Limited utility of adding 3T cervical spinal cord MRI to monitor disease activity in multiple sclerosis.

BACKGROUND: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable. OBJECTIVE: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value. METHODS: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI. RESULTS: In 1285 pwMS (median interval: 13-14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses (p = 0.04), no disease-modifying therapy (DMT) use (p = 0.048), and ⩾ 3 new BLs (p < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3-11.7, p < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months). CONCLUSION: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity.

Plasma glial fibrillary acidic protein levels correlate with paramagnetic rim lesions in people with radiologically isolated syndrome.

BACKGROUND: There are no specific, evidence-based recommendations for the management of individuals with radiologically isolated syndrome. Imaging and blood biomarkers may have prognostic utility. OBJECTIVE: To determine whether plasma neurofilament light protein (NfL) or glial fibrillary acidic protein (GFAP) levels in people with radiologically isolated syndrome correlate with imaging measures that have been shown to be associated with negative clinical outcomes in people with multiple sclerosis. METHODS: Cross-sectional analysis of people with radiologically isolated syndrome. Participants underwent magnetic resonance imaging (MRI) of the brain and cervical spinal cord, and plasma was collected. Plasma NfL and GFAP levels were measured with a single-molecule array, and correlations with MRI measures were assessed, including the number of: T1-black holes, white-matter lesions demonstrating the central vein sign, paramagnetic rim lesions, cervical spinal cord lesions and infratentorial lesions. RESULTS: Plasma GFAP levels, but not NfL levels, showed correlations with the number of T1-black holes, white matter lesions demonstrating the central vein sign and paramagnetic rim lesions (all p < 0.05). CONCLUSION: We found correlations between plasma GFAP levels and imaging measures associated with poor clinical outcomes and chronic inflammation in individuals with radiologically isolated syndrome. Plasma GFAP may have prognostic utility in clinical trials and clinical practice.

Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign.

PURPOSE: T2-FLAIR mismatch serves as a highly specific but insensitive marker for IDH-mutant (IDHm) astrocytoma with potential limitations in real-world application. We aimed to assess the utility of a broader definition of T2-FLAIR discordance across a cohort of adult-type diffuse lower-grade gliomas (LrGG) to see if specific patterns emerge and additionally examine factors determining deviation from the classic T2-FLAIR mismatch sign. METHODS: Preoperative MRIs of non-enhancing adult-type diffuse LrGGs were reviewed. Relevant demographic, molecular, and MRI data were compared across tumor subgroups. RESULTS: Eighty cases satisfied the inclusion criteria. Highest discordance prevalence and > 50% T2-FLAIR discordance volume were noted with IDHm astrocytomas (P < 0.001), while < 25% discordance volume was associated with oligodendrogliomas (P = 0.03) and IDH-wildtype (IDHw) LrGG (P = 0.004). "T2-FLAIR matched pattern" was associated with IDHw LrGG (P < 0.001) and small or minimal areas of discordance with oligodendrogliomas (P = 0.03). Sensitivity and specificity of classic mismatch sign for IDHm astrocytoma were 25.7% and 100%, respectively (P = 0.06). Retained ATRX expression and/or non-canonical IDH mutation (n = 10) emerged as a significant factor associated with absence of classic T2-FLAIR mismatch sign in IDHm astrocytomas (100%, P = 0.02) and instead had minimal discordance or matched pattern (40%, P = 0.04). CONCLUSION: T2-FLAIR discordance patterns in adult-type diffuse LrGGs exist on a diverging but distinct spectrum of classic mismatch to T2-FLAIR matched patterns. Specific molecular markers may play a role in deviations from classic mismatch sign.

Topographical distribution and prevalence of basal duct-like recess sign in a cohort of Papillary Craniopharyngioma-novel findings and implications.

PURPOSE: Basal duct-like recess (DR) sign serves as a specific marker of papillary craniopharyngiomas (PCPs) of the strictly third-ventricular (3 V) topography. Origins of this sign are poorly understood with limited validation in external cohorts. METHODS: In this retrospective study, MRIs of pathologically proven PCPs were reviewed and evaluated for tumor topography, DR sign prevalence, and morphological subtypes. RESULTS: Twenty-three cases with 24 MRIs satisfied our inclusion criteria. Median age was 44.5 years with a predominant male distribution (M/F ratio 4.7:1). Overall, strictly 3 V was the commonest tumor topography (8/24, 33.3%), and tumors were most commonly solid-cystic (10/24, 41.7%). The prevalence of DR sign was 21.7% (5/23 cases), all with strictly 3 V topography and with a predominantly solid consistency. The sensitivity, specificity and positive and negative predictive value of the DR sign for strict 3 V topography was 62.5%, 100%, 100% and 84.2% respectively. New pertinent findings associated with the DR sign were observed in our cohort. This included development of the cleft-like variant of DR sign after a 9-year follow-up initially absent at baseline imaging. Additionally, cystic dilatation of the basal tumor cleft at the pituitary stalk-tumor junction and presence of a vascular structure overlapping the DR sign were noted. Relevant mechanisms, hypotheses, and implications were explored. CONCLUSION: We confirm the DR sign as a highly specific marker of the strictly 3 V topography in PCPs. While embryological and molecular factors remain pertinent in understanding origins of the DR sign, non-embryological mechanisms may play a role in development of the cleft-like variant.

