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Background: Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with structural brain damage and cognitive impairment. The hypothalamus plays a crucial role in regulating sleep and wakefulness. We aimed to evaluate hypothalamic subunit volumes in patients with OSA., Methods: We enrolled 30 participants (15 patients with OSA and 15 healthy controls (HC)). Patients with OSA underwent complete overnight polysomnography (PSG) examination. All the participants underwent MRI. The hypothalamic subunit volumes were calculated using a segmentation technique that trained a 3D convolutional neural network., Results: Although hypothalamus subunit volumes were comparable between the HC and OSA groups (lowest p = .395), significant negative correlations were found in OSA patients between BMI and whole left hypothalamus volume (R = -0.654, p = .008), as well as between BMI and left posterior volume (R = -0.556, p = .032). Furthermore, significant positive correlations were found between ESS and right anterior inferior volume (R = 0.548, p = .042), minimum SpO 2 and the whole left hypothalamus (R = 0.551, p = .033), left tubular inferior volumes (R = 0.596, p = .019), and between the percentage of REM stage and left anterior inferior volume (R = 0.584, p = .022)., Conclusions: While there were no notable differences in the hypothalamic subunit volumes between the OSA and HC groups, several important correlations were identified in the OSA group. These relationships suggest that factors related to sleep apnea severity could affect hypothalamic structure in patients., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Cue-induced craving is central to addictive disorders. Most cue-reactivity functional magnetic resonance imaging studies are analyzed statically and report averaged signals, disregarding the dynamic nature of craving and task fatigue. Accordingly, this study investigates temporal dynamics of the neural response to drug cues as a functional magnetic resonance imaging study among methamphetamine users., Methods: A total of 32 early abstinent methamphetamine users underwent functional magnetic resonance imaging while viewing visual methamphetamine cues. A craving > neutral contrast was obtained in regions of interest. To explore the changes over time, the pre-processed signal was divided into three intervals. Contrast estimates were calculated within each interval, and were compared using the analysis of variance followed by the post hoc t-tests. The results were compared with those from a static analysis across all blocks., Results: A priori expected activations in the prefrontal cortex, insula, and striatum not detected by static analysis were discovered by the dynamic analysis. Post hoc tests revealed distinct temporal activation patterns in several regions. Most patterns showed rapid activation (including both ventral/dorsal striata and most regions in the prefrontal, insular, and cingulate cortices), whereas some had delayed activation (the right anterior insula, left middle frontal gyrus, and left dorsal anterior cingulate cortex)., Conclusion: This study provided preliminary insights into the temporal dynamicity of cue-reactivity, and the potential of a conventional blocked-design task to consider it as a simple dynamic analysis. We highlight regional activations that were only uncovered by dynamic analysis and discuss the interesting and theoretically expected early versus late regional activation patterns. Rapidly activated regions are mostly those involved in the earlier stages of cue reactivity, while regions with later activation participate in cognitive functions relevant later, such as reappraisal, interoception, and executive control., (Copyright© 2024 Iranian Neuroscience Society.)

Background & Aim: The histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets., Materials & Methods: Seven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes., Results: Analyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression., Conclusion: New potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers., Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts., Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders., Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes., Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Objective: To determine the border of glial tumors by diffusion weighted imaging (DWI), apparent diffusion co-efficient (ADC), magnetic resonance spectroscopy (MRS) and perfusion brain MRI., Patients and Methods: Ten patients with brain gliomas were enrolled [mean age: 35.3 ± 13.2, range: 20-62]. Conventional MRI was performed for all patients. Besides, tumor mapping based on Choline (Cho)/Creatine (Cr) color map in MRS, perfusion and diffusion color maps, were gathered. Different tumoral and peritumoral regions [normal tissue, reactive edema, infiltrative edema, and tumor core] were defined. MRI criteria were evaluated in areas targeted for biopsy and histopathologic evaluation was determined., Results: Tumor cell positive samples [one necrosis, 26 infiltrative and nine tumor cores] composed 36 (75%) of the 48 samples. Seven (19.4%) of the positive samples were interpreted as not tumor on MRI. Five were identified as reactive edema and two as normal tissue] [kappa: .67, p -value < .001]. Mean of ADC, median of N-acetylaspartate (NAA) and NAA/Cho were statistically different between positive and negative samples ( p  = .02 and p  < .001, respectively). Mean ADC and median Cho/NAA were statistically different in missed tumor containing tissue presented as reactive edema compared to normal and correctly diagnosed reactive edema samples together ( p -values < .05)., Conclusions: Multimodal MRI could define infiltrated borders of brain gliomas.

Transcranial direct current stimulation (tDCS) is a promising intervention for reducing craving/consumption in individuals with substance use disorders. However, its exact mechanism of action has not yet been well explored. We aimed to examine the network-based effects of tDCS while people with methamphetamine use disorders (MUDs) were exposed to drug cues. In a randomized, double-blind sham-controlled trial with a crossover design, 15 participants with MUDs were recruited to receive 20 min of active/sham tDCS with an anode/cathode over F4/F3. MRI data, including structural and task-based functional MRI during a standard drug cue-reactivity task, were collected immediately before and after stimulation sessions. Craving scores were also recorded before and after MRI scans. Individualized head models were generated to determine brain regions with strong electric fields (EFs). Using atlas-based parcellation of head models, averaged EFs were extracted from the main nodes of three large-scale networks that showed abnormalities in MUDs; executive control (ECN), default mode (DMN), and ventral attention (VAN) networks. Main nodes with high EF intensity were used as seed regions for task-based functional connectivity (FC) [using generalized psychophysiological interaction (gPPI)] and activity [using a general linear model (GLM)] calculations. Subjective craving showed a significant reduction in immediate craving after active (-15.42 ± 5.42) compared to sham (-1 ± 2.63). In seed-to-whole brain results, the PFC node in ECN showed an enhanced PPI connectivity with precuneus and visual cortex; the cluster center in MNI (6, -84, -12); the PFC node in DMN showed a decreased PPI connectivity with contralateral parietal cortex;(-48, -60, 46). ROI-to-ROI results showed increased PPI connectivity within/between ECN-VAN while connectivity between ECN-DMN decreased. In line with connectivity, functional activity in the right PFC node in DMN decreased after tDCS while activity in PFC nodes of ECN/VAN increased. EF calculations in PFC nodes revealed that EF in DMN was outward, while the direction of EFs was inward in ECN/VAN. This study provides new insight into neural circuitry underlying MUDs that can be modulated by tDCS at the network level and specifically suggests that bilateral tDCS increases cortical excitability in ECN and VAN, while it has opposite effects on DMN that may be related to the direction of EFs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Soleimani, Towhidkhah, Oghabian and Ekhtiari.)

Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor-infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs-DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs-DEX to an anti-CD3 monoclonal antibody via cyanogen bromide as a cross-linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs-DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T 2 *-weighted and T 2 -weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non-invasive assessment of TILs to identify patients eligible for immunotherapy., (© 2022 Wiley-VCH GmbH.)

