Imaging Contrast Research Articles

Advancements in Tumor Diagnostics through Carbon Dot‐Assisted Photoacoustic Imaging

AbstractSerendipitously discovered, carbon dots (CDs) have attracted significant attention as a potential contrast agent for photoacoustic imaging (PAI) in the biomedical sector. CDs play an essential role in PAI, contributing significantly to the early detection of diseases and monitoring treatment progress, particularly in tumor imaging. This review emphasizes the role of CDs in the domain of PAI, highlighting their characteristics like biocompatibility, enhanced spatial resolution, optical absorption in the NIR region, and facile surface functionalization for tumor‐ targeted imaging. The study explores the use of CDs for enhancing spatial resolution in PAI for improved detection and visualization of tumors in organs such as the breast, cervical, liver, gastrointestinal, skin, cardiovascular system, nervous system, and others. Challenges associated with PAI, such as optimizing the signal‐to‐noise ratio and ensuring stability under physiological conditions, have also been discussed.

Precision Cancer Therapy Enabled Anti-Epidermal Growth Factor Receptor-Conjugated Manganese Core Phthalocyanine Bismuth Nanocomposite for Dual Imaging-Guided Breast Cancer Treatment

Cancer remains a formidable global health challenge, demanding the exploration of innovative treatment modalities with minimized side effects. One promising avenue involves the synergistic integration of targeted photothermal/photodynamic therapy (PTT/PDT), utilizing specially designed functional nanomaterials for precise cancer diagnosis and treatment. This study introduces a composite biomaterial, anti-epidermal growth factor receptor-conjugated manganese core phthalocyanine bismuth (anti-EGFR-MPB), synthesized for precise cancer imaging and treatment. The biomaterial, synthesized via a solvothermal process, effectively treats and images breast cancer in mouse models. Its biomimetic design targets cancer cells precisely, with dual imaging for real-time monitoring. The biomimetic design of the composite enables precise targeting of cancer cells, whereas the dual imaging allows for real-time visualization and monitoring of the treatment. In vivo examinations confirm substantial damage to tumor tissues with no recurrence following 808-nm laser irradiation. The composite shows strong fluorescence/photoacoustic imaging (PAI) contrast, aiding malignancy detection. Biological assays and histological analyses confirmed the efficacy of the nanocomposite in inducing apoptosis in cancer cells. The integrated targeted dual image-guided phototherapy offered by this composite substantially enhances the precision and efficacy of cancer therapy, achieving an impressive photothermal efficiency of ~33.8%. Our findings demonstrate the utility of the anti-EGFR-MPB nanocomposite for both in vitro and in vivo photoacoustic image-guided PTT and PDT. The optimal treatment strategy for triple-negative breast cancer is found to be the use of 250 μg/ml of nanocomposite irradiated with 1.0 W/cm 2 808-nm laser for 7 min.

Development and validation of a controlled heating apparatus for long‐term MRI of 3D microfluidic tumor models

AbstractConventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and in vivo MRI is limited by regulatory approval of long‐term anesthesia use. Microfluidic tumor models (MTMs) offer a cost‐effective, reproducible, and high throughput platform for bridging cell and animal models. Yet, MRI of microfluidic devices is challenging, due to small fluid volumes generating low sensitivity. For the first time, an MRI of MTMs was performed at low field strength (1 T) using conventional imaging equipment without microcoils. To enable longitudinal MRI, we developed (1) CHAMP‐3 (controlled heating apparatus for microfluidics and portability) which heats MTMs during MRI scans and (2) an MRI‐compatible temperature monitoring system. CHAMP‐3 maintained chip surface temperature at ~37°C and the media inside at ~35.5°C. Enhanced T1‐weighted MRI contrast was achieved in 3D MTMs with free manganese (Mn2+) solutions and Mn2+ labeled tumor cells.

Can the second phase of contrast-enhanced MRA of the neck provide additional information in the acute stroke setting?

