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Background Chronic migraine (CM) is a common and disabling neurological disorder that affects 1-2% of the global population. The aim of the present study was to identify the functional characteristics of the CM brain using static functional connectivity (s-FC), static functional network connectivity (s-FNC), and dynamic functional network connectivity (d-FNC) analyses. Methods In the present study, 17 CM patients and 20 sex- and age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We utilized independent component (IC) analysis to identify 13 ICs. These 13 ICs were then classified into the following 6 resting-state networks (RSNs): the default mode network (DMN), executive control network (ECN), dorsal attention network, auditory network (AN), visual network (VN), and cerebellum network. Subsequently, s-FC, s-FNC, and d-FNC analyses of 13 ICs were employed for between-group comparisons. Three temporal metrics (fraction of time spent, mean dwell time, and number of transitions), which were derived from the state-transition vector, were calculated for group comparisons. In addition, correlation analyses were performed between these dynamic metrics and clinical characteristics [mean visual analog scale (VAS) scores, days with headache per month, days with migraine pain feature per month, and disease duration]. Results In the comparison of s-FC of 13 ICs within RSNs between the CM and HC groups, increased connectivity was observed in the left angular gyrus (Angular_L) of the ECN (IC 2) and the right superior parietal gyrus (Parietal_Sup_R) of the AN (IC 5), and reduced connectivity was found in the left superior frontal gyrus (Frontal_Sup_2_L) of the AN (IC 5) and DMN (IC 19), the right calcarine sulcus (Calcarine_R) of the VN (IC 7), and the left precuneus (Precuneus_L) of the DMN (IC 17) in CM patients. In the comparison of the d-FNC of 13 IC pairs within RSNs between the two groups, the CM group exhibited significantly decreased connections between the DMN (IC 11) and AN (IC 5), and increased connections between the ECN (IC 2, IC 4) and DMN (IC 19), ECN (IC 4) and AN (IC 5), and ECN (IC 4) and VN (IC 13) in state 1. However, no significant differences in s-FNC were observed between the two groups during the s-FNC analysis. Between-group comparisons of three dynamic metrics between the CM and HC groups showed a longer fraction of time spent and mean dwell time in state 2 for CM patients. Furthermore, from the correlation analyses between these metrics and clinical characteristics, we observed a significant positive correlation between the number of transitions and mean VAS scores. Conclusions Our findings suggest that functional features of the CM brain may fluctuate over time instead of remaining static, and provide further evidence that migraine chronification may be related to abnormal pattern connectivity between sensory and cognitive brain networks.

Hydrocephalus is often treated with a cerebrospinal fluid shunt (CFS) for excessive amounts of cerebrospinal fluid in the brain. However, it is very difficult to distinguish whether the ventricular enlargement is due to hydrocephalus or other causes, such as brain atrophy after brain damage and surgery. The non-trivial evaluation of the consciousness level, along with a continuous drainage test of the lumbar cistern is thus clinically important before the decision for CFS is made. We studied 32 secondary mild hydrocephalus patients with different consciousness levels, who received T1 and diffusion tensor imaging magnetic resonance scans before and after lumbar cerebrospinal fluid drainage. We applied a novel machine-learning method to find the most discriminative features from the multi-modal neuroimages. Then, we built a regression model to regress the JFK Coma Recovery Scale-Revised (CRS-R) scores to quantify the level of consciousness. The experimental results showed that our method not only approximated the CRS-R scores but also tracked the temporal changes in individual patients. The regression model has high potential for the evaluation of consciousness in clinical practice.

Gait disturbance is considered to be a significant clinical manifestation of cerebral small vessel disease (CSVD). We aimed to investigate the association between different imaging markers of CSVD or total CSVD burden and gait disturbance in a community-dwelling population. In the cross-sectional Taizhou Imaging Study (TIS), 314 participants free of neurological disorders underwent MRI scanning and gait assessment with quantitative wearable devices as well as clinical rating scales. In linear regression, after adjustment for demographics and vascular risks, total CSVD burden was associated with prolonged 3-m walking (β=0.118, P=0.035), shorter stride length (β=-0.106, P=0.042), and poorer Timed-Up-and-Go (TUG) performance (β=0.146, P=0.009). Lacunes were positively associated with 3-m walking (β=0.118, P=0.037) and duration of TUG test (β=0.112, P=0.047). White matter hyperintensities and cerebral microbleeds were associated with prolonged stride time (β=0.134, P=0.024) and increased stance phase time percentage (β=0.115, P=0.038), respectively. Logistic regression revealed that participants with high CSVD burden or more lacunes were more likely to have an impaired gait velocity and an impaired TUG test. These results suggest that total CSVD burden and CSVD imaging markers are associated with gait disturbance among community-dwelling elderly people. Different CSVD imaging markers may cause gait disturbance through different pathways.

Objectives: To investigate how PM2.5 exposure affects the microstructure, metabolites or functions of the visual system. Methods: C57BL/6J mice were randomly assigned to groups exposed to the filtered air (the control group) or the concentrated ambient PM2.5 (the PM2.5 group). Visual evoked potentials (VEP), electroretinograms (ERG), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting-state functional MRI (rsfMRI) were performed. Parameters were obtained and compared between the two groups, including latencies and amplitudes of the P1 wave, N1 wave and P2 wave from VEP, latencies and amplitudes of the a wave and b wave from ERG, fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) from DTI, visual cortex (VC) metabolites from 1H-MRS, and regional homogeneity (ReHo) from rsfMRI. Results: Compared with the values of the control group, the PM2.5 group showed a prolonged N1 latency (43.11 ± 7.94 ms vs. 38.75 ± 4.60 ms) and lowered P1 amplitude (5.62 ± 4.38 μV vs. 8.56 ± 5.92 μV) on VEP (all p

