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To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT).Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed.The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048).In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.

Objective This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy. Methods This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity. Results The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001). Interpretation There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022

Non-invasive differential diagnosis of brain tumours is currently based on the assessment of tumour vascularity through magnetic resonance imaging (MRI) coupled with dynamic susceptibility contrast (DSC). However, given its limited accuracy, reaching a definitive diagnosis often requires complex neurosurgical interventions that compromise the patients’ quality of life. We applied deep learning on DSC images from histology-confirmed patients with glioblastoma, metastasis or lymphoma, the three most common brain malignancies. The convolutional neural network trained on ~ 50,000 voxels from 40 patients provided intra-tumour probability maps that yielded clinical-grade diagnosis. Performance was tested in 400 additional cases and an external validation cohort (n = 128). The tool reached a three-way accuracy of 0.78, superior to standard diagnosis with cerebral blood volume (0.55) and percentage of signal recovery (0.59) perfusion metrics. Our open-access software, Brain Enhancing Region Radiological analysis (BERRY), demonstrates the potential of voxel-wise probability maps for differential diagnosis of brain tumours using standard-of-care MRI.

Background The objective of this study is to evaluate oral hydration compared to intravenous (i.v.) hydration in the prevention of post-contrast acute kidney injury (PC-AKI) in the oncologic subgroup of patients with stage IIIb chronic kidney disease (CKD) included in the NICIR study referred for elective contrast-enhanced computed tomography (CE-CT). Material and Methods We performed a retrospective subanalysis of the oncological subgroup (174/228 patients, 74%) from a continuous prospective database of patients included in the recently published non-inferiority NICIR study. Patients received prophylaxis against PC-AKI with either oral hydration (500 mL of water two hours before and 2000 mL during the 24 hours after CE-CT) or i.v. hydration (sodium bicarbonate (166 mmol/L)3 mL/kg/h starting one hour before and 1 mL/kg/h during the first hour after CE-CT). The primary outcome was to compare the proportion of PC-AKI in the first 48 to 72 hours after CE-CT in the two hydration groups. Secondary outcomes were to compare persistent PC-AKI, the need for hemodialysis, and the occurrence of adverse events related to prophylaxis in each group. Results Of 174 patients included in the subanalysis, 82 received oral hydration and 92 received i.v. hydration. There were no significant differences in clinical characteristics or risk factors between the two study arms. Overall the PC-AKI rate was 4.6% (8/174 patients), being 3.7% in the oral hydration arm (3/82 patients) and 5.4% (5/92 patients) in the i.v. hydration arm. The persistent PC-AKI rate was 1.8% (1/82 patients) in the oral hydration arm and 3.3% (3/92 patients) in the i.v. hydration arm. No patient required dialysis during the first month after CE-CT or had adverse effects related to the hydration regime. Conclusion In oncological patients with stage IIIb CKD referred for elective CE-CT, the rate of PC-AKI in those receiving oral hydration did not significantly differ from that of patients receiving i.v. hydration.

In recent years, there has been a notable increase of migratory movements into Europe with the arrival of not (reliably) documented young individuals within EU-Member States. Accordingly, the need for forensic age assessments likewise increased in order to administratively differentiate along the legally relevant cut-off age of 18 completed years. The objective of our study was to analyse the expert reports of forensic age estimation issued in Barcelona between 2011 and 2018.In all cases, data on the medical history, physical examination, radiology of the left hand and orthopantomography were collected. In cases without third molars and a complete ossification of the hand, a CT scan of the clavicles was also performed.A total of 2754 expert reports were evaluated; 96.7% were males, the majority were of North African origin, mainly from Morocco (63.6%), and 19.6% were sub-Saharan Africans; 65.4% had a level of bone maturation corresponding to the last three standards of Greulich and Pyle. Most cases had mineralization of the third molar corresponding to the F, G or H stages of Demirjian. In 85.9%, there was a correspondence between bone and dental age. A total of 28.8% of the subjects were evaluated as being aged over 18 years; 86.2% of North Africans were considered to be younger than 18, and 82% of sub-Saharan Africans were considered to be over 18 years old.In Barcelona, most of the subjects evaluated were male and North African, and 71.2% of the cases were considered to be minors.

