Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging.

Purpose: Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. Methods: In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. Results: The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. Conclusion: The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.

NSF evaluation of gadolinium biodistribution in renally impaired rats: Using novel metabolic Gd2O3 nanoparticles coated with ß-cyclodextrin (Gd2O3@PCD) in MR molecular imaging.

The use of conventional gadolinium(Gd)-based contrast agents in magnetic resonance imaging (MRI) poses a significant risk of Nephrogenic Systemic Fibrosis (NSF) syndrome in patients with impaired renal function (grades 4 and 5). To address this issue, a new study has introduced a novel metabolic Gadolinium oxide nanoparticle (Gd2O3 NPs) coated with ß-cyclodextrin (ßCD). The study aims to investigate NSF syndrome by quantifying tissue Gd deposition biodistribution in renal impairment rats using MR molecular imaging. This is the first study of its kind to use this approach. A group of 20 rats were divided into four groups, each containing five rats that underwent 5/6 nephrectomy. The rats received 12 intravenous injections of a novel homemade synthesized gadolinium oxide polycyclodextrin (Gd2O3@PCD) at a dose of 0.1 mmol/kg, conventional contrast agents (CAs) drugs of Omniscan (Gd-DTPA-BMA) and Dotarem (Gd-DOTA), at a dose of 2.5 mmol/kg, and 250 µl saline for two injections per week during six weeks. T1-weighted MR imaging was performed before the injections and once a week for six weeks to quantify Gd deposition in four different organs (skin, liver, heart, and lung) in rats using inductively coupled plasma mass spectrometry (ICP-MS). The relationship between Signal-to-Noise Ratio (SNR) and biodistribution of Gd deposition due to NSF-induced syndrome was also calculated. The results of the study showed that the Gd concentrations in tissues were significantly higher in the Gd2O3@PCD group compared to the other groups, without any significant histopathological changes (P < 0.05). In the Gd2O3@PCD group, Gd was mainly deposited in the skin, followed by the liver, lung, and heart, without any symptoms of thickening or hardening of the skin. The Gd concentrations in the skin, liver, lung, and heart were significantly lower in the Dotarem group than in the Omniscan group (P < 0.05). In the histopathological examinations, the Omniscan group showed increased cellularity in the dermis. A significant hyperintensity was observed in the Gd2O3@PCD-treated rats compared to the Dotarem and Omniscan groups in the liver, heart, and lung. Compared to conventional Gd-based CAs, the novel metabolically Gd2O3@PCD with increased SNR, biosafety, and a considerably lower probability of developing NSF, has potential applicability for diagnosing patients with renal diseases in clinical MR Molecular Imaging (MRMI).

Measurement of Post-Treatment Changes in Brain Metabolites in Patients with Generalized Anxiety Disorder using Magnetic Resonance Spectroscopy.

BACKGROUND: From previous studies, we know the correlations of some brain metabolites with a generalized anxiety disorder (GAD) and its symptoms. The response of GAD patients to various treatments is not the same and finding the best treatment option for each patient takes a long period of time. OBJECTIVE: In this study, we try to examine if there is any relationship between a special treatment option and GAD patients' response and brain metabolite correlation with anxiety level change. MATERIAL AND METHODS: This study is a clinical trial type of studies. We have used proton MRS (1H-MRS) with field strength of 3 Tesla to assess whether a different treatment option makes different responses based on metabolite changes. We chose 16 patients based on Hamilton's anxiety rate and a psychiatrist diagnosis. Patients were divided into two groups randomly. Each group took different treatments. Before treatment started, patients underwent MRS imaging and 8 weeks after treatment as well. Our study lacked a control group, and the results were analyzed by comparing the measured values of metabolites and clinical scores before and after treatment. RESULTS: The NAA and Cho concentration increased after treatments and Cr concentration remained constant in both groups. Both groups showed improvements in their symptoms of anxiety and also in their clinical score rates. Sertraline group showed a more increase in NAA concentration than CBT and also a more decrease in HAMA and HAMD-17 scores. CONCLUSION: A simultaneously increase in NAA and Cho in both groups and a decrease in clinical anxiety levels demonstrate that NAA and Cho concentration are associated negatively with anxiety levels. In addition, both CBT and sertraline are effective in the improvement of anxiety symptoms.

Brain Cortical Activation during Imagining of the Wrist Movement Using Functional Near-Infrared Spectroscopy (fNIRS).

