Magnetic Resonance Imaging Tracking Research Articles

MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Insulin-producing cells (IPCs) derived from a patient’s own stem cells offer great potential for autologous transplantation in diabetic patients. However, the limited survival of engrafted cells remains a bottleneck in the application of this strategy. The present study aimed to investigate whether nanoparticle-based magnetic resonance (MR) tracking can be used to detect the loss of grafted stem cell-derived IPCs in a sensitive and timely manner in a diabetic monkey model. Pancreatic progenitor cells (PPCs) were isolated from diabetic monkeys and labeled with superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-labeled cells presented as hypointense signals on MR imaging (MRI). The labeling procedure did not affect the viability or IPC differentiation of PPCs. Importantly, the total area of the hypointense signal caused by SPION-labeled IPCs on liver MRI decreased before the decline in C-peptide levels after autotransplantation. Histological analysis revealed no detectable immune response to the grafts and many surviving insulin- and Prussian blue-positive cell clusters on liver sections at one year post-transplantation. Collectively, this study demonstrates that SPIO nanoparticles can be used to label stem cells for noninvasive, sensitive, longitudinal monitoring of stem cell-derived IPCs in large animal models using a conventional MR imager.

Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke

Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic resonance imaging (MRI) is imperative for better understanding cellular survival and migrational dynamics over time. In this study, we develop a novel biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing spermine and the image label, ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity of the nanocomplex in transferring SPIONs into green fluorescence protein-modified MSCs were tested; and the performance of in vivo MRI tracking of the transplanted cells in acute ischemic stroke was determined. The results demonstrated that the new class of SPIONs-complexed nanoparticles based on biodegradable amylose can serve as a highly effective and safe carrier to transfer magnetic label into stem cells. A reliable tracking of transplanted stem cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic benefit of stem cells on stroke retained. With the advantages of a relatively low SPIONs concentration and a short labeling period, the biocompatible complex of cationic amylose with SPIONs is highly translatable for clinical application. It holds great promise in efficient, rapid, and safe labeling of stem cells for subsequent cellular MRI tracking in regenerative medicine.

Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia.

Superparamagnetic iron oxide nanoparticles (SPIO) are applied as contrast media for magnetic resonance imaging (MRI) and treatment of neurologic diseases despite the fact that important information concerning their local interactions is still lacking. Due to their small size, SPIO have great potential for magnetically labeling different cell populations, facilitating their MRI tracking in vivo. Before SPIO are applied, however, their effect on cell viability and tissue homoeostasis should be studied thoroughly. We have previously published data showing how citrate-coated very small superparamagnetic iron oxide particles (VSOP) affect primary microglia and neuron cell cultures as well as neuron-glia cocultures. To extend our knowledge of VSOP interactions on the three-dimensional multicellular level, we further examined the influence of two types of coated VSOP (R1 and R2) on murine organotypic hippocampal slice cultures. Our data show that 1) VSOP can penetrate deep tissue layers, 2) long-term VSOP-R2 treatment alters cell viability within the dentate gyrus, 3) during short-term incubation VSOP-R1 and VSOP-R2 comparably modify hippocampal cell viability, 4) VSOP treatment does not affect cytokine homeostasis, 5) microglial depletion decreases VSOP uptake, and 6) microglial depletion plus VSOP treatment increases hippocampal cell death during short-term incubation. These results are in line with our previous findings in cell coculture experiments regarding microglial protection of neurite branching. Thus, we have not only clarified the interaction between VSOP, slice culture, and microglia to a degree but also demonstrated that our model is a promising approach for screening nanoparticles to exclude potential cytotoxic effects.

Parkinson's disease diffusion MRI is not affected by acute antiparkinsonian medication.

