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1.
PLoS One ; 19(7): e0306142, 2024.
Article in English | MEDLINE | ID: mdl-38954698

ABSTRACT

Developing T1-weighted magnetic resonance imaging (MRI) contrast agents with enhanced biocompatibility and targeting capabilities is crucial owing to concerns over current agents' potential toxicity and suboptimal performance. Drawing inspiration from "biomimetic camouflage," we isolated cell membranes (CMs) from human glioblastoma (T98G) cell lines via the extrusion method to facilitate homotypic glioma targeting. At an 8:1 mass ratio of ferric chloride hexahydrate to gallic acid (GA), the resulting iron (Fe)-GA nanoparticles (NPs) proved effective as a T1-weighted MRI contrast agent. T98G CM-coated Fe-GA NPs demonstrated improved homotypic glioma targeting, validated through Prussian blue staining and in vitro MRI. This biomimetic camouflage strategy holds promise for the development of targeted theranostic agents in a safe and effective manner.


Subject(s)
Contrast Media , Gallic Acid , Magnetic Resonance Imaging , Gallic Acid/chemistry , Humans , Magnetic Resonance Imaging/methods , Cell Line, Tumor , Contrast Media/chemistry , Iron/chemistry , Biomimetic Materials/chemistry , Glioblastoma/drug therapy , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Nanoparticles/chemistry , Ferric Compounds/chemistry , Cell Membrane/metabolism
2.
Biomed Phys Eng Express ; 10(5)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968931

ABSTRACT

Quantitative contrast-enhanced breast computed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional CT methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promising for breast PCD-CT due to its high quantum efficiency and reduction of fluorescence x-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100µm, a thickness of 500µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and and a mean glandular dose of 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast phantom were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods for estimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breast phantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimating iodine intake in the breast. Furthermore, the study demonstrated the effectiveness of both material decomposition methods in making accurate and precise iodine concentration predictions using a GaAs-based photon counting breast CT system, with better performance when applying the projection-based material decomposition approach. The study highlights the potential of GaAs-based photon counting breast CT systems as viable alternatives to traditional imaging methods in terms of material decomposition and iodine concentration estimation, and proposes phantoms and figures of merit to assess their performance.


Subject(s)
Arsenicals , Breast Neoplasms , Breast , Contrast Media , Gallium , Iodine , Mammography , Phantoms, Imaging , Photons , Tomography, X-Ray Computed , Gallium/chemistry , Humans , Female , Tomography, X-Ray Computed/methods , Contrast Media/chemistry , Mammography/methods , Breast Neoplasms/diagnostic imaging , Breast/diagnostic imaging , Computer Simulation , Monte Carlo Method , Image Processing, Computer-Assisted/methods , Radiation Dosage
3.
Sci Adv ; 10(28): eado2483, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996017

ABSTRACT

Noninvasive tracking of biochemical processes in the body is paramount in diagnostic medicine. Among the leading techniques is spectroscopic magnetic resonance imaging (MRI), which tracks metabolites with an amplified (hyperpolarized) magnetization signal injected into the subject just before scanning. Traditionally, the brief enhanced magnetization period of these agents limited clinical imaging. We propose a solution based on amalgamating two materials-one having diagnostic-metabolic activity and the other characterized by robust magnetization retention. This combination slows the magnetization decay in the diagnostic metabolic probe, which receives continuously replenished magnetization from the companion material. Thus, it extends the magnetization lifetime in some of our measurements to beyond 4 min, with net magnetization enhanced by more than four orders of magnitude. This could allow the metabolic probes to remain magnetized from injection until they reach the targeted organ, improving tissue signatures in clinical imaging. Upon validation, this metabolic MRI technique promises wide-ranging clinical applications, including diagnostic imaging, therapeutic monitoring, and posttreatment surveillance.


