bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP473: Investigating the Pathogenesis of Moyamoya Disease Using Patient Derived Induced Pluripotent Stem Cells
Authors: Rao Shailaja , Zhang Qian , Uchino Haruto , Pendharkar Arjun , Cheng Michelle , Steinberg Gary
Published: June 2021

Background:
Moyamoya disease (MMD) is a rare, progressive steno-occlusive cerebrovascular disorder of the internal carotid artery, leading to stroke. Affected arteries exhibit thickened intima with depleted elastic lamina and media, indicating a dysfunction of the vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). However the pathogenesis of the disease is still unclear. We aim to address this gap in knowledge by using patient derived induced pluripotent stem cells (iPSCs), to generate VSMCs and ECs.

Methods:
Peripheral blood mononuclear cells (PBMCs) from controls and MMD patients (n=3 per group) were used for generating iPSCs. VSMC functionality was measured by collagen gel contraction assay and scratch assay. EC proliferative function was assessed by BrDU incorporation assay, and its migration capacity was evaluated by scratch assay and in vitro tube formation. VSMCs and ECs were also exposed to either hydrogen peroxide (H2O2) or normoxia/ hypoxia model (1%O
2
) to investigate how cells respond to these insults. Hypoxia inducible factor 1α (HIF1α) activation was determined using western blot.

Results:
MMD VSMCs trended towards being more contractile and migrating faster than control VSMCs, in response to 10%FBS or SDF1α. On the other hand, MMD ECs migrated slower than control ECs in response to 10%FBS (p=0.0081) or VEGF (p=0.0072). MMD ECs also formed lesser tubes and exhibited fewer branch points when compared to controls. The rate of EC proliferation was similar between both groups. Cell death assays indicate that MMD VSMCs and ECs were more sensitive to the deleterious effects of H2O2 exposure when compared to control cells. Interestingly, MMD VSMCs had elevated HIF1α protein expression in normoxia, which was further increased after hypoxia.

Conclusions:
Our preliminary results indicate that both MMD VSMCs and ECs are dysfunctional and may be related to the elevated basal expression of HIF1α, possibly contributing to MMD pathology. We are currently investigating the interactions between VSMCs and ECs in MMD compared with controls using co-cultures. Ongoing studies also include transcriptome analysis of these differentiated cells, which will advance the understanding of the cellular and molecular mechanisms underlying MMD.
Abstract TP474: High Middle Cerebral Artery Pulsatility Index Predicts an Unfavorable Outcome and Correlates With Heart Functions in Acute Ischemic Stroke Without Vessel Stenosis
Authors: Sato Takeo , Niijima Akira , Arai Ayumi , Maku Takahiro , Motegi Haruhiko , Takahashi Maki , Takatsu Hiroki , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Umehara Tadashi , Omoto Shusaku , Murakami Hidetomo , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: June 2021

Background and Purpose:
To determine the parameters of transcranial color-coded duplex sonography (TCCS) related to unfavorable outcomes, and further to clarify the correlation between those parameters and heart functions in acute ischemic stroke without vessel stenosis.

Methods:
Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: acute ischemic stroke or TIA; able to measure blood flow of either the left or right middle cerebral artery (M1) by TCCS with ≤7 days from onset; and have no vessel stenoses or occlusions assessed by MRA and carotid artery ultrasonography. An unfavorable outcome was defined as mRS score of 2 to 6 at 3 months from the onset. First, we investigated the parameters of TCCS related to unfavorable outcomes (cohort A). Second, the correlation between those parameters and heart functions assessed by transthoracic echocardiography was evaluated (cohort B).

Results:
We screened 1,529 consecutive ischemic stroke patients, including 173 in cohort A (146 (84%) male, median age 59 years) and 192 in cohort B (162 (84%) male, median age 60 years) (Figure A). In cohort A, high M1 pulsatility index (PI) (OR 0.043; 95% CI 0.005-0.407;
p
= 0.006) was independently associated with an unfavorable outcome (Figure B). In cohort B, higher age (OR 1.532; 95% CI 1.118-2.009;
p
= 0.008), higher E/e' (OR 1.143; 95% CI 1.011-1.292;
p
= 0.033), and aortic valve regurgitation (AR
>
mild) (OR 4.780; 95% CI 1.261-18.114;
p
= 0.021) were factors independently associated with high M1 PI (Figure C).

Conclusions:
High M1 PI predicts an unfavorable outcome and correlates with high E/e' suggesting diastolic heart dysfunction and aortic valve regurgitation in acute ischemic stroke without vessel lesion.
Abstract TP476: White Matter Hyperintensity Burden is Associated With Poor Collateral Flow and Worse Outcomes in an Acute Ischemic Stroke Cohort
Authors: Assadi Rami-James , An Hongyu , Chen Yasheng , Ford Andria , Lee Jin-Moo
Published: June 2021

Introduction:
White matter hyperintensity volume (WMHv), a quantitative neuroimaging biomarker of cerebral small vessel disease (CSVD), is associated worse outcomes after ischemic stroke. In this study, we hypothesized that worse outcomes in CSVD patients were due to poor collateral flow during acute ischemia.

Methods:
47 patients with acute ischemic stroke (AIS) were prospectively enrolled in this study. Serial MRIs were performed at 3 hours and 30 days after stroke onset. 3-hour FLAIR images were used to determine WMHv, after manually delineating lesions with MIPAV. An index of collateral flow (delayed perfusion to the penumbra) was determined by subtracting core volume (volume of tissue with ADC<600) from the volume of brain tissue with Tmax>2. Patient’s NIHSS was scored at 3 hours and 30 days after stroke onset and the difference was calculated (ΔNIHSS). Log-transformed WMHv was correlated to ΔNIHSS and the collateral flow index, using Pearson correlation.

