bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP560: Cerebral Small Vessel Disease is Associated With Poor Collateral Recruitment in Large-Vessel Occlusive Stroke
Authors: Lin Michelle P , Liebeskind David S , Brott Thomas G , Meschia James F , Sam Kevin , Gottesman Rebecca F
Published: January 2019

Introduction:
Cerebral small-vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate if chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke.

Methods:
Consecutive patients with MCA±ICA occlusion presenting within 6 hours after stroke symptoms onset from 2012- 2016 were included. Primary outcome was collateral flow, which was assessed on baseline CT-angiogram (poor ≤50% filling, good >50% filling). Markers of chronic SVD on brain MRI were rated for the presence of WMH (Fazekas scale 2-3), enlarged perivascular spaces (EPVS), chronic lacunae, and any cerebral microbleeds (CMB) using the STRIVE criteria. Severity of SVD was quantified by adding the presence of each SVD feature to a maximum score of 4. Multivariable logistic regression models were performed to evaluate the relationships between SVD and poor collaterals.

Results:
Of the 100 patients, the mean age was 65±16, median NIHSS was 15, and 68% had SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals (aOR 1.9; 95%CI 1.1-3.2) than patients without SVD. Of the SVD types, poor collaterals were associated with WMH (aOR 2.9 per Fazekas increment; 95%CI 1.6-5.3) but not EPVS (aOR 1.3; 0.4-4.0), lacunae (aOR 2.1; 0.6-7.1), or CMB (aOR 2.1; 0.6-7.8). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend p<.001; adjusted p=.056). There was a dose-dependent relationship between WMH burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1-3 (trends P=.015, Table). No patient with SVD score of 4 had good collaterals.

Conclusions:
Chronic cerebral small-vessel disease is associated with poor recruitment of collaterals in large-vessel occlusive stroke. A prospective study to elucidate the mechanism of how SVD may impair the recruitment of collaterals is ongoing.
Abstract WP563: Risk Factors Related to the Development of Post Stroke Cognitive Impairment in Shanghai Stroke Population
Authors: Dong Yi , Cui Mei , Fang Min , Gong Li , Wang Xiuzhe , Xu Xiaofeng , Xu Zhuojun , Zhang Yue , Chen Lingyun , Liu Xueyuan , Li Gang , Zhao Yuwu , Han Xiang , Dong Qiang
Published: January 2019

Background:
Post-stroke cognitive impairment (PSCI) or post-stroke dementia (PSD) may affect one third of stroke patients. Understanding the risk factors related to the development of PSCI or PSD in acute stroke may help prevent and treat PSCI or PSD. A large-scale examination of PSCI risk factors was done for the first time in Shanghai stroke population

Method:
This was a multicenter observational registry study. The inclusion criteria were: >18-year-old, had an ischemic stroke within 2 weeks. Those with preexisting cognitive impairment, language, impaired hearing or reading or without education were excluded. Once informed consents signed, MOCA, mini-MOCA and MMSE were completed. Rate of PSCI and its related risk factors were examined. Statistical analysis was conducted by STATA 15. Logistic regression was performed to evaluate the risk factors and their odds ratios.

Results:
Of 1006 AIS patients with stroke onset within 14 days, 516 (51.8%, 95% CI 46.3-58.2%) had PSCI. These patients performed poorly in MOCA spatial, naming, registration, abstraction, language, orientation and short-term memory tests. Multiple regression model showed that patients with advance aging (OR 1.846 95%CI 1.806-2.826), severe stroke (OR 2.182, 95%CI 1.296-3.273), previous stroke history (OR 1.507, 95%CI 1.053-2.057) were likely to develop PSCI in acute phase of ischemic stroke. However, high level of education (OR 0.374, 95%CI 0.273-0.589) and LDL level>1.8 mmol/L may relate to the less PSCI rate in post stroke patients (OR 0.499, 95%CI 0.279-0.892). There is no significant correlation between stroke type and PSCI.

Conclusion:
In this post-stroke cognitive study cohort, PSCI was common among stroke patients in Shanghai. The risk factors of PSCI are age, previous stroke and less educated, however, the strategy of how to prevent PSCI is still unknown. The paradoxical phenomenon of protective effect of hyperlipidemia in PSCI remains to be further studied.
Abstract WP564: Deep Immune Profiling of the Post-Stroke Peripheral Immune Response Reveals Tri-phasic Response and Correlations With Long-Term Cognitive Outcomes
Authors: Tsai Amy S , Berry Ketura , Beneyto Maxime M , Gaudilliere Dyani , Ganio Edward A , Choisy Benjamin , Djebali Karim , Baca Quentin , Quach Lisa , Drag Lauren , Lansberg Maarten G , Angst Martin S , Gaudilliere Brice , Buckwalter Marion S , Aghaeepour Nima
Published: January 2019

Introduction:
Stroke produces profound local and systemic immune responses that engage all major innate and adaptive immune compartments. The aim of this study was to characterize the systemic immune response to stroke and to determine if it contributes to long-term cognitive disability.

Methods:
We included 24 consecutive subjects with ischemic stroke and excluded patients for autoimmune disorders, use of immunosuppressant drugs, or life expectancy <90 days. Blood samples were collected for up to 9 timepoints after stroke (days 1, 2, 3, 5, 7, 14, 30, 90, and 365). Change in cognitive function between days 90 and 365 was assessed using the Montreal Cognitive Assessment (MoCA). Control samples were from a cohort of 24 sex- and age-matched patients prior to hip replacement surgery. We used mass cytometry to acquire 240 immune features from each sample, representing 20 immune cell subtypes, their frequency, cell surface markers, and activation states. Elastic Net (EN) regularized regression modeling was used to characterize phases of the immune response and to correlate stages of the immune response with change in cognitive function.