Background To assess heart rate variability (HRV) among patients with arteriosclerotic cerebral small vessel disease (CSVD) by comparing with control subjects, and to determine whether HRV parameters were related to structural alterations in brain regions involved in autonomic regulation among CSVD patients. Methods We consecutively recruited subjects aged between 50 and 80 years who visited the Stroke Prevention Clinic of our hospital and have completed brain magnetic resonance imaging examination from September 1, 2018 to August 31, 2019. Polysomnography and synchronous analyses of HRV were then performed in all participants. Multivariable binary logistic regression was used to identify the relationship between HRV parameters and CSVD. Participants were invited to further undergo three-dimensional brain volume scan, and the voxel based morphometry (VBM) analysis was used to identify gray matter atrophy. Results Among 109 participants enrolled in this study, 63 were assigned to the arteriosclerotic CSVD group and 46 to the control group. Lower standard deviation of normal-to-normal intervals (SDNN, OR = 0.943, 95% CI 0.903 to 0.985, P = 0.009) and higher ratio of low to high frequency power (LF/HF, OR = 4.372, 95% CI 1.033 to 18.508, P = 0.045) during the sleep period were associated with CSVD, independent of traditional cerebrovascular risk factors and sleep disordered breathing. A number of 24 CSVD patients and 21 controls further underwent three-dimensional brain volume scan and VBM analysis. Based on VBM results, SDNN during the awake time (β = 0.544, 95% CI 0.211 to 0.877, P = 0.001) and the sleep period (β = 0.532, 95% CI 0.202 to 0.862, P = 0.001) were both positively related with gray matter volume within the right inferior frontal gyrus only among CSVD patients. Conclusions Decreased nocturnal HRV is associated with arteriosclerotic CSVD independent of traditional cerebrovascular risk factors and sleep disordered breathing. The structural atrophy of some brain regions associated with cardiac autonomic regulation sheds light on the potential relationship. Trial registration Trial registration number: ChiCTR1800017902. Date of registration: 20 Aug 2018.

BackgroundLittle is known about the specificity of manganese-enhanced magnetic resonance imaging (MEMRI) and its neurotoxic effect of the whole visual pathway.PurposeTo explore the specificity of M...

Background Impaired neurodevelopment of children has become a growing public concern; however, the associations between metals exposure and neurocognitive function have remained largely unknown. Objectives We systematically evaluated the associations of multiple metals exposure during pregnancy and childhood on the neurodevelopment of children aged 2–3 years. Methods We measured 22 metals in the serum and urine among703 mother-child pairs from the Guangxi Birth Cohort Study. The neurocognitive development of children was assessed by the Gesell Development Diagnosis Scale (GDDS; Chinese version). Multiple linear regression models were used to evaluate the relationship between the metals (selected by elastic net regression) and the outcomes. The Bayesian kernel machine regression (BKMR) was used to evaluate the possible joint effect between the multiple metal mixture and the outcomes. Results Prenatal aluminum (Al) exposure was negatively associated with the fine motor developmental quotient (DQ) (β = −1.545, 95%CI: 2.231, −0.859), adaption DQ (β = −1.182, 95%CI: 1.632, −0.732), language DQ (β = −1.284, 95% CI: 1.758, −0.809), and social DQ (β = −1.729, 95% CI: 2.406, −1.052) in the multi-metal model. Prenatal cadmium (Cd) exposure was negatively associated with gross motor DQ (β = −2.524, 95% CI: 4.060, −0.988), while postpartum Cd exposure was negatively associated with language DQ (β = −1.678, 95% CI: 3.227, −0.129). In stratified analyses, infants of different sexes had different sensitivities to metal exposure, and neurobehavioral development was more significantly affected by metal exposure in the first and second trimester. BKMR analysis revealed a negative joint effect of the Al, Cd, and selenium (Se) on the language DQ score; postpartum Cd exposure played a major role in this relationship. Conclusion Prenatal exposure to Al, Ba, Cd, molybdenum (Mo), lead (Pb), antimony (Sb), and strontium (Sr), and postpartum exposure to cobalt (Co), Cd, stannum (Sn), iron (Fe), nickel (Ni), and Se are associated with neurological development of infants. The first and second trimester might be the most sensitive period when metal exposure affects neurodevelopment.

The neural correlates of consciousness, defined as the minimum neuronal mechanisms sufficient for any conscious percept, are usually subject to different interpretations depending on whether one uses measures of local or global brain activities. We argue that the local regions may support consciousness by serving as hubs within the brain’s global network. We adopt a unique functional magnetic resonance imaging resting state dataset that encompasses various conscious states, including non-rapid eye movement (NREM)-sleep, rapid eye movement (REM)-sleep, anesthesia, and brain injury patients. Using a graph-theoretical measure for detecting local hubs within the brain’s global network, we identify various higher-order sensory and motor regions as hubs with significantly reduced degree centrality during unconsciousness. Additionally, these regions form a sensorimotor circuit which correlates with levels of consciousness. Our findings suggest that integration of higher-order sensorimotor function may be a key mechanism of consciousness. This opens novel perspectives for therapeutic modulation of unconsciousness.

Polylactic acid (PLA) nanoparticles coated with Gd(III)-based metallosurfactants (MS) are prepared using a simple and rapid one-step method, flash nanoprecipitation (FNP), for magnetic resonance imaging (MRI) applications. By co-assembling the Gd(III)-based MS and an amphiphilic polymer, methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone) (mPEG-b-PCL), PLA cores were rapidly encapsulated to form biocompatible T1 contrast agents with tunable particle size and narrow size distribution. The hydrophobic property of Gd(III)-based MS were finely tuned to achieve their high loading efficiency. The size of the nanoparticles was easily controlled by tuning the stream velocity, Reynolds number and the amount of the amphiphilic block copolymer during the FNP process. Under the optimized condition, the relaxivity of the nanoparticles was achieved up to 35.39 mM-1 s-1 (at 1.5 T), which is over 8 times of clinically used MRI contrast agents, demonstrating the potential application for MR imaging.

