Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Significance: Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. Aim: We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). Approach: We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. Results: We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ϕ ) for nEGs fabricated using 100 µ M of BrCy112 is ∼ 41 -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their ϕ as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Conclusions: Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

The influence of contrast media on calcium-based imaging of the spine in dual-layer CT.

This study aimed to evaluate the impact of contrast media application on CT attenuation of the bone using a novel calcium-only imaging technique (VCa) from dual-layer spectral detector CT (DLCT), which enables CT-based bone mineral density measurement unimpeded by soft tissue components. For this, true non-contrast (TNC) and venous phase images (VP) of n = 97 patients were acquired. CT attenuation of the first lumbar vertebra (L1) was measured in TNC-VCa, VP-VCa, and in virtual non-contrast images (VNC). CT attenuation was significantly higher in VP-VCa than in TNC-VCa (p < 0.001), although regression analyses revealed a strong linear association between these measures (R2 = 0.84). A statistical model for the prediction of TNC-VCa CT attenuation was established (TNC-VCa[HU] = - 6.81 + 0.87 × VP-VCa[HU]-0.55 × body weight[kg]) and yielded good agreement between observed and predicted values. Furthermore, a L1 CT attenuation threshold of 293 HU in VP-VCa showed a sensitivity of 90% and a specificity of 96% for detecting osteoporosis. The application of contrast media leads to an overestimation of L1 CT attenuation in VCa. However, CT attenuation values from VP-VCa can be used within CT-based opportunistic osteoporosis screening eighter by applying a separate threshold of 293 HU or by converting measured data to TNC-VCa CT attenuation with the given regression equation.

Noninvasive Photothermal Therapy of Nasopharyngeal Cancer Guided by High Efficiency Optical-Absorption Nanomaterial Enhanced by NIR-II Photoacoustic Imaging.

Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Ultrahigh-Resolution Visualization of Vascular Heterogeneity in Brain Tumors via Magnetic Nanoparticles-Enhanced Susceptibility-Weighted Imaging.

The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.

Correction for partial volume averaging in the quantification of radiopaque nanomaterial-embedded resorbable polymers.

Resorbable inferior vena cava (IVC) filters require embedded contrast for image-guided placement and integrity monitoring. We calculated correction factors to account for partial volume averaging of thin nanoparticle (NP)-embedded materials, accounting for object and slice thicknesses, background signal, and nanoparticle concentration. We used phantoms containing polycaprolactone disks embedded with bismuth (Bi) or ytterbium (Yb): 0.4- to 1.2-mm-thick disks of 20 mg ml-1NPs (thickness phantom), 0.4-mm-thick disks of 0-20 mg ml-1NPs in 2 mg ml-1iodine (concentration phantom), and 20 mg ml-1NPs in 0.4-mm-thick disks in 0-10 mg ml-1iodine (background phantom). Phantoms were scanned on a dual-source CT with 80, 90, 100, and 150 kVp with tin filtration and reconstructed at 1.0- to 1.5-mm slice thickness with a 0.1-mm interval. Following scanning, disks were processed for inductively coupled plasma optical emission spectrometry (ICP-OES) to determine NP concentration. Mean and maximum CT numbers (HU) of all disks were measured over a 0.5-cm2area for each kVp. HU was converted to concentration using previously measured calibrations. Concentration measurements were corrected for partial volume averaging by subtracting residual slice background and extrapolating disk thickness to both nominal and measured slice sensitivity profiles (SSP, mm). Slice thickness to agreement (STTA, mm) was calculated by replacing the CT-derived concentrations with ICP-OES measurements and solving for thickness. Slice thickness correction factors improved agreement with ICP-OES for all measured data. Yb corrections resulted in lower STTA than Bi corrections in the concentration phantom (1.01 versus 1.31 STTA/SSP, where 1.0 is perfect agreement), phantoms with varying thickness (1.30 versus 1.87 STTA/SSP), and similar ratio in phantoms with varying background iodine concentration (1.34 versus 1.35 STTA/SSP). All measured concentrations correlated strongly with ICP-OES and all corrections for partial volume averaging increased agreement with ICP-OES concentration, demonstrating potential for monitoring the integrity of thin IVC resorbable filters with CT.

Electron Transfer Drives the Photosensitized Polymerization of Contrast Agents by Flavoprotein Tags for Correlative Microscopy.

Singlet oxygen generation has long been considered the key feature that allows genetically encoded fluorescent tags to produce polymeric contrast agents for electron microscopy. Optimization of the singlet oxygen sensitization quantum yield has not included the effects of electron-rich monomers on the sensitizer's photocycle. We report that at monomer concentrations employed for staining, quenching by electron transfer is the primary deactivation pathway for photoexcitations. A simple photochemical model including contributions from both processes reproduces the observed reaction rates and indicates that most of the product is driven by pathways that involve electron transfer with monomers─not by the sensitization of singlet oxygen. Realizing the importance of these competing reaction pathways offers a new paradigm to guide the development of genetically encodable tags and suggests opportunities to expand the materials scope and growth conditions for polymeric contrast agents (e.g., biocompatible monomers, O2 poor environments).