Results:
Mean age = 63.9 years (SD 13.5); 37% female; median 3-hour NIHSS = 13 (IQR 6.5-20); median change in NIHSS between 3h and 30d = 4 (IQR: 0-7); median core volume = 13cm3 (IQR 4.3-35.6); median WMHv = 1.257cm3 (IQR 641-3595). WMHv was associated with reduced improvement in ΔNIHSS (R=-0.42, ρ=0.005). Furthermore, WMHv demonstrated a trend for association with poor collateral flow (R=-0.28, ρ=0.062). In this dataset, we will explore the relationship between WMHv and other tissue-based metrics of collateral flow, including the hypoperfusion intensity ratio (HIR) and the cerebral blood volume ratio (rCBV).

Conclusions:
Our study confirms that patients with CSVD have worse outcomes after AIS. The data also raise the possibility that these worse outcomes in CSVD patients may be mediated by compromised collateral flow in the setting of acute ischemia.
Abstract TP481: Deep and Superficial Brain Arteries Flow Pattern Suggest Differential Risks to Systemic Hemodynamics
Authors: Gutierrez Jose , Blanco Pablo J , Spence J David
Published: June 2021

Introduction:
Penetrating arteries supplying the basal ganglia and the brain stem are often affected by chronic hypertension whereas distal branching arteries supplying the brain convexity and corona radiata may be injured by hypoperfusion. We hypothesized that under equal systemic flow dynamics, distal branching brain arteries will have a lower pressure peak than penetrating arteries.

Methods:
We used an Anatomically Detailed Arterial Network (ADAN) model to predict pressure waveforms for brain and systemic arteries. The anatomical details were obtained from published literature and match for an average man, height of 170 cms and body surface area of 1.65 m2. Arterial length and radius were obtained from published literature for each organ. Standard governing equations for the flow of an incompressible fluid in compliant pipes are considered in each arterial segment. Proper coupling conditions at junctions are also postulated, as well as terminal Windkessel models.

Results:
Compared to systemic arteries, brain arteries have an early peak in flow and pressure, followed by a gradual decline in flow and pressure over time (figure 1). The posterior parietal artery has the lowest MAP and pulse pressure of the four brain arteries tested, even if the pulsatility and resistance indices remained relatively the same. Consequently, the pressure pulse peak for the posterior parietal artery hovers around 80 mmhg compared with approximately 110 mmHg for the lenticulostriate arteries and the middle cerebral and basilar arteries. Lenticulostriate arteries had similar hemodynamic profiles to the large artery branches of the circle of Willis.

Conclusion:
Penetrating brain arteries are susceptible to high pressure remodeling because of their immediate branching from a large artery, while distal cortical arteries are more susceptible to hypoperfusion. These regional susceptibilities to systemic hemodynamic may influence brain health and contribute to neurodegeneration.
Abstract TP482: Carotid Calcification Predicts Systemic Vascular Events
Authors: Sano Noritaka , Kobayashi Tamaki , Kataoka Hiroharu , Morita Naomi , Takahashi Jun , Iihara Koji
Published: June 2021

Background and Objective:
It is well known that systemic arterial calcifications progress simultaneously. And coronary calcifications are a well-known predictor of coronary event in the future. Impact of carotid artery calcifications for cerebral stroke is still controversial among various articles, and the relationship between carotid artery calcifications and systemic vascular events are not known either. In this study, we aim to examine if the carotid calcification can be used as a predictor of systemic vascular events.

Methods:
This is a prospective study, which enrolled 199 subjects who have already suffered from vascular events, including carotid stenosis, coronary syndromes or stroke. We collected data at entry on risk factors, blood examination, and whole-body computed tomography analysis to assess the calcifications of carotid, coronary, aorta (three distinct part; arch, abdominal, and bifurcation) and renal artery using modified Agatston calcium score (ACS) for each vessel. According to the median carotid ACS, subjects were divided into two groups. And during 5 years of follow up period, cerebrovascular events, coronary events and other systemic vascular events were counted.

Results:
Carotid ACS has a stronger correlation with aortic ACS than coronary ACS. Hypertension and low renal function have significant impact on increasing carotid ACS, while a diabetes mellitus increase coronary calcification. On Kaplan-Meier estimates, subjects with higher carotid ACS (higher group) suffered more systemic vascular events than lower group (p=0.03, log rank correlation coefficient), and hazard ratio was 1.88 (95%CI; 1.02-3.46). There was no significant difference in the risk of cerebral or coronary events, however, higher group have tendency to be treated for aortic or peripheral arterial disease in the follow up period (HR6.86, 0.9-54.7).

Conclusion:
Carotid ACS have strong correlation with systemic large vascular bed including aorta, and can be a useful tool to extract a subject who will be suffered from systemic vascular event in the future.
Abstract TP486: Role of Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 2 in the Metabolism of Amyloid Precursor Protein in Human Brain Microvascular Endothelial Cells
Authors: He Tongrong , Katusic Zvonimir S
Published: June 2021

