Search Results (49)

Background/Objectives: Magnetic resonance imaging (MRI) is a powerful, non-invasive diagnostic tool capable of capturing detailed anatomical and physiological information. MRI contrast agents enhance image contrast but, especially linear gadolinium-based compounds, have been associated with safety concerns. This has prompted interest in alternative contrast agents. Manganese-based contrast agents offer a promising substitute, owing to manganese’s favorable magnetic properties, natural biological role, and strong T1 relaxivity. This review aims to critically assess the structure, mechanisms, applications, and challenges of manganese-based contrast agents in MRI. Methods: This review synthesizes findings from preclinical and clinical studies involving various types of manganese-based contrast agents, including small-molecule chelates, nanoparticles, theranostic platforms, responsive agents, and controlled-release systems. Special attention is given to pharmacokinetics, biodistribution, and safety evaluations. Results: Mn-based agents demonstrate promising imaging capabilities, with some achieving relaxivity values comparable to gadolinium compounds. Targeted uptake mechanisms, such as hepatocyte-specific transport via organic anion-transporting polypeptides, allow for enhanced tissue contrast. However, concerns remain regarding the in vivo release of free Mn²⁺ ions, which could lead to toxicity. Preliminary toxicity assessments report low cytotoxicity, but further comprehensive long-term safety studies should be carried out. Conclusions: Manganese-based contrast agents present a potential alternative to gadolinium-based MRI agents pending further validation. Despite promising imaging performance and biocompatibility, further investigation into stability and safety is essential. Additional research is needed to facilitate the clinical translation of these agents. Full article

Introduction: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction secondary to systemic infection, occurring without direct central nervous system involvement. Despite its clinical relevance, reliable biomarkers for diagnosing SAE and assessing its severity remain limited. This study aimed to evaluate the feasibility of amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI as a non-invasive molecular imaging technique for detecting metabolic alterations related to neuroinflammation in SAE. Using a lipopolysaccharide (LPS)-induced rat model, we focused on hippocampal changes associated with neuronal inflammation. Materials and Methods: Twenty-one Sprague–Dawley rats (8 weeks old, male) were divided into three groups: control (CTRL, n = 7), LPS-induced sepsis at 5 mg/kg (LPS05, n = 7), and 10 mg/kg (LPS10, n = 7). Sepsis was induced via a single intraperitoneal injection of LPS. APTw imaging was performed using a 7 T preclinical MRI system, and signal quantification in the hippocampus was conducted using the magnetization transfer ratio asymmetry analysis. Results and Discussion: APTw imaging at 7 T demonstrated significantly elevated hippocampal APTw signals in SAE model rats (LPS05 and LPS10) compared to the control (CTRL) group: CTRL (−1.940 ± 0.207%) vs. LPS05 (−0.472 ± 0.485%) (p < 0.001) and CTRL vs. LPS10 (−0.491 ± 0.279%) (p < 0.001). However, no statistically significant difference was observed between the LPS05 and LPS10 groups (p = 0.994). These results suggest that APTw imaging can effectively detect neuroinflammation-related metabolic alterations in the hippocampus. Conclusion: Our findings support the feasibility of APTw CEST imaging as a non-invasive molecular MRI technique for SAE, with potential applications in diagnosis, disease monitoring, and therapeutic evaluation. Full article

Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and member 3 (T1R3), are now recognised as being widely distributed throughout the body, including the gastrointestinal tract. Preclinical studies suggest these receptors are central to nutrient and glucose sensing, detecting energy availability and triggering metabolic and behavioural responses to maintain energy balance. Both internal and external factors tightly regulate their signalling pathways, and dysfunction within these systems may contribute to the development of metabolic disorders such as obesity and type 2 diabetes (T2D). Functional magnetic resonance imaging (fMRI) has provided valuable insights into the neural mechanisms underlying sweet sensing by mapping brain responses to both lingual/oral and gastrointestinal sweet stimuli. This review highlights key findings from fMRI studies and explores how these neural responses are modulated by metabolic state and individual characteristics such as body mass index, habitual intake and metabolic health. By integrating current evidence, this review advances our understanding of the complex interplay between sweet sensing, brain responses, and health and identifies key gaps and directions for future research in nutritional neuroscience. Full article

