bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP430: Analyses of CSF and Serum miRNA Expression in Subarachnoid Hemorrhage Patients Suggest Important Roles in Restoration of Impaired Vascular Homeostasis
Authors: Kikkawa Yuichiro , Uramaru Koichi , Sato Hiroki , Yanagawa Taro , Suzuki Kaima , Okuma Masahiro , Nakajima Hiroyuki , Takeda Ririko , Kurita Hiroki
Published: June 2021

Backgrounds:
MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Furthermore, in various human disease, miRNAs have been identified as potential biomarkers. However, it remains to be elucidated whether and how miRNAs play roles in the development of cerebral vasospasm (CVS) or delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). The purposes of this study are to detect differential miRNAs in cerebrospinal fluid (CSF) and serum in SAH patients and to identify possible miRNAs involved in the mechanisms of the vascular proliferation or phenotypic changes after SAH.

Methods:
The CSF and serum samples were taken every other day for 2 weeks after SAH in patients with endovascular aneurysm repair. Microarray analysis of exosomal miRNA from samples was performed using 3D-Gene miRNA labeling kit (Toray). The temporal changes in the expression of differentially expressed miRNAs in early phase after SAH and its associated molecules were evaluated using quantitative RT-PCR.

Results:
Among over 2500 miRNAs screened out, microarray analysis revealed 12 diffrentially expressed genes which were up- and/or down-regulated (FC>2-fold) both in the CSF and serum during early phase after SAH. RT-PCR analysis revealed that miRNAs involving vascular angiogenesis were up-regulated on day3 in serum and day5 in CSF. Contrarily, RT-PCR also revealed mRNAs of those associated molecules which exert anti-angiogenic and anti-proliferative effects were down-regulated on day1 in CSF and day3 in serum. These results suggest that these miRNAs expressions are controlled by negative-feedback regulation of associated molecules participating in maintaining vascular homeostasis.

Conclusion:
Our present study indicates that some miRNAs and molecules may be involved in vascular proliferation or angiogenesis by interacting each other after SAH.
Abstract TP435: Remote Ischemic Conditioning Augments Collateral Circulation and Angiogenesis in a Bilateral Carotid Artery Stenosis Model in Mice
Authors: Khan Mohammad B , Hafez Sherif , Awad Mohamed , Wagner Jesse D , Baban Babak , Hoda M N , Hess David C
Published: June 2021

Background and Purpose:
The Bilateral carotid artery stenosis model in mice (BCAS) is regarded as a model for vascular cognitive impairment (VCI) and cerebral small vessel disease (SVD). We have shown that repetitive remote ischemic conditioning (RIC) increases cerebral blood flow (CBF), reduces white matter damage and improves cognition in the BCAS mouse model. The purpose of this study was to determine whether RIC increased angiogenesis and increased endothelial progenitor cells (EPC) in the blood or changed the polarization of macrophages in the blood.

Methods:
Microcoil induced bilateral common carotid artery (BCAS) model was used to induce chronic hypoperfusion. Adult C57BL/6J male mice of (10-weeks) were randomized to 3-different groups (N=9), and subjected to Sham-(procedures of BCAS and RIC), BCAS+shamRIC and BCAS+RIC. RIC was started 7d post-surgery daily for 3 weeks. In all the experimental groups and after 3 weeks blood were collected through cardiac puncture and perfused with BriteVu. EPC (CD31, VEFR2, CD34) and M1/M2 macrophages were assessed through flow cytometry and angioarchitecture (vascular volume, number of vessels, linear spacing between vessels, density, average lumen thickness, and collateral circulation vessels) was performed with micro-CT scanner. All observers were blinded. Statistical significance was determined at p <0.05.

Results:
RIC-therapy significantly improved CBF in the BCAS+RIC group compared to BCAS +shamRIC. EPCs were increased in the blood of the BCAS+RIC compared to BCAS+sham RIC and there was increased polarization (ratio of M2/M1) of macrophages in the blood in BCAS+RIC group compared to BCAS+shamRIC. RIC increased angiogenesis compared to sham RIC with increased vascular volume, number of vessels and decreased space between vessels.

Conclusions:
Repetitive RIC increases angiogenesis and increases EPCs in the blood after BCAS. RIC also polarizes macrophages to the M2 (anti-inflammatory subset). Repetitive RIC may be an effective therapy to slow down the progression of VCI and SVD by promoting angiogenesis and vascular remodeling.
Abstract TP438: Nanoparticulate Matter Exposure Mediates White Matter Changes in a Murine Model
Authors: Babadjouni Robin , Liu Qinghai , Cheng Hank , Durazo Ramon , Hodis Drew M , Patel Arati , Radwanski Ryan , Sioutas Constantinos , Morgan Todd E , Finch Caleb E , Mack William J
Published: June 2021

Background:
Clinical and epidemiologic studies suggest a relationship between long-term nano-particulate matter (nPM) exposure and white matter injury
1
. Accumulating laboratory evidence suggests that nPM exposure causes inflammation in multiple brain regions
2
.

Objective:
We sought to study the effects nano-particulate matter exposure on microglia activation and complement upregulation within the corpus callosum in a murine model.

Methods:
C57 black 6J mice were randomized to re-aerosolized nPM (n=18, nPM <200 nm) or filtered air (n=18) cohorts. Exposures were conducted for a total of 150 cumulative hours. Post-exposure, brains were harvested and immunohistochemical analysis performed. Reactive microglia (IBA-1), reactive astrocytes (GFAP) and C5α deposition (C5α antibody) were quantified in the medial corpus callosum.

