Peaglet: A user-friendly probabilistic Kernel density estimation of intracranial cortical and subcortical stimulation sites.

BACKGROUND: Data on human brain function obtained with direct electrical stimulation (DES) in neurosurgical patients have been recently integrated and combined with modern neuroimaging techniques, allowing a connectome-based approach fed by intraoperative DES data. Within this framework is crucial to develop reliable methods for spatial localization of DES-derived information to be integrated within the neuroimaging workflow. NEW METHOD: To this aim, we applied the Kernel Density Estimation for modelling the distribution of DES sites from different patients into the MNI space. The algorithm has been embedded in a MATLAB-based User Interface, Peaglet. It allows an accurate probabilistic weighted and unweighted estimation of DES sites location both at cortical level, by using shortest path calculation along the brain 3D geometric topology, and subcortical level, by using a volume-based approach. RESULTS: We applied Peaglet to investigate spatial estimation of cortical and subcortical stimulation sites provided by recent brain tumour studies. The resulting NIfTI maps have been anatomically investigated with neuroimaging open-source tools. COMPARISON WITH EXISTING METHODS: Peaglet processes differently cortical and subcortical data following their distinguishing geometrical features, increasing anatomical specificity of DES-related results and their reliability within neuroimaging environments. CONCLUSIONS: Peaglet provides a robust probabilistic estimation of the cortical and subcortical distribution of DES sites going beyond a region of interest approach, respecting cortical and subcortical intrinsic geometrical features. Results can be easily integrated within the neuroimaging workflow to drive connectomic analysis.

Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery.

Introduction: The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping. Methods: A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate. Results: We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection. Discussion: The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.

Intraoperative AIRO mobile computer tomography in frameless stereotactic procedures.

BACKGROUND: Multiple factors can affect the accuracy of neuronavigation, that is a relevant issue, particularly for frameless stereotactic procedures, where precision and optimal image-guidance is crucial for the surgical performance, workflow, and outcome. OBJECTIVE: To investigate the impact of AIRO Mobile Computer Tomography in frameless stereotactic approaches. METHODS: A retrospective study on 12 patients was performed. All the procedures were deployed using a frameless stereotactic technique, both for the collection of biopsy pathological specimens for diagnosis and insertion of drainage in the treatment of intracranial cystic lesions. RESULTS: Twelve patients (eight males, four females) underwent the frameless stereotactic procedure. Mean age at surgery was 55 (±5 SE). The mean volume of the lesion was 23.85 cm3 (±3.13). Six diagnostic biopsies and six cyst drainages were performed. The mean trajectory length was 75.9 ± 11.8 mm. Three posterior fossa lesions (27%) were approached through a retro-sigmoidal burr-hole. A craniotomy for draining a haematoma was performed after detection with AIRO-CT. No permanent neurological dysfunction, in-hospital or 30-day mortality were recorded. CONCLUSION: The AIRO-CT resulted feasible with a potential utility for stereotactic procedures. We showed how it could grant the efficacy of the stereotactic procedures reducing some technical and physical sources of inaccuracy, also enhancing safety and allowing prompt detection and management of intraoperative complications.

TGF-ß promotes microtube formation in glioblastoma through thrombospondin 1.

BACKGROUND: Microtubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs are abundant in chemoresistant gliomas, in particular, glioblastomas (GBMs), while they are uncommon in chemosensitive IDH-mutant and 1p/19q co-deleted oligodendrogliomas. The aim of this study was to identify potential signaling pathways involved in MT formation. METHODS: Bioinformatics analysis of TCGA was performed to analyze differences between GBM and oligodendroglioma. Patient-derived GBM stem cell lines were used to investigate MT formation under transforming growth factor-beta (TGF-ß) stimulation and inhibition in vitro and in vivo in an orthotopic xenograft model. RNA sequencing and proteomics were performed to detect commonalities and differences between GBM cell lines stimulated with TGF-ß. RESULTS: Analysis of TCGA data showed that the TGF-ß pathway is highly activated in GBMs compared to oligodendroglial tumors. We demonstrated that TGF-ß1 stimulation of GBM cell lines promotes enhanced MT formation and communication via calcium signaling. Inhibition of the TGF-ß pathway significantly reduced MT formation and its associated invasion in vitro and in vivo. Downstream of TGF-ß, we identified thrombospondin 1 (TSP1) as a potential mediator of MT formation in GBM through SMAD activation. TSP1 was upregulated upon TGF-ß stimulation and enhanced MT formation, which was inhibited by TSP1 shRNAs in vitro and in vivo. CONCLUSION: TGF-ß and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT-driven invasion/resistance network.