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Arterial recanalization to restore the blood supply and limit the brain damage is the primary goal in the management of acute ischemic stroke (AIS). Since the publication of pivotal randomized clinical trials in 2015, endovascular thrombectomy has become part of the standard of care in selected cases of AIS from large-vessel occlusions up to 6 hours after the onset of symptoms. However, the association between endovascular reperfusion and improved functional outcome is not strictly time dependent. Rather than on rigid time windows, candidates should be selected based on vascular and physiologic information. This approach places imaging data at the center of treatment decisions. Advances in imaging-based management of AIS provide crucial information about vessel occlusion, infarct core, ischemic penumbra, and degree of collaterals. This information is invaluable in identifying patients who are likely to benefit from reperfusion therapies and excluding those who are unlikely to benefit or are at risk of adverse effects. The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work-up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from "Time is Brain" to "Imaging is Brain." This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS.

IntroductionSevere traumatic brain injury (TBI) is a catastrophic neurological condition with significant economic burden. Early in-hospital mortality (Methods and analysisThe Early Diagnosis of Mortality using Admission CT Perfusion in Severe Traumatic Brain Injury Patients study, is a prospective cohort study in patients with severe TBI funded by a grant from the Canadian Institute of Health Research. Adults aged 18 or older, with evidence of a severe TBI (Glasgow Coma Scale score ≤8 before initial resuscitation) and, on mechanical ventilation at the time of imaging are eligible. Patients will undergo CTP at the time of first imaging on their hospital admission. Admission CTP compares with the reference standard of an accepted bedside clinical assessment for brainstem function. Deferred consent will be used. The primary outcome is a binary outcome of mortality (dead) or survival (not dead) in the first 48 hours of admission. The planned sample size for achieving a sensitivity of 75% and a specificity of 95% with a CI of ±5% is 200 patients.Ethics and disseminationThis study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed through forums at the end of the study.Trial registration numberNCT04318665

OBJECTIVELaser Ablation After Stereotactic Radiosurgery (LAASR) is a multicenter prospective study of laser interstitial thermal (LITT) ablation in patients with radiographic progression after stereotactic radiosurgery for brain metastases.METHODSPatients with a Karnofsky Performance Scale (KPS) score ≥ 60, an age > 18 years, and surgical eligibility were included in this study. The primary outcome was local progression-free survival (PFS) assessed using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Secondary outcomes were overall survival (OS), procedure safety, neurocognitive function, and quality of life.RESULTSForty-two patients—19 with biopsy-proven radiation necrosis, 20 with recurrent tumor, and 3 with no diagnosis—were enrolled. The median age was 60 years, 64% of the subjects were female, and the median baseline KPS score was 85. Mean lesion volume was 6.4 cm3 (range 0.4–38.6 cm3). There was no significant difference in length of stay between the recurrent tumor and radiation necrosis patients (median 2.3 vs 1.7 days, respectively). Progression-free survival and OS rates were 74% (20/27) and 72%, respectively, at 26 weeks. Thirty percent of subjects were able to stop or reduce steroid usage by 12 weeks after surgery. Median KPS score, quality of life, and neurocognitive results did not change significantly for either group over the duration of survival. Adverse events were also similar for the two groups, with no significant difference in the overall event rate. There was a 12-week PFS and OS advantage for the radiation necrosis patients compared with the recurrent tumor or tumor progression patients.CONCLUSIONSIn this study, in which enrolled patients had few alternative options for salvage treatment, LITT ablation stabilized the KPS score, preserved quality of life and cognition, had a steroid-sparing effect, and was performed safely in the majority of cases.Clinical trial registration no.: NCT01651078 (clinicaltrials.gov)