A shift from open to endovascular repair in the treatment of ruptured middle cerebral artery aneurysms: a single institution experience.

PURPOSE: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. METHODS: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. RESULTS: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. CONCLUSION: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS.

OBJECTIVE: The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS). METHODS: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures. RESULTS: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory(ß =-0.024, p = 0.03) while PRL predicted performance on verbal memory (ß = -0.040, p = 0.04) and processing speed (ß = -0.039, p = 0.03). CONCLUSIONS: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.

The painter who changed her brain at the flick of a switch.

The study of artists with acquired brain damage is an empirical way to investigate the multiplicity of cerebral changes that occur with artistic training. We describe a talented painter with a left progressive cerebral lesion. In spite of losing function of her right hand, she regained dexterity of the left one in ten days for painting and drawing but not for writing. We discuss two potential explanations for her rapid recovery: (a) her extensive artistic training and/or (b) the slow-growing nature of her cerebral lesion.

Clinical outcomes of isolated deep grey matter infarcts after endovascular treatment of large vessel occlusion stroke.

PURPOSE: There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome. METHODS: Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories ("other infarcts"). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0-2 at 90 days), excellent outcome (mRS 0-1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome. RESULTS: Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (adjOR: 1.45 [CI95: 1.04-2.02]), but not with good outcome (adjOR: 1.24 [CI95: 0.86-1.80]) or mortality (adjOR: 0.73 [CI95:0.39-1.35]) CONCLUSION: Predominantly deep grey matter infarct patterns were seen in 1/3rd of patients and were significantly associated with increased chances of excellent outcome, independent of patient baseline status and infarct size.

Seven-Year Follow-Up of a Patient With a Retained Needlefish Jaw Fragment Abutting Against His Left Internal Carotid Artery.

ABSTRACT: A 51-year-old man presented to the ophthalmology service with binocular diplopia and facial numbness. The patient was returning from a trip to Mexico. He reported having been hit in the left periocular region by a fish while swimming. Local doctors repaired a laceration in the left lateral canthus shortly after the incident. Orbital imaging revealed 2 needle-like foreign bodies corresponding to retained pieces of a needlefish jaw in the left orbit. Given the location of the foreign bodies, observation with repeat imaging was deemed more appropriate than surgical exploration. Subsequent imaging studies showed no migration of the foreign body, and the patient did not suffer from any related complications more than 7 years after the initial injury.

Contained Rupture of a Posterior Communicating Artery Aneurysm in a Patient With a Third Nerve Palsy.

ABSTRACT: It is recommended that every patient with a new third nerve palsy undergo urgent neuroimaging (computed tomography angiography or magnetic resonance angiography) to exclude a posterior communicating artery aneurysm. Because of the novel coronavirus (COVID-19) pandemic, our institution noted a significant decline in the number of patients with aneurysmal subarachnoid hemorrhage presenting to the hospital. We report one such example of a patient who developed new-onset severe headache and vomiting and did not seek medical attention because of COVID-19. Two months later, she was noted to have ptosis during a routine follow-up and was found to have a complete, pupil-involving third nerve palsy. Computed tomography angiography was performed and revealed an irregular bilobed saccular aneurysm (7 × 9 × 5 mm) of the right posterior communicating (PComm) artery, but no acute hemorrhage was visible on CT. On MRI, immediately adjacent to the aneurysm, there was a small subacute hematoma in the right medial temporal lobe with surrounding vasogenic edema. This case had a fortunate and unique outcome as she had a contained hematoma adjacent to the ruptured PComm aneurysm and did not experience severe morbidity from the subarachnoid hemorrhage nor did she rebleed in the interval in which she did not seek care. This case highlights the importance of providing neuro-ophthalmic care even during a pandemic.

CNS demyelination after initiating the tyrosine kinase inhibitor imatinib: A report of two cases.