ObjectiveA prior longitudinal study demonstrates that free-water diffusion magnetic resonance imaging (dMRI) tracks progression in the substantia nigra (Ofori et al., 2015b). Here, we test the acute effects of antiparkinsonian medication on this established imaging progression marker for the first time.MethodsFifteen PD patients underwent dMRI OFF and ON-medication one day apart. ON-medication, patients were tested approximately 45 min after their usual dose of antiparkinsonian medication. OFF-medication, patients were tested after not taking antiparkinsonian medication for > 12 h. OFF and ON-medication was counter-balanced across subjects. For dMRI, we computed free-water and free-water corrected fractional anisotropy (FAt) within the following regions: caudate, putamen, substantia nigra, and subthalamic nucleus.ResultsON-medication significantly reduced parkinsonian motor symptoms compared with OFF-medication (p < 0.001). dMRI measures (free-water and FAt) were not different between the OFF and ON-medication conditions.ConclusionsAdministration of an acute does of anti-parkinsonian medication in PD does not affect free-water and FAt in key nigrostriatal structures. Free-water and FAt biomarkers reflect the chronic state of the nigrostriatal circuit, and therefore are potential viable biomarkers for disease-modifying therapeutic studies in PD.

A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

Novel cationic polymeric micelles based on biodegradable poly(aspartic acid-dimethylethanediamine)–lysine–cholic acid were synthesized for in vivo tracking therapeutic stem cells using MRI.

Influences of High-Level Features, Gaze, and Scene Transitions on the Reliability of BOLD Responses to Natural Movie Stimuli.

Complex, sustained, dynamic, and naturalistic visual stimulation can evoke distributed brain activities that are highly reproducible within and across individuals. However, the precise origins of such reproducible responses remain incompletely understood. Here, we employed concurrent functional magnetic resonance imaging (fMRI) and eye tracking to investigate the experimental and behavioral factors that influence fMRI activity and its intra- and inter-subject reproducibility during repeated movie stimuli. We found that widely distributed and highly reproducible fMRI responses were attributed primarily to the high-level natural content in the movie. In the absence of such natural content, low-level visual features alone in a spatiotemporally scrambled control stimulus evoked significantly reduced degree and extent of reproducible responses, which were mostly confined to the primary visual cortex (V1). We also found that the varying gaze behavior affected the cortical response at the peripheral part of V1 and in the oculomotor network, with minor effects on the response reproducibility over the extrastriate visual areas. Lastly, scene transitions in the movie stimulus due to film editing partly caused the reproducible fMRI responses at widespread cortical areas, especially along the ventral visual pathway. Therefore, the naturalistic nature of a movie stimulus is necessary for driving highly reliable visual activations. In a movie-stimulation paradigm, scene transitions and individuals’ gaze behavior should be taken as potential confounding factors in order to properly interpret cortical activity that supports natural vision.

Iron sucrose (Venofer®) labelled Adipose derived stem cell by using 3T Magnetic Resonance Imaging Tracking: In vitro study

Iron sucrose (Venofer®) labelled Adipose derived stem cell by using 3T Magnetic Resonance Imaging Tracking: In vitro study

356 Microsurgical Anatomy of the Brainstem Safe Entry Zones

Abstract Operative management of intrinsic brainstem lesions remains challenging despite advances in electrophysiological monitoring and neuroimaging. Surgical intervention in this region requires detailed knowledge of adjacent, critical white matter tracts and cranial nerve nuclei. Our aim was to systematically verify internal anatomy associated with each brainstem safety zone entry zone (BSEZ) using a cadaveric model supplemented with neuroimaging modalities commonly used in preoperatively planning, namely high-resolution magnetic resonance imaging (MRI) and fiber tracking. Twelve BSEZs were simulated in 8 formalin-fixed, cadaveric heads. Specimens then underwent radiological investigation including T2-weighted imaging and fiber tracking using 4.7 T MRI. The distance between simulated BSEZs and predefined, adjacent, critical structures was systemically recorded. Entry points and anatomic limits on the surface of the brainstem are described for each BSEZ, along with description of neurological sequelae if such limits are violated. With high-resolution imaging, we verified maximal depth and optimal angle of entry for each BSEZ. The relationship between BSEZs and adjacent, critical structures was quantified. Orbitozygomatic, suboccipital, retrosigmoid, retrolabyrinthine, and petrosectomy approaches were used to simulate BSEZs in the ventral, dorsal, and lateral brainstem. Critical structures most at risk for injury during BSEZ approach included the oculomotor nerve, trochlear nerve, red nucleus, medial lemniscus, medial longitudinal fasciculus, corticospinal tract, and hypoglossal nucleus. Once thought to be universally inoperable, select lesions of the brainstem may now be treated by experienced surgeons with adjunct instrumentation, imaging, neuromonitoring, and intricate knowledge of BSEZs. All approaches adhered to the 2-point rule while minimizing neural and vascular damage. In combination with cadaveric dissection, high-resolution MRI and fiber tracking allow the surgical team to develop a better understanding of the internal architecture of the brainstem, particularly as related to BSEZs. The careful study of such imaging may lead to more accurate and safe surgery through use of optimal surgical corridors.