Background: Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant., Methods: 62 individuals with MUD were scanned when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition and their interactions were estimated, and methamphetamine cue-reactivity was compared between individuals with MUD and 23 healthy controls. Relationships between behavioral characteristics and observed activations were investigated., Results: Individuals with MUD had longer reaction times and more errors in drug and negative-emotional compared to blank blocks, and more omission errors in drug compared to neutral blocks. They showed higher drug cue-reactivity than controls across prefrontal, fusiform, and visual regions (Z > 3.1, p-corrected<0.05). Response-inhibition was associated with precuneal, inferior parietal, anterior cingulate, temporal, and inferior frontal activations (Z > 3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z > 3.1, p-corrected<0.05)., Conclusion: Drug cue-reactivity may impair response inhibition partly through activating dis-inhibitory regions, while temporal and parietal activations associated with response-inhibition in negative blocks suggest compensatory activity. Results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understanding of methamphetamine use disorder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these phenomena develop and interact across time, the temporal dynamics of their underlying neural activity remain under-investigated. To explore these dynamics, an analysis of time-varying activation was applied to fMRI data from 62 men with methamphetamine use disorder in their first weeks of recovery in an abstinence-based treatment program. Using a mixed block-event, factorial cue-reactivity/Go-NoGo task and a sliding window across the task duration, dynamically-activated regions were identified in three linear mixed effects models (LMEs). Habituation to drug cues across time was observed in the superior temporal gyri, amygdalae, left hippocampus, and right precuneus, while response inhibition was associated with the sensitization of temporally-dynamic activations across many regions of the inhibitory frontoparietal network. Methamphetamine-related response inhibition was associated with temporally-dynamic activity in the parahippocampal gyri and right precuneus (corrected p-value < 0.001), which show a declining cue-reactivity contrast and an increasing response inhibition contrast. Overall, the declining craving-related activations (habituation) and increasing inhibition-associated activations (sensitization) during the task duration suggest the gradual recruitment of response inhibitory processes and a concurrent habituation to drug cues in areas with temporally-dynamic methamphetamine-related response inhibition. Furthermore, temporally dynamic cue-reactivity and response inhibition were correlated with behavioral and clinical measures such as the severity of methamphetamine use and craving, impulsivity and inhibitory task performance. This exploratory study demonstrates the time-variance of the neural activations undergirding cue-reactivity, response inhibition, and response inhibition during exposure to drug cues, and suggests a method to assess this dynamic interplay. Analyses that can capture temporal fluctuations in the neural substrates of drug cue-reactivity and response inhibition may prove useful for biomarker development by revealing the rate and pattern of sensitization and habituation processes, and may inform mixed cue-exposure intervention paradigms which could promote habituation to drug cues and sensitization in inhibitory control regions., (© 2022. The Author(s).)

Background: Nicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention., Methods: Eleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with dependence on cocaine (n = 147), methamphetamine (n = 132) and nicotine (n = 189), as well as non-dependent controls (n = 333). We compared the fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) of 20 bilateral tracts. Also, we compared the performance of various machine learning algorithms in deriving brain-based classifications on stimulant dependence., Results: The cocaine and methamphetamine groups had lower regional FA and higher RD in several association, commissural, and projection white matter tracts. The methamphetamine dependent group additionally showed lower regional AD. The nicotine group had lower FA and higher RD limited to the anterior limb of the internal capsule. The best performing machine learning algorithm was the support vector machine (SVM). The SVM successfully classified individuals with dependence on cocaine (AUC = 0.70, p < 0.001) and methamphetamine (AUC = 0.71, p < 0.001) relative to non-dependent controls. Classifications related to nicotine dependence proved modest (AUC = 0.62, p = 0.014)., Conclusions: Stimulant dependence was related to FA disturbances within tracts consistent with a role in addiction. The multivariate pattern of white matter differences proved sufficient to identify individuals with stimulant dependence, particularly for cocaine and methamphetamine., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Introduction: blood-brain-barrier perfusion characterization impaired in MS as some studies have shown recently but a comparison between perfusion parameters in contrast-enhanced and non-enhanced lesions not have been well documented. Pharmacokinetic quantitative parameters have obtained from dynamic contrast-enhanced in magnetic resonance imaging is a useful way to quantify blood-brain barrier permeability leakage., Methods: MR examination was performed on 28 patients with Relapsing-remitted Multiple Sclerosis (RRMS) with (Mean±SD age: 34.7±9.28) which had multiple lesions in the brain.3D dynamic T1-weighted spoiled gradient echo was obtained and Perfusion parameters and its map assessed in enhanced and non-enhanced lesions after intravascular injection differences in parameters and map obtained by analyzing ROI in Extended Toft model., Results: permeability as measured Krtans was a significantly higher value in CE to compare NE lesions. Ktrans and Kep have significant differences in NAWM and CE and NE lesions. Vb was slightly different in NE and CE lesions., Conclusion: Permeability measured as Ktrans was the good parameter to show permeability impairment of BBB in CE lesions. Dysregulation in BBB is an acceptable sign to indicate existence inflammation in CE lesions., Highlights: Multiple Sclerosis,Inflammation,Blood-brain-barrier dysregulation., Plain Language Summary: Inflammation activity in MS patients has an important role to cause BBB dysfunction.in this article to achieve results to confirm the inflammation importance in MS patients with acute lesions. MRI modality have been used and with comparison between acute and chronic lesions and NAWM of MS patient's presence of inflammation have been proved., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2022 Iranian Neuroscience Society.)

The conjugation of monoclonal antibodies with superparamagnetic iron oxide nanoparticles (SPIONs) has appeared as a potential multifunctional clinical tool, which can effectively diagnose cancers and monitor their treatment, specifically. Despite the presence of different methods for conjugating antibodies to iron oxide nanoparticles, novel cost-effective and simpler conjugation techniques should be performed in this regard. In current study, an anti-CD3 monoclonal antibody was conjugated to the Fe3O4 coated by carboxymethyl dextran (CMD) using cyanogen bromide (CNBr). Moreover, EDC/NHS techniques were applied as a positive control. The experimental results showed that the Conjugation was performed and the presence of the antibody conjugated to the MNPs in human xenograft tumors was confirmed using Prussian blue (PB) staining, following magnetic resonance imaging (MRI), 30 min after injection. This conjugation method was shown to be able to separate CD3+ T lymphocytes efficiently from whole blood with high purity. Accordingly, this type of bio-conjugation method can be utilized in the future for cell sorting, and can be applied for adopted cell therapies such as CAR-T cell (Chimeric antigen receptor T cell) therapy, as well as targeted MRI imaging., (Copyright © 2021. Published by Elsevier B.V.)

