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Machine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI 0 ), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI 24h ) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI 24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI 0 as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median [IQR] Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 [0.29-0.68]) than U-Net (0.48 [0.18-0.68]), Random Forests (0.51 [0.27-0.66]), and clinical thresholding method (0.45 [0.25-0.62]) ( P  < 0.001). In this benchmark of ML models for tissue outcome prediction in AIS, Gradient Boosting outperformed other ML models and clinical thresholding method and is thus promising for future decision-making.

In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR ( P  = 0.006), shorter thrombus on T2*-imaging ( P  < 0.001) and more distal occlusion ( P  = 0.006). However, the relationship between HIR and early recanalization was robust only for thrombus length <14 mm. In summary, the present study disclosed an association between lower HIR and early post-thrombolysis recanalization. Early post-thrombolysis recanalization is therefore determined not only by thrombus site and length but also by severity of ischemia.

Background and Purpose: Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWI volume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome., Methods: We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically., Results: Among 53 patients with DWI volume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P =0.046) and less history of smoking (1/10 versus 12/31; P =0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L-occluded patients ( P =0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P =0.050)., Conclusions: Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory., (© 2018 American Heart Association, Inc.)

Background and Purpose: Triage imaging facilitates the timely recognition of acute stroke with prognostic implications. Improvement in MR acquisition speed is needed given the extreme time constraints before treatment. We compared an ultrafast Echo-Planar FLAIR sequence (EPI-FLAIR) and a conventional FLAIR sequence (cFLAIR) for their diagnostic performances and ability to estimate the age of infarction., Material and Methods: Between June and August 2014, 125 consecutive patients (age 69±18 years, 48% men) admitted for a suspicion of acute (≤48-hrs) stroke were explored by both FLAIR sequences at 1.5-Tesla. EPI-FLAIR (15-sec) and cFLAIR (2-min and 15-sec) were compared by two readers, blinded to clinical data., Results: EPI-FLAIR was less prone to kinetic artefacts than cFLAIR (2-3% vs. 23-49% depending on the reader, P<0.001). Diagnostic concordance was excellent for both readers (к>0.9). Amongst 8 hemorrhages, one subarachnoid hemorrhage presenting as a sudden deficit was missed on EPI-FLAIR sequence. Amongst 60 infarctions, cFLAIR and EPI-FLAIR were concordant in 50 (83%), while signal changes were visible on cFLAIR only in the remaining 10 (17%) cases. Amongst the 43 patients with known onset time (n=17 within 4.5hrs), FLAIR-DWI mismatch identified<4.5-hrs infarction with the same sensitivity (65%) using cFLAIR and EPI-FLAIR, but the positive predictive value (PPV) was higher for cFLAIR than for EPI-FLAIR (73% vs. 50%, P=0.008)., Conclusion: EPI-FLAIR allows a drastic reduction of acquisition time devoted to FLAIR sequence and minimizes motion artifacts. Compared with cFLAIR, it is however associated with increased risk of undiagnosed stroke mimics and lower PPV for identifying<4.5-hrs infarctions., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Rapid and reliable assessment of the perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch is required to promote its wider application in both acute stroke clinical routine and trials. We tested whether an evaluation based on the Alberta Stroke Program Early CT Score (ASPECTS) reliably identifies the PWI/DWI mismatch., Methods: A total of 232 consecutive patients with acute middle cerebral artery stroke who underwent pretreatment magnetic resonance imaging (PWI and DWI) were retrospectively evaluated. PWI-ASPECTS and DWI-ASPECTS were determined blind from manually segmented PWI and DWI volumes. Mismatch-ASPECTS was defined as the difference between PWI-ASPECTS and DWI-ASPECTS (a high score indicates a large mismatch). We determined the mismatch-ASPECTS cutoff that best identified the volumetric mismatch, defined as VolumeTmax>6s/VolumeDWI≥1.8, a volume difference≥15 mL, and a VolumeDWI<70 mL., Results: Inter-reader agreement was almost perfect for PWI-ASPECTS (κ=0.95 [95% confidence interval, 0.90-1]), and DWI-ASPECTS (κ=0.96 [95% confidence interval, 0.91-1]). There were strong negative correlations between volumetric and ASPECTS-based assessments of DWI lesions (ρ=-0.84, P<0.01) and PWI lesions (ρ=-0.90, P<0.01). Receiver operating characteristic curve analysis showed that a mismatch-ASPECTS ≥2 best identified a volumetric mismatch, with a sensitivity of 0.93 (95% confidence interval, 0.89-0.98) and a specificity of 0.82 (95% confidence interval, 0.74-0.89)., Conclusions: The mismatch-ASPECTS method can detect a true mismatch in patients with acute middle cerebral artery stroke. It could be used for rapid screening of patients with eligible mismatch, in centers not equipped with ultrafast postprocessing software., (© 2016 American Heart Association, Inc.)

