Superparamagnetic Iron Oxide Particles Research Articles

A systematic 3-D magnetic particle imaging simulation model for quantitative analysis of reconstruction image quality

Background and objectiveMagnetic particle imaging (MPI) is an emerging imaging technology in medical tomography that utilizes the nonlinear magnetization response of superparamagnetic iron oxide (SPIO) particles to determine the in vivo spatial distribution of nanoparticle contrast agents. The reconstruction image quality of MPI is determined by the characteristics of magnetic particles, the setting of the MPI scanner parameters, and the hardware interference of MPI systems. We explore a feasible method to systematically and quickly analyze the impact of these factors on MPI reconstruction image quality. MethodsWe propose a systematic 3-D MPI simulation model. The MPI simulation model has the capability of quickly producing the simulated reconstruction images of a scanned phantom, and quantitative analysis of MPI reconstruction image quality can be achieved by comparing the differences between the input image and output image. These factors are mainly classified as imaging parameters and interference parameters in our model. In order to reduce the computational time of the simulation model, we introduce GPU parallel programming to accelerate the processing of large complex matrix data. For ease of use, we also construct a reliable, high-performance, and open-source 3-D MPI simulation software tool based on our model. The efficiency of our model is evaluated by using OpenMPIData. To demonstrate the capabilities of our model, we conduct simulation experiments using parameters consistent with a real MPI scanner for improving MPI image quality. ResultsThe experimental results show that our simulation model can systematically and quickly evaluate the impact of imaging parameters and interference parameters on MPI reconstruction image quality. ConclusionsWe developed an easy-to-use and open-source 3-D MPI simulation software tool based on our simulation model incorporating all the stages of MPI formation, from signal acquisition to image reconstruction. In the future, our simulation model has potential guiding significance to practical MPI images.

Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study.

Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not yet been studied. This study aimed to investigate the effect of multiple intravenous injections of VSOPs in atherosclerotic mice. Taurine-formulated VSOPs (VSOP-T) were repeatedly intravenously injected at 100 µmol Fe/kg in apolipoprotein E-deficient (ApoE KO) mice with diet-induced atherosclerosis. Angiographic imaging was carried out by in vivo MRI. Magnetic particle spectrometry was used to detect tissue VSOP content, and tissue iron content was quantified photometrically. Pathological changes in organs, atherosclerotic plaque development, and expression of hepatic iron-related proteins were evaluated. VSOP-T enabled the angiographic imaging of heart and blood vessels with a blood half-life of one hour. Repeated intravenous injection led to VSOP deposition and iron accumulation in the liver and spleen without affecting liver and spleen pathology, expression of hepatic iron metabolism proteins, serum lipids, or atherosclerotic lesion formation. Repeated injections of VSOP-T doses sufficient for MRA analyses had no significant effects on plaque burden, steatohepatitis, and iron homeostasis in atherosclerotic mice. These findings underscore the safety of VSOP-T and support its further development as a contrast agent and molecular imaging tool.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

A novel extracellular vesicles production system harnessing matrix homeostasis and macrophage reprogramming mitigates osteoarthritis

Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Inorganic Phosphate-Induced Extracellular Vesicles from Vascular Smooth Muscle Cells Contain Elevated Levels of Hyaluronic Acid, Which Enhance Their Interaction with Very Small Superparamagnetic Iron Oxide Particles.

Patients with chronic kidney disease (CKD) have a high prevalence of hyperphosphatemia, where uremic toxins like inorganic phosphate (Pi) induce a cardiovascular remodeling. Related disorders like atherosclerosis bear the risk of increased morbidity and mortality. We previously found that Pi stimulates the synthesis and sulfation of the negatively charged glycosaminoglycans (GAGs) heparan sulfate and chondroitin sulfate in vascular smooth muscle cells (VSMC). Similar GAG alterations were detected in VSMC-derived exosome-like extracellular vesicles (EV). These EV showed a strong interaction with very small superparamagnetic iron oxide particles (VSOP), which are used as imaging probes for experimental magnetic resonance imaging (MRI). Hyaluronic acid (HA) represents another negatively charged GAG which is supposed to function as binding motif for VSOP as well. We investigated the effects of Pi on the amounts of HA in cells and EV and studied the HA-dependent interaction between VSOP with cells and EV. Rat VSMC were treated with elevated concentrations of Pi. CKD in rats was induced by adenine feeding. EV were isolated from culture supernatants and rat plasma. We investigated the role of HA in binding VSOP to cells and EV via cell-binding studies, proton relaxometry, and analysis of cellular signaling, genes, proteins, and HA contents. Due to elevated HA contents, VSMC and EV showed an increased interaction with VSOP after Pi stimulation. Amongst others, Pi induced hyaluronan synthase (HAS)2 expression and activation of the Wnt pathway in VSMC. An alternative upregulation of HA by iloprost and an siRNA-mediated knockdown of HAS2 confirmed the importance of HA in cells and EV for VSOP binding. The in vitro-derived data were validated by analyses of plasma-derived EV from uremic rats. In conclusion, the inorganic uremic toxin Pi induces HA synthesis in cells and EV, which leads to an increased interaction with VSOP. HA might therefore be a potential molecular target structure for improved detection of pathologic tissue changes secondary to CKD like atherosclerosis or cardiomyopathy using EV, VSOP and MRI.

