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.

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.

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.

Neural correlates of audiotactile phonetic processing in early-blind readers: an fMRI study.

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.

Synthesizing and staining manganese oxide nanoparticles for cytotoxicity and cellular uptake investigation.

BACKGROUND: For decades, contrast agents have been used to reduce longitudinal (T1) or transverse (T2) relaxation times. High toxicity of gadolinium-based contrast agents leads researchers to new T1 contrast agents. Manganese oxide (MnO) nanoparticle (NP) with the lower peril and good enough signal change ability has been offered as a new possibility for magnetic resonance imaging (MRI). METHODS: The synthesized NPs were investigated for physicochemical and biological properties by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscope, dynamic light scattering (DLS), inductively coupled plasma, enzyme-linked immunosorbent assay, and 3T magnetic resonance imaging. RESULTS: Due to physical contact importance of T1 contrast agents with tissues' protons, extremely thin layer of the surfactant, less than 2nm, was coated on NPs for aqueous stabilizing. The hydrophilic gentisic acid with low Dalton, around 154, did that role truly. Moreover, decreasing NP size to 5nm which increases available surface for the proton relaxation is another important parameter to reach an appropriate longitudinal relaxation rate. The NPs didn't reveal any side effects on the cells, and cellular uptake was considerable. CONCLUSIONS: The synthesized NPs represented a promising result in comparison to clinical gadolinium chelates, due to higher r1 relaxivity and lower toxicity. GENERAL SIGNIFICANCE: In addition to considerable signal change and cellular uptake, Prussian blue was tried on MnO NPs for the initial time, which can be observed within cells by pale blue color.

Anal sphincter repair with muscle progenitor cell transplantation: serial assessment with iron oxide-enhanced MRI.

OBJECTIVE: The purpose of this study was to assess homing of ultrasmall superparamagnetic iron oxide (USPIO)-labeled muscle progenitor cells in an experimental rabbit model of anal sphincter repair using MRI. MATERIALS AND METHODS: Twelve rabbits underwent external anal sphincterotomy and randomly received injection of either autologous muscle progenitor cells labeled with USPIO at a concentration of 4 mg/10(6) cells (experimental group) or saline (control group) at the site of sphincter damage. In vivo MRI, electromyography, and manometry were performed before, 1 hour after, and 1, 2, and 4 weeks after the injection. At the end time point, anal sphincter sections were obtained for histologic analysis. Semiquantitative analysis of fibrosis, desmin, iron, CD3, and CD68 was performed using two microscopic fields in two distinct regions of the sphincter according to either presence (zone I) or absence (zone II) of signal loss on the corresponding MR images. RESULTS: Labeling efficiency was 88.67% and did not influence cell viability. On follow-up images of the cell-transplanted rabbits, significant influence was reported at 1 hour, 1 and 2 weeks after transplantation. The maximum signal loss was detected at 1 hour (75.7%). Regenerating myofibers stained positively for desmin and mainly correlated to zone I on MR images. Clusters of iron-positive particles were detectable in the myofibers located mainly at the site of injection, which correlated well to zone I. Significant signal loss and Perls Prussian blue-positive area were not detected in the control group. Functional studies showed significant improvement in sphincter pressure and electrical activity in the experimental group after 4 weeks (p<0.001). CONCLUSION: Our results support the potential of iron oxide-enhanced MRI for serial monitoring of transplanted cells in an animal model of anal sphincter repair.

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.

Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease.

In this study we segment the hippocampus according to functional connectivity assessed from resting state functional magnetic resonance images in healthy subjects and in patients with Alzheimer's disease (AD). We recorded the resting FMRI signal from 16 patients and 22 controls. We used seed-based functional correlation analyses to calculate partial correlations of all voxels in the hippocampus relative to characteristic regional signal changes in the thalamus, the prefrontal cortex (PFC) and the posterior cingulate cortex (PCC), while controlling for ventricular CSF and white matter signals. Group comparisons were carried out controlling for age, gender, hippocampal volume and brain volume. The strength of functional connectivity in each region also was correlated with neuropsychological measures. We found that the hippocampus can be segmented into three distinct functional subregions (head, body, and tail), according to the relative connectivity with PFC, PCC and thalamus, respectively. The AD group showed stronger hippocampus-PFC and weaker hippocampus-PCC functional connectivity, the magnitudes of which correlated with MMSE in both cases. The results are consistent with an adaptive role of the PFC in the context of progression of dysfunction in PCC during earlier stages of AD. Extension of our approach could integrate regional volume measures for the hippocampus with their functional connectivity patterns in ways that should increase sensitivity for assessment of AD onset and progression.

