DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions.

PURPOSE: The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. METHODS: This retrospective study, spanning 2016-2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. RESULTS: The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. CONCLUSION: Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma's pure edema.

The T1-dark-rim: A novel imaging sign for detecting smoldering inflammation in multiple sclerosis.

PURPOSE: Paramagnetic rim lesions (PRLs), usually identified in susceptibility-weighted imaging (SWI), are a promising prognostic biomarker of disability progression in multiple sclerosis (MS). However, SWI is not routinely performed in clinical practice. The objective of this study is to define a novel imaging sign, the T1-dark rim, identifiable in a standard 3DT1 gradient-echo inversion-recovery sequence, such as 3D T1 turbo field echo (3DT1FE) and explore its performance as a SWI surrogate to define PRLs. METHODS: This observational cross-sectional study analyzed MS patients who underwent 3T magnetic resonance imaging (MRI) including 3DT1TFE and SWI. Rim lesions were evaluated in 3DT1TFE, processed SWI, and SWI phase and categorized as true positive, false positive, or false negative based on the value of the T1-dark rim in predicting SWI phase PRLs. Sensitivity and positive predictive values of the T1-dark rim for detecting PRLs were calculated. RESULTS: Overall, 80 rim lesions were identified in 63 patients (60 in the SWI phase and 78 in 3DT1TFE; 58 true positives, 20 false positives, and two false negatives). The T1-dark rim demonstrated 97% sensitivity and 74% positive predictive value for detecting PRLs. More PRLs were detected in the SWI phase than in processed SWI (60 and 57, respectively). CONCLUSION: The T1-dark rim sign is a promising and accessible novel imaging marker to detect PRLs whose high sensitivity may enable earlier detection of chronic active lesions to guide MS treatment escalation. The relevance of T1-dark rim lesions that are negative on SWI opens up a new field for analysis.

Differentiating IDH-mutant astrocytomas and 1p19q-codeleted oligodendrogliomas using DSC-PWI: high performance through cerebral blood volume and percentage of signal recovery percentiles.

OBJECTIVE: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. METHODS: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010-2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. RESULTS: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. CONCLUSIONS: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. CLINICAL RELEVANCE STATEMENT: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. KEY POINTS: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification.

Early pseudoprogression and progression lesions in glioblastoma patients are both metabolically heterogeneous.

The standard treatment in glioblastoma includes maximal safe resection followed by concomitant radiotherapy plus chemotherapy and adjuvant temozolomide. The first follow-up study to evaluate treatment response is performed 1 month after concomitant treatment, when contrast-enhancing regions may appear that can correspond to true progression or pseudoprogression. We retrospectively evaluated 31 consecutive patients at the first follow-up after concomitant treatment to check whether the metabolic pattern assessed with multivoxel MRS was predictive of treatment response 2 months later. We extracted the underlying metabolic patterns of the contrast-enhancing regions with a blind-source separation method and mapped them over the reference images. Pattern heterogeneity was calculated using entropy, and association between patterns and outcomes was measured with Cramér's V. We identified three distinct metabolic patterns-proliferative, necrotic, and responsive, which were associated with status 2 months later. Individually, 70% of the patients showed metabolically heterogeneous patterns in the contrast-enhancing regions. Metabolic heterogeneity was not related to the regions' size and only stable patients were less heterogeneous than the rest. Contrast-enhancing regions are also metabolically heterogeneous 1 month after concomitant treatment. This could explain the reported difficulty in finding robust pseudoprogression biomarkers.

Deeply 3D-T1-TFE hypointense voxels are characteristic of phase-rim lesions in multiple sclerosis.

