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Background: Functional Magnetic resonance imaging (fMRI) measures the small fluctuation of blood flow happening during task-fMRI in brain regions. Objective: This research investigated these active, imagery and passive movements in volunteers design to permit a comparison of their capabilities in activating the brain areas. Material and Methods: In this applied research, the activity of the motor cortex during the right-wrist movement was evaluated in 10 normal volunteers under active, passive, and imagery conditions. T2* weighted, three-dimensional functional images were acquired using a BOLD sensitive gradient-echo EPI (echo planar imaging) sequence with echo time (TE) of 30 ms and repetition time (TR) of 2000 ms. The functional data, which included 248 volumes per subject and condition, were acquired using the blocked design paradigm. The images were analyzed by the SPM12 toolbox, MATLAB software. Results: The findings determined a significant increase in signal intensity of the motor cortex while performing the test compared to the rest time (p< 0.05). It was also observed that the active areas in hand representation of the motor cortex are different in terms of locations and the number of voxels in different wrist directions. Moreover, the findings showed that the position of active centers in the brain is different in active, passive, and imagery conditions. Conclusion: Results confirm that primary motor cortex neurons play an essential role in the processing of complex information and are designed to control the direction of movement. It seems that the findings of this study can be applied for rehabilitation studies.

β-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic s...

In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). The developed Gd2O3@PCD–FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD–FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD–FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD–FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. The results indicate the potential of Gd2O3@PCD–FA to serve as a novel targeted nano-contrast agent in MRI.

Purpose: Targeted magnetic drug delivery is one of the methods of cancer treatment. In this method, magnetic factors are conducted inside the body by a variable external magnetic field and deliver the drug agents to the tumor area. The present study aimed to investigate the performance of the drug magnetic conduction by using Differential Current Coil (DCC) and the effect of gravity force on it. Materials and Methods: In mathematical modeling, magnetic, hydrodynamic and gravity forces were assumed to affect the movement of magnetic nanoparticles inside the vessels. Helmholtz coils with a circular cross-section and different currents were simulated in the software environment. The trajectory of nanoparticles within the static fluid, Y-shape channel and multi-branch vascular network was calculated. The relations between the magnetic force applied on the magnetic nanoparticles and the parameters of coil flow, radius and relative permeability of the nanoparticles were investigated. Results: The magnetic flux generated in the coils was calculated and the particles moved in the direction of the magnetic gradient. The diagram of magnetophoresis force changes with the physical parameters was calculated. Particle trajectory and correct exit rate were obtained in simulated vessels. The output changes in the state of with-the-effect and without-the-effect of gravity were about 1.5 to 3%. The output changes of the correct and incorrect branches were calculated by changing the angle of the branches. Conclusion: From the approximate reduction of 2% of the correct output, it can be concluded that the effect of gravity on the conductivity of the system can be neglected. Besides, it seems that as the injection point is closer to the conduction point, the amount of the correct output will increase more.

We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using RIntra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing CThe intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for RSequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R

Cryptochromes (CRYs) have been suggested to involve in the magnetic sensing for navigation of migratory birds in response to Earth’s magnetic fields. Magnetic fields (MFs) through wireless penetration change the cell physiology by effect on physicochemical reactions. Here, we aimed to investigate the behavior of HEK 293T cells overexpressing human CRY-based magnetoreception complexes undergo doxorubicin (DOX) treatment and exposure to moderate intensity static magnetic field (SMF) and extremely low frequency-pulsed electromagnetic field (ELF-PEMF). The ability of this magnetosensor is depended on CRY-photoreceptor proteins that complemented with putative magnetosensor proteins (MagR). The results indicate that magnetic sensitivity of CRY-based magnetosensor can effects on the intracellular reactive oxygen species (ROS) production and cell growth, cell cycle progression and expression of DNA damage-related genes due to treatment of DOX, SMF and ELF-PEMF. Our findings show that ROS accumulation significantly decreased in the cells expressing CRY/MagR complexes in response to all treatments, and also cell viability is decreased in contrast to MFs exposure. In addition, magnetosensitive complexes mediated the upregulation of genes in the base excision repair (BER) pathway including ITPA in presence of SMF as well as MTH1 in presence of ELF-PEMF in the DOX treated-cells. Furthermore, CRY/MagR induced a remarkable cell cycle arrest at G0/G1 phase in the all treatments. These results demonstrated that CRY/MagR complexes modify the DNA damage responses during genotoxic stresses by controlling the cell cycle progression and ROS levels. Therefore, our data suggest that CRY-based magnetosensitive complexes can increase the cytotoxic effects of DOX even when SMF and/or ELF-PEMF exposure were provided, exclusively.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Overcoming the tumor radioresistance along with protecting the adjacent normal tissues is considered as the ultimate goal of the radiation therapy. To achieve this goal, extensive studies have demonstrated the radiosensitization potential of the gold nanoparticles (AuNPs) during treatment with low-energy ionizing radiation due to their high-photoelectric absorption coefficient. Compared to the AuNPs, the bismuth nanoparticles (BiNPs) with higher atomic number, low cost, high biocompatibility and high biodegradability are attractive candidates for amplifying the radiation dose. Accordingly, the aim of this study was to quantify dose enhancement factors (DEFs) from BiNPs compared to AuNPs at clinically relevant energies. To quantitatively monitor the three-dimensional distribution of the absorption dose, we synthesized the nPAG polymer gel impregnated with 0.2 mM (0.04 mg/ml tissue) of AuNPs and BiNPs separately. In parallel, the samples were exposed to iridium-192 internal (380 keV) and cobalt-60 external (1.25 MeV) sources to explore the effect of energy. Finally, the R2-weighted dose maps of the calibration and test tubes were acquired by a Siemens 1.5 T MRI scanner. The mean dose enhancements obtained by AuNPs and BiNPs following irradiation of iridium-192 source were 14.72% ± 0.34 and 16.35% ± 0.38, respectively. Conversely, these values decreased to less than 4% for the samples irradiated with cobalt-60 γ-rays. Taken together, our experimental results suggest BiNPs-enhanced iridium-192 brachytherapy can potentially be a promising therapeutic tool in improving the efficacy of cancer radiation therapy. However, enhancement factors obtained from the cobalt-60 source decreased more significantly, highlighting the strong energy dependence of dose enhancement.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