Results:
There were significant differences in IBA-1 cell count staining between the groups (filtered air- 94.7± 18.87; nPM- 158.5 ± 41.69, p<0.05). No differences in GFAP cell count staining existed between the filtered air (677.5 ± 96.09) and nPM mice (656.6 ± 120.3, p=ns). There were significant differences in C5α density staining between filtered air (8.181 ± 3.863) and nPM mice (14.77 ± 5.989, p<0.01).

Conclusion:
Chronic particulate matter exposure is associated with white matter changes in a murine model. Regional increases in microglia number and C5α deposition suggest an inflammatory mechanism.

References:
1. Calderon-Garciduenas L, Mora-Tiscareno A, Ontiveros E, Gomez-Garza G, Barragan-Mejia G, Broadway J, Chapman S, Valencia-Salazar G, Jewells V, Maronpot RR, Henriquez-Roldan C, Perez-Guille B, Torres-Jardon R, Herrit L, Brooks D, Osnaya-Brizuela N, Monroy ME, Gonzalez-Maciel A, Reynoso-Robles R, Villarreal-Calderon R, Solt AC, Engle RW. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 2008;68(2):117-27. 2. Block, M. L., & Calderón-Garcidueñas, L. (2009). Air pollution: mechanisms of neuroinflammation and CNS disease.
Trends in neurosciences
,
32
(9), 506-516.
Abstract TP44: Quantifying Edema in Acute Stroke
Authors: Harston George , Kennedy James
Published: June 2021

Introduction:
The Acute Stroke Imaging Roadmap III identifies structural distortion due to vasogenic edema and hemorrhage as a research priority for defining final infarction. Non-linear registration (NLR) of a follow up scan to an undistorted presenting scan could correct for distortions due to edema, hemorrhage or atrophy, achieving this goal. In addition, the difference between the volume of infarction following NLR and the volume following a rigid body registration (RBR) reflects the degree of anatomical distortion. In this study we evaluate this technique to correct for subacute edema at different timepoints, and generate a metric to quantify brain swelling at these times. We determine whether early edema at 24 hours predicts edema at 1 week.

Methods:
Patients with non-lacunar ischemic stroke were recruited into a MRI study. Patients had structural T1-weighted, T2-weighted FLAIR and diffusion-weighted imaging (DWI, b=1000/0) at presentation, 24hrs, 1wk and 1mo. Infarction was defined manually at 24hrs using DWI, and at 1wk and 1mo using FLAIR image by 2 raters. To quantify edema, both NLR warps and RBR matrices were generated between the T1 images at each timepoint to the presenting T1 scan. Infarct masks were transformed to presenting image space using RBR and NLR, and the relative difference in volumes used to quantify the Edema Metric (EM).

Results:
34 patients were recruited into the study. NLR corrected for distortions due to edema and hemorrhagic transformation at the 24hr and 1wk timepoints. The EM at 24 hours, 1 week and 1 month were 17.7% (p=0.009), 26.5% (p=0.02), and 7.1% (p=0.05) respectively for the manually defined infarct masks. EM at 24 hours predicted edema at 1 week (r
2
=37%, p=0.009), but not at 1 month (r
2
=3%, p=0.6).

Conclusions:
NLR provides an opportunity to correct for edema at subacute timepoints and by comparing infarct volumes to those following RBR provides a measure of edema. The EM quantifies the contribution of edema at 24hrs and 1wk, and potentially allows the selection of patients at 24hrs who are likely to develop significant swelling at 1 week. The EM may also be useful in stroke trials to quantify the effect sizes of treatments aimed at minimizing edema in stroke.
Abstract TP445: Bevacizumab Therapy for Brain Arteriovenous Malformations
Authors: Cooke Daniel L , Kim Helen , Smith Wade , Lawton Michael , Clarke Jennifer , Saloner David , Ko Nerissa , Sneed Patricia , McCulloch Charles , Su Hua
Published: June 2021

Introduction:
Brain arteriovenous malformations (bAVM) are dynamic vascular malformations and a significant source of intracranial hemorrhage (ICH). Obliteration by interventional therapy is the only proven method to remove this hemorrhagic risk. Partial bAVM volume reduction using combination therapy does not lessen the risk of future ICH, though such adjuvant treatment is routinely practiced to permit definitive microsurgical resection or radiosurgery. High expression of vascular endothelial growth factor (VEGF) has been reported in bAVM and there is evidence for the beneficial effects of bevacizumab on AVMs from studies using the hereditary hemorrhagic telangiectasia (HHT) bAVM model and in liver AVMs in HHT patients. There is, however, no medical therapy approved to treat bAVMs. The goal of this study is to determine the beneficial effects of the anti-vascular endothelial growth factor drug, Bevacizumab, on bAVM.

Hypothesis:
Our hypothesis is that bAVM volume will decrease after 12 weeks of bevacizumab treatment. Additionally, we expect that bevacizumab treatment for bAVMs will not increase the occurrence of symptomatic ICH beyond that expected for natural history.

Methods:
The trial is a 10 patient one-armed, open-label study that will administer bevacizumab (5 mg/kg every 2 weeks) by IV infusion over the course of 12 weeks. The study will assess feasibility, safety, and preliminary evidence of efficacy in bAVMs deemed inoperable by current interventional means. For the purpose of estimating our effect size, we assumed that the bevacizumab treatment effect on bAVM volume will be proportional to the reduction of blood flow measured by the cardiac index in the hepatic AVM-bevacizumab trial. With a sample size of 10 paired observations and a one-tailed α =0.05, we have 84% power to detect a change in bAVM volume of 13%. We will compare pre- and post-treatment (26 weeks) volumes using a paired t-test.