Diffusion Tensor Imaging (DTI) enabled the investigation of brain White Matter (WM), both qualitatively to study the macrostructure, and quantitatively to study the microstructure. The quantitative analyses are mostly performed at the whole-tract level, i.e., providing one measure of interest per tract; however, along-tract approaches may provide finer details of the quality of the WM tracts. In this study, using the DWI data collected from 40 young and 40 old individuals, we compared the DTI measures of FA, MD, AD, and RD, estimated by both whole-tract and along-tract approaches in 18 WM bundles, between the two groups. The results of the whole-tract quantitative analysis showed a statistically significant (p-FWER < 0.05) difference between the old and young groups in 6 tracts for FA, 8 tracts for MD, 1 tract for AD, and 7 tracts for RD. On the contrary, the along-tract approach showed differences between the two groups in 10 tracts for FA, 14 tracts for MD, 8 tracts for AD, and 11 tracts for RD. All the differences between the along-tract measures of the two groups had a large effect size (Cohen'd > 0.80). This study showed that the along-tract approach for the analysis of brain WM reveals changes in some WM tracts which had not shown any changes in the whole-tract approach, and therefore this finding emphasizes the utilization of the along-tract approach along with the whole-tract method for a more accurate study of the brain WM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: The Iranian Brain Imaging Database (IBID) was initiated in 2017, with 5 major goals: provide researchers easy access to a neuroimaging database, provide normative quantitative measures of the brain for clinical research purposes, study the aging profile of the brain, examine the association of brain structure and function, and join the ENIGMA consortium. Many prestigious databases with similar goals are available. However, they were not done on an Iranian population, and the battery of their tests (e.g. cognitive tests) is selected based on their specific questions and needs., Methods: The IBID will include 300 participants (50% female) in the age range of 20 to 70 years old, with an equal number of participants (#60) in each age decade. It comprises a battery of cognitive, lifestyle, medical, and mental health tests, in addition to several Magnetic Resonance Imaging (MRI) protocols. Each participant completes the assessments on two referral days., Results: The study currently has a cross-sectional design, but longitudinal assessments are considered for the future phases of the study. Here, details of the methodology and the initial results of assessing the first 152 participants of the study are provided., Conclusion: IBID is established to enable research into human brain function, to aid clinicians in disease diagnosis research, and also to unite the Iranian researchers with interests in the brain., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2021 Iranian Neuroscience Society.)

Introduction: Functional Magnetic Resonance Imaging (fMRI) methods have been used to study sensorimotor processing in the spinal cord. However, these techniques confront unwanted noises to the measured signal from the physiological fluctuations. In the spinal cord imaging, most of the challenges are consequences of cardiac and respiratory movement artifacts that are considered as significant sources of noise, especially in the thoracolumbar region. In this study, we investigated the effect of each source of physiological noise and their contribution to the outcome of the analysis of the blood-oxygen-level-dependent signal in the human thoracolumbar spinal cord., Methods: Fifteen young healthy male volunteers participated in the study, and pain stimuli were delivered on the L5 dermatome between the two malleoli. Respiratory and cardiac signals were recorded during the imaging session, and the generated respiration and cardiac regressors were included in the general linear model for quantification of the effect of each of them on the task-analysis results. The sum of active voxels of the clusters was calculated in the spinal cord in three correction states (respiration correction only, cardiac correction only, and respiration and cardiac noise corrections) and analyzed with analysis of variance statistical test and receiver operating characteristic curve., Results: The results illustrated that cardiac noise correction had an effective role in increasing the active voxels (Mean±SD = 23.46±9.46) compared to other noise correction methods. Cardiac effects were higher than other physiological noise sources., Conclusion: In summary, our results indicate great respiration effects on the lumbar and thoracolumbar spinal cord fMRI, and its contribution to the heartbeat effect can be a significant variable in the individual fMRI data analysis. Displacement of the spinal cord and the effects of this noise in the thoracolumbar and lumbar spinal cord fMRI results are significant and cannot be ignored., Competing Interests: Conflict of interest All authors confirm that they have no conflicts of interest., (Copyright© 2020 Iranian Neuroscience Society.)

Study Design: Method development., Objectives: To develop a reliable protocol for automatic segmentation of Thoracolumbar spinal cord using MRI based on K-means clustering algorithm in 3D images., Setting: University-based laboratory, Tehran, Iran., Methods: T2 structural volumes acquired from the spinal cord of 20 uninjured volunteers on a 3T MR scanner. We proposed an automatic method for spinal cord segmentation based on the K-means clustering algorithm in 3D images and compare our results with two available segmentation methods (PropSeg, DeepSeg) implemented in the Spinal Cord Toolbox. Dice and Hausdorff were used to compare the results of our method (K-Seg) with the manual segmentation, PropSeg, and DeepSeg., Results: The accuracy of our automatic segmentation method for T2-weighted images was significantly better or similar to the SCT methods, in terms of 3D DC (p < 0.001). The 3D DCs were respectively (0.81 ± 0.04) and Hausdorff Distance (12.3 ± 2.48) by the K-Seg method in contrary to other SCT methods for T2-weighted images., Conclusions: The output with similar protocols showed that K-Seg results match the manual segmentation better than the other methods especially on the thoracolumbar levels in the spinal cord due to the low image contrast as a result of poor SNR in these areas.

Objectives: Memory is an important brain function, and is impaired with brain lesions. Resection of the lesion is one solution for that, but presurgical planning (PSP) is needed to guide the surgery for maximum removal of the lesion, as well as maximum preservation of the function. Functional Magnetic Resonance Imaging (fMRI) is one of the best approaches for such a purpose, but performing an fMRI study needs careful consideration of the factors which influence its results. Studies have shown that mental fatigue does have the potential to alter brain functions, and therefore this study aims to identify if mental fatigue should also be considered as a confounding factor when performing an fMRI study, particularly for clinical purposes., Patients and Methods: Using 57 healthy young volunteers, face and word encoding tasks were performed, with half of the participants performing the memory tasks after a set of language tasks and half of them before that., Results: The results showed that mental fatigue led to increased activity in the bilateral thalamus and caudate in the face encoding task, and in the right thalamus, posterior cingulate and medial temporal lobe in word encoding. In addition, activation was declined with mental fatigue in the left lingual, precuneus, and posterior cingulate gyri in face encoding., Conclusion: This study has shown the importance of the number and sequence of cognitive/mental tasks when performing an fMRI study, which could help to obtain more reliable fMRI maps in clinical applications. This finding is also important for performing research/cognitive studies using fMRI., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Cancer detection in early stage using a powerful and noninvasive tool is of high global interest. In this experiment, a small-molecular-weight glucose based derivative of Gd 3+ -1-(4-isothiocyanatobenzyl) diethylene tri amine penta acetic acid (Gd 3+ -p-SCN-Bn-DTPA-DG) as a novel potential MR imaging contrast agents was synthesized. Gd 3+ -p-SCN-Bn-DTPA-DG was synthesized with reacting of Glucosamine and 1-(4-isothiocyanatobenzyl) diethylene triamine penta acetic acid then loaded by gadolinium to make novel agent of functional MR imaging. The relaxivity, T 1 , T 2 relaxation times, and cell toxicity of this contrast agent were studied. The results demonstrated that the sugar moieties linked to Gd 3+ -p-SCN-Bn-DTPA efficiently increase its cellular uptake in normal cells 25% and in cancereous cells upto 67%. The Gd 3+ -p-SCN-Bn-DTPA-DG significantly ( p < 0.05) decreased MCF-7 tumor cell numbers without any significant toxicity on normal human kidney cells. Finally, it displayed an intense signal on T 1 weighted with respect to the unlabeled cells. Based on the findings from the present research Gd 3+ -p-SCN-Bn-DTPA-DG be a potential breast molecular imaging. However, further investigations by anticancer studies are in the pipeline.