Tailoring the pore structure of iron oxide core@stellate mesoporous silica shell nanocomposites: effects on MRI and magnetic hyperthermia properties and applicability to anti-cancer therapies.

Core-shell nanocomposites made of iron oxide core (IO NPs) coated with mesoporous silica (MS) shells are promising theranostic agents. While the core is being used as an efficient heating nanoagent under alternating magnetic field (AMF) and near infra-red (NIR) light and as a suitable contrast agent for magnetic resonance imaging (MRI), the MS shell is particularly relevant to ensure colloidal stability in a biological buffer and to transport a variety of therapeutics. However, a major challenge with such inorganic nanostructures is the design of adjustable silica structures, especially with tunable large pores which would be useful, for instance, for the delivery of large therapeutic biomolecule loading and further sustained release. Furthermore, the effect of tailoring a porous silica structure on the magneto- or photothermal dissipation still remains poorly investigated. In this work, we undertake an in-depth investigation of the growth of stellate mesoporous silica (STMS) shells around IO NPs cores and of their micro/mesoporous features respectively through time-lapse and in situ liquid phase transmission electron microscopy (LPTEM) and detailed nitrogen isotherm adsorption studies. We found here that the STMS shell features (thickness, pore size, surface area) can be finely tuned by simply controlling the sol-gel reaction time, affording a novel range of IO@STMS core@shell NPs. Finally, regarding the responses under alternating magnetic fields and NIR light which are evaluated as a function of the silica structure, IO@STMS NPs having a tunable silica shell structure are shown to be efficient as T2-weighted MRI agents and as heating agents for magneto- and photoinduced hyperthermia. Furthermore, such IO@STMS are found to display anti-cancer effects in pancreatic cancer cells under magnetic fields (both alternating and rotating).

Therapeutic and Contrast Agents for Photoacoustic Imaging-Guided Photothermal Therapy: A Narrative Review.

Photoacoustic imaging is a hybrid modality that combines high-contrast and spectroscopy-based optical imaging specificity with the high spatial resolution of ultrasonography. This review highlights the development and progress of photoacoustic imaging technology over the past decade. This imaging technology has evolved to be more user-friendly, cost-effective, and portable, demonstrating its potential for diverse clinical applications. A potential clinical application lies in the use of photoacoustic imaging as a guiding tool for photothermal therapy. This review was conducted by initially filtering through three databases, namely, Google Scholar, PubMed, and Scopus, resulting in 460 articles published between 2019 and May 2023. Of these, 54 articles were deemed suitable for review after identification. The selected articles were research papers focusing on the development of therapeutic agents that enhance contrast in photoacoustic imaging. All reviewed articles tested these agents both in vitro and in vivo. This review focuses on wavelength absorption and radiation sources for photothermal therapy. The developed agents predominantly used NIR-I wavelengths, whereas the NIR-II region has been less explored, indicating significant potential for future research. This review provides comprehensive insights into the advancement of compounds serving as therapeutic agents and contrast agents in photoacoustic imaging-guided photothermal therapy.

Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile.

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.

Revealing Detailed Cartilage Function Through Nanoparticle Diffusion Imaging: A Computed Tomography & Finite Element Study.

The ability of articular cartilage to withstand significant mechanical stresses during activities, such as walking or running, relies on its distinctive structure. Integrating detailed tissue properties into subject-specific biomechanical models is challenging due to the complexity of analyzing these characteristics. This limitation compromises the accuracy of models in replicating cartilage function and impacts predictive capabilities. To address this, methods revealing cartilage function at the constituent-specific level are essential. In this study, we demonstrated that computational modeling derived individual constituent-specific biomechanical properties could be predicted by a novel nanoparticle contrast-enhanced computer tomography (CECT) method. We imaged articular cartilage samples collected from the equine stifle joint (n = 60) using contrast-enhanced micro-computed tomography (µCECT) to determine contrast agents' intake within the samples, and compared those to cartilage functional properties, derived from a fibril-reinforced poroelastic finite element model. Two distinct imaging techniques were investigated: conventional energy-integrating µCECT employing a cationic tantalum oxide nanoparticle (Ta2O5-cNP) contrast agent and novel photon-counting µCECT utilizing a dual-contrast agent, comprising Ta2O5-cNP and neutral iodixanol. The results demonstrate the capacity to evaluate fibrillar and non-fibrillar functionality of cartilage, along with permeability-affected fluid flow in cartilage. This finding indicates the feasibility of incorporating these specific functional properties into biomechanical computational models, holding potential for personalized approaches to cartilage diagnostics and treatment.

