MRI of cerebral oedema in ischaemic stroke and its current use in routine clinical practice.

Currently, with the knowledge of the role of collateral circulation in the development of cerebral ischaemia, traditional therapeutic windows are being prolonged, with time not being the only criterion. Instead, a more personalised approach is applied to select additional patients who might benefit from active treatment. This review briefly describes the current knowledge of the pathophysiology of the development of early ischaemic changes, the capabilities of MRI to depict such changes, and the basics of the routinely used imaging techniques broadly available for the assessment of individual phases of cerebral ischaemia, and summarises the possible clinical use of routine MR imaging, including patient selection for active treatment and assessment of the outcome on the basis of imaging.

Predictive value of DWI-FLAIR Mismatch in patients with Ischemic Stroke and receiving Endovascular treatment beyond Time Window.

OBJECTIVE: To investigate the efficacy and safety of endovascular treatment in patients having acute ischemic stroke with over-time window under DWI-FLAIR mismatch. METHODS: From January 2018 to January 2020, 80 patients who met the research criteria in the First Central Hospital of Baoding, China were selected. According to the time of onset, they were divided into test group and control group, with 40 cases in each group. Forty patients in the test group were beyond time window (6~24h) and the MRI showed a DWI-FLAIR mismatch. Forty patients in the control group were within the time window (< 6h). All patients received endovascular treatment (EVT). The mRS, NIHSS and infarct volume of patients in the test group were compared and analyzed before and 30 and 90 days after treatment, as well as the indicators of both groups of patients before and after treatment, to determine therapeutic effect in patients receiving EVT beyond time window. Meanwhile, the recanalization of the blood vessel and the incidence of cerebral hemorrhage of patients in both groups were compared to determine the safety in patients receiving EVT beyond time window under DWI-FLAIR mismatch. RESULTS: The mRS, NIHSS and infarct size in the test group were significantly improved before and 30 and 90 days after treatment (p<0.05). The test group showed no significant difference in mRS, NIHSS and other indicators when compared with the control group (p>0.05). There was no significant difference in the rate of recanalization of the blood vessel and intracranial hemorrhage after treatment between both groups (p>0.05). CONCLUSION: DWI-FLAIR mismatch can be used as an objective imaging basis for intravascular interventional therapy in patients with stroke with over-time window and large vessel occlusion. It has the advantages of short examination time, non-invasiveness, no need for contrast agents, simple implementation, clear guidance.

Modified DWI-FLAIR mismatch guided thrombolysis in unknown onset stroke.

DWI-FLAIR mismatch has been recently proven to identify patients with unknown onset stroke (UOS) eligible for thrombolysis. However, this concept may exclude patients from thrombolysis who may eventually benefit as well. We aimed to examine the feasibility, safety and potential efficacy of thrombolysis in wake-up stroke (WUS) and UOS patients using a modified DWI-FLAIR mismatch allowing for partial FLAIR positivity. WUS/UOS patients fulfilling the modified DWI-FLAIR mismatch and treated with intravenous thrombolysis (IVT) were compared to propensity score matched WUS/UOS patients excluded from IVT due to FLAIR positivity. The primary endpoint was a symptomatic intracranial hemorrhage (SICH), the secondary endpoints were improvement of ≥ 4 in NIHSS score and mRS score at 3 months. 64 IVT-treated patients (median NIHSS 9) and 64 controls (median NIHSS 8) entered the analysis (p = 0.2). No significant difference in SICH was found between the IVT group and the controls (3.1% vs. 1.6%, p = 0.9). An improvement of ≥ 4 NIHSS points was more frequent in IVT patients as compared to controls (40.6% vs. 18.8%, p = 0.01). 23.4% of IVT patients achieved a mRS score of 0-1 at 3 months as compared to 18.8% of the controls (p = 0.8). SICH, improvement of NIHSS ≥ 4 and mRS 0-1 at 3 months were comparable in thrombolyzed patients with negative FLAIR images versus those thrombolyzed with partial positive FLAIR images (3% vs. 3%, p = 0.9; 40% vs. 41%, p = 0.9; 19% vs. 22%, p = 0.8). Our study signalizes that thrombolysis may be feasible in selected WUS/UOS patients with partial FLAIR signal positivity.