T1-weighted MRI of targeting atherosclerotic plaque based on CD40 expression on engulfed USPIO’s cell surface

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of cholesterol within the arterial wall. Its progression can be monitored via magnetic resonance imaging (MRI). Ultrasmall Superparamagnetic Particles of Iron Oxide (USPIO) (<5 nm) have been employed as T1 contrast agents for MRI applications. In this study, we synthesized USPIO with an average surface carboxylation of approximately 5.28 nm and a zeta potential of −47.8 mV. These particles were phagocytosed by mouse aortic endothelial cells (USPIO-MAECs) and endothelial progenitor cells (USPIO-EPCs), suggesting that they can be utilized as potential contrast agent and delivery vehicle for the early detection of atherosclerosis. However, the mechanism by which this contrast agent is delivered to the plaque remains undetermined. Our results demonstrated that with increasing USPIO concentration during 10–100 μg ml−1, consistent change appeared in signal enhancement on T1-weighted MRI. Similarly, T1-weighted MRI of MAECs and EPCs treated with these concentrations exhibited a regular change in signal enhancement. Prussian blue staining of USPIO revealed substantial absorption into MAECs and EPCs after treatment with 50 μg ml−1 USPIO for 24 h. The iron content in USPIO-EPCs was much higher (5 pg Fe/cell) than in USPIO-MAECs (0.8 pg Fe/cell). In order to substantiate our hypothesis that CD40 protein on the cell surface facilitates migration towards inflammatory cells, we utilized AuNPs-PEI (gold nanoparticles-polyethylenimine) carrying siRNACD40 to knockout CD40 expression in MAECs. It has been documented that gold nanoparticle-oligonucleotide complexes could be employed as intracellular gene regulation agents for the control of protein level in cells. Our results confirmed that macrophages are more likely to bind to MAECs treated with AuNPs-PEI-siRNANC (control) for 72 h than to MAECs treated with AuNPs-PEI-siRNACD40 (reduced CD40 expression), thus confirming CD40 targeting at the cellular level. When USPIO-MAECs and MAECs (control) were delivered to mice (high-fat-fed) via tail vein injection respectively, we observed a higher iron accumulation in plaques on blood vessels in high-fat-fed mice treated with USPIO-MAECs. We also demonstrated that USPIO-EPCs, when delivered to high-fat-fed mice via tail vein injection, could indeed label plaques by generating higher T1-weighted MRI signals 72 h post injection compared to controls (PBS, USPIO and EPCs alone). In conclusion, we synthesized a USPIO suitable for T1-weighted MRI. Our results have confirmed separately at the cellular and tissue and in vivo level, that USPIO-MAECs or USPIO-EPCs are more accessible to atherosclerotic plaques in a mouse model. Furthermore, the high expression of CD40 on the cell surface is a key factor for targeting and USPIO-EPCs may have potential therapeutic effects.