Computed tomography angiography (CTA) collateral scoring can identify patients most likely to benefit from mechanical thrombectomy and those more likely to have good outcomes and ranges from 0 (no collaterals) to 3 (complete collaterals). In this study, we used a machine learning approach to categorise the degree of collateral flow in 98 patients who were eligible for mechanical thrombectomy and generate an e-CTA collateral score (CTA-CS) for each patient (e-STROKE SUITE, Brainomix Ltd., Oxford, UK). Three experienced neuroradiologists (NRs) independently estimated the CTA-CS, first without and then with knowledge of the e-CTA output, before finally agreeing on a consensus score. Addition of the e-CTA improved the intraclass correlation coefficient (ICC) between NRs from 0.58 (0.46–0.67) to 0.77 (0.66–0.85, p = 0.003). Automated e-CTA, without NR input, agreed with the consensus score in 90% of scans with the remaining 10% within 1 point of the consensus (ICC 0.93, 0.90–0.95). Sensitivity and specificity for identifying favourable collateral flow (collateral score 2–3) were 0.99 (0.93–1.00) and 0.94 (0.70–1.00), respectively. e-CTA correlated with the Alberta Stroke Programme Early CT Score (Spearman correlation 0.46, p < 0.001) highlighting the value of good collateral flow in maintaining tissue viability prior to reperfusion. In conclusion, ­e-CTA provides a real-time and fully automated approach to collateral scoring with the potential to improve consistency of image interpretation and to independently quantify collateral scores even without expert rater input.

2041 Background: Patients with glioblastoma are often treated with radiation and chemotherapy following surgery. Disease recurrence often occurs early in the disease course and during initial therapy, yet assessment of treatment response with MRI is highly variable in some situations. We sought to describe the clinical and imaging assessment and outcomes of an unselected cohort of patients with glioblastoma following the publication of the Response Assessment in Neuro-Oncology criteria. Methods: Patients diagnosed with glioblastoma in Manitoba, Canada, from 2012-2018 were identified from the Manitoba Cancer Registry. Chart review was performed to identify treatments given and decisions made by the treating team, and imaging analysis was performed to assess based on RANO and mRANO criteria. Determination of progression versus pseudoprogression according to these criteria was performed using clinical decision-making and review of follow-up imaging for confirmation. At time of the response assessment visit, patients were assessed by a primary oncologist (Radiation or Medical) and were also discussed at multidisciplinary Case Conference (comprised of Medical and Radiation Oncology, Neurosurgery, Neuropathology, and Neuroradiology). Treatment decisions were made with patient and primary oncologist, guided by input from the Case Conference. Tumour measurements were performed both in 2D using Product of Perpendicular Diameter analysis (PPD) and 3D volumetric measurements with/without necrotic region. Overall Survival (OS) and Progression Free Survival (PFS) were estimated to evaluate the effectiveness of response assessments and Kaplan-Meier method was used to compare the time to progression resulted from RANO, mRANO, and clinical impression. Results: A total of 285 patients were identified with a pathological diagnosis of glioblastoma. Of those, 199 (35% male, 65% female) were treated with concurrent temozolomide and radiation (75% 60Gy and 25% < 60Gy), and more than 90% went on to receive adjuvant temozolomide. Median Overall Survival of the 199 was 13.2 months. Of those treated with concurrent therapy, 122 (61%) had MRI studies with equivocal results within the first 6 months, with confirmatory MRI showing true progression in 73 (59.8%), pseudoprogression in 45 (36.9%), and 4 patients with undetermined outcome. Formal RANO and mRANO comparison is ongoing. Conclusions: Response assessment for patients with glioblastoma remains a frequent challenge despite the use of MRI and established response criteria, with more than half of patients having equivocal imaging changes and a high frequency of pseudoprogression.