[Acute treatment of ischemic stroke : Current standards]. / Akutbehandlung des ischämischen Schlaganfalls : Aktuelle Standards.

Important milestones of acute ischemic stroke (AIS) treatment were achieved in recent years. The results of two randomized controlled trials revealed that intravenous thrombolysis is efficacious for treatment of AIS patients with a symptom onset <9 h or an unknown time of symptom onset in the presence of beneficial patterns in advanced stroke imaging. These patterns comprise the evidence of salvageable tissue at risk of infarction in perfusion of computed tomography (so-called penumbral imaging) or a mismatch between the diffusion-weighted imaging (DWI) und fluid-attenuated inversion recovery (FLAIR) sequences in magnetic resonance imaging (so-called DWI-FLAIR mismatch). Another two randomized controlled trials resulted in evidence of a high effectiveness of mechanical thrombectomy using advanced imaging of selected AIS patients with a symptom onset <24 h or an unknown time window. This article provides an overview of the current study results and recommendations for the selection of imaging for evidence-based effective acute treatment of stroke patients.

Management of a wake-up stroke.

Current national guidelines advocate intravenous thrombolysis to treat patients with acute ischaemic stroke presenting within 4.5 hours from symptom onset, and thrombectomy for patients with anterior circulation ischaemic stroke from large vessel occlusion presenting within 6 hours from onset. However, a substantial group of patients presents with acute ischaemic stroke beyond these time windows or has an unknown time of onset. Recent studies are set to revolutionise treatment for these patients. Using MRI diffusion/FLAIR (fluid-attenuated inversion recovery) mismatch, it is possible to identify patients within 4.5 hours from onset and safely deliver thrombolysis. Using CT perfusion imaging, it is possible to identify subjects with a middle cerebral artery syndrome who have an extensive area of ischaemic brain but as yet have only a small area of infarction who may benefit from urgent thrombectomy in up to 24 hours. Here, we highlight the recent advances in late window stroke treatment and their potential contribution to clinical practice.

Unknown-onset strokes with anterior circulation occlusion treated by thrombectomy after DWI-FLAIR mismatch selection.

BACKGROUND AND PURPOSE: The DAWN trial recently showed compelling evidence in treating late window and wake-up stroke patients with thrombectomy using a clinical-imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown-onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI-FLAIR) mismatch based selection. METHODS: A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from 'last seen normal' were compared with known-onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia. RESULTS: Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a 'last time seen well' beyond 6 h and DWI-FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, P = 0.022). After pre-specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80-1.04; P = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS. CONCLUSION: Thrombectomy of UOS with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.

The challenge of basilar artery occlusion wake-up stroke: too late for intravenous thrombolysis?

We describe the case of a patient carried to our emergency department, with the wake-up finding of dysarthria, right hemiplegia and worsening consciousness impairment (NIHSS 12). After performing a CT angiography, which showed complete basilar occlusion, we determined the MR DWI-FLAIR mismatch to estimate the stroke onset time. Because of the favorable mismatch (DWI hyperintensity in the left pons, no FLAIR hyperintensity in the same region), the patient underwent thrombolysis with sudden neurological improvement. In addition, the DWI hyperintensity first observed in the left pons totally regressed after thrombolysis. Wake-up stroke constitutes about 14 % of all strokes, while the percentage of basilar artery occlusion wake-up strokes is still unknown. Although thrombolysis in patients with unknown-onset time is still an off-label therapy, basilar artery occlusion is a potentially fatal event. In our case we used RM DWI-FLAIR mismatch to rapidly estimate the stroke onset time and to treat the patient with an off-label but potentially effective and safe therapy.

Multicenter validation of synthetic FLAIR as a substitute for FLAIR sequence in acute ischemic stroke.