Objectives: The goal of this study is to examine the effect of contrast agent (CA) dose and diffusion coefficient on the estimation of vessel size index (VSI)., Materials and Methods: Three groups of four participants were enrolled in this study and two different experiments were performed. Different dose of CA, namely 0.1 mmol/kg and 0.05 mmol/kg were assessed in two groups of normal subjects. Diffusion coefficient effect was assessed in the third group with high-grade glioma. Imaging included gradient echo and spin-echo DSC and DTI on a 3-T MR Scanner., Results: VSI estimation using half of standard dose of CA showed higher values compared to the application of standard, with a ratio of 2 for the WM and 1.5 for the GM. VSI estimates for tumor tissues (22 µm) were considerably higher compared to contra-lateral Normal-Appearing WM (NAWM, 4 µm, P < 0.01) and Normal-Appearing GM (NAGM, 8 µm, P < 0.04)., Discussion: Application of standard dose for CA injection and also taking into account the effect of diffusion coefficient can lead to a better correlation of VSI with previous theoretically predicted values and improvement of individual diagnostics in tumor evaluations.

Objective: The present study aimed to compare the qualitative (time intensity curve analysis), the semi-quantitative and the quantitative multiphase 3T dynamic contrast-enhanced (DCE) MRI parameters as predictors of malignancy in adnexal masses. Materials and Methods: In this prospective study, women with an adnexal mass who were scheduled for surgical resection or were followed for more than one year period to confirm the benignity of their lesions, underwent multiphase 3T DCE-MRI. The qualitative (time intensity curve), semi-quantitative (SImax, SIrel, WIR) and quantitative (Ktrans, Kep, Vb) analyses were performed on DCE-MRI sequences and their predictive values were compared. Results: A total of 17 benign and 14 malignant lesions were included. According to the qualitative analysis, none of the lesions with Type I time intensity curves (TIC) were malignant and none of the masses with Type III TICs were benign. The accuracy of the quantitative parameters in detection of malignancy was found to be higher than that of semi-quantitative variables, particularly when calculated for a small ROI within the high signal area of the mass (sROI) rather than the largest ROI including the whole mass (lROI), and when inter-MRI variations were omitted using ratios. The Kep(tumor)/Kep(myometrium) ratio measured from sROI was the best parameter for differentiating a malignant lesion with a sensitivity of 100% and a specificity of 92.3%. Conclusion: We concluded that a Type I TIC confirms a benign lesion, and a type III TIC confirms the malignancy and further evaluation is not recommended for these lesions. So complementary quantitative analysis is only recommended for adnexal masses with type II TICs.

Antiepileptic drugs (AEDs) have repeatedly shown inconsistent and almost contradictory effects on the neurocognitive system, from substantial impairments in processing speed to the noticeable improvement in working memory and executive functioning. Previous studies have provided a novel insight into the cognitive improvement by bumetanide as a potential antiepileptic drug. Through the current investigation, we evaluated the longitudinal effects of bumetanide, an NKCC1 co-transporter antagonist, on the brain microstructural organization as a probable underlying component for cognitive performance. Microstructure assessment was completed using SPM for the whole brain assay and Freesurfer/TRACULA for the automatic probabilistic tractography analysis. Primary cognitive operations including selective attention and processing speed, working memory capacity and spatial memory were evaluated in 12 patients with a confirmed diagnosis of refractory epilepsy. Participants treated with bumetanide (2 mg/ day) in two divided doses as an adjuvant therapy to their regular AEDs for 6 months, which followed by the re-assessment of their cognitive functions and microstructural organizations. Seizure frequency reduced in eight patients which accompanied by white matter reconstruction; fractional anisotropy (FA) increased in the cingulum-cingulate gyrus (CCG), anterior thalamic radiation (ATR), and temporal part of the superior longitudinal fasciculus (SLFt) in correlation with the clinical response. The voxel-based analysis in responder patients revealed increased FA in the left hippocampus, right cerebellum, and right medial temporal lobe, while mean diffusivity (MD) values reduced in the right occipital lobe and cerebellum. Microstructural changes in SLFt and ATR accompanied by a reduction in the error rate in the spatial memory test. These primary results have provided preliminary evidence for the effect of bumetanide on cognitive functioning through microstructural changes in patients with drug-resistant epilepsy.

Dysregulations in the expression level of Na-K-Cl cotransporter (NKCC1) and K-Cl cotransporter (KCC2) genes have been detected in the brain tissues of patients with refractory epilepsy. Given the importance of these proteins in the determination of Cl equilibrium potential (ECl), evaluation of the expression changes of these transporters might assist in optimizing the diagnostic approaches and therapeutic strategies. The present investigation evaluates the expression level chloride transporters in polymorphonuclear cells and their correlation with microstructural abnormalities. Thirty cases of drug-resistant epilepsy (confirmed with temporal lobe epilepsy diagnosis) fulfilled the considered inclusion criteria. Cases were divided into two groups, one with a detectable MRI lesion (19 participants; right side) and another with no MRI findings (11 participants). Whole-brain voxel-based analysis was performed on diffusion tensor imaging to measure fractional anisotropy and mean diffusivity; neurite orientation dispersion and density imaging was performed to map neurite density index and orientation dispersion index. Our results indicated that fractional anisotropy and mean diffusivity changed in temporal and extratemporal parts of the brain, whereas the changes in neurite density index and orientation dispersion index were exclusively obvious in the temporal lobe. Molecular studies revealed significantly lower levels of KCC2 expression in patients with epilepsy, a finding that remarkably correlated with microstructural changes as well. Our research showed that downregulation of KCC2 and microstructural abnormalities might contribute to the observed refractoriness in temporal lobe epilepsy.

