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1.
PLoS One ; 15(9): e0237856, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877415

RESUMO

BACKGROUND AND PURPOSE: MR contrast-enhanced techniques are undergoing increased scrutiny since the FDA applied a warning for gadolinium-based MR contrast agents due to gadolinium deposition within multiple organ systems. While CE-MRA provides excellent image quality, is it required in a screening carotid study? This study compares 2D TOF and 3D TOF MRA vs. CE-MRA in defining carotid stenosis in a large clinical patient population, and with multiple readers with varying experience. MATERIALS AND METHODS: 200 consecutive patients had their carotid bifurcations evaluated with 2D TOF, 3D TOF and CE-MRA sequences by 6 board-certified neuroradiologists. Stenosis and quality of examinations were defined for each study. Inter-rater reliability was assessed using two-way random effects intraclass correlation coefficients. Intra-reader reliability was computed via weighted Cohen's κ. Weighted Cohen's κ were also computed to assess agreement in stenosis ratings between enhanced images and unenhanced images. RESULTS: Agreement between unenhanced and enhanced ratings was substantial with a pooled weighted κ of 0.733 (0.628-0.811). For 5 of the 6 readers, the combination of unenhanced 2D TOF and 3D TOF showed better agreement with contrast-enhanced than either 2D TOF or 3D TOF alone. Intra-reader reliability was substantial. CONCLUSIONS: The combination of 2D TOF and 3D TOF MRA showed substantial agreement with CE-MRA regarding degree of carotid stenosis in this large outpatient population across multiple readers of varying experience. Given the scrutiny that GBCA are undergoing due to concerns regarding CNS and soft tissue deposition, it seems prudent to reserve CE-MRA for cases which are not satisfactorily answered by the nonenhanced study or other noninvasive examinations.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Meios de Contraste/química , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
2.
Int J Nanomedicine ; 15: 4811-4824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753867

RESUMO

Purpose: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe3O4@AuNPs) as potential contrast agents. Methods: Fe3O4@AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe3O4@AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe3O4@AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe3O4@AuNPs. Results: Stable Fe3O4@AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe3O4@AuNPs at small concentrations of Fe (<1.95×10-8 mg/cell). Whereas, at higher Fe concentrations (eg 7.5×10-8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe3O4@AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis. Conclusion: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T2 signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.


Assuntos
Meios de Contraste/química , Compostos Férricos/química , Ouro/química , Imagem por Ressonância Magnética , Nanopartículas Metálicas/química , Animais , Sobrevivência Celular , Endocitose , Inflamação/patologia , Masculino , Nanopartículas Metálicas/ultraestrutura , Ratos Wistar , Difração de Raios X
3.
PLoS One ; 15(8): e0237939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813730

RESUMO

INTRODUCTION: Quantitative analysis of multi-detector computed tomography (MDCT) plays an increasingly important role in assessing airway disease. Depending on the algorithms used, airway dimensions may be over- or underestimated, primarily if contrast material was used. Therefore, we tested a modified integral-based method (IBM) to address this problem. METHODS: Temporally resolved cine-MDCT was performed in seven ventilated pigs in breath-hold during iodinated contrast material (CM) infusion over 60s. Identical slices in non-enhanced (NE), pulmonary-arterial (PA), systemic-arterial (SA), and venous phase (VE) were subjected to an in-house software using a standard and a modified IBM. Total diameter (TD), lumen area (LA), wall area (WA), and wall thickness (WT) were measured for ten extra- and six intrapulmonary airways. RESULTS: The modified IBM significantly reduced TD by 7.6%, LA by 12.7%, WA by 9.7%, and WT by 3.9% compared to standard IBM on non-enhanced CT (p<0.05). Using standard IBM, CM led to a decrease of all airway parameters compared to NE. For example, LA decreased from 80.85±49.26mm2 at NE, to 75.14±47.96mm2 (-7.1%) at PA (p<0.001), 74.96±48.55mm2 (-7.3%) at SA (p<0.001), and to 78.95±48.94mm2 (-2.4%) at VE (p = 0.200). Using modified IBM, the differences were reduced to -3.1% at PA, -2.9% at SA and -0.7% at VE (p<0.001; p<0.001; p = 1.000). CONCLUSIONS: The modified IBM can optimize airway wall segmentation and reduce the influence of CM on quantitative CT. This allows a more precise measurement as well as potentially the comparison of enhanced with non-enhanced scans in inflammatory airway disease.


