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Numerous traditional linguistic theories propose that semantic language pathways convert sounds to meaningful concepts, generating interpretations ranging from simple object descriptions to communicating complex, analytical thinking. Although the dual-stream model of Hickok and Poeppel is widely employed, proposing a dorsal stream, mapping speech sounds to articulatory/phonological networks, and a ventral stream, mapping speech sounds to semantic representations, other language models have been proposed. Indeed, despite seemingly congruent models of semantic language pathways, research outputs from varied specialisms contain only partially congruent data, secondary to the diversity of applied disciplines, ranging from fibre dissection, tract tracing, and functional neuroimaging to neuropsychiatry, stroke neurology, and intraoperative direct electrical stimulation. The current review presents a comprehensive, interdisciplinary synthesis of the ventral, semantic connectivity pathways consisting of the uncinate, middle longitudinal, inferior longitudinal, and inferior fronto-occipital fasciculi, with special reference to areas of controversies or consensus. This is achieved by describing, for each tract, historical concept evolution, terminations, lateralisation, and segmentation models. Clinical implications are presented in three forms: (a) functional considerations derived from normal subject investigations, (b) outputs of direct electrical stimulation during awake brain surgery, and (c) results of disconnection syndromes following disease-related lesioning. The current review unifies interpretation of related specialisms and serves as a framework/thinking model for additional research on language data acquisition and integration.

Background Presence of residual neurovascular activity within glioma lesions have been recently demonstrated via functional MRI (fMRI) along with active electrical synapses between glioma cells and healthy neurons that influence survival. In this study, we aimed to investigate whether gliomas demonstrate synchronized neurovascular activity with the rest of the brain, by measuring Blood Oxygen Level Dependent (BOLD) signal synchronization, that is, functional connectivity (FC), while also testing whether the strength of such connectivity might predict patients’ overall survival (OS). Methods Resting-state fMRI scans of patients who underwent pre-surgical brain mapping were analyzed (total sample, n = 54; newly diagnosed patients, n = 18; recurrent glioma group, n = 36). A seed-to-voxel analysis was conducted to estimate the FC signal profile of the tumor mass. A regression model was then built to investigate the potential correlation between tumor FC and individual OS. Finally, an unsupervised, cross-validated clustering analysis was performed including tumor FC and clinical OS predictors (e.g., Karnofsky Performance Status - KPS - score, tumor volume, and genetic profile) to verify the performance of tumor FC in predicting OS with respect to validated radiological, demographic, genetic and clinical prognostic factors. Results In both newly diagnosed and recurrent glioma patients a significant pattern of BOLD synchronization between the solid tumor and distant brain regions was found. Crucially, glioma-brain FC positively correlated with variance in individual survival in both newly diagnosed glioma group (r = 0.90–0.96; P < .001; R2 = 81–92%) and in the recurrent glioma group (r = 0.72; P < .001; R2 = 52%), outperforming standard clinical, radiological and genetic predictors. Conclusions Results suggest glioma’s synchronization with distant brain regions should be further explored as a possible diagnostic and prognostic biomarker.

International audience; Objective: A craniotomy is the removal of a part of the skull to allow surgeons to have access to the brain and treat tumors. When accessing the brain, a tissue deformation occurs and can negatively influence the surgical procedure outcome. In this work, we present a novel Augmented Reality neurosurgical system to superimpose pre-operative 3D meshes derived from MRI onto a view of the brain surface acquired during surgery. Methods: Our method uses cortical vessels as main features to drive a rigid then non-rigid 3D/2D registration. We first use a feature extractor network to produce probability maps that are fed to a pose estimator network to infer the 6-DoF rigid pose. Then, to account for brain deformation, we add a nonrigid refinement step formulated as a Shape-from-Template problem using physics-based constraints that helps propagate the deformation to sub-cortical level and update tumor location. Results: We tested our method retrospectively on 6 clinical datasets and obtained low pose error, and showed using synthetic dataset that considerable brain shift compensation and low TRE can be achieved at cortical and sub-cortical levels. Conclusion: The results show that our solution achieved accuracy below the actual clinical errors demonstrating the feasibility of practical use of our system. Significance: This work shows that we can provide coherent Augmented Reality visualization of 3D cortical vessels observed through the craniotomy using a single camera view and that cortical vessels provide strong features for performing both rigid and non-rigid registration.

Digital Subtraction Angiography (DSA) provides high resolution image sequences of blood flow through arteries and veins and is considered the gold standard for visualizing cerebrovascular anatomy for neurovascular interventions. However, acquisition frame rates are typically limited to 1-3 fps to reduce radiation exposure, and thus DSA sequences often suffer from stroboscopic effects. We present the first approach that permits generating high frame rate DSA sequences from low frame rate acquisitions eliminating these artifacts without increasing the patient’s exposure to radiation. Our approach synthesizes new intermediate frames using a phase-aware Convolutional Neural Network. This network accounts for the non-linear blood flow progression due to vessel geometry and initial velocity of the contrast agent. Our approach out-performs existing methods and was tested on several low frame rate DSA sequences of the human brain resulting in sequences of up to 17 fps with smooth and continuous contrast flow, free of flickering artifacts.

Given the difficulty and importance of achieving maximal resection in chordomas and chondrosarcomas, all available tools offered by modern neurosurgery are to be deployed for planning and resection of these complex lesions. As demonstrated by the review of our series of skull base chordoma and chondrosarcoma resections in the Advanced Multimodality Image-Guided Operating (AMIGO) suite, as well as by the recently published literature, we describe the use of advanced multimodality intraoperative imaging and neuronavigation as pivotal to successful radical resection of these skull base lesions while preventing and managing eventual complications.

To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 − 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 − 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 − 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.

International audience; During a craniotomy, the skull is opened to allow surgeons to have access to the brain and perform the procedure. The position and size of this opening are chosen in a way to avoid critical structures, such as vessels, and facilitate the access to tumors. Planning the operation is done based on pre-operative images and does not account for intra-operative surgical events. We present a novel image-guided neurosurgical system to optimize the craniotomy opening. Using physics-based modeling we define a cortical deformation map that estimates the displacement field at candidate craniotomy locations. This deformation map is coupled with an image analogy algorithm that produces realistic synthetic images that can be used to predict both the geometry and the appearance of the brain surface before opening the skull. These images account for cortical vessel deformations that may occur after opening the skull and is rendered in a way that increases the surgeon's understanding and assimilation. Our method was tested retrospectively on patients data showing good results and demonstrating the feasibility of practical use of our system.

PURPOSE We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health–supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors. PATIENTS AND METHODS In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI. RESULTS We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each. CONCLUSION SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.

To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 − 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 − 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 − 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.

Background and ObjectiveProlactinomas may cause drastic hormone fluctuations throughout the body. It is not fully understood how endogenous hormone disorders such as prolactinomas reshape the patient’s brain. By employing the resting-state functional magnetic resonance imaging technique, we aimed to investigate the whole-brain functional connectivity (FC) and its relationship with hormone levels in patients with prolactinomas.MethodsUsing whole-brain and seed-based functional connectivity analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched with age, sex, and handedness. Then we performed partial correlation analysis to examine the relationship between FC metrics and hormone levels.ResultsCompared to healthy controls, we found that prolactinoma patients showed significantly increased thalamocortical (visual cortex) and cerebellar-cerebral connectivity. In addition, endogenous hormone levels were positively correlated with the increased FC, and the hormone-FC relationships showed sex difference in prolactinoma patients.ConclusionsOur findings are the first to reveal the altered FC patterns and sex-dependent hormone-FC relationships in prolactinoma patients, indicating the important role of hormone levels in the neural mechanism of brain reorganization and hyperactive intrinsic connections in prolactinomas.

