Autonomous animal heating and cooling system for temperature-regulated magnetic resonance experiments.

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T1 , T2 , proton density, and diffusion). In the preclinical setting, temperature has a large influence on animal physiology (e.g., respiration rate, heart rate, metabolism, and oxidative stress) and needs to be carefully regulated, especially when the animal is under anesthesia and thermoregulation is disrupted. We present an open-source heating and cooling system capable of regulating the temperature of the animal. The system was designed using Peltier modules capable of heating or cooling a circulating water bath with active temperature feedback. Feedback was obtained using a commercial thermistor, placed in the animal rectum, and a proportional-integral-derivative controller was used to modulate the temperature. Its operation was demonstrated in a phantom as well as in mouse and rat animal models, where the standard deviation of the temperature of the animal upon convergence was less than a 10th of a degree. An application where brain temperature of a mouse was modulated was demonstrated using an invasive optical probe and noninvasive magnetic resonance spectroscopic thermometry measurements.

ISMRM Clinical Focus Meeting 2023: "Imaging the Fire in the Brain".

Set during the Annual Meeting of the International Society for Magnetic Resonance in Medicine (ISMRM), the "Clinical Focus Meeting" (CFM) aims to bridge the gap between innovative magnetic resonance imaging (MRI) scientific research and daily patient care. This initiative is dedicated to maximizing the impact of MRI technology on healthcare outcomes for patients. At the 2023 Annual Meeting, clinicians and scientists from across the globe were invited to discuss neuroinflammation from various angles (entitled "Imaging the Fire in the Brain"). Topics ranged from fundamental mechanisms and biomarkers of neuroinflammation to the role of different contrast mechanisms, including both proton and non-proton techniques, in brain tumors, autoimmune disorders, and pediatric neuroinflammatory diseases. Discussions also delved into how systemic inflammation can trigger neuroinflammation and the role of the gut-brain axis in causing brain inflammation. Neuroinflammation arises from various external and internal factors and serves as a vital mechanism to mitigate tissue damage and provide neuroprotection. Nonetheless, excessive neuroinflammatory responses can lead to significant tissue injury and subsequent neurological impairments. Prolonged neuroinflammation can result in cellular apoptosis and neurodegeneration, posing severe consequences. MRI can be used to visualize these consequences, by detecting blood-brain barrier damage, characterizing brain lesions, quantifying edema, and identifying specific metabolites. It also facilitates monitoring of chronic changes in both the brain and spinal cord over time, potentially leading to better patient outcomes. This paper represents a summary of the 2023 CFM, and is intended to guide the enthusiastic MR user to several key and novel sequences that MRI offers to image pathophysiologic processes underlying acute and chronic neuroinflammation. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

Acetazolamide-augmented BOLD MRI to Assess Whole-Brain Cerebrovascular Reactivity in Chronic Steno-occlusive Disease Using Principal Component Analysis.

Background Exhaustion of cerebrovascular reactivity (CVR) portends increased stroke risk. Acetazolamide-augmented blood oxygenation level-dependent (BOLD) MRI has been used to estimate CVR, but low signal-to-noise conditions relegate its use to terminal CVR (CVRend) measurements that neglect dynamic features of CVR. Purpose To demonstrate comprehensive characterization of acetazolamide-augmented BOLD MRI response in chronic steno-occlusive disease using a computational framework to precondition signal time courses for dynamic whole-brain CVR analysis. Materials and Methods This study focused on retrospective analysis of consecutive patients with unilateral chronic steno-occlusive disease who underwent acetazolamide-augmented BOLD imaging for recurrent minor stroke or transient ischemic attack at an academic medical center between May 2017 and October 2020. A custom principal component analysis-based denoising pipeline was used to correct spatially varying non-signal-bearing contributions obtained by a local principal component analysis of the MRI time series. Standard voxelwise CVRend maps representing terminal responses were produced and compared with maximal CVR (CVRmax) as isolated from binned (per-repetition time) denoised BOLD time course. A linear mixed-effects model was used to compare CVRmax and CVRend in healthy and diseased hemispheres. Results A total of 23 patients (median age, 51 years; IQR, 42-61, 13 men) who underwent 32 BOLD examinations were included. Processed MRI data showed twofold improvement in signal-to-noise ratio, allowing improved isolation of dynamic characteristics in signal time course for sliding window CVRmax analysis to the level of each BOLD repetition time (approximately 2 seconds). Mean CVRmax was significantly higher than mean CVRend in diseased (5.2% vs 3.8%, P < .01) and healthy (5.5% vs 4.0%, P < .01) hemispheres. Several distinct time-signal signatures were observed, including nonresponsive; delayed/blunted; brisk; and occasionally nonmonotonic time courses with paradoxical features in normal and abnormal tissues (ie, steal and reverse-steal patterns). Conclusion A principal component analysis-based computational framework for analysis of acetazolamide-augmented BOLD imaging can be used to measure unsustained CVRmax through twofold improvements in signal-to-noise ratio. © RSNA, 2023 Supplemental material is available for this article.