Subject(s)
Contrast Media , Magnetic Resonance Imaging , Magnetic Resonance Imaging/methods , Contrast Media/chemistry , Humans , Animals , Magnetics
4.
Sci Rep ; 14(1): 16126, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997313

ABSTRACT

Microbubble contrast agents in ultrasound/echocardiography are used to increase the echogenicity of the target tissues, thereby raising the contrast resolution of the resultant image. Recently, the trend has shifted toward the development of phase-convertible nanodroplets as ultrasound contrast agents due to their promising theragnostic potential by switching capability at the active site. Herein, we fabricated pre-PGS- perfluoropentane phase convertible nanodroplets and checked their in vitro and in vivo enhancement and safety profile. For this, we performed experiments on 20 male Wistar rats and 2 dogs. Biochemical assays of both rats and dogs included complete blood profiles, liver function tests, and renal function tests. For rat vitals, monitoring and histopathological analysis were also performed. Converted nanodroplets showed excellent contrast enhancement, better than Sonovue upon in vitro testing, with an enhancement time of up to 14 min. In vivo, experiments showed comparable opacification of the ventricles of both rats and dogs. All biochemical assays remained within the normal range during the study period. The histopathological analysis did not show any signs of drug-induced toxicity, showing the safety of these nanodroplets. Pre-PGS-PFP nanodroplets hold great potential for use in echocardiography and abdominal imaging in both human and veterinary applications after clinical trials.


Subject(s)
Contrast Media , Rats, Wistar , Ultrasonography , Animals , Dogs , Contrast Media/chemistry , Male , Rats , Ultrasonography/methods , Nanoparticles/chemistry , Microbubbles , Echocardiography/methods , Fluorocarbons/chemistry
5.
J Nanobiotechnology ; 22(1): 419, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014410

ABSTRACT

BACKGROUND: Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments. RESULTS: The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM- 1s- 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg. CONCLUSIONS: This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.


Subject(s)
Contrast Media , Magnetic Iron Oxide Nanoparticles , Magnetic Resonance Imaging , Micelles , Particle Size , Animals , Contrast Media/chemistry , Contrast Media/pharmacokinetics , Tissue Distribution , Magnetic Resonance Imaging/methods , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Iron Oxide Nanoparticles/toxicity , Mice , Rats , Male , Humans , Female
6.
Nat Commun ; 15(1): 5832, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992020

ABSTRACT

While second near-infrared (NIR-II) fluorescence imaging is a promising tool for real-time surveillance of surgical operations, the previously reported organic NIR-II luminescent materials for in vivo imaging are predominantly activated by expensive lasers or X-ray with high power and poor illumination homogeneity, which significantly limits their clinical applications. Here we report a white-light activatable NIR-II organic imaging agent by taking advantages of the strong intramolecular/intermolecular D-A interactions of conjugated Y6CT molecules in nanoparticles (Y6CT-NPs), with the brightness of as high as 13315.1, which is over two times that of the brightest laser-activated NIR-II organic contrast agents reported thus far. Upon white-light activation, Y6CT-NPs can achieve not only in vivo imaging of hepatic ischemia reperfusion, but also real-time monitoring of kidney transplantation surgery. During the surgery, identification of the renal vasculature, post-reconstruction assessment of renal allograft vascular integrity, and blood supply analysis of the ureter can be vividly depicted by using Y6CT-NPs with high signal-to-noise ratios upon clinical laparoscopic LED white-light activation. Our work provides efficient molecular design guidelines towards white-light activatable imaging agent and highlights an opportunity for precision imaging theranostics.


Subject(s)
Optical Imaging , Surgery, Computer-Assisted , Animals , Surgery, Computer-Assisted/methods , Mice , Optical Imaging/methods , Light , Nanostructures/chemistry , Kidney Transplantation/methods , Humans , Liver/diagnostic imaging , Liver/surgery , Nanoparticles/chemistry , Infrared Rays , Luminescence , Kidney/diagnostic imaging , Kidney/surgery , Male , Spectroscopy, Near-Infrared/methods , Contrast Media/chemistry
7.
J Mater Chem B ; 12(29): 7090-7102, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-38984662

ABSTRACT

Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with a T2 relaxation time of 5 ms and an r1 value of 0.31 mM-1 s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.


Subject(s)
Contrast Media , Magnetic Resonance Imaging , Nanostructures , Polymers , Contrast Media/chemistry , Contrast Media/chemical synthesis , Magnetic Resonance Imaging/methods , Animals , Mice , Nanostructures/chemistry , Polymers/chemistry , Humans , Fluorine/chemistry , Particle Size
8.
ACS Nano ; 18(24): 15590-15606, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38847586

ABSTRACT

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.


