Changes in brain functional network connectivity after stroke

Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.

Apparent diffusion coefficient evaluation for secondary changes in the cerebellum of rats after middle cerebral artery occlusion

Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffu- sion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially in- creased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion co- efficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions （cerebellum） varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis.

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.

Facile synthesis of magnetic-plasmonic nanocomposites as T1 MRI contrast enhancing and photothermal therapeutic agents

Nanocomposites combining magnetic and plasmonic components have received widespread attention in recent years due to their potential applications in biomedical research. Herein, we describe a facile method for growing small iron oxide nanoparticles on various plasmonic core materials with different shapes and surfaces by utilizing a polypyrrole interlayer. By focusing on Au nanorod@polypyrrole@iron oxide （Au NR@PPy@FexO） nanocomposites, we show that these systems exhibit a low r2/rl ratio of 4.8, making them efficient T1 positive contrast-enhancing agents for magnetic resonance imaging （MRI）. Moreover, we show that the nanocomposites are excellent photothermal agents in the second near infrared region, with high photothermal conversion efficiency, reaching up to 46%. In addition, the Au NR@PPy@FexO nanocomposites show very low cytotoxicity. In summary, the present results highlight the great potential of the synthetic method and the nanocomposites developed in this study for T~ MRI and/or infrared thermal imaging-guided photothermal cancer therapeutic applications.

Catalase-imprinted Fe3O4/Fe@fibrous SiO2/polydopamine nanoparticles： An integrated nanoplatform of magnetic targeting, magnetic resonance imaging, and dual-mode cancer therapy

Recent advances in the research on the molecular mechanism of cell death and methods for preparation of nanomaterials make the integration of various therapeutic approaches, targeting, and imaging modes into a single nanoscale complex a new trend for the development of future nanotherapeutics. Hence, a novel ellipsoidal composite nanoplatform composed of a magnetic Fe3O4/Fe nanorod core （-120 nm） enwrapped by a catalase （CAT）-imprinted fibrous SiO2/ polydopamine （F-SiO2/PDA） shell with thickness 70 nm was prepared in this work. In vitro experiments showed that the Fe3O4/Fe@F-SiO2/PDA nanoparticles can selectively inhibit the bioactivity of CAT in tumor cells by the molecular imprinting technique. As a result, the H2O2 level in tumor cells was elevated dramatically. At the same time, the Fe304FFe core released Fe ions to catalyze the conversion of H2O2 to ＊OH in tumor cells. Eventually, the concentration of ＊OH in tumor cells rapidly rose to a lethal level thus triggering apoptosis. Combined with the remarkable near-infrared light （NIR） photothermal effect of the CAT- imprinted PDA layer, the Fe3O4/Fe@F-SiO2/PDA nanoparticles can effectively kill MCF-7, HeLa, and 293T tumor cells but are not toxic to nontumor cells. Furthermore, these nanoparticles show good capacity for magnetic targeting and suitability for magnetic resonance imaging （MRI）. Therefore, the integrated multifunctional nanoplatform opens up new possibilities for high-efficiency visual targeted nonchemo therapy for cancer.

Abnormal functional connectivity with mood regulating circuit in unmedicated individual with major depression： a resting-state functional magnetic resonance study

Background Reports on mood regulating circuit （MRC） indicated different activities between depressed patients and healthy controls. The functional networks based on MRC have not been described in major depression disorder （MDD）. Both the anterior cingulate cortex （ACC） and thalamus are all the key regions of MRC. This study was to investigate the two functional networks related to ACC and thalamus in MDD. Methods Sixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging （fMRI） during resting-state. The pregenual anterior cingulate cortex （pgACC） was used as seed region to construct the functional network by cortex section. The thalamus was used as seed region to construct the functional network by limbic section. Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2. Results Depressed subjects exhibited significantly great functional connectivity （FC） between pgACC and the parahippocampus gyrus in one cluster （size 923） including left parahippocampus gyrus （-21, -49,7）, left parietal lobe （-3, -46, 52） and left frontal lobe （-27, -46, 28）. The one cluster （size 962） of increased FC on thalamus network overlapped the precuneus near to right parietal lobe （9, -52,46） and right cingulate gyrus （15, -43, 43） in health controls. Conclusions Abnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections. The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