PURPOSE: To evaluate performance of synthetic and real FLAIR for identifying early stroke in a multicenter cohort. METHODS: This retrospective study was conducted using DWI and FLAIR extracted from the Endovascular Treatment in Ischemic Stroke image registry (2017-2021). The database was partitioned into subsets according to MRI field strength and manufacturer, and randomly divided into training set (70%) used for model fine-tuning, validation set (15%), and test set (15%). In test set, five readers, blinded to FLAIR sequence type, assessed DWI-FLAIR mismatch using real and synthetic FLAIR. Interobserver agreement for DWI-FLAIR rating and concordance between synthetic and real FLAIR were evaluated with kappa statistics. Sensitivity and specificity for identification of ⩽4.5 h AIS were compared in patients with known onset-to-MRI delay using McNemar's test. RESULTS: 1454 complete MRI sets (1172 patients, median (IQR) age: 73 years (62-82); 762 women) acquired on 125 MRI units were analyzed. In test set (207 MRI), interobserver reproducibility for DWI-FLAIR mismatch labeling was substantial for real and synthetic FLAIR (Fleiss κ = 0.79 (95%CI: 0.73-0.84) and 0.77 (95%CI: 0.71-0.82), respectively). After consensus, concordance between real and synthetic FLAIR was excellent (κ = 0.85 (95%CI: 0.78-0.92)). In 141 MRI sets with known onset-to-MRI delay, diagnostic performances for ⩽4.5 h AIS identification did not differ between real and synthetic FLAIR (sensitivity: 60/71 (85%) vs 59/71 (83%), p = .56; specificity: 65/70 (93%) vs 65/70 (93%), p > 0.99). CONCLUSION: A deep-learning-based FLAIR fine-tuned on multicenter data can provide comparable performances to real FLAIR for early AIS identification. This approach may help reducing MR protocol duration and motion artifacts.

Unveiling Opportunities for Intervention: A Prospective Cohort Study Investigating the Clinical Significance of Diffusion-Weighted Imaging (DWI)-Fluid-Attenuated Inversion Recovery (FLAIR) Mismatch Beyond the Window Period in Acute Ischemic Stroke.

INTRODUCTION: Acute ischemic stroke causes irreversible damage to the brain parenchyma surrounded by salvageable tissue known as the ischemic penumbra. Magnetic resonance imaging (MRI), particularly the mismatch between abnormal diffusion-weighted imaging (DWI) signals and normal fluid-attenuated inversion recovery (FLAIR) signals, plays a critical role in detecting ischemic penumbra. It also allows for the identification of patients who may benefit from reperfusion therapy. Hence, this prospective cohort study aimed to explore the correlation between DWI-FLAIR mismatch and clinical outcomes in acute ischemic stroke patients, specifically those with delayed or uncertain symptom onset, offering potential insights into reperfusion therapy. METHODOLOGY: A total of 38 thrombotic stroke patients aged above 18 were included in this prospective cohort study. Baseline data, including demographics, lifestyle factors, and medical history, were recorded. DWI-FLAIR mismatch was evaluated through brain MRI within 4.5 hours to 12 hours of symptom onset. RESULTS:  Of the cohort, 63.2% were males, predominantly in the 61-70 age group. Smoking and alcohol consumption were reported by 15.79% each. DWI-FLAIR mismatch was present in 20 out of 38 subjects. No statistically significant differences were noted in the mean National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) scores between subjects with and without DWI-FLAIR mismatch. Thrombolysis in wake-up stroke subjects demonstrated a substantial reduction in mean MRS at discharge (1.29±0.95) and at six to eight weeks (1.71±1.11), suggesting potential benefits on functional outcomes. CONCLUSION:  The prevalence of DWI-FLAIR mismatch was seen in the majority of patients beyond their window period and also showed beneficiary outcomes with a mean reduction in NHISS and MRS scores following thrombolysis.

Thrombolysis in wake-up stroke based on MRI mismatch.