BACKGROUND According to the updated RANO criteria, MRI contrast enhancement and peritumoral edema during the initial 12 weeks within the radiation field following chemoradiation may be pseudoprogression (PP) or true progression (TP). This ambiguity results in diagnostic uncertainty and delays in effective therapies. MRI perfusion and permeability imaging markers, including relative blood volume (rBV), and volume transfer constant (Ktrans), may be useful in differentiating PP from TP. Both techniques rely on identification of a vascular input function (VIF) to produce reliable output maps. METHODS Perfusion and permeability maps were acquired from 7 patients on a Siemens 3T Verio MRI as part of an ongoing prospective study on glioblastoma multiforme. Patients received standard surgical resection with concurrent chemo-radiotherapy treatment and MRI follow-up at one and every 2 months. Maps were based on the follow-up MRI. The 3D contrast enhancing lesion (CEL) was segmented from the T1-Post-Gd MRI. VIF pixels were identified in the internal carotid artery (ICA), the M2 segment of the middle cerebral artery (MCA2), the superior sagittal sinus (SSS), automatically using software (Olea Sphere 3.0.22), and auto-edited (removed pixels from the auto VIF definition that were outside the brain). RESULTS For the different VIF pixel selections (ICA, MCA2, SSS, Auto, Auto-edited), mean Ktrans values from CEL were 0.32, 0.48, 0.05, 0.09, 0.08, respectively, showing a 10-fold variation. Mean rBV values from CEL were 2.70, 2.36, N/A, 3.10, 3.19, respectively, showing a 1.3-fold variation. CONCLUSIONS VIF pixel selection is a critical step in generating reliable perfusion and permeability MRI maps. Variation of up to a factor of 10 in the Ktrans values, depending on VIF selection, was observed. SSS for the permeability VIF resulted in maps that most closely matched literature values, whereas perfusion imaging showed less sensitivity to VIF selection.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50–64 years versus older group (n = 310); age range, 65–91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local–global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain. A.E. was supported by the Catalan project Imagenoma de L'Envelliment (Aging Imageomics Study). G.D. was supported by the Spanish Ministry of Economy and Competitiveness, Spain (grant agreement number PSI2016- 75688-P, MINECO/AEI/FEDER-EU); European Union's Horizon 2020 FET Flagship Human Brain Project (grant agreement number 785907, HBP SGA2); the Catalan Research Support, Spain (grant agreement number 2017 SGR 1545) and La Marató TV3 2017 (grant agreement 201725.33).

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged >= 50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

There is growing interest in developing magnetic resonance imaging (MRI) biomarkers of brain connectivity from resting-state functional (rs-fMRI) and diffusion tensor imaging (DTI) to aid in the diagnosis and management of patients with mild traumatic brain injury (mTBI). To determine whether early MRI biomarkers of brain connectivity are useful in predicting outcome after mTBI, we conducted a systematic review using the following inclusion criteria: 1) patients aged16 years with mTBI, 2) MRI performed during the first month post-injury, 3) outcome measure available, 4) control group, and 5) original article published in a peer-reviewed journal. Of the 1351 citations identified, 14 studies met inclusion criteria (5 rs-fMRI and 10 DTI; 680 patients with mTBI vs. 436 controls) including those where MRI was performed from12 h to 1 month post-injury. The most common clinical outcome measure used in these studies was symptom burden using the Rivermead Post-Concussion Questionnaire. The most frequently studied brain connectivity MRI biomarkers were global functional connectivity, default-mode network, and fractional anisotropy (FA). Despite the scant evidence and considerable methodological heterogeneity observed among studies, we conclude that brain connectivity MRI biomarkers obtained within 1 month of injury may be potentially useful in predicting outcome in mTBI. Further longitudinal studies are needed to evaluate the effect of mTBI on MRI-based brain connectivity biomarkers and examine how incorporation of these tests can inform the clinical care of individual mTBI patients.

OBJECTIVE The impact of weight loss induced by bariatric surgery (BS) and nonsurgical approaches on cardiovascular risk factors (CVRFs) has not been fully elucidated. We assessed the effects of BS and a nonsurgical approach on carotid intima-media thickness (CIMT) and CVRFs in participants with class 3 obesity. METHODS A total of 87 participants with obesity (59 women; 46 [37-52] years old; BMI, 43 [40-47]) and 75 controls were recruited; 21 (25%) participants with obesity underwent BS. BMI, blood pressure, cholesterol, triglycerides, fasting plasma glucose, C-reactive protein, CIMT, and Framingham Risk Score were measured at baseline and at 3-year follow-up. Independent factors for reduction in CIMT were analyzed. The literature on the effects of BS and CIMT was reviewed. RESULTS After BS, BMI decreased from 45.45 to 27.28 (P