Significance:
This study is the first medical intervention trial for bAVM. The study will meaningfully impact the clinical and research communities managing AVMs, regardless their anatomic location, and in turn those patients who suffer from them.
Abstract TP446: Predictors of Hemorrhagic Severity in Arteriovenous Malformation Patients
Authors: Yu Jay , Nicholson Andrew , Nelson Jeffrey , Tse Stephanie , Hetts Steven , Hemphill Claude , Kim Helen , Cooke Daniel
Published: June 2021

Introduction:
One of the most frequent causes of non-traumatic intracerebral hemorrhage (ICH) in young adults is from a brain arteriovenous malformation (AVM) rupture. Understanding the potential spectrum of AVM outcomes is crucial in assessing treatment options. Although ICH mortality from ruptured brain AVMs is less frequent than for primary ICH, the severity of brain AVM hemorrhage is not well documented. We aimed to identify the clinical and anatomical variables associated with: (1) ICH volume and (2) intraventricular hemorrhage (IVH) presence to better prognosticate eventual clinical hemorrhage severity in brain AVM patients.

Methods:
ICH volume and presence of IVH (outcomes) were retrospectively assessed based on CT images for 150 patients admitted with ruptured AVMs and prospectively enrolled in our AVM database between 2000-2015. Parenchymal hemorrhage volumes were calculated using the ABC/2 method. Regression analysis was performed to assess the relationship between clinical and anatomical factors and ICH volume (proportional increase, PI) and presence of IVH (odds ratio, OR).

Results:
Older patients were less likely to have IVH (p=0.036). Exclusively deep venous drainage was associated with both smaller hemorrhage volumes (p<0.001) and an increased likelihood of IVH (p<0.001). Lobar AVM locations were associated with larger hemorrhage volumes (p<0.001). Venous stenosis, based on a 5-point grading scale (5 = complete occlusion), was associated with larger hemorrhage volumes (p=0.006) and a decreased likelihood of IVH (p=0.014). Exclusively deep venous drainage (PI=0.29, 95% CI: 0.19 - 0.44), lobar location (PI=2.18, 95% CI: 1.47 - 3.24), and venous stenosis (PI=1.34, 95% CI: 1.09 - 1.64) remained significant independent predictors of hemorrhage volume in a multi-predictor model (P<0.05). Similarly, exclusively deep venous drainage (OR=7.51, 95% CI: 2.69 – 21.00) and venous stenosis (OR=0.61, 95% CI: 0.41 – 0.90) remained significantly associated with IVH (P<0.05).

Conclusions:
With the lack of a widely adopted AVM natural history score, our study provides further information regarding potential hemorrhage severity in addition to the current knowledge of hemorrhagic risk to better scrutinize patients with unruptured AVMs.
Abstract TP46: A Support Vector Machine Approach for Prediction of Subclinical Language Deficit using Post-Stroke White Matter Tracts
Authors: Mohanty Rosaleena , Vergun Svyatoslav , Mossahebi Pouria , Nair Veena A , Prabhakaran Vivek
Published: June 2021

Post-stroke neuropsychological evaluation can take a long time to assess motor, cognitive, language impairments, etc. in subjects with no overt clinical deficits. A ten-minute non-invasive diffusion tensor imaging (DTI) can potentially pick subtle impairments like subclinical language deficit. Machine learning can supplement neuropsychological test to detect language deficit from white matter tracts in post-stroke DTI with high accuracy. Thirty subjects were categorized into three groups based on stroke status and language neuropsychological test (verbal fluency task): ten healthy controls, ten ischemic stroke subjects with language deficit (normed verbal fluency score < -1.5) and ten ischemic stroke subjects with no language deficit (normed fluency score >= -1.5). Subjects were age and gender matched across groups. DTI with 56 directions acquired on 3T GE MRI 750 scanners were processed using standard steps to generate fractional anisotropy (FA) maps that measure microstructural integrity of the brain. Individual 48 white matter tracts were extracted using Johns Hopkins University (JHU) ICBM-DTI-81 white matter atlas. Mean FA per tract per subject was computed. A support vector machine (SVM) used mean FA to classify among groups. With a Gaussian kernel and leave-one-out cross validation, SVM ranked tracts predicting language deficit. Groups were age and gender matched resulting in no significant difference in the age across groups (
p
> 0.05). While a three-class SVM yields a 57% classification accuracy, binary SVM on pairs of groups provides accuracy of 80% (healthy controls vs. stroke with language deficit), 85% (healthy controls vs. stroke with no language deficit) and 75% (stroke with language deficit vs. stroke with no language deficit). Top independent white matter tract with highest weight given by classifier was: splenium of corpus callosum, right superior corona radiata, right external capsule respectively for the three classifications above. In conclusion, SVM classifier can predict whether a given subject has language deficit from post-stroke DTI with accuracy significantly higher than random chance. Weights obtained from SVM indicate importance of specific tracts driving the classifier and distinguishing the groups.
Abstract TP47: Intracranial Intraplaque Hemorrhage in Acute Stroke: Interim Results of the Stroke Imaging Package Study
Authors: Liu Changyun , Chen Huisheng , Yang Yi , Xu Jun , Zhang Meng , Lu Baoquan , Wu Shiwen , You Yong , Hu Hongtao , Fang Le , Lu Zhengqi , Lou Min , Song Haiqing , Li Mingli , Huang Yining , Xu Wei-hai
Published: June 2021

Introdution:
Intracranial artery atherosclerosis is an important cause of ischemic stroke, especially in people of Asian origin. Intraplaque hemorrhage is supposed to be a predictor of ischemic event. The goal of this study was to examine the occurrence of intraplaque hemorrhage in a large cohort of Chinese patients with acute ischemic stroke.