Assuntos
Algoritmos , Meios de Contraste/química , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Animais , Feminino , Pulmão/anatomia & histologia , Reprodutibilidade dos Testes , Suínos
4.
Int J Nanomedicine ; 15: 5017-5026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764933

RESUMO

Background: Molecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge. Materials and Methods: We firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging. Results and Discussion: The DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect. Conclusion: The biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.


Assuntos
Cetonas/química , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Tomografia por Emissão de Pósitrons/métodos , Pirróis/química , Animais , Meios de Contraste/química , Radioisótopos de Cobre/administração & dosagem , Radioisótopos de Cobre/farmacocinética , Feminino , Células Hep G2 , Humanos , Injeções , Camundongos , Camundongos Nus , Imagem Multimodal/métodos , Células NIH 3T3 , Nanopartículas/administração & dosagem , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Polímeros/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Int J Nanomedicine ; 15: 4289-4309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606678

RESUMO

Objective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin-avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately -23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.


Assuntos
Verde de Indocianina/química , Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Fluorescência , Humanos , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Tamanho da Partícula , Peptídeos/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/terapia , Ligação Proteica
6.
Int J Nanomedicine ; 15: 4691-4703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636625

RESUMO

Purpose: Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized. Materials and Methods: Gd@C-dots were developed and modified with Ac-Cys-ZEGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-ZEGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs. Results: Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-ZEGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-ZEGFR:1907 was reduced, when Ac-Cys-ZEGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-ZEGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-ZEGFR:1907. Conclusion: Gd@C-dots-Cys-ZEGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Pontos Quânticos/química , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Meios de Contraste/química , Receptores ErbB/metabolismo , Feminino , Gadolínio/química , Gadolínio/farmacocinética , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Nanopartículas/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Nanomedicine ; 15: 3953-3964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581539

RESUMO

Objective: To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism. Design: A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment. Results: The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer. Conclusion: LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.


Assuntos
Neoplasias da Mama/terapia , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Hematoporfirinas/química , Humanos , Lipídeos/química , Lipossomos/química , Camundongos Nus , Nanopartículas/uso terapêutico , Oligopeptídeos/química , Coelhos , Ultrassonografia de Intervenção/métodos
8.
PLoS One ; 15(6): e0235130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579595

RESUMO

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) enables the assessment of real-time renal microcirculation. This study investigated CEUS-driven parameters as hemodynamic predictors for renal outcomes in patients with acute kidney injury (AKI). METHODS: Forty-eight patients who were diagnosed with AKI were prospectively enrolled and underwent CEUS at the occurrence of AKI. Parameters measured were the wash-in slope (WIS), time to peak intensity, peak intensity (PI), area under the time-intensity curve (AUC), mean transit time (MTT), time for full width at half maximum, and rise time (RT). The predictive performance of the CEUS-driven parameters for Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, initiation of renal replacement therapy (RRT), AKI recovery, and chronic kidney disease (CKD) progression was assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CEUS. RESULTS: Cortical RT (Odds ratio [OR] = 1.21) predicted the KDIGO stage 3 AKI. Cortical MTT (OR = 1.07) and RT (OR = 1.20) predicted the initiation of RRT. Cortical WIS (OR = 76.23) and medullary PI (OR = 1.25) predicted AKI recovery. Medullary PI (OR = 0.78) and AUC (OR = 1.00) predicted CKD progression. The areas under the ROC curves showed reasonable performance for predicting the initiation of RRT and AKI recovery. The sensitivity and specificity of the quantitative CEUS parameters were 60-83% and 62-77%, respectively, with an area under the curve of 0.69-0.75. CONCLUSION: CEUS may be a supplemental tool in diagnosing the severity of AKI and predicting renal prognosis in patients with AKI.