Cardiac Chemical Exchange Saturation Transfer MR Imaging Tracking of Cell Survival or Rejection in Mouse Models of Cell Therapy.

Purpose To examine whether cardiac chemical exchange saturation transfer (CEST) imaging can be serially and noninvasively used to probe cell survival or rejection after intramyocardial implantation in mice. Materials and Methods Experiments were compliant with the National Institutes of Health Guidelines on the Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee. One million C2C12 cells labeled with either europium (Eu) 10-(2-hydroxypropyl)-1,4,7-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) or saline via the hypotonic swelling technique were implanted into the anterior-lateral left ventricular wall in C57BL/6J (allogeneic model, n = 17) and C3H (syngeneic model, n = 13) mice. Imaging (frequency offsets of ±15 parts per million) was performed 1, 10, and 20 days after implantation, with the asymmetrical magnetization transfer ratio (MTRasym) calculated from image pairs. Histologic examination was performed at the conclusion of imaging. Changes in MTRasym over time and between mice were assessed by using two-way repeated-measures analysis of variance. Results MTRasym was significantly higher in C3H and C57BL/6J mice in grafts of Eu-HP-DO3A-labeled cells (40.2% ± 5.0 vs 37.8% ± 7.0, respectively) compared with surrounding tissue (-0.67% ± 1.7 vs -1.8% ± 5.3, respectively; P < .001) and saline-labeled grafts (-0.4% ± 6.0 vs -1.2% ± 3.6, respectively; P < .001) at day 1. In C3H mice, MTRasym remained increased (31.3% ± 9.2 on day 10, 28.7% ± 5.2 on day 20; P < .001 vs septum) in areas of in Eu-HP-DO3A-labeled cell grafts. In C57BL/6J mice, corresponding MTRasym values (11.3% ± 8.1 on day 10, 5.1% ± 9.4 on day 20; P < .001 vs day 1) were similar to surrounding myocardium by day 20 (P = .409). Histologic findings confirmed cell rejection in C57BL/6J mice. Estimation of graft area was similar with cardiac CEST imaging and histologic examination (R2 = 0.89). Conclusion Cardiac CEST imaging can be used to image cell survival and rejection in preclinical models of cell therapy. © RSNA, 2016 Online supplemental material is available for this article.

Of mice and women: How animal models helped in the identification of potential treatments in obstetric APS

Transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising approach for treatment of epilepsy. To our knowledge, there is little research on magnetic resonance imaging (MRI) tracking of BMSCs labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a rat model of temporal lobe epilepsy (TLE). In this study, BMSCs were pre-labeled with USPIO nanoparticles, and then the cell apoptosis, proliferation, surface antigens, and multipotency were investigated. Lithium chloride-pilocarpine induced TLE models were administered by USPIO-labeled BMSCs (U-BMSCs), BMSCs, and saline through lateral ventricle injection as the experimental group, control I group and control II group, respectively, followed by MRI examination, electroencephalography (EEG) and Prussian blue staining. The cell experimental results showed that the labeled USPIO did not affect the biological characteristics and multiple potential of BMSCs. The U-BMSCs can be detected using MRI in vitro and in vivo, and observed in the hippocampus and adjacent parahippocampal cortical areas of the epileptic model. Moreover, electroencephalographic results showed that transplanted U-BMSCs, as well as BMSCs, were capable of reducing the number of epileptiform waves significantly (P < 0.01) compared with control II group. All of these findings suggest that it is feasible to track transplanted BMSCs using MRI in a rat model of TLE, and support that USPIO labeling is a valuable tool for cell tracking in the study of seizure disorders.