Subject(s)
Contrast Media , Ultrasonography , Contrast Media/chemistry , Contrast Media/pharmacology , Humans , Animals , Mice , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/therapy , Optical Imaging , Gases/chemistry , Cell Line, Tumor , Female , Mice, Nude
9.
J Mater Chem B ; 12(26): 6371-6383, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38864345

ABSTRACT

The self-assembly of peptides and peptide analogues may be exploited to develop platforms for different biomedical applications, among which CEST-MRI (chemical exchange saturation transfer magnetic resonance imaging) represents one of the most attractive techniques to be explored as a novel metal-free contrast approach in imaging acquisitions. A lysine-containing peptide sequence (LIVAGK-NH2, named K2) was thus modified by insertion, at the N-terminus, of a peptide nucleic acid (PNA) base, leading to a primary amine suitable for the signal generation. a-K2, c-K2, g-K2 and t-K2 peptides were synthesized and characterized. The c-K2 sequence displayed gelling properties and the Watson and Crick pairing, arising from its combination with g-K2, allowed a significant increase in the mechanical responsivity of the hydrogel. These matrices were able to generate a CEST signal around 2.5 ppm from water and, after assessing their cytocompatibility on GL261 (murine glioma), TS/a (murine breast carcinoma), and 3T3-NIH (murine fibroblasts) cell lines, their capability to work as implants for in vivo detection, was proved by intratumor injection in Balb/c mice inoculated with TS/a murine breast cancer cells.


Subject(s)
Contrast Media , Hydrogels , Magnetic Resonance Imaging , Mice, Inbred BALB C , Peptide Nucleic Acids , Peptides , Animals , Hydrogels/chemistry , Hydrogels/chemical synthesis , Mice , Peptide Nucleic Acids/chemistry , Peptides/chemistry , Peptides/chemical synthesis , Contrast Media/chemistry , Contrast Media/chemical synthesis , Female , NIH 3T3 Cells , Cell Line, Tumor
10.
Chem Soc Rev ; 53(13): 6779-6829, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38828885

ABSTRACT

This review focusses on the significance of fluorescent, phosphorescent labelling and tracking of extracellular vesicles (EVs) for unravelling their biology, pathophysiology, and potential diagnostic and therapeutic uses. Various labeling strategies, such as lipid membrane, surface protein, luminal, nucleic acid, radionuclide, quantum dot labels, and metal complex-based stains, are evaluated for visualizing and characterizing EVs. Direct labelling with fluorescent lipophilic dyes is simple but generally lacks specificity, while surface protein labelling offers selectivity but may affect EV-cell interactions. Luminal and nucleic acid labelling strategies have their own advantages and challenges. Each labelling approach has strengths and weaknesses, which require a suitable probe and technique based on research goals, but new tetranuclear polypyridylruthenium(II) complexes as phosphorescent probes have strong phosphorescence, selective staining, and stability. Future research should prioritize the design of novel fluorescent probes and labelling platforms that can significantly enhance the efficiency, accuracy, and specificity of EV labeling, while preserving their composition and functionality. It is crucial to reduce false positive signals and explore the potential of multimodal imaging techniques to gain comprehensive insights into EVs.


Subject(s)
Extracellular Vesicles , Fluorescent Dyes , Extracellular Vesicles/chemistry , Extracellular Vesicles/metabolism , Humans , Fluorescent Dyes/chemistry , Radioactive Tracers , Magnetic Resonance Imaging/methods , Animals , Contrast Media/chemistry , Contrast Media/metabolism
11.
ACS Nano ; 18(26): 16516-16529, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38912600

ABSTRACT

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.


Subject(s)
Gadolinium , Magnetic Resonance Imaging , Nanoparticles , Uterine Cervical Neoplasms , Gadolinium/chemistry , Humans , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/pathology , Female , Nanoparticles/chemistry , Middle Aged , Brachytherapy , Contrast Media/chemistry , X-Rays , Adult , Aged , Chemoradiotherapy
12.
Biomed Mater ; 19(5)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38870928

ABSTRACT

In this investigation, we embarked on the synthesis of polyethylene glycol coated NaGdF4:Tm3+/Yb3+upconversion nanoparticles (UCNPs), aiming to assess their utility in enhancing image contrast within the context of swept source optical coherence tomography (OCT) and photo-thermal OCT imaging. Our research unveiled the remarkable UC emissions stemming from the transitions of Tm3+ions, specifically the1G4→3H6transitions, yielding vibrant blue emissions at 472 nm. We delved further into the UC mechanism, meticulously scrutinizing decay times and the nanoparticles' capacity to convert radiation into heat. Notably, these nanoparticles exhibited an impressive photo-thermal conversion efficiency of 37.5%. Furthermore, our investigations into their bio-compatibility revealed a promising outcome, with more than 90% cell survival after 24 h of incubation with HeLa cells treated with UCNPs. The nanoparticles demonstrated a notable thermal sensitivity of 4.7 × 10-3K-1at 300 K, signifying their potential for precise temperature monitoring at the cellular level.


