Abstract TP271: Improvement of Cerebral Blood Flow With DS-1040 in a Rat Thromboembolic Stroke Model

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kengo Noguchi ◽  
Naoko Edo ◽  
Yusuke Ito ◽  
Yoshiyuki Morishima ◽  
Kyoji Yamaguchi
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Saline Control ◽  
Control Group ◽  
Stroke Model ◽  
Thromboembolic Stroke ◽  
Doppler Flowmetry ◽  
Autologous Whole Blood

Introduction: DS-1040 is a novel inhibitor of the activated thrombin-activatable fibrinolysis inhibitor (TAFIa) and is in clinical development for the treatment of acute ischemic stroke (AIS). The objective of this study was to investigate the effect of DS-1040 on cerebral blood flow (CBF) in a rat thromboembolic stroke model. Methods: The CBF was transcranially and continuously monitored during the experiment by laser Doppler flowmetry system using a probe fixed to the skull above the territory of the right middle cerebral artery (MCA) of an anesthetized male SHR/Izm rat. After recording basal CBF, non-autologous whole blood clot was injected into the internal carotid artery. We conducted a 3-arm study. Saline (control) and DS-1040 (3.0 mg/kg) were intravenously injected as a bolus 5 min after the clot injection. The dosage of DS-1040 was set to achieve full inhibition of TAFIa during the experiment. Recombinant tissue plasminogen activator (rt-PA, 7.0 mg/kg; positive control) was intravenously injected 5 min after the clot injection by 10% bolus and 90% infusion for 60 min. The CBF(%) was defined as percent of the CBF at each time point to the mean basal CBF and the area under the curve of the CBF(%) after the drug injection, AUC 5-110min , was calculated. Results: The CBF(%) decreased after the clot injection, indicating the clot embolized the MCA. A significant increase of the AUC 5-110min was observed in the rt-PA group (8416.2 %·min ± 642.4 %·min, mean ± SE) compared to the control group (3728.7 %·min ± 684.2 %·min), indicating the model is sensitive to tPA. DS-1040 also significantly increased the AUC 5-110min (6645.3 %·min ± 861.9 %·min) compared to the control group. Conclusions: DS-1040 restored CBF in a rat thromboembolic stroke model suggesting DS-1040 is expected to be beneficial for the treatment of patients with acute ischemic stroke. To the authors’ knowledge, this is the first report of an inhibitor of TAFIa improving the CBF in a thromboembolic stroke model.

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Early microvascular cerebral blood flow response to head-of-bed elevation is related to outcome in acute ischemic stroke

2019 ◽  
Vol 266 (4) ◽  
pp. 990-997 ◽  
Author(s):  
Clara Gregori-Pla ◽  
Igor Blanco ◽  
Pol Camps-Renom ◽  
Peyman Zirak ◽  
Isabel Serra ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Flow Response ◽  
Bed Elevation ◽  
Flow Response ◽  
Head Of Bed Elevation

scholarly journals Computed Tomography Perfusion–Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 223-231
Author(s):  
Hulin Kuang ◽  
Wu Qiu ◽  
Anna M. Boers ◽  
Scott Brown ◽  
Keith Muir ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Interquartile Range ◽  
Time Dependent ◽  
Computed Tomography Perfusion

Background and Purpose: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion–based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke. Methods: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, T max , cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent T max thresholds were compared with the ML model. Results: In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4–54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1–70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74–0.86, P <0.001) while the volumetric difference was −3.2 mL (interquartile range, −16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent T max threshold ( P <0.001). Conclusions: A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.

scholarly journals Optical Bedside Monitoring of Cerebral Blood Flow in Acute Ischemic Stroke Patients During Head-of-Bed Manipulation

Stroke ◽  
2014 ◽  
Vol 45 (5) ◽  
pp. 1269-1274 ◽  
Author(s):  
Christopher G. Favilla ◽  
Rickson C. Mesquita ◽  
Michael Mullen ◽  
Turgut Durduran ◽  
Xiangping Lu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Stroke Patients ◽  
Bedside Monitoring

scholarly journals Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke

2021 ◽  
Vol 23 (3) ◽  
pp. 377-387
Author(s):  
Johanna M. Ospel ◽  
Ondrej Volny ◽  
Wu Qiu ◽  
Mohamed Najm ◽  
Moiz Hafeez ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Decision Making ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Computed Tomography Angiography ◽  
Estimation Methods ◽  
Good Outcome