Background: Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal., Aim: To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction., Methods: We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57-80), National Institute of Health Stroke Score at admission 14 (8-19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after i.v.-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score., Results: Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23-38.9) vs. 16.98 (4.4-45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82-0.90) vs. 0.82 (0.78-0.87), P = 0.003)., Conclusion: At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point., (© 2016 World Stroke Organization.)

Background and Purpose: Fluid-attenuated inversion recovery vascular hyperintensities (FVH) beyond the boundaries of diffusion-weighted imaging (DWI) lesion (FVH-DWI mismatch) have been proposed as an alternative to perfusion-weighted imaging (PWI)-DWI mismatch. We aimed to establish whether FVH-DWI mismatch can identify patients most likely to benefit from recanalization., Methods: FVH-DWI mismatch was assessed in 164 patients with proximal middle cerebral artery occlusion before intravenous thrombolysis. PWI-DWI mismatch (PWITmax>6sec/DWI>1.8) was assessed in the 104 patients with available PWI data. We tested the associations between 24-hours complete recanalization on magnetic resonance angiography and 3-month favorable outcome (modified Rankin Scale score ≤2), stratified on FVH-DWI (or PWI-DWI) status., Results: FVH-DWI mismatch was present in 121/164 (74%) patients and recanalization in 50/164 (30%) patients. The odds ratio for favorable outcome with recanalization was 16.2 (95% confidence interval, 5.7-46.5; P<0.0001) in patients with FVH-DWI mismatch and 2.6 (95% confidence interval, 0.6-12.1; P=0.22) in those without FVH-DWI mismatch (P=0.048 for interaction). Recanalization was associated with favorable outcome in patients with PWI-DWI mismatch (odds ratios, 9.9; 95% confidence interval, 3.1-31.3; P=0.0001) and in patients without PWI-DWI mismatch (odds ratios, 7.0; 95% confidence interval, 1.1-44.1; P=0.047), P=0.76 for interaction., Conclusion: The FVH-DWI mismatch may rapidly identify patients with proximal occlusion most likely to benefit from recanalization., (© 2016 American Heart Association, Inc.)

Background and Purpose: In acute stroke with proximal artery occlusion, FLAIR vascular hyperintensities observed beyond the boundaries of the cortical lesion on DWI (newly defined "FLAIR vascular hyperintensity-DWI mismatch") may be a marker of tissue at risk of infarction. Our aim was to compare the occurrence of FLAIR vascular hyperintensity-DWI mismatch relative to that of perfusion-weighted imaging-DWI mismatch in patients with proximal MCA occlusion before IV thrombolysis., Materials and Methods: In 141 consecutive patients with proximal MCA occlusion, 2 independent observers analyzed FLAIR images for the presence of FLAIR vascular hyperintensity-DWI mismatch before IV thrombolysis. PWI-DWI mismatch was defined as Volumehypoperfusion > 1.8 × VolumeDWI, with Volumehypoperfusion > 6 seconds on time to maximum value of the residue function maps in the 94 patients with available PWI. The presence of FLAIR vascular hyperintensity-DWI mismatch, PWI-DWI mismatch, and infarct growth on 24-hour follow-up DWI was compared., Results: A FLAIR vascular hyperintensity-DWI mismatch was present in 102/141 (72%) patients, with an excellent interobserver reliability (κ = 0.91), and a PWI-DWI mismatch, in 61 of the 94 (65%) patients with available PWI. FLAIR vascular hyperintensity-DWI mismatch predicted PWI-DWI mismatch with a sensitivity of 92% (95% CI, 85%-99%) and a specificity of 64% (95% CI, 47%-80%). Patients with FLAIR vascular hyperintensity-DWI mismatch had smaller initial DWI lesion and larger infarct growth (P < .001) than patients without FLAIR vascular hyperintensity-DWI mismatch, even though their final infarcts remained smaller (P < .001)., Conclusions: Albeit being moderately specific, probably due to inclusion of oligemic tissue, the FLAIR vascular hyperintensity-DWI mismatch identifies large PWI-DWI mismatch with high sensitivity., (© 2015 by American Journal of Neuroradiology.)