Under physiological conditions, β-site amyloid precursor protein (APP)-cleaving enzyme 2 (BACE2) cleaves APP within Aβ sequence thereby functioning like a α-secretase. However, BACE2 could also function as a conditional β-secretase during aging, contributing to Alzheimer’s disease pathogenesis. To date the physiological functions of BACE2 in endothelium are largely unknown. The present study is therefore designed to investigate the role of BACE2 in APP metabolism in human BMECs. Cultured human BMECs (passage 5-6 or passage 22) were treated with BACE2siRNA (30 nM, for 3 days), levels of soluble APPα (sAPPα, a neurotrophic product of non-amyloidogenic processing of APP) and Aβ40 in the supernatant were measured. In human BMECs (passage 5-6), genetic inactivation of BACE2 significantly decreased production of sAPPα (n=12, P<0.05), but had no effect on production of Aβ40 (n=9, P>0.05). BACE2siRNA treatment significantly suppressed APP protein expression (n=7, P<0.05), but augmented protein levels of BACE1 (n=7, P<0.05). Genetic inactivation of BACE2 did not change protein levels of mature ADAM10 (n=7, P>0.05). Thus, reduced sAPPα secretion by BACE2siRNA treatment is likely caused not only by decreased α-secretase-like function of BACE2, but also by reduced APP expression. We further examined the effects of BACE2siRNA in senescent human BMECs. In cultured human BMECs (passage 22), protein expressions of senescent markers (p
21Cip1
and p
16INK4a
) were significantly increased (n=4, P<0.05). Genetic inactivation of BACE2 in senescent human BMECs also significantly suppressed secretion of sAPPα (n=8, P<0.05), but did not affect Aβ40 production (n=8, P>0.05). BACE2-siRNA treatment significantly inhibited protein expressions of APP and mature ADAM10 (n=7, P<0.05), but did not change BACE1 protein expression (n=7, P>0.05). Thus in senescent human BMECs, reduced APP expression and impaired α-processing may play important roles in the decreased sAPPα production. Since our previous studies have demonstrated that endothelial production of sAPPα significantly contributes to the sAPPα content in the hippocampus, our current findings suggests that inhibition of BACE2 could impair protective function of sAPPα in the hippocampus.
Abstract TP490: Long Term Clinical Results of Linear Accelerator Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Single Institution Experience of 18 Years
Authors: Park Yung Ki , Koo Hae-Won
Published: June 2021

Introduction:
Cerebral arteriovenous malformation (AVM) is an intracranial pial vascular lesion which is treated with microsurgery, endovascular treatment or stereotactic radiosurgery (SRS). We introduce the long-term clinical results of linear accelerator (LINAC) stereotactic radiosurgery for cerebral AVM which is treated in single institution for 18 years period.

Methods:
Retrospective chart review was held in cerebral AVM patients treated with Novalis (BrainLAB AG, Heimstetten, Germany) stereotactic radiotherapy from 2001 to 2018. Clinical results such as obliteration rate, hemorrhage rate after SRS, and radiosurgery related adverse event was analyzed. Furthermore, predictors for obliteration and symptomatic radiosurgery induced adverse event was analyzed with multivariate logistic regression test.

Results:
Among 117 patients with cerebral AVMs treated with LINAC-based SRS, 72 were included in study. Total obliteration rate was 80.6% (58/72) for mean 57.0±48.3 months follow up period. Post-SRS hemorrhage and mortality rate was 6.9% (4/72) and 1.4% (1/72), respectively. Mean radiation dose and volume was 22.8Gy and 3.7cc, respectively. Independent predictive factors for nidus obliteration was: (1) radiation dose (OR 1.43, 95% CI 1.04-2.08, p=0.0374), (2) Ruptured AVM (OR 12.18, 95% CI 2.38-86.47, p=0.0054), (3) Virginia AVM score (OR 0.21, 95% CI 0.07-0.53, p=0.0028), and (4) follow up period months (OR 1.03, 95% CI 1.01-1.06, p=0.0261). Independent risk factors for symptomatic radiosurgery related adverse event was radiation volume (OR 1.61, 95% CI 1.09-2.65, p=0.0326).

Conclusion:
LINAC-based SRS is effective and relatively safe method for treatment of cerebral AVMs. Independent predictive factors for obliteration was high radiation dosage, ruptured status, low Virginia AVM score, and long follow up period. High radiation volume was related to symptomatic radiation induced adverse event.
Abstract TP494: Estimated tPA Dosing Weight on a Mobile Stroke Unit: Comparison between Estimated and Hospital-measured Weights
Authors: Jacob Asha , Kus Teresa , Wang Mengxi , Okpala Munachi , Yamal Jose-Miguel , Grotta James C , Parker Stephanie
Published: June 2021

Introduction:
The purpose of the Houston Mobile Stroke Unit (MSU) is to expedite stroke care by treating patients in the pre-hospital setting where obtaining a measured body weight, critical for accurate pre-hospital tPA dosing, is challenging and impossible. The paramedic and nurse on the MSU subjectively estimate by assessment (with patient report if possible) the weight for calculating tPA dosing. We aimed to determine the accuracy of the estimated weight method compared to the actual weight of patients treated with tPA on the MSU.

Methods:
Data were prospectively collected for MSU tPA-treated patients as part of the BEST-MSU study comparing MSU to standard EMS management. We collected the first-documented hospital-measured weight (bed scale) within 24 hours of hospital arrival, and the estimated weight used on the MSU for treatment. Mean absolute and percent difference in weights were calculated; less than 10% difference in weights was considered acceptable. To compare the estimated and measured weights, we conducted a Wilcoxon signed-rank test. Differences between weights were set as 0 if both weights were above 100kg. Fisher’s exact test was used to explore association between weight difference > 10% and patient outcomes.

Results:
Among 337 patients, mean age was 67.8 (15.6) and average measured weight was 81.2 kg (SD 22.3). Median absolute difference in measured versus estimated weight was 2.70 kg (IQR 0.55-7.60), and both weights were significantly different from each other (p value < 0.0001). The average absolute percent difference in weight was 7.04% (SD 9.11%). The absolute mean difference in tPA dosage was 3.49 mg (SD 6.06). Among patients whose estimated and measured weights were not both ≥100 kg, 56 (16.6%) had weight difference >10%. In patients with overestimation of weight by >10%, there were no symptomatic intracerebral hemorrhages. There was no association between weight difference and discharge modified Rankin score (p value = 0.5921).