Objective Intravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma. Methods Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm(2). Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses. Results We found that f(CER) and D*(CER) correlated with rCBF(CER). The best cutoffs for 6-month survival were f(CER)>9.86% and D*(CER)>21.712 x 10(-3)mm(2)/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC: 0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031); f(CER) combined with treatment predicted survival with 100% accuracy. Conclusions The IVIM-metrics f(CER) and D*(CER) are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

A higher degree of angiogenesis is associated with shortened survival in glioblastoma. Feasible morphometric parameters for analyzing vascular networks in brain tumors in clinical practice are lacking. We investigated whether the macrovascular network classified by the number of vessel-like structures (nVS) visible on three-dimensional T1-weighted contrast&ndash, enhanced (3D-T1CE) magnetic resonance imaging (MRI) could improve survival prediction models for newly diagnosed glioblastoma based on clinical and other imaging features. Ninety-seven consecutive patients (62 men, mean age, 58 &plusmn, 15 years) with histologically proven glioblastoma underwent 1.5T-MRI, including anatomical, diffusion-weighted, dynamic susceptibility contrast perfusion, and 3D-T1CE sequences after 0.1 mmol/kg gadobutrol. We assessed nVS related to the tumor on 1-mm isovoxel 3D-T1CE images, and relative cerebral blood volume, relative cerebral flow volume (rCBF), delay mean time, and apparent diffusion coefficient in volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter. We also assessed Visually Accessible Rembrandt Images scoring system features. We used ROC curves to determine the cutoff for nVS and univariate and multivariate cox proportional hazards regression for overall survival. Prognostic factors were evaluated by Kaplan-Meier survival and ROC analyses. Lesions with nVS &gt, 5 were classified as having highly developed macrovascular network, 58 (60.4%) tumors had highly developed macrovascular network. Patients with highly developed macrovascular network were older, had higher volumeCEL, increased rCBFCEL, and poor survival, nVS correlated negatively with survival (r = &minus, 0.286, p = 0.008). On multivariate analysis, standard treatment, age at diagnosis, and macrovascular network best predicted survival at 1 year (AUC 0.901, 83.3% sensitivity, 93.3% specificity, 96.2% PPV, 73.7% NPV). Contrast-enhanced MRI macrovascular network improves survival prediction in newly diagnosed glioblastoma.

In metabolic diseases we normally differentiate between congenital and acquired diseases.Metabolic diseases in children are mostly congenital inborn errors of metabolism, whereas metabolic diseases in adults are usually acquired.Congenital metabolic disorders in children are a vast and highly specialist field and detailed knowledge of these belongs to the remit of tertiary referral or specialty centres.The syllabus will focus on the most common inborn errors of metabolism that can present or persist into adulthood, as well as on adult or acquired metabolic disorders.As a number of metabolic disorders are closely related to alcohol abuse or other toxic substances, the role of toxic effects from other substances, including therapeutic and recreational drugs, will be discussed in the second part of this section. Disorders of iron accumulation (Wilson’s disease and NBIA) have been previously discussed above under movement disorders but will be also reflected in the course.

Background and Purpose— Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods— We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results— Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions— These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