OBJECTIVES: The development of new drugs for the treatment of progressive multiple sclerosis (MS) highlights the need for new prognostic biomarkers. Phase-rim lesions (PRLs) have been proposed as markers of progressive disease but are difficult to identify and quantify. Previous studies have identified T1-hypointensity in PRLs. The aim of this study was to compare the intensity profiles of PRLs and non-PRL white-matter lesions (nPR-WMLs) on three-dimensional T1-weighted turbo field echo (3DT1TFE) MRI. We then evaluated the performance of a derived metric as a surrogate for PRLs as potential markers for risk of disease progression. METHODS: This study enrolled a cohort of relapsing-remitting (n = 10) and secondary progressive MS (n = 10) patients for whom 3 T MRI was available. PRLs and nPR-WMLs were segmented, and voxel-wise normalized T1-intensity histograms were analyzed. The lesions were divided equally into training and test datasets, and the fifth-percentile (p5)-normalized T1-intensity of each lesion was compared between groups and used for classification prediction. RESULTS: Voxel-wise histogram analysis showed a unimodal histogram for nPR-WMLs and a bimodal histogram for PRLs with a large peak in the hypointense limit. Lesion-wise analysis included 1075 nPR-WMLs and 39 PRLs. The p5 intensity of PRLs was significantly lower than that of nPR-WMLs. The T1 intensity-based PRL classifier had a sensitivity of 0.526 and specificity of 0.959. CONCLUSIONS: Profound hypointensity on 3DT1TFE MRI is characteristic of PRLs and rare in other white-matter lesions. Given the widespread availability of T1-weighted imaging, this feature might serve as a surrogate biomarker for smoldering inflammation. CLINICAL RELEVANCE STATEMENT: Quantitative analysis of 3DT1TFE may detect deeply hypointense voxels in multiple sclerosis lesions, which are highly specific to PRLs. This could serve as a specific indicator of smoldering inflammation in MS, aiding in early detection of disease progression. KEY POINTS: • Phase-rim lesions (PRLs) in multiple sclerosis present a characteristic T1-hypointensity on 3DT1TFE MRI. • Intensity-normalized 3DT1TFE can be used to systematically identify and quantify these deeply hypointense foci. • Deep T1-hypointensity may act as an easily detectable, surrogate marker for PRLs.

Proton MR spectroscopy shows improved performance to segregate high-grade astrocytoma subgroups when defined with the new 2021 World Health Organization classification of central nervous system tumors.

OBJECTIVES: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups. METHODS: Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared. RESULTS: The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838). CONCLUSION: Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria. CLINICAL RELEVANCE STATEMENT: The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy. KEY POINTS: • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.

MR dynamic-susceptibility-contrast perfusion metrics in the presurgical discrimination of adult solitary intra-axial cerebellar tumors.

OBJECTIVES: Adult solitary intra-axial cerebellar tumors are uncommon. Their presurgical differentiation based on neuroimaging is crucial, since management differs substantially. Comprehensive full assessment of MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) may reveal key differences between entities. This study aims to provide new insights on perfusion patterns of these tumors and to explore the potential of DSC-PWI in their presurgical discrimination. METHODS: Adult patients with a solitary cerebellar tumor on presurgical MR and confirmed histological diagnosis of metastasis, medulloblastoma, hemangioblastoma, or pilocytic astrocytoma were retrospectively retrieved (2008-2023). Volumetric segmentation of tumors and normal-appearing white matter (for normalization) was semi-automatically performed on CE-T1WI and coregistered with DSC-PWI. Mean normalized values per patient tumor-mask of relative cerebral blood volume (rCBV), percentage of signal recovery (PSR), peak height (PH), and normalized time-intensity curves (nTIC) were extracted. Statistical comparisons were done. Then, the dataset was split into training (75%) and test (25%) cohorts and a classifier was created considering nTIC, rCBV, PSR, and PH in the model. RESULTS: Sixty-eight patients (31 metastases, 13 medulloblastomas, 13 hemangioblastomas, and 11 pilocytic astrocytomas) were included. Relevant differences between tumor types' nTICs were demonstrated. Hemangioblastoma showed the highest rCBV and PH, pilocytic astrocytoma the highest PSR. All parameters showed significant differences on the Kruskal-Wallis tests (p < 0.001). The classifier yielded an accuracy of 98% (47/48) in the training and 85% (17/20) in the test sets. CONCLUSIONS: Intra-axial cerebellar tumors in adults have singular and significantly different DSC-PWI signatures. The combination of perfusion metrics through data-analysis rendered excellent accuracies in discriminating these entities. CLINICAL RELEVANCE STATEMENT: In this study, the authors constructed a classifier for the non-invasive imaging presurgical diagnosis of adult intra-axial cerebellar tumors. The resultant tool can be a support for decision-making in the clinical practice and enables optimal personalized patient management. KEY POINTS: • Adult intra-axial cerebellar tumors exhibit specific, singular, and statistically significant different MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) signatures. • Data-analysis, applied to MR DSC-PWI, could provide added value in the presurgical diagnosis of solitary cerebellar metastasis, medulloblastoma, hemangioblastoma, and pilocytic astrocytoma. • A classifier based on DSC-PWI metrics yields excellent accuracy rates and could be used as a support tool for radiologic diagnosis with clinician-friendly displays.