Conclusion:
Weight estimation on a mobile stroke unit can lead to similar tPA dosing for 82% of subjects compared to if dosing were determined based on actual weight. Weight over- or under-estimation had no detected significant impact on tPA outcomes.
Abstract TP59: Atherosclerosis and Unsuccessful Recanalization in Acute Stroke Patients
Authors: Zevallos Cynthia , Ume Kiddy , Weber Matthew , Levy Abigail , Holcombe Andrea , Dajles Andres , Lopez Gloria , Ansari Sameer , Quispe-Orozco Darko , Dandapat Sudeepta , Siddiqui Fazeel , Ortega-Gutierrez Santiago
Published: June 2021

Unsuccessful recanalization rates in acute ischemic stroke patients range between 8-18%. Currently, there are no models to predict thrombectomy reperfusion success with current thrombectomy techniques. We aimed to describe the clinical and radiological features of patients with unsuccessful thrombectomy (UT) and its association with intracranial atherosclerosis (ICAD). A cohort of 413 consecutive, adult, thrombectomy patients admitted to two comprehensive stroke centers were reviewed from 2014 to 2017. Patients with anterior circulation large vessel occlusions (LVOs) and a thrombolysis in cerebral infarction (TICI) score of ≤2a were selected. Demographics, clinical and imaging data were obtained from electronic medical records. Head CT, CT angiography and digital subtraction angiography (DSA) images were reviewed by one independent investigator to evaluate ASPECTS score, vessel calcifications, clot burden score and CTA and DSA collateral score. Proposed causes of UT were categorized based on angiography evaluation by two independent neurointerventionalists. Analysis was performed using descriptive frequency analysis and univariate logistic regression models. A total of 87 low TICI score (≤2a) patients from 413 procedures were included. The median age was 74 years (IQR 58.5-84) and 58% were female. The most common comorbidity was hypertension (73.5%), followed by hyperlipidemia (46%). TICI score of 0 was found in 23% (N=20), 1 in 9.2% (N=8), and 2a in 67.8% (N=59). The inpatient mortality rate was 19.5% (17/87). Out of the remaining 70 patients, 78.5% (N=55) had a 3-month follow up modified Rankin Scale (mRS) of 3-6. The most common proposed cause of poor revascularization in our study was presence of ICAD [29.9% (n=32) of patients]. In our cohort of UT patients with ICAD, 68.8% (N=22) had TICI 2a score with majority (96.8%) having a 3 months mRS of 3-6. Patients with ICAD had 7.3% increased odds of having angiographic collateral score of 5 (p=0.035) and 15.2% increased odds of having an absence of hyperdense MCA in noncontrast CT scan (p=0.003). ICAD is frequently found in patients that undergo UT. Identification of radiological predictors of ICAD may be helpful to consider alternative revascularization strategies for LVOs.
Abstract TP6: Current Trends in Thrombolytic Use for Acute Ischemic Stroke
Authors: Decker-Palmer Marquita , Wu Ning , Biscossi Michele , Savitz Sean I
Published: June 2021

Introduction:
Alteplase is approved in the United States for acute ischemic stroke (AIS). Guidelines recommend IV weight-based alteplase dosing for AIS treatment with or without endovascular therapy (EVT). With increasing use of EVT, current thrombolytic use and dosing practices in AIS are poorly understood. This study assesses current and historical trends in thrombolytic use.

Methods:
All patients who received alteplase from 2007 to 2017 in the US Premier Hospital database were included. Hierarchical categorization identified indications by the presence of primary or secondary diagnoses including AIS > pulmonary embolism (PE) > myocardial infarction (MI) > or other. Patients undergoing EVT were subcategorized. Dosing was estimated by vial size. Demographics were analyzed descriptively.

Results:
Of 78,216 patients included, 33,530 (43%) had AIS, 7442 (9%) PE, 1696 (2%) MI, and 35,548 (45%) off-label indications. Patients with AIS had mean age of 68, and 2409 (7%) received alteplase + EVT. Of those with alteplase + EVT, 1428 (59%) were solely Medicare beneficiaries and 600 (25%) had solely commercial insurance vs 19,572 (63%) Medicare and 6585 (21%) commercially insured patients receiving alteplase alone. Only 37 patients (2%) with AIS receiving alteplase + EVT had care at rural hospitals, whereas 2946 rural patients with AIS (9%) received alteplase alone. Before 2011, EVT was associated with use of 50-mg vials of alteplase to treat AIS (Fig). After 2011, more patients with AIS receiving EVT had 100-mg vials of alteplase, consistent with dosing closer to the 90-mg maximum.

Conclusions:
AIS is the most common indication for current alteplase use. Since 2011, weight-based dosing has been widely adopted for treatment with and without EVT, which represents adherence to guidelines. Differences in payer mix and rurality among patients receiving alteplase + EVT may represent opportunities to improve access to care.
Abstract TP61: The Predictive Ability of Aspects vs Ct Perfusion for Large-vessel Occlusions Less Than 6 Hours
Authors: Manchanda Monika , Moore Justin , Leever John , Ledbetter Luke , Slavin Sabreena , Abraham Michael , Gronseth Gary , Qureshi Abid Y
Published: June 2021

Background:
While CT perfusion (CTP) has become invaluable in the selection of acute ischemic stroke patients for endovascular therapy (EVT) ≥6 hours of symptom onset, there continues to be uncertainty in its role within 6 hours.

Hypothesis:
CTP will select patients for EVT better than ASPECTS - as RAPID software can provide quantitative volumetric thresholds, while ASPECTS is subject to interpersonal variability.