Superparamagnetic iron oxide assisted transformation of graphene oxide nanolayers to nanoscrolls for supercapacitor electrode materials: Effect of morphology and electrolyte on supercapacitor performance

The study illustrates a facile preparative strategy of graphene oxide (GO) nanoscrolls through surface engineering of GO nanosheets by superparamagnetic iron oxide as the transformative and its application as a supercapacitor electrode. Superparamagnetic iron oxide particles acted like localized magnetic fields, which can establish inter particle attractive force within a GO nanosheet and metamorphose the morphology to nanoscrolls. The morphological transformation effectively restricted the restacking of exfoliated nanomaterials, thereby exterminating one of the major obstructions to acquire the expected electrochemical performances. The mechanism of scrolling process has been unveiled by preparing various combinations of GO:iron oxide and studying the sequential transformation in morphology using TEM, XRD and Raman followed by magnetization study and XPS. The critical ratio of GO:Iron Oxide was optimized at (1:6) and the combination was subjected for detailed electrochemical analysis under a three-electrode system using KOH and Na2S2O3 electrolytes. Cyclic voltammetry, impedance and galvanoscopic charge discharge study suggested an impressive electrode performance with specific capacitance, energy density and power density values of 849 Fg−1, 66.3 Whkg−1 and 416.7 Wkg−1, respectively in Na2S2O3 with an excellent cycle stability by retaining 85 % performance characteristics after 4000 cycles. The surface engineering method has been validated as a reversible strategy since successful unwinding and rewinding process of nanoscrolls made viable followed by the electrochemical performance evaluation. This has been further underlined the critical role of iron oxide for the improved storage/discharge performance via amending the morphology of GO.

Folic acid-decorated vitamin E Poly(ethylene glycol) monoplatinum ester with disulfide bond as theranostic nanoparticle for drug resistant tumor diagnosis and treatment

Vitamin E Poly(ethylene glycol) monoplatinum ester (TPGS) nanoparticles have attracted much attention in recent years for overcome multidrug resistance. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked polymer (FA-SS-TPGS) was synthesized. These polymer nanoparticles were utilized as theranostic agents for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. By loading doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) particles into TPGS nanoparticles, FA-SS-TPGS@DOX/SPIO nanoparticles are obtained. In vitro drug release studies revealed that under a reducing environment in the presence of glutathione (GSH), approximately 100% of the doxorubicin (DOX) was released from the disulfide bond-linked theranostic nanoparticles within 24 h. DOX and SPIO were efficiently delivered into HepG2-ADM cells due to the folate receptor-mediated endocytosis process of the nanoparticles. Additionally, the presence of glutathione (GSH) triggered the cleaving of the disulfide bonds, further facilitating the delivery of DOX and SPIO into the cells. Furthermore, the FA-SS-TPGS @DOX-SPIO nanoparticles exhibited strong MRI contrast enhancement properties. In conclusion, FA-SS-TPGS@DOX/SPIO are potential nanoparticles for tumor-targeted MRI and chemotherapy, which can also overcome multidrug resistance.

Uremic Toxin-Induced Exosome-like Extracellular Vesicles Contain Enhanced Levels of Sulfated Glycosaminoglycans which Facilitate the Interaction with Very Small Superparamagnetic Iron Oxide Particles.

Uremic toxins exert pathophysiological effects on cells and tissues, such as the generation of a pro-calcifying subtype of exosome-like extracellular vesicles (EVs) in vascular cells. Little is known about the effects of the toxins on the surface structure of EVs. Thus, we studied the effects of uremic toxins on the abundance of sulfated glycosaminoglycans (GAGs) in EVs, and the implications for binding of ligands such as very small superparamagnetic iron oxide particles (VSOPs) which could be of relevance for radiological EV-imaging. Vascular cells were treated with the uremic toxins NaH2PO4 and a mixture of urea and indoxyl sulfate. Uremia in rats was induced by adenine feeding. EVs were isolated from culture supernatants and plasma of rats. By proton T1-relaxometry, magnetic particle spectroscopy, and analysis of genes, proteins, and GAG-contents, we analyzed the roles of GAGs in the ligand binding of EVs. By influencing GAG-associated genes in host cells, uremic toxins induced higher GAG contents in EVs, particularly of sulfated chondroitin sulfate and heparan sulfate chains. EVs with high GAG content interacted stronger with VSOPs compared to control ones. This was confirmed by experiments with GAG-depleted EVs from genetically modified CHO cells and with uremic rat-derived EVs. Mechanistically, uremic toxin-induced PI3K/AKT-signaling and expression of the sulfate transporter SLC26A2 in host cells contributed to high GAG contents in EVs. In conclusion, uremic conditions induce enhanced GAG contents in EVs, which entails a stronger interaction with VSOPs. VSOPs might be suitable for radiological imaging of EVs rich in GAGs.