Methods:
Patients with first ever stroke within 72 hours from onset, confirmed by diffusion weighted imaging, were recruited from 16 medical centers. Conventional MRI, magnetic resonance angiography, HRMRI (including 3-dimentional T1 images and 2-dimentional T2 images), and SWI were performed. Intraplaque hemorrhage was identified if hyperintense signals on 3-dimentional T1 images of HRMRI were observed within intracranial plaques.

Results:
Six hundred and one patients (70% male, mean age 61±16 years old, mean NIHSS 6± 5) were enrolled. Median time from symptom onset to MRI was 44 ± 20 hours. Of them, 240(40%) were diagnosed with large artery atherosclerosis (LAA) stroke. Intracranial intraplaque hemorrhage was identified in 15 intracranial plaques of 13 patients with LAA stroke. Six plaques with intraplaque hemorrhage were asymptomatic and irrelevant to ischemic infarct lesions. In 2 patients, both symptomatic and asymptomatic intraplaque hemorrhage were observed.

Conclusions:
The prevalence of intracranial intraplaque hemorrhage was low (5.4%)in acute stroke patients. The clinical importance of asymptomatic intraplaque hemorrhage need further investigations.
Abstract TP49: Racial Difference in Cerebral Microbleed Burden in the Mid-South United States
Authors: Noorbakhsh-Sabet Nariman , Tsivgoulis Georgios , Goyal Nitin , Alexandrov Andrei , Zand Ramin
Published: June 2021

Introduction:
Although intracerebral hemorrhage (ICH) is more common among African Americans, data on the burden of cerebral microbleeds (CMBs) among different racial populations is limited. The purpose of this study is to compare the number, associated factors, and topography of CMBs between African-American and white populations in the Mid-South United States.

Methods:
We reviewed consecutive patients who had magnetic resonance imaging (MRI) of brain at four tertiary centers in Memphis, Tennessee in a two-year period. T2*-weighted MRIs were assessed for the number, location, and topography of CMBs as well as other acute and chronic cerebrovascular diseases. We compared, by race, the baseline characteristics and clinical findings of patients with CMBs.

Results:
Out of 6,107 patients screened for this study, 176 (3%) patients (mean age: 63±15 years, 49% men, 77% African American, median CMB count: 8) had CMB on their brain imaging. There was a significant difference between African-American and white patients in terms of number of CMBs (16.5±18 vs. 6.5±5.5, p<001). There was no significant difference between two groups in terms of CMB location, gender, body mass index, history of head trauma as well as seizure, coronary artery, peripheral vascular, liver, and kidney disease. However, African-American group had a higher rate of clinical and silent stroke (92% vs. 71%, p=003), ICH (29% vs. 3%, p=.001), and severe leukoaraiosis (62% vs. 39%, p=.003). After adjusting for potential confounders, the African-American race was independently (p<0.014) associated with a higher CMB burden in multivariable logistic regression analyses.

Conclusion:
Our results suggest that African-American race might be independently associated with a higher CMB burden.
Abstract TP5: What is “Near Complete” Recanalization? Rethinking TICI 2b in Modern Thrombectomy Era
Authors: Tung Eric L , McTaggart Ryan A , Baird Grayson , Yaghi Shadi , Hemendinger Morgan L , DiBiasio Eleanor , Hidlay Douglas T , Tung Glenn A , Jayaraman Mahesh V
Published: June 2021

Background and purpose:
The Thrombolysis in Cerebral Infarction (TICI) 2b classification is defined as “near complete” recanalization for acute ischemic stroke. While this category has historically combined with TICI 3 (“complete reperfusion”) as “successful recanalization”, recent studies have suggested that TICI 3 and a proposed intermediate TICI 2c (“near complete reperfusion except for slow flow or distal emboli”) should be distinguished from TICI 2b due to differences in outcomes. In this study, we examined if early neurologic improvement differed significantly between patients with TICI 2b, TICI 2c, and TICI 3 recanalization for emergent large vessel occlusions treated with mechanical thrombectomy (MT).

Methods:
Retrospective analysis was performed using data from 133 consecutive patients with middle cerebral artery or internal carotid artery occlusions treated with MT from January 2015 to June 2016. Patient angiograms were graded independently and blinded to clinical data by two experienced readers based on original TICI (oTICI), modified TICI (mTICI), and modified TICI with TICI 2c (mTICI 2c) grading scales. Early neurologic improvement was assessed using change in NIHSS by discharge. General linear modeling was used to evaluate difference in NIHSS delta scores between TICI scales with SAS/PROC GLIMMIX. Multiple comparisons were evaluated using Tukey corrections with significance established at the .05 level.

Results:
Without the TICI 2c category, there was not a significant difference in change in NIHSS observed between TICI 3 and TICI 2b for both the oTICI (delta 1.4, p=0.355) and mTICI scales (delta 2.1, p=0.190). However, when an additional category (TICI 2c) was added, there was a significant difference in change in NIHSS observed between TICI 3 and TICI 2b (delta 3.8, p= 0.026) as well as between TICI 2c and TICI 2b (delta 3.7, p=0.019).

Conclusion:
Utilizing a TICI recanalization grading system that adds an additional category beyond TICI 2b allows for improved prediction of neurological improvement in patients treated with MT. Higher levels of recanalization are associated with greater neurologic improvement.
Abstract TP51: When Can Aspects be Read Reliably?
Authors: Dey Sadanand , Evans James , Tham Carol , Assis Zarina , Teleg Ericka , Pordeli Pooneh , Eswaradass Prasanna , Najm Mohamed , Neweduk Anneliese , Horn MacKenzie , Demchuk Andrew , Goyal Mayank , Menon Bijoy
Published: June 2021

Introduction:
Alberta Stroke Program Early CT Score (ASPECTS) is a systematic approach to assess early ischemic change on non-contrast CT (NCCT). Concerns have however been expressed about its reliability when making clinical decisions in patients with acute ischemic stroke. We chose to systematically assess technical, environmental and patient specific variables that potentially affect ASPECTS interpretation.

