensitivity,specificity,and versatility,thereby impeding the achievement of satisfactory imaging outcomes.In recent years,the development of magnetic nanoparticle-based CAs has emerged as a promising avenue to enhance the capabilities of MRI.Here,we review the advances in magnetic nanoparticle-based MRI CAs,including blood pool CAs,biochemically-targeted CAs,stimulus-responsive CAs,and ultra-high field MRI CAs,as well as the use of CAs for cell labeling and tracking.Additionally,we offer insights into the future prospects and challenges associated with the integration of these nanoparticles into clinical practice.
文摘In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents （CAs） available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells （RBCs） as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.
基金supported by the Hematopoietic Biorepository and Cellular Therapy Shared Resource of the Case Comprehensive Cancer Center(P30CA043703)the NIH grants T32GM007250,T32HL134622,,F30HL160111the National Institute of Biomedical Imaging and Bioengineering(R01EB025741,R01EB028144).
文摘Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.