Background and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared.Results Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT.Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Abstract TMP86: Early Microvascular Cerebral Blood Flow Response to Head-of-bed Elevation is Related to Outcome in Acute Ischemic Stroke: A Diffuse Correlation Spectroscopy Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Clara Gregori-Pla ◽  
Raquel Delgado-Mederos ◽  
Pol Camps-Renom ◽  
Peyman Zirak ◽  
Igor Blanco ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Correlation Spectroscopy ◽  
Stroke Onset ◽  
Diffuse Correlation Spectroscopy ◽  
Blood Flow Response ◽  
Poor Outcome ◽  
Flow Response

Introduction: The microvascular cerebral blood flow response (rCBF) to orthostatic stress has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS). However, its relevance to the outcome is unknown. Hypothesis: CBF response to head-of-the-bed (HOB) elevation within the first hours after AIS is related to outcome. Methods: Patients with a large anterior circulation stroke of less than 48h from the stroke onset were monitored with DCS to follow rCBF in the frontal lobes during a HOB elevation from supine to 30°. All patients were placed flat during the first 24 hours and later, mobilization was initiated depending on the clinical condition. We categorized measurements as early (<12h) or late (>12h) from stroke onset. NIHSS was recorded at baseline, during HOB, at 24h and 48h. The modified Rankin scale (mRS) score was utilized as the outcome measure (favorable when 0-2). Results: We studied 34 patients (age 78±13y, male 47%, median NIHSS 19 (14-21)) at 16±11 hours from stroke. Ipsilateral extracranial and/or intracranial occlusion was present in 61%. Frontal CBF decreased in both hemispheres after HOB (-5±14%). A paradoxical response (increase/no change) was observed in 18%. rCBF was not correlated to NIHSS and age. Unfavorable outcome was found in 85%. Only at early hours (<12h, n=16), rCBF to HOB elevation in the ipsilateral (not in contralateral) hemisphere (p=0.04, Figure 1) and NIHSS HOB (p=0.008) were associated with poor outcome. Conclusions: This result suggests that paradoxical CBF response to a mild HOB elevation in the early hours of stroke onset is associated with a poor outcome in patients with AIS. Optical continuous monitoring in the bedside may help to individualize management strategies in the early hours of AIS. Figure 1: rCBF due to HOB elevation versus mRS for the ipsi-lateral side in patients measured <12h after stroke.

Abstract WP48: Relationship of Cerebral Blood Flow by Pseudo-continuous Arterial Spin Labeling and Stenosis in Middle Cerebral Artery Territory in Patients Evaluated for Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Eric Lai ◽  
Raja Rizal Azman Raja Aman ◽  
Hui Zhang ◽  
Pui-Wai Chiu ◽  
Queenie Chan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Arterial Spin Labeling ◽  
Spin Labeling ◽  
Arterial Stenosis ◽  
Vascular Territory

Purpose: Correlation of arterial stenosis with cortical and subcortical cerebral blood flow (CBF) in the middle cerebral artery (MCA) territory. Methods: 126 patients with acute cerebrovascular symptoms from March to June 2015 underwent MRI and MR Angiography (MRA) in a University hospital using a 3.0 Tesla scanner. Sequences included T1W, T2W, FLAIR, DWI, MRA, Pseudocontinuous Arterial Spin Labeling (pcASL, post-labeling delay 1.525 s). 13 patients (corrupted pcASL data) were excluded, with 113 patients (mean age: 67.74±14.19) evaluated (61 acute ischemic stroke, 52 patients transient ischemic attack). Institutionally developed software was used to determine CBF. MCA stenosis was graded into 4 categories by a neuroradiologist: 0 (no stenosis), 1 (mild <50%), 2 (moderate 50-70%) and 3 (severe >70%). Mean and standard deviation of MCA categories (leptomeningeal and perforating) CBF and corresponding degree of MCA stenosis were measured. Spearman correlation coefficients between CBF of cortical and subcortical regions and degree of MCA stenoses were calculated using SPSS (version 23.0). Results: The table showed the descriptive statistics. There was significant correlation between CBF of cortical region of MCA vascular territory and degree of stenosis of MCA in both left (r s = -0.296, p =0.001) and right (r s = -0.306, p =0.001) side. In the contrary, there was no correlation between subcortical CBF of MCA vascular territory and degree of stenosis of MCA in both sides. Conclusion: pcASL is a feasible non-invasive method to measure CBF in clinical setting. In MCA territory, the cortical blood flow correlated (fairly) with large vessel stenosis but not subcortical flow. We conclude that cortical CBF correlated with large artery stenosis, though being attenuated by collateral blood supply. No such relationship in subcortical CBF might be due to differential grey and white matter CBF flow, variable MCA stenotic location, and perforators originating from other territories.

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