Because of its excellent sensitivity and specificity to diagnose arterial ischemic stroke (AIS) in the acute phase, MRI answers the main questions to guide treatment in "candidates" for thrombolysis. It lasts less than ten minutes, can confirm the diagnosis of AIS and distinguish it from hematomas and other "stroke mimics". It can identify the ischemic penumbra (perfusion-diffusion mismatch), determine the site of occlusion and provide prognostic information to adapt treatment in some cases in which the indications are poorly defined. In light of the most recent scientific findings, MRI can guide the treatment turning it into the investigation of choice in "candidates" for thrombolysis., (Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The early identification of patients who are unlikely to respond to intravenous recombinant tissue plasminogen activator (IV-tPA) could help select candidates for additional intra-arterial therapy or add-on antithrombotic drugs during the acute stage of stroke. Given that very early neurological improvement (VENI) is a reliable surrogate of early recanalization, we assessed the clinical and magnetic resonance imaging predictors of lack of VENI., Methods and Results: We reviewed consecutive ischemic stroke patients with middle cerebral artery occlusion and treated within 4.5 hours by IV-tPA between 2003 and 2012 in our center, where magnetic resonance imaging is systematically implemented as first-line diagnostic workup. Lack of VENI was defined as a <40% decrease in baseline National Institutes of Health Stroke Scale (NIHSS) score 1 hour after start of IV-tPA. Poor outcome was defined as a 3-month modified Rankin scale ≥2. Associations between lack of VENI and potential determinants were assessed in logistic regression models. In all, 186 patients were included (median baseline NIHSS score, 16; median onset to treatment time, 155 minutes). One hundred forty-three patients (77%) had no VENI. The variables significantly associated with lack of VENI in multivariable analysis were baseline NIHSS (OR, 1.08; 95% CI, 1.01 to 1.16 per 1-point increase; P=0.03), onset to treatment time >120 minutes (OR, 2.94; 95% CI, 1.31 to 6.63; P=0.009) and diffusion weighted imaging--Alberta Stroke Programme Early CT Score ≤5 (OR, 3.60; 95% CI, 1.14 to 11.35; P=0.03). Patients without VENI were more likely to have a modified Rankin Scale ≥2 than those without VENI (68% versus 24%; OR, 5.01; 95% CI, 2.12 to 11.82) and less likely to have recanalization after 24 hours (OR, 0.41; 95% CI, 0.19 to 0.88)., Conclusions: Lack of VENI provides an early estimate of 3-month outcome and recanalization after IV-tPA. Baseline NIHSS, onset to treatment time, and diffusion weighted imaging--Alberta Stroke Programme Early CT Score could help to predict lack of VENI and, in turn, might help early selection of candidates for complementary reperfusion strategies.