Background: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. Methods: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. Results: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. Conclusions: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Severe acute respiratory syndrome coronavirus 2 has spread across the world since December 2019, infecting 100 million and killing millions. The impact on health care institutions during the coronavirus disease 2019 pandemic has been considerable, with exhaustion of institutional and personal protective equipment resources during local outbreaks and crushing financial consequences for many institutions. Establishing adaptive principles of leadership is necessary during crises, fostering quick decision-making and workflow modifications, while a rapid review of data must determine necessary course corrections. This report describes concepts of crisis leadership teams that can help maximize their effectiveness during the current and future pandemics. © RSNA, 2021

The European Society of Urogenital Radiology (ESUR) updated its guidelines for prophylaxis against postcontrast acute kidney injury (PC-AKI) in 2018 (ESUR 10.0). These guidelines drastically reduce the indications for prophylaxis against PC-AKI after iodine-based contrast administration, lowering the cutoff for administering prophylaxis to glomerular filtration rates

Objectives To evaluate ESR eGUIDE—the European Society of Radiology (ESR) e-Learning tool for appropriate use of diagnostic imaging modalities—for learning purposes in different clinical scenarios. Methods This anonymized evaluation was performed after approval of ESR Education on Demand leadership. Forty clinical scenarios were developed in which at least one imaging modality was clinically most appropriate, and the scenarios were divided into sets 1 and 2. These sets were provided to medical students randomly assigned to group A or B to select the most appropriate imaging test for each scenario. Statistical comparisons were made within and across groups. Results Overall, 40 medical students participated, and 31 medical students (78%) answered both sets. The number of correctly chosen imaging methods per set in these 31 paired samples was significantly higher when answered with versus without use of ESR eGUIDE (13.7 ± 2.6 questions vs. 12.1 ± 3.2, p = 0.012). Among the students in group A, who first answered set 1 without ESR eGUIDE (11.1 ± 3.2), there was significant improvement when set 2 was answered with ESR eGUIDE (14.3 ± 2.5, p = 0.013). The number of correct answers in group B did not drop when set 2 was answered without ESR eGUIDE (12.4 ± 2.6) after having answered set 1 first with ESR eGUIDE (13.0 ± 2.7, p = 0.66). Conclusion The clinical decision support tool ESR eGUIDE is suitable for training medical students in choosing the best radiological imaging modality in typical scenarios, and its use in teaching radiology can thus be recommended. Key Points • ESR eGUIDE improved the number of appropriately selected imaging modalities among medical students. • This improvement was also seen in the group of students which first selected imaging tests without ESR eGUIDE. • In the student group which used ESR eGUIDE first, appropriate selection remained stable even without the teaching tool.

Editor's Note.-Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technologic advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article. ©RSNA, 2020.

IMPORTANCE: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. OBJECTIVE: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. INTERVENTIONS: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. RESULTS: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%). CONCLUSIONS AND RELEVANCE: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40

To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. Background: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. Methods: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. Results: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. Conclusions: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.

Cerebral venous thrombosis (CVT) is uncommon, representing approximately 0.5% of all cases of cerebrovascular disease worldwide. Many factors, alone or combined, can cause CVT. Although CVT can occur at any age, it most commonly affects neonates and young adults. CVT is difficult to diagnose clinically because patients can present with a wide spectrum of nonspecific manifestations, the most common of which are headache in 89%-91%, focal deficits in 52%-68%, and seizures in 39%-44% of patients. Consequently, imaging is fundamental to its diagnosis. MRI is the most sensitive and specific technique for diagnosis of CVT. The different MRI sequences, with and without the use of contrast material, have variable strengths. Contrast material-enhanced MR venography has the highest accuracy compared with sequences without contrast enhancement.Online supplemental material is available for this article.©RSNA, 2019.