Assuntos
Lesão Renal Aguda/diagnóstico , Meios de Contraste/química , Aumento da Imagem/métodos , Rim/diagnóstico por imagem , Ultrassonografia/métodos , Lesão Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Curva ROC , Insuficiência Renal Crônica/diagnóstico , Terapia de Substituição Renal/métodos
9.
Recent Results Cancer Res ; 216: 319-336, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594391

RESUMO

Gas-filled particles (microbubbles) can be prepared and stabilized for intravascular use as contrast agents in ultrasound imaging. Microbubbles are used in clinics as blood pool contrast materials for the past two decades. Shell of these bubbles is made of biocompatible and biodegradable lipids, proteins, and/or polymers. Gas core is air, or, lately, a perfluorinated gas, poorly soluble in water and blood. Making them useful for molecular targeting and molecular imaging in oncology is accomplished by decorating the shell of these particles with targeting ligands, that will selectively bind to the specific markers of tumor vasculature. In this review we discuss the formulation strategy for microbubble preparation, the logic of bubble shell selection, coupling tools that are used for the attachment of targeting ligands, and examples of the application of gas-filled bubbles for molecular imaging in oncology.


Assuntos
Meios de Contraste/química , Microbolhas , Imagem Molecular , Neoplasias/diagnóstico por imagem , Ultrassonografia , Humanos
10.
Int J Nanomedicine ; 15: 3057-3070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431501

RESUMO

Background: Position of gadolinium atom(s) plays a key role in contrast enhancement of gadolinium-based contrast agents. To gain a better understanding of effects of distance of gadolinium in relation to the nanoconjugate platform, we designed and synthesized single- and multi-arm ("star") gadolinium conjugates equipped with antibody and peptides for targeting. The contrast agents were studied for their tumor imaging performance in a glioma mouse model. Materials and Methods: Antibody- and peptide-targeted nano contrast agents (NCAs) were synthesized using polymalic acid platforms of different sizes. Gadolinium-DOTA and intermediates were attached as amides and targeting agents such as antibodies and peptides as thioethers. For in vivo experiments, we used human U87MG xenografts as glioma models. Magnetic resonance imaging (MRI) was performed on a Bruker BioSpec 94/20USR 9.4 T small-animal scanner. Delivery of contrast agents across the blood-brain barrier was studied by fluorescent microscopy. Results: All contrast agents accumulated into tumor and showed composition-dependent imaging performance. Peptide-targeted mini-NCAs had hydrodynamic diameters in the range 5.2-9.4 nm and antibody-targeted NCAs had diameters in the range 15.8-20.5 nm. Zeta potentials were in the range of -5.4--8.2 mV and -4.6--8.8 mV, respectively. NCAs showed superior relaxivities compared to MultiHance at 9.4 T. The signal enhancement indicated maximum accumulation in tumor 30-60 minutes after intravenous injection of the mouse tail vein. Only targeted NCAs were retained in tumor for up to 3 hours and displayed contrast enhancement. Conclusion: The novel targeted NCAs with star-PEG features displayed improved relaxivity and greater contrast compared with commercial MultiHance contrast agent. The enhancement by mini-NCAs showed clearance of tumor contrast after 3 hours providing a suitable time window for tumor diagnosis in clinics. The technology provides a great tool with the promise of differential MRI diagnosis of brain tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Glioblastoma/diagnóstico por imagem , Compostos Heterocíclicos/administração & dosagem , Imagem por Ressonância Magnética/métodos , Compostos Organometálicos/administração & dosagem , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacocinética , Modelos Animais de Doenças , Feminino , Humanos , Meglumina/administração & dosagem , Meglumina/análogos & derivados , Meglumina/farmacocinética , Camundongos Nus , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Compostos Organometálicos/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Pharm Res ; 37(6): 97, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409985

RESUMO

PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. METHODS: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (µCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. RESULTS: Our findings demonstrate that synchrotron µCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. CONCLUSIONS: The method outlined in this study provides a proof of concept feasibility for µCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design. Graphical abstract.


Assuntos
Materiais Biocompatíveis/química , Meios de Contraste/química , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Suspensões/química , Tomografia Computadorizada por Raios X/métodos , Animais , Composição de Medicamentos , Imageamento Tridimensional , Injeções Subcutâneas , Intensificação de Imagem Radiográfica , Suínos , Síncrotrons , Tecidos Suporte/química
13.
Int J Nanomedicine ; 15: 3023-3038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431499

RESUMO

Introduction: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ε-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT). Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning. Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation. Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética , Nanopartículas/química , Imagem Óptica , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Feminino , Fluorescência , Células Hep G2 , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polilisina/síntese química , Polilisina/química , Espectroscopia de Prótons por Ressonância Magnética , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Zhonghua Zhong Liu Za Zhi ; 42(4): 319-324, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375448