Methods:
Patients over 18 years old with last known well (LKW) time to imaging less than 6 hours, and a confirmed large-vessel occlusion at the ICA, M1 or M2 were reviewed retrospectively. ASPECTS ratings were assessed by two blinded neuroradiologists. A diagnostic odds ratio (OR) was calculated by dichotomizing ASPECTS ≥6 vs <6, and comparing to the modified Rankin score (mRS) ≤0-2 vs >2. A separate diagnostic OR was calculated for CTP by dichotomizing the infarct core (cerebral blood flow (CBF) <30%) ≤50 ml vs >50 ml.

Results:
Ninety-six subjects were evaluated. Mean age was 65.4±14, 42% female, presenting with a mean NIHSS 16.4±8, 65% were treated with IV tPA, and mean clot retrieval was 5.3±2 hours for those who underwent EVT (70/96). The mean ASPECTS was 7.6±2, and mean infarct core (CBF<30%) of 34.4±50. Inter-rater reliability for ASPECTS grading was ICC=0.797 (95%CI 0.378-0.932). ASPECTS and CTP were found to be in agreement in 83.3% (80/96) of cases on whether or not to pursue EVT. In incongruent cases, in which ASPECTS was favorable but CTP was unfavorable - 54% (6/11) had mRS between 4-6, and similarly 50% (8/16) had a poor mRS when CTP was favorable but ASPECTS was unfavorable. In general, both ASPECTS and CTP poorly correlated with the utility-mRS (r = 0.14 and r = -0.15 respectively) when controlling for age, sex, time (LKW-to-CTP), and treatment (EVT± tPA, tpA alone, or none). Overall, diagnostic OR for prediction of a good outcome (mRS 0-2) for ASPECTS was 1.5 (95% CI 0.4-4.5) vs 3.4 for CTP (95% CI of 1.2-9.2), p=0.29. When accounting for treatment subtype, the diagnostic OR was 1.2 (0.4-3.6) for ASPECTS vs 2.9 for CTP (1.1-8.1), p=0.24.

Conclusion:
Approximately 1:6 patients will have incongruent results between ASPECTS and CTP. ASPECTS was not significantly better than CTP in cases <6 hours. In fact, a trend for better predictive ability was seen with CTP.
Abstract TP62: Frequency, Characteristics, and Outcomes of Acute Ischemic Stroke Patients With “Total Mismatch” on Penumbral Imaging Before Reperfusion Therapy
Authors: CHU Hai Jui , Liebeskind David , Yu Yannan , Yoo Bryan , Sharma Latisha , Jahan Reza , Duckwiler Gary , Tateshima Satoshi , Nour May , Szeder Victor , Starkman Sidney , Rao Neal , Bahr Hosseini Mersedeh , Saver Jeffrey ,   UCLA Penumbra Imaging Investigators
Published: June 2021

Background:
When penumbral imaging shows “total mismatch” (large perfusion lesion and no irreversibly infarcted core), the entirety of jeopardized brain is still salvageable and the benefits of reperfusion therapy may be enhanced. The frequency, characteristics, and reperfusion therapy outcomes of total mismatch patients has not been well-characterized.

Methods:
Analysis of consecutive acute cerebral ischemia patients in anterior circulation undergoing CT or MR penumbral imaging prior to intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Patients were classified in four groups: 1) total mismatch (core 0% of perfusion lesion), 2) non-total but substantial mismatch (core 1-20% of perfusion lesion), 3) moderate or no mismatch (core 20-100% of perfusion lesion), and 4) small perfusion lesion (perfusion lesion volume <10 ml).

Results:
Among 180 patients, pretreatment imaging patterns were: total mismatch 28.9%, substantial mismatch 22.8%, moderate or no mismatch 22.8%, and small perfusion lesion 25.6%. Among total mismatch patients, the Tmax>6 sec perfusion lesion volume was 56.5 ml (IQR 28.3-85.6) and time from last known well to imaging was 89 mins (IQR 65-296). Compared to moderate patients, clinical features of total mismatch patients were: older (76.0 vs 65.9, p=0.006), lower NIHSS (median 12 vs 18, p=0.019), and more cardioembolism (76.9% vs 48.8%, p=0.005). Total mismatch patients more often had CT than MR (65.4% vs 14.6%, p=0.000), less ICA occlusion (15.4% vs 34.1%, p=0.035), and smaller perfusion lesions (median 56.5 vs 82.1 ml, p=0.007). Total mismatch patients were treated with combined IVT+EVT in 32.7%, IVT alone in 26.9%, and EVT alone in 40.4%. Freedom from disability (mRS 0-1) at discharge was more frequent, 35.6% vs 16.2%, p=0.049 and disability levels at day 90 were lower in total mismatch patients, mean mRS 2.7 vs 3.9, p=0.029.

Conclusion:
Total mismatch is present in one-quarter of patients undergoing reperfusion therapy, more often in older patients with cardioembolism as etiology of stroke. Total mismatch patients have better disability outcomes from reperfusion therapy, but more than half show disability indicating need for more complete reperfusion.
Abstract TP63: Risk of Contrast Induced Nephropathy After Emergency CTA in Stroke Patients: A Meta-Analysis
Authors: Dhasakeerthi Thirumalaivasan , Ishfaq Muhammad , Krishnaiah Balaji , Alexandrov Andrei , Tsivgoulis Georgios
Published: June 2021

Background:
Contrast agents for computed tomographic angiography (CTA) and perfusion (CTP) are presumed to be nephrotoxic prompting many hospitals to require serum creatinine values prior to imaging likely causing delays in door to needle times. The objective of this study is to assess the risk of developing contrast induced acute kidney injury (AKI) in patients who are undergoing CTA and CTP.

Materials and Methods:
We have searched the electronic databases up to July 2019 for studies that reported incidence of AKI in patients who have undergone CTA and CTP. We calculated pooled odds ratios and 95% CIs by using random-effects models for the primary end point being AKI due to contrast induced nephropathy. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses.