Background: 18 F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients. Methods: The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static 18 F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated. Results: Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms. Conclusions: This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.

Context Chronic excess of growth hormone (GH) often leads to systemic complications. The reversibility of these complications after GH resolution is not fully understood. Objective To investigate when and to what extent will the comorbidities be ameliorated. Design We conducted a prospective study comprising 24 patients with acromegaly, who achieved remission after transsphenoidal surgery. The dynamic changes of endocrine, cardiovascular, respiratory, sleep, bone and morphology parameters were evaluated at enrollment and 1 week, 1 month, 3 months, 6 months and 12 months after surgery. Results Random GH dropped by 98.4% at the first day postoperatively. IGF-I index dropped by 50% and 64% at 1 week and 1 month respectively and remained unchanged onwards. Glucose metabolism improved significantly at 1 week and stabilized at 1 month. Testosterone in male patients recovered to normal range since 1 month. Systolic blood pressures dropped markedly at 3 months while diastolic blood pressures fell mildly at later visits. Abnormal lung function showed no improvement. The decrease of bone formation and resorption markers occurred at 1 week and 3 months, respectively. At 1 month, the tongue area declined while the airway volume increased significantly, accompanied with improved obstructive sleep apnea syndrome. Extremities, lips and nasal ala became smaller since 1 week. Liver, kidney and spleen volumes declined by 6.4, 15.9, 9.2%, respectively at 1 month. The volumes of pancreas and adrenal showed no change. Conclusions The rapid resolution of excessive GH led to the reversible changes of systemic comorbidities in a time-dependent and organ-specific manner.

ObjectiveTo explore the value of plasma fibrillin-1 levels in patients with spontaneous cerebral artery dissection (sCeAD).MethodsA single-center prospective cohort of 99 consecutive patients with sCeAD between February 2013 and December 2015 were age and sex matched with 115 patients with non-sCeAD ischemic stroke and 20 healthy participants undergoing routine physical examination. The plasma fibrillin-1 level was measured with ELISA and compared among the 3 groups. The associations of fibrillin-1 with site, acuity, and severity of dissection, as well as clinical and radiographic prognosis of patients, were analyzed.ResultsOne hundred nine plasma samples from 99 patients with sCeAD, 115 from disease control patients, and 20 from healthy participants were collected. The plasma fibrillin-1 level of the dissection group (mean 85.56 ng/mL [95% confidence interval 81.53–89.59]) was higher than that of non-sCeAD ischemic stroke group (77.13 ng/mL [73.64–80.63], p = 0.015) or healthy controls (73.04 ng/mL [65.94–80.13], p = 0.029). Such differences were most prominent in the acute stage (97.64 ng/mL [91.64–103.64], 74.39 ng/mL [68.95–79.84], and 73.04 ng/mL [65.95–80.13], respectively). A cutoff value of 88.455 ng/mL was determined to differentiate acute dissection from nondissection stroke with a sensitivity of 0.778 and a specificity of 0.800. Higher fibrillin-1 level was detected in patients with more severe dissection radiographically (p < 0.001), while patients with lower fibrillin-1 concentration at baseline achieved better morphologic recovery on follow-up imaging tests (p = 0.003).ConclusionPlasma fibrillin-1 is a promising biomarker for aiding the diagnosis of acute sCeAD and may have potential value in lesion severity grading and radiographic prognosis prediction.Classification of evidenceThis study provides Class III evidence that patients with sCeAD have significantly higher levels of plasma fibrillin-1 than patients with ischemic stroke attributable to a cause other than sCeAD.

Objective Functional magnetic resonance imaging (fMRI) analysis of the effects of acupuncturing the Tongli (HT5) and Tongli (HT5)–Xuanzhong (GB39) acupoints on the normal language areas with a view to providing a theoretical basis for using acupuncture to treat patients with aphasia. Methods This study enrolled healthy volunteers. The following acupoints were stimulated: right Tongli (HT5), right Tongli (HT5)–Xuanzhong (GB39), right Tongli (HT5) sham acupuncture, left Tongli (HT5), and left Tongli (HT5)–Xuanzhong (GB39) acupoints. Acupuncture stimulation was delivered whilst fMRI scanning of the brain was undertaken. Results Ten healthy volunteers (five males) were included in this study (mean age 44.5 ± 2.5 years; range 40–55 years). Based on the statistical analyses, only acupuncturing the right Tongli (HT5) acupoint resulted in activation of multiple regions of the bilateral cerebral hemisphere that were closely related to the language regions. The right Tongli (HT5) stimulation had a laterality index of 0.0952; with the activated voxels on the left side language-related areas being greater than those on the right side. Conclusions Acupuncturing the right Tongli (HT5) acupoint results in activation of the bilateral language-related areas, so this acupoint might be useful for the acupuncture treatment of aphasia caused by cerebral infarction.

Background In our previous studies, the rapid diagnosis of aneuploidy has been achieved using the segmental duplication molecular markers-based SD-QF-PCR technique. However, it is also insufficient due to the drawbacks including less detection loci and incompetence in single-tube detection. Methods In this paper, we developed 13 new segmental duplications as molecular markers, as well as designed 13 pairs of primers and 1 fluorescence-labeled universal primer, which could detect chromosome aneuploidies in one PCR tube. Results Two hundred and thirty samples were detected using SD-QF-PCR, the samples were collected from individuals with trisomy 21 (n = 16); trisomy 18 (n = 4); trisomy 13 (n = 3); 45,X (n = 3); 47,XXY (n = 2); 47,XYY (n = 2); suspected mosaic 46,XX/46,XY (n = 2); and unaffected controls (n = 198). Conclusions The detection results of SD-QF-PCR were consistent with those of conventional karyotype analysis. SD-QF-PCR based on the newly developed segmental duplications enables the single-tube and multi-locus simultaneous detection on the number of chromosomes 13, 18, 21, X and Y. Therefore, this technique offers a new alternative for the diagnosis of chromosome aneuploidies.