© 2017 Elsevier B.V. Brain tumor is a lethal, fast growing cancer and a difficult case for treatment. Receptor-mediated endocytosis has been recognized as one of the most effective methods for drug delivery to brain tissue by overcoming obstacles associated with conventional therapeutics. In this work, a targeted theranostic drug delivery system (DDS) was prepared based on gold‑iron oxide nanocomposites (Fe3O4@Au NCs). Lipoic acid-curcumin (LA-CUR) was synthesized and introduced as a novel anticancer drug, and glutathione (GSH) was exploited as the targeting ligand. Both LA-CUR and GSH were easily attached to Fe3O4@Au NCs via Au-S interaction. As a negatively charged nanocarrier, the prepared DDS showed relatively less protein adsorption. Accordingly, hemocompatibility assays (complement, platelet, and leucocyte activation) revealed its hemocompatible virtue, especially in respect of free LA-CUR. GSH functionalization led to 2-fold increase of cellular uptake in GSH receptor-positive astrocyte cells which could primarily indicate the probable ability of the DDS to bypass BBB. Cytotoxicity and apoptosis assays together showed the noticeably enhanced cytotoxicity of LA-CUR against cancerous U87MG cells (IC50 = 2.69 μg/ml) in comparison with curcumin (IC50 = 21.31 μg/ml); moreover, the DDS demonstrated relatively higher cytotoxicity against cancerous U87MG cells than normal astrocyte cells which was in accordance with pH sensitive mechanism of LA-CUR release. Besides, the results of in vitro magnetic resonance imaging (MRI) (relaxation rate (r2) = 80.73 (s− 1·mM− 1)) primarily revealed that the DDS can be applied as a negative MRI contrast agent. In sum, the prepared DDS appeared to be a promising candidate for brain cancer treatment and a favorable MRI contrast agent.

Imaging methods have an important role in the management of patient’s health care. Some of the advantages made magnetic resonance imaging (MRI) as an exclusive modality. Gd-DTPA is one of the most common contrast agents in clinical applications. In this study, the concentrations of three gadolinium-based MRI contrast agents were measured and quantification accuracy of these contrast agents by MRI method was investigated. Different concentrations from the Gd-DTPA, Gd2O3–DEG and paramagnetoliposome nanoparticles (encapsulated Gd2O3–DEG nanoparticles in liposome) samples were prepared. Physical characteristics of the contrast agents were investigated by DLS and TEM methods. The T 1-weighted images of the prepared samples were recorded using MRI scanner. For each sample, gadolinium concentrations were determined using the relaxation rates and relaxivities. Determined concentrations by the experimental and ICP/OES methods were compared and the standard errors of the results were determined. Morphology, dimension and hydrodynamic diameter of the contrast agents were investigated. The hydrodynamic diameter of Gd2O3–DEG and PML nanoparticles were 90 ± 7.2 nm (with PdI = 0.328) and 96.8 ± 6.5 nm (with PdI = 0.299), respectively. In assessment of gadolinium concentrations, standard deviations of the experimental and ICP/OES data were ranged from 0.007 to 0.04. P values of all data points were higher than 0.05 that confirm there is no significant difference between the experimental and ICP/OES measurements. From the results, it could be concluded that MR systems could be used as an accurate and available method to estimate gadolinium concentrations.