VIEWING ONLY POSTERS1323Evaluation of right ventricular transverse strain and strain rate in patients with acute ST-segment elevation myocardial infarction: a cardiac magnetic resonance feature tracking study1333Cardiac resynchronization in ischemic heart failure patients: a comparison between therapy guided by cardiac magnetic resonance imaging and 2D-speckle tracking echocardiography1338Cardiac magnetic resonance versus bisphosphonate scintigraphy for diagnosis of cardiac amyloidosis1341Strain relaxation index, a novel

VIEWING ONLY POSTERS1323Evaluation of right ventricular transverse strain and strain rate in patients with acute ST-segment elevation myocardial infarction: a cardiac magnetic resonance feature tracking study1333Cardiac resynchronization in ischemic heart failure patients: a comparison between therapy guided by cardiac magnetic resonance imaging and 2D-speckle tracking echocardiography1338Cardiac magnetic resonance versus bisphosphonate scintigraphy for diagnosis of cardiac amyloidosis1341Strain relaxation index, a novel

Four Gadolinium(III) Complexes Appended to a Porphyrin: A Water-Soluble Molecular Theranostic Agent with Remarkable Relaxivity Suited for MRI Tracking of the Photosensitizer.

A molecular theranostic agent for magnetic resonance imaging (MRI) and photodynamic therapy (PDT) consisting of four [GdDTTA](-) complexes (DTTA(4-) = diethylenetriamine-N,N,N″,N″-tetraacetate) linked to a meso-tetraphenylporphyrin core, as well as its yttrium(III) analogue, was synthesized. A variety of physicochemical methods were used to characterize the gadolinium(III) conjugate 1 both as an MRI contrast agent and as a photosensitizer. The proton relaxivity measured in H2O at 20 MHz and 25 °C, r1 = 43.7 mmol(-1) s(-1) per gadolinium center, is the highest reported for a bishydrated gadolinium(III)-based contrast agent of medium size and can be related to the rigidity of the molecule. The complex displays also a remarkable singlet oxygen quantum yield of ϕΔ = 0.45 in H2O, similar to that of a meso-tetrasulfonated porphyrin. We also evidenced the ability of the gadolinium(III) conjugate to penetrate in cancer cells with low cytotoxicity. Its phototoxicity on Hela cells was evaluated following incubation at low micromolar concentration and moderate light irradiation (21 J cm(-2)) induced 50% of cell death. Altogether, these results demonstrate the high potential of this conjugate as a theranostic agent for MRI and PDT.

Visualization of Cranial Nerves Using High-Definition Fiber Tractography.

Recent studies have demonstrated diffusion tensor imaging tractography of cranial nerves (CNs). Spatial and angular resolution, however, is limited with this modality. A substantial improvement in image resolution can be achieved with high-angle diffusion magnetic resonance imaging and atlas-based fiber tracking to provide detailed trajectories of CNs. To use high-definition fiber tractography to identify CNs in healthy subjects and patients with brain tumors. Five neurologically healthy adults and 3 patients with brain tumors were scanned with diffusion spectrum imaging that allowed high-angular-resolution fiber tracking. In addition, a 488-subject diffusion magnetic resonance imaging template constructed from the Human Connectome Project data was used to conduct atlas space fiber tracking of CNs. The cisternal portions of most CNs were tracked and visualized in each healthy subject and in atlas fiber tracking. The entire optic radiation, medial longitudinal fasciculus, spinal trigeminal nucleus/tract, petroclival portion of the abducens nerve, and intrabrainstem portion of the facial nerve from the root exit zone to the adjacent abducens nucleus were identified. This suggested that the high-angular-resolution fiber tracking was able to distinguish the facial nerve from the vestibulocochlear nerve complex. The tractography clearly visualized CNs displaced by brain tumors. These tractography findings were confirmed intraoperatively. Using high-angular-resolution fiber tracking and atlas-based fiber tracking, we were able to identify all CNs in unprecedented detail. This implies its potential in localization of CNs during surgical planning. CN, cranial nerveDSI, diffusion spectrum imagingDTI, diffusion tensor imagingHCP, Human Connectome ProjectHDFT, high-definition fiber tractographyMLF, medial longitudinal fasciculusODF, orientation distribution functionROI, region of interest.