RESUMO

Objective: To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion. Methods: The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability in vitro was evaluated by in vitro uptake test, and the imaging effect of the contrast agent in vitro was evaluated by in vitro developing test. Results: The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect in vitro. Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence in vitro than those with low expression of gelsolin protein (P<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration (P<0.05). Conclusion: Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect in vitro.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste/química , Diagnóstico por Imagem/métodos , Neoplasias Hepáticas , Ácido Poliglicólico/química , Ultrassonografia/métodos , Animais , Ascite , Linhagem Celular , Gelatina , Ácido Láctico/química , Metástase Linfática , Camundongos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
15.
Clin Hemorheol Microcirc ; 74(4): 353-361, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-116593

RESUMO

In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.


Assuntos
Abdome/irrigação sanguínea , Infecções por Coronavirus/diagnóstico por imagem , Microcirculação , Pneumonia Viral/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Abdome/diagnóstico por imagem , Idoso , Betacoronavirus , Meios de Contraste/química , Feminino , Humanos , Inflamação/diagnóstico por imagem , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Perfusão , Risco , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
16.
Clin Hemorheol Microcirc ; 74(4): 353-361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32333581

RESUMO

In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.


Assuntos
Abdome/irrigação sanguínea , Infecções por Coronavirus/diagnóstico por imagem , Microcirculação , Pneumonia Viral/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Abdome/diagnóstico por imagem , Idoso , Betacoronavirus , Meios de Contraste/química , Feminino , Humanos , Inflamação/diagnóstico por imagem , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Perfusão , Risco , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
17.
Chemosphere ; 253: 126701, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32302902

RESUMO

In this study, we investigated the impact of a TiO2 nanotube (NT) interlayer on the electrochemical performance and service life of Sb and Bi-doped SnO2-coatings synthesized on a titanium mesh. Ti/SnO2-SbBi electrode was synthetized by a thermal decomposition method using ionic liquid as a precursor solvent. Ti/TiO2-NT/SnO2-SbBi electrode was obtained by a two-step electrochemical anodization, followed by the same process of thermal decomposition. The synthesized electrodes were electrochemically characterized and analyzed by scanning electron microscopy and energy dispersive X-ray spectroscopy. Terephthalic acid (TA) experiments showed that Ti/SnO2-SbBi and Ti/TiO2-NT/SnO2-SbBi electrodes formed somewhat higher amounts of hydroxyl radicals (HO) compared with the mesh boron doped diamond (BDD) anode. Electrochemical oxidation experiments were performed using iodinated contrast media (ICM) as model organic contaminants persistent to oxidation. At current density of 50 A m-2, BDD clearly outperformed the synthesized mixed metal oxide (MMO) electrodes, with 2 to 3-fold higher oxidation rates observed for ICM. However, at 100 and 150 A m-2, Ti/SnO2-SbBi had similar performance to BDD, whereas Ti/TiO2-NT/SnO2-SbBi yielded even higher oxidation rates. Disappearance of the target ICM was followed by up to 80% removal of adsorbable organic iodide (AOI) for all three materials, further demonstrating iodine cleavage and thus oxidative degradation of ICM mediated by HO. The presence of a TiO2 NT interlayer yielded nearly 4-fold increase in anode stability and dislocated the oxygen evolution reaction by +0.2 V. Thus, TiO2 NT interlayer enhanced electrode stability and service life, and the electrocatalytic activity for the degradation of persistent organic contaminants.


Assuntos
Meios de Contraste/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Boro/química , Diamante/química , Eletrodos , Nanotubos/química , Oxirredução , Óxidos/química , Titânio/química
18.
Nanoscale Horiz ; 5(3): 573-579, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32118222