Some studies have used diffusion tensor imaging (DTI) to investigate white matter development of the visual pathway in humans and animals after visual deprivation. However, the alterations in the bilateral optic tract after the transection of unilateral optic nerve have not been well explored. In this study, we attempted to investigate the structural integrity of and pathological changes to the bilateral optic tract after transection of the unilateral optic nerve in rats using DTI. Eight healthy male Sprague-Dawley (SD) rats were randomly divided into 2 groups, with 4 in each group. Group A served as a control group. Transection of the unilateral (right) optic nerve was performed in the four rats in group B at seven days after birth to establish the early monocular blind model. Four months after the operation, MnCl2 was injected into the left eyes of all rats, and MRI examinations were performed 24h after injection. We detect the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values of the bilateral optic tract in all rats. In a comparison of the ipsilateral optic tract of group B with group A, a significant decrease in FA (P

Yingchan Wang,1 Weijun Tang,2 Xiaoduo Fan,3 Jianye Zhang,1 Daoying Geng,2 Kaida Jiang,1 Dianming Zhu,1 Zhenhua Song,1 Zeping Xiao,1 Dengtang Liu1 1First-Episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 2Department of Radiology, Huashan Hospital, Fu Dan University, Shanghai, People’s Republic of China; 3Psychotic Disorders Program, UMass Memorial Medical Center, UMass Medical School, Worcester, MA, USA Objective: Abnormal resting-state functional connectivity (FC), particularly in the default mode network (DMN) and the salience network (SN), has been reported in schizophrenia, but little is known about the effects of antipsychotics on these networks. The purpose of this study was to examine the effects of atypical antipsychotics on DMN and SN and the relationship between these effects and symptom improvement in patients with schizophrenia.Methods: This was a prospective study of 33 patients diagnosed with schizophrenia and treated with antipsychotics at Shanghai Mental Health Center. Thirty-three healthy controls matched for age and gender were recruited. All subjects underwent functional magnetic resonance imaging (fMRI). Healthy controls were scanned only once; patients were scanned before and after 6–8weeks of treatment.Results: In the DMN, the patients exhibited increased FC after treatment in the right superior temporal gyrus, right medial frontal gyrus, and left superior frontal gyrus and decreased FC in the right posterior cingulate/precuneus (P

Induced pluripotent stem cells (iPS cells) are promising cell source for stem cell replacement strategy applied to brain injury caused by traumatic brain injury (TBI) or stroke. Neural stem cell (NSCs) derived from iPS cells could aid the reconstruction of brain tissue and the restoration of brain function. However, tracing the fate of iPS cells in the host brain is still a challenge. In our study, iPS cells were derived from skin fibroblasts using the four classic factors Oct4, Sox2, Myc, and Klf4. These iPS cells were then induced to differentiate into NSCs, which were incubated with superparamagnetic iron oxides (SPIOs) in vitro. Next, 30 TBI rat models were prepared and divided into three groups ( n = 10). One week after brain injury, group A&B rats received implantation of NSCs (labeled with SPIOs), while group C rats received implantation of non-labeled NSCs. After cell implantation, all rats underwent T2*-weighted magnetic resonance imaging (MRI) scan at day 1, and 1 week to 4 weeks, to track the distribution of NSCs in rats’ brains. One month after cell implantation, manganese-enhanced MRI (ME-MRI) scan was performed for all rats. In group B, diltiazem was infused during the ME-MRI scan period. We found that (1) iPS cells were successfully derived from skin fibroblasts using the four classic factors Oct4, Sox2, Myc, and Klf4, expressing typical antigens including SSEA4, Oct4, Sox2, and Nanog; (2) iPS cells were induced to differentiate into NSCs, which could express Nestin and differentiate into neural cells and glial cells; (3) NSCs were incubated with SPIOs overnight, and Prussian blue staining showed intracellular particles; (4) after cell implantation, T2*-weighted MRI scan showed these implanted NSCs could migrate to the injury area in chronological order; (5) the subsequent ME-MRI scan detected NSCs function, which could be blocked by diltiazem. In conclusion, using an in vivo MRI tracking technique to trace the fate of iPS cells-induced NSCs in host brain is feasible.

Background Early improvement (EI) following treatment with antidepressants is a widely reported predictor to the treatment response. This study aimed to identify the resting-state functional connectivity (rs-FC) and its related clinical features that link the treatment response at the time of EI. Methods This study included 23 first-episode treatment-naive patients with MDD. After 2 weeks of antidepressant treatment, these patients received 3.0 Tesla resting-state functional magnetic resonance imaging scanning and were subgrouped into an EI group (N = 13) and a non-EI group (N = 10). Using the anterior insula (rAI) as a seed region, this study identified the rs-FC that were associated with both EI and the treatment response at week 12, and further tested the associations of the identified rs-FC with either the clinical features or the early symptom improvement. Results Rs-FC between rAI and the left dorsolateral prefrontal cortex (dlPFC) was associated with EI (t21 = −6.091, p = 0.022 after FDR correction for multiple comparisons). This rs-FC was also associated with an interaction between EI and the treatment response at the week 12 (t21 = −5.361, p = 6.37e-5). Moreover, among the clinical features, this rs-FC was associated with the early symptom improvement in the insomnia, somatic symptoms, and anxiety symptoms, and these early symptom improvements were associated with the treatment response. Conclusion Rs-FC between the rAI and the left dlPFC played a crucial role in the early antidepressant effect, which linked the treatment response. The early treatment effect relating to rAI may represent an early symptom improvement in self-perceptual anxiety, somatic symptoms and insomnia.

