Imaging Contrast Research Articles

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.

Investigation of magnetic resonance contrast properties of PEG-Coated gadolinium oxide nanoparticles in various biological environments

Abstract Magnetic nanoparticles (MNPs) are promising tools for biomedical applications, particularly in molecular imaging using magnetic resonance imaging (MRI). The unique magnetic properties of MNPs, combined with their similarity in size to biological objects, make them ideal candidates for in-situ imaging probes. The present study explores the use of magnetic nanoparticles (MNPs) as contrast agents in magnetic resonance imaging (MRI) for improved diagnostic accuracy. Specifically, the study investigates the MR contrast properties of polyethylene glycol-coated gadolinium oxide nanoparticles (PEG@GONPs) in five different biological fluids. The nanoparticles were synthesized using the polyol route and their size, shape, and morphology were characterized using TEM, SEM, and FT-IR spectroscopy. The magnetic resonance (MR) relaxivity of PEG@GONPs was studied in different biologically relevant media, and results revealed highest relaxivity in plasma as compared to other media. In addition, comparative analysis of proton relaxivity of the synthesized nanoparticles was carried out with a well-known gadolinium-based contrast agent, Omniscan, in various medium. The present findings revealed that PEG@GONPs can serve as an effective contrast agent for MRI imaging in biological fluids such as plasma, which is crucial for preclinical diagnosis of specific diseases and lesions. The high relaxivity observed in plasma could be attributed to the interaction of the nanoparticles with plasma proteins, amplifying their magnetic properties which further improve their ability to produce contrast in MR images.

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.

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.

Standardized diagnosis of gastrointestinal tumors: an update regarding the situation in Germany.

To evaluate the current status of the diagnosis of gastrointestinal tumors in Germany by means of a survey of the oncological imaging working group of the German Radiological Society (DRG) with a focus on the CT protocols being used.Radiologists working in outpatient or inpatient care in Germany were invited. The survey was conducted between 10/2022 and 06/2023 using the SurveyMonkey web tool. Questions related to gastrointestinal cancer were asked with regard to the commonly used imaging modalities, body coverage, and contrast agent phases in CT as well as the use of oral or rectal contrast. The results of the survey were analyzed using descriptive statistics.Clear differences were identified regarding the acquired contrast phases in relation to the place of work - outpatient care, smaller hospitals, maximum care hospitals, or university hospitals. Variances were also recognized regarding oral and rectal contrast. Based on the results and international guidelines, proposals for CT protocols were derived.CT protocols in Germany show a heterogeneous picture regarding acquired contrast phases, as well as oral and rectal contrast for the staging of gastrointestinal cancer. Clear recommendations in the respective guidelines would aid in quality assurance and comparability between different centers. · The examination protocols for the staging of gastrointestinal tumors are heterogeneous in Germany.. · The application of oral and rectal contrast is handled differently at the various radiological centers.. · Standardization of imaging should be targeted.. · Gerwing M, Ristow I, Afat S et al. Standardized diagnosis of gastrointestinal tumors: an update regarding the situation in Germany. Fortschr Röntgenstr 2024; DOI 10.1055/a-2378-6451.

EDITORIAL: RETURNING THE CENTRAL LYMPHATIC SYSTEM TO THE CENTER OF LYMPHOLOGY

After the introduction of conventional oil contrast lymphography and the founding of the discipline of lymphology, great impetus was given to investigating central lymphatic system and its disorders along with lymphatic involvement and specifically lymphostasis in common diseases of major organs such as the liver (cirrhosis) and heart (heart failure). Gradually interest shifted to more peripheral disorders such as limb lymphedema and its treatment by physical and surgical measures. At the same time, basic lymphology turned to the study of isolated ex vivo and in vitro, including lymphatic endothelial models and more recently, molecular lymphology focusing on lymphatic growth and modulating factors, genes and proteins underlying primary lymphedema, and more potential biomarkers of lymphatic disease have gained prominence. However, it has been advances in lymphatic imaging, namely lymphoscintigraphy with SPECT-CT high resolution 3-D pictures and magnetic resonance imaging (contrast and non-contrast) of the peripheral and particularly central lymphatic system by more invasive means combined with endovascular interventional techniques to treat complex and life-threatening lymphatic disorders that has returned the central lymphatic system to the center of lymphology, where the journey began.

Recent advances of nanomaterials in imaging liver fibrosis

AbstractLiver fibrosis is a pathological process resulting from prolonged exposure to various injury factors. It is characterized by the abnormal proliferation and activation of hepatic stellate cells and excessive deposition of extracellular matrix. If left untreated, it can progress to cirrhosis, liver failure, and even liver cancer. There is currently no efficient and accurate clinical diagnostic method for early liver fibrosis. Therefore, there is an urgent need to address the challenge of accurate staging and early diagnosis of liver fibrosis in clinical practice. Recently, nanomaterials have demonstrated significant potential for enhancing the diagnosis of liver fibrosis. Nanomaterials possess the ability to precisely identify and target the microenvironment associated with liver fibrosis. By enhancing their enrichment in the target area, nanomaterials can improve imaging contrast of fibrosis lesions in the liver, thereby enabling accurate diagnosis of liver fibrosis. Accordingly, this review delves into the latest research and advancements concerning nanomaterials in liver fibrosis diagnosis.