How can clinicians detect and treat autism early? Methodological trends of technology use in research.

We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965 to 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye tracking were the most frequently used technologies. The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated, and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention.

MRI tracking of bone marrow mesenchymal stem cells labeled with ultra-small superparamagnetic iron oxide nanoparticles in a rat model of temporal lobe epilepsy

Transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising approach for treatment of epilepsy. To our knowledge, there is little research on magnetic resonance imaging (MRI) tracking of BMSCs labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a rat model of temporal lobe epilepsy (TLE). In this study, BMSCs were pre-labeled with USPIO nanoparticles, and then the cell apoptosis, proliferation, surface antigens, and multipotency were investigated. Lithium chloride-pilocarpine induced TLE models were administered by USPIO-labeled BMSCs (U-BMSCs), BMSCs, and saline through lateral ventricle injection as the experimental group, control I group and control II group, respectively, followed by MRI examination, electroencephalography (EEG) and Prussian blue staining. The cell experimental results showed that the labeled USPIO did not affect the biological characteristics and multiple potential of BMSCs. The U-BMSCs can be detected using MRI in vitro and in vivo, and observed in the hippocampus and adjacent parahippocampal cortical areas of the epileptic model. Moreover, electroencephalographic results showed that transplanted U-BMSCs, as well as BMSCs, were capable of reducing the number of epileptiform waves significantly (P<0.01) compared with control II group. All of these findings suggest that it is feasible to track transplanted BMSCs using MRI in a rat model of TLE, and support that USPIO labeling is a valuable tool for cell tracking in the study of seizure disorders.

Abstract 215: Tracking transplanted cells with paramagnetic fluorinated nanoemulsions

Abstract Visualization of distinct cell populations in vivo is one of the most formidable challenges in biomedical sciences. Clinical translation of cutting-edge therapies that involve administration of live immunotherapeutic or stem cells can benefit from understanding the fate of injected cells in vivo. Magnetic resonance imaging (MRI) is emerging as a prime method for non-invasive, longitudinal cell tracking. Fluorine-19 MRI (19F MRI) involves the use of non-radioactive 19F label in the form of biologically inert, cytocompatible perfluorocarbons (PFC). Immediately prior to injection, cells of interest are labeled ex vivo with water-based PFC nanoemulsions. 19F MRI yields background-free images of labeled cells in an anatomical context provided by conventional 1H MRI. Both datasets are acquired on the same scanner in one imaging session. This technology has recently been used to detect immunotherapeutic dendritic cells delivered to colorectal adenocarcinoma patients. We sought to enhance sensitivity and versatility of 19F MRI by using paramagnetic relaxation agents. Covalent modification of clinically relevant PFCs with metal-binding ligands enabled stable and uniform incorporation of gadolinium and iron in the fluorous phase of nanoemulsions. Paramagnetic relaxation enhancement resulted in up to 50-fold reduction in 19F longitudinal relaxation time (T1) compared to state-of-the-art commercial tracers. The ultralow 19F T1 of our paramagnetic tracers enabled in vivo cell tracking with rapid, three-dimensional, zero time-to-echo (ZTE) 19F MRI pulse sequences in mice bearing subcutaneous allografts of 19F-labeled GL261 cells. Moreover, the high local concentration of paramagnetic metals imparted negative contrast in T2*-weighted 1H images. Combination of the new agents with conventional 19F tracers comprises a previously unavailable toolbox of 19F contrast agents, selectively detectable by appropriate acquisition methods. This enables “multicolor” 19F MRI tracking of multiple cell populations, e.g., for monitoring the interaction of host immune cells with injected therapeutic cells or cancer xenografts. Overall, the design of biocompatible, fast-relaxing 19F tracers addresses the issue of modest sensitivity of 19F MRI and reduces the barriers to widespread adoption of this powerful imaging technique. Citation Format: Alexander A. Kislukhin, Hongyan Xu, Stephen R. Adams, Kazim Narsinh, Roger Y. Tsien, Eric T. Ahrens. Tracking transplanted cells with paramagnetic fluorinated nanoemulsions. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 215. doi:10.1158/1538-7445.AM2015-215

Cortico-pallidal oscillatory connectivity in patients with dystonia.

