Search

Recent studies highlighted the triple-network model which illustrated the interactions among three large-scale networks including salience network (SN). The functional magnetic resonance imaging used in this study was designed to investigate the characteristics of three large-scale networks associated with the thought-action fusion (TAF) in patients with obsessive-compulsive disorder (OCD) using power spectral density (PSD) analysis.This study included 32 OCD patients and 38 age-matched healthy controls (HC). The TAF task was modified from the experiment of Rassin. PSD from time courses in large-scale networks of each subject was measured to compare between the groups for both TAF and resting state.In SN, OCD reported lower power in the low-frequency domain of SN compared to HC using the two-sample t test during the TAF task (t = -2.395, p = 0.019) but not in the resting state. The PSD in the low-frequency domain of the SN had a significant negative correlation with state score in the guilty inventory (r = -0.361, p = 0.042) in OCD patients.This study suggests that OCD patients showed reduced SN power which can be prominent in a certain situation, such as TAF. In addition, the PSD alterations in SN cause difficulty in processing ambiguous emotional cues in social situations, and the difficulty can be connected with a negative feeling (e.g., guilt).

Changes in the brain with age can provide useful information regarding an individual's chronological age. studies have suggested that functional connectomes identified via resting-state functional magnetic resonance imaging (fMRI) could be a powerful feature for predicting an individual's age. We applied connectome-based predictive modeling (CPM) to investigate individual chronological age predictions via resting-state fMRI using open-source datasets. The significant feature for age prediction was confirmed in 168 subjects from the Southwest University Adult Lifespan Dataset. The higher contributing nodes for age production included a positive connection from the left inferior parietal sulcus and a negative connection from the right middle temporal sulcus. On the network scale, the subcortical-cerebellum network was the dominant network for age prediction. The generalizability of CPM, which was constructed using the identified features, was verified by applying this model to independent datasets that were randomly selected from the Autism Brain Imaging Data Exchange I and the Open Access Series of Imaging Studies 3. CPM via resting-state fMRI is a potential robust predictor for determining an individual's chronological age from changes in the brain.

Synthetic MRI is a time-efficient imaging technique that provides both quantitative MRI and contrast-weighted images simultaneously. However, a rather long single scan time can be challenging for children.To evaluate the clinical feasibility of time-saving synthetic MRI protocols adjusted for echo train length and receiver bandwidth in pediatric neuroimaging based on image quality assessment and quantitative data analysis.In total, we included 33 children ages 1.6-17.4 years who underwent synthetic MRI using three sets of echo train length and receiver bandwidth combinations (echo train length [E]12-bandwidth [B in KHz]22, E16-B22 and E16-B83) at 3 T. The image quality and lesion conspicuity of synthetic contrast-weighted images were compared between the suggested protocol (E12-B22) and adjusted protocols (E16-B22 and E16-B83). We also compared tissue values (T1, T2, proton-density values) and brain volumetry.For the E16-B83 combination, image quality was sufficient except for 15.2% of T1-W and 3% of T2-W fluid-attenuated inversion recovery (FLAIR) images, with remarkable scan time reduction (up to 35%). The E16-B22 combination demonstrated a comparable image quality to E12-B22 (Pgt;0.05) with a scan time reduction of up to 8%. There were no significant differences in lesion conspicuity among the three protocols (Pgt;0.05). Tissue value measurements and brain tissue volumes obtained with the E12-B22 protocol and adjusted protocols showed excellent agreement and strong correlations except for gray matter volume and non-white matter/gray matter/cerebrospinal fluid volume in E12-B22 vs. E16-B83.The adjusted synthetic protocols produced image quality sufficient or comparable to that of the suggested protocol while maintaining lesion conspicuity with reduced scan time. The quantitative values were generally consistent with the suggested MRI-protocol-derived values, which supports the clinical application of adjusted protocols in pediatric neuroimaging.

Paramagnetic ultrasmall Ho2O3 and Tm2O3 nanoparticles grafted with various hydrophilic and biocompatible ligands as a new class of efficient T2 MRI contrast agents were investigated in this study.

Childhood maltreatment (CM) causes early deviations in cognitive and affective processes, leading to future adaptation failures and psychopathology. Specifically, CM has been linked to cognitive distortions, and recent studies have focused on the impact of CM on the higher level of metacognitive beliefs. However, only a few studies have revealed the neural mechanisms underlying the association between altered metacognition and CM. Therefore, this functional magnetic resonance imaging (fMRI) study investigated the neural correlates of thought–action fusion (TAF) tendency and CM experiences. Overall, 40 young adults (21 men) participated in this study and underwent fMRI during the TAF task as well as psychological evaluation for CM, TAF tendency, anxiety, and depressive symptoms. During the TAF task, they were asked to read negative (Neg) or neutral (Neu) statements about neutral or close people (CP). Notably, significant activations were found in regions such as the bilateral anterior insula, dorsal anterior cingulate cortex (dACC), caudate, thalamus, medial prefrontal cortex, precuneus, and right amygdala in the NegCP > NeuCP contrast. Furthermore, anterior insula and dACC activities were significantly correlated with total scores of CM experiences and TAF. Exaggerated TAF tendency in CM victims was associated with increased response of the anterior insula and dACC, which are two core hubs of the salience network. Our results therefore seem to suggest insights for a better understanding of the neural mechanisms underlying metacognitive beliefs related to CM experiences.