Purpose/Objective(s) To evaluate the impact on decision making and radiotherapy (RT) treatment planning of brain metastases (BM) using gadopiclenol, a new gadolinium-based contrast agent (GBCA). Materials/Methods Patients who underwent two separate magnetic resonance imaging (MRI) examinations, one with gadopiclenol and one with gadobenate dimeglumine, both at 0.1 mmol/kg were included in the analysis. Those with ≥1 BM detected in any of both scans were subjected to a blinded reader analysis and contouring. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, 3 experts blindly of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results A total of 13 adult patients (31% females) presenting with at least one BM were analyzed. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Treatment indication was changed in 2 (15%) patients, from no treatment to SRS and SRS to WBRT. The mean GTVs and V12 were comparable between gadopiclenol and gadobenate dimeglumine (P = 0.694, P = 1.974). The mean DSC was 0.70 (± 0.14, ρ 0.82). From a total 36 answers, an improvement in enhancement was qualified in 58.3% (n = 21) with g, while no difference was obtained in 19.4% (n = 7). Conclusion Gadopiclenol improved BM detection and characterization with impact on RT treatment decisions. Further trials are warranted to determine the impact of this novel MRI contrast agent on a clinical setting. Author Disclosure G.R. Sarria: Honoraria; Roche Pharma AG. Travel Expenses; Carl Zeiss Meditec AG. Volunteer; Rayos Contra Cancer Inc. J. Fleckenstein: None. M. Eckl: None. F. Stieler: None. M. Bendszus: None. L.C. Schmeel: None. D. Koch: None. A. Feist: None. M. Essig: None. F. Wenz: Honoraria; Carl Zeiss Meditec AG, Celgene GmbH, Roche Pharma AG, Eli Lilly and Co., Ipsen Pharma GmbH, Elekta AB.F.A. Giordano: Research Grant; Carl Zeiss Meditec AG, NOXXON Pharma AG. Honoraria; Implacit GmbH, Oncare GmbH, Roche Pharma AG, AstraZeneca GmbH.

Temporal lobe epilepsy (TLE) is a common form of epilepsy that presents with complex partial seizures and in some cases with generalization to tonic-clonic activity that are often well controlled with antiepileptic medication in up to two thirds of patients. The remaining one third with “medically i

Background Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O2 and expired CO2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O2 and CO2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. Methods We examine the effects of controlled alterations in both ET O2 and CO2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2 and O2 in various combinations commonly observed during anesthesia. Results Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. Conclusions Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. Trial registration ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

Background Pseudoprogression refers to areas of enhancement on MRI postadjuvant chemoradiation that arise as a result of treatment-related effects. Pseudoprogression has been well described with temozolomide-based chemoradiation but has not been studied in the setting of procarbazine, lomustine, and vincristine (PCV) chemotherapy. We reviewed patients treated with PCV to investigate the occurrence of pseudoprogression. Methods Adults diagnosed with World Health Organization grade II or III gliomas between 2010 and 2015 and treated with PCV or temozolomide were identified. Patient, tumor, treatment, and MRI data were retrospectively collected and analyzed. Pseudoprogression was defined as new enhancement seen on MRI within 6 months of completion of adjuvant radiotherapy or concurrent chemoradiation, which improved or remained stable on subsequent scans without therapeutic intervention. If MRI showed areas of new enhancement outside the 6-month post-treatment window, which resolved or remained stable without treatment, or in patients who did not receive adjuvant treatment, it was referred to as “atypical pseudoprogression.” Results Fifty-seven patients were identified. Nine (16%) patients were identified as having pseudoprogression on MRI. Two (4%) of these patients were treated with PCV and 7 (12%) were treated with temozolomide. Seventeen (30%) patients had atypical pseudoprogression: 8 (14%) treated with temozolomide, 8 (14%) treated with PCV, and 1 (2%) treated with both types of chemotherapy. Conclusions We describe the first 2 cases of PCV-related pseudoprogression and 17 cases of atypical pseudoprogression. As the re-emergence of adjuvant PCV occurs in clinical practice, the occurrence of classical and atypical pseudoprogression could have a significant impact on clinical decision making.

Quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) measures the rate of transfer of contrast agent from the vascular space to the tissue space by fitting signal-time data to pharmacokinetic models. However, these models are very sensitive to errors in T1 mapping. Accurate T1 mapping is necessary for high quality quantitative DCE-MRI studies. This study compares magnetization prepared rapid (two) gradient echo sequence (MP2RAGE) T1-mapping accuracy to the conventional variable flip angle (VFA) approach, and also determines the effect of the new T1-mapping method on the Ktrans parameter. VFA and MP2RAGE T1 values were compared to the gold standard inverse recovery (IR) method in phantom over manually drawn ROIs. In vivo, ROIs were manually drawn over prostate and prostatic lesions. Average T1 values over ROIs were compared and Ktrans maps for each method were calculated via the extended Tofts model. VFA-T1 maps overestimated T1 values by up to 50% compared to gold standard IR T1 values in phantom. MP2RAGE differed by up to 9%. MP2RAGE-T1 and Ktrans values were significantly different from VFA values over prostatic lesions (p

Diffusion-weighted echo planar imaging (DW-EPI) suffers from geometric distortion due to low phase-encoding bandwidth. Read-out segmented echo planar imaging (RS-EPI) reduces distortion but residual distortion remains in extreme cases. Additional corrections need to be applied, especially for radiotherapy applications where a high degree of accuracy is needed. In this study the use of magnetic field map corrections are assessed in DW-EPI and RS-EPI, to reduce geometric uncertainty for MRI-guided radiotherapy applications. Magnetic field maps were calculated from gradient echo images and distortion corrections were applied to RS-EPI images. Distortions were assessed in a prostate phantom by comparing to the known geometry, and in vivo using a modified Hausdorff distance metric using a T2-weighted spin echo as ground truth. Across 10 patients, field map-corrected RS-EPI reduced maximum distortion by 5 mm on average compared to DW-EPI (σ = 1.9 mm). Geometric distortions were also reduced significantly using field mapping with RS-EPI, compared to RS-EPI alone (p ≤ 0.05). The increased geometric accuracy of these techniques can potentially allow diffusion-weighted images to be fused with other MR or CT images for radiotherapy treatment purposes.

The authors prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. Intracerebral hemorrhage, perihematomal edema location and volume, and corticospinal tract involvement were assessed. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage and/or the perihematomal edema. The authors calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively. BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level–dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques—including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging—can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology.

Traumatic optic neuropathy is a rare cause of visual disturbance after head injury that can be difficult to distinguish from coexisting vestibulo-ocular dysfunction because of the overlap in presenting symptoms in patients with these conditions. We present a case report of a 13-year-old girl who sustained a head injury during a ringette game leading to blurred vision and diplopia persisting 5 months after injury. Clinical history and physical examination findings were consistent with a traumatic optic neuropathy, convergence insufficiency, and postconcussion syndrome. Neuroimaging was normal. The patient was managed using a multidisciplinary approach. At 6 months of follow-up, neuro-ophthalmological examination demonstrated evidence of permanent partial optic nerve injury, and formal neuropsychological testing fell primarily within normal limits. The patient was advised to retire from collision sports. The authors discuss the value of a comprehensive multidisciplinary approach to the evaluation and management of concussion patients presenting with persistent visual symptoms.

The above article was published with one author name being incorrect. The published paper states "H. von Tengg", whereas it should be "H. von Tengg-Kobligk". The author name has been corrected above.