Perfusion Imaging Predicts Favorable Outcomes after Basilar Artery Thrombectomy.

OBJECTIVE: Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar artery occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (time to reach maximum concentration in seconds [Tmax] > 10) would have a favorable response to ET compared to patients with more extensive regions involved. METHODS: We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We prespecified a Critical Area Perfusion Score (CAPS; 0-6 points), which quantified severe hypoperfusion (Tmax > 10) in cerebellum (1 point/hemisphere), pons (2 points), and midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS ≤ 3) and unfavorable (CAPS > 3) groups. The primary outcome was a favorable functional outcome 90 days after ET (modified Rankin Scale = 0-3). RESULTS: One hundred three patients were included. CAPS ≤ 3 patients (87%) had a lower median National Institutes of Health Stroke Scale score (NIHSS; 12.5, interquartile range [IQR] = 7-22) compared to CAPS > 3 patients (13%; 23, IQR = 19-36; p = 0.01). Reperfusion was achieved in 84% of all patients, with no difference between CAPS groups (p = 0.42). Sixty-four percent of reperfused CAPS ≤ 3 patients had a favorable outcome compared to 8% of nonreperfused CAPS ≤ 3 patients (odds ratio [OR] = 21.0, 95% confidence interval [CI] = 2.6-170; p < 0.001). No CAPS > 3 patients had a favorable outcome, regardless of reperfusion. In a multivariate regression analysis, CAPS ≤ 3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre-ET NIHSS (OR = 39.25, 95% CI = 1.34->999, p = 0.04). INTERPRETATION: BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. ANN NEUROL 2022;91:23-32.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.

BACKGROUND: Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. PURPOSE: To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. STUDY TYPE: Retrospective. POPULATION: A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. FIELD STRENGTH/SEQUENCE: A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. ASSESSMENT: A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. STATISTICAL TESTS: Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. RESULTS: CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r = 0.728) as compared to CVRmax (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r = 0.739) than for CVRend (r = 0.705). DATA CONCLUSION: CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3.

Continued Infarction Growth and Penumbral Consumption After Reperfusion in Vaccine-Naive Patients With COVID-19: A Case-Control Study.

BACKGROUND. Neurologic sequelae of SARS-CoV-2 include potentially malignant cerebrovascular events arising from complex hemodynamic, hematologic, and inflammatory processes occurring in concert. OBJECTIVE. This study concerns the hypothesis that despite angiographic reperfusion COVID-19 promotes continued consumption of at-risk tissue volumes after acute ischemic stroke (AIS), yielding critical insights into prognostication and monitoring paradigms in vaccine-naive patients experiencing AIS. METHODS. This retrospective study compared 100 consecutive COVID-19 patients with AIS presenting between March 2020 and April 2021 with a contemporaneous cohort of 282 AIS patients without COVID-19. Reperfusion classes were dichotomized into positive (extended thrombolysis in cerebral ischemia [eTICI] score = 2c-3) and negative (eTICI score < 2c) groups. All patients underwent endovascular therapy after initial CT perfusion imaging (CTP) to document infarction core and total hypoperfusion volumes. RESULTS. Ten COVID-positive (mean age ± SD, 67 ± 12 years; seven men, three women) and 144 COVID-negative patients (mean age, 71 ± 16 years; 76 men, 68 women) undergoing endovascular reperfusion, with antecedent CTP and follow-up imaging, comprised the final dataset. Initial infarction core and total hypoperfusion volumes (mean ± SD) were 1.5 ± 18 mL and 85 ± 100 mL in COVID-negative patients and 30.5 ± 34 mL and 117 ± 80.5 mL in COVID-positive patients, respectively. Final infarction volumes were significantly larger in patients with COVID-19, with median volumes of 77.8 mL versus 18.2 mL among control patients (p = .01), as were normalized measures of infarction growth relative to baseline infarction volume (p = .05). In adjusted logistic parametric regression models, COVID positivity emerged as a significant predictor for continued infarct growth (OR, 5.10 [95% CI, 1.00-25.95]; p = .05). CONCLUSION. These findings support the potentially aggressive clinical course of cerebrovascular events in patients with COVID-19, suggesting greater infarction growth and ongoing consumption of at-risk tissues, even after angiographic reperfusion. CLINICAL IMPACT. SARS-CoV-2 infection may promote continued infarction progression despite angiographic reperfusion in vaccine-naive patients with large-vessel occlusion AIS. The findings carry potential implications for prognostication, treatment selection, and surveillance for infarction growth among revascularized patients in future waves of infection by novel viral strains.