Tumoral and normal brain tissue extraction protocol for wide-scope screening of organic pollutants.

Little is known about the presence of organic pollutants in human brain (and even less in brain tumors). In this regard, it is necessary to develop new analytical protocols capable of identifying a wide range of exogenous chemicals in this type of samples (by combining target, suspect and non-target strategies). These methodologies should be robust and simple. This is particularly challenging for solid samples, as reliable extraction and clean-up techniques should be combined to obtain an optimal result. Hence, the present study focuses on the development of an analytical methodology that allows the screening of a wide range of organic chemicals in brain and brain tumor samples. This protocol was based on a solid-liquid extraction based on bead beating, solid-phase extraction clean-up with multi-layer mixed-mode cartridges, reconstitution and LC-HRMS analysis. To evaluate the performance of the extraction methodology, a set of 66 chemicals (e.g., pharmaceuticals, biocides, or plasticizers, among others) with a wide range of physicochemical properties was employed. Quality control parameters (i.e., linear range, sensitivity, matrix effect (ME%), and recoveries (R%)) were calculated and satisfactory results were obtained for them (e.g., R% within 60-120% for 32 chemicals, or ME% higher than 50% (signal suppression) for 79% of the chemicals).

High Myoinositol on Proton MR Spectroscopy Could Be a Potential Signature of Papillary Tumors of the Pineal Region-Case Report of Two Patients.

Papillary tumor of the pineal region (PTPR) is an uncommon entity in which a presurgical suspicion may be crucial for patient management. Maximal safe neurosurgical resection is of choice when PTPR is suspected, whereas non-surgical approaches can be considered in other tumors of the pineal region, such as pineocytoma or concrete subtypes of germ-cell tumors. In general terms, imaging features of tumors of the pineal region have been reported to be unspecific. Nevertheless, in this report, we describe two pathology-confirmed PTPRs in which presurgical proton MR spectroscopy demonstrated extremely high myoinositol, a pattern which drastically differs from that of other pineal tumors. We hypothesize that this high myoinositol may be related to PTPR's known ependymal component, and that it could be used as a specific non-invasive diagnostic signature.