PURPOSE: Brain shift during tumor resection can progressively invalidate the accuracy of neuronavigation systems and affect neurosurgeons’ ability to achieve optimal resections. This paper compares two methods that have been presented in the literature to compensate for brain shift: a thin-plate spline deformation model and a finite element method (FEM). For this comparison, both methods are driven by identical sparse data. Specifically, both methods are driven by displacements between automatically detected and matched feature points from intraoperative 3D ultrasound (iUS). Both methods have been shown to be fast enough for intraoperative brain shift correction (Machado et al. in Int J Comput Assist Radiol Surg 13(10):1525–1538, 2018; Luo et al. in J Med Imaging (Bellingham) 4(3):035003, 2017). However, the spline method requires no preprocessing and ignores physical properties of the brain while the FEM method requires significant preprocessing and incorporates patient-specific physical and geometric constraints. The goal of this work was to explore the relative merits of these methods on recent clinical data. METHODS: Data acquired during 19 sequential tumor resections in Brigham and Women’s Hospital’s Advanced Multi-modal Image-Guided Operating Suite between December 2017 and October 2018 were considered for this retrospective study. Of these, 15 cases and a total of 24 iUS to iUS image pairs met inclusion requirements. Automatic feature detection (Machado et al. in Int J Comput Assist Radiol Surg 13(10):1525–1538, 2018) was used to detect and match features in each pair of iUS images. Displacements between matched features were then used to drive both the spline model and the FEM method to compensate for brain shift between image acquisitions. The accuracies of the resultant deformation models were measured by comparing the displacements of manually identified landmarks before and after deformation. RESULTS: The mean initial subcortical registration error between preoperative MRI and the first iUS image averaged 5.3 ± 0.75 mm. The mean subcortical brain shift, measured using displacements between manually identified landmarks in pairs of iUS images, was 2.5 ± 1.3 mm. Our results showed that FEM was able to reduce subcortical registration error by a small but statistically significant amount (from 2.46 to 2.02 mm). A large variability in the results of the spline method prevented us from demonstrating either a statistically significant reduction in subcortical registration error after applying the spline method or a statistically significant difference between the results of the two methods. CONCLUSIONS: In this study, we observed less subcortical brain shift than has previously been reported in the literature (Frisken et al., in: Miller (ed) Biomechanics of the brain, Springer, Cham, 2019). This may be due to the fact that we separated out the initial misregistration between preoperative MRI and the first iUS image from our brain shift measurements or it may be due to modern neurosurgical practices designed to reduce brain shift, including reduced craniotomy sizes and better control of intracranial pressure with the use of mannitol and other medications. It appears that the FEM method and its use of geometric and biomechanical constraints provided more consistent brain shift correction and better correction farther from the driving feature displacements than the simple spline model. The spline-based method was simpler and tended to give better results for small deformations. However, large variability in the spline results and relatively small brain shift prevented this study from demonstrating a statistically significant difference between the results of the two methods.

Fluorescence guided surgery (FGS) has fueled the development of novel technologies aimed at maximizing the utility of fluorescence imaging to help clinicians diagnose and in certain cases treat diseases across a breadth of disciplines such as dermatology, gynecology, oncology, ophthalmology, and neurosurgery. In neurosurgery, the goal of FGS technologies is to provide the neurosurgeon with additional information which can serve as a visual aid to better identify tumor tissue and associated margins. Yet, current clinical FGS technologies are qualitative in nature, limiting the ability to make accurate, reliable, and repeatable measurements. To this end, developments in fluorescence quantification are needed to overcome current limitations of FGS. Here we present an overview of the recent developments in quantitative fluorescence guidance technologies and conclude with the most recent developments aimed at wide-field quantitative fluorescence imaging approaches in neurosurgery.