Results:
The EN model identified three distinct phases of the systemic immune response to ischemic stroke: The acute phase (day 2) was characterized by increased STAT3 (signal transducer and activator of transcription 3) signaling responses in innate immune cell types. The intermediate phase (day 5) was characterized by increased CREB (cAMP response element-binding protein) signaling responses in adaptive immune cell types. The late phase (day 90) was characterized by persistent elevation of neutrophils and IgM+ B cells. By day 365 there was a return to baseline immune responses, comparable to the controls. A decline in MoCA scores between day 90 and day 365 after stroke correlated with a stronger inflammatory response in the acute phase (r = -0.692, Bonferroni-corrected p = 0.04).

Conclusions:
The results demonstrate three distinct phases of the peripheral immune response that occur after stroke, spanning from days 2 to day 90. The acute phase immune response predicts post-stroke cognitive decline, suggesting that therapies aimed at optimizing this response could lead to preservation of cognitive functioning post-stroke.
Abstract WP567: The Association Between Decreased Cerebral Blood Flow in Transient Ischemic Attack Patients and Cognition
Authors: Reid Meaghan , McDougall Connor , Forkert Nils , Frayne Richard , Coutts Shelagh , Gupta Sah Rani , d'Esterre Christopher D , Barber Philip
Published: January 2019

Patients with transient ischemic attack (TIA) have a 4-fold increase in developing late-life dementia. Cerebral blood flow has shown to be reduced approximately 30% in patients with Alzheimer’s disease (AD). Vascular abnormalities may initiate and aggravate AD pathology prior to the development of clinical symptoms. We hypothesize that middle-aged patients with a history of TIA will have lower cerebral blood flow (CBF) in the hippocampus, thalamus, white matter and grey matter compared to healthy controls. Additionally, we hypothesize that individuals with lower cerebral blood flow in our regions of interest will have lower cognitive scores.

Participants between the ages of 45-85 years old without dementia were subject to a clinical brain MRI arterial-spin-labelling CBF sequence accompanied by a cognitive battery. The cognitive battery included the Montreal Cognitive Assessment (MOCA) and a composite memory score created with the Addenbrooke’s Cognitive Examination, the Brief Visuospatial Memory Test Revised, and the Rey Auditory Verbal Learning Test. TIA patients had their assessments within 14-days of ictus. Atlas-based imaging analysis was performed using FSL.

Sixty-three (63) healthy controls (63
+
10 years of age) and 51 TIA (69
+
9 years of age) participants were analyzed. In an independent one-tailed t-test, TIA patients had significantly (p<0.05) lower CBF than healthy controls in the left/right hippocampus and thalamus, and right white matter. A multiple regression was performed to predict MOCA and composite memory scores from CBF, while correcting for age, gender and premorbid intelligence. Lower hemispheric CBF in the hippocampus, thalamus, white matter and grey matter each significantly predicted lower MOCA scores (F(4,101), R
2
=[0.1701-0.2013], p<0.05) and lower composite memory scores (F(4,101), R
2
=[0.2429-0.2864], p<0.05) in all participants. In conclusion
,
TIA patients have significantly lower CBF values in regions of interest compared to healthy control subjects and decreased CBF values in all participants are associated with poorer cognitive scores. By investigating neuroimaging biomarkers associated with cognition in mid-life, we may begin to understand why TIA patients have a higher risk of developing AD in late-life.
Abstract WP569: Gut Microbiota and Dementia: A Cross-Sectional Study
Authors: Saji Naoki , Niida Shumpei , Murotani Kenta , Hisada Takayoshi , Sugimoto Taiki , Kimura Ai , Toba Kenji , Sakurai Takashi
Published: January 2019

Background:
The gut microbiota is associated with several life-threatening conditions andthus might represent a useful strategy for the prevention of dementia. However, the association between gut microbiota and dementia has not yet been fully clarified.

Hypothesis:
There are differences in the components of gut microbiota between demented and non-demented patients.

Methods:
We recruited outpatients who visited our memory clinic to participate in this study. Information on patients’ demographics, risk factors, activities of daily living was collectedand cognitive function was assessed using neuropsychological tests and brain MRI scans. Faecal samples were obtained and the gut microbiota was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia.

Results:
We analyzed 128 eligible patients (female: 59%, mean age: 74.2 years). Silent lacunar infarcts and cerebral microbleeds were more frequently observed on MRI scans of patients with dementia. The T-RFLP analysis revealed differences in the components of gut microbiota: levels of Bacteroides (enterotype I) were decreased and other bacteria (enterotype III) were increased in demented compared with non-demented patients. Multivariable analyses showed that enterotype I (OR 0.1, 95%CI 0.02-0.4, P<0.001) and enterotype III (OR 12.7, 95%CI 3.3-65.8, P<0.001) were strongly associated with dementia, independent of the traditional dementia biomarkers. Faecal concentrations of ammonia, indole, skatole, and phenol were higher in demented compared with non-demented patients.

Conclusion:
Gut microbiota is an independent and strong risk factor for dementia.
Abstract WP58: ADAMTS13/vWF Regulates the Efficacy of tPA in Ischemic Stroke Patients
Authors: Deng Wenjun , Liu Kai , Fisher Lindsay , Chou Richard , Bunda Bridget , Wang Andrew , D'Souza Erica , McMullin David , Buonanno Ferdinando , Lo Eng H , Ning MingMing
Published: January 2019

Background:
Intravenous tissue plasminogen activator (tPA), an efficacious thrombolytic, is sometimes ineffective due to various clinical factors and high clot burden. Recent animal data show that elevated von Willebrand Factor (vWF) content in thrombi may impair the recanalization efficacy of tPA, which can be improved by administering ADAMTS13 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 13), a vWF-cleaving protease. In the current study, we investigated the role of ADAMTS13 and vWF in regulating the early response to tPA in ischemic stroke patients.