Purpose: To propose a computer-assisted method for distinguishing uterine sarcoma from leiomyomas based on perfusion weighted magnetic resonance imaging (PWI)., Materials and Methods: Forty-two women confirmed to have a total of 60 masses (10 uterine sarcomas and 50 benign leiomyomas) were included. The reference diagnosis was based on postoperative histopathological examination. All women underwent the standard MRI protocol with 3-Tesla MR imager (Magnetom Trio, Siemens, Erlangen, Germany) for assessment of myometrial masses, followed by PWI. For each mass, two regions of interest (ROI) were outlined manually by an experienced radiologist; one (ROI L ) represented the entire tumor while the other (ROIs) was placed on the area of the lesion with the most marked contrast enhancement. Two additional ROI s with diameters similar to ROI s (3.0 to 3.1 mm) were placed on psoas muscle (ROI P ) and myometrium (ROI M ) in order to provide baselines for comparisons. The obtained ROIs of PWI images were then analyzed using the DCE Tool plug-in (version 2.0SP1) within ClearCanvas (Toronto, Ontario, Canada) framework. The DCE Tool provides seven parameters (K trans , k ep , V b , IAUC, initial slope, peak, the mean squared error) for modelling contrast uptake within an ROI using the modified Tofts model. Parameters extracted from the ROIs were fed into a decision tree ensemble, which classified the corresponding lesions either as malignant or benign. The leave-one-out cross validation (LOOCV) was utilized to evaluate the performance of the classifier., Results: None of the parameters extracted from ROI L or ROI s differed significantly between uterine sarcoma and benign leiomyomas (all p > 0.05). The overall accuracy of 66.7% was obtained by feeding seven parameters extracted from ROI L to the classifier. When 21 features extracted from ROI L , ROI M , and ROI P were fed into the classifier an accuracy of 91.7%, sensitivity of 100%, and specificity of 90% were achieved in the optimal operating point of classifier., Conclusion: Although none of the PWI parameters differed significantly between benign and malignant lesions, when the information provided by the extracted features was aggregated using a machine learning method, a promising discriminative power was obtained. This suggests that the proposed model for combining the PWI parameters is potentially useful for differentiating uterine sarcoma from leiomyomas., (Copyright © 2018. Published by Elsevier B.V.)

Background: Presurigical planning for glioma tumor resection and radiotherapy treatment require proper delineation of tumoral and peritumoral areas of brain. Diffusion tensor imaging (DTI) is the most common mathematical model applied for diffusion weighted MRI data. Neurite orientation dispersion and density imaging (NODDI) is another mathematical model for DWI data modeling., Objective: We studied whether extracted parameters of DTI, and NODDI models can be used to differentiate between edematous, tumoral, and normal areas in brain white matter (WM)., Material and Methods: 12 patients with peritumoral edema underwent 3T multi-shell diffusion imaging with b-values of 1000 and 2000 smm-2 in 30 and 64 gradient directions, respectively. We fitted DTI and NODDI to data in manually drawn regions of interest and used their derived parameters to characterize edematous, tumoral and normal brain areas., Results: We found that DTI parameters fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) all significantly differentiated edematous from contralateral normal brain WM (p<0.005). However, only FA was found to distinguish between edematous WM fibers and tumor invaded fibers (p = 0.001). Among NODDI parameters, the intracellular volume fraction (ficvf) had the best distinguishing power with (p = 0.001) compared with the isotropic volume fraction (fiso), the orientation dispersion index (odi), and the concentration parameter of Watson distribution (κ), while comparing fibers inside normal, tumoral, and edematous areas., Conclusion: The combination of two diffusion based methods, i.e. DTI and NODDI parameters can distinguish and characterize WM fibers involved in edematus, tumoral, and normal brain areas with reasonable confidence. Further studies will be required to improve the detectability of WM fibers inside the solid tumor if they hypothetically exist in tumoral parenchyma.

Purpose: NODDI (Neurite Orientation Dispersion and Density Imaging) and DTI (Diffusion tensor imaging) may be useful in identifying abnormal regions in patients with MRI-negative refractory epilepsy. The aim of this study was to determine whether NODDI and DTI maps including neurite density (ND), orientation dispersion index (ODI), mean diffusivity (MD) and fractional anisotropy (FA) can detect structural abnormalities in cortical and subcortical gray matter (GM) in these patients. The correlation between these parameters and clinical characteristics of the disease was also investigated., Methods: NODDI and DTI maps of 17 patients were obtained and checked visually. Region of interest (ROI) was drawn on suspected areas and contralateral regions in cortex. Contrast-to-noise ratio (CNR) was determined for each region. Furthermore volumetric data and mean values of ND, ODI, FA and MD of subcortical GM structures were calculated in both of the patients and controls. Finally, the correlations of these parameters in the subcortical with age of onset and duration of epilepsy were investigated., Results: Cortical abnormalities on ODI images were observed in eight patients qualitatively. CNR of ODI was significantly greater than FA and MD. The subcortical changes including decrease of FA and ND and increase of ODI in left nucleus accumbens and increase of the volume in right amygdala were detected in the patients., Conclusions: The results revealed that NODDI can improve detection of microstructural changes in cortical and subcortical GM in patients with MRI negative epilepsy., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool suited to alter cortical excitability and activity via the application of weak direct electrical currents. An increasing number of studies in the addiction literature suggests that tDCS modulates subjective self-reported craving through stimulation of dorsolateral prefrontal cortex (DLPFC). The major goal of this study was to explore effects of bilateral DLPFC stimulation on resting state networks (RSNs) in association with drug craving modulation. We targeted three large-scale RSNs; the default mode network (DMN), the executive control network (ECN), and the salience network (SN)., Methods: Fifteen males were recruited after signing written informed consent. We conducted a double-blinded sham-controlled crossover study. Twenty-minute "real" and "sham" tDCS (2 mA) were applied over the DLPFC on two separate days in random order. Each subject received both stimulation conditions with a 1-week washout period. The anode and cathode electrodes were located over the right and left DLPFC, respectively. Resting state fMRI was acquired before and after real and sham stimulation. Subjective craving was assessed before and after each fMRI scan. The RSNs were identified using seed-based analysis and were compared using a generalized linear model., Results: Subjective craving decreased significantly after real tDCS compared to sham stimulation ( p  = .03). Moreover, the analysis shows significant modulation of DMN, ECN, and SN after real tDCS compared to sham stimulation. Additionally, alteration of subjective craving score was correlated with modified activation of the three networks., Discussion: Given the observed alteration of the targeted functional brain networks in methamphetamine users, new potentials are highlighted for tDCS as a network intervention strategy and rsfMRI as a suitable monitoring method for these interventions.