PURPOSE Endovascular treatment with mechanical thrombectomy devices demonstrated high recanalization rates but functional outcome did not correlate with high rates of recanalization obtained. Patient selection prior to the endovascular treatment is very important in the final outcome of the patient. The primary aim of our study was to evaluate the prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and Pons-Midbrain Index (PMI) scores in patients with Basilar Artery Occlusion (BAO) treated with successful angiographic recanalization after mechanical thrombectomy. METHODS Retrospective single-center study including 18 patients between 2008 and 2013 who had acute basilar artery occlusion managed with endovascular treatment within 24hours from symptoms onset and with successful angiographic recanalization. The patients were initially classified into two groups according to clinical outcome and mortality at 90 days. For analysis we also divided patients into groups based on pc-ASPECTS (≥8vs.

Resumen Objetivo El tratamiento endovascular con dispositivos de trombectomia mecanica demostro altos indices de recanalizacion, si bien el resultado funcional no guardo relacion con los altos indices de recanalizacion obtenidos. La seleccion de los pacientes previa al tratamiento endovascular es muy importante en el resultado final de estos pacientes. El objetivo principal de nuestro estudio fue hacer una valoracion del valor pronostico de la escala ASPECTS (Escala Precoz por TC del Programa de ACV de Alberta) y del indice puente-mesencefalo (IPM) en pacientes con oclusiones de la arteria basilar (OAB) sometidos, con exito, a recanalizacion angiografica tras trombectomia mecanica. Metodos Este estudio retrospectivo de un unico centro incluyo 18 pacientes entre los anos 2008 y 2013 con oclusiones de la arteria basilar que fueron sometidos a tratamiento endovascular dentro de las 24 horas siguientes al inicio de los sintomas y con una exitosa recanalizacion angiografica. Inicialmente, los pacientes fueron clasificados en dos grupos segun el resultado clinico y la mortalidad a los 90 dias. Para el analisis, los pacientes tambien fueron divididos en grupos de imagenes utilizando, para ello, la escala ASPECTS-CP (≥8 vs. Resultados La escala ASPECTS-CP mediante IFATC, dicotomizada a Conclusion La escala ASPECTS-CP mediante IFATC sirve de ayuda a la hora de predecir el resultado funcional tras recanalizacion de la OAB mediante tratamiento endovascular. Estos resultados deberian ser validados en un ensayo controlado aleatorizado para decidir si tratar, o no, a un paciente con OAB.

Background: White matter (WM) transgression is an unexplored concept in neuroendoscopy. Diffusion tensor image (DTI) tractography could be implemented as a planning and postoperative evaluation tool in functional disconnection procedures (FDPs), which are, currently, the subject of technological innovations. We intend to prove the usefulness of this planning method focused on the assessment of WM injury that is suitable for planning FDPs. Methods: Ten cranial magnetic resonance studies (20 sides) without pathological findings were processed. Fascicles were defined by two regions of interest (ROIs) using the fiber assignment method by the continuous tracking approach. Using three-dimensional (3D) simulation and DTI tractography, we created an 8-mm virtual endoscope and an uninjured inferior fronto-occipital fasciculus (IFOF) from two ROIs. The injured tract was generated using a third ROI built from the 3D model of the intersection of the oriented trajectory of the endoscope with the fascicle. Data and images were quantitatively and qualitatively analyzed. Results: The average percentage of the injured fibers was 32.0% (range: 12.4%–70%). The average intersected volume was 1.1 cm3 (range: 0.3–2.3 cm3). Qualitative analysis showed the inferior medial quadrant of the inferior fronto-occipital fasciculus (IFOF) as the most frequently injured region. No hemispherical asymmetry was found (P > 0.5). Conclusion: DTI tractography is a useful surgical planning tool that could be implemented in several endoscopic procedures. Together with a functional atlas, the presented technique provides a noninvasive method to assess the potential sequelae and thus to optimize the surgical route. The suggested method could be implemented to analyze pathological WM fascicles and to assess the surgical results of FDP such as hemispherotomy or amygdalohippocampectomy. More studies are needed to overcome the limitations of the tractography based information and to develop more anatomically and functionally reliable planning systems.

