Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity.

The clinical applications of immunocytokines are severely restricted by dose-limiting toxicities. To address this challenge, here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug. LH05 innovatively masks IL-15 with steric hindrance, mitigating the "cytokine sink" effect of IL-15 and reducing systemic toxicities associated with wild-type anti-PD-L1/IL-15. Moreover, upon specific proteolytic cleavage within the tumor microenvironment, LH05 releases an active IL-15 superagonist, exerting potent antitumor effects. Mechanistically, the antitumor efficacy of LH05 depends on the increased infiltration of CD8+ T and natural killer cells by stimulating the chemokines CXCL9 and CXCL10, thereby converting cold tumors into hot tumors. Additionally, the tumor-conditional anti-PD-L1/IL-15 can synergize with an oncolytic virus or checkpoint blockade in advanced and metastatic tumor models. Our findings provide a compelling proof of concept for the development of next-generation immunocytokines, contributing significantly to current knowledge and strategies of immunotherapy.

Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial.

BACKGROUND: Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. METHODS: Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) CONCLUSIONS: It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.

Visualizing the intracellular aggregation behavior of gold nanoclusters via structured illumination microscopy and scanning transmission electron microscopy.

Given the growing concerns about nanotoxicity, numerous studies have focused on providing mechanistic insights into nanotoxicity by imaging the intracellular fate of nanoparticles. A suitable imaging strategy is necessary to uncover the intracellular behavior of nanoparticles. Although each conventional technique has its own limitations, scanning transmission electron microscopy (STEM) and three-dimensional structured illumination microscopy (3D-SIM) combine the advantages of chemical element mapping, ultrastructural analysis, and cell dynamic tracking. Gold nanoclusters (AuNCs), synthesized using 6-aza-2 thiothymine (ATT) and L-arginine (Arg) as reducing and protecting ligands, referred to as Arg@ATT-AuNCs, have been widely used in biological sensing and imaging, medicine, and catalyst yield. Based on their intrinsic fluorescence and high electron density, Arg@ATT-AuNCs were selected as a model. STEM imaging showed that both the single-particle and aggregated states of Arg@ATT-AuNCs were compartmentally distributed within a single cell. Real-time 3D-SIM imaging showed that the fluorescent Arg@ATT-AuNCs gradually aggregated after being located in the lysosomes of living cells, causing lysosomal damage. The aggregate formation of Arg@ATT-AuNCs was triggered by the low-pH medium, particularly in the lysosomal acidic environment. The proposed dual imaging strategy was verified using other types of AuNCs, which is valuable for studying nano-cell interactions and any associated cytotoxicity, and has the potential to be a useful approach for exploring the interaction of cells with various nanoparticles.

Development of a lung-liver in vitro coculture model for inhalation-like toxicity assessment.

Animal models are considered prime study models for inhalation-like toxicity assessment. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalation-like exposures. A coculture platform was established to emulate inter-organ crosstalks between a pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism. Both compartments (Calu-3 insert and HepG2/C3A biochip) were jointly cultured in a dynamically-stimulated environment for 72 h. The present model was characterized using acetaminophen (APAP), a well-documented hepatotoxicant, to visibly assess the passage and circulation of a xenobiotic through the device. Based on viability and functionality parameters the coculture model showed that the bronchial barrier and the liver biochip can successfully be maintained viable and function in a dynamic coculture setting for 3 days. In a stress-induced environment, present results reported that the coculture model emulated active and functional in vitro crosstalk that seemingly was responsive to xenobiotic exposure doses. The hepatic and bronchial cellular responses to xenobiotic exposure were modified in the coculture setting as they displayed earlier and stronger detoxification processes, highlighting active and functional organ crosstalk between both compartments.

Deep Learning-Assisted Quantitative Susceptibility Mapping as a Tool for Grading and Molecular Subtyping of Gliomas.

