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Background and purpose In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). Methods We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. Results We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase). Conclusion Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Purpose Glioblastoma (GBM) is associated with a poorer prognosis when leptomeningeal dissemination (LMD) occurs. Recently, the role of both ventricular entry (VE) during surgery and subventricular zone localization of tumors in promoting LMD in GBM patients has been debated. This article investigates the role of VE in causing LMD in GBM patients. Methods We conducted a retrospective analysis of GBMs operated on at our Institution between March 2018 and December 2020. We collected pre- and post-surgical images, anamnestic information, and surgical reports. Results Two hundred cases were collected. The GBM localization was periventricular in 69.5% of cases, and there was a VE during the surgical procedure in 51% of cases. The risk of post-surgical LMD in the case of VE was 16%. The rate of LMD was higher in the case of VE than not-VE (27.4% vs. 4%, p Conclusion According to our data, VE is an independent factor associated with a higher rate of post-surgical LMD, and the periventricular localization is not independently correlated to this negative outcome. Neurosurgeons should avoid VE when possible. The correct surgical strategy should be founded on balancing the need for maximal EOR and the risks associated with VE.

The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed.

The ictal-interictal continuum represents a diagnostic challenge even for expert neurrophysiologists, often requiring an additional multimodal diagnostic workup to understand its clinical significance. Lateralised rhythmic delta activity (LRDA) is an ictal-interictal continuum pattern that has only recently been investigated and recognised as potentially ictogenic or sometimes even ictal. We describe a patient who presented with acute-onset aphasia, initially suspected of having a stroke; advanced brain imaging with CT-perfusion showed features suggesting regional left temporo-parietal hyperperfusion and an EEG revealed LRDA with fluctuations and intermixed sharp waves in the same areas. Treatment with lacosamide caused both clinical and EEG improvement after a few hours, supporting the hypothesis that the EEG pattern represented an ictal/interictal phenomenon. In the literature, a correlation between metabolic/perfusion imaging and ictal-interictal continuum patterns is described regarding lateralised periodic discharges but less studied for LRDA. In this case, we adopted a multimodal approach, integrating advanced imaging, EEG, clinical features, and response to therapy, to consider the overall clinical presentation as focal NCSE.

INTRODUCTION Oncological aggressiveness and the ability to present distant localizations are known in high-grade gliomas (HGGs), but the knowledge about the possible aggressiveness of LGGs is scarce, especially concerning possible spinal localization. EVIDENCE ACQUISITION A systematic search of LGGs with spinal localization on the three primary online databases (PubMed/MEDLINE, Embase, and Cochrane) was conducted. We included adult patients with histological diagnosis of intracranial LGG and specified WHO grade showing a remote spinal localization during follow-up. Additionally, we present a case of a left temporal LGG presenting a spinal localization fourteen years after the first appearance. We compared the survival rates of LGGs in our series with those of LGGs without spinal localizations. EVIDENCE SYNTHESIS Seven articles dealing with the subject and eight patients were considered (including our case), with a mean age at diagnosis of 42.25 years (range 26-69 years). The mean latency between a diagnosis of intracranial LGGs and a spinal localization occurrence was 7.37 years (range 2-14 years), and an increased WHO grade of the spinal localization compared to the brain LGG was observed in all patients. There was no sign of intracranial progression at the time of spinal glioma diagnosis in four cases, including ours. Survival at ten years was 28% against a 10-year survival rate of 65-71% for LGGs without distant localization, as reported in the literature. CONCLUSIONS Spinal metastasis of intracranial LGGs is an adverse prognostic factor. Surgical violation of ventricles can play a role in the pathophysiology of CSF spread of tumor cells in LGGs.

To investigate the association and agreement between magnetic resonance dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and computed tomography perfusion (CTP) in determining vascularity and permeability of primary and secondary brain tumors.DSC-PWI and CTP studies from 97 patients with high-grade glioma, low-grade glioma and solitary brain metastasis were retrospectively reviewed. Normalized cerebral blood flow (nCBF), cerebral blood volume (nCBV), capillary transfer constant (nK2) and permeability surface area product (nPS) values were obtained. Variables among groups were compared, and correlation and agreement between DSC-PWI and CTP were tested.All DSC-PWI and CTP parameters were higher in high-grade than in low-grade gliomas (p 0.01 and p 0.001). Metastases had greater DSC-PWI nCBV (p 0.05), nCTP-CBF (p 0.05), nCTP-CBV (p 0.01) and nCTP-PS (p 0.0001) than low-grade gliomas and more elevated nCTP-PS (p 0.01) than high-grade gliomas. The correlation was strong between DSC-PWI nCBF and CTP nCBF (r = 0.79; p 0.00001) and between DSC-PWI nCBV and CTP nCBV (r = 0.83; p 0.00001), weaker between DSC-PWI nK2 and CTP nPS (r = 0.29; p 0.01). Bland-Altman plots indicated that the agreement was strong between DSC-PWI nCBF and CTP nCBF, good between DSC-PWI nCBV and CTP nCBV and poorer between DSC-PWI nK2 and CTP nPS.DSC-PWI and CTP CBF and CBV maps were comparable and interchangeable in the assessment of tumor vascularity, unlike DSC-PWI K2 and CTP PS maps that were more discordant in the analysis of tumor permeability. CTP could be an alternative method to quantify tumor neoangiogenesis when MRI is not available or when the patient does not tolerate it.