The purpose of this study was to analyze the new combined indicators on noncontrast computed tomography (NCCT) to predict functional outcome at discharge, compared to previously individual radiological NCCT signs. Patients with spontaneous intracerebral hemorrhage (ICH) who underwent baseline CT scan were retrospectively analyzed. Black hole (BH) sign, blend sign (BS), island sign (IS), swirl sign (SwS), Barras classification, any hypodensity, any irregularity, and two combined novel indicators—Combined Barras Total Score (CBTS) and Hematoma Maturity Score—were assessed independently by two radiologists blinded to clinical information. Patients were trichotomized depending on the disability or dependency at discharge according to the Modified Rankin Scale (mRS): no symptoms or no significant/mild disability (mRS 0–2); moderate or severe disability (mRS 3–5); and mortality (mRS 6). One hundred fourteen patients with spontaneous ICH confirmed by NCCT were included in the analysis. Multivariable statistical analysis was adjusted for anticoagulation, hematoma volume, ventricular expansion, hypertension, blood glucose level at admission, age, and history of atrial fibrillation and demonstrated that any hypodensity (OR 4.768, p 0.006), any irregularity (OR 4.768, p 0.006), CBTS ≥ 4 (OR 3.205, p 0.025), and the new Hematoma Maturity Score (Immature) (OR 5.872, p 0.006) are independent predictors of functional outcome at discharge. The new concept of the Hematoma Maturity Score was the radiological sign on NCCT with the highest impact on clinical outcome in comparison with the rest of the evaluated radiological signs. • This is the first manuscript where density and shape characteristics of the ICH had been evaluated together and integrated in a new Hematoma Maturity Score. • The new Hematoma Maturity Score is the radiological sign on NCCT with the highest impact on clinical outcome at discharge.

Rationale The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. Aim The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. Sample size estimates A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). Methods and design We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20–30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). Study outcome(s) The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0–1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. Discussion The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

Purpose: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials. Experimental Design: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes. Results: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype–negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes. Conclusions: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0–5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

Immunotherapy is changing the treatment paradigm for cancer and has introduced new challenges in medical imaging. Because not all patients benefit from immunotherapy, pretreatment imaging should be performed to identify not only prognostic factors but also factors that allow prediction of response to immunotherapy. Follow-up studies must allow detection of nonresponders, without confusion of pseudoprogression with real progression to prevent premature discontinuation of treatment that can benefit the patient. Conventional imaging techniques and classic tumor response criteria are limited for the evaluation of the unusual patterns of response that arise from the specific mechanisms of action of immunotherapy, so advanced imaging methods must be developed to overcome these shortcomings. The authors present the fundamentals of the tumor immune microenvironment and immunotherapy and how they influence imaging findings. They also discuss advances in functional and molecular imaging techniques for the assessment of immunotherapy in clinical practice, including their use to characterize immune phenotypes, assess patient prognosis and response to therapy, and evaluate immune-related adverse events. Finally, the development of radiomics and radiogenomics in these therapies and the future role of imaging biomarkers for immunotherapy are discussed.

Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials.From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes.We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors andTCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