Subject(s)
Cell Survival , Contrast Media , Nanoparticles , Polyethylene Glycols , Tomography, Optical Coherence , Ytterbium , Tomography, Optical Coherence/methods , Humans , HeLa Cells , Polyethylene Glycols/chemistry , Ytterbium/chemistry , Nanoparticles/chemistry , Contrast Media/chemistry , Thermometry/methods , Gadolinium/chemistry , Thulium/chemistry , Fluorides/chemistry , Temperature , Coated Materials, Biocompatible/chemistry , Infrared Rays
13.
J Mater Chem B ; 12(27): 6521-6531, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38860874

ABSTRACT

Contrast-enhanced magnetic resonance angiography (CE-MRA) plays a critical role in diagnosing and monitoring various vascular diseases. Achieving high-sensitivity detection of vascular abnormalities in CE-MRA depends on the properties of contrast agents. In contrast to clinically used gadolinium-based contrast agents (GBCAs), the new generation of ultrasmall ferrite nanoparticles-based contrast agents have high relaxivity, long blood circulation time, easy surface functionalization, and high biocompatibility, hence showing promising prospects in CE-MRA. This review aims to comprehensively summarize the advancements in ultrasmall ferrite nanoparticles-enhanced MRA for detecting vascular diseases. Additionally, this review also discusses the future clinical translational potential of ultrasmall ferrite nanoparticles-based contrast agents for vascular imaging. By investigating the current status of research and clinical applications, this review attempts to outline the progress, challenges, and future directions of using ultrasmall ferrite nanoparticles to drive the field of CE-MRA into a new frontier of accuracy and diagnostic efficacy.


Subject(s)
Contrast Media , Ferric Compounds , Magnetic Resonance Angiography , Humans , Ferric Compounds/chemistry , Contrast Media/chemistry , Magnetic Resonance Angiography/methods , Animals , Nanoparticles/chemistry , Particle Size , Vascular Diseases/diagnostic imaging , Vascular Diseases/diagnosis
15.
Nat Commun ; 15(1): 5070, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871729

ABSTRACT

In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T2*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.


Subject(s)
Contrast Media , Disease Models, Animal , Ferric Compounds , Indoles , Magnetic Resonance Imaging , Polymers , Thrombosis , Animals , Polymers/chemistry , Magnetic Resonance Imaging/methods , Indoles/chemistry , Mice , Contrast Media/chemistry , Ferric Compounds/chemistry , Thrombosis/diagnostic imaging , Male , Stroke/diagnostic imaging , Humans , Fibrinogen/metabolism , Ischemic Stroke/diagnostic imaging , Mice, Inbred C57BL , Protein Corona/chemistry , Protein Corona/metabolism , Brain/diagnostic imaging , Brain/metabolism , Brain/pathology
16.
Int J Nanomedicine ; 19: 6099-6126, 2024.
Article in English | MEDLINE | ID: mdl-38911500

ABSTRACT

The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on nanocomposites. Nanocomposites, a combination of nanomaterials with diverse properties, have emerged as versatile tools in oncology, offering multifunctional platforms for targeted delivery, imaging, and therapeutic interventions. Nanocomposites exhibit great potential for early detection and accurate imaging in cancer diagnosis. Integrating various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, into nanocomposites enables the development of contrast agents with enhanced sensitivity and specificity. Moreover, functionalizing nanocomposites with targeting ligands ensures selective accumulation in tumor tissues, facilitating precise imaging and diagnostic accuracy. On the therapeutic front, nanocomposites have revolutionized cancer treatment by overcoming traditional challenges associated with drug delivery. The controlled release of therapeutic agents from nanocomposite carriers enhances drug bioavailability, reduces systemic toxicity, and improves overall treatment efficacy. Additionally, the integration of stimuli-responsive components within nanocomposites enables site-specific drug release triggered by the unique microenvironment of the tumor. Despite the remarkable progress in the field, challenges such as biocompatibility, scalability, and long-term safety profiles remain. This article provides a comprehensive overview of recent developments, challenges, and prospects, emphasizing the transformative potential of nanocomposites in revolutionizing the landscape of cancer diagnostics and therapeutics. In Conclusion, integrating nanocomposites in cancer diagnosis and treatment heralds a new era for precision medicine.