Methods:
We randomly selected 150 patients with acute ischemic stroke from the PRoveIT database. All patients had baseline NCCT and CT angiography head and neck. Three raters (expert, fellow and trainee) read ASPECTS on the same NCCT three times (Sessions 1-3) at minimum interval of 10-14 days. Raters were kept blinded to follow-up data throughout the study. No baseline clinical information was provided in Session 1. Raters were provided clinical information (age, baseline NIHSS and side of stroke) in session 2 and additional multiphase CTA in session 3. Reading environment [room light and time pressure (<60 s for interpretation) vs. core lab] was altered during readings. Data on motion artifact, leukoaraiosis, old infarcts on NCCT were collected. Time taken for ASPECTS interpretation was collected across all the readings. Reliability was assessed using Intra-cluster correlation coefficient (ICC).

Results:
The highest inter-rater reliability was found in session 3 (ICC 0.47; p<0.001). The rest of the analyses was restricted to session 3. Reliability in session 3 was not affected by time pressure or ambient light settings (all p<0.01). In session 3, patient motion (ICC 0.35 present vs. 0.49 absent) and old infarcts (ICC 0.42 present vs. 0.48 absent) worsened reliability; however presence of leukoaraiosis did not affect reliability (ICC 0.48 present vs. 0.46 absent). Mean time for ASPECT interpretation by trainee, fellow and expert were 38.9 s (+/-12.8s), 49.8 s (+/-15.4s) and 38.9 s (+/-14s) respectively.

Conclusion:
ASPECTS interpretation on NCCT is most reliable when clinical and CTA information is available. Interpretation with this information is reliable even in a well-lit room and under time pressure, the environment that mimics real life acute stroke.
Abstract TP55: Spatio-temporal Flow Tractography (SFT) for Evaluation of Collateral Patterns in Acute Stroke
Authors: Wang Yao , Shattuck David , Saver Jeffrey , Liebeskind David , Scalzo Fabien
Published: June 2021

Background:
Collateral blood flow plays a major role to sustain oxygenation to the ischemic tissue at risk of irreversible infarction. It is an important marker during diagnosis and treatment decision in acute stroke. Presence of reliable collateral flow to the region at risk has been linked to better outcome and may be used in the future to extend the treatment window for endovascular thrombectomy. Automatic and objective scoring of collaterals would greatly facilitate treatment decisions. However, such capability remains beyond current imaging methods. In this study, we introduce an imaging marker computed from routine magnetic resonance (MR) perfusion studies that directly reflects the trajectories and the strength of the blood flow within the major arteries of the brain.

Methods:
MR perfusion studies were analyzed retrospectively from patients treated for acute ischemic stroke. All patients were diagnosed with a large artery occlusion (ICA or proximal M1 MCA) as observed on single-phase CT angiography (CTA) acquired immediately prior to endovascular thrombectomy. Spatial-temporal gradient was automatically extracted for every voxel to quantify the direction and the magnitude of the flow. A tractography algorithm was then used to recover the trajectories of the flow and a color mapping was applied to visualize both direction and strength of the flow. Regions of interest were delineated bilaterally and each image was reviewed by a neurologist for the ASITN score immediately prior to endovascular intervention.

Results:
The data of 80 patients satisfied the inclusion criteria (33 female, average age 71) and was included in the study. Collateral grade prior to intervention included 2 ASITN grade 4, 26 grade 3, 23 grade 2, 6 grade 1 and 0 grade 0. oTICI2C reperfusion scores after thrombectomy included 2 TICI 3 (100%), 22 TICI 2C (90-99%), 25 TICI o2B (67-89%), 9 TICI m2B (50-66%), 19 TICI 2A (<50%) and 3 TICI 0/1. The spatio-temporal flow tracks were predictive of the ASITN when used as input to a machine learning model that mapped the tractography patterns of the collaterome to a continuous score.

Conclusion:
SFT, or Spatio-temporal Flow Tractography, is introduced to provide an automatic assessment of collateral flow from routine perfusion MRI.
Abstract TP56: Angiographic Flow Index on DSA Correlates with Cerebral Flow Measured by Quantitative MRA
Authors: Hussein Ahmed E , Brunozzi Denise , Shakur Sophia F , Linninger Andreas , Hsu Chih-Yang , Charbel Fady T , Alaraj Ali
Published: June 2021

Introduction:
Digital subtraction angiography (DSA) has traditionally been used to provide high-resolution anatomical imaging but is not readily used to assess cerebral hemodynamics. Here we examine the relationship between time density transit time (TT) on DSA, vessel cross-sectional area and flow obtained from QMRA of the same artery.

Methods:
Patients seen at our institution between 2009 and 2015 who had concomitant DSA and Quantitative MRA prior to any treatment for a vascular lesion were retrospectively reviewed. Transit time (TT) on DSA was defined as time needed for contrast to change image intensity from 25%-25%. Flow volume rate (mL/min) and vessel cross-sectional area were measured using QMRA. Angio flow index (FI) = [Cross sectional area/TT
25-25%]
was calculated and analyzed relative to flow.

Results:
48 patients (mean age was 51 years) were included. There was a significant correlation (Spearman’s) between the MCA and ACA flows and the angio flow index (
P
<0.001, rho=0.66). The same positive correlation was present for the individual MCA flows (
P
<0.001, rho=0.81) and ACA flows (
P
<0.001, rho=0.52) and the angio flow index.