This paper presents the efficacy of a contrast agent based on H₂N-Fe₃O₄ nanoparticles for the detection of prostate cancer in an animal model using a preclinical 9.4 T MRI system. The relaxivities r₁ and r₂ of the nanoparticles were 6.31 mM⁻¹s⁻¹ and 8.33 mM⁻¹s⁻¹, respectively. Nanoparticles injected in a concentration of 2 mg Fe/mL decreased the tumor-relative T₁ relaxation across all animals from 100 to 76 ± 26, 85 ± 27, 89 ± 20, and 97 ± 16 12 min 1 h, 2 h, and 24 h post injection, respectively. The corresponding T₁ decrease in muscle tissues was 90 ± 20, 94 ± 23, 99 ± 12, and 99 ± 14. The relative T₂ changes in the tumor were 82 ± 17, 89 ± 19, 97 ± 14, and 99 ± 8 12 min, 1 h, 2 h, and 24 h post injection, respectively, while, for muscle tissues, these values were 95 ± 11, 95 ± 8, 97 ± 6, and 95 ± 10 at the corresponding time points. The differences in the relative T₁ and T₂ were only significant 12 min after injection (p < 0.05), although a decrease was visible at each time point, but it was statistically insignificant (p > 0.05). The results showed the potential application of H₂N-Fe₃O₄ nanoparticles as contrast agents for enhanced prostate cancer MRI. Full article

In this research, resorbable phosphate-based glass (PBG) compositions were developed using varying modifier oxides including iron (Fe₂O₃), copper (CuO), and manganese (MnO₂), and then processed via a rapid single-stage flame spheroidisation process to manufacture dense (i.e., solid) and highly porous microspheres. Solid (63–200 µm) and porous (100–200 µm) microspheres were produced and characterised via SEM, XRD, and EDX to investigate their surface topography, structural properties, and elemental distribution. Complementary NMR investigations revealed the formation of Q², Q¹, and Q⁰ phosphate species within the porous and solid microspheres, and degradation studies performed to evaluate mass loss, particle size, and pH changes over 28 days showed no significant differences among the microspheres (63–71 µm) investigated. The microspheres produced were then investigated using clinical (1.5 T) and preclinical (7 T) MRI systems to determine the R₁ and R₂ relaxation rates. Among the compositions investigated, manganese-based porous and solid microspheres revealed enhanced levels of R₂ (9.7–10.5 s⁻¹ for 1.5 T; 17.1–18.9 s⁻¹ for 7 T) and R₁ (3.4–3.9 s⁻¹ for 1.5 T; 2.2–2.3 s⁻¹ for 7 T) when compared to the copper and iron-based microsphere samples. This was suggested to be due to paramagnetic ions present in the Mn-based microspheres. It is also suggested that the porosity in the resorbable PBG porous microspheres could be further explored for loading with drugs or other biologics. This would further advance these materials as MRI theranostic agents and generate new opportunities for MRI contrast-enhancement oral-delivery applications. Full article

Atherosclerosis, marked by plaque accumulation within arteries, results from lipid dysregulation, inflammation, and vascular remodeling. Plaque composition, including lipid-rich cores and fibrous caps, determines stability and vulnerability. Photodynamic therapy (PDT) has emerged as a promising treatment, leveraging photosensitizers to induce localized cytotoxicity upon light activation. PDT targets plaque components selectively, reducing burden and inflammation. Challenges remain in optimizing PDT parameters and translating preclinical success to clinical efficacy. Nonetheless, PDT offers a minimally invasive strategy for atherosclerosis management, promising personalized interventions for cardiovascular health. The objective of the current study was to present the findings from quantitative non-contrast MRI of atherosclerosis post-PDT by assessing relaxation times. The study aimed to utilize and optimize a 1.5T MRI system. Clinical scanners were used for MRI examinations. The research involved analyzing T1 and T2 relaxation times. Following treatment of the samples with Rose Bengal and exposure to pure oxygen, PDT irradiation was administered. The results indicated that the therapy impacted the crus, evidenced by a significant decrease in relaxation times in the MRI data. Full article

Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood–brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [¹⁸F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R² = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [¹⁸F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion. Full article

The DSL-6A/C1 murine pancreatic ductal adenocarcinoma (PDAC) tumor model was established in Lewis rats and characterized through a comprehensive multiparametric analysis to compare it to other preclinical tumor models and explore potential diagnostic and therapeutical targets. DSL-6A/C1 tumors were histologically analyzed to elucidate PDAC features. The tumor microenvironment was studied for immune cell prevalence. Multiparametric MRI and PET imaging were utilized to characterize tumors, and ⁶⁸Ga-FAPI-46-targeting cancer-associated fibroblasts (CAFs), were used to validate the histological findings. The histology confirmed typical PDAC characteristics, such as malformed pancreatic ductal malignant cells and CAFs. Distinct immune landscapes were identified, revealing an increased presence of CD8⁺ T cells and a decreased CD4⁺ T cell fraction within the tumor microenvironment. PET imaging with ⁶⁸Ga-FAPI tracers exhibited strong tracer uptake in tumor tissues. The MRI parameters indicated increasing intralesional necrosis over time and elevated contrast media uptake in vital tumor areas. We have demonstrated that the DSL-6A/C1 tumor model, particularly due to its high tumorigenicity, tumor size, and ⁶⁸Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC. Full article

Magnetic nanoparticles (MNPs), either paramagnetic or superparamagnetic depending on their composition and size, have been thoroughly studied as magnetic resonance imaging (MRI) contrast agents using in vitro and in vivo biomedical preclinical studies, while some are clinically used. Their magnetic properties responsible in some cases for high magnetization values, together with large surface area-to-volume ratios and the possibility of surface functionalization, have been used in MRI-based diagnostic and theranostics applications. MNPs are usually used as positive (T₁) or negative (T₂) MRI contrast agents, causing brightening or darkening of selected regions in MRI images, respectively. This review focusses on recent developments and optimization of MNPs containing Gd, Mn, Fe and other lanthanide ions which may function as dual-mode T₁–T₂ MRI contrast agents (DMCAs). They induce positive or negative contrast in the same MRI scanner upon changing its operational mode between T₁-weighted and T₂-weighted pulse sequences. The type of contrast they induce depends critically on their r₂/r₁ relaxivity ratio, which for DMCAs should be in the 2–10 range of values. After briefly discussing the basic principles of paramagnetic relaxation in MNPs, in this review, the basic strategies for the rational design of DMCAs are presented and typical examples are discussed, including in vivo preclinical applications: (1) the use of NPs with a single type of contrast material, Gd- or Mn-based NPs or superparamagnetic NPs with appropriate size and magnetization to provide T₂ and T₁ contrast; and (2) inclusion of both types of T₁ and T₂ contrast materials in the same nanoplatform by changing their relative positions. Full article

The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood–brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice. Full article

Background: Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation. Methods: This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation. Results: The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method. Conclusions: The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages. Full article

Radiofrequency (RF) surface coils are extensively used as receivers in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) systems thanks to their high signal-to-noise ratio (SNR). For specific magnetic resonance applications, the design of dedicated RF surface coils with a transverse (to the coil’s plane) RF magnetic field pattern can be necessary. Such transverse-field RF coils are constituted by several central linear (parallel or crossing) conductor elements connected by return current paths. Typically, the outer shape of such RF coils is circular or squared, although other geometries can be used. This paper describes the implementation and validation of a transverse-field RF surface coil simulator based on magnetostatic analysis, which permits the design and optimization of square butterfly and figure-of-eight RF coils with adjustable size and mutual distance between the central linear current elements. The simulation results, compared with the ones provided by a standard square loop RF coil, were validated with 100 MHz workbench measurements performed on three home-built prototypes. Finally, two novel quadrature RF coil structures designed by overlapping two orthogonal square butterfly and figure-of-eight RF coils were simulated and theoretically characterized. The RF coils described here should be suitable for a wide range of MRI/MRS preclinical/clinical applications, mainly at fields below 3 T. Full article