Objective: MR-perfusion post-processing still lacks standardization. This study evaluates the results of perfusion analysis with two established software solutions in a large series of patients with different diseases when a highly standardized processing workflow is ensured. Methods: Multicenter data of 260 patients (80 with brain tumors, 124 with cerebrovascular disease and 56 with dementia examined with the same MR protocol) were analyzed. Raw data sets were processed with two software suites: Olea sphere and NordicICE. Group differences were analyzed with paired t-tests and one-way ANOVA. Results: Perfusion metrics were significantly different for all examined diseases in the unaffected brain for both software suites [ratio cortex/white matter left hemisphere: mean transit time (MTT) 0.991 vs 0.847, p < 0.05; relative cerebral bloodflow (rBF) 3.23 vs 4.418, p < 0.001; relative cerebral bloodvolume (rBVc) 2.813 vs 3.884, p < 0.001; right hemisphere: MTT 1.079 vs 0.854, p < 0.05; rBF 3.262 vs 4.378, p < 0.001; rBVc 2.762 vs 3.935, p < 0.001)]. Perfusion results were also significantly different in patients with stroke (ratio cortex/white matter affected hemisphere: MTT 1.058 vs 0.784; p < 0.001), dementia (ratio cortex/white matter left hemisphere: rBVc 1.152 vs 1.795, p < 0.001; right hemisphere: rBVc 1.396 vs 1.662, p < 0.05) and brain tumors (ratio cortex/whole tumor rBVc: 0.778 vs 0.919, p < 0.001 and ratio cortex/tumor hotspot rBVc: 0.529 vs 0.512, p < 0.05). Conclusion: Despite a highly standardized workflow, parametric perfusion maps are depended on the chosen software. Radiologists should consider software related variances when using dynamic susceptibility contrast perfusion for clinical imaging and research. Advances in knowledge: This multicenter study compared perfusion parameters calculated by two commercial dynamic susceptibility contrast perfusion post-processing software solutions in different central nervous system disorders with a large sample size and a highly standardized processing workflow. Despite, parametric perfusion maps are depended on the chosen software which impacts clinical imaging and research.

Background: Magnetic resonance imaging (MRI) is used to diagnose and monitor disease activity in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to explore the association of “ultrabright” axial fluid-attenuated inversion recovery (FLAIR) lesions with gadolinium enhancement in patients with RRMS using qualitative and quantitative approaches. Methods: MRIs from patients with RRMS from 2010 to 2015 were reviewed. Two radiologists independently identified ultrabright lesions on axial FLAIR sequences. The contrast-to-noise ratio (CNR) was measured for ultrabright and control lesions. Results: Of 301 lesions included in the study, 77 (26%) were identified by both radiologists as ultrabright. Interrater agreement was moderate (κ = 0.77, P < .001). Lesions identified by both radiologists as ultrabright demonstrated an association with gadolinium enhancement (χ21 = 30.8, P < .001) but were not associated with MRI magnet strength (χ21 = 0.24, P = .65). Higher CNR values were associated with gadolinium enhancement for 1.5-T studies (OR, 1.05; 95% CI, 1.02–1.07; P = .001) and 3-T studies (OR, 1.02; 95% CI, 1.02–1.03; P < .001). Diagnostic accuracy of the quantitative model was good for 1.5-T studies (area under the curve, 0.79; 95% CI, 0.68–0.9; P < .001) and 3-T studies (area under the curve, 0.78; 95% CI, 0.73–0.84; P < .001). Positive predictive value of 100% was obtained for CNR values of 92 for 1.5-T and 184 for 3-T studies. Conclusions: Qualitatively and quantitatively identified ultrabright axial FLAIR lesions are significantly associated with gadolinium enhancement.

BACKGROUND: The benefits of increasing extent of resection (EOR) for both overall survival and progression-free survival (PFS) in glioblastoma has been well documented. However, models predicting surgical outcomes have failed to incorporate a patients IDH status, a known prognostic factor. We isolate the impact of IDH on surgical outcomes. We determine the effect modification of increasing EOR and decreasing residual tumor volume (RTV) on IDH status. METHODS: We performed a retrospective cohort study of 98 patients with glioblastoma who had undergone either biopsy or surgical resection. Tumor volumes were determined by volumetric analysis. Univariable and multivariable Cox PH Regression models were built using overall survival and PFS as endpoints. RESULTS: Increasing EOR and decreasing RTV were both associated with prolonged overall survival and PFS. When IDH status was added to multivariable models, the model utilizing RTV provided a slightly better fit compared to EOR. An interaction term between RTV and IDH status was characterized, such that at low RTVs the prognosis of an IDH mutant is significantly better than that of an IDH wild-type, an effect that is less important as RTV increases. The significance of this term was confirmed by improved fit upon insertion into multivariable models. CONCLUSION: Minimizing RTV and increasing EOR are important prognostic factors for both IDH wild-type and IDH mutant glioblastoma. The protective benefit of the IDH mutation at lower RTVs suggests these patients are the best candidates for aggressive surgical resection.