Precise synthesis of discrete and dispersible carbon- protected magnetic nanoparticles for efficient magnetic resonance imaging and photothermal therapy

Carbon-protected magnetic nanoparticles exhibit long-term stability in acid or alkaline medium, good biocompatibility, and high saturation magnetization. As a result, they hold great promise for magnetic resonance imaging, photothermal therapy, etc. However, since pyrolysis, which is often required to convert the carbon precursors to carbon, typically leads to coalescence of the nanoparticles, the obtained carbon-protected magnetic nanoparticles are usually sintered as a non-dispersible aggregation. We have successfully synthesized discrete, dispersible, and uniform carbon-protected magnetic nanoparticles via a precise surface/interface nano-engineering approach. Remarkably, the nanoparticles possess excellent water-dispersibility, biocompatibility, a high T2 relaxivity coefficient （384 mM^-1·s^-1）, and a high photothermal heating effect. Furthermore, they can be used as multifunctional core components suited for future extended investigation in early diagnosis, detection and therapy, catalysis, separation, and magnetism.

Acid-degradable gadolinium-based nanoscale coordination polymer： A potential platform for targeted drug delivery and potential magnetic resonance imaging

During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium- doxorubicin-loaded nanoscale coordination polymer （Gd-Dox NCPs） was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma （HeLa） cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and ＂turned on＂T1 signals in vitro, showing great promise for diagnosis and treatment.

Single ultrasmall Mn2＋-doped NaNdF4 nanocrystals as multimodal nanoprobes for magnetic resonance and second near-infrared fluorescence imaging

Multimodal imaging probes have attracted wide attention and have potential to diagnose diseases accurately because of the complementary advantages of multiple imaging modalities. However, intractable issues remain with regard to their complicated multi-step fabrication for hybrid nanostructure and interference of different modal imaging. In the present stud we present, for the first time, T1 and T2-weighted magnetic resonance imaging （MRI） of ultrasmaU Mn2＋-doped NaNdF4 nanocrystals （NCs）, which can also be used simultaneously for second near infrared （NIR-U） fluorescence and computed tomography （CT） imaging, thus enabling high-performance multimodal MRI/NIR-II/CT imaging of single NaNdF4：Mn NCs. The NaNdF4：Mn was demonstrated as a nanoprobe for in vitro and in vivo multimodal MRI and NIR-II fluorescence imaging of human mesenchymal stem cells. The results provide a new strategy to simplify the nanostructure and preparation of probes, based on the features of NaNdF4：Mn NCs, which offer highly efficient multimodal MRI/NIR-II/CT imaging.

Positively charged graphene/Fe3O4/polyethylenimine with enhanced drug loading and cellular uptake for magnetic resonance imaging and magnet-responsive cancer therapy

Enhanced cellular uptake efficiency of nanoparticles is important for their biomedical applications, including photothermal therapy （PTT） for cancer. In this study, a one-pot method was used to construct a positively charged and magnet-responsive nanocomposite comprising reduced graphene oxide anchoring iron oxide （RGI） with a polyethylenimine （PEI） modification, to improve the efficiency of cell internalization. The surface charge can be finely tuned using PEIs of different molecular weights. The obtained RGIlsk composite （RGI modified by 1.8 kDa PEI） could load indocyanine green （ICG） at a high mass ratio of 10：3 and ablate cancer cells using low-density laser irradiation because of its positively charged surface. In addition, the hybrids of RGI1.8k and ICG could kill most cancer cells at a laser density of 0.7 W/cm2 in vitro and 0.3 W/cm2 in vivo. At the same time, cell viability could be controlled by converting the external magnetic-field direction because of the enrichment of the magnet-responsive composite in vitro and in vivo. Furthermore, RGIr8k-ICGs could be used as T2-weighted magnetic resonance and infrared thermal imaging agents. Coupled with the magnetic target effect, the imaging signal could be improved significantly. Therefore, RGII^sk-ICGs represent a new highly efficient PTT and imaging agent with great potential for cancer treatment.

Intravascular contrast agents in diagnostic applications： Use of red blood cells to improve the lifespan and efficacy of blood pool contrast agents

In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents （CAs） available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells （RBCs） as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.

Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells

Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient （LDLR^-/-） mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy （TEM） at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TEM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. Experiments with endocytosis inhibitors and small interfering RNA （siRNA） revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.