Objective Thought-action fusion (TAF), one of the most-studied dysfunctional beliefs in obsessive-compulsive disorder, represents an individual’s belief that his/her thoughts directly influence events. TAF belief types are divided into personal thoughts relating to positive (positive TAF) and negative outcomes (negative TAF). However, the neural mechanisms underlying both aspects of the TAF response remain elusive. Methods This functional magnetic resonance imaging study aimed to investigate the neural circuits related to positive and negative TAF and their relationships with psychological measures. Thirty-one healthy male volunteers participated in a modified TAF task wherein they were asked to read the name of a close person embedded in positive statements (PS) or negative statements (NS). Results Conjunction analysis revealed activation of the fusiform and lingual gyri, midcingulate and superior medial frontal gyri, inferior orbitofrontal gyrus, and temporoparietal junction. The NS > PS comparison showed additional activation in the precuneus and medial prefrontal cortex, superior frontal gyrus, insula, globus pallidus, thalamus, and midbrain. Precuneus activity was associated with the TAF score among these areas. Moreover, activity in the inferior orbitofrontal gyrus, insula, superior, middle and medial frontal gyri, globus pallidus, inferior parietal lobule, and precuneus was associated with dimensional obsessive-compulsive scores. In contrast, the PS > NS comparison revealed no significant activation. Conclusion These results suggest that negative TAF, relative to positive TAF, recruits additional regions for self-referential processing, salience, and habitual responding, which may contribute to the activation of the belief that a negative thought increases the probability of that negative outcome.

PURPOSE J-Difference editing (MEGA) provides an effective spectroscopic means of selectively measuring low-concentration metabolites having weakly coupled spins. The fractional inphase and antiphase coherences are determined by the radiofrequency (RF) pulses and inter-RF pulse intervals of the sequence. We examined the timings of the spectrally selective editing 180° pulses (E180) in MEGA-PRESS to maximize the edited signal amplitude in lactate at 3T. METHODS The time evolution of the lactate spin coherences was analytically and numerically calculated for non-volume localized and single-voxel localized MEGA sequences. Single-voxel localized MEGA-PRESS simulations and phantom experiments were conducted for echo time (TE) 60-160 ms and for all possible integer-millisecond timings of the E180 pulses. Optimized E180 timings of 144, 103, and 109 ms TEs, tailored with simulation and phantom data, were tested in brain tumor patients in vivo. Lactate signals, broadened to singlet linewidths (~6 Hz), were compared between simulation, phantom, and in vivo data. RESULTS Theoretical and experimental data indicated consistently that the MEGA-edited signal amplitude and width are sensitive to the E180 timings. In volume-localized MEGA, the lactate peak amplitudes in E180-on and difference spectra were maximized at specific E180 timings for individual TEs, largely due to the chemical-shift displacement effects. The E180 timings for maximum lactate peak amplitude were different from those of maximum inphase coherence in in vivo linewidth situations. CONCLUSION In in vivo MEGA editing, the E180 pulse timings can be effectively used for manipulating the inphase and antiphase coherences and increasing the edited signal amplitude, following TE optimization.

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).

In this study, we designed, synthesized, and evaluated gadolinium compounds conjugated with flavonoids as potential theranostic agents for the treatment of inflammation. These novel theranostic agents combine a molecular imaging agent and one of three flavonoids (galangin, chrysin, and 7-hydroxyflavone) as anti-inflammatory drugs as a single integrated platform. Using these agents, MR imaging showed contrast enhancement (>10 in CNR) at inflamed sites in an animal inflammation model, and subsequent MR imaging used to monitor the therapeutic efficacy of these integrated agents revealed changes in inflamed regions. The anti-inflammatory effects of these agents were demonstrated both in vitro and in vivo. Furthermore, the antioxidant efficacy of the agents was evaluated by measuring their reactive oxygen species scavenging properties. For example, Gd-galangin at 30 μM showed a three-fold higher ROS scavenging of DPPH. Taken together, our findings provide convincing evidence to indicate that flavonoid-conjugated gadolinium compounds can be used as potentially efficient theranostic agents for the treatment of inflammation.

In this study, hydrophilic and biocompatible chitosan oligosaccharide lactate (COL)-coated ultra-small gadolinium oxide nanoparticles (NPs) were synthesized through a one-pot polyol method and characterized by various experimental techniques. The In Vitro cellular cytotoxicity assay indicated that the COL-coated gadolinium oxide NPs were non-toxic up to 500 μM Gd. In addition, their water proton spin relaxivities (i.e., r1 and r2) were estimated to be 13.0 and 27.0 s−1mM−1, respectively, which are higher than those of commercial magnetic resonance imaging (MRI) contrast agents. The application potential of the solution sample as a T1 MRI contrast agent was demonstrated In Vitro by measuring map images in which dose-dependent contrast enhancements were observed.

In gamma knife radiosurgery, the tumor response to radiation is an important predictor of clinical treatment results. Since brain tumors have different characteristics and growth patterns, depending on the type, the tumors' response to radiation are also different. Compared with various other clinical treatments, there is a dearth of research on the development of gamma knife-magnetic resonance imaging (MRI) preclinical experimental equipment. Hence, the identification of preclinical equipment necessity for experimental animals will provide meaningful data for the provision of clinical assistance to humans.A device for stereotactic radiosurgery capable of MRI in small animals was developed. The feasibility of creating a preplan by means of small animal images was then assessed.A device for stereotaxic surgery of small animals using a 48-channel MRI coil was developed using a 3 dimensional printer. Rat brain-MRI images were obtained with a 3.0 T MRI scanner using a multi-channel coil. The acquired MRI images were transferred to a GammaPlan workstation to establish a preplan.To gamma rays to the targeted site on animals, a positioning device combined with a G-frame was mounted on a gamma knife. Planning of radiosurgery based on MRI images became possible with GammaPlan workstations.Preclinical experiments using small animals are possible with the use of stereotactic devices. In clinical treatment, preclinical experimental results will provide meaningful information.

Objective Although cognitive models of obsessive-compulsive disorder (OCD) fall into two categories: cognitive deficit models and dysfunctional belief models, these approaches have their own ways and have hardly been reconciled. Therefore, this study aimed to investigate the potential relationships between cognitive deficit (using the Wisconsin Card Sorting Task, WCST) and dysfunctional belief (measured by scales of dysfunctional beliefs) mediated by neural activity in OCD patients. Methods Thirty OCD patients and 30 healthy participants performed the WCST condition and a baseline MATCH condition during the 3T-functional magnetic resonance imaging (fMRI) acquisition. Results Engagement of additional frontoparietal networks with poorer performance of WCST was found during the fMRI scan in OCD patients. Selected regions of interest from activated regions have positive relationships with dysfunctional beliefs and with the unacceptable thoughts symptom dimension in the OCD group. Conclusion Findings suggest that alteration in frontoparietal networks related to cognitive deficits can be associated with dysfunctional beliefs while performing conventional neurocognitive tasks and this association with dysfunctional beliefs may be pronounced in the unacceptable thoughts domain-dominant OCD patients.

Magnetic resonance imaging (MRI) is increasingly used to diagnose focal and diffuse liver disorders. Despite their enhanced efficacy, liver-targeted gadolinium-based contrast agents (GBCAs) raise safety concerns owing to the release of toxic Gd3+ ions. A π-conjugated macrocyclic chelate, Mn-NOTA-NP, was designed and synthesized as a non-gadolinium alternative for liver-specific MRI. Mn-NOTA-NP exhibits an r1 relaxivity of 3.57 mM−1 s−1 in water and 9.01 mM−1 s−1 in saline containing human serum albumin at 3 T, which is significantly greater than the clinically utilized Mn2+-based hepatobiliary drug, Mn-DPDP (1.50 mM−1 s−1), and comparable with that of GBCAs. Furthermore, the in vivo biodistribution and MRI enhancement patterns of Mn-NOTA-NP were similar to those of the Gd3+-based hepatobiliary agent, Gd-DTPA-EOB. Additionally, a 0.05 mmol/kg dose of Mn-NOTA-NP facilitated high-sensitivity tumor detection with tumor signal enhancement in a liver tumor model. Ligand-docking simulations further indicated that Mn-NOTA-NP differed from other hepatobiliary agents in their interactions with several transporter systems. Collectively, we demonstrated that Mn-NOTA-NP could be a new liver-specific MRI contrast agent.

Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M−1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1β, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2.

BACKGROUND: Post-stroke depression (PSD) is a consequential neuropsychiatric sequela that occurs after stroke. However, the pathophysiology of PSD are not well understood yet. OBJECTIVE: To explore alterations in functional connectivity (FC) between anterior insula and fronto-cortical and other subcortical regions in the non-affected hemisphere in patients with PSD compared to without PSD and healthy control. METHODS: Resting-state FC was estimated between the anterior insula and cortical and subcortical brain regions in the non-affected hemisphere in 13 patients with PSD, 12 patients without PSD, and 13 healthy controls. The severity of depressive mood was measured by the Beck Depression Inventory (BDI)-II. RESULTS: Patients with PSD showed significant differences in FC scores between the anterior insula and the superior frontal, middle frontal, and orbitofrontal gyrus in the non-affected hemisphere than healthy control or patients without PSD (P< 0.05). In post-hoc, patients with PSD showed higher FC scores between the anterior insula and the superior frontal region than patients without PSD (P< 0.05). Furthermore, alterations in FC of the superior frontal, middle frontal, and orbitofrontal gyrus were positively correlated with depression severity, as measured with the BDI-II (P< 0.001).

Glutamate is an important excitatory neurotransmitter, and vesicular glutamate transporters (VGLUTs) are critical in regulating the extent of glutamate release. Because initial increase and late stage decrease in VGLUT expression were implicated in progressive Alzheimer’s disease (AD), VGLUTs can be a new imaging target for diagnosing AD. In this study, we have designed and synthesized a new multimodal gadolinium contrast agent conjugated with rose bengal to target VGLUTs (Gd-DO3A-RB). In addition to high kinetic and pH stability, magnetic resonance and fluorescence imaging using Gd-DO3A-RB showed high affinity to VGLUT1. Using the AD animal model (5XFAD), in vivo MRI with a Gd-DO3A-RB showed less MR signal enhancement in 5XFAD mouse brain than that of age-matched normal C57BL/6 mouse, suggesting a late stage decrease in VGLUT expression in AD animal model. Therefore, this new VGLUT targeting gadolinium contrast agent demonstrated a strong potential as a new diagnostic tool for AD with multimodal imaging capability.

Apoferritin (APO) with a diameter of ~12 nm is a naturally occurring protein assembly in living organisms. APO is made of 24 protein subunits that form a nanocage with an inner diameter of ~8 nm. Thus far, the loading of only a few nanoparticles inside the nanocage of APO has been reported. In this study, the mass loading of D-glucuronic acid (GA)-coated ultrasmall gadolinium oxide (Gd2O3) nanoparticles (UGNPs) (GA-UGNPs) (davg = 1.9 nm) inside and outside the nanocage of APO was investigated. The in vitro cytotoxicity and relaxometric properties were investigated. This study indicates that APO is an extremely useful bio-material, which can be used for mass loading of various nanoparticles for biomedical applications.

Here, we describe the synthesis, characterization, and in vitro biological evaluation of a series of transition metal complexes containing benzothiazole aniline (BTA). We employed BTA, which is known for its selective anticancer activity, and a salen-type Schiff-based ligand to coordinate several transition metals to achieve selective and synergistic cytotoxicity. The compounds obtained were characterized by NMR spectroscopy, mass spectrometry, Fourier transform infrared spectroscopy, and elemental analysis. The compounds L, MnL, FeL, CoL, and ZnL showed promising in vitro cytotoxicity against cancer cells, and they had a lower IC50 than that of the clinically used cisplatin. In particular, MnL had synergistic cytotoxicity against liver, breast, and colon cancer cells. Moreover, MnL, CoL, and CuL promoted the production of reactive oxygen species in HepG2 tumor cell lines. The lead compound of this series, MnL, remained stable in physiological settings, and docking results showed that it interacted rationally with the minor groove of DNA. Therefore, MnL may serve as a viable alternative to platinum-based chemotherapy.

Hydrophilic and biocompatible PAA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd2O3 and cRGD/FA-PAA-Gd2O3 nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T1 magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd2O3 nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd2O3 nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd2O3 nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd2O3 nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd2O3 nanoparticles, which prolonged their circulation in the blood.

The purpose of this study is to assess the physicochemical properties and MRI diagnostic efficacy of two newly synthesized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd chelates, Gd-SucL and Gd-GluL, with an asymmetric α-substituted pendant arm as potential hepatocyte-specific magnetic resonance imaging contrast agents (MRI CAs). Our findings show that fine conformational changes in the chelating arm affect the

Maltreatment experiences alter brain development associated with emotion processing, and dysregulation of emotion may trigger mental health problems in maltreated people. However, studies revealing alterations in brain networks during cognitive reappraisal in victims of maltreatment are strikingly insufficient. In this study, 27 healthy subjects were recruited. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Cognitive Emotion Regulation Questionnaire (CERQ), respectively. A cognitive reappraisal task using the International Affective Picture System (IAPS) was designed for functional magnetic resonance imaging (fMRI) experiments. Cognitive reappraisal induced more activities in the bilateral inferior parietal lobes and bilateral middle temporal gyri compared to the condition of “look” (false discovery rate (FDR) corrected p

Multifunctional imaging of the deposition of amyloid-beta (Aβ) aggregates in the brain is of great importance in diagnosing Alzheimer’s disease. Herein, we report a multifunctional Aβ-targeting small-molecular-weight gadolinium (Gd)-based contrast agent (CA), Gd-DO3A-Chal (a new Gd-chelate conjugated with chalcone), that showed 8 times higher binding affinity to Aβ aggregates than a previously reported Gd-chelate conjugated with Pittsburgh compound B. Gd-DO3A-Chal showed multimodal imaging capability. As a new fluorescence imaging probe, Gd-DO3A-Chal showed a good match with immunostained images using 6E10 monoclonal antibodies for the detection of Aβ aggregates in 5XFAD transgenic mouse brain sections. For in vivo magnetic resonance (MR) imaging without blood-brain barrier disruption, longitudinal relaxation time (T1)-weighted MR images after intravenous administration of Gd-DO3A-Chal showed signal enhancement of the Aβ distribution in living 5XFAD transgenic mouse brain. Therefore, in vivo MR images for Aβ detection in addition to fluorescent optical images of Aβ aggregates with high specificity and sensitivity using this new multifunctional Aβ-targeting CA were successfully demonstrated.

An increased understanding of how odors are processed in the central nervous system may provide comprehensive information about the neural basis of odor-related behavior and learning. In this study, we investigated how different odors are processed from the olfactory bulb to the deep cerebral structures through various olfactory pathways. To do this, we employed a novel manganese-enhanced magnetic resonance imaging (MEMRI) method to map the activity-dependent functional connectivity of the olfactory and non-olfactory pathways associated with various odorants. Our MEMRI data revealed odor-specific neural pathways that correspond to different odorant stimulations, suggesting that different neural circuits may process different odorants. Among the odorants tested, formic acid, an alarm pheromone, stimulated not only the primary and secondary olfactory pathways but also the mesolimbic neural circuit, which overlaps with the dopaminergic neural pathway. Linalool, which is a major component of aroma oils, showed high Mn2+ uptake in the hypothalamus, which plays a role in the stress response through the secretion of corticotropin-releasing hormone (CRH), and consequently, the stimulation of corticotropin secretion. Acetone mainly activated the primary olfactory pathway, whereas saline acted as a non-odorous trigeminal stimulus. Taken together, our functional MEMRI using anatomic standardization and statistical analyses could be a promising in vivo imaging method to map neural connectivity, enabling further understanding of the neural processing of different odorants.

This study investigates how moderate and addictive exercise influence the executive function network of the brain using fMRI. Sixty-five healthy participants performed the Wisconsin Card Sorting Test (WCST) during a functional magnetic resonance imaging (fMRI) scan. Participants were divided into three groups, according to the Korean exercise addiction scale (K-EAS): addictive exercise (AE), moderate exercise (ME), and no exercise (NE). We compared the extracted volumes of activity from the fMRI data between groups and analyzed the correlation between the volumes and the behavioral data. The activated area in the executive function network was significantly smaller in the AE and ME groups than in the NE group. In contrast, there was no difference between the AE and the ME group in the size of the activated area of the executive function network. The groups did not differ in behavioral performance. There was no significant correlation between the behavioral measurements and the activation volumes. A focused reorganization of the executive brain network through exercise may suggest improved neural efficiency for executive functions, and exercise may be helpful in maintaining executive functions and behavioral performance levels. Addictive exercise did not show an added benefit for the efficiency of executive functions.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (davg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

While boron neutron capture therapy (BNCT) depends primarily on the short flight range of the alpha particles emitted by the boron neutron capture reaction, gadolinium neutron capture therapy (GdNCT) mainly relies on gamma rays and Auger electrons released by the gadolinium neutron capture reaction. BNCT and GdNCT can be complementary in tumor therapy. Here, we studied the combined effects of BNCT and GdNCT when boron and gadolinium compounds were co-injected, followed by thermal neutron irradiation, and compared these effects with those of the single therapies. In cytotoxicity studies, some additive effects (32‒43%) were observed when CT26 cells were treated with both boron- and gadolinium-encapsulated PEGylated liposomes (B- and Gd-liposomes) compared to the single treatments. The tumor-suppressive effect was greater when BNCT was followed by GdNCT at an interval of 10 days rather than vice versa. However, tumor suppression with co-injection of B- and Gd-liposomes into tumor-bearing mice followed by neutron beam irradiation was comparable to that observed with Gd-liposome-only treatment but lower than B-liposome-only injection. No additive effect was observed with the combination of BNCT and GdNCT, which could be due to the shielding effect of gadolinium against thermal neutrons because of its overwhelmingly large thermal neutron cross section.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (davg = 1.76 nm). Higher positive (brighter or T1) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T1 MRI contrast agents in tumor imaging via GlcN effects.