This study investigated a method for improving the quality of images with a low number of excitations (NEXs) based on deep learning using T₂-weighted magnetic resonance imaging (MRI) of the heads of normal Wistar rats to achieve higher image quality and a shorter acquisition time. A 7T MRI was used to acquire T₂-weighted images of the whole brain with NEXs = 2, 4, 8, and 12. As a preprocessing step, non-rigid registration of the acquired low NEX images (NEXs = 2, 4, 8) and NEXs = 12 images was performed. A residual dense network (RDN) was used for training. A low NEX image was used as the input to the RDN, and the NEX12 image was used as the correct image. For quantitative evaluation, we measured the signal-to-noise ratio (SNR), peak SNR, and structural similarity index measure of the original image and the image obtained by RDN. The NEX2 results are presented as an example. The SNR of the cortex was 10.4 for NEX2, whereas the SNR of the image reconstructed with RDN for NEX2 was 32.1. (The SNR NEX12 was 19.6) In addition, the PSNR in NEX2 was significantly increased to 35.4 ± 2.0 compared to the input image and to 37.6 ± 2.9 compared to the reconstructed image (p = 0.05). The SSIM in NEX2 was 0.78 ± 0.05 compared to the input image and 0.91 ± 0.05 compared to the reconstructed image (p = 0.0003). Furthermore, NEX2 succeeded in reducing the shooting time by 83%. Therefore, in preclinical 7T MRI, supervised learning between the NEXs using RDNs can potentially improve the image quality of low NEX images and shorten the acquisition time. Full article

This study aimed to evaluate cardiac function in a young mouse model of Duchenne muscular dystrophy (mdx) using cardiac magnetic resonance imaging (MRI) with feature tracking and self-gated magnetic resonance cine imaging. Cardiac function was evaluated in mdx and control mice (C57BL/6JJmsSlc mice) at 8 and 12 weeks of age. Preclinical 7-T MRI was used to capture short-axis, longitudinal two-chamber view and longitudinal four-chamber view cine images of mdx and control mice. Strain values were measured and evaluated from cine images acquired using the feature tracking method. The left ventricular ejection fraction was significantly less (p < 0.01 each) in the mdx group at both 8 (control, 56.6 ± 2.3% mdx, 47.2 ± 7.4%) and 12 weeks (control, 53.9 ± 3.3% mdx, 44.1 ± 2.7%). In the strain analysis, all strain value peaks were significantly less in mdx mice, except for the longitudinal strain of the four-chamber view at both 8 and 12 weeks of age. Strain analysis with feature tracking and self-gated magnetic resonance cine imaging is useful for assessing cardiac function in young mdx mice. Full article

This study validates the usefulness of myocardial strain analysis with cardiac cine magnetic resonance imaging (MRI) by evaluating the changes in the cardiac function and myocardial strain values longitudinally in a myocardial disease model. Six eight-week-old male Wistar rats were used as a model of myocardial infarction (MI). Cine images were taken in the short axis, two-chamber view longitudinal axis, and four-chamber view longitudinal axis directions in rats 3 and 9 days after MI and in control rats, with preclinical 7-T MRI. The control images and the images on days 3 and 9 were evaluated by measuring the ventricular ejection fraction (EF) and the strain values in the circumferential (CS), radial (RS), and longitudinal directions (LS). The CS decreased significantly 3 days after MI, but there was no difference between the images on days 3 and 9. The two-chamber view LS was −9.7 ± 2.1% at 3 days and −13.9 ± 1.4% at 9 days after MI. The four-chamber view LS was −9.9 ± 1.5% at 3 days and −11.9 ± 1.3% at 9 days after MI. Both the two- and four-chamber LS values were significantly decreased 3 days after MI. Myocardial strain analysis is, therefore, useful for assessing the pathophysiology of MI. Full article