Introduction: The conventional methods of dosimetry are not capable of dosimetry in such a small volume of less than one cubic millimeter. Although the polymer gel dosimetry method based on magnetic resonance imaging (MRI) could achieve three dimensional dosimetry with high resolution, a spatial resolution evaluation based on gel dose modulation transfer function has not been investigated yet. Therefore, in this study, the spatial resolution of two systems of film densitometry and polymer gel dosimetry based on MRI has been evaluated by using the dose modulation transfer function (DMTF). Material and Methods: Kodak therapy verification films and MAGICA polymer gel samples were positioned below a brass absorption grid with different periodic slices (a/2= 280, 525, 1125 μm), which was placed in a water bath container to avoid regions of dose build-up just below the absorption grid and then irradiated with Cobalt-60 photons on a Theratron external-beam treatment unit. Dose variation under the brass grid was determined using a calibration curve, while transverse relaxation time (T2) as the selective parameter in a dose image based on multiple echo MRI with 1.5 Tesla GE Signa Echo Speed system (FOV=10 cm, matrix size=512 ×512, pixel size =0.199×0.199 mm2, TE = 20, 40, 60, 80 ms, TR=4200 ms, NEX = 4, slice thickness=2 mm, gap=1 mm) was calculated. DMTF from the modulation depths of T2 and variation in film optical density after calibration would be achieved. The results of polymer gel were compared with film. Results: After deriving the dose distribution profile under the absorption grid, minima and maxima at the smallest period of a = 560 μm could scarcely be resolved, but the modulations due to a=2250 μm and a = 1050 μm grids could be discerned. The modulation depth for a=2250 μm grid was set to 100% and the other modulations were subsequently referred to this maximum modulation. For film densitometry at a = 1050 μm, the modulation depth was reduced to 35% (30% for MR based polymer gel dosimetry; MRPD) and at a = 560 μm the modulation in dose was reduced to about 9% of the maximum amplitude (7% for MRPD). The DMTF for the two systems at 200 micron spatial resolution for the 2250, 1050 and 560 μm grids (0.4, 0.9 and 1.7 line pairs per mm) were equal to 1, 0.35 and 0.09 for film densitometry and 1, 0.30 and 0.07 for polymer gel. Discussion and Conclusions: Based on the results of this study, the decrease in DMTF at higher frequencies in a system in its operating resolution limit, is dependent on the type of the dosimetry system. Therefore, the assessment of DMTF for film densitometry system implied a higher spatial resolution in comparison with polymer gel dosimetry at 200 micron spatial resolution.

Context: In radiation treatments, estimation of the dose distribution in the target volume is one of the main components of the treatment planning procedure. To estimate the dose distribution, the information of electron densities is necessary. The standard curves determined by computed tomography (CT) scanner that may be different from that of other oncology centers. In this study, the changes of dose calculation due to the different calibration curves (HU-ρel ) were investigated. Materials and Methods: Dose values were calculated based on the standard calibration curve that was predefined for the treatment planning system (TPS). The calibration curve was also extracted from the CT images of the phantom, and dose values were calculated based on this curve. The percentage errors of the calculated values were determined. Statistical Analysis Used: The statistical analyses of the mean differences were performed using the Wilcoxon rank-sum test for both of the calibration curves. Results and Discussion: The results show no significant difference for both of the measured and standard calibration curves (HU-ρel ) in 6, 15, and 18 MeV energies. In Wilcoxon ranked sum nonparametric test for independent samples with P < 0.05, the equality of monitor units for both of the curves to transfer 200 cGy doses to reference points was resulted. The percentage errors of the calculated values were lower than 2% and 1.5% in 6 and 15 MeV, respectively. Conclusion: From the results, it could be concluded that the standard calibration curve could be used in TPS dose calculation accurately.

We developed biofunctionalized nanoparticles with magnetic properties by immobilizing diethyleneglycol (DEG) on Gd2O3, and PEGilation of small particulate gadolinium oxide (SPGO) with two methoxy-polyethyleneglycol-silane (mPEG-Silane 550 and 2000 Da) using a new supervised polyol route, described recently. In conjunction to the previous study to achieve a high quality synthesis and increase in the product yield of nanoparticles; assessment of the effects of functionalization, chemisorption and altered reaction conditions, such as NaOH concentration, temperature, reaction time and their solubility, on size reproducibility were determined as the goals of this study. Moreover, the effects of centrifugation, filtration and dialysis of the solution on the nono magnetic particle size values and their stability against aggregation have been evaluated. Optimization of reaction parameters led to strong coating of magnetic nanoparticles with the ligands which increases the reproducibility of particle size measurements. Furthermore, the ligand-coated nanoparticles showed enhanced colloidal stability as a result of the steric stabilization function of the ligands grafted on the surface of particles. The experiments showed that DEG and mPEG-silane (550 and 2000 Dalton) are chemisorbed on the particle surfaces of Gd2O3 and SPGO which led to particle sizes of 5.9 ± 0.13 nm, 51.3 ± 1.46 nm and 194.2 ± 22.1 nm, respectively. The small size of DEG-Gd2O3 is acceptably below the cutoff of 6nm, enabling easy diffusion through lymphatics and filtration from kidney, and thus provides a great deal of potential for further in-vivo and in-vitro application.

Introduction: Multiple sclerosis (MS) is characterized by lesions in the white matter (WM) of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI) is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the "standard space", and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR) MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR), magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse), T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR). Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS