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Background : Elastic image fusion (EIF) using an intraoperative CT (iCT) scan may enhance neuronavigation accuracy and compensate for brain shift. Objective : To evaluate the safety and reliability of the EIF algorithm (Virtual iMRI Cranial 4.5, Brainlab AG, Munich Germany, for the identification of residual tumour in glioblastoma surgery. Moreover, the impact of brain shift on software reliability is assessed. Methods : This ambispective study included 80 patients with a diagnosis of glioblastoma. Pre-operative MRI was elastically fused with an intraoperative CT scan (BodyTom; Samsung-Neurologica, Danvers, MA, USA) acquired at the end of the resection. Diagnostic specificity and the sensitivity of each tool was determined. The impact of brain shift on residual tumour was statistically analysed. An analysis of accuracy was performed through Target Registration Error (TRE) measurement after rigid image fusion (RIF) and EIF. A qualitative evaluation of each Virtual MRI image (VMRI) was performed. Results : VMRI identified residual tumour in 26/80 patients (32.5%), confirmed by post-operative MRI (true positive). Of these, 5 cases were left intentionally due to DES-positive responses, 8 cases underwent near maximal or subtotal resection, and 13 cases were not detected by iCT. However, in the other 27/80 cases (33.8%), VMRI reported residual tumour that was present neither on iCT nor on post-operative MRI (false positive). i-CT showed a sensitivity of 56% and specificity of 100%; VMRI demonstrated a sensitivity of 100% and specificity of 50%. Spearman correlation analysis showed a moderate correlation between pre-operative volume and VMRI tumour residual. Moreover, tumour involving insula or infiltrating more than one lobe displayed higher median values ( p = 0.023) of virtual residual tumour. A statistically significant reduction towards lower TRE values after EIF was observed for test structures. Conclusions : Virtual iMRI was proven to be a feasible option to detect residual tumour. Its integration within a multimodal imaging protocol may provide neurosurgeons with intraoperatively updated imaging.

The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity areas of GBM IDHwt are often visible beyond the conventional EC. Therefore, the need to extend the surgical resection also to the FLAIR hyperintensity areas is a matter of debate. Since little is known about the histological composition of FLAIR hyperintensity regions, in this study we aimed to provide a comprehensive description of the histological features of EC and FLAIR hyperintensity regions sampled intraoperatively using neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence, in 33 patients with GBM, IDHwt. Assessing a total 109 histological samples, we found that FLAIR areas consisted in: (i) fragments of white matter focally to diffusely infiltrated by tumor cells in 76% of cases; (ii) a mixture of white matter with reactive astrogliosis and grey matter with perineuronal satellitosis in 15% and (iii) tumor tissue in 9%. A deeper knowledge of the histology of FLAIR hyperintensity areas in GBM, IDH-wt may serve to better guide neurosurgeons on the choice of the most appropriate surgical approach in patients with this neoplasm.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation.

Cellular composition and molecular signatures of the glioma core compared with infiltrative margins are different, and it is well known that the tumor edge is enriched in microglia. In this review of the literature, we summarize the role of the peritumoral area in high-grade gliomas (HGGs) from surgical and biological points of view. There is evidence on the dual role of microglia in HGGs-a scavenger-tumoricidal role when microglia are activated in an M1 phenotype and a role favoring tumor growth and infiltration/migration when microglia are activated in an M2 phenotype. Microglia polarization is mediated by complex pathways involving cross-talk with glioma cells. In this scenario, extracellular vesicles and their miRNA cargo seem to play a central role. The switch to a specific phenotype correlates with prognosis and the pathological assessment of a specific microglial setting can predict a patient's outcome. Some authors have designed an engineered microglial cell as a biologically active vehicle for the delivery of intraoperative near-infrared fluorescent dye with the aim of helping surgeons detect peritumoral infiltrated areas during resection. Furthermore, the pharmacological modulation of microglia-glioma cross-talk paves the way to more effective therapies.