Enhanced radiosensitivity and chemoradiation efficacy in nasopharyngeal carcinoma via a dual-targeted SPION@polymer hybrid nanosensitizer

Cisplatin-based nanoparticles show good potential in enhancing the effect of nasopharynx carcinoma (NPC) therapy but are still limited by their low radiation sensitization and poor tumor targeting ability. Herein, an ingenious design of multifunctional superparamagnetic iron oxide nanoparticle (SPION)@polymer hybrid nanosensitizer (SPHN) with enhanced radiosensitization and dual-targeting capability is described. SPHN have a core-shell structure, in which radiosensitizer superparamagnetic iron oxide particle (SPION) and cis-platinum (CDDP) are encapsulated in RGD-conjugated amphiphilic block copolymers. These unique structures endow SPHN with outstanding radiosensitization and tumor targeting abilities. When combined with X-rays, SPHN showed strong promotion of the apoptosis of CNE-1 cells in vitro. In addition, RNA-seq and KEGG enrichment analyses indicated that the PI3K-Akt and TNF signaling pathways were closely related to the molecular mechanism of SPHN in chemoradiotherapy. Furthermore, gene set enrichment analysis (GSEA) revealed that SPHN + X-rays treatment decreased translation initiation pathways and the cytoplasmic translation pathway. Through a combination of radiation and chemotherapy, SPHN can achieve remarkable inhibition of tumor growth in vivo, making this nanotechnology a general platform for the chemoradiation therapy of NPC in the future.

Influence of SPIO labelling on the function of BMSCs in chemokine receptors expression and chemotaxis.

Bone marrow-derived mesenchymal stem cells (BMSCs) are increasingly being used in bone marrow transplantation (BMT) to enable homing of the allogeneic hematopoietic stem cells and suppress acute graft versus host disease (aGVHD). The aim of this study was to optimize the labelling of BMSCs with superparamagnetic iron oxide particles (SPIOs), and evaluate the impact of the SPIOs on the biological characteristics, gene expression profile and chemotaxis function of the BMSCs. The viability and proliferation rates of the SPIO-labeled BMSCs were analyzed by trypan blue staining and CCK-8 assay respectively, and the chemotaxis function was evaluated by the transwell assay. The expression levels of chemokine receptors were measured by RT-PCR and flow cytometry. The SPIOs had no effect on the viability of the BMSCs regardless of the labelling concentration and culture duration. The labelling rate of the cells was higher when cultured for 48 h with the SPIOs. Furthermore, cells labeled with 25µg/ml SPIOs for 48 h had the highest proliferation rates, along with increased expression of chemokine receptor genes and proteins. However, there was no significant difference between the chemotaxis function of the labeled and unlabeled BMSCs. To summarize, labelling BMSCs with 25µg/ml SPIOs for 48h did not affect their biological characteristics and chemotaxis function, which can be of significance for in vivo applications.

Extrapolation of System Matrices in Magnetic Particle Imaging.

Magnetic particle imaging exploits the non-linear magnetization of superparamagnetic iron-oxide particles to generate a tomographic image in a defined field-of-view. For reconstruction of the particle distribution, a time-consuming calibration step is required, in which system matrices get measured using a robot. To achieve artifact-free images, system matrices need to cover not only the field-of-view but also a larger area around it. Especially for large measurements- inevitable for future clinical application- this leads to long calibration time and high consumption of persistent memory. In this work, we analyze the signal in the outer part of the system matrix and motivate the usage of extrapolation methods to computationally expand the system matrix after restricting the calibration to the field-of-view. We propose a suitable extrapolation method and show its applicability on measured 2D and 3D data. In doing so, we achieve a considerable reduction of calibration time and consumption of persistent memory while preserving an artifact-free result.

Integration of Hybrid Dendrimers and Their Generations for Modulated Spatio‐Temporal Action

Hybrid dendrimers constitute a unique class of well-defined complex architecture featured with a central domain and bifurcated branches with two different dendritic sequences for their atomic configuration and functional groups at the periphery. This review article pioneers the field of new hybrid dendrimers using different generations by nanoconjugation with metals, carbohydrates, nucleotides, proteins/peptides, carbosilane, urea, silica, stem cells, guanidine, etc. The smart dendrimers contain desirable electrical, magnetic, optical, and biological attributes to increase surface area, monodisperse behavior, dose reduction, dissolution, permeability, long-term stability, and significant decrement in nanotoxicity studies. The higher encapsulation of lipid soluble and insoluble moieties explores an excellent platform for the delivery of drugs (ibuprofen, indomethacin, etc.), nucleic acids (oligonucleotide, siRNA, and aptamer), genetic materials , and chemical diagnostic agents (gadolinium chelates and superparamagnetic iron oxide particles) for imaging. Owing to their flexibility in structural adaptability, different health conditions like glaucoma, inflammation, microbial infection, neurodegenerative problems (Alzheimer's disease and Parkinsonism), and cancer are benefited using such long-lasting drug delivery. Advancements in molecular engineering techniques, 3D printing, artificial intelligence, robotic, green synthesis, and microwave-assisted methods aid in the development of economically reliable and personalized pharmaceutical hybrid dendritic systems resembling antibodies, globular proteins, stem cells, enzymes, and genetic materials.

