Francesco Vergani

Background/Objectives: Navigated intraoperative ultrasound (N-ioUS) compensates for brain shift, but its place within a multimodal workflow alongside neuronavigation, 5-aminolevulinic acid (5-ALA) fluorescence and neurophysiological monitoring is not well defined. We describe functional and surgical outcomes in a single-centre series of functional-eloquent tumours resected with N-ioUS within such a workflow. Methods: Retrospective descriptive cohort study, reported per STROBE, of 104 consecutive patients who underwent N-ioUS-assisted resection of functionally eloquent intracranial tumours between 2011 and 2023. N-ioUS was an inclusion criterion, so no comparison group was available; the same-institution 5-ALA cohorts are cited as context only. Results: The cohort comprised WHO grade 4 gliomas (n = 42), WHO grade 2–3 gliomas (n = 33), metastases (n = 21) and other tumours (n = 8); 5-ALA was used in 74.0% and neurophysiological monitoring in 94.2%. No residual tumour was described in 22.5% of grade 4 gliomas, 53.3% of grade 2–3 gliomas and 73.7% of metastases with a documented extent of resection. Among patients at risk with documented postoperative status, a new motor deficit occurred in 4/16 (25.0%) grade 4, 4/21 (19.0%) grade 2–3 and 1/7 (14.3%) metastases patients. Median overall survival was 12.7 months for grade 4 gliomas and 22.2 months for metastases and was not reached for grade 2–3 gliomas; within grade 4 gliomas, no difference by extent of resection was detected in an underpowered exploratory comparison (log-rank p = 0.593). Conclusions: In this single-arm series the resection endpoint in eloquent tumours was set by functional rather than anatomical boundaries, and rates of complete resection and new deficit were in keeping with that constraint. The design permits no inference about the independent effect of N-ioUS, whose contribution may be greatest where the endpoint is anatomical, as in metastases, and requires prospective controlled evaluation.

Background: Brain tumours impose complex, spatially heterogeneous disturbances on neural circuits that extend far beyond the immediate lesion site. While gross anatomical displacement of the cortico-spinal tract (CST) has been extensively studied, the topological reorganization of the functionally informed structural connectome—and its dependence on tumour molecular phenotype—remains incompletely understood. Objectives: This study aimed to characterize upper-limb functionally informed network topology in brain tumour patients, identify histological and molecular patterns of structural reorganization at the cortical and subcortical level, and determine the impact on neurophysiological parameters. Methods: Forty-eight patients with supratentorial motor-eloquent tumours (MET’s) underwent diffusion-weighted imaging (DWI) as part of their preoperative motor mapping. Connectivity matrices based on streamline passing counts were extracted from 426 nodes of the HCPex atlas using DSI Studio^® upon seeding the structural connectome in the motor hotspot (best motor response) for the functional area of the upper limb identified using preoperative navigated transcranial magnetic stimulation (nTMS). Paired-sample t-tests compared tumour versus healthy hemispheres across network topology metrics. The impact of nTMS-derived excitability metrics—interhemispheric resting motor threshold ratio (iRMTr) and cortical silent period (CSP)—and tumour histological and molecular characteristics on the connectome was assessed. Results: The global network topology of the tumour hemisphere was preserved when compared to the healthy baseline hemisphere across all tumour types (p > 0.05). Subcortical analysis revealed significant hyper-connectivity in the tumour hemisphere, with elevated degree, strength, clustering coefficient, local efficiency, and eigenvector centrality (p < 0.05). Basal ganglia motor loop degree was increased in the tumour hemisphere (mean 7.37 versus 5.19; p = 0.0009). IDH-mutant tumours generated significantly more topologically organized compensatory networks than IDH-wildtype tumours (Clustering Coefficient 0.345 versus 0.273; p = 0.018). Of the cortical nodes on the side of the tumour, significant hyper-connectivity was seen in the supplementary motor area (p = 0.0011), premotor cortex (Area 6), with increased connection seen in 6 mp (medial premotor at p =0.0033) and 6 d (dorsal premotor at p = 0.025) and primary somatosensory cortex (p = 0.027). The presence of the tumour induced significant changes across all three domains: loss of CST volume (p < 0.001), prolongation of the cortical silent period indicative of intracortical inhibition (p < 0.0001), with significant prolongation in glioblastoma versus an oligodendroglioma. Conclusions: Brain tumours significantly impact the upper limb-centred structural connectome. While global network topology is preserved, tumours induce substantial subcortical and basal ganglia network reorganization by inducing compensatory hyper-connectivity. These findings suggest that structural connectomics offers a novel framework for non-invasive tumour characterization and surgical planning.

