Abstract WMP16: Relative Dwi Signal Intensity as a Predictor of Stroke Onset Time Compared to the Visual DWI/FLAIR Mismatch

Introduction: The DWI/FLAIR mismatch has been proposed as an imaging pattern to predict stroke onset before 4.5h in patients with unknown time of symptom duration. Limitations of the DWI/FLAIR mismatch include the additional imaging time required to obtain FLAIR, difficulty of assessment in patients with severe white matter disease, poor interrater agreement, and motion sensitivity of longer MRI sequences. We hypothesised that automated analysis of DWI imaging would be at least as accurate to predict stroke onset before 4.5h. Methods: Data from the Axis 2 trial were used and patients were included in whom a DWI lesion was detected by automated software (RAPID). The visual DWI/FLAIR mismatch was rated in accordance with the criteria of the ongoing WAKE-UP trial. For every patient the relative DWI (rDWI) was calculated in a voxel based manner as the ratio of the diffusion intensity in that voxel and the median diffusion intensity of a sphere with radius 15 mm around the homologue voxel in the contralateral hemisphere. The mean and standard deviation (SD) of the rDWI was obtained in the DWI lesion. Receiver operating curves (ROC) and corresponding area under the curves (AUC) for predicting the 4.5h time-window were determined. Results: We included 200 patients. In 8 patients (4%) the visual DWI/FLAIR rating was hampered due to either extensive white matter disease or poor quality of FLAIR imaging. The DWI/FLAIR mismatch had an AUC of 0.66 to predict stroke onset before 4.5h vs an AUC of 0.71 for rDWI SD (p for difference=0.4). The optimal rDWI SD threshold for predicting stroke ≤ 4.5h was 0.23. Using this threshold, stroke onset was accurately predicted in 73% of patients vs 65% accuracy with the visual DWI/FLAIR mismatch (p for difference=0.1). (table 1) Conclusion: Our results suggest that rDWI may have advantages over the visual DWI/FLAIR mismatch for predicting the time of stroke onset. rDWI provides an accurate and objective assessment with the potential for fully automated processing.

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Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.wp32 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Nandakumar Nagaraja ◽

Marie Luby ◽

Matthew Edwardson ◽

Ramin Zand ◽

Lawrence L Latour

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Volume ◽

Early Phase ◽

Cerebral Blood Volume ◽

Time Window ◽

Linear Regression Analysis ◽

Onset Time ◽

Stroke Onset ◽

Imaging Biomarker

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR<1.15, “Low CBV” was defined as CBV SIR <0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p <0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

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Collateral response modulates the time–penumbra relationship in proximal arterial occlusions

Neurology ◽

10.1212/wnl.0000000000004858 ◽

2017 ◽

Vol 90 (4) ◽

pp. e316-e322 ◽

Cited By ~ 13

Author(s):

Smriti Agarwal ◽

Andrew Bivard ◽

Elizabeth Warburton ◽

Mark Parsons ◽

Christopher Levi

Keyword(s):