Decreasing false-positive detection of intracranial hemorrhage (ICH) using RAPID ICH 3.

INTRODUCTION: The prompt detection of intracranial hemorrhage (ICH) on a non-contrast head CT (NCCT) is critical for the appropriate triage of patients, particularly in high volume/high acuity settings. Several automated ICH detection tools have been introduced; however, at present, most suffer from suboptimal specificity leading to false-positive notifications. METHODS: NCCT scans from 4 large databases were evaluated for the presence of an ICH (IPH, IVH, SAH or SDH) of >0.4 ml using fully-automated RAPID ICH 3.0 as compared to consensus detection from at least two neuroradiology experts. Scans were excluded for (1) severe CT artifacts, (2) prior neurosurgical procedures, or (3) recent intravenous contrast. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by were determined. RESULTS: A total of 881 studies were included. The automated software correctly identified 453/463 ICH-positive cases and 416/418 ICH-negative cases, resulting in a sensitivity of 97.84% and specificity 99.52%, positive predictive value 99.56%, and negative predictive value 97.65% for ICH detection. The positive and negative likelihood ratios for ICH detection were similarly favorable at 204.49 and 0.02 respectively. Mean processing time was <40 seconds. CONCLUSIONS: In this large data set of nearly 900 patients, the automated software demonstrated high sensitivity and specificity for ICH detection, with rare false-positives.

T1 and T2 quantification using magnetic resonance fingerprinting in mild traumatic brain injury.

OBJECTIVES: To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. METHODS: Clinical imaging, MRF, and DTI were acquired in patients (24 ± 10 days after injury (timepoint 1) and 90 ± 17 days after injury (timepoint 2)) and once in controls. Patient outcome was assessed with global functioning, symptom profile, and neuropsychological testing. ADC and fractional anisotropy (FA) from DTI and T1 and T2 from MRF were compared in 12 gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. RESULTS: Data from 22 patients (38 ± 12 years; 17 women) and 18 controls (32 ± 8 years; 12 women) were analyzed. Fourteen patients (37 ± 12 years; 11 women) returned for timepoint 2, while two patients provided only timepoint 2 clinical outcome data. At timepoint 1, there were no differences between patients and controls in T1, T2, and ADC, while FA was lower in mTBI frontal white matter. T1 at timepoint 1 and the change in T1 exhibited more (n = 18) moderate to strong correlations (|r|= 0.6-0.85) with clinical outcome at timepoint 2 than T2 (n = 3), FA (n = 7), and ADC (n = 2). High T1 at timepoint 1, and serially increasing T1, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). CONCLUSION: T1 derived from MRF was found to have higher utility than T2, FA, and ADC for predicting 3-month outcome after mTBI. KEY POINTS: • In a region-of-interest approach, FA, ADC, and T1 and T2 all showed limited utility in differentiating patients from controls at an average of 24 and 90 days post-mild traumatic brain injury. • T1 at 24 days, and the serial change in T1, revealed more and stronger predictive correlations with clinical outcome at 90 days than did T2, ADC, or FA. • T1 showed better prospective identification of non-recovered patients at 90 days than ADC, T2, and FA.

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS: We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS: We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS: The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial.