Review: Application Trends of Contrast Media in PET/MRI

Research on medical imaging contrast agents to improve diagnostic performance and optimize treatment strategies has been ongoing for a long time. Recently, hybrid imaging technology in which two different devices such as PET/CT, SPECT/CT, and PET/MRI are fused is emerging as a new trend in medical imaging. The high spatial resolution of Magnetic Resonance Imaging (MRI) and the high-sensitivity molecular-level information of Positron Emission Tomography (PET) by these convergence devices are leading to the development of new hybrid imaging technologies along with hybrid contrast agents. To create a hybrid contrast agent for simultaneous PET-MRI devices, the radiotracer for PET should be combined with the MRI contrast agent. The most common approach to achieve this is to coat radioisotopes to the surface of small superparamagnetic iron oxide (SPIO) particles. These contrast agents are used for pH change monitoring, non-invasive angiography, and early imaging diagnosis of atherosclerosis. In addition, tumor detection and cardiovascular imaging are becoming important research areas for the development of simultaneous PET/MRI imaging systems and hybrid contrast agents. Therefore, tumor detection and cardiovascular imaging are major areas for development of simultaneous PET/MRI imaging systems and hybrid contrast agents. The goal of developing hybrid contrast agents for this purpose is to combine high spatial resolution, high sensitivity, and morphological and functional information. The future prospect is considered to be the development of a multimodal hybrid contrast agent that detects diseases early, provides information before and after surgery for treatment, and provides treatment prognosis.

Three-dimensional MR Neurography of the Brachial Plexus: Vascular Suppression with Low-dose Ferumoxytol.

Background The efficacy of ferumoxytol, an ultrasmall superparamagnetic iron oxide particle for three-dimensional (3D) MR neurography, has yet to be evaluated. Purpose To evaluate the effects of low-dose ferumoxytol for vascular suppression and nerve visualization in 3D brachial plexus MR neurography as a pilot study. Materials and Methods Volunteers without anemia were prospectively enrolled in July 2021. Brachial plexus MR neurography was performed 30 minutes following infusion of 25% of the standard (510 mg of iron) therapeutic ferumoxytol dose with use of a 3D short-tau inversion recovery T2-weighted fast spin-echo sequence. The 3D fast spin-echo was acquired with and without the use of additional flow suppression techniques. Two musculoskeletal radiologists qualitatively evaluated examinations for the degree of vascular suppression (0-3, none to complete), nerve visualization (0-2, none to full), and motion artifact (0-4, none to severe). Nerve-to-fat, muscle, or vessel contrast ratios were calculated with use of manually drawn regions of interests. Comparisons of the proportion of scans with adequate image quality (vascular suppression, 3; nerve visualization, 1, 2; motion artifacts, 0, 1) were made with use of the McNemar test. Comparisons of quantitative contrast ratios were performed with use of Wilcoxon signed rank tests. P < .05 was deemed statistically significant. Results There were 12 volunteers (mean age, 25 years ± 3; six women) evaluated. The scans with adequate vascular suppression increased from 0% to 98% with and without ferumoxytol, respectively (P < .001). All individual nerve assessments of adequate nerve visualization increased from 4%-63% to 36%-100% without and with ferumoxytol, respectively (P < .001-.010), while motion artifacts were unchanged (from 33% to 52%, P = .212). Quantitatively, nerve-to-vessel contrast ratios increased from 0.6 without to 7.6 with ferumoxytol (P < .001). The addition of flow suppression did not change nerve-to-vessel contrast ratio quantitatively (from 7.5 to 8.4, P > .99) following ferumoxytol. Conclusion Low-dose ferumoxytol improved vascular suppression and nerve visualization in three-dimensional MR neurography of the brachial plexus compared to imaging without ferumoxytol. © RSNA, 2022.

