Our study is the first large-scale implementation of iCEUS in neurosurgery as a dynamic and continuous real-time imaging tool for brain surgery and provides the first iCEUS characterization of different brain neoplasms. The ability of CEUS to highlight and characterize brain tumor will possibly provide the neurosurgeon with important information anytime during a surgical procedure.

Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5a High ). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma. Cancer Res; 77(4); 996-1007. Ó2016 AACR.

Background. Contrast enhanced ultrasound (CEUS) is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before. Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas. Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology. Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns. Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors' biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

The survival of tumor-bearing animals was improved with local delivery of TMZ compared with systemic administration. XRT in combination with intracranial TMZ did not cause additional toxicity and prolonged the survival even further.

Subcutaneous administration of simvastatin after the onset of SAH attenuates perivascular granulocyte migration and ameliorates basilar artery vasospasm after experimental SAH in rabbits. 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, such as simvastatin, may potentially serve as agents in the prevention of cerebral vasospasm after SAH.

The major shortcoming of image-guided navigation systems is the use of presurgically acquired image data, which does not account for intra-operative changes such as brain shift, tissue deformation and tissue removal occurring during the surgical procedure. Intra-operative ultrasound (iUS) is becoming widely used in neurosurgery but they lack orientation and panoramic view. In this article, we describe our procedure for US-based real-time neuro-navigation during surgery. We used fusion imaging between preoperative magnetic resonance imaging (MRI) and iUS for brain lesion removal in 67 patients so far. Surgical planning is based on preoperative MRI only. iUS images obtained during surgery are fused with the preoperative MRI. Surgery is performed under intra-operative US control. Relying on US imaging, it is possible to recalibrate navigated MRI imaging, adjusting distortion due to brain shift and tissue resection, continuously updating the two modalities. Ultrasound imaging provides excellent visualization of targets, their margins and surrounding structures. The use of navigated MRI is helpful in better understanding cerebral ultrasound images, providing orientation and panoramic view. Intraoperative US-guided neuro-navigation adjustments are very accurate and helpful in the event of brain shift. The use of this integrated system allows for a true real-time feedback during surgery.Keywords Navigation Á Brain shift Á Intraoperative imaging Á Ultrasound Á Brain tumor Á Fusion imaging Sommario Il principale difetto della neurochirurgia guidata da immagini è il basarsi su immagini acquisite prima dell'intervento, che per ovvie ragioni non possono tenere conto di fenomeni intra-operatori come il brain-shift, la deformazione dei tessuti e l'asportazione di tessuto patologico. L'ecografia intra-operatoria (iUS) sta acquisendo sempre maggior rilevanza in ambito neurochirurgico ma è limitata dalla difficoltosa interpretazione dell'orientamento delle immagini e dalla scarsa panoramicità. In questo articolo descriviamo la nostra tecnica di neuronavigazione real-time basata sull'ecografia intra-operatoria. Fino ad ora abbiamo impiegato la fusione d'immagini tra la risonanza magnetica (MRI) pre-operatoria e l'iUS in 67 pazienti affetti da neoplasie cerebrali. La pianificazione dell'intervento e l'approccio chirurgico è basata sulla (MRI) pre-operatoria mentre l'intervento è guidato dall'iUS. Basandosi sull'iUS è possibile correggere la calibrazione delle immagini (MRI) pre-operatorie correggendo il brain-shift, aggiornando continuamente le due modalità. L'ecografia intra-operatoria permette una eccellente identificazione dei target, dei margini e delle strutture circostanti. L'uso del navigatore basato su (MRI) pre-operatoria è utile nella comprensione delle immagini ecografiche soprattutto per quanto riguarda l'orientazione e la visione panoramica. Le correzione del sistema di neuronavigazione basate sull'iUS sono accurate e utili nel caso di fenomeni intra-operatori come il brain-shift, la deformazione dei tessuti ...

OncoGel containing 6.3 mg/ml of paclitaxel is safe for intracranial injection in rats and effective when administered on Day 0. When combined with radiation therapy, the combination was more effective than either therapy alone and should be studied clinically for the treatment of malignant glioma.

The main goal in meningioma surgery is to achieve complete tumor removal, when possible, while improving or preserving patient neurological functions. Intraoperative imaging guidance is one fundamental tool for such achievement. In this regard, intra-operative ultrasound (ioUS) is a reliable solution to obtain real-time information during surgery and it has been applied in many different aspect of neurosurgery. In the last years, different ioUS modalities have been described: B-mode, Fusion Imaging with pre-operative acquired MRI, Doppler, contrast enhanced ultrasound (CEUS), and elastosonography. In this paper, we present our US based multimodal approach in meningioma surgery. We describe all the most relevant ioUS modalities and their intraoperative application to obtain precise and specific information regarding the lesion for a tailored approach in meningioma surgery. For each modality, we perform a review of the literature accompanied by a pictorial essay based on our routinely use of ioUS for meningioma resection.