MRI Assessment of Brain Frailty and Clinical Outcome in Patients With Acute Posterior Perforating Artery Infarction.

BACKGROUND: Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. PURPOSE: To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. STUDY TYPE: Prospective. POPULATION: One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. ASSESSMENT: Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. RESULTS: Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). DATA CONCLUSION: Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Deep medullary vein damage correlates with small vessel disease in small vessel occlusion acute ischemic stroke.

OBJECTIVES: We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. METHODS: The DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. RESULTS: We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. CONCLUSION: The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. CLINICAL RELEVANCE STATEMENT: The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. KEY POINTS: • The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

Arterial Spin Labeling-Based MRI Estimation of Penumbral Tissue in Acute Ischemic Stroke.

BACKGROUND: Arterial spin labeling (ASL) has shown potential for the assessment of penumbral tissue in patients with acute ischemic stroke (AIS). The postlabeling delay (PLD) parameter is sensitive to arterial transit delays and influences cerebral blood flow measurements. PURPOSE: To assess the impact of ASL acquisition at different PLDs for penumbral tissue quantification and to compare their performance regarding assisting patient selection for endovascular treatment with dynamic susceptibility contrast MRI (DSC-MRI) as the reference method. STUDY TYPE: Retrospective. POPULATION: A total of 53 patients (59.98 ± 12.60 years, 32% women) with AIS caused by internal carotid or middle cerebral artery occlusion. FIELD STRENGTH/SEQUENCE: A 3-T, three-dimensional pseudo-continuous ASL with fast-spin echo readout. ASSESSMENT: Hypoperfusion volume was measured using DSC-MRI and ASL with PLDs of 1.500 msec and 2.500 msec, respectively. Eligibility for endovascular treatment was retrospectively determined according to the imaging criteria of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial (DEFUSE 3). STATISTICAL TESTS: Kruskal-Wallis tests, Bland-Altman plots, Cohen's kappa, and receiver operating characteristic analyses were used. The threshold for statistical significance was set at P Ë‚ 0.05. RESULTS: Hypoperfusion volume for ASL with a PLD of 1.500 msec was significantly larger than that for DSC-MRI, while the hypoperfusion volume for a PLD of 2.500 msec was not significantly different from that of DSC-MRI (P = 0.435). Bland-Altman plots showed that the mean volumetric error between the hypoperfusion volume measured by DSC-MRI and ASL with PLDs of 1.500/2.500 msec was -107.0 mL vs. 4.49 mL. Cohen's kappa was 0.679 vs. 0.773 for DSC-MRI and ASL, respectively, with a PLD of 1.500/2.500 msec. The sensitivity and specificity for ASL with a PLD of 1.500/2.500 msec in identifying patients eligible for treatment were 89.74% vs. 97.44% and 92.86% vs. 64.29%, respectively. DATA CONCLUSION: In AIS, PLDs for ASL acquisition may have a considerable impact on the quantification of the hypoperfusion volume. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Severity of Intracranial Large Artery Disease Correlates With Cerebral Small Vessel Disease.

BACKGROUND: Small vessel disease (SVD) shares common vascular risk factors with large artery disease (LAD). However, little is known about the relationship between intracranial artery stenosis and SVD burden. PURPOSE: To investigate whether SVD burden correlates with severity of intracranial LAD. STUDY TYPE: Retrospective. POPULATION: Five hundred and sixteen patients with LAD of arterial circulation were enrolled from one hospital, including 384 males (59 ± 11 years) and 132 females (60 ± 12 years). FIELD STRENGTH/SEQUENCE: 3 T. T1 -weighted fast spin echo (T1 W FSE), T2 W FSE, T2 fluid attenuated inversion recovery, diffusion-weighted imaging, susceptibility-weight imaging, and time-of-flight magnetic resonance angiography. ASSESSMENT: The LAD was divided into mild stenosis (<30%), moderate stenosis (30%-69%), and severe stenosis (≥70%). The Standard for Reporting Vascular Changes on Neuroimaging criteria was used to rate the SVD burden according to the level of white matter hyperintensity (WMH), perivascular space (PVS), cerebral microbleed (CMB), and lacunes. STATISTICAL TESTS: Lilliefors test, ANOVA, chi-squared test, Mann-Whitney U test, Wilcoxon signed rank test, Bonferroni test, Spearman's correlation, logistic regression, and Cohen's kappa test. RESULTS: The grade scores for centrum semiovale PVS (CS-PVS) were positively correlated with the degree of stenosis (R = 0.413), whereas the presence of severe basal ganglia PVS (BG-PVS) was associated with CMB (R = 0.508), lacunes (R = 0.365), and severe WMH (R = 0.478). In multivariate analysis, severe CS-PVS (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.9-4.8) and lacunes (aOR, 2.1; 95% CI, 1.3-3.4) were associated with severe stenosis of LAD. In addition, CS-PVS was related to severe stenosis in a dose-dependent manner: when CS-PVS score was 3 and 4, the aORs of severe stenosis were 1.9 and 7.7, respectively. DATA CONCLUSION: The severity of LAD in anterior circulation is associated with SVD burden, which suggests that different SVD burden may be used for risk stratification in LAD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

FLAIR vessel hyperintensities predict functional outcomes in patients with acute ischemic stroke treated with medical therapy.