OBJECTIVES: Wake-up stroke (WUPS) patients can be selected to intravenous thrombolysis (IVT) treatment based on the Magnetic Resonance Imaging (MRI) mismatch concept. However, recent studies suggest the introduction of modified MRI mismatch criteria, allowing IVT in WUPS patients with a partial mismatch. MATERIAL AND METHODS: WUPS patients treated with IVT in the NOR-TEST trial and consecutively thereafter at Stavanger University Hospital were included in this study. Patient selection for treatment was performed based on the clinical presentation and the MRI DWI/FLAIR mismatch criteria. MRI examinations were reassessed according to the modified DWI-FLAIR mismatch criteria, allowing partial mismatch. Improvement in NIHSS and mRS at 3 months were used to analyze clinical outcome, and the rate of intracranial hemorrhage (ICH) to analyze safety. RESULTS: 78 WUPS patients were treated with IVT. Only 68 of these patients were independent pre-stroke and included in the clinical analysis. When reassessing the MRI examinations, 41 (60 %) were rated as DWI/ FLAIR mismatch, 14 (21 %) as partial mismatch and 13 (19 %) as match. The results show that the patient groups had a mRS score 0-1 at 3 months measured as primary outcome to respectively 27 (65.9 %), 11 (78.6 %) and 8 (61.5 %); (P = 0.629). The mismatch group showed the best clinical improvement (3-points NIHSS reduction, p = 0.005). No ICH was seen in any of the groups. CONCLUSION: Our study extended the mismatch concept in clinical praxis to treat WUPS patients with partial mismatch, showing the best clinical outcome in the mismatch group.

CDC42 Might Be a Molecular Signature of DWI-FLAIR Mismatch in a Nonhuman Primate Stroke Model.

No definitive blood markers of DWI-FLAIR mismatch, a pivotal indicator of salvageable ischemic penumbra brain tissue, are known. We previously reported that CDC42 and RHOA are associated with the ischemic penumbra. Here, we investigated whether plasma CDC42 and RHOA are surrogate markers of DWI-FLAIR mismatch. Sixteen cynomolgus macaques (3 as controls and 13 for the stroke model) were included. Guided by digital subtraction angiography (DSA), a middle cerebral artery occlusion (MCAO) model was established by occluding the middle cerebral artery (MCA) with a balloon. MRI and neurological deficit scoring were performed to evaluate postinfarction changes. Plasma CDC42 and RHOA levels were measured by enzyme-linked immunosorbent assay (ELISA). The stroke model was successfully established in eight monkeys. Based on postinfarction MRI images, experimental animals were divided into a FLAIR (-) group (N = 4) and a FLAIR (+) group (N = 4). Plasma CDC42 in the FLAIR (-) group showed a significant decrease compared with that in the FLAIR (+) group (p < 0.05). No statistically significant difference was observed for plasma RHOA. The FLAIR (-) group showed a milder neurological function deficit and a smaller infarct volume than the FLAIR (+) group (p < 0.05). Therefore, plasma CDC42 might be a new surrogate marker for DWI-FLAIR mismatch.

Predicting DWI-FLAIR mismatch on NCCT: the role of artificial intelligence in hyperacute decision making.

Background: The presence of diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was used to determine eligibility for intravenous thrombolysis in clinical trials. However, due to the restricted availability of MRI and the ambiguity of image assessment, it is not widely implemented in clinical practice. Methods: A total of 222 acute ischemic stroke patients underwent non-contrast computed tomography (NCCT), DWI, and FLAIR within 1 h of one another. Human experts manually segmented ischemic lesions on DWI and FLAIR images and independently graded the presence of DWI-FLAIR mismatch. Deep learning (DL) models based on the nnU-net architecture were developed to predict ischemic lesions visible on DWI and FLAIR images using NCCT images. Inexperienced neurologists evaluated the DWI-FLAIR mismatch on NCCT images without and with the model's results. Results: The mean age of included subjects was 71.8 ± 12.8 years, 123 (55%) were male, and the baseline NIHSS score was a median of 11 [IQR, 6-18]. All images were taken in the following order: NCCT - DWI - FLAIR, starting after a median of 139 [81-326] min after the time of the last known well. Intravenous thrombolysis was administered in 120 patients (54%) after NCCT. The DL model's prediction on NCCT images revealed a Dice coefficient and volume correlation of 39.1% and 0.76 for DWI lesions and 18.9% and 0.61 for FLAIR lesions. In the subgroup with 15 mL or greater lesion volume, the evaluation of DWI-FLAIR mismatch from NCCT by inexperienced neurologists improved in accuracy (from 0.537 to 0.610) and AUC-ROC (from 0.493 to 0.613). Conclusion: The DWI-FLAIR mismatch may be reckoned using NCCT images through advanced artificial intelligence techniques.