Consciousness is a mental characteristic of the human mind, whose exact neural features remain unclear. We aimed to identify the critical nodes within the brain's global functional network that support consciousness. To that end, we collected a large fMRI resting state dataset with subjects in at least one of the following three consciousness states: preserved (including the healthy awake state, and patients with a brain injury history (BI) that is fully conscious), reduced (including the N1-sleep state, and minimally conscious state), and lost (including the N3-sleep state, anesthesia, and unresponsive wakefulness state). We also included a unique dataset of subjects in rapid eye movement sleep state (REM-sleep) to test for the presence of consciousness with minimum movements and sensory input. To identify critical nodes, i.e., hubs, within the brain's global functional network, we used a graph-theoretical measure of degree centrality conjoined with ROI-based functional connectivity. Using these methods, we identified various higher-order sensory and motor regions including the supplementary motor area, bilateral supramarginal gyrus (part of inferior parietal lobule), supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus, that could be important hubs whose degree centrality was significantly reduced when consciousness was reduced or absent. Additionally, we identified a sensorimotor circuit, in which the functional connectivity among these regions was significantly correlated with levels of consciousness across the different groups, and remained present in the REM-sleep group. Taken together, we demonstrated that regions forming a higher-order sensorimotor integration circuit are involved in supporting consciousness within the brain's global functional network. That offers novel and more mechanism-guided treatment targets for disorders of consciousness.

Complexes of gadolinium(iii) have proven to be especially effective magnetic resonance imaging (MRI) contrast agents. One essential strategy to achieve more sensitive small-molecule gadolinium-based MRI contrast agents is to increase the hydration number q in order to improve the relaxivity. In this work, a series of diethylenetriamine-N-oxide pentaacetic acid-bisamide-based Gd(iii) complexes with 3 coordinated water molecules have been synthesized, in which the hydration numbers are verified by luminescence measurements. Relaxivities of all the complexes are about triple of those commercial MRI contrast agents, ranging from 12.5 to 18.8 mM-1 s-1 (1.5 T; 25 °C). The formation constants of the Gd(iii) complexes were calculated from potentiometric titration data at 25 °C using the HYPERQUAD program, which demonstrate superior stability over the commercial MRI contrast agent Gd-DTPA-BMA (Omniscan®). The kinetic inertness of the complexes was also higher than Omniscan® and comparable to another commercial MRI contrast agent Gd-DTPA (Magnevist®). Meanwhile, the viability of HeLa cells remained unaffected after the exposure to the complexes. The efficacy of these complexes as potential positive contrast agents in MRI was further evaluated using in vivo studies, and the complexes were found to exhibit superb positive contrast.

Objective. To determine whether and how longitudinal acupuncture modulates the impaired default mode network (DMN) in chronic migraine (CM) patients without aura. Methods. Resting-state functional magnetic resonance imaging (fMRI) data from 14 CM patients treated with longitudinal pre- and postacupuncture treatment (PPAT) and data of 18 age- and gender-matched healthy controls (HCs) were analyzed using independent component analysis (ICA) and seed-based correlation analysis (SCA) to investigate connectivity within the DMN. Correlation analyses were performed to identify associations between changes in functional connectivity (FC) and in clinical pain based on PPAT observations. The monthly mean visual analog scale (VAS) scores, monthly mean headache attacks, monthly headache days, monthly amount of acute headache medications, and immediate VAS scores were assessed for evaluation of pain. Results. The decreased FC within the DMN found in the left superior prefrontal gyrus (L_SPFG) and left precuneus (L_PRECUN) of CM patients was returned to the healthy control level after acupuncture treatments. Furthermore, the diminished pairwise FC strengths in some regions of interest (ROIs) within the DMN were also increased, mainly distributed between the right temporal lobe (R_TPL) and left anterior cingulate cortex, between the R_TPL and bilateral superior medial gyrus, and between the R_TPL and right precuneus. Increased z-scores within the DMN (L_SPFG and L_PRECUN) were associated with reduced immediate VAS scores, and increases in z-scores of the L_PRECUN were negatively correlated with reductions in the monthly amount of acute headache medications. However, no association existed between the increased DMN connectivity and reduced monthly mean VAS scores, monthly mean headache attacks, and monthly headache days. Conclusion. Altered DMN connectivity and its normalization postacupuncture can be employed to monitor CM and its modulating effects. The DMN is useful for understanding the therapeutic mechanisms of acupuncture in CM.

Background Cerebral microbleeds (CMBs) are considered to be risk factors for cognitive dysfunction. The specific pathology and clinical manifestations of CMBs are different based on their locations. We investigated the association between CMBs at different locations and cognitive dysfunction and explored the potential underlying pathways in a rural Han Chinese population. Methods We used baseline data from 562 community-dwelling adults (55–65 years old) in the Taizhou Imaging Study between 2013 and 2015. All individuals underwent multimodal brain magnetic resonance imaging (MRI) and 444 subjects completed neuropsychological tests: the Mini-Mental Status Examination and the Montreal Cognitive Assessment. Multinomial logistic regression was used to estimate the association between CMBs and cognitive dysfunction. The volume of brain regions and white matter microstructure were analyzed using Freesurfer and tract-based spatial statistics, respectively. Results CMBs were detected in 104 individuals (18.5%) in our study. Multinomial logistic regression found deep/mixed CMBs were associated with global cognitive dysfunction (OR 3.52; 95% CI 1.21 to 10.26), whereas lobar CMBs (OR 1.76; 95% CI 0.56 to 5.53) were not. Quantification of multimodal brain MRI showed that deep/mixed CMBs were accompanied by decreased thalamic volume and loss of fractional anisotropy of bilateral anterior thalamic radiations. Conclusion Deep/mixed CMBs were associated with cognitive dysfunction in this Chinese cross-sectional study. Disruption of thalamocortical connectivity might be a potential pathway underlying this relationship., Highlights • Cerebral microbleeds (CMBs) are found in 18.5% of middle-aged Chinese population. • Deep/mixed CMBs, not lobar CMBs, are associated with cognitive dysfunction. • Atrophy and fiber connectivity disruption might be the underlying neural pathways.