Ultrasmall platinum nanoparticles (Pt-NPs) grafted with three types of hydrophilic and biocompatible polymers, i.e., poly(acrylic acid), poly(acrylic acid-co-maleic acid), and poly(methyl vinyl ether-alt-maleic acid) were synthesized using a one-pot polyol method. Their physicochemical and X-ray attenuation properties were characterized. All polymer-coated Pt-NPs had an average particle diameter (davg) of 2.0 nm. Polymers grafted onto Pt-NP surfaces exhibited excellent colloidal stability (i.e., no precipitation after synthesis for >1.5 years) and low cellular toxicity. The X-ray attenuation power of the polymer-coated Pt-NPs in aqueous media was stronger than that of the commercial iodine contrast agent Ultravist at the same atomic concentration and considerably stronger at the same number density, confirming their potential as computed tomography contrast agents.

157Gd (natural abundance = 15.7%) has the highest thermal neutron capture cross section (σ) of 254,000 barns (1 barn = 10–28 m2) among stable (nonradioactive) isotopes in the periodic table. Another stable isotope, 155Gd (natural abundance = 14.8%), also has a high σ value of 60,700 barns. These σ values are higher than that of 10B (3840 barns, natural abundance = 19.9%), which is currently used as a neutron-absorbing isotope for boron neutron capture therapy agents. Energetic particles such as electrons and γ-rays emitted from Gd-isotopes after neutron beam absorption kill cancer cells by damaging DNAs inside cancer-cell nuclei without damaging normal cells if Gd-chemicals are positioned in cancer cells. To date, various Gd-chemicals such as commercial Gd-chelates used as magnetic resonance imaging contrast agents, modified Gd-chelates, nanocomposites containing Gd-chelates, fullerenes containing Gd, and solid-state Gd-nanoparticles have been investigated as gadolinium neutron capture therapy (GdNCT) agents. All GdNCT agents had exhibited cancer-cell killing effects, and the degree of the effects depended on the GdNCT agents used. This confirms that GdNCT is a promising cancer therapeutic technique. However, the commercial Gd-chelates were observed to be inadequate in clinical use because of their low accumulation in cancer cells due to their extracellular and noncancer targeting properties and rapid excretion. The other GdNCT agents exhibited higher accumulation in cancer cells, compared to Gd-chelates; consequently, they demonstrated higher cancer-cell killing effects. However, they still displayed limitations such as poor specificity to cancer cells. Therefore, continuous efforts should be made to synthesize GdNCT agents suitable in clinical applications. Herein, the principle of GdNCT, current status of GdNCT agents, and general design strategy for GdNCT agents in clinical use are discussed and reviewed.

Recent progress in functionalized lanthanide oxide (Ln2O3) nanoparticles for tumor targeting, medical imaging, and therapy is reviewed. Among the medical imaging techniques, magnetic resonance imaging (MRI) is an important noninvasive imaging tool for tumor diagnosis due to its high spatial resolution and excellent imaging contrast, especially when contrast agents are used. However, commercially available low-molecular-weight MRI contrast agents exhibit several shortcomings, such as nonspecificity for the tissue of interest and rapid excretion in vivo. Recently, nanoparticle-based MRI contrast agents have become a hot research topic in biomedical imaging due to their high performance, easy surface functionalization, and low toxicity. Among them, functionalized Ln2O3 nanoparticles are applicable as MRI contrast agents for tumor-targeting and nontumor-targeting imaging and image-guided tumor therapy. Primarily, Gd2O3 nanoparticles have been intensively investigated as tumor-targeting T1 MRI contrast agents. T2 MRI is also possible due to the appreciable paramagnetic moments of Ln2O3 nanoparticles (Ln = Dy, Ho, and Tb) at room temperature arising from the nonzero orbital motion of 4f electrons. In addition, Ln2O3 nanoparticles are eligible as X-ray computed tomography contrast agents because of their high X-ray attenuation power. Since nanoparticle toxicity is of great concern, recent toxicity studies on Ln2O3 nanoparticles are also discussed.

Gadolinium (Gd) based contrast agents (CAs) (Gd-CAs) represent one of the most advanced developments in the application of Gd for magnetic resonance imaging (MRI). Current challenges with existing CAs generated an urgent requirement to develop multimodal CAs with good biocompatibility, low toxicity, and prolonged circulation time. This review discussed the Gd-CAs used in bioimaging applications, addressing their advantages and limitations. Future research is required to establish the safety, efficacy and theragnostic capabilities of Gd-CAs. Nevertheless, these Gd-CAs offer extraordinary potential as imaging CAs and promise to benefit bioimaging applications significantly.

We describe the synthesis, characterization, molecular modeling, and in vitro anticancer activity of three benzothiazole aniline (BTA) ligands and their corresponding platinum (II) complexes. We designed the compounds based on the selective antitumor properties of BTA, along with three types of metallic centers, aiming to take advantage of the distinctive and synergistic activity of the complexes to develop anticancer agents. The compounds were characterized using nuclear magnetic resonance spectrometry, Fourier transform infrared spectroscopy, mass spectrometry, elemental analysis, and tested for antiproliferative activity against multiple normal and cancerous cell lines. L1, L2, and L1Pt had better cytotoxicity in the liver, breast, lung, prostate, kidney, and brain cells than clinically used cisplatin. Especially, L1 and L1Pt demonstrated selective inhibitory activities against liver cancer cells. Therefore, these compounds can be a promising alternative to the present chemotherapy drugs.