Operando lateral state-of-charge inhomogeneity mapping via wavelength-resolved neutron imaging

The continuous advancement in battery technology requires the development of robust and more precise diagnostic tools for the characterization of commercial-scale battery cells. In this work, operando Bragg edge imaging (BEI), based on a time-of-flight approach, provides spatially resolved state-of-charge (SoC) mapping of a commercial-size pouch cell. The changes in the position and intensity of Bragg edges are used to track the Li intercalation into the graphite, thereby identifying the spatial distribution of various lithiation stages and the corresponding SoC. The operando wavelength-resolved BEI assessment revealed an inhomogeneous Li+ intercalation, dependent on the distance to the electrical tabs, effectively identifying features that contribute to the overall loss of performance and the accelerated degradation of battery materials. The presented results demonstrate the potential of advanced wavelength-resolved neutron imaging to be used as a diagnostic tool for commercial battery cells in a configuration without special casings or isotopes for enhancement of imaging contrast. It thus highlights its applicability for operando characterization of future batteries for portable and automotive applications.

2-[18F]Fluoropropionic Acid PET Imaging of Doxorubicin-induced Cardiotoxicity.

Purpose Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA). Therefore, we explored the utility of 2-[ 18 F]fluoropropionic acid ([ 18 F]FPA), an SCFA analog, as an imaging biomarker of cardiac injury in mice exposed to doxorubicin. Procedures : Cardiotoxicity and cardiac dysfunction were induced in mice by an 8-dose regimen of doxorubicin (cumulative dose 24 mg/kg) administered over 14 days. The effects of doxorubicin exposure were assessed by measurement of heart weights, left ventricular ejection fractions, and blood cardiac troponin levels. Whole body and cardiac [ 18 F]FPA uptakes were determined by PET and tissue gamma counting in the presence or absence of AZD3965, a pharmacological inhibitor of monocarboxylate transporter 1 (MCT1). Radiation absorbed doses were estimated using tissue time-activity concentrations. Results Significantly higher cardiac [ 18 F]FPA uptake was observed in doxorubicin-treated animals. This uptake remained constant from 30 min to 120 min post-injection. Pharmacological inhibition of MCT1-mediated transport by AZD3965 selectively decreased the uptake of [ 18 F]FPA in tissues other than the heart. Co-administration of [ 18 F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity. Conclusions [ 18 F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.

One-Pot Fabrication of Kinetically Inert Ultrasmall Manganese(II) Chelate-Backboned Polymer Contrast Agents for High-Performance Magnetic Resonance Imaging.

Traditional macromolecules or nanoscale Mn2+ chelate-based magnetic resonance imaging (MRI) contrast agents (CAs) suffer from complicated and laborious synthesis processes, relatively low kinetic stability and T1 relaxivity, limiting their clinical applications. Herein, we fabricated a series of kinetically inert Mn2+ chelate-backboned polymers, P(MnL-PEG), through a facile and one-pot polymerization process. Particularly, P(MnL-PEG)-3 demonstrates a significantly higher T1 relaxivity of 23.9 Mn mM-1 s-1 at 1.5 T than that of previously reported small molecules and macromolecules or nanoscale Mn2+ chelate-based CAs. Due to its high T1 relaxivity, extended blood circulation, hepatocyte-specific uptake, and kidneys metabolism, P(MnL-PEG)-3 presents significantly enhanced contrast in blood vessel, liver, and kidneys imaging compared to clinical Gd3+-based CAs (Gd-EOB-DTPA and Gd-DOTA) at a dosage of 0.05 mmol Mn/Gd kg-1 BW, and can accurately diagnose orthotopic H22 liver tumors in vivo in animal models. We anticipate that this work will promote the development of clinically relevant MRI CAs.

A Macrocyclic Hybrid PET/MRI Probe for Quantitative Perfusion Imaging In Vivo.

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction, a condition that is typically challenging to diagnose. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for practical synthesis and improved diagnostic accuracy.

Hierarchical Nanostructures as Acoustically Manipulatable Multifunctional Agents in Dynamic Fluid Flow.

Acoustic waves provide a biocompatible and deep-tissue-penetrating tool suitable for contactless manipulation in in vivo environments. Despite the prevalence of dynamic fluids within the body, previous studies have primarily focused on static fluids, and manipulatable agents in dynamic fluids are limited to gaseous core-shell particles. However, these gas-filled particles face challenges in fast-flow manipulation, complex setups, design versatility, and practical medical imaging, underscoring the need for effective alternatives. In this study, flower-like hierarchical nanostructures (HNS) into microparticles (MPs) are incorporated, and demonstrated that various materials fabricated as HNS-MPs exhibit effective and reproducible acoustic trapping within high-velocity fluid flows. Through simulations, it is validated that the HNS-MPs are drawn to the focal point by acoustic streaming and form a trap through secondary acoustic streaming at the tips of the nanosheets comprising the HNS-MPs. Furthermore, the wide range of materials and modification options for HNS, combined with their high surface area and biocompatibility, enable them to serve as acoustically manipulatable multimodal imaging contrast agents and microrobots. They can perform intravascular multi-trap maneuvering with real-time imaging, purification of wastewater flow, and highly-loaded drug delivery. Given the diverse HNS materials developed to date, this study extends their applications to acoustofluidic and biomedical fields.