Subject(s)
Nanocomposites , Neoplasms , Humans , Nanocomposites/chemistry , Neoplasms/diagnostic imaging , Neoplasms/diagnosis , Neoplasms/drug therapy , Neoplasms/therapy , Animals , Antineoplastic Agents/administration & dosage , Drug Delivery Systems/methods , Magnetic Resonance Imaging/methods , Contrast Media/chemistry , Nanomedicine/methods , Tomography, X-Ray Computed , Drug Carriers/chemistry
17.
J Nanobiotechnology ; 22(1): 356, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902773

ABSTRACT

BACKGROUND: Ultrasound and photoacoustic (US/PA) imaging is a promising tool for in vivo visualization and assessment of drug delivery. However, the acoustic properties of the skull limit the practical application of US/PA imaging in the brain. To address the challenges in targeted drug delivery to the brain and transcranial US/PA imaging, we introduce and evaluate an intracerebral delivery and imaging strategy based on the use of laser-activated perfluorocarbon nanodroplets (PFCnDs). METHODS: Two specialized PFCnDs were developed to facilitate blood‒brain barrier (BBB) opening and contrast-enhanced US/PA imaging. In mice, PFCnDs were delivered to brain tissue via PFCnD-induced BBB opening to the right side of the brain. In vivo, transcranial US/PA imaging was performed to evaluate the utility of PFCnDs for contrast-enhanced imaging through the skull. Ex vivo, volumetric US/PA imaging was used to characterize the spatial distribution of PFCnDs that entered brain tissue. Immunohistochemical analysis was performed to confirm the spatial extent of BBB opening and the accuracy of the imaging results. RESULTS: In vivo, transcranial US/PA imaging revealed localized photoacoustic (PA) contrast associated with delivered PFCnDs. In addition, contrast-enhanced ultrasound (CEUS) imaging confirmed the presence of nanodroplets within the same area. Ex vivo, volumetric US/PA imaging revealed PA contrast localized to the area of the brain where PFCnD-induced BBB opening had been performed. Immunohistochemical analysis revealed that the spatial distribution of immunoglobulin (IgG) extravasation into the brain closely matched the imaging results. CONCLUSIONS: Using our intracerebral delivery and imaging strategy, PFCnDs were successfully delivered to a targeted area of the brain, and they enabled contrast-enhanced US/PA imaging through the skull. Ex vivo imaging, and immunohistochemistry confirmed the accuracy and precision of the approach.


Subject(s)
Blood-Brain Barrier , Brain , Contrast Media , Fluorocarbons , Lasers , Nanoparticles , Photoacoustic Techniques , Animals , Blood-Brain Barrier/metabolism , Fluorocarbons/chemistry , Contrast Media/chemistry , Mice , Photoacoustic Techniques/methods , Brain/diagnostic imaging , Brain/metabolism , Nanoparticles/chemistry , Drug Delivery Systems/methods , Ultrasonography/methods , Male
18.
Ecotoxicol Environ Saf ; 280: 116506, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38875817

ABSTRACT

The study aims at assessing the potential of graphene-based adsorbents to reduce environmental impacts of Iodinated Contrast Media Agents (ICMs). We analyze an extensive collection of ICMs. A modeling approach resting on molecular docking and Density Functional Theory simulations is employed to examine the adsorption process at the molecular level. The study also relies on a Quantitative Structure-Activity Relationship (QSAR) modeling framework to correlate molecular properties with the adsorption energy (Ead) of ICMs, thus enabling identification of the key mechanisms underpinning adsorption and of the key factors contributing to it. A collection of distinct QSAR-based models is developed upon relying on Multiple Linear Regression and a standard genetic algorithm method. Having at our disposal multiple models enables us to take into account the uncertainty associated with model formulation. Maximum Likelihood and formal model identification/discrimination criteria (such as Bayesian and/or information theoretic criteria) are then employed to complement the traditional QSAR modeling phase. This has the advantage of (a) providing a rigorous ranking of the alternative models included in the selected set and (b) quantifying the relative degree of likelihood of each of these models through a weight or posterior probability. The resulting workflow of analysis enables one to seamlessly embed DFT and QSAR studies within a theoretical framework of analysis that explicitly takes into account model and parameter uncertainty. Our results suggest that graphene-based surfaces constitute a promising adsorbent for ICMs removal, π-π stacking being the primary mechanism behind ICM adsorption. Furthermore, our findings offer valuable insights into the potential of graphene-based adsorbent materials for effectively removing ICMs from water systems. They contribute to ascertain the significance of various factors (such as, e.g., the distribution of atomic van der Waals volumes, overall molecular complexity, the presence and arrangement of Iodine atoms, and the presence of polar functional groups) on the adsorption process.