Double-concentration magnetic resonance imaging (MRI) contrast agents are frequently used in contrast-enhanced MR angiography (CE-MRA) of the head and neck. To avoid mistiming the peak concentration of intraluminal contrast (due to shorter duration of peak), a second acquisition is sometimes performed. To evaluate additional information from the second acquisition of CE-MRA and compare the collateral scoring to the hypoperfusion index obtained on MR perfusion, and to investigate presence of pseudo-occlusion using the second phase of CE-MRA. A retrospective study was conducted. CE-MRA of the brain/neck, dynamic susceptibility contrast (DSC) MR perfusion scan (in majority) and subsequent digital subtraction angiography (DSA) were evaluated in patients with previous acute internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion. Evaluation of CE-MRA/MR perfusion and DSA was performed by three experienced neuroradiologists and one neurointerventionist, respectively. The site of ICA occlusion was seen to be distal to the site noted on early arterial phase (pseudo-occlusion of ICA) in 28.5% of patients. A significant negative correlation was seen between a higher HIR and collateral score. Evaluation of second phase CE-MRA can provide valuable information that may be otherwise lost if only the early arterial phase is evaluated.

Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging in Magnetic Resonance in the Assessment of Peritoneal Recurrence of Ovarian Cancer in Patients with or Without BRCA Mutation

Background: The aim of this study was to determine the differences in diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) parameters between patients with peritoneal high-grade serous ovarian cancer (HGSOC) recurrence with BRCA mutations (BRCAmut) or BRCA wild type (BRCAwt). Materials and Methods: We retrospectively analyzed the abdominal and pelvic magnetic resonance (MR) images of 43 patients suspected of having recurrent HGSOC, of whom 18 had BRCA1/2 gene mutations. Patients underwent MRI examination via a 1.5 T MRI scanner, and the analyzed parameters were as follows: apparent diffusion coefficient (ADC), time to peak (TTP) and perfusion maximum enhancement (Perf. Max. En.). Results: The mean ADC in patients with BRCAwt was lower than that in patients with BRCAmut: 788.7 (SD: 139.5) vs. 977.3 (SD: 103), p-value = 0.00002. The average TTP value for patients with BRCAwt was greater than that for patients with mutations: 256.3 (SD: 50) vs. 160.6 (SD: 35.5), p-value < 0.01. The Perf. Max. En. value was lower in the BRCAwt group: 148.6 (SD: 12.3) vs. 233.6 (SD: 29.2), p-value < 0.01. Conclusion: Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.

Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring.

Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19 to 60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24 hr pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2 ‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼ ±0.2-0.3 ‰) over timescales>160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB is presented.

TME-Activated MnO2/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma.

Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy. To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM. This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.

Ultrathin visible-light OCT endomicroscopy for in vivo ultrahigh-resolution neuroimaging in deep brain

Deep-brain neuroimaging, a task that demands high-resolution imaging techniques for visualizing intricate brain structures, assessing deep-seated disease histopathology, and offering real-time intervention guidance, is challenged by the resolution-depth trade-off of current methods. We propose an optical coherence tomography (OCT) endomicroscopy device for high-resolution in vivo imaging of deep brain microstructures and histopathology. A unique liquid shaping technique enables the direct fabrication of a microlens on the fiber tip of the imaging probe, optimizing imaging performance parameters, such as longitudinal focal shift, focused spot size, and working distance. In addition, a broadband visible-light source enhances axial resolution and OCT imaging contrast. As a result, the first monolithic visible-light OCT (vis-OCT) endomicroscope, with a submillimeter outer diameter (∼0.4 mm), is presented, achieving an ultrahigh resolution of 1.4 μm axial × 4.5 μm transverse in air. This compact probe allows minimally invasive in vivo deep-brain imaging in mice at a depth of 7.2 mm. Key regions in the mouse deep brain, such as the isocortex, corpus callosum, and caudate putamen, were successfully identified using our vis-OCT endomicroscope. In addition, we examined the myeloarchitectures and cytoarchitectures in the isocortex. Our findings demonstrate that the vis-OCT endomicroscope offers enhanced visualization of myelinated axon fibers and nerve fiber bundles compared to its 800 nm counterpart. This vis-OCT endomicroscope, overcoming resolution and imaging depth limitations of conventional methods, offers a novel tool for minimally invasive, ultrahigh-resolution in vivo deep brain neuroimaging.