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p

The aim of this study was to analyze the characteristics of time-velocity curve acquired by phase-contrast magnetic resonance imaging (PC-MRI) using an in-vitro flow model as a reference for hemodynamic studies. The time- velocity curves of the PC-MRI were compared with Doppler ultrasonography (US) and also compared with those obtained in the electromagnetic flowmeter. The correlation between techniques was analyzed using an electromagnetic flowmeter as a reference standard; the maximum, minimum, and average velocities, full-width at half-maximum (FWHM), and ascending gradient (AG) were measured from time-velocity curves. The correlations between an electromagnetic flowmeter and the respective measurement technique for the PC-MRI and Doppler US were found to be high (mean R2 > 0.9, p

Background Mixed reality (MR) technology, which combines the best features of augmented reality and virtual reality, has recently emerged as a promising tool in cognitive rehabilitation therapy. Objective To investigate the effectiveness of an MR-based cognitive training system for individuals with mild cognitive impairment (MCI). Methods Twenty-one individuals aged 65 years and older who had been diagnosed with MCI were recruited for this study and were divided into two groups. Participants in the MR group (n=10, aged 70.5±4.2 years) received 30 minutes of training 3 times a week for 6 weeks using a newly developed MR-based cognitive training system. Participants in the control group (n=11, aged 72.6±5.3 years) received the same amount of training using a conventional computer-assisted cognitive training system. Both groups took the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) both before and after intervention. To determine the effect of the intervention on cognitive function, we compared the difference in each group's CERAD-K scores. Results There was a statistically significant interaction between intervention (MR group vs control group) and time (before vs after intervention) as assessed by the Constructional Recall Test. The individuals with MCI who participated in the MR training showed significantly improved performance in visuospatial working memory compared with the individuals with MCI who participated in the conventional training. Conclusion An MR-based cognitive training system can be used as a cognitive training tool to improve visuospatial working memory in individuals with MCI.

To date, it is unknown whether the combination of Dy ions and superparamagnetic iron oxide (SPIO; Fe3O4) NPs can offer improved performance in UHF-MRI. In this work, we provide a paradigm of hierarchical surface-structured (His) DyxFe3-xO4 NPs as T2 MRI nanoprobes at UHF (9.4 T). We found that His-DyxFe3-xO4 NPs (x = 0.2) possess a higher transverse relaxivity than unmodified His-SPIO NPs and a significantly enhanced r2/r1 ratio (up to ˜10.4 times higher) than those of reported Dy-based T2 MRI probes at 9.4 T. Furthermore, we demonstrate the effects of surface design of DyxFe3-xO4 NPs on their magnetic relaxivity and in vivo performance at UHF. The markedly enhanced r2/r1 of His-DyxFe3-xO4 NPs (x = 0.2) at 9.4 T is mainly attributed to decreased r1 relaxivity owing to the surface design and the possible disturbance of the Dy-Fe superexchange interaction. This work could provide an insightful strategy for the design of lanthanide-doped magnetic nanosystems as potential T2 MRI nanoprobes in UHF.

Ultrasmall heavy metal oxide nanoparticles are potential candidate materials for X-ray computed tomography (CT) contrast agents because they possess high X-ray attenuation powers owing to high X-ray attenuation coefficients of heavy metal atoms and high density of heavy metal atoms per nanoparticle. In this study, five kinds of polyacrylic acid (PAA)-coated ultrasmall heavy metal oxide (Bi2O3, Yb2O3, NaTaO3, Dy2O3, and Gd2O3) nanoparticles were synthesized and their X-ray attenuation properties were investigated. The estimated average particle diameters were 2.3 ± 0.1, 1.7 ± 0.1, 1.5 ± 0.1, 1.8 ± 0.1, and 1.9 ± 0.1 nm for PAA-coated ultrasmall Bi2O3, Yb2O3, NaTaO3, Dy2O3, and Gd2O3 nanoparticles, respectively. All of the nanoparticle suspension samples exhibited a high colloidal stability, a high biocompatibility, and X-ray attenuation powers which were stronger than that of a commercial iodine contrast agent Ultravist® at the same atomic concentration and much stronger, at the same number density. The effectiveness of the nanoparticle suspension samples as CT contrast agents was demonstrated by acquiring in vivo CT images by using one of the samples (i.e., PAA-coated ultrasmall Bi2O3 nanoparticles). After intravenous injection into the mouse tail vein, positive contrast enhancements in various organs were observed.