Inferior fronto-occipital fascicle displacement in temporoinsular gliomas using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Brain tumors can result in displacement or destruction of important white matter tracts such as the inferior fronto-occipital fascicle (IFOF). Diffusion tensor imaging (DTI) can assess the extent of this effect and potentially provide neurosurgeons with an accurate map to guide tumor resection; analyze IFOF displacement patterns in temporoinsular gliomas based on tumor grading and topography in the temporal lobe; and assess whether these patterns follow a predictable pattern, to assist in maximal tumor resection while preserving IFOF function. METHODS: Thirty-four patients with temporal gliomas and available presurgical MRI were recruited. Twenty-two had insula infiltration. DTI deterministic region of interest (ROI)-based tractography was performed using commercial software. Tumor topographic imaging characteristics analyzed were as follows: location in the temporal lobe and extent of extratemporal involvement. Qualitative tractographic data obtained from directional DTI color maps included type of involvement (displaced/edematous-infiltrated/destroyed) and displacement direction. Quantitative tractographic data of ipsi- and contralateral IFOF included whole tract volume, fractional anisotropy, and fractional anisotropy of a 2-dimensional coronal ROI on the tract at the point of maximum tumor involvement. RESULTS: The most common tract involvement pattern was edematous/infiltrative displacement. Displacement patterns depended on main tumor location in the temporal lobe and presence of insular involvement. All tumors showed superior displacement pattern. In lateral tumors, displacement tendency was medial. In medial tumors, displacement tendency was lateral. When we add insular involvement, the tendency was more medial displacement. A qualitative and quantitative assessment supported these results. CONCLUSIONS: IFOF displacement patterns are reproducible and suitable for temporoinsular gliomas presurgical planning.

Voxel-level analysis of normalized DSC-PWI time-intensity curves: a potential generalizable approach and its proof of concept in discriminating glioblastoma and metastasis.

OBJECTIVE: Standard DSC-PWI analyses are based on concrete parameters and values, but an approach that contemplates all points in the time-intensity curves and all voxels in the region-of-interest may provide improved information, and more generalizable models. Therefore, a method of DSC-PWI analysis by means of normalized time-intensity curves point-by-point and voxel-by-voxel is constructed, and its feasibility and performance are tested in presurgical discrimination of glioblastoma and metastasis. METHODS: In this retrospective study, patients with histologically confirmed glioblastoma or solitary-brain-metastases and presurgical-MR with DSC-PWI (August 2007-March 2020) were retrieved. The enhancing tumor and immediate peritumoral region were segmented on CE-T1wi and coregistered to DSC-PWI. Time-intensity curves of the segmentations were normalized to normal-appearing white matter. For each participant, average and all-voxel-matrix of normalized-curves were obtained. The 10 best discriminatory time-points between each type of tumor were selected. Then, an intensity-histogram analysis on each of these 10 time-points allowed the selection of the best discriminatory voxel-percentile for each. Separate classifier models were trained for enhancing tumor and peritumoral region using binary logistic regressions. RESULTS: A total of 428 patients (321 glioblastomas, 107 metastases) fulfilled the inclusion criteria (256 men; mean age, 60 years; range, 20-86 years). Satisfactory results were obtained to segregate glioblastoma and metastases in training and test sets with AUCs 0.71-0.83, independent accuracies 65-79%, and combined accuracies up to 81-88%. CONCLUSION: This proof-of-concept study presents a different perspective on brain MR DSC-PWI evaluation by the inclusion of all time-points of the curves and all voxels of segmentations to generate robust diagnostic models of special interest in heterogeneous diseases and populations. The method allows satisfactory presurgical segregation of glioblastoma and metastases. KEY POINTS: • An original approach to brain MR DSC-PWI analysis, based on a point-by-point and voxel-by-voxel assessment of normalized time-intensity curves, is presented. • The method intends to extract optimized information from MR DSC-PWI sequences by impeding the potential loss of information that may represent the standard evaluation of single concrete perfusion parameters (cerebral blood volume, percentage of signal recovery, or peak height) and values (mean, maximum, or minimum). • The presented approach may be of special interest in technically heterogeneous samples, and intrinsically heterogeneous diseases. Its application enables satisfactory presurgical differentiation of GB and metastases, a usual but difficult diagnostic challenge for neuroradiologist with vital implications in patient management.

Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells.