Harnessing quantum light for microscopic biomechanical imaging of cells and tissues

The biomechanical properties of cells and tissues play an important role in our fundamental understanding of the structures and functions of biological systems at both the cellular and subcellular levels. Recently, Brillouin microscopy, which offers a label-free spectroscopic means of assessing viscoelastic properties in vivo, has emerged as a powerful way to interrogate those properties on a microscopic level in living tissues. However, susceptibility to photodamage and photobleaching, particularly when high-intensity laser beams are used to induce Brillouin scattering, poses a significant challenge. This article introduces a transformative approach designed to mitigate photodamage in biological and biomedical studies, enabling nondestructive, label-free assessments of mechanical properties in live biological samples. By leveraging quantum-light-enhanced stimulated Brillouin scattering (SBS) imaging contrast, the signal-to-noise ratio is significantly elevated, thereby increasing sample viability and extending interrogation times without compromising the integrity of living samples. The tangible impact of this methodology is evidenced by a notable three-fold increase in sample viability observed after subjecting the samples to three hours of continuous squeezed-light illumination, surpassing the traditional coherent light-based approaches. The quantum-enhanced SBS imaging holds promise across diverse fields, such as cancer biology and neuroscience where preserving sample vitality is of paramount significance. By mitigating concerns regarding photodamage and photobleaching associated with high-intensity lasers, this technological breakthrough expands our horizons for exploring the mechanical properties of live biological systems, paving the way for an era of research and clinical applications.

Changes in the relaxivity of water-organic solvent miscible systems: Hidden forces beyond metal ions.

The relaxivity of magnetic resonance imaging (MRI) contrast agents is primarily attributed to metal ions such as gadolinium (Gd) and iron. However, the impact of organic solutes on relaxivity, particularly through alterations in water molecule dynamics, has not been thoroughly investigated. This research was aimed to explore how organic solutes affect the relaxivities of water and Gd-based contrast agents (GBCAs), potentially revealing new aspects for the development of contrast agents. To investigate the effects of different proportions of water-soluble organic solvents mixed with pure water and GBCA on T1 and T2 relaxivities. Ethanol, dimethyl sulfoxide (DMSO), 1,4-dioxane, glycerin, ethylene glycol, diethylene glycol, polyethylene glycol (PEG) 200, and PEG 400 were mixed with ultrapure water in various ratios (100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90, 0:100). GBCA was added to these mixtures at a concentration of 0.05 mmol/L. The mixtures underwent T1 and T2 mapping scans using a 3.0 Tesla MRI machine, and the relaxivities R1 (1/T1) and R2 (1/T2) were calculated and compared. The relaxivity R1 of ethanol, 1,4-dioxane, and DMSO mixtures with water or GBCA, as well as R2 of DMSO mixtures with GBCA, initially increased and then decreased. Conversely, R1 and R2 increased significantly with higher proportions of diethylene glycol, PEG 200, and glycerin in the mixtures with GBCA. The increase in relaxivity R1 was correlated with greater viscosity. When the proportion of DMSO and diethylene glycol exceeded 20%, minimal variability in R2 was observed as the water content decreased. Adding organic solvents to water and paramagnetic relaxation reagents could alter T1 and T2 relaxivities, suggesting potential new directions for modifying current contrast agents. Additionally, increasing the viscosity of the contrast agent was found to enhance the relaxivity.

Saturation transfer (CEST and MT) MRI for characterization of U-87 MG glioma in the rat.