Artificial Intelligence for Automated DWI/FLAIR Mismatch Assessment on Magnetic Resonance Imaging in Stroke: A Systematic Review.

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)-mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis.

An Automatic DWI/FLAIR Mismatch Assessment of Stroke Patients.

DWI/FLAIR mismatch assessment for ischemic stroke patients shows promising results in determining if patients are eligible for recombinant tissue-type plasminogen activator (r-tPA) treatment. However, the mismatch criteria suffer from two major issues: binary classification of a non-binary problem and the subjectiveness of the assessor. In this article, we present a simple automatic method for segmenting stroke-related parenchymal hyperintensities on FLAIR, allowing for an automatic and continuous DWI/FLAIR mismatch assessment. We further show that our method's segmentations have comparable inter-rater agreement (DICE 0.820, SD 0.12) compared to that of two neuro-radiologists (DICE 0.856, SD 0.07), that our method appears robust to hyper-parameter choices (suggesting good generalizability), and lastly, that our methods continuous DWI/FLAIR mismatch assessment correlates to mismatch assessments made for a cohort of wake-up stroke patients at hospital submission. The proposed method shows promising results in automating the segmentation of parenchymal hyperintensity within ischemic stroke lesions and could help reduce inter-observer variability of DWI/FLAIR mismatch assessment performed in clinical environments as well as offer a continuous assessment instead of the current binary one.

Internuclear Ophthalmoplegia as an Isolated Symptom of Brainstem Wake-up Stroke Responsive to Intravenous Thrombolysis: Evidence from MRI.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a disorder of eye movements caused by a lesion involving the medial longitudinal fasciculus (MLF) within the brainstem, and it is characterized by adduction impairment combined with contralateral dissociated abduction nystagmus. The frequency of acute ischemic stroke (AIS) presenting with INO as a predominant symptom is very low, and many patients suffering from this brainstem AIS are precluded from intravenous thrombolysis (IVT). OBJECTIVE: To provide for the first time a magnetic resonance imaging (MRI) evidence of response to the IVT in brainstem wake-up stroke presenting with INO as an isolated symptom. METHODS: Here, we described a rare case of pons AIS presenting with INO as a unique symptom of awakening. In order to differentiate an ischemic stroke from other stroke mimics, and to determine whether the patient was within the therapeutic window for IVT (wake-up stroke), brain MRI including DWI and FLAIR sequences was acquired. RESULTS: A left paramedian pontine DWI/FLAIR mismatch was detected and the patient was considered eligible for IVT. After IVT, the patient made a full recovery with complete resolution of INO. Follow-up MRI at 1 month demonstrates the absence of ischemic lesions. CONCLUSION: Our case provides neuroradiological evidence of IVT efficacy in brainstem stroke, and it should prompt clinicians to rapidly perform MRI in wake-up onset INO and to just as quickly administer IVT, since INO is a functionally disabling deficit. Finally, this case demonstrates the value of MRI in diagnostic, prognostic, and therapeutic workup of posterior circulation wake-up stroke.

FLAIR vascular hyperintensity-DWI mismatch and DWI-FLAIR mismatch ASPECTS for prediction of good outcome after recanalization in anterior circulation stroke; multicenter observational study.