Improving cellular uptake and in vivo tumor suppression efficacy of liposomal oligonucleotides by urea as a chemical penetration enhancer.

BACKGROUND: Liposomes are among the most widely used carriers for the delivery of antisense oligonucleotides (AsODNs) to intracellular targets. Although different strategies have been employed, the question of how to improve liposomal uptake and enhance the release of AsODN into cytoplasm still remains to be answered with respect to the use of a safe, easy and economic method. In the present study, the possibility of enhancing such processes at cellular and animal levels using urea as a penetration enhancer was investigated. METHODS: To perform this investigation, a cationic liposome containing an AsODN against protein kinase (PKC)-α was prepared, and the effect of urea on its cellular internalization and the related sequence-specific inhibition of gene expression in human lung adenocarcinoma A549 cells were investigated by flow cytometry and the reverse transcriptase-polymerase chain reaction, respectively. In in vivo studies, a xenograft lung tumor was established in nude mice by A549 cells and the enhancement effect of urea toward the effects of liposomal AsODN on tumor growth was investigated. RESULTS: Cellular studies revealed that urea treatment increases liposomal uptake and the release of AsODN into the cytoplasm by approximately 40%. Sequence-specific inhibition of target gene PKC-α expression was also increased by approximately two-fold by urea at 200-300 nM AsODN. In animal studies, urea significantly decreased the tumor volume (approximately 40%) and increased its doubling time from approximately 13 days to 17 days. CONCLUSIONS: Urea, and possibly other membrane fluidizers, could be regarded as penetration enhancers for liposomal AsODN delivery and may improve the therapeutic effect of these gene-therapy vectors at both cellular and animal levels.

Atypical language lateralization: an fMRI study in patients with cerebral lesions.

Differences in the lateralization of language processes between healthy subjects and patients with neurological complaints other than epilepsy have been less documented than those between healthy subjects and epilepsy patients. Moreover, the contribution of factors such as the location and type of lesion in determining interhemispheric shift of language function is poorly understood. Sixty-seven patients who underwent presurgical evaluations at the Medical Imaging Center of the Imam Khomeini University Hospital, Tehran, and the same number of healthy controls, were recruited. The laterality index (LI) of language activation, calculated from two separate functional magnetic resonance imaging tasks, was compared between the patients and the age-/gender-/handedness-matched controls. Chi square testing showed that the percentages of subjects with "typical" and "atypical" language dominance in the patient group were significantly different from the percentages recorded in the matched healthy controls for both tasks (p<0.005). Lesion type, lesion location, lesion hemisphere, presenting symptom and patient gender had no statistically significant effect on the hemispheric LI (p>0.05). In a logistic regression model including all potential determinants of atypical LI, age emerged as the only independent predictor (p<0.05, odds ratio=0.9). Abnormal language lateralization is found in patients with a variety of cerebral lesions and with a diversity of clinical manifestations. In our selected population, symptom duration, lesion hemisphere and anatomical site of the lesion were not found to impact significantly on the development of an abnormal LI while patient age can independently predict the presence of an atypical LI.

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.

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.

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.

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.

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.

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.

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.

Developing optimized fMRI protocol for clinical use: comparison of different language paradigms.

PURPOSE: To compare the potential of five functional magnetic resonance imaging (fMRI) language paradigms in activating language areas in Persian-speaking volunteers in order to optimize these tasks for clinically useful protocol. MATERIALS AND METHODS: 16 healthy right-handed Persian-speaking volunteers were studied. Each individual performed five tasks during the fMRI scan: word generation (WG), object naming (ON), word reading (WR), word production (WP), and reverse word reading (RWR). The ability of each task to activate classical language areas was assessed using group analysis. In addition, the lateralization index (LI) for each subject-task was calculated and compared. RESULTS: We found that WP, RWR, and WG robustly activated language-related areas in the dominant hemisphere. ON and WR failed to sufficiently delineate these activation areas. Highest activation intensities in the frontal lobe (including Broca's area) were seen with WP, whereas RWR showed the highest LI among all examined tasks. CONCLUSION: Our results demonstrated that the Persian version of WG and newly presented WP and RWR tasks can be reliably used for localization of language-related areas in Persian speakers. This type of language evaluation may be used in presurgical planning of neurosurgical procedures in the Persian population. We recommend application of WP and RWR in future researches establishing the optimized protocol for other language speakers.

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.