RESUMO

Gadolinium (Gd)-based chelates are used as clinical T1 contrast agents for magnetic resonance imaging (MRI) due to their demonstrated high sensitivity and positive contrast enhancement capability. However, there has been an increasing safety concern about their use in medicine because of the toxicity of the metal ions released from these contrast agents when used in vivo. Although significant effort has been made in developing metal-free MRI contrast agents, none have matched the magnetic properties achieved by the gold standard clinical contrast agent, Gd diethylene penta-acetic acid (Gd-DTPA). Here, we report the development of a single-layer, boron-doped graphene quantum dot (termed SL-BGQD) that demonstrates better T1 contrast enhancement than Gd-DTPA. The SL-BGQD is shown to provide significantly higher positive contrast enhancement than the Gd-DTPA contrast agent in imaging vital organs, including kidneys, liver, and spleen, and especially, vasculatures. Further, our results show that the SL-BQGD is able to bypass the blood-brain barrier and allows sustained imaging for at least one hour with a single injection. Hematological and histopathological analyses show that the SL-BGQD demonstrates a non-toxic profile in wild-type mice and may, therefore, serve as an improved, safer alternative to currently available clinical MRI contrast agents.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética/métodos , Pontos Quânticos/química , Animais , Barreira Hematoencefálica/metabolismo , Boro , Meios de Contraste/normas , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Grafite , Humanos , Camundongos
19.
Korean J Radiol ; 21(4): 442-449, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32193892

RESUMO

OBJECTIVE: To compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) versus ultrasonography (US) in symptomatic patients with dense breasts, while using histology as the gold standard. MATERIALS AND METHODS: After obtaining approval from the local ethics board, this prospective study collected data from patients with symptomatic breasts who underwent CESM and US examinations from May 1, 2017 to September 30, 2017. We then selected those with dense breasts and pathological results as our sample population. Both CESM and US results were classified by a radiologist through the Breast Imaging Reporting and Data System, and the results were compared with their corresponding histological results. The chi-square test was conducted to compare the diagnostic performance of CESM and US, and the receiver operating characteristic curves for the two imaging modalities were obtained. RESULTS: A total of 131 lesions from 115 patients with dense breasts were included in this study. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 93.8%, 88.1%, 88.2%, 93.7%, and 90.8% for CESM, and 90.6%, 82.1%, 82.9%, 90.2%, and 86.3% for US, respectively. The p values for sensitivity, specificity, PPV, NPV, and accuracy were 0.687, 0.388, 0.370, 0.702, and 0.238, respectively. The area under the curve of CESM (0.917) was comparable with that of US (0.884); however, the differences between CESM and US were not statistically significant (p = 0.225). Eight false-positive cases and 4 false-negative cases for breast cancer were found in CESM, while 12 false-positive cases and 6 false-negative cases were found in US. CONCLUSION: The diagnostic performances of CESM and US are comparable in symptomatic women with dense breasts; however, the routine use of additional US imaging is questionable for lesions that can be detected by CESM.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/diagnóstico por imagem , Meios de Contraste/química , Mamografia/métodos , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Área Sob a Curva , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem
20.
Korean J Radiol ; 21(4): 462-470, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32193894

RESUMO

OBJECTIVE: To demonstrate that human visual illusion can contribute to sub-endocardial dark rim artifact in contrast-enhanced myocardial perfusion magnetic resonance images. MATERIALS AND METHODS: Numerical phantoms were generated to simulate the first-passage of contrast agent in the heart, and rendered in conventional gray scale as well as in color scale with reduced luminance variation. Cardiac perfusion images were acquired from two healthy volunteers, and were displayed by the same gray and color scales used in the numerical study. Before and after k-space windowing, the left ventricle (LV)-myocardium boarders were analyzed visually and quantitatively through intensity profiles perpendicular the boarders. RESULTS: k-space windowing yielded monotonically decreasing signal intensity near the LV-myocardium boarder in the phantom images, as confirmed by negative finite difference values near the board ranging -1.07 to -0.14. However, the dark band still appears, which is perceived by visual illusion. Dark rim is perceived in the in-vivo images after k-space windowing that removed the quantitative signal dip, suggesting that the perceived dark rim is a visual illusion. The perceived dark rim is stronger at peak LV enhancement than the peak myocardial enhancement, due to the larger intensity difference between LV and myocardium. In both numerical phantom and in-vivo images, the illusory dark band is not visible in the color map due to reduced luminance variation. CONCLUSION: Visual illusion is another potential cause of dark rim artifact in contrast-enhanced myocardial perfusion MRI as demonstrated by illusory rim perceived in the absence of quantitative intensity undershoot.


Assuntos
Artefatos , Coração/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Meios de Contraste/química , Ventrículos do Coração/diagnóstico por imagem , Humanos , Interpretação de Imagem Assistida por Computador , Imagem por Ressonância Magnética
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