INTRODUCTION: Acute ischemic stroke is a medical emergency caused by decreased blood flow to the brain, leading cause of long-term disability. Recanalization, one of the most concerning difficulties linked with intracranial arterial occlusion, has been used to reduce mortality in ischemic stroke treatment. The mismatch concepts MR PWI-DWI or DWI-FLAIR can help identify patients for thrombolysis. PURPOSE: This paper introduces a novel method of predicting revascularization using the value of fluid-attenuated inversion recovery vascular hyperintensity FVH-DWI mismatch and DWI-FLAIR mismatch, which releases anterior circulation large vessel occlusion (LVO) after endovascular thrombectomy (EVT). Moreover, we present a new scoring system following anatomical region distributed for MCA territory called a DWI-FLAIR MISMATCH ASPECTS. RESULT: Statistical analysis was performed to predict revascularization and functional outcome with 110 patients with anterior circulation LVO treated with EVT. We found that FVH-DWI mismatch was present in 71 patients (89.9 %) with complete revascularization and present in 8 patients (10.1 %) with no/partial revascularization, which had no significant difference (p = 0.12), and there was no significant difference between good functional outcome and poor functional outcome. Moreover, in 76 patients with DWI-FLAIR mismatch ASPECTS of > 6 point-group, present FVH-DWI mismatch in 57 patients (83.8 %) with complete revascularization had a significant difference as compared to 11 patients (16.2 %) with absent FVH-DWI mismatch (p < 0.05). The clinical outcome in complete revascularization is better than no/partial revascularization, and complete revascularization is independently associated with good functional outcomes (p < 0.05). CONCLUSION: FVH-DWI mismatch paired with DWI-FLAIR mismatch ASPECTS > 6 points may be possible to predict revascularization in patients with anterior circulation LVO.

A deep learning analysis of stroke onset time prediction and comparison to DWI-FLAIR mismatch.

INTRODUCTION: When time since stroke onset is unknown, DWI-FLAIR mismatch rating is an established technique for patient stratification. A visible DWI lesion without corresponding parenchymal hyperintensity on FLAIR suggests time since onset of under 4.5 h and thus a potential benefit from intravenous thrombolysis. To improve accuracy and availability of the mismatch concept, deep learning might be able to augment human rating and support decision-making in these cases. METHODS: We used unprocessed DWI and coregistered FLAIR imaging data to train a deep learning model to predict dichotomized time since ischemic stroke onset. We analyzed the performance of Group Convolutional Neural Networks compared to other deep learning methods. Unlabeled imaging data was used for pre-training. Prediction performance of the best deep learning model was compared to the performance of four independent junior and senior raters. Additionally, in cases deemed indeterminable by human raters, model ratings were used to augment human performance. Post-hoc gradient-based explanations were analyzed to gain insights into model predictions. RESULTS: Our best predictive model performed comparably to human raters. Using model ratings in cases deemed indeterminable by human raters improved rating accuracy and interrater agreement for junior and senior ratings. Post-hoc explainability analyses showed that the model localized stroke lesions to derive predictions. DISCUSSION: Our analysis shows that deep learning based clinical decision support has the potential to improve the accessibility of the DWI-FLAIR mismatch concept by supporting patient stratification.

DWI-FLAIR mismatch guided thrombolysis in patients without large-vessel occlusion: real-world data from a comprehensive stroke centre.