Conclusion:
Angio flow index correlated significantly with intracranial flows measured by QMRA, and so angio flow index may be used as an indirect tool for assessment of cerebral flow during interventional procedures.
Abstract TP61: Detection of Atherosclerotic Plaque Using Non-contact and Label-free Near-infrared Hyper-spectral Imaging
Authors: Chihara Hideo , Oishi Naoya , Ishii Akira , Munemitsu Toshihiro , Arai Daisuke , Ikeda Hiroyuki , Miyamoto Susumu
Published: June 2021

Background and Aims:
Detecting detailed atherosclerotic plaques is important to reduce risk factors during vascular surgery. However, there are few methods to evaluate them during surgery. The aim of this study was to establish an in vivo, non-contact, and label-free imaging method for identifying atherosclerotic plaque lesions from outside vessels with a diffuse-reflectance near-infrared (NIR) hyperspectral imaging (HSI) system.

Method:
NIR spectra between 1000 and 2350 nm were measured using an NIR HSI imaging system outside the exposed abdominal aorta in 5 Watanabe Heritable Hyperlipidemic (WHHL) rabbits in vivo. Preprocessed data were input to a supervised machine learning algorithm called a support vector machine (SVM) to create pixel-based images that can predict atherosclerotic plaques within a vessel. The images were compared with histological findings.

Result:
Absorbance was significantly higher in plaques than in normal arteries at 1000-1380, 1580-1810, and 1880-2320 nm. Overall predictive performance showed a sensitivity of 0.814 ± 0.017, a specificity of 0.836 ± 0.020, and an accuracy of 0.827 ± 0.008. The area under the receiver operating characteristic curve was 0.905 (95% confidence interval = 0.904-0.906).

Conclusion:
The NIR HSI system combined with a machine learning algorithm enabled accurate detection of atherosclerotic plaques within an internal vessel with high spatial resolution from outside the vessel. The findings indicate that the NIR HSI system can provide non-contact, label-free, and precise localization of atherosclerotic plaques during vascular surgery.
Abstract TP63: Detection of Perfusion Deficits Using FLAIR and GRE Based Vessel Signs
Authors: Reyes Dennys , Hitomi Emi , Simpkins Alexis , Lynch John , Hsia Amie , Benson Richard , Nadareishvili Zurab , Luby Marie , Latour Lawrence , Leigh Richard
Published: June 2021

Background:
The presence of a perfusion deficit in an acute stroke patient can play an important role in their clinical management. However, many patients are unable to have perfusion-weighted imaging (PWI) due to renal disease. Perfusion deficits are often accompanied by FLAIR hyperintense vessels (FHV), presumably due to slow arterial blood flow, and GRE hypointense vessels (GHV), presumably due to venous congestion.

Purpose:
To determine how well FHV and GHV perform at identifying PWI lesions.

Methods:
One rater, blinded to the PWI MR sequences, retrospectively reviewed the DWI, FLAIR and GRE scans of acute stroke patients enrolled in the NIH Natural History of Stroke study during 2013-2014 who had an MRI with PWI prior to being treated with IV tPA. DWI images were used to guide evaluation of the FLAIR and GRE images for FHV and GHV and in each case were classified as definitively present, possibly present or absent. PWI lesion volumes were calculated by thresholding the time-to-peak (TTP) maps at 4 seconds beyond normal tissue. ROC analysis was used to assess the performance of FHV and GHV at various PWI lesion volume thresholds.

Results:
102 patients were included in the analysis; their mean PWI lesion volume was 52 mL with a standard deviation of +/- 66 mL. 22% of patients had no perfusion deficit. The ROC analysis found the presence of any FHV performed the best with an area under the curve (AUC) of 0.925 displayed in the figure. Any GHV performed modestly with an AUC of 0.776. Combining FHV with GHV did not improve the performance over FHV alone (AUC=0.876). The sensitivity and specificity for identifying any perfusion deficit with FHV was 95% and 67% respectively with 87% being correctly classified. For detecting a PWI lesion greater than 10 mL, FHV had an 80% sensitivity and 93% specificity classifying 83% correctly.

Conclusions:
FHV is highly sensitive for identifying a perfusion deficit in stroke patients, and for patients with a lesion volume greater than 10 mL it is highly specific.
Abstract TP69: Safety and Outcomes of IV Thrombolysis with Alteplase for Acute Ischemic Stroke Patients with Thrombocytopenia
Authors: Kamal Haris , Abdelhamid Nour , Zhu Liang , Savitz Sean , Grotta James , Sarraj Amrou
Published: June 2021

Background:
Intravenous tPA (IV tPA) has been the mainstay for reperfusion therapies for acute ischemic stroke (AIS) patients for 2 decades. Many contraindications from the initial NINDS trial were derived from experts’ consensus and not tested in the trial. Many AIS patients present with thrombocytopenia (< 100,000) and may be excluded from treatment in spite of lack of strong evidence. Some clinicians opt to treat these patients weighing the benefits and risks along with the lack of strong evidence behind this exclusion. We sought to evaluate the safety in AIS patients with low platelets receiving IV tPA as compared to those who do not.

Methods:
Restrospective chart review of all patients presenting with AIS between 1/2006 to 7/2016 at our center. We analyzed patients who had platelets <100,000 among this cohort and stratified them into those who were treated with IV tPA and those who received antiplatelet therapy only. Demographic data, medical history, medications, presence of sICH after treatment, presenting NIHSS were collected. Two sample Wilcoxon rank sum test was used to compare continuous variables between the two groups, and chi-square test or Fisher’s exact test used to compare categorical variables.