This study aimed to explore the value of deep learning (DL)-assisted quantitative susceptibility mapping (QSM) in glioma grading and molecular subtyping. Forty-two patients with gliomas, who underwent preoperative T2 fluid-attenuated inversion recovery (T2 FLAIR), contrast-enhanced T1-weighted imaging (T1WI + C), and QSM scanning at 3.0T magnetic resonance imaging (MRI) were included in this study. Histopathology and immunohistochemistry staining were used to determine glioma grades, and isocitrate dehydrogenase (IDH) 1 and alpha thalassemia/mental retardation syndrome X-linked gene (ATRX) subtypes. Tumor segmentation was performed manually using Insight Toolkit-SNAP program (www.itksnap.org). An inception convolutional neural network (CNN) with a subsequent linear layer was employed as the training encoder to capture multi-scale features from MRI slices. Fivefold cross-validation was utilized as the training strategy (seven samples for each fold), and the ratio of sample size of the training, validation, and test dataset was 4:1:1. The performance was evaluated by the accuracy and area under the curve (AUC). With the inception CNN, single modal of QSM showed better performance in differentiating glioblastomas (GBM) and other grade gliomas (OGG, grade II-III), and predicting IDH1 mutation and ATRX loss (accuracy: 0.80, 0.77, 0.60) than either T2 FLAIR (0.69, 0.57, 0.54) or T1WI + C (0.74, 0.57, 0.46). When combining three modalities, compared with any single modality, the best AUC/accuracy/F1-scores were reached in grading gliomas (OGG and GBM: 0.91/0.89/0.87, low-grade and high-grade gliomas: 0.83/0.86/0.81), predicting IDH1 mutation (0.88/0.89/0.85), and predicting ATRX loss (0.78/0.71/0.67). As a supplement to conventional MRI, DL-assisted QSM is a promising molecular imaging method to evaluate glioma grades, IDH1 mutation, and ATRX loss. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00087-6.

Electrical stimulation-induced speech-related negative motor responses in the lateral frontal cortex.

OBJECTIVE: Speech arrest is a common but crucial negative motor response (NMR) recorded during intraoperative brain mapping. However, recent studies have reported nonspeech-specific NMR sites in the ventral precentral gyrus (vPrCG), where stimulation halts both speech and ongoing hand movement. The aim of this study was to investigate the spatial relationship between speech-specific NMR sites and nonspeech-specific NMR sites in the lateral frontal cortex. METHODS: In this prospective cohort study, an intraoperative mapping strategy was designed to identify positive motor response (PMR) sites and NMR sites in 33 consecutive patients undergoing awake craniotomy for the treatment of left-sided gliomas. Patients were asked to count, flex their hands, and simultaneously perform these two tasks to map NMRs. Each site was plotted onto a standard atlas and further analyzed. The speech and hand motor arrest sites in the supplementary motor area of 2 patients were resected. The 1- and 3-month postoperative language and motor functions of all patients were assessed. RESULTS: A total of 91 PMR sites and 72 NMR sites were identified. NMR and PMR sites were anteroinferiorly and posterosuperiorly distributed in the precentral gyrus, respectively. Three distinct NMR sites were identified: 24 pure speech arrest (speech-specific NMR) sites (33.33%), 7 pure hand motor arrest sites (9.72%), and 41 speech and hand motor arrest (nonspeech-specific NMR) sites (56.94%). Nonspeech-specific NMR sites and speech-specific NMR sites were dorsoventrally distributed in the vPrCG. For language function, 1 of 2 patients in the NMA resection group had language dysfunction at the 1-month follow-up but had recovered by the 3-month follow-up. All patients in the NMA resection group had fine motor dysfunction at the 1- and 3-month follow-ups. CONCLUSIONS: The study results demonstrated a functional segmentation of speech-related NMRs in the lateral frontal cortex and that most of the stimulation-induced speech arrest sites are not specific to speech. A better understanding of the spatial distribution of speech-related NMR sites will be helpful in surgical planning and intraoperative mapping and provide in-depth insight into the motor control of speech production.

Cation-Free siRNA Micelles as Effective Drug Delivery Platform and Potent RNAi Nanomedicines for Glioblastoma Therapy.