42 (PB-042) Poster - Comparison of Technetium (Tc)- and SPIO-guided Sentinel Lymph Node Biopsy (SLNB) in Patients with Neoadjuvant Chemotherapy in Early Breast Cancer – first retrospective data

Background: Super-paramagnetic iron oxide particle (SPIO)-techniques are reasonable alternatives to Technetium-(Tc)-localization of SLNB/TAD in early breast cancer with a similar detection rate but superiority in logistics. These results have to be confirmed in a neoadjuvant setting (PST).

Biomimetic Magnetic Particles for the Removal of Gram-Positive Bacteria and Lipoteichoic Acid.

Gram+ bacteria are very common in clinical medicine and responsible for a large number of infectious diseases. For example, Gram+ bacteria play a major role in causing bloodstream infections and sepsis. Therefore, the detection of Gram+ bacteria is of great importance for the diagnosis and treatment of infectious diseases. Furthermore, these bacteria are often present in biofilms that cover implants. Recent research work has mainly focused on the biologic activity and removal of Gram-negative bacteria or bacterial components such as lipopolysaccharides (LPS). In contrast, the effects of lipoteichoic acid (LTA) have been less well studied so the relevance of their removal from body fluids is possibly underestimated. To address this topic, we evaluated superparamagnetic iron oxide particles (SPION) carrying different peptides derived from the innate immune receptor (GP-340) for their ability to bind and remove Gram+ bacteria and LTA from different media. Our results show that, beyond S. aureus, effective agglutinating and removing of S. pneumoniae was possible. Furthermore, we were able to show for the first time that this was possible with LTA alone and that the magnetic removal of bacteria was also efficient under flow conditions. We also found that this method was able to capture Stapyhylococcus aureus from platelet concentrates, which can help to enhance the sensitivity of microbiological diagnostics, quality control measures, and blood product safety.

Tracking of Stem Cells from Human Exfoliated Deciduous Teeth Labeled with Molday ION Rhodamine-B during Periodontal Bone Regeneration in Rats.

Chronic periodontitis can lead to alveolar bone resorption and eventually tooth loss. Stem cells from exfoliated deciduous teeth (SHED) are appropriate bone regeneration seed cells. To track the survival, migration, and differentiation of the transplanted SHED, we used super paramagnetic iron oxide particles (SPIO) Molday ION Rhodamine-B (MIRB) to label and monitor the transplanted cells while repairing periodontal bone defects. We determined an appropriate dose of MIRB for labeling SHED by examining the growth and osteogenic differentiation of labeled SHED. Finally, SHED was labeled with 25 μg Fe/ml MIRB before being transplanted into rats. Magnetic resonance imaging was used to track SHED survival and migration in vivo due to a low-intensity signal artifact caused by MIRB. HE and immunohistochemical analyses revealed that both MIRB-labeled and unlabeled SHED could promote periodontal bone regeneration. The colocalization of hNUC and MIRB demonstrated that SHED transplanted into rats could survive in vivo. Furthermore, some MIRB-positive cells expressed the osteoblast and osteocyte markers OCN and DMP1, respectively. Enzyme-linked immunosorbent assay revealed that SHED could secrete protein factors, such as IGF-1, OCN, ALP, IL-4, VEGF, and bFGF, which promote bone regeneration. Immunofluorescence staining revealed that the transplanted SHED was surrounded by a large number of host-derived Runx2- and Col II-positive cells that played important roles in the bone healing process. SHED could promote periodontal bone regeneration in rats, and the survival of SHED could be tracked in vivo by labeling them with MIRB. SHED are likely to promote bone healing through both direct differentiation and paracrine mechanisms.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles.

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content.

Ultrasmall Superparamagnetic Particles of Iron Oxide and Cardiac Magnetic Resonance: Novel Imaging in Everyday Conditions

Myocardial inflammation has been hypothesised to be the common underlying mechanism through which several cardiovascular diseases develop and progress. Cardiac magnetic resonance (CMR) has become a powerful non-invasive tool that enables the direct visualisation of the myocardium. The emerging use of ultrasmall superparamagnetic particles of iron oxide (USPIO) and their magnetic properties is gaining a lot of research interest. USPIO-enhanced CMR can provide valuable information, as it allows for the identification of active inflammation in the myocardium, a process that has been hypothesised to be the substrate for adverse remodelling and, eventually, heart failure. In this review, we summarise the properties of USPIO and their role in cardiac magnetic resonance imaging as well as their clinical applications.