Magnetic resonance imaging (MRI) is one of the most important medical imaging techniques for clinical diagnosis. Contrast agents (CAs) are commonly necessarily used to enhance the imaging quality of MRI and differentiate diseased tissues from normal ones. Herein, we introduced a macromolecular carrier, spherical polyelectrolyte brushes (SPBs), which consists of a solid polystyrene (PS) core and polyacrylic acid (PAA) chains as a brush layer to host Gd(iii) complexes. The cationic Gd(iii) complex Gd-DTPA-NO-C4 was synthesized through a 6-step approach and then formed electrostatic self-assemblies with SPBs to afford magnetic assemblies. The regular appearance of the core-shell type structure of the assemblies was confirmed by TEM and SEM. Besides, a remarkable enhancement in relaxivity up to 62 mM-1 s-1 of these assemblies was determined, much higher than that of clinically used small molecule CAs (4-5 mM-1 s-1). It is noteworthy that the assemblies exhibit non-cytotoxicity even at the concentration of Gd(iii) up to 150 μM, showing great potential for clinical MRI applications.

Dot-blot hybridization and high-resolution melting curve methods are used to detect G6PD gene mutations; however, the performance and throughput limitations of these methods hinder their use for screening large populations. For simple screening, we developed a novel approach called “Amplification Refractory Mutation System combined with Melting Curve Analysis (ARMS-MC),” which enables rapid and batch-based detection of the 6 most common G6PD mutations. In this method, we established 4 PCR reaction systems that can be used to detect the 6 most common G6PD mutations (c.95A>G, c.392G>T, c.871G>A, c.1024C>T, c.1376G>T, and c.1388G>A) in the Chinese population. The ARMS-MC method was evaluated with 174 cases of clinical G6PD-deficient samples, and the results were verified by direct sequencing at G6PD gene exons. The results showed that 170 samples had ≥1 of the 6 mutations, which accounted for 97.70% of all mutations. These results were consistent with the results of direct sequencing with 100% accuracy and specificity. Sequencing validation revealed other mutations in the 4 samples in which no mutation was detected by the ARMS-MC method. ARMS-MC provides a rapid, simple, inexpensive, and accurate screening method for detecting the most common G6PD mutations in Chinese people.

Objectives Disorders of consciousness (DoC)—that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state—are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker. Experimental design In our preliminary study, we used [11C]Flumazenil positron emission tomography to establish global GABAA receptor binding potential values and the local-to-global (LTG) ratio of these for specific regions. These values were then compared between DoC patients and healthy controls. In addition, they were correlated with behavioral improvements for the patients between the time of scanning and 3 months later. Functional magnetic resonance imaging resting-state functional connectivity was also calculated and the same comparisons made. Principal observations lobal GABAA receptor binding was reduced in DoC, as was the LTG ratio in specifically the supragenual anterior cingulate. Both of these measures correlated with behavioral improvement after 3 months. In contrast to these measures of GABAA receptor binding, functional connectivity did not correlate with behavioral improvement. Conclusions Our preliminary findings point toward GABAA receptor binding being a marker of consciousness recovery in DoC. Hum Brain Mapp 36:3867–3877, 2015. © 2015 Wiley Periodicals, Inc.

Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease.

In this study, we aimed to (1) identify white matter (WM) deficits underlying the consciousness level in patients with disorders of consciousness (DOCs) using diffusion tensor imaging (DTI), and (2) evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest (ROIs), and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-018-0253-3) contains supplementary material, which is available to authorized users.

Hydrocephalus is a condition that causes ventricle enlargement by pathological accumulation of cerebrospinal fluid (CSF) and ends with different levels of disorders of consciousness (DOCs). Assessment of the consciousness level will help for the planning of the treatment of the patients. In this paper, a longitudinal sparse regression model featured by the temporal constraint is proposed to assess the levels of consciousness for hydrocephalus patients and to track their temporal alterations based on magnetic resonance (MR) images. Specifically, for the time points before and after neurosurgeries, we extract features from the corresponding MR scans and then regress out the clinical scores that reflect the respective consciousness levels. The longitudinal regression model can thus be applied to automatically track and evaluate the consciousness level change for individual patients, while the reading of the regression can act as an important indicator for the planning of subsequent treatment in clinical practice.

The short-term insemination technique has been widely applied, although it is not clear whether the mechanical desorption of cumulus cells can affect normal fertilization and birth outcomes. Therefore, the present study aimed to evaluate whether early cumulus cell removal could affect in vitro fertilization outcomes. Based on a history of infertility and semen analysis, 61 patients were identified, and the cumulus cells were mechanically removed at either6 h post-insemination (Group A, 387 mature oocytes) or 18 - 20 h post-insemination as traditional in vitro fertilization (Group B, 424 mature oocytes). There were no significant differences in the rates of fertilization, available embryos, high quality embryos, birth, premature birth, pregnancy, or implantation when we compared the two groups. However, Group A exhibited a significantly higher polyspermy rate, and significantly lower rates of blastocyst formation and high-quality blastocyst formation, compared with Group B. Therefore, the results of present study indicate that early cumulus cell removal (at 6 h post-insemination) may negatively affect the rates of polyspermy, blastocyst formation, and high-quality blastocyst formation.