[EN] Introduction: IDH1/2 wt glioblastoma (GB) represents the most lethal tumour of the central nervous system. Tumour vascularity is associated with overall survival (OS), and the clinical relevance of vascular markers, such as rCBV, has already been validated. Nevertheless, molecular and clinical factors may have different influences on the beneficial effect of a favourable vascular signature. Purpose: To evaluate the association between the rCBV and OS of IDH1/2 wt GB patients for long-term survivors (LTSs) and short-term survivors (STSs). Given that initial high rCBV may affect the patient's OS in follow-up stages, we will assess whether a moderate vascularity is beneficial for OS in both groups of patients. Materials and methods: Ninety-nine IDH1/2 wt GB patients were divided into LTSs (OS >= 400 days) and STSs (OS < 400 days). Mann-Whitney and Fisher, uni- and multiparametric Cox, Aalen's additive regression and Kaplan-Meier tests were carried out. Tumour vascularity was represented by the mean rCBV of the high angiogenic tumour (HAT) habitat computed through the haemodynamic tissue signature methodology (available on the ONCOhabitats platform). Results: For LTSs, we found a significant association between a moderate value of rCBV(mean) and higher OS (uni- and multiparametric Cox and Aalen's regression) (p = 0.0140, HR = 1.19; p = 0.0085, HR = 1.22) and significant stratification capability (p = 0.0343). For the STS group, no association between rCBV(mean) and survival was observed. Moreover, no significant differences (p > 0.05) in gender, age, resection status, chemoradiation, or MGMT methylation were observed between LTSs and STSs. Conclusion: We have found different prognostic and stratification effects of the vascular marker for the LTS and STS groups. We propose the use of rCBV(mean) at HAT as a vascular marker clinically relevant for LTSs with IDH1/2 wt GB and maybe as a potential target for randomized clinical trials focused on this group of patients., DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I +D+i).; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 844646; H2020-SC1-BHC-2018-2020 (No. 825750); MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R); European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie, Grant/Award Number: 844646; Research Council of Norway, Grant/Award Number: 261984; South-Eastern Norway Regional Health Authority, Grant/Award Number: 2017073; European Research Council (ERC) under the European Union's Horizon 2020, Grant/Award Number: 758657

Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T1-weighted MRI, T2- and FLAIR T2-weighted, and dynamic susceptibility contrast (DSC) T2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into 'vascular' groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan–Meier test; Mann–Whitney test. Results The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into 'moderate-' and 'high-vascular' groups (P < 0.05). The Mann–Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02–0.685; LAT: P = 0.010–0.769; IPE: P = 0.093–0.939; VPE: P = 0.016–1.000). Data Conclusion The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478–1486.

[Background]: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). [Objective]: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. [Patients and Methods]: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. [Results]: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6–3.1] and the median overall survival was 32.1 months (95% CI 5.1–59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. [Conclusion]: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO., Palbociclib was provided by Pfizer under a cooperative research agreement with the Spanish Group for Research in NeuroOncology (GEINO). Funding research was supported by Pfzer under the Investigator-Initiated Research Award, number WI174842.

In this chapter, we review the different categories of tumours of the central nervous system with examples of each of them from low-grade to high-grade tumours.

Medical education is evolving and electronic learning (e-Learning) strategies have now become an essential asset in radiology education. Radiology education is a significant part of the undergraduate medical curriculum and the use of e-Learning in radiology teaching in medical schools is on the rise. If coupled with clinical decision support systems, e-Learning can be a practical way of teaching students clinical decision making, such as selecting the diagnostic imaging tests that are best suited in certain clinical scenarios.The innovative concept of flipped classroom learning encourages students to work independently and maximises the application of learnt contents in interactive classroom sessions.For integrated curricula with their student-centred, problem-based, and community-based design, an approach to systematically integrate radiology may be to define diagnostic reasoning as one of the core goals. Radiologists as teachers and scholars may understand themselves as experts in diagnostic reasoning and in mentoring how to make medical decisions.Computer programs simulating the routine work are available and can be used to teach the recognition of anatomical structures and pathological patterns, and also to teach ultrasonography and interventional radiology, maximising patient safety.

Background and purposeThe aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. MethodsThe clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell-based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. ResultsTwelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short-term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm(3) (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. ConclusionsDespite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy. Click for the corresponding questions to this CME article.