Background and Purpose: In stroke attributable to spontaneous dissection of the cervical artery, it is unclear whether the occurrence and pattern of stroke depend on the degree of stenosis., Methods: In 147 consecutive dissection of the cervical artery patients with (n=88) and without stroke (n=59), we compared the number, volume, and patterns of cerebral diffusion-weighted imaging stroke lesions among patients with <70% stenosis (Group 1), ≥70% stenosis (Group 2), and occlusion (Group 3)., Results: The presence (26 of 45 in Group 1, 32 of 59 in Group 2, 30 of 43 in Group 3; P=0.27) and the number of diffusion-weighted imaging lesions (mean±SD [interquartile range], 3.5±3.9 [1-4] in Group 1; 4.2±4.1 [1-5] in Group 2; 3.3±4.0 [1-3] in Group 3; P=0.85) were independent of lumen patency, whereas volume of diffusion-weighted imaging lesions was larger in occlusive dissection of the cervical artery (82±90 mm [17-91] versus 34±54 [2-48]; P=0.03). There were no differences in the breakdown of diffusion-weighted imaging lesion patterns according to degree of stenosis., Conclusions: The occurrence and diffusion-weighted imaging lesion patterns in dissection of the cervical artery patients may not be influenced by the degree of stenosis of the dissected artery. Occlusive dissection of the cervical artery was associated with larger infarcts.

Imaging of water diffusion or diffusion-weighted MR imaging provides physiological information about brain diseases that cannot be obtained from conventional sequences. This technique is very sensitive for the detection of cerebral ischemia from arterial origin and can distinguish cerebral ischemia from other non-vascular brain pathologies in patients presenting with abrupt onset of focal neurological deficit. Diffusion-weighted imaging is used for the evaluation of non-vascular diseases as well. Combined with conventional sequences, it is helpful to differentiate brain abscesses from necrotic tumors. Quantitative diffusion-weighted imaging provides additional information in the characterization of tumors or inflammatory, degenerative and metabolic lesions. Finally, diffusion-weighted imaging data also has prognostic value.

Summary: The high rate of normal diffusion-weighted imaging (DWI) in patients with transient ischemic attack (TIA) raises the question as to its sensitivity for detecting small ischemic lesions. We compared standard and optimized DWI in 36 consecutive patients with TIA. Optimized DWI was positive in more patients than standard DWI (19 versus 16; P < .001) and showed more lesions (56 versus 42; P = .002). At 1.5T, optimizing DWI decreases the rate of false-negative DWI in patients with TIA.

Background and Purpose: Our aim was to improve our understanding of the subinsular white matter microstructural asymmetries in healthy right-handed subjects. Structural brain asymmetries could be related to functional asymmetries such as hemisphere language dominance or handedness. Besides the known gray matter asymmetries, white matter asymmetries could also play a key role in the understanding of hemispheric specialization, notably that of language., Materials and Methods: White matter asymmetries were studied by diffusion tensor imaging at 1.5T (41 diffusion-gradient directions; b-value set to 700 s/mm(2); matrix, 128(2); in-plane resolution, 1.875 x 1.875 mm; section thickness, 2.0 mm) and fiber tracking (BrainVISA software). The main white matter bundles passing through the subinsular area were segmented, and fractional anisotropy (FA) was measured along each of the segmented bundles., Results: In line with published results, we found an asymmetry of the arcuate fasciculus and the subinsular white matter, namely left-greater-than-right FA in right-handed controls. Furthermore, by segmenting major tracts coursing through this region, we showed that the subinsular portions of the uncinate fasciculus (UF) and the inferior occipitofrontal fasciculus (IOF) contribute to this FA asymmetry. Those tracts have been reported to be likely implicated in the language network., Conclusion: Because the left hemisphere hosts language functions in most right-handers, the significant leftward asymmetry observed within the arcuate fasciculus, the subinsular part of the UF and IOF may be related to the hemispheric specialization for language.

Owing to its rapid acquisition time and high sensitivity, diffusion-weighted imaging has turned into a routine sequence for brain imaging. This is the case not only for stroke, but also for various diseases such as abscesses or tumors. Being aware of the artifacts is important for optimal interpretation. After a brief review of the normal patterns, the most frequent artifacts, inherent to the echoplanar imaging technique, are described and we provide suggestions to avoid them. Most current traps are caused by T2-weighting of the diffusion images; the key for avoiding erroneous interpretation relies on the ADC map.