BACKGROUND AND PURPOSE: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (Tmax) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for Tmax delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. METHODS: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume-baseline core infarct volume)/(Tmax 6 or 10 s volume-baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. RESULTS: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%-87.7%) versus 5.3% (1.1%-14.6%) of penumbral tissue was consumed based on Tmax >6 s (P<0.001). In the same comparison for Tmax>10 s, we saw a difference of 165.4% (interquartile range, 56.1%-479.8%) versus 25.7% (interquartile range, 3.2%-72.1%; P<0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on Tmax >6 s (P=0.52) or Tmax >10 s (P=0.92). CONCLUSIONS: Among extended window endovascular thrombectomy patients, Tmax >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the Tmax >6-s mismatch volume may remain viable in untreated patients at 24 hours.

High-Performance Automated Anterior Circulation CT Angiographic Clot Detection in Acute Stroke: A Multireader Comparison.

Background Identification of large vessel occlusion (LVO) is critical to the management of acute ischemic stroke and prerequisite to endovascular therapy in recent trials. Increasing volumes and data complexity compel the development of fast, reliable, and automated tools for LVO detection to facilitate acute imaging triage. Purpose To investigate the performance of an anterior circulation LVO detection platform in a large mixed sample of individuals with and without LVO at cerebrovascular CT angiography (CTA). Materials and Methods In this retrospective analysis, CTA data from recent cerebrovascular trials (CRISP [ClinicalTrials.gov NCT01622517] and DASH) were enriched with local repositories from 11 worldwide sites to balance demographic and technical variables in LVO-positive and LVO-negative examinations. CTA findings were reviewed independently by two neuroradiologists from different institutions for intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) M1 LVO; these observers were blinded to all clinical variables and outcomes. An automated analysis platform was developed and tested for prediction of LVO presence and location relative to reader consensus. Discordance between readers with respect to LVO presence or location was adjudicated by a blinded tertiary reader at a third institution. Sensitivity, specificity, and receiver operating characteristics were assessed by an independent statistician, and subgroup analyses were conducted. Prespecified performance thresholds were set at a lower bound of the 95% CI of sensitivity and specificity of 0.8 or greater at mean times to notification of less than 3.5 minutes. Results A total of 217 study participants (mean age, 64 years ± 16 [standard deviation]; 116 men; 109 with positive findings of LVO) were evaluated. Prespecified performance thresholds were exceeded (sensitivity, 105 of 109 [96%; 95% CI: 91, 99]; specificity, 106 of 108 [98%; 95% CI: 94, 100]). Sensitivity and specificity estimates across age, sex, location, and vendor subgroups exceeded 90%. The area under the receiver operating characteristic curve was 99% (95% CI: 97, 100). Mean processing and notification time was 3 minutes 18 seconds. Conclusion The results confirm the feasibility of fast automated high-performance detection of intracranial internal carotid artery and middle cerebral artery M1 occlusions. © RSNA, 2021 See also the editorial by Kloska in this issue.

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

BACKGROUND AND PURPOSE: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial.

BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.

SARS-CoV-2 and Stroke in a New York Healthcare System.

BACKGROUND AND PURPOSE: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

A dual-tuned 17 O/1 H head array for direct brain oximetry at 3 Tesla.

PURPOSE: To design and build a dual-tuned 17 O/1 H coil for direct brain oximetry at 3T. METHODS: A dual-tuned 17 O/1 H coil comprising 2 degenerate mode birdcage coils was constructed to facilitate high-sensitivity 17 O and 1 H imaging. In vivo 17 O brain images were acquired in a healthy volunteer using a fermat looped orthogonally encoded trajectories sequence, together with high-resolution structural brain 1 H images. RESULTS: Natural abundance 17 O images with a nominal resolution of 8 mm3 were acquired in under 20 minutes exhibiting clear delineation of the physiological 17 O distribution. One-millimeter isotropic 1 H structural brain images demonstrated excellent quality and anatomical detail using routine clinical imaging sequence parameters and parallel acceleration. CONCLUSION: A dual-tuned 17 O/1 H array was constructed to enable high-sensitivity 17 O and 1 H imaging under standard clinical 3 T scanning conditions.

Mechanical Thrombectomy in Nonagenarians: A Propensity Score Matched Analysis.