Resumen Objetivos La resonancia magnetica intraoperatoria (RMi) es una herramienta recientemente introducida en los quirofanos de neurocirugia mas vanguardistas mundialmente. Presentamos nuestra experiencia clinica preliminar con relacion al empleo de la RMi de bajo campo, PoleStar N30®, desde su implementacion en 2013 en el Hospital Clinic de Barcelona, para el tratamiento de neoplasias cerebrales. Material y metodo Se realizo un estudio prospectivo no aleatorizado incluyendo los casos intervenidos mediante RMi con intencion de reseccion completa hasta octubre de 2015. Se registraron los tiempos quirurgicos asi como los grados de reseccion, diagnostico histologico, estancia hospitalaria y la supervivencia durante el seguimiento. Resultados Se incluyeron 50 pacientes con edad media de 55 anos (± 13,7), un Karnofsky preoperatorio de 92 (siendo el postoperatorio de 81); y un seguimiento medio de 10,5 meses (± 6,5). Un 26% fueron reintervenciones por recidiva. Un 56% eran gliomas de alto grado, un 24% gliomas de bajo grado y un 20% otras neoplasias. La estancia hospitalaria global fue de 10 dias (± 4,5). Segun el diagnostico histologico el grupo «otras» fue el que mayor estancia hospitalaria presentaba. Globalmente, se lograron un 52% de reseccion completa, un 18% de resecciones parciales maximas y un 30% de resecciones parciales. La supervivencia durante el seguimiento fue del 84%. Conclusiones La RMi es una herramienta segura y eficaz en la cirugia de neoplasias cerebrales. Su uso permite aumentar el grado de reseccion disminuyendo las complicaciones posquirurgicas. Su empleo conlleva una prolongacion del tiempo quirurgico que mejora con la curva de aprendizaje caracteristica. Mas estudios son necesarios para poder establecer su papel en la supervivencia a largo plazo de los pacientes.

Objectives Intra-operative magnetic resonance imaging (iMRI) is a recently introduced tool in the most advanced neurosurgical operating rooms worldwide. We present our preliminary experience in brain tumour surgery with low field PoleStar N30 ® intraoperative MRI since its introduction in 2013 in the Barcelona Clinic Hospital. Material and methods A prospective non-randomised study was conducted on cases operated on using iMRI and intention of complete removal up to October 2015. A record was made of the data as regards surgical times, resection rates, histological diagnosis, hospital stay, and survival rates during follow-up. Results The study included 50 patients, with a mean age of 55 years (±13.7), a preoperative mean Karnofsky of 92 (being 81 post-operatively), and a mean follow-up of 10.5 months (±6.5). There were 26% re-operations due to recurrence. High-grade gliomas were reported in 56%, low-grade gliomas in 24%, and 20% “Other” tumours. Overall hospital stay was 10 days (±4.5). Depending on the histologiacl diagnosis, the “Others” group had a longer hospital stay. Overall, there were 52% complete removal, 18% of maximum removals, and 30% of partial removals. The overall survival rates during follow-up was 84%. Conclusions iMRI is a safe and effective tool for brain tumour surgery. Its use allows an increase in resection rates, and minimises post-operative complications. Its implementation involves an increase in surgical time, which improves with the characteristic learning curve. More studies are needed to establish its role in the long-term survival of patients.

Background and Purpose— Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood–cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy. Methods— A prospective cohort of acute stroke patients treated with stent retrievers was analyzed. Vessel wall permeability impairment was identified as gadolinium vessel wall enhancement (GVE) in a 24- to 48-hour follow-up contrast-enhanced magnetic resonance imaging, and severe BCSFB disruption was defined as subarachnoid hemorrhage or gadolinium sulcal enhancement (present across >10 slices). Infarct volume was evaluated in follow-up magnetic resonance imaging, and clinical outcome was evaluated with the modified Rankin Scale at day 90. Results— A total of 60 patients (median National Institutes of Health Stroke Scale score, 18) were analyzed, of whom 28 (47%) received intravenous alteplase before mechanical thrombectomy. Overall, 34 (57%) patients had GVE and 27 (45%) had severe BCSFB disruption. GVE was significantly associated with alteplase use before thrombectomy and with more stent retriever passes, along with the presence of severe BCSFB disruption. GVE was associated with poor clinical outcome, and both GVE and severe BCSFB disruption were associated with increased final infarct volume. Conclusions— These findings may support the clinical relevance of direct vessel damage and BCSFB disruption after acute stroke and reinforce the need for further improvements in reperfusion strategies. Further validation in larger cohorts of patients is warranted.

Because of the high risk of nephrogenic systemic fibrosis, which of the following gadolinium-based contrast agents is/are not recommended for use in a patient with end-stage renal failure?