BACKGROUND AND PURPOSE The role of apparent diffusion coefficient (ADC) for preoperative grading and treatment planning of high-grade gliomas (HGG) is still debated since the assumption of inverse correlation between ADC and cellularity is not completely coherent with the results of some studies. It has been recently hypothesized that restricted diffusivity in HGG may be related to hypoxic/ischemic changes inside the tumor. We therefore investigated the differences of ADC values between areas with magnetic resonance spectroscopy (MRS) markers of hypoxia and necrosis (lactate and lipid compounds) and regions with lack of both metabolites. METHODS The MRS datasets and the corresponding ADC maps of 28 patients with HGG were retrospectively reviewed. Circular regions of interest (ROIs) were placed on ADC maps by means of spectral characteristics, considering the solid portions of gliomas. One-way ANOVA or Welch test were performed for multiple comparison of the Mean ADC, minimum ADC (minADC), and standard deviation of pixel-by-pixel ADC measurements (ADC SD) values among the groups of ROIs with lactate, lipids, and lack of both metabolites (LAC, LIP, and NEG group, respectively). RESULTS The minADC values in LAC group (908 ± 161 × 10−6 mm2s−1) were found to be significantly (P = .03) higher than in NEG group (792 ± 122 × 10−6 mm2s−1). We did not find other significant differences by the multiple comparison tests. CONCLUSIONS HGG areas with MRS markers of hypoxia and necrosis are not associated with restricted diffusivity. To explain the trend to diffusion facilitation in HGG lactate-expressing regions, we hypothesize a possible hypoxia-induced volume reduction of glioma cells with extracellular shift of cytoplasmic water.

Purpose Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Methods Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. Results A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. Conclusions This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5–10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5–19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

The role of apparent diffusion coefficient (ADC) for preoperative grading and treatment planning of high-grade gliomas (HGG) is still debated since the assumption of inverse correlation between ADC and cellularity is not completely coherent with the results of some studies. It has been recently hypothesized that restricted diffusivity in HGG may be related to hypoxic/ischemic changes inside the tumor. We therefore investigated the differences of ADC values between areas with magnetic resonance spectroscopy (MRS) markers of hypoxia and necrosis (lactate and lipid compounds) and regions with lack of both metabolites.The MRS datasets and the corresponding ADC maps of 28 patients with HGG were retrospectively reviewed. Circular regions of interest (ROIs) were placed on ADC maps by means of spectral characteristics, considering the solid portions of gliomas. One-way ANOVA or Welch test were performed for multiple comparison of the Mean ADC, minimum ADC (minADC), and standard deviation of pixel-by-pixel ADC measurements (ADC SD) values among the groups of ROIs with lactate, lipids, and lack of both metabolites (LAC, LIP, and NEG group, respectively).The minADC values in LAC group (908 ± 161 × 10HGG areas with MRS markers of hypoxia and necrosis are not associated with restricted diffusivity. To explain the trend to diffusion facilitation in HGG lactate-expressing regions, we hypothesize a possible hypoxia-induced volume reduction of glioma cells with extracellular shift of cytoplasmic water.

Corpus callosum is one of the common sites of brain lesion, whose involvement is an indicator of a more severe prognosis, produced by traumatic shearing stresses resulting in diffuse axonal injury (DAI). Computed tomography (CT) in acute phase is considered to have a limited role for the detection of non-hemorrhagic or petechial hemorrhagic DAI lesions. New generation multidetector CT scanners allow faster acquisition of thinner-slice images and post-processing reformations. Three patients with severe closed head trauma underwent CT examinations using a multidetector scanner, a few hours and the day after injury. The review of original images with narrow window width and integration with reconstruction of thinner slices from raw-data and post-processing multiplanar reformations (MPR) helped to detect the onset of hypodense or predominantly hypodense areas of corpus callosum, not present at admission and afterwards confirmed by MRI.

We evaluated the possibility of improving detection of a dense intracranial artery on CT in acute stroke by narrowing window width, varying window level and performing a thin-slice helical scan for the circle of Willis, in some cases followed by postprocessing maximum-intensity projections. We carried out 32 examinations of 31 patients with a documented cerebral ischaemic attack, performing cranial CT within 6 h of the onset of symptoms. Patients with intracranial haemorrhage were excluded, as were patients who went on to thrombolytic therapy. Varying window width and centre level on standard 5 mm thick contiguous axial slices, we detected a dense proximal middle cerebral artery (MCA) in a higher proportion of patients. A 1.1 mm thick helical scan through the circle of Willis improved recognition of a dense distal horizontal segment and the temporoinsular branches of the MCA and of a dense posterior cerebral artery.

Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntington's disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation.

Maximum intensity projections reconstructions from 2.5 mm unenhanced multidetector computed tomography axial slices were obtained from 49 patients within the first 6 h of anterior-circulation cerebral strokes to identify different patterns of the dense artery sign and their prognostic implications for location and extent of the infarcted areas. The dense artery sign was found in 67.3% of cases. Increased density of the whole M1 segment with extension to M2 of the middle cerebral artery was associated with a wider extension of cerebral infarcts in comparison to M1 segment alone or distal M1 and M2. A dense sylvian branch of the middle cerebral artery pattern was associated with a more restricted extension of infarct territory. We found 62.5% of patients without a demonstrable dense artery to have a limited peripheral cortical or capsulonuclear lesion. In patients with a 7-10 points on the Alberta Stroke Early Programme Computed Tomography Score and a dense proximal MCA in the first hours of ictus the mean decrease in the score between baseline and follow-up was 5.09+/-1.92 points. In conclusion, maximum intensity projections from thin-slice images can be quickly obtained from standard computed tomography datasets using a multidetector scanner and are useful in identifying and correctly localizing the dense artery sign, with prognostic implications for the entity of cerebral damage.

Hyperattenuating middle cerebral arteries on CT in acute stroke should generally not be associated with presence of intraluminal clot when bilaterally seen. We report a case of a woman who underwent emergency CT 60 min after sudden onset of coma. Bilateral dense middle cerebral arteries without parenchymal hypoattenuating areas or indirect signs of cerebral edema were present. CT angiography confirmed occlusion of the right middle cerebral artery and left internal carotid artery and middle cerebral artery.

The aim of this study is to provide a stepwise contouring guide to delineate the organs at risk in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Acute and late toxicity with risk of visual and hearing deficits, hormonal impairment and neurocognitive alterations, is a critical point in radiation treatment of patients affected by brain tumors. Moreover, accurate delineation of organ at risks is essential for the inverse-planning process of intensity modulated radiation treatment (IMRT). However, anatomic cerebral normal structures are not always easily recognizable either on simulation CT scan and on coregistered MRI scan used for radiotherapy planning. We have developed a detailed anatomy atlas on Computed tomography (CT) imaging and magnetic resonance (MR) imaging of brain. The following regions of interest were defined: optic chiasm, cochlea, pituitary gland, temporal lobe and hippocampus. Some main notions of anatomy of the organs at risk are provided together with some landmarks easily to be found on the imaging scans. Detailed contouring recommendations are provided in order to significantly improve the contour accuracy and concordance. This report also provides for all the above-mentioned organs at risk a systematic review for the recommended dose constraints both for adult and pediatric patients. This guide is a useful tool for improving daily practice and decreasing the differences in organs at risk delineation between radiation oncologists.

INTRODUCTION: Accurate assessment of the exact number of brain metastases is of utmost importance in the decision-making process for the appropriate treatment. The diagnostic efficacy in the detection of additional brain metastases of a double dose contrast three-dimensional, T1-Weighted Gradient-Echo Imaging was evaluated. METHODS: Before undergoing radiosurgical treatment, patients underwent a brain magnetic resonance imaging (MRI) scan to be used during the treatment planning in order to contour the targets and to locate the brain lesions as they relate to the stereotactic frame. All the patients underwent a post-contrast study with T1-weighted, 3D Magnetization-Prepared Rapid Acquisition Gradient Echo (MP RAGE) sequence. We used a double dose of gadobenate dimeglumine and slice thickness of 0.9 mm. RESULTS: Starting from October 2012 to February 2014, we treated with Gamma Knife radiosurgery (GKRS) 62 patients with brain metastases. On the diagnostic MRI, all the patients had a number of lesions ≤4. Median time interval between diagnostic MRI scan and the day of GKRS was 11 days (range 5-20) A total of 54 additional lesions were detected on MR imaging performed in the same day of the GKRS in twenty-two patients out of 62 (35.5%). A median number of 2 additional lesions were detected (range 1-8). Among these 22 patients only 14 patients had a number of lesions ≤4 on the day of treatment. Patients with a total number of lesions ≤10 were treated with GKRS. Two patients with a total number of lesions > 10 were treated with whole brain radiotherapy (WBRT). CONCLUSIONS: A double-contrast study with T1-weighted, volumetric MPRAGE sequence may offer better staging for patients with brain metastases. In our opinion, it should be recommended in all the patients with newly diagnosed brain metastases because the detection of the real number of lesions is crucial for an adequate treatment and it also may lead to choose different therapeutic strategies.