Results:
Eight case control studies assessing 4,449 patients have been included in the study. The odds of AKI in CTA/CTP patients versus non-contrast CT was not statistically significant (odds ratio = 0.53, 95% CI = 0.20-1.39, p=0.199). There was no significant heterogeneity between the studies (Cochran’s Q statistic 3.632, df 4; P = .461, I2=2.514%). Overall, no AKI patient required hemodialysis due to contrast induced nephropathy. The absolute number of patients who developed AKI among CTA/CTP patients was lower than among patients who underwent just non-contrast CT (67 versus 87, NS).

Conclusion:
The use of contrast agents for CTA/CTP in acute stroke is not associated with an increased risk of developing contrast induced nephropathy nor AKI requiring dialysis.
Abstract TP64: Ischemic Stroke Lesion Identification in Non-Contrast CT Using Deep Learning
Authors: Christensen Soren , Federau Christian , Maclaren Julian , Srivatsan Aditya , Albers Greg , Lansberg Maarten
Published: June 2021

Background:
Automatic measurement of the acute stroke lesion volume on DWI and CT-CBF has been used in recent late window trials. Despite non-contrast CT (NCCT) being the most widely used imaging modality in the acute stroke setting, quantification of acute stroke volumes on NCCT has not been employed in trials because of the difficulty outlining territory with very mild Hounsfield unit depression. Deep learning algorithms have been effective at solving many image processing tasks and may outperform human readers given enough training data. The goal of this study was to train and test a deep learning model on NCCT scans with synthetic stroke lesions and to determine the optimal model design.

Methods:
Training: 20 NCCT scans without acute stroke were combined with 20 DWI lesions using co-registration producing 400 non-contrast scans with lesions. The region of the NCCT that coincided with the DWI lesion was depressed by 2 Hounsfield units to simulate an acute infarct. An independent validation dataset of 100 cases was created in the same way. Two models were used: a standard “Unet” model and a symmetry-aware Unet model. The models were compared in terms of segmentation accuracy in the independent validation dataset.

Results:
Both the symmetry aware U-net and the standard U-net detected some part of the true lesion in 100% of the cases. The symmetry aware U-net was more sensitive, median [iqr], (45% [27-68] vs 17% [6-54], p<0.00001) but slightly less specific (98% [93-98] vs 99% [94-99], p<0.0008) than the standard U-net.

Conclusion:
The symmetry aware U-net shows great promise in detection of acute strokes on NCCT; lesions with Hounsfield unit depressions that are barely visible to the eye can be automatically segmented by this model. Additional training data and architectural enhancements are likely to improve the current spatial sensitivity to above 45%.
Abstract TP69: Association Between DWI-FLAIR Mismatch and Functional Outcomes in Patients Undergoing Mechanical Thrombectomy
Authors: Sakakibara Fumihiro , Uchida Kazutaka , Numa Soichiro , Yoshimura Shinichi , Morimoto Takeshi
Published: June 2021

Background and Purpose:
Diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch was well recognized as an early sign of acute ischemic stroke lesions. In the era of mechanical thrombectomy (MT), DWI-FLAIR mismatch could be a good marker for candidates of MT. We thus investigated the association between DWI-FLAIR mismatch and functional outcomes in patients who received MT for acute large vessel occlusion (LVO).

Methods:
We conducted historical cohort study in consecutive patients who were evaluated by MRI for suspected stroke at single stroke center. We enrolled patients with occlusion of the ICA or M1 or M2 segment of MCA who were underwent MT within 24 hours after the last known to be well. FLAIR negative was defined when a visible acute ischemic lesion was present on DWI without traceable parenchymal hyperintensity on FLAIR. We estimated the adjusted OR of FLAIR negative for moderate outcome defined as mRS 0-3 at 90 days after onset. We also estimated the adjusted OR for symptomatic intracranial hemorrhage within 72 hours and mortality at 90 days.

Results:
Among 380 patients who received MT for acute LVO, 202 patients were included in this study. Patients with FLAIR negative was 146 (72%), and the rest were FLAIR positive. Patients with FLAIR negative had significantly higher baseline NIHSS (median 16 vs 13, p=0.01), more transferred-in (78% vs 63%, p=0.02), more intravenous thrombolysis (IVT) (45% vs 18%, P=0.0003), more cardioembolism (69% vs 54%, p=0.03), and shorter times from the onset to hospital door (median 175 vs 371 minutes, p<0.0001). Patients with FLAIR negative had more moderate outcome than the counterparts (61% vs 52%, p=0.24). The adjusted OR of FLAIR negative compared to positive was 2.97 (95%CI, 1.33-6.60, p=0.008). Symptomatic intracranial hemorrhage within 72 hours was less frequent in the FLAIR negative group (10% vs 20%, p=0.06), with an adjusted OR of 0.34 (95%CI, 0.13-0.87, p=0.02).

Conclusions:
DWI-FLAIR mismatch was associated with better functional outcome in patients received MT for acute LVO at 90 days. DWI-FLAIR mismatch should be a good marker for the candidate of MT for acute LVO. Future randomized trial to evaluate the effectiveness of MRI-based MT using DWI-FLAIR mismatch should be considered.
Abstract TP7: Association of Retrieved Thrombus Composition With Measures of Thrombectomy Success
Authors: Rao Neal M , Solano Laura , Atchaneeyasakul Kunakorn , Hongquan Jiang , Jeffrey Gornbein , Yong William H , Lucey Greg , Abdaljaleel Maram , Vinters Harry V , Szeder Viktor , Jahan Reza , Tateshima Satoshi , Duckwiler Gary R , Duckwiler Gary , Nour May , Colby Geoffrey , Restrepo Lucas , Kim Doojin , Raychev Radoslav , Bahr Hosseini Mercedeh , Hinman Jason D , Sharma Latisha K , Starkman Sidney , Yavagal Dileep R , Liebeskind David S , Saver Jeffrey L
Published: June 2021

Introduction:
Emboli retrieved from stroke patients undergoing mechanical thrombectomy vastly differ in histopathologic appearance, likely reflecting varying etiologies of stroke. We investigated whether clot components correlated with clinical features and thrombectomy outcomes.