Introduction: A significant proportion of ischaemic stroke patients present with unknown symptom onset time. DWI-FLAIR mismatch on MRI can help to identify those eligible for thrombolysis. We set out to analyse the short-term efficacy and safety of thrombolysis in a real-world setting. Methods: A retrospective single-centre observational study was conducted. We collected data between January 2017 and April 2020. Patients with a large vessel occlusion (LVO) were excluded. Outcomes were compared between thrombolysed patients and those who did not receive alteplase due to lack of DWI-FLAIR mismatch or other contraindications. We analysed baseline and discharge NIHSS scores for efficacy and defined good outcome as any neurological improvement (ANI) on the NIHSS. In terms of safety, the presence and severity of intracerebral haemorrhage on follow-up imaging was analysed, and mortality at 90 days assessed. Results: Seventy-one patients were included in this study, of whom 29 received thrombolysis. Significantly more patients had ANI in the thrombolysed group (OR, 3.16; 95% CI, 1.178-8.479; p = 0.020). In a multivariable logistic regression analysis, only thrombolysis correlated with ANI (OR, 3.051; 95% CI, 1.135-8.206; p = 0.027). Two thrombolysed patients suffered intracerebral haemorrhage (6.90%), of whom one was symptomatic and eventually fatal. We did not find a significant difference in 90-day mortality between the two groups (OR, 0.81, 95% CI, 0.134-4.856; p = 1.000). Conclusions: Our real-world data demonstrate that thrombolysis based on DWI-FLAIR mismatch in patients without LVO has an early beneficial effect. The rate of intracerebral haemorrhage was similar to this complication reported in large thrombolysis trials with known onset times.

Radiomic signature of DWI-FLAIR mismatch in large vessel occlusion stroke.

BACKGROUND AND PURPOSE: Ischemic diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch may be useful in guiding acute stroke treatment decisions given its relationship to onset time and parenchymal viability; however, it relies on subjective grading. Radiomics is an emerging image quantification methodology that may objectively represent continuous image characteristics. We propose a novel radiomics approach to characterize DWI-FLAIR mismatch. METHODS: Ischemic lesions were visually graded for FLAIR positivity (absent, subtle, obvious) among consecutive large vessel occlusion stroke patients who underwent hyperacute MRI. Radiomic features were extracted from within the lesions on DWI and FLAIR. The DWI-FLAIR mismatch radiomics signature was built with features systematically selected by a cross-validated ElasticNet linear regression model of mismatch. RESULTS: We identified 103 patients with mean age 68 ± 16 years; 63% were female. FLAIR hyperintensity was absent in 25%, subtle in 55%, and obvious in 20%. Inter-rater agreement for visual grading was moderate (Κ = .58). The radiomics signature of DWI-FLAIR mismatch included native FLAIR histogram kurtosis and local binary pattern-filtered FLAIR gray-level cluster shade; both correlated with visual grading (ρ = -.42, p < .001 and ρ = .40, p < .001, respectively). CONCLUSIONS: Radiomics can describe DWI-FLAIR mismatch and may provide objective, continuous biomarkers for infarct evolution using clinical-grade images. These novel biomarkers may prove useful for treatment decisions and future research.

Hyperintense acute reperfusion marker associated with hemorrhagic transformation in the WAKE-UP trial.

INTRODUCTION: Hyperintense acute reperfusion marker (HARM) is an indicator of early disruption of the blood-brain-barrier. Our aim was to investigate the incidence of HARM in patients with a diffusion weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch and determine the association between this marker and hemorrhagic complications as well as clinical outcome. PATIENTS AND METHODS: We included patients from the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial who underwent baseline perfusion weighted imaging (PWI). HARM was defined as a hyperintense signal in the cerebrospinal fluid space on FLAIR imaging at 24 h after baseline imaging. We compared baseline characteristics in patients with and without HARM and investigated the association between HARM and any hemorrhagic transformation (HT) and parenchymal hematoma (PH) in a multivariate logistic regression. We also explored HARM as an independent predictor of poor outcome, defined as a modified Rankin Scale of 3-6 at 90 days. RESULTS: HARM was present in 14 of 223 (6%) patients with a DWI-FLAIR mismatch and baseline characteristics were similar in patients with vs without HARM. HARM showed an independent relationship with any HT (OR 6.67; 95%CI 1.72-26.58) and any PH (OR 6.92; 95%CI 1.34-29.49). The rate of HARM was similar in patients with good and poor outcome (5%, p = 0.90). CONCLUSION: In the WAKE-UP trial, the incidence of HARM was only 6% at 24 h. An association was present between HARM and hemorrhagic complications, but no relationship with functional outcome was observed.