Nanoparticle-based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood-brain-barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation-free siRNA micelles, prepared by the self-assembly of siRNA-disulfide-poly(N-isopropylacrylamide) (siRNA-SS-PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take-up, and effective at-site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non-cationic, these siRNA micelles exert no charge-associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors' results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment.

A nomogram for individualized prediction of overall survival in patients with newly diagnosed glioblastoma: a real-world retrospective cohort study.

BACKGROUND: This study aimed to identify the most valuable predictors of prognosis in glioblastoma (GBM) patients and develop and validate a nomogram to estimate individualized survival probability. METHODS: We conducted a real-world retrospective cohort study of 987 GBM patients diagnosed between September 2010 and December 2018. Computer generated random numbers were used to assign patients into a training cohort (694 patients) and internal validation cohort (293 patients). A least absolute shrinkage and selection operator (LASSO)-Cox model was used to select candidate variables for the prediction model. Cox proportional hazards regression was used to estimate overall survival. Models were internally validated using the bootstrap method and generated individualized predicted survival probabilities at 6, 12, and 24 months, which were compared with actual survival. RESULTS: The final nomogram was developed using the Cox proportional hazards model, which was the model with best fit and calibration. Gender, age at surgery, extent of tumor resection, radiotherapy, chemotherapy, and IDH1 mutation status were used as variables. The concordance indices for 6-, 12-, 18-, and 24-month survival probabilities were 0.776, 0.677, 0.643, and 0.629 in the training set, and 0.725, 0.695, 0.652, and 0.634 in the validation set, respectively. CONCLUSIONS: Our nomogram that assesses individualized survival probabilities (6-, 12-, and 24-month) in newly diagnosed GBM patients can assist healthcare providers in optimizing treatment and counseling patients. TRIAL REGISTRATION: retrospectively registered.

Machine learning models predict coagulopathy in spontaneous intracerebral hemorrhage patients in ER.

AIMS: Coagulation abnormality is one of the primary concerns for patients with spontaneous intracerebral hemorrhage admitted to ER. Conventional laboratory indicators require hours for coagulopathy diagnosis, which brings difficulties for appropriate intervention within the optimal window. This study evaluates the possibility of building efficient coagulopathy prediction models using data mining and machine learning algorithms. METHODS: A retrospective cohort enrolled 1668 cases with acute spontaneous intracerebral hemorrhage from three medical centers, excluding those under antithrombotic therapies. Coagulopathy-related clinical parameters were initially screened by univariate analysis. Two machine learning algorithms, the random forest and the support vector machine, were deployed via an approach of four-fold cross-validation to screen out the most important parameters contributing to the occurrence of coagulopathy. Model discrimination was assessed using metrics, including accuracy, precision, recall, and F1 score. RESULTS: Albumin/globulin ratio, neutrophil count, lymphocyte percentage, aspartate transaminase, alanine transaminase, hemoglobin, platelet count, white blood cell count, neutrophil percentage, systolic and diastolic pressure were identified as major predictors to the occurrence of acute coagulopathy. Compared to support vector machine, the model based on the random forest algorithm showed better accuracy (93.1%, 95% confidence interval [CI]: 0.913-0.950), precision (92.4%, 95% CI: 0.897-0.951), F1 score (91.5%, 95% CI: 0.889-0.964), and recall score (93.6%, 95% CI: 0.909-0.964), and yielded higher area under the receiver operating characteristic curve (AU-ROC) (0.962, 95% CI: 0.942-0.982). CONCLUSION: The constructed models exhibit good prediction accuracy and efficiency. It might be used in clinical practice to facilitate target intervention for acute coagulopathy in patients with spontaneous intracerebral hemorrhage.

The Incidence and Predictors of Postoperative Delirium After Brain Tumor Resection in Adults: A Cross-Sectional Survey.