Time Window ◽

Infarct Volume ◽

Arterial Intervention ◽

Onset Time ◽

Brain Perfusion ◽

Stroke Onset ◽

Therapeutic Window ◽

Large Patient ◽

Collateral Response ◽

Tissue Compartments

ObjectiveWhile clinical benefit from thrombolysis decreases with increase in time from stroke onset, the relationship of acute physiologic tissue compartments and collateral response to stroke onset time remains unclear.MethodsWe studied consecutive patients with proximal arterial occlusions (n = 355) with whole-brain perfusion CT with CT angiography within 6 hours of stroke onset. Penumbra and core were defined using voxel-based thresholds. Tissue mismatch was defined as the ratio of penumbra to core. Collateral scores were assessed using a previously validated visual score.ResultsMean (SD) age was 72.1 (12.4) years, median (interquartile range) NIH Stroke Scale score 16 (4), mean (SD) time to imaging 152.5 (69.7) minutes. Penumbra volume (Spearman ρ = 0.119,p= 0.026) and mismatch increased (Spearman ρ = 0.115,p= 0.030) with time from onset. Core volume decreased (Spearman ρ = −0.112,p= 0.035) while collateral scores increased with time (Spearman ρ = 0.117,p= 0.028). On multivariable regression, good collateral scores predicted longer time since onset (β = 0.101,p= 0.039) while mismatch was not a predictor (β = 0.001,p= 0.351). Good collateral score was the strongest independent predictor of final infarct volume and improvement in clinical deficit.ConclusionsIn our large patient cohort study of proximal arterial occlusions, we found an incremental collateral response and preserved penumbral volume with time. Thus, tissue viability can be maintained in this time window (0–6 hours) after stroke if leptomeningeal collaterals are able to sustain the penumbra. Our findings suggest that a longer therapeutic window may exist for intra-arterial intervention and that multimodal imaging may have a role in strokes of unknown onset time.

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Automated DWI analysis can identify patients within the thrombolysis time window of 4.5 hours

Neurology ◽

10.1212/wnl.0000000000005413 ◽

2018 ◽

Vol 90 (18) ◽

pp. e1570-e1577 ◽

Cited By ~ 2

Author(s):

Anke Wouters ◽

Bastian Cheng ◽

Soren Christensen ◽

Patrick Dupont ◽

David Robben ◽

...

Keyword(s):

Ischemic Stroke ◽

Confidence Interval ◽

Signal Intensity ◽

Time Window ◽

Characteristic Curve ◽

Area Under The Curve ◽

Automated Analysis ◽

Stroke Onset ◽

Derivation Cohort ◽

Independent Cohort

ObjectiveTo develop an automated model based on diffusion-weighted imaging (DWI) to detect patients within 4.5 hours after stroke onset and compare this method to the visual DWI-FLAIR (fluid-attenuated inversion recovery) mismatch.MethodsWe performed a subanalysis of the “DWI-FLAIR mismatch for the identification of patients with acute ischemic stroke within 4.5 hours of symptom onset” (PRE-FLAIR) and the “AX200 for ischemic stroke” (AXIS 2) trials. We developed a prediction model with data from the PRE-FLAIR study by backward logistic regression with the 4.5-hour time window as dependent variable and the following explanatory variables: age and median relative DWI (rDWI) signal intensity, interquartile range (IQR) rDWI signal intensity, and volume of the core. We obtained the accuracy of the model to predict the 4.5-hour time window and validated our findings in an independent cohort from the AXIS 2 trial. We compared the receiver operating characteristic curve to the visual DWI-FLAIR mismatch.ResultsIn the derivation cohort of 118 patients, we retained the IQR rDWI as explanatory variable. A threshold of 0.39 was most optimal in selecting patients within 4.5 hours after stroke onset resulting in a sensitivity of 76% and specificity of 63%. The accuracy was validated in an independent cohort of 200 patients. The predictive value of the area under the curve of 0.72 (95% confidence interval 0.64–0.80) was similar to the visual DWI-FLAIR mismatch (area under the curve = 0.65; 95% confidence interval 0.58–0.72; p for difference = 0.18).ConclusionsAn automated analysis of DWI performs at least as good as the visual DWI-FLAIR mismatch in selecting patients within the 4.5-hour time window.

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Acute Stroke Biomarkers: Are We There Yet?

Frontiers in Neurology ◽

10.3389/fneur.2021.619721 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marie Dagonnier ◽