Purpose Our study aimed to explore the feasibility of manganese-enhanced magnetic resonance imaging (MEMRI) combined with visual evoked potentials (VEP) and auditory evoked visual cortex responses (AVR) in evaluating for the establishment of visual/auditory compensatory pathways after monocular blindness. Materials and Methods A total of 14 healthy neonatal male Sprague-Dawley rats were randomly divided into two groups (n = 7 for Groups A and B). Right optic nerve (ON) transection was performed on the 7 rats of Group A to obtain a monocularly blind model, and the 7 rats of Group B were chosen as the control group. Four months later, 400 mmol MnCl2 was injected into the left eye in both groups via intravitreal injection. The changes in the visual pathways projected from the blind eye and the remaining eye in Group A and the normal eyes in Group B were compared to determine if new visual compensatory pathways were established. Additionally, VEP tests were performed to determine complete blindness, and AVR examinations were performed to help identify the generation of auditory compensatory function. Results The VEP test indicated complete visual loss after ON transection. In the monocularly blind rats, the contrast-to-noise ratio (CNR) of ON, optic tract (OT), lateral geniculate nucleus (LGN), superior colliculus (SC), optic radiation (OR) and visual cortex (VC) of visual pathway projected from the left eye was significantly higher than that of the right pathway (p

Decreased brain activity in the default mode network, particularly in the precuneus (PCU), has been consistently shown in acquired brain injury (ABI) patients. However, it is unclear whether resting-state brain activity recovers longitudinally in ABI patients and whether functional activity restoration is associated with improvements in consciousness level. Here, resting-state fMRI data were acquired from 23 ABI patients and 30 age- and gender-matched controls with two longitudinal observations for each participant. The fMRI data were analyzed using amplitude of low-frequency fluctuation (ALFF) to measure the fluctuation strength of local spontaneous activity, and seed-based functional connectivity was used to measure functional relationship with the seed region in the whole brain. The level of consciousness was assessed using the Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) on both scanning days of the patients. Interaction effect between the two groups and two scans in ALFF was observed in the PCU, which was driven by restored ALFF in the ABI, while a stable ALFF in the control group. Moreover, restoration of ALFF in the PCU correlated with improvements in both the CRS-R and GCS. Specifically, recovery of ALFF in the PCU primarily reflected the signals of the slow-4 frequency band (0.027-0.073 Hz). Based on the functional connectivity maps of the PCU, we observed a nonsignificant interaction effect or correlation with consciousness level. These findings suggest local activity in the PCU but possibly not its functional connectivity, is related to the longitudinal changes in behavioral responsiveness in ABI. Hum Brain Mapp 38:3579-3591, 2017. © 2017 Wiley Periodicals, Inc.

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p

Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgical mapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS). We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI). R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/T-fMRI and DCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a “gold standard”. R-fMRI and T-fMRI performances were compared statistically A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41 %, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p = 0.3198 and p = 0.1431, respectively) R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for presurgical mapping

Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults [1]. However, the etiology of CAD is controversial, and is generally to be considered as the interaction of genetic variants and environmental factors, which may cause weakness of the vessel wall. We present two patients with spontaneous CAD associated with inherited and acquired connective tissue disorders (CTD), respectively.

An fMRI study was launched to understand mechanisms of Alzheimer's disease (AD) patients with apathy. The authors reviewed 7 AD patients with apathy and 6 AD patients without apathy. The block method was adopted, and 24 pictures representing positive, negative, and neutral emotional stimuli were viewed when patients were given brain fMRI. Under "sad versus neutral" stimulation, non-apathetic AD patients had increased activity in bilateral amygdala and bilateral fusiform gyrus, whereas apathetic AD patients only had increased activities in bilateral fusiform gyrus. Thus, the amygdala was the possible anatomical structure related to apathy in AD patients.

Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state=unresponsive wakefulness syndrome and minimally conscious state patients. However, the func- tional implications of these resting-state abnormalities remain unclear. Recent findings in healthy sub- jects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). How- ever, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of con- sciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients

Object The aim of this study is to explore the changes of inter-hemispheric functional connectivity in patients with unilateral brachial plexus injury. Methods Nine patients with five roots of unilateral brachial plexus avulsion injury and 11 healthy controls were recruited in this study. Resting-state functional connectivity magnetic resonance image was used to study the differences of inter-hemispheric functional connectivity between patients and healthy controls. Four areas were defined as regions of interest (ROI): the two primary motor areas (M1 areas) and two supplementary motor areas (SMAs) in the two hemispheres activated when the healthy controls performed unilateral hand grasping movement of the two hands, respectively. Functional connectivity maps were generated by correlating the regional time course of each ROI with that of every voxel in the whole brain. Then, functional connectivity was calculated by correlating the functional magnetic resonance image signal time courses of every two ROIs. Results Resting-state inter-hemispheric functional connectivity of the primary motor areas was reduced following brachial plexus avulsion injury. The correlation coefficients of the SMAs showed no difference between the brachial plexus patients and healthy volunteers. Conclusions Our results indicate that brachial plexus injury decreases resting-state inter-hemispheric functional connectivity of the two primary motor areas. These results provide new insight into functional reorganization of the cerebral cortex after brachial plexus injury.

Objective Peripheral nerve injury can induce immediate and long-standing remodelling of the brain cortex, which may affect outcomes of nerve repair. This study examined changes of corresponding cortical representations in patients with brachial plexus injuries. Methods Resting-state fMRI was acquired for 13 adult patients with total brachial plexus root avulsion, three of whom underwent second scans 7 or 8 months later. The time of examination ranged from 1 to 16 months after injuries. Nine healthy adults were enrolled as control. Seed-based functional connectivity was performed for all subjects. Results For nine patients whose first fMRI was performed from 1 to 4 months after brachial plexus injuries, images showed that their cortical maps of sensorimotor areas corresponding to the hand and arm in the hemisphere contralateral to the injured side had much weaker correlation with the supplementary motor area (SMA) than those ipsilateral to the injured side. Symmetrical maps of bilateral cortical sensorimotor areas corresponding to the hand and arm were observed in other four cases with fMRI tested from 7 to 16 months after injuries. For three of the nine patients with asymmetrical cortical representations, second scans indicated symmetric results or even stronger correlation with SMA in the cerebral cortex contralateral to the injured side. Conclusions Total brachial plexus root avulsion causes cortical representations of the brachial plexus to undergo a change from an inactive to an active state. This implies that peripheral deafferentation after brachial plexus injuries will induce corresponding cortical representations to be occupied by adjacent non-deafferented cortical territories.