Subject(s)
Contrast Media , Graphite , Quantitative Structure-Activity Relationship , Graphite/chemistry , Adsorption , Contrast Media/chemistry , Molecular Docking Simulation , Computer Simulation , Bayes Theorem , Density Functional Theory , Water Pollutants, Chemical/chemistry
19.
Sensors (Basel) ; 24(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38894358

ABSTRACT

Simultaneous dual-contrast imaging of iodine and bismuth has shown promise in prior phantom and animal studies utilizing spectral CT. However, it is noted that in previous studies, Pepto-Bismol has frequently been employed as the source of bismuth, exceeding the recommended levels for human subjects. This investigation sought to assess the feasibility of visually differentiating and precisely quantifying low-concentration bismuth using clinical dual-source photon-counting CT (PCCT) in a scenario involving both iodinated and bismuth-based contrast materials. Four bismuth samples (0.6, 1.3, 2.5, and 5.1 mg/mL) were prepared using Pepto-Bismol, alongside three iodine rods (1, 2, and 5 mg/mL), inserted into multi-energy CT phantoms with three different sizes, and scanned on a PCCT system at three tube potentials (120, 140, and Sn140 kV). A generic image-based three-material decomposition method generated iodine and bismuth maps, with mean mass concentrations and noise levels measured. The root-mean-square errors for iodine and bismuth determined the optimal tube potential. The tube potential of 140 kV demonstrated optimal quantification performance when both iodine and bismuth were considered. Distinct differentiation of iodine rods with all three concentrations and bismuth samples with mass concentrations ≥ 1.3 mg/mL was observed across all phantom sizes at the optimal kV setting.


Subject(s)
Bismuth , Contrast Media , Iodine , Phantoms, Imaging , Photons , Tomography, X-Ray Computed , Bismuth/chemistry , Iodine/chemistry , Tomography, X-Ray Computed/methods , Contrast Media/chemistry , Humans
20.
Phys Med Biol ; 69(13)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38843808

ABSTRACT

Objective.Super-resolution ultrasonography offers the advantage of visualization of intricate microvasculature, which is crucial for disease diagnosis. Mapping of microvessels is possible by localizing microbubbles (MBs) that act as contrast agents and tracking their location. However, there are limitations such as the low detectability of MBs and the utilization of a diluted concentration of MBs, leading to the extension of the acquisition time. We aim to enhance the detectability of MBs to reduce the acquisition time of acoustic data necessary for mapping the microvessels.Approach.We propose utilizing phase patterned waves (PPWs) characterized by spatially patterned phase distributions in the incident beam to achieve this. In contrast to conventional ultrasound irradiation methods, this irradiation method alters bubble interactions, enhancing the oscillation response of MBs and generating more significant scattered waves from specific MBs. This enhances the detectability of MBs, thereby enabling the detection of MBs that were undetectable by the conventional method. The objective is to maximize the overall detection of bubbles by utilizing ultrasound imaging with additional PPWs, including the conventional method. In this paper, we apply PPWs to ultrasound imaging simulations considering bubble-bubble interactions to elucidate the characteristics of PPWs and demonstrate their efficacy by employing PPWs on MBs fixed in a phantom by the experiment.Main results.By utilizing two types of PPWs in addition to the conventional ultrasound irradiation method, we confirmed the detection of up to 93.3% more MBs compared to those detected using the conventional method alone.Significance.Ultrasound imaging using additional PPWs made it possible to increase the number of detected MBs, which is expected to improve the efficiency of bubble detection.


Subject(s)
Microbubbles , Phantoms, Imaging , Ultrasonography , Ultrasonography/methods , Contrast Media/chemistry
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