Minimally invasive parafascicular surgery (MIPS) represents a paradigm shift in the management of deep-seated brain tumors, enabling function-sparing resections previously limited to biopsy and/or medical therapy. Central to MIPS are structured frameworks guiding preoperative planning and intraoperative execution. The six-pillar concept—comprising imaging, navigation, atraumatic access, optics, resection, and postoperative care—provides a comprehensive approach to integrate advanced neuroimaging, tractography, tubular retractor systems, fluorescence-guided resection, and neuromonitoring to optimize functional outcomes. Five-point target-trajectory complex planning—craniotomy, outer radial corridor, inner radial corridor, target, and resection margins—translates preoperative imaging and functional mapping into a precise surgical trajectory, balancing maximal tumor resection with minimal disruption of eloquent brain structures. Preoperative assessment of tumor characteristics, vascular relationships, and cortical eloquence informs trajectory planning and intraoperative adjustments. A critical determinant of MIPS success is the intraoperative golden hour, referring to the high-risk period surrounding brain cannulation with a tubular retractor. Key principles include (1) precannulation system checks to ensure instrument readiness; (2) access injury prevention through optimized craniotomy sizing and sulcal preparation; (3) tubular-tumor targeting accuracy addressing brain and tubular translation, tumor displacement, and white-matter sleeves; and (4) intracranial pressure control strategies to minimize tissue strain and venous congestion. Overcoming this period enables a controlled resection phase guided by the above-mentioned surgical adjuncts. The six-pillar concept and five-point target-trajectory complex planning are the foundations of MIPS planning, whereas the intraoperative golden hour provides a roadmap for successful intraoperative delivery of the surgical plan.

Fluorescence-guided surgery (FGS) was pioneered for glioma and is now established as the standard of care. Gliomas are infiltrative tumours with diffuse margins. FGS provides improved intra-operative identification of tumour margins based on tumour-specific emission visible to the operating surgeon, resulting in increased rates of gross total resection. Multiple fluorescence agents may be used including 5-ALA, fluorescein sodium, and indocyanine green (ICG). This review details the indication, required equipment, mechanism of action, evidence base, limitations, and regulatory issues for each fluorophore as utilised in current clinical practice. FGS for glioma is limited by a reliance on subjective interpretation of visible fluorescence, which is often not present in low-grade glioma (LGG) or at the infiltrative tumour margin. Consequently, there has been a drive to develop enhanced, objective FGS techniques utilising both quantitative fluorescence (QF) imaging systems and novel fluorophores. This review provides an overview of emerging QF imaging systems for FGS. The pipeline for novel fluorophore development is also summarised.

The integration of diffusion MRI tractography into neurosurgical practice raises an essential question: is this technology accurate enough to be used to inform surgery? This short communication summarizes the key points of a debate held at the 2024 Tract-Anat Retreat on the clinical utility and limitations of tractography in neurosurgery. While tractography in neurosurgery offers unique insights into patient-specific white matter anatomy and has proven value for surgical planning, risk stratification and patient counselling, we identified limitations, challenges, and areas for improvement. These include variability in reconstruction methods, the importance of multimodal integration, false negative results and intrinsic limitations at surgery, such as brain shift during navigation. These perspectives highlight the need for standardized protocols, functional validation, and enhanced surgeon training to ensure the cautious and effective use of tractography in the operative setting.

Background: The tubular retractor-assisted minimally invasive parafascicular approach (trMIPS) is a transsulcal approach to deep-seated brain tumours. It is a safe surgical approach but its impact on the microvascular dynamics of the retracted cortex and its clinical implications are unknown. Methods: This was a single-centre prospective study including patients with deep-seated brain tumours operated on with a trMIPS (BrainPath Nico System^©). All patients underwent pre- and post-cannulation indocyanine green study using a FLOW 800 module in a KINEVO Zeiss^© microscope. Speed, delay, time-to-peak (TtP) rise-in-time and cerebral blood flow index (CBFI) metrics were assessed. Results: Thirty-five patients were included, with 144 regions-of-interest (ROIs) selected. The majority of patients were diagnosed with glioblastoma (51.43%), and 37.14% of patients had a preoperative focal neurological deficit (FND) at presentation. A ROI-based analysis concluded that an increase in speed and CBFI was related with a worse neurological outcome when comparing the pre- and post-brain cannulation assessments (speed: deterioration = 43.12 ± 80.60% versus stable = −14.51 ± 57.80% versus improvement = 6.93 ± 31.33%, p < 0.0001; CBFI: deterioration = 50.40 ± 88.17% versus stable = −2.70 ± 67.54% versus improvement = −38.98 ± 26.17%, p = 0.0005). These findings were reproducible in a combined-ROI per patient analysis and confirmed after adjustment for confounding. Conclusion: Microvascular flow dynamics impact trMIPS outcomes as an increase in the speed and CBFI after decannulation was related with worse neurological outcome.

Intracranial dermoid cysts are benign lesions that may be diagnosed incidentally or present symptomatically due to mass effect—focal neurological deficits, seizures and/or hydrocephalus—or chemical meningitis secondary to spontaneous rupture. The use of tubular retractors in minimally invasive parafascicular surgery (tsMIPS) has been described extensively as a technique to preserve neurological function whilst safely maximizing the extent of resection. The authors present the first use of the tsMIPS approach for removal of a dermoid cyst in a 68-year-old female who presented with abulia and seizures due to a large Sylvian fissure dermoid cyst. This approach minimized trauma to surrounding cortical–subcortical structures, as supported by connectome analyses, without sacrificing visualization of the operative field. Additionally, itavoided manipulation of the lenticulostriate arteries attached to the walls of the dermoid cyst. The use of an endoscope ensured complete drainage of the cyst components and therefore the effectiveness of the procedure.