BACKGROUND: Postoperative delirium (POD) describes a multifactorial disease process occurring after surgery. However, few studies have focused on patients undergoing brain tumor resection, and its influencing factors are unclear. METHODS: We performed a 1-year, single-center, cross-sectional, retrospective survey at Huashan Hospital. Patients were screened using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Confusion Assessment Method, and Richmond Agitation Sedation Scale by trained bedside nurses. Perioperative data were collected using demographic and disease-related questionnaires. The primary outcome measures were the incidence of POD and subtype of POD. Independent predictors of POD were estimated from multivariate logistic regression models, and receiver operating characteristic analysis was used to compare the predictive performance of the models. RESULTS: Of the 916 patients included in the study, 893 were analyzed. The overall incidence was 14.78%, 67 had hyperactive delirium (50.76%), 55 had hypoactive delirium (41.67%), and 10 had mixed delirium (7.57%). Age, sex, working status, tobacco use history, comorbidities, physical restraint, axillary temperature (>38.5°C), electrolyte disturbances, duration of anesthesia, pathologic diagnosis, tumor site, length of disease, and duration of operation were risk factors for POD. Conversely, saddle area mass was a protective factor. Age, tobacco use history, electrolyte disturbances, physical restraint, and duration of operation were included in the model. CONCLUSIONS: POD is harmful to patients undergoing brain tumor resection, increasing length of stay in the intensive care unit and hospitalization costs. Intraoperative factors and postoperative factors, in addition to older age and tobacco use history, are associated with POD.

The siRNAsome: A Cation-Free and Versatile Nanostructure for siRNA and Drug Co-delivery.

Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co-delivery of siRNAs, which avoid the problem of cation-associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)-based vesicle (siRNAsome), which consists of a hydrophilic siRNA shell, a thermal- and intracellular-reduction-sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as co-delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction-responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti-P-glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.

Transcortical insular glioma resection: clinical outcome and predictors.

OBJECTIVE: Insular lobe gliomas continue to challenge neurosurgeons due to their complex anatomical position. Transcortical and transsylvian corridors remain the primary approaches for reaching the insula, but the adoption of one technique over the other remains controversial. The authors analyzed the transcortical approach of resecting insular gliomas in the context of patient tumor location based on the Berger-Sinai classification, achievable extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome. METHODS: The authors studied 255 consecutive cases of insular gliomas that underwent transcortical tumor resection in their division. Tumor molecular pathology, location, EOR, postoperative neurological outcome for each insular zone, and the accompanying OS were incorporated into the analysis to determine the value of this surgical approach. RESULTS: Lower-grade insular gliomas (LGGs) were more prevalent (63.14%). Regarding location, giant tumors (involving all insular zones) were most prevalent (58.82%) followed by zone I+IV (anterior) tumors (20.39%). In LGGs, tumor location was an independent predictor of survival (p = 0.003), with giant tumors demonstrating shortest patient survival (p = 0.003). Isocitrate dehydrogenase 1 (IDH1) mutation was more likely to be associated with giant tumors (p < 0.001) than focal tumors located in a regional zone. EOR correlated with survival in both LGG (p = 0.001) and higher-grade glioma (HGG) patients (p = 0.008). The highest EORs were achieved in anterior-zone LGGs (p = 0.024). In terms of developing postoperative neurological deficits, patients with giant tumors were more susceptible (p = 0.038). Postoperative transient neurological deficit was recorded in 12.79%, and permanent deficit in 15.70% of patients. Patients who developed either transient or permanent postsurgical neurological deficits exhibited poorer survival (p < 0.001). CONCLUSIONS: The transcortical surgical approach can achieve maximal tumor resection in all insular zones. In addition, the incorporation of adjunct technologies such as multimodal brain imaging and mapping of cortical and subcortical eloquent brain regions into the transcortical approach favors postoperative neurological outcomes, and prolongs patient survival.

The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface.

Quantitative assessment of changes in hemodynamics of the internal carotid artery after bypass surgery for moyamoya disease.