Results:
21 patients were treated with IV tPA while 122 patients were treated with antiplatelets. Table 1 lists the demographic variables of the two groups with and without IV tPA. Patients included had moderate thrombocytopenia with very few <50,000. No significant differences were found in presenting NIHSS, race, gender, and history of atrial fibrillation between the two groups except platelets (p=0.0128), age (p=0.0462) and glucose (p=0.0279). Table 2 lists the outcome variables of mRS and symptomatic ICH. There was no petechial or sICH among 21 treated patients.

Conclusion:
While limited by small numbers and lack of randomization, our data suggest that IV tPA is safe in patients with moderately reduced platelet counts.
Abstract TP78: Combination of Neuroprotective Drug and Neural Stem Cells Benefits Aged Stroke Mice with Delayed Tissue Plasminogen Activator Treatment
Authors: Eckert Auston , Hamblin Milton H , Lee Jean-Pyo
Published: June 2021

Background:
Presently, tissue plasminogen activator (tPA) is the sole FDA-approved antithrombotic treatment available for stroke. However, tPA’s harmful side effects within the central nervous system can exacerbate blood-brain barrier (BBB) damage and increase mortality. Patients should receive tPA less than 4.5 hours post-stroke. Although age alone is not an impediment for tPA treatment, the harmful effects of delayed tPA (>4.5h), particularly on aged stroke animals, have not been well studied. We reported that intracranial transplantation of neural stem cells (hNSCs) ameliorates BBB damage caused by ischemic stroke. In this study, we examined the combined effects of minocycline (a neuroprotective and anti-inflammatory drug) and hNSC transplantation on the mortality of delayed tPA-treated aged mice within 48h post-stroke.

Methods and Results:
We utilized the middle cerebral artery occlusion stroke mouse model to induce focal cerebral ischemia followed by reperfusion (MCAO/R). 6h post-MCAO, we administered tPA intravenously. Minocycline was administered intraperitoneally at various time points prior to tPA injection. One day post-stroke, we injected hNSCs intracranially. Previously, we reported that hNSCs (both human and mouse) transplanted into the brain 24h post-stroke rapidly improve neurological outcome in young-adult mice (4-5mo). In our current study, tPA administered within 4.5h did not increase mortality in either young-adult or aged mice. However, we found delayed tPA treatment (6h post-stroke) significantly increased the mortality of aged mice (13-18 mo) but not in young-adult mice. Here, we report that by combining minocycline prior to tPA significantly reduced mortality. Furthermore, transplanting hNSCs in minocycline-treated mice further ameliorated the pathophysiology caused by delayed tPA.

Conclusions:
Our findings implicate that administering the anti-apototic and anti-inflammatory drug prior to tPA injection, and then post-treating with multipotent neuroprotective hNSCs might expand the time window of tPA and reduce reperfusion injury.
Abstract TP81: MiR122 Modulates Nos2 to Improve Stroke Outcomes After Middle Cerebral Artery Occlusion in Rats
Authors: Liu DaZhi , Jickling Glen C , Ye Zhouheng , Ander Bradley P , Zhan Xinhua , Stamova Boryana , Lyeth Bruce G , Sharp Frank R
Published: June 2021

Based upon our previous findings that microRNA-122 (miR-122) was decreased in peripheral blood of both humans and rats after ischemic stroke, we hypothesized that elevating miR-122 in blood might improve outcomes after ischemic stroke.

Using the
in vivo
polyethylene glycol 2000 (PEG)-liposome based miRNA transfection system and the rat middle cerebral artery occlusion (MCAO) model, we recently demonstrated that intravenous (i.v.) miR-122 mimic, given immediately after MCAO, elevated miR-122 in peripheral blood, prevented neurological impairments, and reduced brain infarction volume up to 93% after MCAO in rats. Using Taqman PCR based assays, we demonstrate fourteen direct miR-122 target genes (e.g. Nos2, Vcam1, Clic4, Ucp2, Dlg2, and others) were decreased in blood leukocytes following miR-122 mimic treatment after MCAO in rats. Focusing on ONE miR-122 target gene (Nos2), we demonstrated that miR-122 binds to the complementary sequence within three prime untranslated regions (3’UTRs) of Nos2 using luciferase reporter assay, and that miR-122 mimic decreases Nos2 expression in brain microvascular endothelial cells (BMVECs) after MCAO in rats.

These results show that Nos2 is decreased in leukocytes and BMVECs following miR-122 mimic treatment after MCAO, which likely contributes to miR-122 induced protection after MCAO in rats.

Acknowledgements:
This study was supported by NIH grants R01NS089901 (DZL) and NS054652 (FRS). There were no conflicts of interest.
Abstract TP87: Early Quantitative Somatosensory Evoked Potentials Markers after Cardiac Arrest
Authors: Young Leanne M , Deng Ruoxian , Koenig Matthew A , Jia Xiaofeng
Published: June 2021

Background and Purpose:
The high incidence of poor functional outcome following cardiac arrest (CA) signifies the importance of prognostic tools to track recovery. This study evaluates the prognostic value of quantitative somatosensory evoked potentials (SSEPs) under targeted temperature management (TTM). We hypothesize that the integrity of thalamocortical pathways involved in SSEP may be represented by amplitude and latency, which may provide an indication of outcome.

Methods:
Twenty-one Wistar rats underwent 7min asphyxia-CA followed by immediate TTM (n=7/group): hypothermia (33±1
°
C), normothermia (37±0.5
°
C), hyperthermia (39±0.5
°
C). Fourteen additional rats underwent sham surgery followed by TTM. SSEPs were recorded before CA and 30min-4hr post-resuscitation. Functional outcome was evaluated by 72hr Neurologic Deficit Scale (NDS) score. N7 and N10 amplitude and latency during early recovery were normalized to baseline values.