Method:
138 consecutive tPA-treated ischemic stroke patients were prospectively recruited in accordance with IRB protocol. Peripheral venous blood was sampled at 12, 24 and 72hr post tPA administration. tPA responders are defined as patients with rapid clinical improvement (NIHSS≥4) within 7 days post tPA treatment and with mRankins ≤ 2 at 3 months, while non-responders show no improvement and remain disabled (mRankins > 2) after 3 months. ADAMTS13 levels and vWF activity were measured by ELISA.

Result:
ADAMTS13 and vWF are inversely correlated with each other, consistent with a role of ADAMTS13 in degrading vWF multimer (Figure 1A). tPA responders demonstrated significantly elevated level of ADAMTS13 (p<0.001) and reduced vWF activity (p=0.007) as early as 12 hours post tPA treatment, while in non-responders, ADAMTS13 deficiency correlated to delayed vWF reduction after 72hr (Figure 1B).

Conclusion:
Our results point to a crucial role of ADAMTS13 in regulating hyperacute-stage tPA response, and suggest the potential of ADAMTS13 as an adjunct therapy to tPA. Studies in a larger patient cohort with extended time course are still ongoing.
Abstract WP6: Successful Mechanical Thrombectomy Maybe Associated With Reduced Disability in Patients With Large Core Based on CTP: The Forsaken Cannot be Forgotten
Authors: Aghaebrahim Amin N , Granja Manuel F , Agnoletto Guilherme J , Gonsales Douglas , Desai Shashvat M , Jadhav Ashutosh P , Jovin Tudor G , Powers Ciarán J , Savageau Eric , Hanel Ricardo
Published: January 2019

Background and Purpose:
There is disparity on neuroimaging selection for acute stroke thrombectomy. Patients with large core infarcts are often excluded from reperfusion therapies. We aim to assess rates of favorable clinical outcomes in patients with large cores based on CTP (RAPID) and the effect of collaterals in this population.

Methods:
Retrospective study of patients with ischemic cores greater than 50cc on CTP and a proximal anterior circulation occlusion on computed tomographic angiogram who underwent endovascular thrombectomy. Evaluation period was October 2015 to June 2018 on three comprehensive stroke centers. Baseline characteristics, ASPECTS and collaterals scores were evaluated. Primary endpoint was rate of favorable clinical outcome at 3 months.

Results:
45 patients were included in the study. Mean age was 65 ±14.2 years, mean NIHSS score was 20 (10-32) and mean admission infarct volume was 85±31mL (CBF <30%) and Tmax>6 s was 199.5±68mL. The majority of patients presented within 6 hours (82%). Median ASPECTS score was 8 and 33% of patients had a favorable collaterals. Recanalization thrombolysis in cerebral ischemia 2b-3 was 88%. Post-thrombectomy mean infarct volume at 24 to 48 hours was 107±68.3mL, A total of 42% (19/45) had tPA. A 3-month favorable clinical outcome (mRS 0-2) was present in 31% (14/45) of patients. Rate of intracranial hemorrhage (ph1 or ph2) was 11% (5/45). A total of 92% (13/14) of all patients older than 75 years had a poor clinical outcome (mRS score >2). Among patients with good collaterals 46% (7/15) had good clinical outcomes whereas 23% (7/30) of patients with poor collaterals score had good clinical outcomes at 3 months. The rate of good outcome at three months for patients with ASPECTS> 6 was 31% (11/35), while 41% of patients with both favorable ASPECTS and Collaterals had a good clinical outcome. Hemicraniectomy was performed in 4% (2/45) of all patients.

Conclusions:
Acute stroke thrombectomy may be beneficial in some patients with large core based on CTP with good collaterals and it should not be withhold solely based on the core infarct volume on CTP in patients presenting within 6 hours.
Abstract WP61: Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3
Authors: Rao Vaishnavi , Christensen Søren , Yennu Amarnath , Mylnash Michael , Zaharchuk Greg , Heit Jeremy , Marks Michael P , Lansberg Maarten G , Albers Gregory W
Published: January 2019

Background and Purpose:
Accurate prediction of 24-hour infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial, we evaluated the accuracy of early ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy vs. medical management. We also assessed if the volume of persistent hypoperfusion at 24 hours predicts infarct volume.

Methods:
Patients in DEFUSE 3 with CT or MRI DWI/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax>6s hypoperfusion volumes at baseline and 24 hours were calculated using RAPID software and compared with the 24-hour infarct volumes. Patients were stratified by reperfusion status for analyses.

Results:
Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volumes and 24-hour infarct volume (r = 0.83; p < 0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax>6s volume and 24-hour infarct volume (r = 0.77; p < 0.001). In the 52 patients with 10-90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the Tmax>6s perfusion volume at 24 hours was highly correlated with 24-hour infarct volume (for N=125, r = 0.83; p < 0.0001), with a median absolute difference of 21.3 ml between observed and predicted infarct volumes.

Conclusions:
The union of the irreversibly injured ischemic core and critically hypoperfused tissue volumes, as identified by CT perfusion or MR DWI/perfusion, predicted infarct volume at 24 hours in DEFUSE 3 patients.