Neuroimaging offers a non-invasive means to probe tumor tissue in order to inform decision making at all phases of brain tumor treatment. Diffusion MRI is particularly sensitive to tumor tissue microstructure, with greater heterogeneity being reflected as a larger diffusional kurtosis. Q-Space Trajectory Imaging (QTI) uses tensor-valued diffusion encoding (encoding along multiple directions per shot) to disentangle Isotropic Mean Kurtosis (MKi) from Anisotropic Mean Kurtosis (MKa), which are otherwise conflated in the Total Mean Kurtosis (MKt). To test whether disentangling MKi and MKa facilitates a more specific probe of tumor tissue heterogeneity and malignancy, we investigated if QTI parameters could distinguish low- from high-grade gliomas and enhancing from non-enhancing regions using pre-operative QTI imaging of 13 W.H.O. grade I-II and 18 grade III-IV glioma patients. We also analyzed these features separately for de novo and recurrent tumors. Regions of Interest (ROIs) were drawn on QTI maps, with support from T1 and T2-weighted images, for enhancing region, non-enhancing region, necrotic cavity, cyst, edema and resection cavity. ROC was used to gauge QTI parameter performance in classifying tumor characteristics. MKi was found to be the strongest predictor of tumor grade (AUC = 0.74, p = 0.019). MKi and MKt separated de novo from recurrent tumors (AUC = 0.80 and 0.76, p < 0.05). MKt separated enhancing regions from non-enhancing regions with an AUC of 0.88 in all tumors and 0.97 in de novo tumors. Our preliminary results highlight that tensor-valued diffusion MRI and QTI analysis have the potential to non-invasively characterize tumor grade. Further, MKt accurately differentiated enhancing from non-enhancing tumors and could potentially substitute for gadolinium injection in some situations thereby decreasing risk, time, and cost. Our ongoing studies in larger groups aim to further correlate molecular tumor markers (eg. IDH1 status) with these diffusion parameters.

Anti-lipid peroxidation effect of aqueous extracts of Ocimum sanctum, Tinospora cordifolia and Withania somnifera was evaluated against Fe2+-ascorbic acid-induced lipid peroxidation using rat liver mitochondria as model system, whereas, anti-arthritic activity was evaluated by proteinase inhibitory assay. O. sanctum showed potent anti-lipid peroxidation and anti-arthritic activities. T. cordifolia exhibited moderate anti-lipid peroxidation activity, but considerable anti-arthritic activity, whereas, W. somnifera revealed least lipid peroxidation inhibitory activity and considerable anti-arthritic activity. Besides, Folin-Ciocalteu reagent in terms of gallic acid equivalent achieved the total phenolic content and the trend was found to be O. sanctum > T. cordifolia > W. somnifera.

Introduction: Oxidative stress resulted from free radicals and reactive oxygen species are associated with many diseases. Several studies are going on worldwide directed towards finding natural antioxidants of plant origin. Plants containing phenolic compounds have been reported to possess strong antioxidant activity. The aim of the present study was to screen phytochemical constituents and in vitro antioxidant activity of Pithecellobium dulce Benth. aqueous and methanolic seed extracts. Methods and Materials: The aqueous (AEPD) and methanolic extract (MEPD) of Pithecellobium dulce seeds were studied for antioxidant potential by using different in vitro assays such as inhibition of DPPH, nitric oxide, hydroxyl, superoxide anions and lipid peroxidation. The total phenolic contents and reducing power of the extracts were also determined by using standard phytochemical reaction methods. Butylated hydroxyl toluene (BHT), ascorbic acid and mannitol were taken as standards. Results: The aqueous and methanolic extract of P. dulce seeds showed good dose dependant free radical scavenging activity in all the models. The total phenolic content of the aqueous and methanolic extract was found to be 1.31 ± 0.006 and 1.74 ± 0.003 mg gallic acid equivalents/g of extract powder respectively. Reducing power was also found to increase with increase in extracts concentrations. Conclusion: All the results of the in vitro antioxidant assays revealed antioxidant and free radical scavenging potential of P. dulce seeds, compared with standard antioxidants. This antioxidant activity may be endorsed to its high phenolic contents. Thus, our findings provide evidence that P. dulce is a potential source of natural antioxidants.