The focus of this work was to identify the optimal magnetic resonance imaging (MRI) contrast between orthotopic U-87 MG tumours and normal appearing brain with the eventual goal of treatment response monitoring. U-87 MG human glioblastoma cells were injected into the brain of RNU nude rats (n= 9). The rats were imaged at 7T at three timepoints for all animals: 3-5, 7-9, and 11-13 days after implantation. Whole-brain T1-weighted (before and after gadolinium contrast agent injection), diffusion, and fluid-attenuated inversion recovery scans were performed. In addition, single-slice saturation-transfer-weighted chemical exchange saturation transfer (CEST), magnetization transfer (MT), and water saturation shift referencing (WASSR) contrast Z-spectra and T1 and T2 maps were also acquired. The MT and WASSR Z-spectra and T1 map were fitted to a two-pool quantitative MT model to estimate the T2 of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M0, MT), and the magnetization exchange rate from the macromolecular pool to the free pool (RMT). The T1-corrected apparent exchange-dependent relaxation (AREX) metric to isolate the CEST contributions was also calculated. The lesion on M0, MT and AREX maps with a B1 of 2μT best matched the hyperintensity on the post-contrast T1-weighted image. There was also good separation in Z-spectra between the lesion and contralateral cortex in the 2-μT CEST and 3- and 5-μT MT Z-spectra at all time points. A pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment on MRI parameters was performed and the differences between enhancing lesion and contralateral cortex for the MT ratio with 2μT saturation at 3.6ppm frequency offset (corresponding to the amide chemical group) and M0, MT were both strongly significant (p< 0.001) at all time points. This work has identified that differences between enhancing lesion and contralateral cortex are strongest in MTR with B1=2μT at 3.6ppm and relative macromolecular pool size (M0, MT) images over entire period of 3-13 days after cancer cell implantation.

Adaptable Plasmonic Membrane Sensors for Fast and Reliable Detection of Trace Low-Micrometer Microplastics in Lake Water.

In freshwater environments, low-micrometer microplastics (LMMPs) have captured significant attention due to their prevalence and toxicity. Yet, rapid detection of LMMPs (1-10 μm) at the single-particle level within complex freshwater matrices remains a hurdle. We developed an adaptable plasmonic membrane sensor for fast detection of individual LMMPs in eutrophic lake waters. The plasmonic membrane sensor functions both as a membrane filter and as a sensor for LMMP collection and analysis. Among the four types of membrane sensors, polycarbonate track-etch (PCTE) membrane sensors exhibit superior imaging quality for LMMPs due to their flat and homogeneous surfaces. Besides the significantly improved imaging contrast and reduced background interferences, the Raman intensity of LMMPs is enhanced by 48% ± 25% on PCTE membrane sensors compared to unmodified membranes. The increased Raman intensities of a chemical probe with an increasing gold layer thickness and a decreasing membrane pore size suggest a surface-enhanced Raman scattering effect from the membrane sensors. The membrane sensors achieve a detection limit of 1 μg/L and an ultrafast scanning time of 0.01 s for individual LMMPs across natural eutrophic lake water. The developed membrane sensors offer an adaptable tool for the swift and reliable detection of individual LMMPs in complex environmental matrices.

Evaluating the impact of gadolinium contamination on the marine bivalve Donax trunculus: Implications for environmental health

Gadolinium (Gd), commonly used in contrast agents for medical imaging, has been detected in hospital wastewater and aquatic environments, raising environmental concerns. This study examined the accumulation and cellular impacts of Gd in the clam species Donax trunculus, commonly used as bioindicator of contamination. Gadolinium accumulation in clams increased with exposure and over time. Biological responses varied with Gd levels: low concentrations (10 and 50 µg/L) led to low metabolic activity and glycogen content, but high antioxidant activities and lipid peroxidation levels (LPO); high concentrations (250 and 500 µg/L) resulted in increased metabolic activity, while antioxidant enzyme activity was inhibited and LPO levels were the lowest. Metabolic activity decreased after two weeks, suggesting limited long-term metabolic resilience. The study underscores D. trunculus as an effective early warning species for Gd pollution and highlights the ecological risks of rising Gd levels, emphasizing the need for environmental monitoring and regulation.

Microstructure of confectionery masses revealed by cryo-planing

Here we present a novel, combined cryo-scanning electron microscopy (cryo-SEM) and confocal laser scanning microscopy (CLSM) method for imaging of chocolate confectionery product microstructures of several millimeters down to about 100 nm. The SEM part of the method is based on cryo-fixation, cryo-polishing, and scanning electron microscopy, at low vacuum and low temperature using the backscattered electron signal. Starting with cryo-fixation of the chocolate sample in a desired state (cooled, ambient, or melted), the sample is cryo-planed in a cryo-ultramicrotome. Once a polished cut is obtained, the sample is analyzed using a cryo-SEM technique, with the unusual combination of low temperature and low vacuum settings, without heavy metal coating. Imaging is done based on material density contrast. Elemental composition of particles is recorded by energy dispersive x-ray spectroscopy (EDS). The combination of imaging contrast and EDS allows identification and measurement of the four main constituents of chocolate (cocoa solids, fat, sugar, and milk solids). Finally, the same cryo-polished sample sections of solid chocolate products are analyzed using a CLSM imaging technique to reveal complementary microstructural details. An obvious application of the method could be the visualization and quantitative analysis of the size, shape, and composition of chocolate confectionery products.