Glioblastoma (GBM) is a highly aggressive brain tumor and almost all patients die because of relapses. GBM-derived cells undergo cell death without nuclear fragmentation upon treatment with different apoptotic agents. Nuclear dismantling determines the point-of-no-return in the apoptotic process. DFF40/CAD is the main endonuclease implicated in apoptotic nuclear disassembly. To be properly activated, DFF40/CAD should reside in the cytosol. However, the endonuclease is poorly expressed in the cytosol and remains cumulated in the nucleus of GBM cells. Here, by employing commercial and non-commercial patient-derived GBM cells, we demonstrate that the natural terpenoid aldehyde gossypol prompts DFF40/CAD-dependent nuclear fragmentation. A comparative analysis between gossypol- and staurosporine-treated cells evidenced that levels of neither caspase activation nor DNA damage were correlated with the ability of each compound to induce nuclear fragmentation. Deconvoluted confocal images revealed that DFF40/CAD was almost completely excluded from the nucleus early after the staurosporine challenge. However, gossypol-treated cells maintained DFF40/CAD in the nucleus for longer times, shaping a ribbon-like structure piercing the nuclear fragments and building a network of bridged masses of compacted chromatin. Therefore, GBM cells can fragment their nuclei if treated with the adequate insult, making the cell death process irreversible.

Perilesional edema in brain metastases as predictive factor of response to systemic therapy in non-small cell lung cancer patients: a preliminary study.

BACKGROUND: The significance of upfront systemic therapies as an alternative to whole brain radiotherapy (WBRT) for multiple brain metastases (BM) is debatable. Our purpose is to investigate if peritumoral edema could predict the intracranial response to systemic chemotherapy (chemo) in patients with advanced non-squamous non-small cell lung cancer (non-SQ-NSCLC) and synchronous multiple BM. METHODS: In this observational cohort study, we evaluated the outcome of 28 patients with multiple BM (≥3) treated with chemo based on cisplatin/carboplatin plus pemetrexed (chemo, group A, n=17) or WBRT plus subsequent chemo (group B, n=11). The intracranial response, assessed by the response assessment neuro-oncology (RANO) BM criteria, was correlated with the degree of BM-associated edema estimated by the maximum diameter ratio among fluid attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1WI (T1Gd) per each BM at the baseline brain magnetic resonance imaging (MRI). RESULTS: No differences were observed in baseline characteristics between both groups, except for the number of patients under steroid treatment that was clearly superior in group B (P=0.007). Median OS was similar between groups. Regarding FLAIR/T1Gd ratio (F/Gd), patients treated with chemo alone exhibited significantly higher values (P=0.001) in those who developed intracranial progression disease (PD) (2.80±0.32 mm), compared with those who achieved partial response (PR) (1.30±0.11 mm) or stable disease (SD) (1.35±0.09 mm). In patients treated with WBRT, F/Gd ratio was not predictive of response. CONCLUSIONS: Peritumoral edema estimated by F/Gd ratio appears a promising predictive tool to identify oligosymptomatic patients with multiple BM in whom WBRT can be postponed.

Precise enhancement quantification in post-operative MRI as an indicator of residual tumor impact is associated with survival in patients with glioblastoma.

Glioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p < 0.001). The prognostic value of several imaging and clinical variables was analyzed individually and combined (radiomics AUC 0.71, p = 0.07; combined AUC 0.72, p < 0.001). Residual enhancement thickness and radiomics complemented clinical data for prognosis stratification in patients with glioblastoma. Significant results were only obtained for scans performed between 24 and 72 h after surgery, raising the possibility of confounding non-tumor enhancement in very early post-surgery MRI. Regarding the extent of resection, and in agreement with recent studies, the association between the measured tumor remnant and survival supports maximal safe resection whenever possible.

COVID-19 and Ischemic Stroke: Clinical and Neuroimaging Findings.