Clinical Trial Registration
- URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415
Abstract WP63: Computed Tomography Perfusion in Stroke Mimics
Authors: Siegler James E , Rosenberg Jon , Cristancho Daniel , Olsen Andrew , Pulst-Korenberg Johannes , Raab Lindsay , Cucchiara Brett , Messé Steven
Published: January 2019

Background:
Automated computed tomography perfusion (CTP) can help select acute ischemic stroke patients for thrombectomy. The prevalence and patterns of abnormal findings on automated CTP in patients with stroke mimic has not been well characterized.

Hypothesis:
Normal perfusion (time-to-tissue maximum, T
max
>6s) or a perfusion pattern that is discordant with a patient’s clinical symptoms or vessel imaging results will be predictive of a stroke mimic diagnosis.

Methods:
We reviewed a retrospective multi-site consecutive cohort of patients undergoing CTP for suspected acute ischemic stroke ≤24 hours from onset (6/2017-12/2017). The primary outcome was the incidence of any T
max
>6s abnormality on RAPID automated perfusion-weighted CT imaging comparing patients with stroke/TIA to those with stroke mimic. The presence of perfusion abnormalities that were discordant with clinical symptoms and CTA findings was also assessed.

Results:
Of 410 consecutive patients who underwent CTP, 348 met inclusion criteria (51.2% stroke, 5.5% TIA, and 43.4% mimic). The median NIHSS at presentation was 8 (IQR 4-15) and was slightly worse among stroke/TIA patients (9 vs. 7, p=0.057). The median time from LKN to CTP acquisition for all patients was 302 minutes (IQR 158-707) and was no different between groups (p=0.148). T
max
abnormalities were seen in 27.8% of patients with stroke mimic and 61.9% of patients with stroke/TIA (p<0.001). Stroke mimics were more likely to have a normal T
max
pattern (volume=0mL; adjusted OR 4.01, 95%CI 2.34-6.87, p<0.001). Mimics were more likely to have T
max
patterns discordant with clinical symptoms and CTA findings than patients with stroke/TIA (91.3% vs. 28.2%, p<0.001). Patients with only discordant T
max
abnormalities were more likely to have a stroke mimic (adjusted OR 30.05, 95%CI 5.27-171.39, p<0.001), with a positive predictive value for identifying mimic of 90.5% (85.2-94.1%).

Conclusion:
While one-quarter of patients with stroke mimic show abnormalities on automated CTP maps using RAPID, the vast majority of patterns were discordant with symptoms and vessel status. Normal or only discordant T
max
abnormalities are strongly associated with stroke mimics and may inform stroke treatment decision making.
Abstract WP66: CT and Multiphase CTA Alone Can Identify Thrombectomy Candidates Beyond 6 Hours
Authors: Hays Sarah , DiBiasio Eleanor , Caine Audra , Baird Grayson , Cutting Shawna , Yaghi Shadi , Boxerman Jerrold , Jindal Gaurav , Burton Tina , Saad Ali , Mac Grory Brian , Furie Karen , McTaggart Ryan , Jayaraman Mahesh V
Published: January 2019

Introduction:
Current stroke guidelines recommend CT Perfusion (CTP) or MRI to identify thrombectomy candidates beyond 6 hours from stroke onset. The efficacy of more readily available NCCT and CTA in the identification of such patients is unknown. In this study, we compared the accuracy of arterial phase CTA only (sCTA) and multi-phase CTA (mCTA) with MRI in patients beyond 6 hours from onset.

Methods:
We retrospectively reviewed 45 consecutive patients, presenting 6 to 24 hours from stroke onset, with known ICA or M1 occlusions. All patients had pre-treatment CTA and MRI, with diffusion weighted (DWI) and perfusion weighted imaging (PWI). MRI images were processed using RAPID. Five experienced readers independently scored ASPECTS (0-10), sCTA collateral score (0-5), and whether patients would have met DAWN or DEFUSE-3 MRI imaging criteria. After a one-month delay, grading was repeated by the same readers using NCCT and mCTA. The sensitivity and specificity for DAWN and DEFUSE-3 eligibility was examined for both sCTA and mCTA. We also examined the median DWI volume based on the combination of NCCT ASPECTS and collateral score, for both sCTA and mCTA.

Results:
Sensitivity and specificity for DAWN eligibility was 91.4% and 74.8% for sCTA; 87.2% and 76.8% for mCTA. For DEFUSE-3, sensitivity and specificity was 92.3% and 46.3% for sCTA; 94.5% and 57.5% for mCTA. The higher specificity for DAWN is likely due to the more restrictive imaging criteria used in that trial. For DWI volume, the results are summarized in the graph, and show that the combination of mCTA collateral score and NCCT ASPECTS is significantly more correlated with DWI volume than sCTA (p=.0018).

Conclusions:
In conclusion, the combination of NCCT ASPECTS and mCTA collateral score has high sensitivity and moderate specificity for identifying patients who meet DAWN or DEFUSE-3 criteria. NCCT ASPECTS and Multi-phase CTA collateral score are significantly more correlated with DWI volume than single-phase.
Abstract WP67: Selecting Stroke Patients for Late Thrombectomy Using non-RAPID Software: A Real-world Experience
Authors: Zhao Wenbo , Jiang Fang , Li Sijie , Wu Chuanjie , Li Chuanhui , Chen Jian , Ding Yuchuan , Ji Xunming
Published: January 2019

Background:
Clinical trials have determined the superiority of late thrombectomy for acute ischemic stroke (AIS) patients if selected based on pretreatment images postprocessed using RAPID software. However, RAPID software is not accessible in many regions.

Objective:
To evaluate the performance of a widely accessible imaging postprocessing software in selecting AIS patients for late thrombectomy, and compare the outcomes with those of the DAWN trial.