Primary dystonia has been associated with an underlying dysfunction of a wide network of brain regions including the motor cortex, basal ganglia, cerebellum, brainstem and spinal cord. Dystonia can be effectively treated by pallidal deep brain stimulation although the mechanism of this effect is not well understood. Here, we sought to characterize cortico-basal ganglia functional connectivity using a frequency-specific measure of connectivity-coherence. We recorded direct local field potentials from the human pallidum simultaneously with whole head magnetoencephalography to characterize functional connectivity in the cortico-pallidal oscillatory network in nine patients with idiopathic dystonia. Three-dimensional cortico-pallidal coherence images were compared to surrogate images of phase shuffled data across patients to reveal clusters of significant coherence (family-wise error P < 0.01, voxel extent 1000). Three frequency-specific, spatially-distinct cortico-pallidal networks have been identified: a pallido-temporal source of theta band (4-8 Hz) coherence, a pallido-cerebellar source of alpha band (7-13 Hz) coherence and a cortico-pallidal source of beta band (13-30 Hz) coherence over sensorimotor areas. Granger-based directionality analysis revealed directional coupling with the pallidal local field potentials leading in the theta and alpha band and the magnetoencephalographic cortical source leading in the beta band. The degree of pallido-cerebellar coupling showed an inverse correlation with dystonic symptom severity. Our data extend previous findings in patients with Parkinson's disease describing motor cortex-basal ganglia oscillatory connectivity in the beta band to patients with dystonia. Source coherence analysis revealed two additional frequency-specific networks involving the temporal cortex and the cerebellum. Pallido-cerebellar oscillatory connectivity and its association with dystonic symptoms provides further confirmation of cerebellar involvement in dystonia that has been recently reported using functional magnetic resonance imaging and fibre tracking.

Stem Cell Labeling with Superparamagnetic Iron Oxide Nanoparticles Using Focused Ultrasound and Magnetic Resonance Imaging Tracking

Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a "closed" MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labeling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs) were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43 ± 9.55 nm) had the highest T2 relaxivity (136.62 Fe mM(-1) S(-1)) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally, confirmed by histological evaluation, pronounced signal attenuation on T2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the "closed" device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking.

Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells

Particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) are commonly based on nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present a proof of concept for multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference. Antisense locked nucleic acids (α-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO-α-LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 h) that was accompanied by significant depletion of the targeted microRNA Let7g (80%), up-regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO-α-LNA-labeled cells were successfully detected by fluorescence imaging and could be visualized by MRI after intrasplenic transplantation in rats. This new theranostic particle provides a promising tool for cell transplantation where cellular imaging and microRNA-based manipulation is needed. [165]

Interaction between Iron Oxide Nanoparticles and HepaRG Cells: A Preliminary In Vitro Evaluation

Nowadays, the use of iron oxide nanoparticles is widespread to label cells for magnetic resonance imaging tracking. More recently, magnetic labeling provides promising new opportunities for tissue engineering by controlling and manipulating cells through the action of an external magnetic field. The present work describes nonspecific labeling of metabolically competent HepaRG hepatocytes with anionic iron oxide nanoparticles. An interaction was observed between nanoparticles and studied cells, which were easily attracted when exposed to a magnet. No cytotoxicity was detected in the hepatocytes after 24 hours of incubation with iron oxide nanoparticles. Impact on HepaRG metabolization activity was assessed. Although a slight decrease in the metabolite generation was observed after exposure to nanoparticles (2 mM in iron), the enzymatic capacity was maintained. These results pave the way for 3D cultures of magnetic labeled HepaRG cells by using a magnetic field.