Objectives: Language is an important human function, and is a determinant of the quality of life. In conditions such as brain lesions, disruption of the language function may occur, and lesion resection is a solution for that. Presurgical planning to determine the language-related brain areas would enhance the chances of language preservation after the operation; however, availability of a normative language template is essential., Patients and Methods: In this study, using data from 60 young individuals who were meticulously checked for mental and physical health, and using fMRI and robust imaging and data analysis methods, functional brain maps for the language production, perception and semantic were produced., Results: The obtained templates showed that the language function should be considered as the product of the collaboration of a network of brain regions, instead of considering only few brain areas to be involved in that., Conclusion: This study has important clinical applications, and extends our knowledge on the neuroanatomy of the language function., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Brain tumor is one of the most common tumors. A successful treatment might be achieved with an early identification. Pathological investigation as the gold standard method for tumor identification has some limitations. Noninvasive assessment of tumor specifications may be possible using perfusion-weighted magnetic resonance imaging (MRI). Cerebral blood volume (CBV) and cerebral blood flow (CBF) could be calculated based on dynamic contrast-enhanced MRI (DCE-MRI) in addition to dynamic susceptibility contrast MRI (DSC-MRI) modality. Each category of the cerebral hemodynamic and permeability indices revealed the specific tumor characteristics and their collection could help for better identification of the tumor. Some mathematical methods were developed to determine both cerebral hemodynamic and permeability indices based on a single-dose DCE perfusion MRI. There are only a few studies available on the comparison of DSC- and DCE-derived cerebral hemodynamic indices such as CBF and CBV., Aim: The objective of the study was to validate first-pass perfusion parameters derived from T1-based DCE method in comparison to the routine T2*-based DSC protocol., Materials and Methods: Twenty-nine patients with brain tumor underwent DCE- and DSC-MRIs to evaluate the agreement between DSC- and DCE-derived cerebral hemodynamic parameters. Agreement between DSC- and DCE-derived cerebral hemodynamic indices was determined using the statistical method described by Bland and Altman. The reliability between DSC- and DCE-derived cerebral hemodynamic indices was measured using the intraclass correlation analysis., Results: The achieved magnitudes for DCE-derived CBV (gray matter [GM]: 5.01 ± 1.40 mL/100 g vs. white matter [WM]: 1.84 ± 0.74 mL/100 g) and DCE-derived CBF (GM: 60.53 ± 12.70 mL/100 g/min vs. WM: 32.00 ± 6.00 mL/100 g/min) were in good agreement with other studies. The intraclass correlation coefficients showed that the cerebral hemodynamic indices could accurately be estimated based on the DCE-MRI using a single-compartment model (>0.87), and DCE-derived cerebral hemodynamic indices are significantly similar to the magnitudes achieved based on the DSC-MRI ( P < 0.001). Furthermore, an acceptable agreement was observed between DSC- and DCE-derived cerebral hemodynamic indices., Conclusion: Based on the measurement of the cerebral hemodynamic and blood-brain barrier permeability using DCE-MRI, a more comprehensive collection of the physiological parameters cloud be achieved for tumor evaluations., Competing Interests: There are no conflicts of interest.

Introduction: Graph theoretical analysis of functional Magnetic Resonance Imaging (fMRI) data has provided new measures of mapping human brain in vivo. Of all methods to measure the functional connectivity between regions, Linear Correlation (LC) calculation of activity time series of the brain regions as a linear measure is considered the most ubiquitous one. The strength of the dependence obligatory for graph construction and analysis is consistently underestimated by LC, because not all the bivariate distributions, but only the marginals are Gaussian. In a number of studies, Mutual Information (MI) has been employed, as a similarity measure between each two time series of the brain regions, a pure nonlinear measure. Owing to the complex fractal organization of the brain indicating self-similarity, more information on the brain can be revealed by fMRI Fractal Dimension (FD) analysis., Methods: In the present paper, Box-Counting Fractal Dimension (BCFD) is introduced for graph theoretical analysis of fMRI data in 17 methamphetamine drug users and 18 normal controls. Then, BCFD performance was evaluated compared to those of LC and MI methods. Moreover, the global topological graph properties of the brain networks inclusive of global efficiency, clustering coefficient and characteristic path length in addict subjects were investigated too., Results: Compared to normal subjects by using statistical tests (P<0.05), topological graph properties were postulated to be disrupted significantly during the resting-state fMRI., Conclusion: Based on the results, analyzing the graph topological properties (representing the brain networks) based on BCFD is a more reliable method than LC and MI., Competing Interests: Conflict of Interest All authors certify that this manuscript has neither been published in whole nor in part nor being considered for publication elsewhere. The authors have no conflicts of interest to declare.

Introduction: Various treatment methods for drug abusers will result in different success rates. This is partly due to different neural assumptions and partly due to various rate of relapse in abusers because of different circumstances. Investigating the brain activation networks of treated subjects can reveal the hidden mechanisms of the therapeutic methods., Methods: We studied three groups of subjects: heroin abusers treated with abstinent based therapy (ABT) method, heroin abusers treated with Methadone Maintenance Therapy (MMT) method, and a control group. They were all scanned with functional magnetic resonance imaging (fMRI), using a 6-block task, where each block consisted of the rest-craving-rest-neutral sequence. Using the dynamic causal modeling (DCM) algorithm, brain effective connectivity network (caused by the drug craving stimulation) was quantified for all groups. In this regard, 4 brain areas were selected for this analysis based on previous findings: ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum., Results: Our results indicated that the control subjects did not show significant brain activations after craving stimulations, but the two other groups showed significant brain activations in all 4 regions. In addition, VMPFC showed higher activations in the ABT group compared to the MMT group. The effective connectivity network suggested that the control subjects did not have any direct input from drug-related cue indices, while the other two groups showed reactions to these cues. Also, VMPFC displayed an important role in ABT group. In encountering the craving pictures, MMT subjects manifest a very simple mechanism compared to other groups., Conclusion: This study revealed an activation network similar to the emotional and inhibitory control networks observed in drug abusers in previous works. The results of DCM analysis also support the regulatory role of frontal regions on bottom regions. Furthermore, this study demonstrates the different effective connectivity patterns after drug abuse treatment and in this way helps the experts in the field., Competing Interests: Conflict of Interest The authors declared no conflicts of interest.