BACKGROUND AND PURPOSE: SARS-CoV-2 causes multiorgan disease due to altered coagulability and microangiopathy. Patients may have an increased risk of cerebrovascular accidents (CVA). Our objective was to analyze clinical and neuroimaging characteristics of patients with ischemic CVA during the pandemic peak in our region, in order to identify atypical presentations. METHODS: We performed a cross-sectional analysis of patients admitted under code-stroke protocol to our center with a final diagnosis of ischemic brain infarction. We analyzed the main imaging and demographic characteristics and reviewed neuroimaging for atypical presentations. RESULTS: One-hundred patients with confirmed ischemic CVA were included. Nineteen had positive polymerase chain reaction testing for SARS-CoV-2 on admission. These patients had a lower prevalence of proximal arterial occlusion on imaging, higher in-hospital mortality, and worse baseline disability. No differences were identified in affected vascular territory, volume of infarction, initial CT stroke score, prevalence of hemorrhagic transformation, gender, age, cardiovascular risk factors, time to admission, symptom severity on entry, or decision to treat with thrombolysis or mechanical thrombectomy. Prevalence of COVID-19 in our code-stroke sample was higher than that for our province during this time period. CONCLUSION: The COVID-19 group had more in-hospital mortality, less proximal arterial occlusion on CT or MR angiography, and lower baseline modified Rankin Scale score. We suggest a possibly higher proportion of microangiopathic involvement or undetected distal large-vessel occlusion in the COVID-19 stroke group. Excess mortality was explained by severe respiratory failure. Otherwise, stroke patients with COVID-19 did not differ demographically or clinically from those without the illness.

Tumor necrosis factor antagonists for paradoxical inflammatory reactions in the central nervous system tuberculosis: Case report and review.

RATIONALE: Paradoxical reaction/immune reconstitution inflammatory syndrome is common in patients with central nervous system tuberculosis. Management relies on high-dose corticosteroids and surgery when feasible. PATIENT CONCERN: We describe 2 cases of HIV-negative patients with corticosteroid-refractory paradoxical reactions of central nervous system tuberculosis. DIAGNOSES: The 2 patients experienced clinical impairment shortly after starting therapy for TB, and magnetic resonance imaging showed the presence of tuberculomas, leading to the diagnosis of a paradoxical reaction. INTERVENTIONS: We added infliximab, an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, to the dexamethasone. OUTCOMES: Both patients had favorable outcomes, 1 achieving full recovery but 1 suffering neurologic sequelae. LESSONS: Clinicians should be aware of the risk of paradoxical reactions/immune reconstitution inflammatory syndrome when treating patients with tuberculosis of the central nervous system and should consider the prompt anti-TNF-α agents in cases not responding to corticosteroids.

Imaging of skull vault tumors in adults.

The skull vault, formed by the flat bones of the skull, has a limited spectrum of disease that lies between the fields of neuro- and musculoskeletal radiology. Its unique abnormalities, as well as other ubiquitous ones, present particular features in this location. Moreover, some benign entities in this region may mimic malignancy if analyzed using classical bone-tumor criteria, and proper patient management requires being familiar with these presentations. This article is structured as a practical review offering a systematic diagnostic approach to focal calvarial lesions, broadly organized into four categories: (1) pseudolesions: arachnoid granulations, meningo-/encephaloceles, vascular canals, frontal hyperostosis, parietal thinning, parietal foramina, and sinus pericrani; (2) lytic: fibrous dysplasia, epidermal inclusion and dermoid cysts, eosinophilic granuloma, hemangioma, aneurysmal bone cyst, giant cell tumor, metastasis, and myeloma; (3) sclerotic: osteomas, osteosarcoma, and metastasis; (4) transdiploic: meningioma, hemangiopericytoma, lymphoma, and metastasis, along with other less common entities. Tips on the potential usefulness of functional imaging techniques such as MR dynamic susceptibility (T2*) perfusion, MR spectroscopy, diffusion-weighted imaging, and PET imaging are provided.