Methods:
This study was based on a prospective registry study in a high-volume stroke center. AIS patients who presented later than 6 hours after the time last known well (TLKW) underwent multimodal CT, and all images were postprocessed using conventional software (Siemens Healthcare). All images were visually inspected by experienced doctors who determined whether patients were eligible for thrombectomy. The primary outcome was the proportion of functional independence (i.e., mRS score 0 to 2) at 90 days.

Results:
A total of 27 consecutive AIS patients (aged 60.6±12.7 years) were recruited in this study. The median interval between TLKW to groin puncture was 9.5 hours, baseline NIHSS score was 15.7±8.1, the median ASPECT score was 8. After endovascular procedures, 23 patients (85%) achieved substantial recanalization (mTICI≥2b). Twelve patients (44%) experienced early therapeutic response, whereas 3 patients (8%) suffered from neurological deterioration, and 2 patients (7%) experienced symptomatic intracranial hemorrhage. At 3-month follow up, 14 patients (52%) achieved functional independence and 3 patients (11%) died. There were no significant differences between the DAWN trial and this study with respect to the above outcomes (Figure, p>0.05 each).

Conclusions:
In a high-volume stroke center, it would be practical to select AIS patients for late thrombectomy based on pretreatment multimodal CT images postprocessed without RAPID software, with clinical outcomes similar to those of the DAWN trial.
Abstract WP68: Interpretable Deep Learning-based Characterization of Intracranial Hemorrhage on Head CT
Authors: Bizzo Bernardo , Hashemian Behrooz , McNitt Troy , Caton Michael T , Wiggins Walter , Hillis James , Tenenholtz Neil , Kitamura Felipe , Gonzalez Gilberto , Michalski Mark , Andriole Katherine , Pomerantz Stuart R
Published: January 2019

Background:
Machine learning algorithms have proven accurate in the detection of intracranial hemorrhage (ICH) on head CT. Most reported algorithms, however, are limited to binary detection and global lesion volume estimation. We developed a pipeline to additionally perform subtype classification for clinical risk stratification, while also providing visual displays to improve interpretability of algorithm output (“black box problem”) and enable clinical systems integration.

Methods:
We developed a convolutional neural network (CNN) for ICH detection and subtype classification. The algorithm was trained on 2,209 head CT exams (hemorrhage-negative controls and the 5 major ICH subtypes) and outputs class-activation heatmaps to aid interpretability. We quantify intraparenchymal hemorrhage (IPH) volume using a modified U-Net CNN trained on a cohort of 110 manually-segmented hematomas to precisely delineate lesion boundaries. Algorithm output was stored as DICOM segmentation objects which can be overlaid on native images within our existing viewer applications, enabling the user to dynamically adjust characteristics such as color and transparency.

Results:
Diagnostic performance for ICH detection was high with ROC area-under-curve of 0.98. Fig 1A shows a heatmap highlighting different ICH foci. IPH subtype classification performance is summarized in Fig 1B with area-under-curve of 0.95. Fig 1C shows IPH segmentation and volume estimation overlays with automatically generated text for the medical record. Dice similarity coefficient for segmentation was 0.87.

Conclusion:
We describe a machine-learning approach for ICH detection, subtype classification, and IPH-specific volume estimation. Utilizing easily interpretable heatmaps, dynamically-adjustable overlays, and automated result text generation, our pipeline is capable of providing accurate information optimized for clinical integration.
Abstract WP69: Computed Tomography Perfusion Imaging in Evaluation of Patients With Acute Stroke is Not Associated With Increased Risk of Acute Kidney Injury
Authors: Satkowiak Kelsey , Carrera Joseph , Southerland Andrew
Published: January 2019

Introduction:
Mechanical thrombectomy has become standard of care in acute ischemic stroke with proximal arterial occlusion. For patients 6-24 hours from last known well, computed tomography perfusion (CTP) is now frequently used for assessment of endovascular therapy (EVT) eligibility. CTP requires an increased contrast load compared to computed tomographic angiography (CTA).

Hypothesis:
In patient assessment for EVT, CTA/CTP is not associated with higher incidence of acute kidney injury (AKI) compared to CTA alone.

Methods:
We reviewed data from consecutive acute stroke alerts at our institution from January-July 2018, and recorded baseline serum creatinine and creatinine at 24, 48, and 72 hours post-alert. AKI was defined by an increase in serum creatinine of 0.3, or more than a 1.5 fold increase in baseline creatinine, according to the Acute Kidney Injury Network definition. We compared patients receiving CTA/CTP versus CTA alone using independent samples t-test, including variables of age, NIHSS, baseline creatinine, and creatinine at 24, 48, and 72 hours. Chi-square testing was performed to compare incidence of AKI between groups. A binary logistic regression model was performed including covariates of age, sex, location of alert (emergency room or inpatient), NIHSS, baseline creatinine and imaging group. Significance was defined as p < 0.05 for all tests.

Results:
Analysis included 285 patients: 210 receiving CTA alone, and 75 receiving CTA/CTP. Incidence of AKI was 4.7% in the CTA alone group versus 4% in the CTA/CTP group (χ2=0.74, p=0.786). The two groups did not differ with regard to age, NIHSS, or serum creatinine at any time point. In the binary logistic regression model, addition of CTP to CTA did not increase the odds ratio of developing AKI (OR 1.076 [95% CI 0.276-4.193]; p=0.916).