On the lifespan of Enchytraeus crypticus - impact of iron (nanomaterial and salt) on aging.

Iron oxide nanomaterials (Fe3O4 NMs) have important biomedical and environmental applications, e.g. drug delivery, chemotherapy, magnetic resonance imaging contrast agents, etc. However, the environmental risks of such Fe3O4 are not fully assessed, particularly for soil living invertebrates, which are among the ones in the first line of exposure. Research has showed that longer-term exposure time is required to assess hazards of NMs, not predicted when based on shorter time and are therefore recommended. Thus, in the present study the effects of Fe3O4 NMs and FeCl3 were assessed in the terrestrial environment, using the soil model species Enchytraeus crypticus (Oligochaeta), throughout its entire lifespan (202 days). Two animals' density were used: 1 (D1) and 40 (D40) animals per replicate, in LUFA 2.2 soil. The endpoints were survival and reproduction monitored over-time, up to 202 days. Results showed that density clearly affected the toxicity response, with higher toxicity and lower lifespan in D1 compared to D40. Overall, FeCl3 was more toxic than Fe3O4 NM in terms of reproduction, however, adult animals can be at higher (long-term) risk when exposed to Fe3O4 NM. Differences might be linked to slower Fe kinetics for the Fe3O4 NMs, i.e., slower Fe dissolution and release of ions.

Development of Radiolabeled Probes with Improved Imaging Contrast by Releasing Urinary Excretable Radiolabeled Compounds from Thermosensitive Liposomes in the Blood.

In this study, thermosensitive liposomes (TSLs) encapsulating urinary excretable radiolabeled compounds were developed. We considered that the release of the radiolabeled compounds from the TSLs in the blood by heating the blood in peripheral tissues can achieve rapid clearance of radioactivity, resulting in improved imaging contrast. To demonstrate the hypothesis, classical TSLs mainly composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine with a phase transition temperature of 41 °C were used. The optimal composition of TSLs was determined by an in vitro release test using [111In]In-diethylenetriaminepentaacetic acid (DTPA)-encapsulated liposomes, which showed that the cholesterol content drastically changed the release characteristics of classical TSLs. In the biodistribution experiments, [111In]In-DTPA was significantly released from the TSLs in the blood when the tails of mice were heated at 43 °C. The tumor-to-blood ratio of the heated group was three times higher than that of the nonheated group, and accumulation in normal tissues of the heated group was lower than that of the nonheated group. These results demonstrate the usefulness of the method using TSLs to encapsulate urinary excretable radiolabeled compounds for improving imaging contrast.

Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p &lt; 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p &lt; 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

Ultrasound protein-copolymer microbubble library engineering through poly(vinylpyrrolidone-co-acrylic acid) structure

HypothesisWhile albumin-coated microbubbles are routine contrast agents for ultrasound imaging, their short duration of contrast enhancement limits their use, yet can be improved by incorporating protein-copolymer hybrids into microbubble shells. The incorporation of N-vinyl-2-pyrrolidone and acrylic acid copolymer (P(VP–AA)) has been shown to enhance the performance of bovine serum albumin (BSA)-coated microbubbles. However, the impact of the copolymer structural properties on key microbubble characteristics (i.e., concentration, mean diameter and acoustic response) remains poorly understood. Therefore, we hypothesize that the copolymer structure affects its capacity to form micelle-like nanoaggregates, protein-copolymer hybrids, and microbubble shells, ultimately influencing the physicochemical and acoustic properties of the microbubbles. ExperimentsHere we evaluate the production and performance of BSA@P(VP–AA) microbubbles synthesized using a series of P(VP–AA) copolymers with –C8H17 and –C18H37 end groups and molecular weight cutoffs between 3.5 and 15 kDa. Both simulation and experimental data demonstrate that interactions between BSA and the copolymers significantly influence the performance of the resulting microbubbles across the library of 60 formulations. FindingsThe introduction of –C8H17 terminated copolymers into microbubble shells resulted in up to 200-fold higher concentration, 7-fold greater acoustic response, and 5-fold longer ultrasound contrast enhancement compared to plain BSA microbubbles. The enhanced acoustic performance was sustained during in vivo cardiac ultrasound imaging, without altering liver accumulation after copolymer introduction. These findings underscore how optimizing copolymer structure (specifically the terminal end group and molecular weight) can tailor the formation and performance of protein-copolymer-coated microbubbles, offering valuable insights for designing ultrasound contrast agents.