Tumefactive demyelination refers to large focal demyelinating lesions in the brain, which can be mistaken for malignancy. In some patients, these lesions are monophasic with a self-limited course; however, other patients demonstrate recurrent disease with new tumefactive or non-tumefactive lesions, and a subsequent diagnosis of relapsing-remitting multiple sclerosis is not uncommon. Owing to the limited data available in the literature, many questions about the patterns and prognostic significance of recurrent tumefactive lesions remain unanswered. The current case report involves a patient who recovered from tumefactive demyelination and presented two years later with a new recurrent tumefactive lesion in the contralateral brain.

OBJECT The goal in this review was to summarize the results of clinical neuroimaging studies performed in patients with sports-related concussion (SRC) who were referred to a multidisciplinar ypediatric concussion program. METHODS The authors conducted a retrospective review of medical records and neuroimaging findings for all patients referred to a multidisciplinary pediatric concussion program between September 2013 and July 2014. Inclusion criteria were as follows: 1) age ≤ 19 years; and 2) physician-diagnosed SRC. All patients underwent evaluation and follow-up by the same neurosurgeon. The 2 outcomes examined in this review were the frequency of neuroimaging studies performed in this population (including CT and MRI) and the findings of those studies. Clinical indications for neuroimaging and the impact of neuroimaging findings on clinical decision making were summarized where available. This investigation was approved by the local institutional ethics review board. RESULTS A total of 151 patients (mean age 14 years, 59% female) were included this study. Overall, 36 patients (24%) underwent neuroimaging studies, the results of which were normal in 78% of cases. Sixteen percent of patients underwent CT imaging; results were normal in 79% of cases. Abnormal CT findings included the following: arachnoid cyst (1 patient), skull fracture (2 patients), suspected intracranial hemorrhage (1 patient), and suspected hemorrhage into an arachnoid cyst (1 patient). Eleven percent of patients underwent MRI; results were normal in 75% of cases. Abnormal MRI findings included the following: intraparenchymal hemorrhage and sylvian fissure arachnoid cyst (1 patient); nonhemorrhagic contusion (1 patient); demyelinating disease (1 patient); and posterior fossa arachnoid cyst, cerebellar volume loss, and nonspecific white matter changes (1 patient). CONCLUSIONS Results of clinical neuroimaging studies are normal in the majority of pediatric patients with SRC. However, in selected cases neuroimaging can provide information that impacts decision making about return to play and retirement from the sport.

Gadobutrol (GB) is reported to provide improved relaxivity and concentration compared to gadoterate (GT). This study was designed to intraindividually compare quantitative and qualitative enhancement characteristics of GB to GT in cervicocranial magnetic resonance angiography (MRA) of patients with cerebrovascular disease (CVD). Patients (n = 54) with CVD underwent two identical contrast-enhanced magnetic resonance angiography (CE-MRA) examinations of the cervical and intracranial vasculature in randomized order, using GB and GT in equimolar dose. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were obtained by two independent neuroradiologists, blinded to the applied contrast agents. Qualitative assessment was performed using a three-point scale with a focus on M1/M2 segments. One thousand and twenty-six vessel segments were analyzed. GB revealed a significantly higher SNR (p = 0.032) and CNR (p = 0.031) in all vessel segments. GB featured a significantly higher SNR and CNR in thoracic (p = 0.022; p = 0.016) and cervical vessels (p = 0.03; p = 0.038), as well as in the posterior circulation (p = 0.012; p = 0.005). In blinded qualitative assessment, overall preference was given to GB (p = 0.02), showing a significant better delineation of the M1/M2 segments (p = 0.041). Compared to GT, the use of GB results in a significantly higher SNR and CNR in cervical and cerebral CE-MRA, leading to a better delineation of the intracranial vasculature. Present results underline the potential of GB for improved CE-MRA assessment of vasculature in CVD patients.

Brain tumors are among the top causes of cancer-related deaths both in Europe and North America.