Conclusions:
In acute stroke assessment for EVT eligibility, the addition of CTP to CTA did not increase rates of AKI. While this retrospective analysis includes the possibility of selection bias, the two groups were similar in baseline characteristics including kidney function. These results provide Level II, Class B evidence supporting the safety of CTP in patient selection for EVT and may inform future AHA/ASA guidelines for management of acute ischemic stroke.
Abstract WP7: Does Administration of IV Contrast Impact Outcomes on Acute Ischemic Stroke Patients? A Propensity Score Matched Single Center Study
Authors: Shah Kavit , Mayer Stephan A , Van Harn Meredith G , Ismail Mohammed , Schultz Lonni , Marin Horia L , Kole Maximilian K , Miller Daniel J
Published: January 2019

Introduction:
The AHA/ASA strongly recommend urgent noninvasive vascular imaging for suspected LVO patients.
1
There remains concern about developing acute kidney injury (AKI) and/or contrast induced nephropathy (CIN) secondary to contrast exposure for CTA or DSA.
2-8
It is unclear if contrast has any impact upon outcomes of endovascular thrombectomy (ET) patients, and if this differs from patients who do not undergo ET.

Methods:
A retrospective chart review was conducted upon 2384 consecutive patients who were admitted with acute ischemic stroke from 1/2014 - 8/2017. Patients were grouped into: ET (CTA+DSA), CTA Only, and No Contrast. Propensity score matching (PSM) was conducted for a 1:1:1 match between these 3 groups. The primary outcome was 90-day modified rankin scal (mRS). Patients were grouped into favorable (mRS ≤ 2) and unfavorable (mRS > 2). AKI was defined as an increase in serum creatinine (SCr) ≥ 0.3 within 48 hours while CIN was defined as an increase in SCr ≥ 0.5 or 25% at 48 - 72 hours
9
.

Results:
124 patients were matched into each group. Patients that received contrast had higher rates of AKI at 48-72 hours; however, this was not statistically significant (8% CTA+DSA, 5% CTA only, and 3% no contrast, p = 0.228). Patients with poor outcome amongst all groups had statistically significant higher rates of baseline CKD (37% vs 24%, p = 0.038) and AKI (22% vs 11%, p = 0.025). Multivariable analysis for the ET subgroup shows no significant difference in outcomes with or without AKI; however, in the non-ET subgroup, presence of AKI was significantly associated with poor outcome (OR 1.25 (0.36, 4.34) and 19.05 (2.13, 170.72), respectively; p < 0.05).

Conclusion:
Rates of AKI do not differ significantly based on the administration of contrast. In our PSM population, those not undergoing ET have poorer outcomes if they suffer AKI; however, there is no difference in outcomes if patients receive ET.
Abstract WP74: Right Hemispheric Infarcts Have Higher CT Perfusion Penumbra Volume for Given NIH Stroke Scale: Results From BEST Prospective Cohort Study
Authors: Mistry Eva A , Sucharew Heidi , Mehta Tapan , Arora Niraj , Starosciak Amy , De Los Rios La Rosa Felipe , Siegler James , Barnhill Natasha , Mistry Akshitkumar , Patel Kishan , Assad Salman , Tarboosh Amjad , Dakay Katarina , Wagner Jeff , Bennett Alicia , Cruz Aurora S , Fortuny Enzo , James Robert F , Jagadeesan Bharathi , Streib Christopher , Weber Stewart , Chitale Rohan , Volpi John , Mayer Stephan , Yaghi Shadi , Jayaraman Mahesh , Khatri Pooja , Woo Daniel
Published: January 2019

Introduction:
Right hemispheric strokes have a higher average infarct volume than left hemisphere strokes for the same severity of NIH stroke scale (NIHSS). This phenomenon, although well documented by CT and MRI based volume calculation of final infarct volume, is yet to be confirmed with automated acute CT/MR perfusion imaging in acute large vessel stroke setting. Additionally, penumbral volumes have not been well studied with regard to laterality of stroke.

Methods:
Data from the BEST prospective cohort study, a multicenter study that enrolled consecutive patients with anterior cerebral large vessel occlusion undergoing endovascular treatment were used for analysis. We determined the correlation between baseline NIHSS and CTP penumbra volume (CTPp; total volume of Tmax>6sec) as well as core infarct volume (CTPc) for right sided and left sided strokes. We also determined the difference in CTPp and CTPc between right and left sided stroke for every 5-point increase in the baseline NIHSS.

Results:
Of the 443 enrolled patients, 165 (82 female, median age 69 [IQR 57, 81]) had complete data for baseline CTPp and CTPc; one patient with bilateral strokes was excluded. Median CTPp for right sided (n=74) strokes was 127.5 cc [IQR 83, 167] and for left sided (n=90) strokes was 93.0 cc [IQR 62, 155]. Median CTPc for right sided strokes was 15.0 cc [IQR 0, 35] and that for left sided strokes was 6.5 cc [0, 24]. After adjusting for baseline NIHSS, right sided strokes had significantly higher CTPp than did left sided (p=0.001), but no evidence of laterality for CTPc was observed (p=0.09). The correlation coefficient for NIHSS and CTPp was 0.23 and 0.33, and that for CTPc was 0.16 and 0.19 for right and left side, respectively. Highest difference in CTPp between sides was observed at NIHSS 16-25 (table).

Conclusions:
Right hemispheric strokes have higher CTPp but not CTPc as compared to the left. For a given NIHSS, right hemispheric strokes may have larger salvageable tissue.
Abstract WP75: Ischemic Core Volume Modifies the Association Between ASPECT Score and Clinical Outcome
Authors: Sarraj Amrou , Hassan Ameer , Grotta James , Sitton Clark , Chen Peng R , Cai Chunyan , Cutter Gary , Pujara Deep , Imam Bita , Reddy Sujan , Kamal Haris , Abraham Michael , McCullough Louise , Lansberg Maarten , Savitz Sean , Albers Gregory , Gupta Rishi
Published: January 2019

Background:
While CT ASPECT scores predict clinical outcomes, the association between the scores and ischemic lesion volume is not linear as the subcortical regions involve small volumes while the cortical areas often involve large volumes. We evaluated whether ASPECTS and CTP ischemic core volume, modify each other’s association with clinical outcome in patients undergoing endovascular thrombectomy (EVT).