Geoffrey A. Donnan ◽

Stephen M. Davis ◽

Helen M. Dewey ◽

David W. Howells

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Matrix Protein ◽

Time Window ◽

Onset Time ◽

Stroke Onset ◽

Blood Biomarkers ◽

Vessel Occlusion ◽

Specificity And Sensitivity ◽

Stroke Diagnosis

Background: Distinguishing between stroke subtypes and knowing the time of stroke onset are critical in clinical practice. Thrombolysis and thrombectomy are very effective treatments in selected patients with acute ischemic stroke. Neuroimaging helps decide who should be treated and how they should be treated but is expensive, not always available and can have contraindications. These limitations contribute to the under use of these reperfusion therapies.Aim: An alternative approach in acute stroke diagnosis is to identify blood biomarkers which reflect the body's response to the damage caused by the different types of stroke. Specific blood biomarkers capable of differentiating ischemic from hemorrhagic stroke and mimics, identifying large vessel occlusion and capable of predicting stroke onset time would expedite diagnosis and increase eligibility for reperfusion therapies.Summary of Review: To date, measurements of candidate biomarkers have usually occurred beyond the time window for thrombolysis. Nevertheless, some candidate markers of brain tissue damage, particularly the highly abundant glial structural proteins like GFAP and S100β and the matrix protein MMP-9 offer promising results. Grouping of biomarkers in panels can offer additional specificity and sensitivity for ischemic stroke diagnosis. Unbiased “omics” approaches have great potential for biomarker identification because of greater gene, protein, and metabolite coverage but seem unlikely to be the detection methodology of choice because of their inherent cost.Conclusion: To date, despite the evolution of the techniques used in their evaluation, no individual candidate or multimarker panel has proven to have adequate performance for use in an acute clinical setting where decisions about an individual patient are being made. Timing of biomarker measurement, particularly early when decision making is most important, requires urgent and systematic study.

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Abstract WP86: MRI-Guided Mismatch Imaging to Identify Patients for Thrombolysis in the Unknown Time Window: Insights From the WAKE-UP Trial

Stroke ◽

10.1161/str.51.suppl_1.wp86 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Lauranne Scheldeman ◽

Anke Wouters ◽

Soren Christensen ◽

Patrick Dupont ◽

Bastian Cheng ◽

...

Keyword(s):

Treatment Effect ◽

Time Window ◽

Onset Time ◽

Stroke Onset ◽

Favorable Outcome ◽

Neurological Deficits ◽

Primary Efficacy ◽

Efficacy And Safety ◽

Inclusive Approach ◽

Fluid Attenuated Inversion Recovery

Background: Two imaging paradigms, the diffusion-weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) and perfusion-weighted imaging (PWI) - DWI mismatch, used in the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) and Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial respectively, can identify patients eligible for thrombolysis if stroke onset time is unknown. Objectives: We explored presence and influence of the PWI-DWI mismatch on outcome in WAKE-UP. Methods: We included patients screened for DWI-FLAIR mismatch in WAKE-UP who also underwent PWI. We defined PWI-DWI mismatch according to EXTEND as core <70 ml, mismatch ratio >1.2 and mismatch volume >10 ml. Primary efficacy end point was favorable outcome defined as modified Rankin Scale score of 0-1, adjusted for age and symptom severity. Results: The analysis included 343 screened patients of which 162 were randomized and treated. Of 343 screened patients, 162 had a DWI-FLAIR mismatch, 80 had a PWI-DWI mismatch and of those, 36 had both mismatches. Proportions of PWI-DWI mismatch did not differ in those with (22%, 36/162) vs without (24%, 44/181) DWI-FLAIR mismatch (p=0.74). PWI-DWI mismatch status did not modify treatment effect of thrombolysis (p for interaction=.68). In patients with both DWI-FLAIR and PWI-DWI mismatch, favorable outcome was present in 52% of those treated with alteplase (11/21) vs 38% (5/13) in those receiving placebo (adjusted OR 2.02; 95% CI 0.44-9.24, p=0.36). Selection based on the presence of the DWI-FLAIR mismatch identified more thrombolysis eligible patients (47%; 95% CI 42%-53%) compared to the PWI-DWI mismatch (23%; 95% CI 19%-28%, p<.0001). Screening for either one of the mismatch profiles resulted in a yield of 60% (95% CI 55%-65%) candidates for thrombolysis. Conclusion: We did not identify an association between the DWI-FLAIR and PWI-DWI mismatch. PWI-DWI mismatch status did not modify treatment effect in patients with DWI-FLAIR mismatch, but the analysis was underpowered. Screening for the presence of either one of the mismatch profiles with MRI seems the most inclusive approach to identify patients who can still benefit from thrombolysis in the unknown time window after stroke onset.

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