Ultrasmall Gd2O3 nanoparticles can potentially be used as a positive magnetic resonance imaging (MRI) contrast agent owing to their high content of Gd(III), which exhibits the highest spin magnetic moment of all elements due to its seven unpaired 4f electrons. Herein, the above nanoparticles (average diameter = 2.0 nm) were coated with hydrophilic biocompatible polyacrylic acids (PAAs) of different molecular weights (Mw = 1200, 5100, 15000 Da), and the PAA-size-dependent relaxometric properties of the thus obtained composites were investigated. In addition, the biocompatibility of these composites was assessed by in-vitro cell viability measurements. Finally, dose-dependent R1 map images were acquired, proving that PAA-coated nanoparticles can be used as a T1 MRI contrast agent.

Ultrasmall heavy metal-oxide nanoparticles can be utilized for highly enhancing contrasts in computed tomography (CT). In this study, ultrasmall Yb2O3 nanoparticles coated with biocompatible and hydrophilic D-glucuronic acid were for the first time prepared through a simple one-step polyol process, and their X-ray attenuation properties were investigated by measuring phantom images and X-ray attenuation powers. The average particle diameter of the nanoparticles was estimated to be 2.1 ± 0.1 nm by using transmission electron microscopy. The observed X-ray attenuation power was stronger than that of a commercial iodine CT contrast agent (i.e., Ultravist®) at the same atomic concentration and much stronger at the same number density, proving the potential of ultrasmall Yb2O3 nanoparticles for use as a powerful CT contrast agent.

To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. In total, 106 children aged 4.7–18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87–0.98; r = 0.78–0.96; relative volume difference other than CSFV = 6.8–18.5% [SyMRI vs. SPM T1] and 11.3–22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78–0.91. The Bland–Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject’s age (p

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ -rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 μM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 104 cm−2 s−1, tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment.

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T2) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r1 values were negligible at all MR fields, indicating their exclusive induction of T2 relaxations with negligible induction of T1 relaxations. Their effectiveness as T2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T2 MR images at a 9.4 T MR field after intravenous administration into mice tails.

In this study, hydrophilic and biocompatible chitosan oligosaccharide lactate (COL)-coated ultra-small gadolinium oxide nanoparticles (NPs) were synthesized through a one-pot polyol method and characterized by various experimental techniques. The

Water proton spin relaxivities, colloidal stability, and biocompatibility of nanoparticle magnetic resonance imaging (MRI) contrast agents depend on surface-coating ligands. In this study, hydrophilic and biocompatible polyethylenimines (PEIs) of different sizes (Mn = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho2O3) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho2O3 nanoparticles, with an average particle diameter of 2.05 and 1.90 nm, respectively, demonstrated low cellular cytotoxicities, good colloidal stability, and appreciable transverse water proton spin relaxivities (r2) of 13.1 and 9.9 s−1mM−1, respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r1) (i.e., 0.1 s−1mM−1) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R1) and transverse (R2) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T2 MRI contrast agents in vitro.

The use of cancer-derived exosomes has been studied in several cancer types, but the cancer-targeting efficacy of glioma-derived exosomes has not been investigated in depth for malignant glioblastoma (GBM) cells. In this study, exosomes were derived from U87MG human glioblastoma cells, and selumetinib, a new anticancer drug, was loaded into the exosomes. We observed the tropism of GBM-derived exosomes in vitro and in vivo. We found that the tropism of GBM-derived exosomes is in contrast to the behavior of non-exosome-enveloped drugs and non-GBM-specific exosomes in vitro and in vivo in an animal GBM model. We found that the tropism exhibited by GBM-derived exosomes can be utilized to shuttle selumetinib, with no specific targeting moiety, to GBM tumor sites. Therefore, our findings indicated that GBM-derived exosomes loaded with selumetinib had a specific antitumor effect on U87MG cells and were non-toxic to normal brain cells. These exosomes offer improved therapeutic prospects for glioblastoma therapy.

Magnetic nanobeads can be applied to the magnetic separation of nucleic acids which can be used for diagnosing infectious and genetic diseases of patients. In this study, core-shell structured silica-coated iron oxide (Fe3O4@SiO2) nanobeads with a core size distribution of 40–50 nm and a shell thickness of ∼ 10 nm were synthesized and applied to the magnetic separation of nucleic acids from various biological samples such as cancer cells, viruses, and bacteria. The iron oxide core provided strong superparamagnetic properties with a high saturation magnetization suitable for magnetic separation, and the silica shell provided binding surfaces for nucleic acids. The Fe3O4@SiO2 nanobeads showed the successful magnetic separation performance for all samples.

BackgroundCognitive theories of obsessive–compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients.MethodsForty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements.ResultsThe conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex–insula FC was correlated with TAF and responsibility scores.ConclusionsOur TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.