BACKGROUND: fNIRS is a useful tool designed to record the changes in the density of blood's oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) molecules during brain activity. This method has made it possible to evaluate the hemodynamic changes of the brain during neuronal activity in a completely non-aggressive manner. OBJECTIVE: The present study has been designed to investigate and evaluate the brain cortex activities during imagining of the execution of wrist motor tasks by comparing fMRI and fNIRS imaging methods. MATERIAL AND METHODS: This novel observational Optical Imaging study aims to investigate the brain motor cortex activity during imagining of the right wrist motor tasks in vertical and horizontal directions. To perform the study, ten healthy young right-handed volunteers were asked to think about right-hand movements in different directions according to the designed movement patterns. The required data were collected in two wavelengths, including 845 and 763 nanometers using a 48 channeled fNIRS machine. RESULTS: Analysis of the obtained data showed the brain activity patterns during imagining of the execution of a movement are formed in various points of the motor cortex in terms of location. Moreover, depending on the direction of the movement, activity plans have distinguishable patterns. The results showed contralateral M1 was mainly activated during imagining of the motor cortex (p<0.05). CONCLUSION: The results of our study showed that in brain imaging, it is possible to distinguish between patterns of activities during wrist motion in different directions using the recorded signals obtained through near-infrared Spectroscopy. The findings of this study can be useful in further studies related to movement control and BCI.

Assessment of Motor Cortex in Active, Passive and Imagery Wrist Movement Using Functional MRI.

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.

Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery.

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.

Size reproducibility of gadolinium oxide based nanomagnetic particles for cellular magnetic resonance imaging: effects of functionalization, chemisorption and reaction conditions.

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.

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging.

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd2O3-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner.As a result, the nanoparticle sizes of Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal (r1) and transverse relaxivity (r2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r2/r1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively.The achievement of new synthesis route of Gd2O3-DEG resulted in lower r2/r1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r2/r1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r2/r1 ratio of previous PEGylation (r2/r1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.

Properties evaluation of a new MRI contrast agent based on Gd-loaded nanoparticles.

Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The aim of this research was to characterize a novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and gadolinium (III) oxide (Gd2O3) nanoparticles. The size and morphological structure of this nanoparticle are determined by particle size analysis device (zeta sizer) and transmission electronic microscope. We determined composition of Gd2O3 nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic resonance signal by T1-weighted MRI. Cytotoxicity of Gd2O3 nanoparticles in SK-MEL-3 cancer cells was evaluated. Zeta sizer showed Gd2O3 nanoparticles to be 75 nm in size. EDXA indicated the two main chemical components of gadolinium-nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a significantly higher incremental relaxivity for Gd2O3 nanoparticles compared to Magnevist (conventional contrast agent). In such concentrations, the slope of R1 relaxivity (1/T1) vs. concentration curve of Magnevist and Gd2O3 were 4.33, 7.98 s⁻¹ mM⁻¹. The slope of R2 relaxivity (1/T2) vs. concentration curve of Magnevist and Gd2O3 were 5.06, 13.75 s⁻¹ mM⁻¹. No appreciable toxicity was observed with Gd2O3 nanoparticles. Gadolinium-nanocomposite polymer emulsion is well characterized and has potential as a useful contrast agent for magnetic resonance molecular imaging.

Spatial frequency modulates visual cortical response to temporal frequency variation of visual stimuli: an fMRI study.

The brain response to temporal frequency (TF) variation has already been reported, but with no study for different TF with respect to various spatial frequencies (SF). Functional magnetic resonance imaging (fMRI) was performed with a 1.5 Tesla General Electric system in 14 volunteers during square-wave reversal checkerboard visual stimulation with different temporal frequencies of 4, 6, 8 and 10 Hz in two states of low SF of 0.4 and high SF of 8 cpd (cycles/degree). The activation map was created using the data obtained from the block-designed fMRI study. Voxels whose Z value was above a threshold of 3.0, at a significance level P = 0.05, were considered activated. The results demonstrated that the percentage BOLD signal change in response to different TFs was the maximum value at 6 Hz for a high SF of 8 cpd, whereas it was the maximum at TF of 8 Hz for a low SF of 0.4 cpd. The results of this study agree with the results of animal invasive neurophysiological studies showing spatial and temporal frequency selectivity of neurons in visual cortical areas. These results can be useful for vision therapy (such as the treatment of amblyopia) and selecting a visual task in fMRI studies.