Clinical feasibility of deep learning based synthetic contrast enhanced abdominal CT in patients undergoing non enhanced CT scans.

Our objective was to develop and evaluate the clinical feasibility of deep-learning-based synthetic contrast-enhanced computed tomography (DL-SynCCT) in patients designated for nonenhanced CT (NECT). We proposed a weakly supervised learning with the utilization of virtual non-contrast CT (VNC) for the development of DL-SynCCT. Training and internal validations were performed with 2202 pairs of retrospectively collected contrast-enhanced CT (CECT) images with the corresponding VNC images acquired from dual-energy CT. Clinical validation was performed using an external validation set including 398 patients designated for true nonenhanced CT (NECT), from multiple vendors at three institutes. Detection of lesions was performed by three radiologists with only NECT in the first session and an additionally provided DL-SynCCT in the second session. The mean peak signal-to-noise ratio (PSNR) and structural similarity index map (SSIM) of the DL-SynCCT compared to CECT were 43.25 ± 0.41 and 0.92 ± 0.01, respectively. With DL-SynCCT, the pooled sensitivity for lesion detection (72.0% to 76.4%, P < 0.001) and level of diagnostic confidence (3.0 to 3.6, P < 0.001) significantly increased. In conclusion, DL-SynCCT generated by weakly supervised learning showed significant benefit in terms of sensitivity in detecting abnormal findings when added to NECT in patients designated for nonenhanced CT scans.

Efficient one-step amide formation using amino porphyrins.

Amide bonds are one of the most prevalent phenomena in nature and are utilized frequently in drug and material design. However, forming amide bonds is not always efficient or high yielding, particularly when the amine used to conjugate to a carboxylic acid is a weak nucleophile. This limitation precludes many useful amino compounds from participating in conjugation reactions to form amides. A particularly valuable amino compound, which is also a very weak nucleophile, is the amino porphyrin, valued for its role as a photosensitizer, fluorescent agent, catalyst, or, upon metalation, even a very efficient contrast agent for magnetic resonance imaging (MRI). In this work, we propose fast and high-yield coupling of an unreactive amine - the amino porphyrin - to carboxylic acid via isothiocyanate conjugation. Reactions can be achieved in one step at room temperature in one hour, achieving quantitative conversion and near perfect selectivity. Both metalated and unmetalated porphyrin, as well as fluorescein isothiocyanate (FITC), demonstrated efficient conjugation. To illustrate the value of the proposed method, we created a new blood-pool MRI contrast agent that reversibly binds to serum albumin. This new blood-pool agent, known as MITC-Deox (MRI isothiocyanate that links with deoxycholic acid), substantially reduced T1 relaxation times in blood vessels in mice, remained stable for 1 hour, cleared from blood by 24 hours, and was eliminated from the body after 4 days. The proposed method for efficient amide formation is a superior alternative to existing coupling methods, opening a door to novel synthesis of MRI contrast agents and beyond.

Visualization of distribution in the vitreous cavity via eye drops using ultra-heavily T2-weighted sequences in MRI: a preliminary study with enucleated pig eyes.

We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H217O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to "No drop." The T1 and T2 values of samples treated with gadobutrol and H217O decreased over time. The SIR of samples treated with gadobutrol and H217O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H217O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops.

Novel Gd-DTPA-peptide for targeted breast tumor magnetic resonance imaging.

The prevalence of breast cancer underscores the imperative for early diagnosis in guiding treatment decisions. This study introduces a novel contrast agent, Gd-DTPA-VGB3, derived from the peptide VGB3 targeting vascular endothelial growth factor receptor-1 (VEGFR1) and VEGFR2, to enhance the contrast of conventional drug Magnevist in breast tumor MRI. The MRI contrast agent was synthesized on rink amide resin via Fmoc strategy, incorporating amino acids, and coupling to diethylenetriaminepentaacetic acid (DTPA). Gadolinium (Gd)-DTPA-VGB3 displayed specific binding to VEGFR1/2 in a displacement binding assay. Gd-DTPA-VGB3 exhibited minimal cytotoxicity to normal MCF-10 cells while inhibiting 4T1 mammary carcinoma cell proliferation. Compared to Magnevist, Gd-DTPA-VGB3 demonstrated a 2.8-fold increase in contrast-to-noise ratio (CNR) (355 vs. 125). Gd-DTPA-VGB3 exhibited enhanced accumulation in 4T1 tumor-bearing mice, resulting in significant signal intensity improvement. The findings highlight Gd-DTPA-VGB3's specific binding to VEGFRs, substantiating its potential as a candidate for enhancing MRI contrast in breast cancer diagnostics.