Recent advances have shown that inorganic nanoparticles (NPs) based on heavy elements are highly appropriate for X-ray computed tomography (CT). In this contribution, tungsten trioxide NPs are prepared by the electrical arc discharge (EAD) method in DI water. The effect of chitosan (CTS) and glutaraldehyde (GTA) as coating and cross-linking agent, respectively, on the hydrodynamic size and zeta potential of prepared tungsten trioxide NPs is investigated. It is found that zeta potential increases by increasing the amounts of CTS. Meanwhile, by increasing the volume of glutaraldehyde (GTA), the final particle size increases whereas the zeta potential deceases. Chitosan coated tungsten trioxide demonstrated no significant cytotoxicity at concentration up to 5mg/mL after 24h. Finally, the X-ray attenuation of prepared chitosan coated tungsten trioxide NPs are higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Graphene/cobalt nanocomposites are promising materials for theranostic nanomedicine applications, which are defined as the ability to diagnose, provide targeted therapy and monitor the response to the therapy. In this study, the composites were synthesized via chemical method, using graphene oxide as the source material and assembling cobalt nanoparticles of 15nm over the surface of graphene sheets. Various characterization techniques were then employed to reveal the morphology, size and structure of the nanocomposites, such as X-ray diffraction analysis, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, high resolution transmission electron microscopy and ultraviolet visible spectroscopy. Using ion-coupled plasma optical emission spectroscopy, cobalt concentration in the nanocomposites was found to be 80%. In addition, cytotoxicity of graphene/cobalt nanocomposites were evaluated using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide or MTT assay. MTT viability assay exhibited biocompatibility to L929 mouse fibroblasts cells, under a high dose of 100μg/mL over 24h. Hyperthermia results showed the superior conversion of electromagnetic energy into heat at 350kHz frequency for 0.01 and 0.005g/L of the nanocomposites solution. The measured heat generation and energy transfer results were anticipated by the finite element analysis, conducted for the 3D structure. Magnetic resonance imaging characteristics also showed that negatively charge graphene/cobalt nanocomposites are suitable for T1-weighted imaging., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Brain lesions cause functional deficits, and one treatment for this condition is lesion resection. In most cases, presurgical planning (PSP) and the information from laterality indices are necessary for maximum preservation of the critical functions after surgery. Language laterality index (LI) is reliably estimated using functional magnetic resonance imaging (fMRI); however, this measure is under the influence of some external factors. In this study, we investigated the influence of a number of factors on language LI, using data from 120 patients (mean age=35.65 (±13.4) years) who underwent fMRI for PSP. Using two proposed language tasks from our previous works, brain left hemisphere was showed to be dominant for the language function, although a higher LI was obtained using the "Word Generation" task, compared to the "Reverse Word Reading". In addition, decline of LIs with age, and lower LI when the lesion invaded brain language area were observed. Meanwhile, gender, lesion side (affected hemisphere), LI calculation strategy, and fMRI analysis Z-values did not statistically show any influences on the LIs. Although fMRI is widely used to estimate language LI, it is shown here that in order to present a reliable language LI and to correctly select the dominant hemisphere of the brain, the influence of external factors should be carefully considered., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objective: Drug Craving could be defined as a subjective motivational state associated with a strong desire to consume drugs. Craving is a subjective phenomenon; therefore, self-report (subjective) craving measures are usually referenced. Two well-known questionnaires for measurement of drug craving severity are Desire for Drug Questionnaire or DDQ (for instant craving) and Obsessive Compulsive Drug Use Scale or OCDUS [for craving in a period of time (periodic craving), usually one week]. In this study, we evaluated the content-related validity of these questionnaires for Persian-language speaking crystalline-heroin abusers., Methods: After translation by two different groups, back translation and retranslation process of the DDQ and OCDUS questionnaires were achieved by an expert team in English language; we used them for evaluation of instant and periodic craving among 131 male crystalline-heroin abusers. Then, both DDQ and OCDUS questionnaire's scores were subjected to an exploratory principal components factor analysis (PCA). The criterion for factor extraction was an eigenvalue equal to or more than 1., Results: The factor analysis of DDQ and OCDUS led to three factors for DDQ and four factors for OCDUS; each group of factors together explained 62% and 65% of the common factor variance, respectively. There was no significant correlation between different DDQ and OCDUS components and demographic factors. Nevertheless, approximately all of the seven OCDUS and DDQ components were significantly correlated to each other., Conclusion: The Persian version of DDQ and OCDUS questionnaires could be considered as valid and reliable instruments for evaluation of drug craving in male crystalline-heroin Persian-language speaking abusers.

Reading is a multisensory function that relies on arbitrary associations between auditory speech sounds and symbols from a second modality. Studies of bimodal phonetic perception have mostly investigated the integration of visual letters and speech sounds. Blind readers perform an analogous task by using tactile Braille letters instead of visual letters. The neural underpinnings of audiotactile phonetic processing have not been studied before. We used functional magnetic resonance imaging to reveal the neural correlates of audiotactile phonetic processing in 16 early-blind Braille readers. Braille letters and corresponding speech sounds were presented in unimodal, and congruent/incongruent bimodal configurations. We also used a behavioral task to measure the speed of blind readers in identifying letters presented via tactile and/or auditory modalities. Reaction times for tactile stimuli were faster. The reaction times for bimodal stimuli were equal to those for the slower auditory-only stimuli. fMRI analyses revealed the convergence of unimodal auditory and unimodal tactile responses in areas of the right precentral gyrus and bilateral crus I of the cerebellum. The left and right planum temporale fulfilled the 'max criterion' for bimodal integration, but activities of these areas were not sensitive to the phonetical congruency between sounds and Braille letters. Nevertheless, congruency effects were found in regions of frontal lobe and cerebellum. Our findings suggest that, unlike sighted readers who are assumed to have amodal phonetic representations, blind readers probably process letters and sounds separately. We discuss that this distinction might be due to mal-development of multisensory neural circuits in early blinds or it might be due to inherent differences between Braille and print reading mechanisms.

Objectives: Iron oxide nanoparticles have found prevalent applications in various fields including drug delivery, cell separation and as contrast agents. Super paramagnetic iron oxide (SPIO) nanoparticles allow researchers and clinicians to enhance the tissue contrast of an area of interest by increasing the relaxation rate of water. In this study, we evaluate the dependency of hydrodynamic size of iron oxide nanoparticles coated with Polyethylene glycol (PEG) on their relativities with 3 Tesla clinical MRI., Materials and Methods: We used three groups of nanoparticles with nominal sizes 20, 50 and 100 nm with a core size of 8.86 nm, 8.69 nm and 10.4 nm that they were covered with PEG 300 and 600 Da. A clinical magnetic resonance scanner determines the T1 and T2 relaxation times for various concentrations of PEG-coated nanoparticles., Results: The size measurement by photon correlation spectroscopy showed the hydrodynamic sizes of MNPs with nominal 20, 50 and 100 nm with 70, 82 and 116 nm for particles with PEG 600 coating and 74, 93 and 100 nm for particles with PEG 300 coating, respectively. We foud that the relaxivity decreased with increasing overall particle size (via coating thickness). Magnetic resonance imaging showed that by increasing the size of the nanoparticles, r2/r1 increases linearly., Conclusion: According to the data obtained from this study it can be concluded that increments in coating thickness have more influence on relaxivities compared to the changes in core size of magnetic nanoparticles.

In order to improve patient's benefit and safety, comprehensive regulatory guidelines on specificities of Non-Biological Complex Drugs (NBCDs), such as doxorubicin-encapsulated liposomes, and their follow-on versions are needed. Here, we compare Doxil® and its European analog Caelyx® with the two follow-on products DOXOrubicin (approved by the US Food and Drug Administration) and SinaDoxosome (produced in Iran) by cryogenic transmission electron microscopy, dynamic light scattering and Nanoparticle Tracking Analysis, and assess their potential in activating the complement system in human sera. We found subtle physicochemical differences between the tested liposomal products and even between the tested batches of Doxil® and Caelyx®. Notably, these included differences in vesicular population aspect ratios and particle number. Among the tested products, only SinaDoxosome, in addition to the presence of unilamellar vesicles with entrapped doxorubicin crystals, contained empty circular disks. Differences were also found in complement responses, which may be related to some morphological differences. This study has demonstrated an integrated biophysical and immunological toolbox for improved analysis and detection of physical differences among vesicular populations that may modulate their clinical performance. Combined, these approaches may help better product selection for infusion to the patients as well as for improved design and characterization of future vesicular NBCDs with enhanced clinical performance and safety., (Copyright © 2015 Elsevier B.V. All rights reserved.)