The purpose of this study was to determine frequency and the characteristics of diffusion-weighted imaging (DWI) abnormalities in patients with transient ischaemic attack (TIA). We analysed data of 98 consecutive patients (mean age: 60.6+/-15.4 years, 56 men) admitted between January 2003 and April 2004 for TIA. Age, gender, symptom type and duration, delay from onset to magnetic resonance imaging (MRI), probable or possible TIA and cause of TIA were compared in patients with (DWI+) and without (DWI-) lesions on DWI. Volume and apparent diffusion coefficient (ADC) values of DWI lesions were computed. DWI revealed ischaemic lesions in 34 patients (34.7%). Lesions were small (mean volume: 1.9 cm(3)+/-3.3), and ADC was moderately decreased (mean ADC ratio: 79.5%). The diagnosis of TIA was considered as probable in all DWI+ patients. A multiple logistic regression model demonstrated that TIA duration greater than or equal to 60 min (OR, 7.6; 95% CI, 2.3-25.7), aphasia (OR, 9.2; 95% CI, 2.7-31.4) and motor deficit (OR, 5.1; 95% CI, 1.5-17.8) were independent predictors of DWI lesions. Prolonged TIA duration, aphasia and motor deficits are associated with DWI lesions. More than half of TIA patients with symptoms lasting more than 60 min have DWI lesions.

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.

Purpose: Diffusion-weighted imaging (3 directions) and diffusion tensor imaging (9 directions) were compared for their sensitivity to detect ischemic lesion., Materials and Methods: 41 patients (18 supposed transient ischemic attacks, 23 arterial stroke, MRI

Diffusion tensor MR imaging is a technique that provides details on tIssue microstructure and organization well beyond the usual image resolution. With diffusion tensor MR imaging, diffusion anisotropy can be quantified and subtle white matter changes not normally seen on conventional MRI can be detected. The purpose of this article is to review the current applications of diffusion tensor MR imaging for the study of the brain, including normal aging, Alzheimer's disease, neuropsychiatric disorders, strokes, multiple sclerosis, brain tumors and intractable seizures.

Background and Purpose: The number of clot retrieval attempts required to achieve complete reperfusion by mechanical thrombectomy impacts functional outcome in acute ischaemic stroke (AIS). Complete reperfusion [expanded Treatment In Cerebral Infarction (eTICI) score = 3] at first pass (FP), is associated with the highest rates of favorable outcome compared to complete reperfusion by multiple passes. The aim of the present study was to investigate the relationship between FP complete reperfusion and infarct growth (IG). Methods: Anterior AIS patients with baseline and 24‐h diffusion‐weighted magnetic resonance imaging were included from two prospective registries. IG was measured by voxel‐based segmentation of initial and 24‐h diffusion‐weighted imaging lesions. IG and favorable 3‐month modified Rankin Scale (mRS) score (≤ 2) were compared between patients in whom complete reperfusion (eTICI 3) was achieved with a single pass (FP group) and those for whom multiple passes were required (MP group), after matching for confounding factors. Mediation analysis was performed to examine the association between FP and 3‐month mRS score, with IG as mediating variable. Results: A total of 200 patients were included, of whom 118 (28.9%) had FP complete reperfusion. In case–control analysis, the FP group had lower IG than the MP group [8.7 (5.4–12.9) ml vs. 15.2 (11–22.6) ml, respectively; P = 0.03). Favorable outcome was higher in the FP population compared to a matched MP population (70.9% vs. 53.2%, respectively; P = 0.04). FP compete reperfusion (eTICI 3) was independently associated with favorable outcome in multivariable regression analysis [odds ratio 1.86, 95% confidence interval (CI) 1.01–4.39; P = 0.04]. The effect of complete reperfusion at FP on functional outcome was explained by limited IG in mediation analysis [indirect effect: −0.32 (95% CI −0.47 to −0.09)]. Conclusion: Complete reperfusion at FP is independently associated with significant decrease in IG compared to complete reperfusion by multiple attempts, explaining better functional outcomes. [ABSTRACT FROM AUTHOR]