Charged Gold Nanoparticles for Target Identification-Alignment and Automatic Segmentation of CT Image-Guided Adaptive Radiotherapy in Small Hepatocellular Carcinoma.

Because of the challenges posed by anatomical uncertainties and the low resolution of plain computed tomography (CT) scans, implementing adaptive radiotherapy (ART) for small hepatocellular carcinoma (sHCC) using artificial intelligence (AI) faces obstacles in tumor identification-alignment and automatic segmentation. The current study aims to improve sHCC imaging for ART using a gold nanoparticle (Au NP)-based CT contrast agent to enhance AI-driven automated image processing. The synthesized charged Au NPs demonstrated notable in vitro aggregation, low cytotoxicity, and minimal organ toxicity. Over time, an in situ sHCC mouse model was established for in vivo CT imaging at multiple time points. The enhanced CT images processed using 3D U-Net and 3D Trans U-Net AI models demonstrated high geometric and dosimetric accuracy. Therefore, charged Au NPs enable accurate and automatic sHCC segmentation in CT images using classical AI models, potentially addressing the technical challenges related to tumor identification, alignment, and automatic segmentation in CT-guided online ART.

Optimizing pseudo-spiral sampling for abdominal DCE MRI using a digital anthropomorphic phantom.

PURPOSE: For reliable DCE MRI parameter estimation, k-space undersampling is essential to meet resolution, coverage, and signal-to-noise requirements. Pseudo-spiral (PS) sampling achieves this by sampling k-space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k-space sampling patterns for abdomin al DCE MRI. METHODS: The optimal PS k-space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient. RESULTS: The best PS reconstruction was found to be PS-diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient. CONCLUSION: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient.

Trimetallic nanocomposites developed for efficient in vivo bimodal imaging via fluorescence and magnetic resonance.

Despite several attempts, in vivo bimodal imaging still represents a challenge. Generally, it is accepted that dual-modality in imaging can improve sensitivity and spatial resolution, namely, when exploiting fluorescence (FI) and magnetic resonance imaging (MRI), respectively. Here, a newly developed combination of (i) protein-protected luminescent Au-Ag nanoclusters (LGSN) manifesting themselves by fluorescent emission at 705 nm and (ii) superparamagnetic iron oxide nanoparticles (SPION) embedded within the same protein and creating contrast in MR images, has been investigated in phantoms and applied for in vivo bimodal imaging of a mouse as a proof of principle. Unique LGSN-SPION nanocomposites were synthesized in a specific sequential one-pot green preparation procedure and characterized thoroughly using many physicochemical experimental techniques. The influence of LGSN-SPION samples on the viability of healthy cells (RPE-1) was tested using a calcein assay. Despite the presence of Ag (0.12 mg mL-1), high content of Au (above 0.75 mg mL-1), and moderate concentrations of Fe (0.24 mg mL-1), LGSN-SPION samples (containing approx. 15 mg mL-1 of albumin) were revealed as biocompatible (cell viability above 80%). Simultaneously, these concentration values of all components in the LGSN-SPION nanocomposite were used for achieving both MRI and fluorescence signals in phantoms as well as in a living mouse with sufficiently high resolution. Thus, the LGSN-SPION samples can serve as new efficient bimodal FI and MRI probes for in vivo imaging.

Graphene-based nanomaterials for adsorption of iodinated X-ray contrast media from contaminated water: A comparative study.

Iodinated X-ray contrast media (ICM) was frequently detected in the aqueous environment. In this work, the applicability of three graphene-based nanomaterials (graphene nanosheets (GNS), graphene oxide (GO), and reduced graphene oxide (rGO)) for the adsorptive removal of the six ICMs including iohexol, iopamidol, iomeprol, iopromide, iodixanol and ioversol from aqueous solution was firstly evaluated by batch adsorption method. Among the three graphene-based nanomaterials, the GNS displayed the best adsorption performances for the adsorption of the six ICMs. The maximum uptakes of the six ICMs by the GNS (161.5 mg g-1 for iohexol, 267.2 mg g-1 for iodixanol, 197.7 mg g-1 for iopromide, 197.0 mg g-1 for iopamidol, 109.6 mg g-1 for iomeprol, and 168.2 mg g-1 for ioversol) can rapidly achieved within 10 min and indicate no dependence on pH in the range of 4-9. The results obtained from the calculations of isotherms, kinetics and thermodynamic supported the occurrence of a chemisorption of the GNS for the six ICMs. The π-π interactions between benzene ring of the ICMs and the sp2-hybridized two-dimensional sheet of GNS were deemed the predominant adsorption mechanism.