Methods:
Retrieved thrombi from endovascular thrombectomy in consecutive AIS-LVO patients at 2 academic medical centers were fixed in formalin and sections stained by hematoxylin and eosin. The RBC, WBC and fibrin percentages of the clot were quantified by a neuropathologist blinded to the clinical details. We evaluated the association of these clot components, patient demographic and clinical features, with TICI score (both ordinal and dichotomized at 2c), AOL score, number of thrombectomy passes, and first-pass substantial recanalization (≥TICI 2b result on the first thrombectomy device pass). Non-parametric values were computed via Spearman correlation and pairwise interaction of clinical features was analyzed by ordinal logistic regression.

Results:
Among the 75 analyzed patients, mean age was 71.4 (SD 17.7), 50.7% were female and presenting NIHSS mean was 16.1 (SD 7.6). Devices employed were stent retrievers in 71% of patients, aspiration in 10%, and both stent retrievers and aspiration in 19%. Number of passes per procedure was mean 2.16 (SD 1.21). Substantial reperfusion (TICI 2B-3) was achieved in 88% and excellent reperfusion (TICI 2C-3) in 44%. In retrieved thrombi, mean RBC% was 44.8% (SD 31.9) and mean fibrin% was 49.8% (SD 31.4). Rates of first-pass substantial reperfusion, final substantial reperfusion, and final excellent reperfusion were homogenous across wide ranges of retrieved thrombus RBC% and fibrin% in correlation analysis.

Conclusion:
RBC and fibrin composition range widely among retrieved thrombi causing acute ischemic stroke. Current generation thrombectomy devices perform well across a broad range of clot compositions.
Abstract TP74: Aspects Scoring Applied to CTA Source Images is Predictive of Final Infarct Volume and Good Functional Outcome
Authors: Carrera Joseph F , Donahue Joseph H , Batchala Prem P , Southerland Andrew M , Worrall Bradford B
Published: June 2021

Introduction:
CTP and MRI are increasingly used to assess endovascular thrombectomy (EVT) candidacy in large vessel occlusion stroke. Unfortunately, availability of these advanced neuroimaging techniques is not widespread and this can lead to over-triage to EVT-capable centers.

Hypothesis:
ASPECTS scoring applied to computed tomography angiography source images (CTA-SI) will be predictive of final infarct volume (FIV) and functional outcome.

Methods:
We reviewed data from consecutive patients undergoing EVT at our institution for anterior circulation occlusion between 01/14 - 01/19. We recorded demographics, comorbidities, NIHSS, treatment time parameters, and outcomes as defined by mRS (0-2 = good outcome). Cerebrovascular images were assessed by outcome-blinded raters and collateral score, TICI score, FIV, and both CT and CTA-SI ASPECTS scores were noted. Patients were grouped by ASPECTS score into low (0-4), intermediate (5-7), and high (8-10) for some analyses. FIV was predicted using a linear regression with NIHSS, good reperfusion (TICI 2b/3), collateral score, CT to groin puncture, CT and CTA-SI ASPECTS as independent variables. After excluding those with baseline mRS≥2, a binary logistic regression was performed including covariates of age, NIHSS, good reperfusion, and diabetes (factors significant at p<0.05 on univariate analysis) to assess the impact of CTA-SI ASPECTS group on outcome.

Results:
Analysis included 137 patients for FIV and 102 for outcome analysis (35 excluded for baseline mRS≥ 2). Linear regression found CTA-SI ASPECTS (Beta -10.8, p=0.002), collateral score (Beta -42.9, p=0.001) and good reperfusion (Beta 72.605, p=0.000) were independent predictors of FIV. Relative to the low CTA-SI ASPECTS group, the high CTA-SI ASPECTS group was more likely to have good outcome (OR 3.75 [95% CI 1.05-13.3]; p=0.41). CT ASPECTS was not predictive of FIV or good outcome.

Outcomes:
In those undergoing EVT for anterior circulation occlusion, CTA-SI ASPECTS is predictive of both FIV and functional outcome, while CT ASPECTS predicts neither. CTA-SI ASPECTS holds promise as a lower-cost, more widely available option for triage of patients with large vessel occlusion. Further study is needed comparing CTA-SI ASPECTS to CTP parameters.
Abstract TP77: Impact of Time and Aspects on Clinical Core Mismatch in Large Vessel Occlusion Strokes
Authors: Desai Shashvat , Molyneaux Bradley J , Rocha Marcelo , Starr Matthew , Jovin Tudor G , Jadhav Ashutosh P
Published: June 2021

Introduction:
Patient selection for endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion (LVO) strokes in the 6-24-hour time window is dependent on delineating clinical core mismatch (CCM) as defined by DAWN trial criteria. In contrast, patient selection in the early window (0-6 hours) can be performed using ASPECTS on CT head. We aim to determine the prevalence of DAWN-CCM in LVO strokes and the impact of time and ASPECTS.

Methods:
Retrospective analysis of large vessel occlusion [internal carotid and middle cerebral artery-M1] strokes at a CSC. Consecutive patients who underwent CT perfusion or MRI within 120 minutes of CT head were included in the study (treated and untreated). Ischemic core volume was assessed using RAPID [IschemaView] and ASPECTS using automated ASPECTS [Brainomix]. CCM was defined using DAWN trial criteria [DAWN-CCM: NIHSS ≥10 and core <31 ml, NIHSS ≥20 and core <51 ml].