BACKGROUND: Little data exists on outcomes of mechanical thrombectomy (MT) in nonagenarians. We aimed to compare the procedural and discharge outcomes of MT for acute ischemic stroke (AIS) in nonagenarians versus younger patients. METHODS: Procedural outcomes and discharge disposition were compared in propensity score-matched groups of nonagenarians versus patients aged≤69 with AIS who underwent MT. Patients aged 70-89 were excluded in order to compare nonagenarians to a younger cohort that most closely approximates the age of patients in the seminal MT trials. Good discharge disposition was defined as a discharge to home or acute rehabilitation. RESULTS: Of 3010 AIS patients, 46/297(16%) nonagenarians underwent MT compared to 159/1337(12%) aged≤69 (P = 0.091). Of 78 propensity score-matched patients (N = 39 ≥90, N = 39 ≤69), the median admission NIHSS was 22 versus 20, median ASPECTS was 9 versus 9, pre-stroke mRS<4 was 82% versus 87%, 18% versus 8% received IV tPA, and mTICI≥2b was 90% versus 90%, respectively (all P>0.05). Revascularization time (569 versus 372 min), door to groin puncture time (82 versus 71 min) and groin puncture to revascularization times (39 versus 24 min) were similar in between nonagenarians and ≤69, respectively (both P>0.05). Symptomatic ICH (2.6% versus 10.3%; p = 0.165) and in-hospital death rates (10% vs 26%; p = 0.077) trended lower among nonagenarians versus aged≤69. Good discharge disposition occurred in 44% of nonagenarians versus 51% aged≤69 years (p = 0.496). CONCLUSIONS: In propensity score analysis, 90% of nonagenarians achieved successful recanalization and almost half (44%) were discharged to home/acute rehabilitation, which was similar to a younger (aged≤69 years) cohort.

Fast Automatic Detection of Large Vessel Occlusions on CT Angiography.

Background and Purpose- Accurate and rapid detection of anterior circulation large vessel occlusion (LVO) is of paramount importance in patients with acute stroke due to the potentially rapid infarction of at-risk tissue and the limited therapeutic window for endovascular clot retrieval. Hence, the optimal threshold of a new, fully automated software-based approach for LVO detection was determined, and its diagnostic performance evaluated in a large cohort study. Methods- For this retrospective study, data were pooled from: 2 stroke trials, DEFUSE 2 (n=62; 07/08-09/11) and DEFUSE 3 (n=213; 05/17-05/18); a cohort of endovascular clot retrieval candidates (n=82; August 2, 2014-August 30, 2015) and normals (n=111; June 6, 2017-January 28, 2019) from a single quaternary center; and code stroke patients (n=501; January 1, 2017-December 31, 2018) from a single regional hospital. All CTAs were assessed by the automated algorithm. Consensus reads by 2 neuroradiologists served as the reference standard. ROC analysis was used to assess diagnostic performance of the algorithm for detection of (1) anterior circulation LVOs involving the intracranial internal carotid artery or M1 segment middle cerebral artery (M1-MCA); (2) anterior circulation LVOs and proximal M2 segment MCA (M2-MCA) occlusions; and (3) individual segment occlusions. Results- CTAs from 926 patients (median age 70 years, interquartile range: 58-80; 422 females) were analyzed. Three hundred ninety-five patients had an anterior circulation LVO or M2-MCA occlusion (National Institutes of Health Stroke Scale 14 [median], interquartile range: 9-19). Sensitivity and specificity were 97% and 74%, respectively, for LVO detection, and 95% and 79%, respectively, when M2 occlusions were included. On analysis by occlusion site, sensitivities were 90% (M2-MCA), 97% (M1-MCA), and 97% (intracranial internal carotid artery) with corresponding area-under-the-ROC-curves of 0.874 (M2), 0.962 (M1), and 0.997 (intracranial internal carotid artery). Conclusions- Intracranial anterior circulation LVOs and proximal M2 occlusions can be rapidly and reliably detected by an automated detection tool, which may facilitate intra- and inter-instutional workflows and emergent imaging triage in the care of patients with stroke.

Automated Detection of Intracranial Large Vessel Occlusions on Computed Tomography Angiography: A Single Center Experience.