During last 20 years, neuroimaging with functional magnetic resonance imaging (fMRI) in people with drug addictions has introduced a wide range of quantitative biomarkers from brain's regional or network level activities during different cognitive functions. These quantitative biomarkers could be potentially used for assessment, planning, prediction, and monitoring for "addiction medicine" during screening, acute intoxication, admission to a program, completion of an acute program, admission to a long-term program, and postgraduation follow-up. In this chapter, we have briefly reviewed main neurocognitive targets for fMRI studies associated with addictive behaviors, main study types using fMRI among drug dependents, and potential applications for fMRI in addiction medicine. Main challenges and limitations for extending fMRI studies and evidences aiming at clinical applications in addiction medicine are also discussed. There is still a significant gap between available evidences from group-based fMRI studies and personalized decisions during daily practices in addiction medicine. It will be important to fill this gap with large-scale clinical trials and longitudinal studies using fMRI measures with a well-defined strategic plan for the future., (© 2016 Elsevier B.V. All rights reserved.)

Introduction: Drug craving could be described as a motivational state which drives drug dependents towards drug seeking and use. Different types of self-reports such as craving feeling, desire and intention, wanting and need, imagery of use, and negative affect have been attributed to this motivational state. By using subjective self-reports for different correlates of drug craving along with functional neuroimaging with cue exposure paradigm, we investigated the brain regions that could correspond to different dimensions of subjective reports for heroin craving., Methods: A total of 25 crystalline-heroin smokers underwent functional magnetic resonance imaging (fMRI), while viewing heroin-related and neutral cues presented in a block-design task. During trial intervals, subjects verbally reported their subjective feeling of cue induced craving (CIC). After fMRI procedure, participants reported the intensity of their "need for drug use" and "drug use imagination" on a 0-100 visual analog scale (VAS). Afterwards, they completed positive and negative affect scale (PANAS) and desire for drug questionnaire (DDQ) with 3 components of "desire and intention to drug use," "negative reinforcement," and "loss of control.", Results: The study showed significant correlation between "subjective feeling of craving" and activation of the left and right anterior cingulate cortex, as well as right medial frontal gyrus. Furthermore, the "desire and intention to drug use" was correlated with activation of the left precentral gyrus, left superior frontal gyrus, and left middle frontal gyrus. Subjects also exhibited significant correlation between the "need for drug use" and activation of the right inferior temporal gyrus, right middle temporal gyrus, and right parahippocampal gyrus. Correlation between subjective report of "heroin use imagination" and activation of the cerebellar vermis was also observed. Another significant correlation was between the "negative affect" and activation of the left precuneus, right putamen, and right middle temporal gyrus., Discussion: This preliminary study proposes different neural correlates for various dimensions of subjective craving self-reports. It could reflect multidimensionality of cognitive functions corresponding with drug craving. These cognitive functions could represent their motivational and affective outcomes in a single item "subjective craving feeling" or in self-reports with multiple dissociable items, such as intention, need, imagination, or negative feeling. The new psychological models of drug craving for covering various dimensions of subjective craving self-reports based on their neurocognitive correspondence could potentially modify craving assessments in addiction medicine.

MUC1 antigen is recognized as a high-molecular-weight glycoprotein that is unexpectedly over-expressed in human breast and other carcinomas. In contrast, C595 a monoclonal antibody (mAb) against the protein core of the human urinary epithelial machine, is commonly expressed in breast carcinomas. The aim of this study was to conjugate ultra-small super paramagnetic iron oxide nanoparticles (USPIO) with C595 mAb, in order to detect in vivo MUC1 expression. A dual contrast agent (the C595 antibody-conjugated USPIO labeled with 99mTc) was prepared for targeted imaging and therapy of anti-MUC1-expressing cancers. The C595 antibody-conjugated USPIO had good stability and reactivity in the presence of blood plasma at 37 °C. No significant differences were observed in immunoreactivity results between conjugated and nonconjugated nanoparticles. The T1 and T2 measurements show >79 and 29% increments (for 0.02 mg/ml iron concentrations) in T1 and T2 values for USPIO-C595 in comparison with USPIO, respectively. The nanoprobes showed the interesting targeting capability of finding the MUC1-positive cell line in vitro. However, we found disappointing in vivo results (i.e. very low accumulation of nanoprobes in the targeted site while >80% of the injected dose per gram was taken up by the liver and spleen), not only due to the coverage of targeting site by protein corona but also because of absorption of opsonin-based proteins at the surface of nanoprobes., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Multifunctional core-shell magnetic nanocomposite particles with tunable characteristics have been paid much attention for biomedical applications in recent years. A rational design and suitable preparation method must be employed to be able to exploit attractive properties of magnetic nanocomposite particles., Objectives: Herein, we report on a simple approach for the synthesis of magnetic mesoporous silica nanocomposite particles (MMSPs), consisted of a Fe 3 O 4 cluster core, a nonporous silica shell and a second shell of the mesoporous silica of suitable sizes for biomedical applications and evaluate their cytotoxicity effects on human cancer prostate cell lines., Materials and Methods: Clusters of magnetite (Fe 3 O 4 ) nanoparticles were coated by a layer of nonporous silica using Stöber method. The coating step was completed by an outer layer of mesoporous silica via template-removing method. Structural properties of MMSPs were investigated by FTIR, HR-S(T)EM, BET, XRD techniques and magnetic properties of MMSPs by VSM instrument. MTT and LDH assays were employed to study the cytotoxicity of MMSPs., Results: Obtained results revealed that decreasing the precursor concentration and the reaction time at the nonporous silica shell formation step decreases the thickness of the nonporous silica shell and consequently leads to the formation of smaller MMSPs. The as-prepared MMSPs have a desirable average size of 180±10 nm, an average pore size of 3.01 nm, a high surface area of 390.4 m 2 .g -1 and a large pore volume of 0.294 cm 3 .g -1 . In addition, the MMSPs exhibited a superparamagnetic behavior and a high magnetization saturation value of 21±0.5 emu/g. Furthermore, the viability tests of DU-145 cell lines exposed to various concentrations of these particles demonstrated negligible cytotoxicity effects of the as-prepared particles., Conclusions: These results demonstrate interesting properties of MMSPs prepared in this study for biomedical applications.

Objectives: P In vitro chemosensitivity and resistance assays (CSRAs) are a promising tool for personalized treatment of glioblastoma multiform (GBM). These assays require a minimum of 1 to 2 g of tumor specimen for testing, but this amount is not always accessible. We aimed to assess the feasibility and validity of utilizing stereotactic biopsies of GBM in CSRAs., Materials and Methods: Single cell suspension was prepared from 1 g weight explants of the established xenograft tumor of GBM. Also, primary culture was carried out on 35 mg weight specimens, as a surrogate for stereotactic biopsies. Then, chemoresponse profile of cells obtained by direct cell disaggregation and primary culture was determined using temozolomide and carmustine by clonogenic assay., Results: There was no statistically significant difference in the cytotoxicity of temozolomide and carmustine between cells obtained from both methods., Conclusion: This work supports the feasibility of using stereotactic biopsies of GBM in CSRAs.