Results:
A total of 116 patients were included. Mean age was 71 ±14 and 62% were females. Mean ischemic core volume and median ASPECTS were 46 ±65 ml and 8 (6-9), respectively. In patients with NIHSS score ≥10 (98), 57% had DAWN-CCM in the 0-24-hour window. Proportion of patients with DAWN-CCM in 6-24-hour window was 70% (6-12 hours), 50% (12-18 hours), and 50% (18-24 hours) [p=0.35]. Proportion of patients with DAWN-CCM by ASPECTS group was 88% (ASPECTS 9-10), 64% (ASPECTS 6-8) and 13% (ASPECTS 0-5) [p=<0.01] (Figure 1). Probability of DAWN-CCM declines by 7% for every 2 hours increase in TLKW to imaging, and by 13% for every 1-point decrease in ASPECTS.

Conclusion:
Approximately 57% of LVO strokes have clinical core mismatch. LVO strokes with DAWN-CCM decline with increasing time and decreasing ASPECTS. ASPECTS alone may be sufficient to identify patients with DAWN-CCM in a resource limited setting and avoid time consuming advanced imaging.
Abstract TP78: Classification of Ischemic Core Distribution Pattern Using Computed Tomography Perfusion in Anterior Circulation Acute Large Vessel Occlusion
Authors: Morita Takumi , Ishibashi Ryota , Yamamoto Hiroyuki , Fujiwara Toshio , Kaneko Ryosuke , Hayashi Tomoko , Fujimoto Yuki , Takada Kensuke , Uezato Minami , Kinosada Masanori , Kurosaki Yoshitaka , Handa Akira , Chin Masaki , Yamagata Sen
Published: June 2021

Introduction:
The evaluation of ischemic core is important in acute cerebral infarction with large vessel occlusion. The ischemic core is thought to approximate the region that is difficult to receive collateral circulation. We classified the ischemic core distribution pattern into four types on the basis of the tendency of cerebral blood volume (CBV) decrease in the ischemic core, and examined the prognostic ability.

Methods:
We included M1 or ICA occlusion which completely recanalized (TICI3) by thrombectomy in our institute from January 2015 to May 2019. The ischemic core was defined as a region where CBV were reduced less than 1.9 ml/100cc. Ischemic core distribution pattern was classified into the following 4 types. Type A: absent of ischemic core. Type B: ischemic core is confined to the basal ganglia and white matter. Type C1: ischemic core is present in the cortex but less than half of MCA region. Type C2: ischemic core is present in the cortex, and more than half of MCA region. The patient characteristics, temporal parameters, ASPECTS and ischemic core distribution pattern were analyzed with mRS0-2 at discharge as a good outcome group.

Results:
A total of 47 cases (14 ICA, 33 M1) were included. Ischemic core distribution pattern correlated well with mRS at discharge (p<0.004). Factors that showed a significance in univariate analysis between the good outcome group (n=19) and the poor outcome group (n=28) were age (76 vs 80.5, p=0.037), ASPECTS (10 vs 9, p=0.027), ischemic core distribution type (B vs C1, p=0.002), last known well to recanalization time (191 vs 272.5, p=0.027). Among these factors, multivariate analysis correlated significantly with age (OR, 1.18; 95CI,1.01-1.36), ischemic core distribution pattern (OR, 5.01; 95CI, 1.8-13.9), and recanalization time (OR, 1.46; 95CI, 1.01-2.12).

Conclusions:
The distribution pattern of ischemic core defined by reduced CBV have good correlation with outcome. There is a possibility that it can be used as a simple tool to predict prognosis using CT perfusion in anterior circulation acute large vessel occlusion.
Abstract TP79: Utilization and Costs Associated With Diagnostic Imaging in Acute Stroke
Authors: Federico Alyssa , Gilray Brenda , Stewart Errol , MacMillan Mark , Eesa Muneer , Almekhlafi Mohammed A , Menon Bijoy K
Published: June 2021

Introduction:
Diagnosis and treatment of acute stroke depends upon imaging, namely non-contrast CT (NCCT), CT angiography (CTA), CT perfusion (CTP), and MRI. We sought to i) examine available data from around the world on six categories related to acute stroke imaging: utilization, time to imaging, radiation exposure, contrast dose, availability, and cost, and ii) compare that information with similar data from our province (Alberta).

Methods:
Using a scoping review methodology, six categories related to acute stroke diagnostic imaging were examined: utilization, time to imaging, radiation exposure, contrast dose, availability, and cost. Metadata for these categories in Alberta were collected from Alberta Health Services administrative records for comparison.

Results:
A total of 6693 articles/documents were initially identified through database searches, of which 83 were included for analysis. CT (range = 55-100%) was used more frequently than MRI (range = 23.6-94.0%) in acute stroke, with high CTA use in Alberta (55.7%) compared to other centres (range = 8.6-36.0%; Table 1). CT time to imaging was < 25 min (target time) in most centres, but not in Alberta (mean = 3.2 hr, median = 2.0 hr). MRI was not used urgently in most centres (mean = 0.4-21.0 hr), including Alberta (mean = 15.4 hr, median = 13.0 hr). CTA radiation exposure was greater in Alberta compared to other centres (5.7 mSv vs 2.8-5.4 mSv) whereas it was similar for NCCT and CTP. Contrast doses for CTA and CTP were similar between Alberta (CTA = 50-70 mL, CTP = 45 mL) and other centres (CTA = 40-150 mL, CTP = 30-60 mL). Lastly, the number of CT and MRI scanners per million population and cost of operating them was similar worldwide.

Conclusions:
In conclusion, no studies were identified that provide a comprehensive overview of all six factors relevant to diagnostic imaging in acute stroke. The Alberta metadata fills in this literature gap, specifically in the context of Canadian stroke care.