Background and Purpose- Endovascular thrombectomy is highly effective in acute ischemic stroke patients with an anterior circulation large vessel occlusion (LVO), decreasing morbidity and mortality. Accurate and prompt identification of LVOs is imperative because these patients have large volumes of tissue that are at risk of infarction without timely reperfusion, and the treatment window is limited to 24 hours. We assessed the accuracy and speed of a commercially available fully automated LVO-detection tool in a cohort of patients presenting to a regional hospital with suspected stroke. Methods- Consecutive patients who underwent multimodal computed tomography with thin-slice computed tomography angiography between January 1, 2017 and December 31, 2018 for suspected acute ischemic stroke within 24 hours of onset were retrospectively identified. The multimodal computed tomographies were assessed by 2 neuroradiologists in consensus for the presence of an intracranial anterior circulation LVO or M2-segment middle cerebral artery occlusion (the reference standard). The patients' computed tomography angiographies were then processed using an automated LVO-detection algorithm (RAPID CTA). Receiver-operating characteristic analysis was used to determine sensitivity, specificity, and negative predictive value of the algorithm for detection of (1) an LVO and (2) either an LVO or M2-segment middle cerebral artery occlusion. Results- CTAs from 477 patients were analyzed (271 men and 206 women; median age, 71; IQR, 60-80). Median processing time was 158 seconds (IQR, 150-167 seconds). Seventy-eight patients had an anterior circulation LVO, and 28 had an isolated M2-segment middle cerebral artery occlusion. The sensitivity, negative predictive value, and specificity were 0.94, 0.98, and 0.76, respectively for detection of an intracranial LVO and 0.92, 0.97, and 0.81, respectively for detection of either an intracranial LVO or M2-segment middle cerebral artery occlusion. Conclusions- The fully automated algorithm had very high sensitivity and negative predictive value for LVO detection with fast processing times, suggesting that it can be used in the emergent setting as a screening tool to alert radiologists and expedite formal diagnosis.

Cerebral MR oximetry during acetazolamide augmentation: Beyond cerebrovascular reactivity in hemodynamic failure.

BACKGROUND: Oxygen extraction fraction (OEF) elevation predicts increased ischemic stroke incidence among patients with carotid steno-occlusive disease, and can be estimated from quantitative susceptibility mapping (QSM) MRI. PURPOSE: To explore QSM oximetry during acetazolamide (ACZ) challenge, hypothesizing that detectable OEF alterations will reflect hemodynamic compromise in unilateral cerebrovascular disease (CVD) patients. STUDY TYPE: Retrospective. SUBJECTS: Fourteen unilateral CVD patients, and 24 healthy controls (HC). FIELD STRENGTH/SEQUENCE: Multiecho gradient echo (GRE) and T1 -weighted images at 3T. ASSESSMENT: We constructed QSM images and R2* maps from multiecho GRE images. QSM-OEF maps were generated from the susceptibility difference between venous blood and background brain tissue. Intrasubject diseased/contralateral hemisphere OEF ratios in the middle cerebral artery (MCA) territories were calculated. Intravascular susceptibility in the straight sinus (SS) and MCA was also measured. STATISTICAL TESTS: The result significance was determined using t-tests and Pearson's correlation. RESULTS: Mean and standard deviation for the patient diseased/contralateral OEF ratios were 1.15 ± 0.14 at baseline and 1.23 ± 0.17 post-ACZ. Disease group R2* ratios were 0.95 ± 0.05 at baseline and 1.03 ± 0.08 post-ACZ. Left/right OEF and R2* ratios for the HC group were 0.98 ± 0.06 and 0.99 ± 0.038, respectively. Susceptibility (ppb) in the SS and MCA in patients was 162.63 ± 35.4 and -22.33 ± 13.70, respectively, at baseline, 124.56 ± 37.43 and -19.27 ± 23.14 post-ACZ. The HC group SS and MCA susceptibility was 146.10 ± 24.79 and -19.59 ± 12.37, respectively. Patient group OEF ratios were greater than 1.0 before and after ACZ challenge (P < 0.01 and < 0.001, respectively, one-sample t-test), and were greater than HC ratios (P < 0.001 unpaired t-test). OEF and R2* ratios increased from baseline to post-ACZ (P = 0.024, 0.004, respectively, paired t-test). Detectable blood oxygenation change was confirmed by finding SS susceptibility decreased from baseline to post-ACZ (P < 0.001, paired t-test), while MCA susceptibility did not change significantly (P = 0.67, paired t-test). DATA CONCLUSION: These results suggest QSM is sensitive to dynamic OEF modulation during hemodynamic augmentation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:175-182.

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke.

OBJECTIVE: To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS: We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging. RESULTS: Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140). INTERPRETATION: The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.