Patients with frontal lobe gliomas often experience neurocognitive dysfunctions before surgery, which affects the default mode network (DMN) to different degrees. This study quantitatively analyzed this effect from the perspective of cerebral hemispheric functional connectivity (FC). We collected resting-state fMRI data from 20 frontal lobe glioma patients before treatment and 20 healthy controls. All of the patients and controls were right-handed. After pre-processing the images, FC maps were built from the seed defined in the left or right posterior cingulate cortex (PCC) to the target regions determined in the left or right temporal-parietal junction (TPJ), respectively. The intra- and cross-group statistical calculations of FC strength were compared. The conclusions were as follows: (1) the intra-hemisphere FC strength values between the PCC and TPJ on the left and right were decreased in patients compared with controls; and (2) the correlation coefficients between the FC pairs in the patients were increased compared with the corresponding controls. When all of the patients were grouped by their tumor’s hemispheric location, (3) the FC of the subgroups showed that the dominant hemisphere was vulnerable to glioma, and (4) the FC in the dominant hemisphere showed a significant correlation with WHO grade.

Background The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging (1H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. Method Eighteen patients with different grades of glioma were examined using 1H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. Results In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. Conclusions HGG and LGG exhibit different spectroscopic patterns. Using 1H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.

Retrospective assessment was performed of the minimum apparent diffusion coefficient (minADC) together with quantitative assessment of the histopathological features of resected tumour tissue and the Ki-67 labelling index (LI) for predicting pineal parenchymal tumour (PPT) grade. Magnetic resonance images of tumours from 26 male and female patients (mean age 27.7 years) with pathologically confirmed PPTs, comprising 10 pineocytomas (PCs), seven pineal parenchymal tumours of intermediate differentiation (PPTIDs) and nine pineoblastomas (PBs), were reviewed retrospectively. Using ADC maps derived from isotropic diffusion-weighted images, the minADC value of each tumour was determined postoperatively from several regions of interest defined in the tumour, excluding cystic, necrotic, haemorrhagic or calcified components. Surgical intervention was undertaken in all cases. The Ki-67 LI was measured in surgical specimens. Mean minADC and Ki-67 LI showed significant differences among PCs, PPTIDs and PBs, and minADC was negatively correlated with Ki-67 LI. It is concluded that the minADC of PPTs provide useful additional information when predicting tumour grading.

Objective Resection of gliomas invading primary motor cortex and subcortical motor pathway is difficult in both surgical decision-making and functional outcome prediction. In this study, magnetic resonance (MR) diffusion tensor imaging (DTI) data were used to perform tractography to visualize pyramidal tract (PT) along its whole length in a stereoscopic virtual reality (VR) environment. The potential value of its clinical application was evaluated. Methods Both three-dimensional (3-D) magnetic resonance imaging (MRI) and DTI datasets were obtained from 45 eligible patients with suspected cerebral gliomas and then transferred to the VR system (Dextroscope; Volume Interactions Pte. Ltd., Singapore). The cortex and tumor were segmented and reconstructed via MRI, respectively, while the tractographic PTs were reconstructed via DTI. All those were presented in a stereoscopic 3-D display synchronously, for the purpose of patient-specific presurgical planning and surgical simulation in each case. The relationship between increasing amplitude of the number of effective fibers of PT (EPT) at affected sides and the patients’ Karnofsky Performance Scale (KPS) at 6 months was addressed out. Results In VR presurgical planning for gliomas, surgery was aided by stereoscopic 3-D visualizing the relative position of the PTs and a tumor. There was no significant difference between pre- and postsurgical EPT in this population. A positive relationship was proved between EPT increasing amplitude and 6-month KPS. Conclusions 3-D stereoscopic visualization of tractography in this VR environment enhances the operators to well understand the anatomic information of intra-axial tumor contours and adjacent PT, results in surgical trajectory optimization initially, and maximal safe tumor resection finally. In accordance to the EPT increasing amplitude, surgeon can predict the long-term motor functional outcome.

Little is known about the propensity for certain emotional stimuli, such as historically familiar pictures, to activate a large neural network in patients exhibiting a minimally conscious state (MCS). A study was conducted in nine MCS patients and 10 healthy control subjects to explore the degree to which passive stimulation of pictures with different emotional valences--intimate family pictures (FPs), high-stimulating pictures (HSPs), and medium-stimulating pictures (MSPs), all selected from the International Affective Picture System (IAPS)--could elicit activation of large-scale visual networks during functional magnetic resonance imaging (fMRI) scaning. Good cortical activity was evoked in control subjects through visual networks, including the occipital, temporal, parietal, prefrontal, and orbito-frontal gyrus. Although the activation volume was less than that of normal control subjects, similar visual activation was found for MCS patients: six cases with FP, two cases with HSP, and three cases with MSP. We concluded that MCS patients can retain widely distributed visual cortical networks with the potential for visual cognitive function. Picture stimulation, especially with strong emotional FPs with which patients were familiar before brain injury, can elicit conscious brain activity. In this study, we have provided further evidence of the residual functional substrates in MCS patients with respect to increased cortical activity with emotional visual stimulation. The results of this study underscore the need for further research to confirm whether this type of stimulation can facilitate emergence from the MCS status.

A highly efficient palladium-catalyzed Heck coupling reaction of heteroaryl halides with electron-rich vinyl ether and hydroxyalkyl vinyl ethers is described. It was found that the choice of solvent, ligand, and reaction temperature had a fundamental influence on the regioselectivity and reactivity of the reaction, and the combination of Pd(OAc)2 and DPPF in ethylene glycol led to the most effective catalytic system. Under these conditions, a variety of heteroaryl halides reacted very quickly with electron-rich olefins to afford exclusively the branched products in good to excellent yields without employing triflates, halide scavengers, or ionic liquids.