Cognitive and brain structural changes in long-term oligodendroglial tumor survivors.

BACKGROUND: We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with chemotherapy (CT) (79%). METHODS: Oligodendroglial tumor patients (based on the World Health Organization [WHO] 2007 classification) who completed RT ± CT at least 2 years before the study initiation, were classified into 3 groups according to the time treatment was completed: Group 1 = 2-5 years (n = 22), Group 2 = 6-10 years (n = 13), and Group 3 >10 years (n = 13). All patients had a cross-sectional neuropsychological evaluation (n = 48) and a longitudinal volumetric analysis (gray matter [GM; n = 34]) between postsurgical and last follow-up MRI. White matter (WM) changes on MRI were assessed using a qualitative scale. RESULTS: There were no differences regarding tumor or treatment-related characteristics between groups. Six of 22 patients (27.3%) in Group 1; 5/13 (38.5%) in Group 2; and 9/13 (69.2%) in Group 3 had cognitive impairment that was considered severe in 3/22 patients (13.6%) in Group 1; 4/13 (30.8%) in Group 2; and 6/13 (46.2%) in Group 3. Patients in Groups 2 and 3 showed significant GM atrophy and more leukoencephalopathy than Group 1. Cognitive deficits were associated with brain atrophy and WM changes. CONCLUSIONS: Long-term oligodendroglial tumor survivors who underwent standard RT ± CT treatment, mainly >5 years of its completion, present cognitive impairment, especially on memory and executive functions, associated with late GM and WM damage, thus highlighting the need of developing future strategies in patients with oligodendroglial tumor and long expected survival.

Magnetic resonance spectroscopy in posterior fossa tumours: the tumour spectroscopic signature may improve discrimination in adults among haemangioblastoma, ependymal tumours, medulloblastoma, and metastasis.

OBJECTIVES: Assessing a posterior fossa tumour in an adult can be challenging. Metastasis, haemangioblastoma, ependymal tumours, and medulloblastoma are the most common diagnostic possibilities. Our aim was to evaluate the contribution of magnetic resonance spectroscopy (MRS) in the diagnosis of these entities. METHODS: We retrospectively evaluated 56 consecutive patients with a posterior fossa tumour and histological diagnosis of ependymal tumour, medulloblastoma, haemangioblastoma, and metastasis in which good-quality spectra at short (TE 30 ms) or/and intermediate (TE, 136 ms) TE were available. Spectra were compared using the Mann-Whitney U non-parametric test in order to select the spectral datapoints and the intensity ratios that showed significant differences between groups of lesions. Performance of these datapoints and their ratios were assessed with ROC curves. RESULTS: The most characteristic signatures on spectroscopy were high choline (Cho) in medulloblastoma (p < 0.001), high myoinositol (mIns) in ependymal tumours (p < 0.05), and high lipids (LIP) in haemangioblastoma (p < 0.01) and metastasis (p < 0.01). Selected ratios between normalised intensity signals of resonances provided accuracy values between 79 and 95% for pairwise comparisons. Intensity ratio NI3.21ppm/3.55ppm provided satisfactory discrimination between medulloblastoma and ependymal tumours (accuracy, 92%), ratio NI2.11ppm/1.10ppm discriminated ependymal tumours from haemangioblastoma (accuracy, 94%), ratio NI3.21ppm/1.13ppm discriminated haemangioblastoma from medulloblastoma (accuracy, 95%), and ratio NI1.28ppm/2.02pmm discriminated haemangioblastoma from metastasis (accuracy, 83%). CONCLUSIONS: MRS may improve the non-invasive diagnosis of posterior fossa tumours in adults. KEY POINTS: • High choline suggests a medulloblastoma in a posterior fossa tumour. • High myoinositol suggests an ependymal lesion in a posterior fossa tumour. • High lipids suggest a metastasis or a haemangioblastoma in a posterior fossa tumour.