Methods:
In a prospective multicenter cohort study of imaging selection (SELECT), anterior circulation large vessel occlusion patients up to 24 hours from last known well were enrolled at 9 centers. All patients received a unified imaging profile (NCCT, CTA, and CTP with ischemic core volume [rCBF <30%] by RAPID software). A blinded core lab adjudicated all images.

Results:
Of 445 enrolled, 284 received EVT and are included in this analysis. Median (IQR) ASPECTS was 8 (7-9), median (IQR) ischemic core volume 10 ml (0-33). Both ASPECTS and ischemic core volume independently correlated with good outcome after EVT. For ASPECTS, the probability of good outcome decreased by 14% per point (aOR 1.18, 95% CI 1.01-1.38, p=0.03). For CTP mRS 0-2 probability dropped by 25% for each 10 ml increase in core volume (aOR 0.75, 95% CI 0.67-0.84, P<0.001). The correlation between ASPECTS and good outcome was substantially altered when adjusted for ischemic core size (fig 1). Outcomes were poor irrespective of ASPECTS in patients with large core lesions while outcomes were generally favorable in patients with a small ischemic core, even with lower ASPECTS. In contrast, the relationship between CTP ischemic core and favorable outcome was not altered when adjusted for ASPECTS (pre-ASPECTS aOR: 0.75 (0.67-0.84), p<0.001 vs post-ASPECTS aOR: 0.75 (0.67-0.85), p<0.001) (fig 2).

Conclusion:
ASPECTS association with clinical outcome after EVT was strongly modified by ischemic core volumes. Favorable outcomes were achieved in patients with small ischemic core volume despite low ASPECTS.
Abstract WP77: Automated Accurate Determinations of Acute Infarct Core Volumes From CT Angiography Using Machine Learning
Authors: Sheth Sunil A , Inam Mehmet E , Barman Arko , Lee Songmi , Savitz Sean I , Giancardo Luca
Published: January 2019

Background:
Guideline-based acute ischemic stroke (AIS) evaluations require the use of advanced parenchymal imaging including CT perfusion (CTP) to determine the presence of large vessel occlusion (LVOs) and infarct core. The availability of CTP in all hospitals that receive patients with possible AIS is limited. An accurate method to evaluate possible AIS patients that does not require CTP is urgently needed.

Methods:
Consecutive patients from 3/2018 - 5/2018 evaluated emergently for possible AIS within 24 hours of onset at our institution were identified. Patients were included if they underwent contemporaneous non-contrast CT, CT angiogram (CTA) and CT Perfusion (CTP) with RAPID (IschemaView) post-processing. A linear Support Vector Machine (SVM) was created using CTA data alone and trained against the CTP-RAPID infarct core volume determinations, which was used as the “gold standard.” Performance parameters were calculated using 10-fold cross-validation.

Results:
Among 139 subjects, median age was 64 [54-73], 48% were female, 40% were white and 34% were African-American. From this population, 16 subjects (12%) were ultimately diagnosed with AIS. Median time from onset to imaging was 3.9 hours [1.7-10.1], NIHSS 16.5 [8-24], and RAPID infarct core and “at risk” volumes were 35.5 mL [13-72] and 128.5 mL [80-165]. The CTA-based SVM classified AIS versus stroke mimic with excellent discrimination (AUC 0.95 ± 0.08) and accuracy of 89% ± 3%. In patients with AIS, CTA-based SVM estimation of infarct core correlated well with the CTP-RAPID (Spearman's rho 0.82 (p<0.001) and
Figure
).

Conclusion:
Our machine learning algorithm was able to accurately discriminate AIS versus stroke-mimic, and reproduce CTP-based infarct core measurements from CTA imaging alone. A complete AIS neuroimaging evaluation, for LVO as well as infarct core, may be obtainable from CTA, an imaging modality with much broader availability than CTP.
Abstract WP78: Deep Learning for Acute Ischemic Stroke on Diffusion MRI: Performance Analysis in a Consecutive Cohort
Authors: Bizzo Bernardo , Bridge Christopher , Gauriau Romane , Wiggins Walter , Caton Michael T , Hillis James , Wright Bradley , Tenenholtz Neil A , Andriole Katherine P , Michalski Mark , Gonzalez Gilberto
Published: January 2019

Background:
Diffusion-weighted imaging (DWI) is the gold standard for detection of acute ischemic stroke (AIS) and may guide patient selection for endovascular therapy. Machine learning algorithms can enhance clinical workflow in suspected AIS by providing early diagnosis and quantitative imaging biomarkers. We tested the hypothesis that our deep learning algorithm for detection of acute ischemia performs robustly in a real-world environment.

Methods:
We developed a novel deep neural network architecture (YNet) that operates on MRI diffusion data at full resolution. YNet demonstrated strong performance in AIS detection and segmentation on test and validation datasets. After validation, we challenged YNet to assess 1081 consecutive brain MRIs acquired from 9 different scanners at our institution over a 2-week period. Studies were labeled as having AIS by a radiologist who used the final clinical imaging report. A series selection algorithm was applied to each study to identify DWI and apparent diffusion coefficient (ADC) series for input to the YNet using DICOM metadata to ensure relevant criteria are met (B value = 1000, axial plane, etc.). Patients with known diagnoses were excluded.