OBJECTIVE Although intracranial vessel remodeling has been observed in moyamoya disease, concerns remain regarding the effect of bypass surgery on hemodynamic changes within the internal carotid artery (ICA). The authors aimed to quantify the surgical effect of bypass surgery on bilateral ICAs in moyamoya disease and to estimate pressure drop (PD) along the length of the ICA to predict surgical outcomes. METHODS Records of patients who underwent bypass surgery for treatment of moyamoya disease and in whom flow rates were obtained pre- and postsurgery by quantitative MR angiography were retrospectively reviewed. Quantitative MR angiography and computational fluid dynamics were applied to measure morphological and hemodynamic changes during pre- and postbypass procedures. The results for vessel diameter, volumetric flow, PD, and mean wall shear stress along the length of the ICA were analyzed. Subgroup analysis was performed for the circle of Willis (CoW) configurations. RESULTS Twenty-three patients were included. The PD in ICAs on the surgical side (surgical ICAs) decreased by 21.18% (SD ± 30.1%) and increased by 11.75% (SD ± 28.6%) in ICAs on the nonsurgical side (contralateral ICAs) (p = 0.001). When the PD in contralateral ICAs was compared between patients with a complete or incomplete CoW, the authors found that the PDI in the former group decreased by 2.45% and increased by 20.88% in the latter (p = 0.05). Regression tests revealed that a greater postoperative decrease in PD corresponded to shrinking of ICAs (R2 = 0.22, p = 0.02). CONCLUSIONS PD may be used as a reliable biomechanical indicator for the assessment of surgical treatment outcomes. The vessel remodeling characteristics of contralateral ICA were related to CoW configurations.

Morphological and Hemodynamic Differences Between Aneurysmal Middle Cerebral Artery Bifurcation and Contralateral Nonaneurysmal Anatomy.

BACKGROUND: The morphological and hemodynamic features differ between middle cerebral artery (MCA) bifurcations with and without aneurysms. OBJECTIVE: To investigate the morphological and hemodynamic differences between aneurysmal MCA bifurcation and contralateral nonaneurysmal anatomy. METHODS: Computed tomography angiography of 36 patients with unilateral small saccular MCA bifurcation aneurysms was evaluated. The parent-daughter angles (φ1 for larger branch and φ2 for smaller branch), bifurcation angle (φ = φ1 + φ2), inclination angle (γ angle), and their relationships with the MCA bifurcation locations were analyzed. Computational fluid dynamics simulation was performed in 6 cases to explore the hemodynamics influenced by the bifurcation morphology. RESULTS: The φ angle was significantly higher in aneurysmal than contralateral nonaneurysmal bifurcations (160.8° ± 31.0° vs 99.0° ± 19.2°, respectively; P = .000); the φ1, φ2, and γ angles were also higher. However, by regression analysis combined with MCA bifurcation locations, only the φ angle might be associated with the aneurysm presence (odds ratio = 1.120, 95% confidence interval = 1.059-1.185) and a φ angle cut-off of 124.8° was established. Computational fluid dynamics simulation demonstrated that flow resistance of the wider aneurysmal MCA bifurcation was significantly higher than that on the contralateral side. CONCLUSION: A larger φ angle was more prevalent in aneurysmal than nonaneurysmal MCA bifurcations, and the higher flow resistance caused by the larger φ angle might be a potential hemodynamic factor associated with MCA aneurysm presence.

Intraoperative Multi-Information-Guided Resection of Dominant-Sided Insular Gliomas in a 3-T Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite.

OBJECTIVE: To evaluate the clinical application of 3-T intraoperative magnetic resonance imaging (iMRI), awake craniotomy, multimodal functional mapping, and intraoperative neurophysiologic monitoring (IONM) for resection of dominant-sided insular gliomas. METHODS: From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0-T iMRI integrated neurosurgical suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. Diffusion tensor imaging tractography-based navigation, continuous motor evoked potential monitoring, and subcortical electrical stimulation mapping were applied to localize and monitor the motor pathway in all cases. iMRI was used to assess the extent of resection. The results of intraoperative imaging, IONM, and the surgical consequences were analyzed. RESULTS: Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median extent of resection was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P = 0.018) in low-grade gliomas. The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P = 0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively. CONCLUSIONS: The combination of iMRI, awake craniotomy, multimodal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma.

Assessing surgical treatment outcome following superficial temporal artery to middle cerebral artery bypass based on computational haemodynamic analysis.