The tyrosine kinase inhibitor, imatinib, used to treat certain malignancies, is in clinical trials as a potential treatment for multiple sclerosis and acute stroke. This is the first report of cases of multifocal central nervous system (CNS) demyelination following exposure to imatinib. One case was severe with bilateral optic neuritis and transverse myelitis that was AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG negative and improved after plasma exchange and withdrawal of imatinib. The second case involved a unilateral optic neuritis with magnetic resonance imaging (MRI) brain confirming other demyelinating lesions. Although the mechanism is unknown, demyelination on imatinib could be related to activation of previously normal T-cells.

Do painters need their whole brain to excel?

Skilled professional artists are sometimes able to maintain their talents while other cognitive functions deteriorate due to brain diseases. The objective of this study is to asses the preserved artistry of a professional painter in spite of the presence of strokes affecting brain areas implicated in art expression. She had a neurologic evaluation and brain imaging after the stroke; painter-curators analyzed and compared the painter's pictorial artwork created before and after the stroke. In spite of cerebellar, visuospatial, motor, cognitive, and functional deficits likely related to strokes affecting bilateral cerebellar, left occipital, and right temporal-occipital areas, the patient was able to maintain most of their artistic painting skills.. After a short period of functional recovery, our patient showed discrepancy among their impaired cerebellar cerebral functions in day activities and their preserved painting abilities.

Endovascular Thrombectomy for Low ASPECTS Large Vessel Occlusion Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The current American Heart Association guidelines for acute ischemic stroke reserve Grade 1A recommendation for the use of endovascular thrombectomy (EVT) for patients with an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of ≥6. OBJECTIVE: We aim to determine the safety and efficacy of EVT for large vessel occlusion ischemic stroke patients with low ASPECTS (5 or less). METHODS: Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for studies appraising the outcomes of EVT for low ASPECTS ischemic stroke. A meta-analysis of proportions compared the clinical outcomes of patients undergoing EVT and those receiving best medical therapy only. RESULTS: Nine studies (1,196 patients) were included. There was a trend (p = 0.11) toward a higher rate of symptomatic intracranial hemorrhage (sICH) in the EVT group (9.2%; 95% CI 6.1-13.6; I2 53.37%) compared to the medical group (5.5%; 95% CI 3.7-8.1; I2 0%). There was no difference (p = 0.41) in the pooled 90-day mortality of EVT patients (30.7%; 95% CI 21.7-41.5; I2 84.23%) and medical patients (36.6%; 95% CI 26.4-48.1; I2 76.2%). EVT patients had better (p = 0.001) 90-day outcomes, with 27.7% (95% CI 21.8-34.5; I2 62.08%) of patients attaining a modified Rankin Scale of 0-2 compared to only 3.7% (95% CI 2.3-5.9; I2 87.21%) in the medical group. CONCLUSIONS: This meta-analysis demonstrates a trend in higher sICH among low ASPECTS patients undergoing EVT. Despite this, a significant proportion of this subset of patients still achieved good functional outcomes at 90 days. Randomized trials are necessary to substantiate this result as significant bias is inherent in the observational studies included in this review.

MR imaging in the presence of ballistic debris of unknown composition: a review of the literature and practical approach.

Due to a combination of increasing indications for MR imaging, increased MRI accessibility, and extensive global armed conflict over the last few decades, an increasing number of patients now and in the future will present with retained metallic ballistic debris of unknown composition. To date, there are no guidelines on how to safely image these patients which may result in patients who would benefit from MRI not receiving it. In this article, we review the current literature pertaining to the MRI safety of retained ballistic materials and present the process we use to safely image these patients.

Emergency Imaging in Pregnancy and Lactation [Formula: see text].

The use of diagnostic imaging studies in the emergency setting has increased dramatically over the past couple of decades. The emergency imaging of pregnant and lactating patients poses unique challenges and calls upon the crucial role of radiologists as consultants to the referring physician to guide appropriate use of imaging tests, minimize risk, ensure timely management, and occasionally alleviate unwarranted trepidation. A clear understanding of the risks and benefits involved with various imaging tests in this patient population is vital to achieve this. This review discusses the different safety and appropriateness issues that could arise with the use of ionizing radiation, iodinated-, and gadolinium-based contrast media and radiopharmaceuticals in pregnant and lactating patients. Special considerations such as trauma imaging, safety concerns with magnetic resonance imaging and ultrasound, management of claustrophobia, contrast extravasation, and allergic reactions are also reviewed. The consent process for these examinations has also been described.

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

BACKGROUND AND PURPOSE: In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. METHODS: All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). RESULTS: CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P=0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P=0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. CONCLUSIONS: The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes.

Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO2) maps. Two intratumoral sites were identified, one with low StO2 and one with high StO2. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO2). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO2 and PtO2, the ratios of low to high StO2 versus low to high PtO2 in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO2 versus high StO2. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.