Dopaminergic- and Serotonergic-Dependent Behaviors Are Altered by Lanthanide Series Metals in Caenorhabditis elegans.

The lanthanide series elements are transition metals used as critical components of electronics, as well as rechargeable batteries, fertilizers, antimicrobials, contrast agents for medical imaging, and diesel fuel additives. With the surge in their utilization, lanthanide metals are being found more in our environment. However, little is known about the health effects associated with lanthanide exposure. Epidemiological studies as well as studies performed in rodents exposed to lanthanum (La) suggest neurological damage, learning and memory impairment, and disruption of neurotransmitter signaling, particularly in serotonin and dopamine pathways. Unfortunately, little is known about the neurological effects of heavier lanthanides. As dysfunctions of serotonergic and dopaminergic signaling are implicated in multiple neurological conditions, including Parkinson's disease, depression, generalized anxiety disorder, and post-traumatic stress disorder, it is of utmost importance to determine the effects of La and other lanthanides on these neurotransmitter systems. We therefore hypothesized that early-life exposure of light [La (III) or cerium (Ce (III))] or heavy [erbium (Er (III)) or ytterbium (Yb (III))] lanthanides in Caenorhabditis elegans could cause dysregulation of serotonergic and dopaminergic signaling upon adulthood. Serotonergic signaling was assessed by measuring pharyngeal pump rate, crawl-to-swim transition, as well as egg-laying behaviors. Dopaminergic signaling was assessed by measuring locomotor rate and egg-laying and swim-to-crawl transition behaviors. Treatment with La (III), Ce (III), Er (III), or Yb (III) caused deficits in serotonergic or dopaminergic signaling in all assays, suggesting both the heavy and light lanthanides disrupt these neurotransmitter systems. Concomitant with dysregulation of neurotransmission, all four lanthanides increased reactive oxygen species (ROS) generation and decreased glutathione and ATP levels. This suggests increased oxidative stress, which is a known modifier of neurotransmission. Altogether, our data suggest that both heavy and light lanthanide series elements disrupt serotonergic and dopaminergic signaling and may affect the development or pharmacological management of related neurological conditions.

Controlled Synthesis of Iron Oxide Nanoparticles via QBD for Biomedical Applications

Introduction: Iron oxide nanoparticles have gained significant attention in pharmaceutical applications because of their unique properties. The hydrothermal method is employed for the synthesis of iron nanoparticles [IONPs], which offers advantages such as uniform composition and size distribution. Method: However, the size and properties of IONPs can be influenced by various factors. In this study, we utilized quality by design [QBD] via response surface methodology to investigate the impact of temperature, time, and pH on the size of hydrothermally prepared IONPs. The optimized synthesis conditions were determined, and the resulting nanoparticles were characterized using techniques such as dynamic light scattering [DLS], scanning electron microscopy [SEM], transmission electron microscopy [TEM], vibrating sample magnetometry [VSM], X-ray diffraction [XRD], and Fourier-transform infrared spectroscopy [FTIR]. Results: The findings contribute to a better understanding of the controlled synthesis of IONPs and their potential applications in nanomedicine. The XRD characterization revealed that the product was Fe3O4. The FTIR results indicate that Fe3O4 nanoparticles were coated with PEG- 400. The SEM and HRTEM images of the Fe3O4 nanoparticles showed that they were spherical and had a well-distributed size with an optimized hydrodynamic size of 65 nm. Conclusion: The magnetic properties of the Fe3O4 nanoparticles indicated that they exhibited ferromagnetic properties. These prepared nanoparticles are suitable for biomedical purposes, like serving as contrast agents for magnetic resonance imaging in different cancers and delivering drugs.