To estimate haemodynamic modification of Internal Carotid Artery (ICA) after bypass surgery using computational fluid dynamic (CFD) technology and thereby aid in our understanding of the influence of hemodynamic parameters on the outcomes of bypass operations. 18 patients who underwent superficial temporal artery to middle cerebral artery bypass and encephaloduromyosynangiosis (EDMS) surgery were included. Reconstructed three-dimensional vessel geometries from MRA were segmented to create computational domains for CFD simulations. All cases were classified as three groups according to the proportion of the MCA area of distribution supplied by revascularization: A, more than two thirds; B, between two-thirds and one-third; and C, less than one-third of the MCA distribution. Pre-operative and follow-up haemodynamic parameters, especially volume flow rate and pressure drop index (PDI) in ICA were compared. For all cases, PDI and volume flow rate in the surgical-side ICA decreased significantly at follow-up (P<0.05). For the cases of group A, volume flow rate in surgical-side ICA decreased by average 24.2%, whilst for the cases of group B and C, flow rate reduced by 10.5% and 3.7%, respectively. An average PDI for cases in group A was -1.67mmHg, conversely average PDI values of group B and C were -0.53 and 0.82mmHg, respectively. The remodelling of ICA after bypass was associated with reduction in the volume flow rate and pressure drop. Good correlation with angiographic grading suggested that CFD might play a critical role as a quantitative haemodynamic technique for predicting treatment outcome during the follow-up of MMD patients.

Predicting Cerebral Hyperperfusion Syndrome Following Superficial Temporal Artery to Middle Cerebral Artery Bypass based on Intraoperative Perfusion-Weighted Magnetic Resonance Imaging.

Moyamoya disease leads to the formation of stenosis in the cerebrovasculature. A superficial temporal artery to middle cerebral artery (STA-MCA) bypass is an effective treatment for the disease, yet it is usually associated with postoperative cerebral hyperperfusion syndrome (CHS). This study aimed to evaluate cerebral hemodynamic changes immediately after surgery and assess whether a semiquantitative analysis of an intraoperative magnetic resonance perfusion-weighted image (PWI) is useful for predicting postoperative CHS. Fourteen patients who underwent the STA-MCA bypass surgery were included in this study. An atlas-based registration method was employed for studying hemodynamics in different cerebral regions. Pre- versus intraoperative and group-wise comparisons were conducted to evaluate the hemodynamic changes. A postoperative increase in relative cerebral blood flow (CBF) at the terminal MCA territory (P = 0.035) and drop in relative mean-time-transit at the central MCA territory (P = 0.012) were observed in all patients. However, a significant raise in the increasing ratio of relative-CBF at the terminal MCA territory was only found in CHS patients (P = 0.023). The cerebrovascular changes of the patients after revascularization treatment were confirmed. Intraoperative PWI might be helpful in predicting the change in relative-CBF at MCA terminal territory which might indicate a risk of CHS.

Localizing hand motor area using resting-state fMRI: validated with direct cortical stimulation.

BACKGROUND: 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). METHODS: 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 RESULTS: 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) CONCLUSIONS: 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.

Association of depression with inflammation in hospitalized patients of myocardial infarction.

OBJECTIVE: The aim of this study was to examine the associations between depression and inflammatory markers in patients admitted to the hospital for myocardial infarction. METHODS: Inflammatory cytokines, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were assessed in a group of 75 depressed participants (score of ≥ 12) and compared to a control group of 75 nondepressed participants (score < 12), all who had been admitted to the hospital for myocardial infarction. The presence of depressive symptoms was assessed using the Beck Depressive Symptoms Inventory II Scale (BDI-II). RESULTS: Depressed myocardial infarction participants had significantly greater levels of TNF-α (t = 2.070, P < 0.05) compared with control myocardial infarction participants. The BDI-II score was positively correlated with TNF-α levels (r = 0.222, P < 0.05). CONCLUSIONS: These results indicate that the presence of depressive symptoms is positively associated with TNF-α levels among patients who have suffered from myocardial infarction.