Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis.

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.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

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.

Evaluation of multimodal MR imaging for differentiating infiltrative versus reactive edema in brain gliomas.

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.

DLPFC stimulation alters large-scale brain networks connectivity during a drug cue reactivity task: A tDCS-fMRI study.

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.

A case report of the sustained and rapid response of bevacizumab in a TP53-positive breast cancer and liver metastatic patient through personalized medicine.

HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant breast cancer requires the identification of reliable biomarkers for personalized medicine to obtain the maximum benefit of this therapy. Any mutations in the TP53 signaling pathway can be considered as a significant causative factor of breast cancer, for which the identification of target genes plays an important role in selecting the appropriate treatment. The use of personalized gene expression profiling could be valuable to find the direct target of the treatment in this case. The present study assessed the genetic profile of an HER2-positive metastatic breast cancer patient (with a liver metastasis) and figured out a complete and sustained response to bevacizumab. According to the results of next-generation sequencing (NGS) analysis, the patient's genetic profile showed an increased expression of p4EBP1 and PTEN and the activation of the mTOR signaling pathway with a mutation in the TP53 gene. Based on the common treatment of similar profiling, we administrated bevacizumab/Taxol/Gemzar chemotherapy up to six courses. Accordingly, as the response to treatment was revealed by reducing the volume of the liver metastasis from 4 to 1.4 cm, metastasectomy was performed as a complementary treatment. Hence, personalized gene expression profiling not only is useful for targeted therapy but also could be recommended to avoid prescription of non-responsive drugs.

Temporally dynamic neural correlates of drug cue reactivity, response inhibition, and methamphetamine-related response inhibition in people with methamphetamine use disorder.

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.

Cue-induced craving and negative emotion disrupt response inhibition in methamphetamine use disorder: Behavioral and fMRI results from a mixed Go/No-Go task.

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.

Magnetic Resonance Imaging of Tumor-Infiltrating Lymphocytes by Anti-CD3-Conjugated Iron Oxide Nanoparticles.

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 T2 *-weighted and T2 -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.

White matter microstructure differences in individuals with dependence on cocaine, methamphetamine, and nicotine: Findings from the ENIGMA-Addiction working group.

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.

Quantification of Blood-Brain-Barrier Permeability Dysregulation and Inflammatory Activity in MS Lesions by Dynamic-Contrast Enhanced MR Imaging.

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.

Along-tract analysis of the white matter is more informative about brain ageing, compared to whole-tract analysis.

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.

Bio-conjugation of anti-human CD3 monoclonal antibodies to magnetic nanoparticles by using cyanogen bromide: A potential for cell sorting and noninvasive diagnosis.

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.

Iranian Brain Imaging Database: A Neuropsychiatric Database of Healthy Brain.

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.

Fully automatic 3D segmentation of the thoracolumbar spinal cord and the vertebral canal from T2-weighted MRI using K-means clustering algorithm.

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.

Effect of Physiological Noise on Thoracolumbar Spinal Cord Functional Magnetic Resonance Imaging in 3T Magnetic Field.

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.

The influence of mental fatigue on the face and word encoding activations.

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.

Evaluation of contrast agent dose and diffusion coefficient measurement on vessel size index estimation.

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.

Comparison of Qualitative (Time Intensity Curve Analysis), Semi-Quantitative, and Quantitative Multi-Phase 3T DCEMRI Parameters as Predictors of Malignancy in Adnexal.

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.

Synthesis and Biological Evaluation of a Novel Glucosylated Derivative of Gadolinium Diethylenetriaminepentaacetic Acid for Tumor Magnetic Resonance Imaging.

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 Gd3+-1-(4-isothiocyanatobenzyl) diethylene tri amine penta acetic acid (Gd3+-p-SCN-Bn-DTPA-DG) as a novel potential MR imaging contrast agents was synthesized. Gd3+-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 Gd3+-p-SCN-Bn-DTPA efficiently increase its cellular uptake in normal cells 25% and in cancereous cells upto 67%. The Gd3+-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 Gd3+-p-SCN-Bn-DTPA-DG be a potential breast molecular imaging. However, further investigations by anticancer studies are in the pipeline.

Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy.

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.