Results:
Sham animals had significantly higher N10 amplitudes (p<0.05) and N7 and N10 latencies (p<0.01) under hypothermia, and shorter N7 and N10 latencies (p<0.05) under hyperthermia, compared to normothermia. N7 and N10 latency and N10 amplitude were significantly higher in hypothermic CA animals than normothermic and hyperthermic CA animals (p<0.01) and in good (72hr NDS≥60) compared to poor (72hr NDS<60) outcome animals (p<0.01). N10 amplitude had 50% sensitivity for good outcome at 30min post-resuscitation with 100% specificity.

Conclusions:
SSEP N10 amplitude during early recovery from CA with TTM is associated with functional outcome and predicts good outcome in a rodent model.
Abstract TP91: Stroke Induced Respiratory Dysfunction: Age, Apnea and Cognitive Decline
Authors: Patrizz Anthony , Ahnstedt Hilda , McCullough Louise
Published: June 2021

Respiratory dysfunction is a common complication of stroke, with an incidence more than 60%, leading to prolonged recovery and increased mortality. Despite the high prevalence of stroke induced respiratory dysfunction (SIRD) little is known regarding how SIRD influences recovery and cognitive outcomes after ischemic stroke. Studies in non-stroke populations have shown that individuals with respiratory dysfunction are drastically more likely to develop cognitive impairment. We propose stroke will induce chronic respiratory dysfunction, instability, and apnea in mice, which are linked to higher mortality and greater post-stroke cognitive deficits. Respiratory dysfunction will be related to progressive cognitive decline following middle cerebral artery occlusion (MCAo) that is worse in aged mice. Whole body plethysmography was performed on C57/B6 young (2-3 month)/aged (20 month) male mice to establish baseline frequency (BPM), tidal volume, minute ventilation and apnea frequency. Animals were exposed to a variety of gas conditions to assess the contribution of peripheral and central chemoreceptors. Mice were subjected to 60 MCAO, producing chronic respiratory dysfunction, instability and apnea, or sham surgery. Days 3, 7 and weekly thereafter plethysmography and a variety of cognitive tests were performed to track respiratory dysfunction and progressive cognitive decline. Young and aged mice displayed hypoventilation (young stroke 181.4±22 vs. sham 264±35 bpm p<.05 and aged stroke 233.7±46.6 bpm vs. sham 369.4±25.9 p<.05) and increased apneas (young stroke 6.8±1.2 vs. 0.8±.8 apnea/min p<.01; aged stroke 16±1 vs. 12±1.5 apneas/min) at day 3 post-stroke. Six weeks later mice were stratified based on # apneas/min into minor (<5 apneas/min N=8) and moderate/severe (>5 apneas/min N=3). Mice with minor apneas perform better in a variety of cognitive tests. Fear conditioning (freezing behavior minor 1.47±.24s/event vs. mod .74±.07s/event, p=.02), Barnes maze: Escape time minor 158.5±35.2 sec vs. 217.9±82. NORT: ratio time novel/familiar object minor 2.2±.6 vs. 1.1±.3. Suggesting incidence of apneas as an indicator of cognitive decline. Therefore, the treatment of respiratory instability is a viable prospect to improve cognitive outcomes.
Abstract TP96: Pexophagy is Neuroprotective in Ischemic Brain
Authors: Zhu Wenbin , Zhang Wenri , Young Jennifer , Barnes Anthony P , Alkayed Nabil J
Published: June 2021

Introduction:
Peroxisomes are highly adaptable and dynamic organelles, undergoing a formation/degradation cycle every 24-48 hours. We have previously demonstrated that increasing peroxisomal biogenesis serves a protective function in neurons experiencing ischemic injury, in part through catalase-mediated antioxidant activity. The role of autophagy in adult cerebral ischemia has been studied, yet the specific role for the targeted destruction of damaged peroxisomes (pexophagy) in ischemic stroke has not yet been explored.

Hypothesis:
We hypothesize that post-ischemic pexophagy is a critical step for neuronal survival. We used a combination of pharmacologic and genetic strategies to test whether perturbation of autophagy in general and pexophagy in particular exacerbates ischemic brain injury by targeting key regulators including mammalian Target Of Rapamycin (mTOR).

Methods:
Transient middle cerebral artery occlusion (MCAO, 60 min) was performed in male mice treated with mTOR rapamycin (1.25 mg/kg, IP) or vehicle at the beginning of reperfusion. Similarly, TSC1 knock-out and wild-type mice underwent 60-min MCAO, and brains were harvested and analyzed for infarct size at 24 hrs of reperfusion. Separate brains we analyzed for peroxisomal membrane protein co-localization with autophagic markers, and for autophagic activity based on microtubule-associated protein 1A/1B-light chain 3 (LC3) turnover.

Results:
Activation of autophagy using rapamycin reduced infarct size after MCAO (27.2 ± 2.8% in rapamycin-treated mice vs. 37.3 ± 1.8 % in vehicle-treated mice in cortex , n=10 and 9 per group respectively, p=0.01), whereas TSC1 knockout mice, which have reduced pexophagy, sustained larger infarcts than WT mice (48.5 ± 4.5% in TSC1 knockout mice vs. 33.0 ± 5.8 % in vehicle-treated mice in cortex , n=4 and 5 per group respectively, p=0.007). The experiments of peroxisomal co-localization and autophagic activity have been finished but no results yet. We’ll report them later.

Conclusions:
We conclude that organelle autophagy, including pexophagy, is an endogenous mechanism of neuroprotection after stroke, and that both biogenesis and pexophagy of peroxisomes are protective by promoting peroxisomal turnover.