Results:
The series selection algorithm identified 826 studies that had DWI and ADC series with the established criteria. After exclusion of patients with known diagnoses, 378 studies were assessed by the YNet algorithm for the presence of AIS. The prevalence of AIS was 11.9% within this consecutive cohort. The algorithm detected 43 out of the 45 studies with AIS. Sensitivity and specificity for detection were 95.5% and 97.0%, respectively.

Conclusion:
Our YNet algorithm demonstrated excellent performance in detecting AIS in a serially-acquired dataset. Fully automated implementation will require further refinement of the series selection algorithm.
Abstract WP8: Stroke Outcomes in Vitamin D-Deficient Conditions: Modulatory Role of Progesterone and Vitamin D
Authors: Yousuf Seema , Atif Fahim , Garcia Claudia Espinosa , Stein Donald
Published: January 2019

Introduction:
We investigated whether vitamin D (VDH) deficiency is associated with worsened outcomes after stroke with lipopolysaccharide (LPS)-induced inflammation as evaluated by measures of behavioral function, inflammation, endoplasmic reticulum (ER) stress, white matter integrity and peripheral immune response and whether combined progesterone (P) and VDH treatment would improve outcomes under these conditions.

Methods:
After 8 weeks on a VDH-deficient diet, adult, male Sprague-Dawley rats underwent transient ischemic stroke (tMCAO). Systemic inflammation was induced 24h post-stroke via 3 doses of LPS (50 μg/kg at 4h intervals). P (8 mg/kg; i.p.) and VDH (1 μg/kg; i.p.) were given 5 min before reperfusion followed by s.c. injections on days 1-7 post-stroke. Groups (n=6) were: Sham VDH-deficient; Sham VDH-sufficient; VDH-deficient tMCAO treated with vehicle; VDH-deficient tMCAO+LPS; VDH-deficient tMCAO+LPS treated with P; VDH-deficient tMCAO+LPS treated with VDH; VDH-deficient tMCAO+LPS treated with P and VDH. At day 7 post-stroke, rats were tested on behavioral parameters, measures of peripheral immune dysfunction, markers of neuronal inflammation (GFAP, Iba-1, IL-6), apoptosis (cleaved caspase-3, TUNEL), ER stress (PERK, eIF2α, CHOP) and white matter integrity (axonal and myelin injury markers SMI-32 and MBP, respectively) in brain. Data were analyzed using ANOVA and the Tukey-HSD
post hoc
test. Statistical significance was set at
P
<0.05.

Results:
We found significant behavioral deficits in MCAO and MCAO+LPS animals compared to controls. P+VDH significantly improved behavioral outcomes and reduced neuronal inflammation, apoptosis, ER stress and white matter injury compared to the MCAO and MCAO+LPS groups. β cell numbers were significantly reduced in both the MCAO and MCAO+LPS compared to the two sham groups. Peripheral immune dysfunctions revealed by flow cytometric analyses of immune cells in blood, spleen and thymus were significantly restored by combinatorial treatment with P and VDH. P+VDH improved all outcomes significantly more than monotherapy.

Conclusion:
The current standard of care for stroke has limited benefit, while combinatorial treatment with P+VDH shows promise for future stroke therapeutics.
Abstract WP85: The Association of White Matter Hyperintensity and Outcomes in Minor Stroke and Tia Patients
Authors: Xu Yu-Yuan , Zong Li-Xia , Pan Yue-Song , Jing Jing , Wang Yi-Long , Wang Yong-Jun
Published: January 2019

Background:
The presence of white matter hyperintensity (WMH) is related to poor outcomes in stroke patients. However, the short-term outcome is unknown in patients with minor stroke and TIA and WMH.

Objective:
We investigated the impact of WMH on 90-day outcome in patients with minor stroke and TIA.

Methods:
We derived data from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. After excluding 45 patients with low quality images, 8 without mRS at 3 months, 1036 patients with baseline MR examinations were included in this analysis. FAZEKAS scores were recorded for each individual. The primary efficacy outcome was ischemic stroke and mRS scores at the 90-day follow-up. We assessed the associations between FAZEKAS scores and prognosis of patients using multivariable Logistic regression models.

Results:
Among the 1,036 patients included in this subgroup analysis, there were 490 (47.3%), 347 (33.5%), and 199 (19.2%) patients identified as score 0-2, 3-4, 5-6, respectively. Compared with those with FAZEKAS 0-2, patients with FAZEKAS 3-4 (13.0% vs 7.6%, OR 1.53, 95% CI 0.93-2.50, p=0.093) and FAZEKAS 5-6 (11.1% vs 7.6%, OR 0.936, 95% CI 0.501-1.748, p=0.835) were not associated with higher mRS scores (2-6) at 90 days; neither did they have an increased risk of ischemic stroke (9.5% vs 8.0%, OR 1.08, 95% CI 0.64-1.81, p=0.779; 7.0% vs 8.0%, OR 0.67, 95% CI 0.33-1.35, p=0.261). However, in subgroup analysis for NIHSS 2-3, compared with FAZEKAS 5-6, FAZEKAS 3-4 was a risk factor for ischemic stroke (OR, 2.29; 95%CI 1.01-5.18; p=0.047) and higher mRS scores (OR, 1.98; 95%CI 1.03-3.82; p=0.041).

Conclusion:
In patients with minor stroke or TIA, Fazekas score was not associated with an increased risk of 90-day ischemic stroke and higher mRS scores. Medium grade WMH might indicate progression of cerebral small vessel disease (CSVD), while severe white matter lesion suggests relatively stabilized condition of CSVD.