OBJECTIVES: The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. METHODS: Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. RESULTS: Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. CONCLUSION: FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. KEY POINTS: • FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.

Association of fluid-attenuated inversion recovery vascular hyperintensity with ischaemic events in internal carotid artery or middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Individuals with intracranial artery occlusion have high rates of ischaemic events and recurrence. It has been challenging to identify patients who had high-risk stroke using a simple, valid and non-invasive screening approach. This study aimed to investigate whether fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH), a specific imaging sign on the FLAIR sequence, could be a predictor of ischaemic events in a population with internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. METHODS: We retrospectively analysed 147 patients (mean 60.43±12.83 years) with 149 lesions, including 37 asymptomatic and 112 symptomatic cases of ICA or MCA occlusion. Symptomatic occlusion was considered if ischaemic events were present in the relevant territory within 90 days. FVH Alberta Stroke Program Early Computed Tomography Score (FVH-ASPECTS: 0-7, with 0 indicating absence of FVH and 7 suggesting prominent FVH) and collateral circulation grade were assessed for each participant. Multivariable logistic regression analysis was performed to detect independent markers associated with symptomatic status. RESULTS: A lower FVH-ASPECTS was associated with a more favourable collateral circulation grade (rho=-0.464, p<0.0001). The FVH-ASPECTS was significantly lower in the asymptomatic occlusion group than in the symptomatic occlusion group (p<0.0001). FVH-ASPECTS (Odd ratio, 2.973; 95% confidence interval, 1.849 to 4.781; p<0.0001) was independently associated with symptomatic status after adjustment for age, sex, lesion location and collateral circulation grade in the multivariate logistic regression. The area under the curve was 0.861 for the use of FVH-ASPECTS to identify symptomatic occlusion. CONCLUSIONS: The ability to discriminate symptomatic from asymptomatic occlusion suggests that FVH may be a predictor of stroke. As a simple imaging sign, FVH may serve as a surrogate for haemodynamic impairments and can be used to identify high-risk stroke cases early in ICA or MCA occlusion.

Small vessel disease burden predicts functional outcomes in patients with acute ischemic stroke using machine learning.

AIMS: Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS). METHODS: We enrolled 398 small-vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis. RESULTS: In the feature evaluation of SVO-AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO-AIS, SVD performed better than regular clinical data, which is the opposite of LAA-AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO-AIS. [0.91 (0.84-0.97)]. CONCLUSIONS: Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO-AIS patients' prognosis.

Collateral-Core Ratio as a Novel Predictor of Clinical Outcomes in Acute Ischemic Stroke.

The interaction effect between collateral circulation and ischemic core size on stroke outcomes has been highlighted in acute ischemic stroke (AIS). However, biomarkers that assess the magnitude of this interaction are still lacking. We aimed to present a new imaging marker, the collateral-core ratio (CCR), to quantify the interaction effect between these factors and evaluate its ability to predict functional outcomes using machine learning (ML) in AIS. Patients with AIS caused by anterior circulation large vessel occlusion (LVO) were recruited from a prospective multicenter study. CCR was calculated as collateral perfusion volume/ischemic core volume. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. An ML model was built and tested with a tenfold cross-validation using nine clinical and four imaging variables with mRS score 3-6 as unfavorable outcomes. Among 129 patients, CCR was identified as the most important variable. The prediction model incorporating clinical factors, ischemic core volume, collateral perfusion volume, and CCR showed better discriminatory power in predicting unfavorable outcomes than the model without CCR (mean C index 0.853 ± 0.108 versus 0.793 ± 0.133, P = 0.70; mean net reclassification index 52.7% ± 32.7%, P < 0.05). When patients were divided into two groups based on their CCR value with a threshold of 0.73, unfavorable outcomes were significantly more prevalent in patients with CCR ≤ 0.73 than in those with CCR > 0.73. CCR is a robust predictor of functional outcomes, as identified by ML, in patients with acute LVO. The prediction model that incorporated CCR improved the model's ability to identify unfavorable outcomes. ClinicalTrials.gov Identifier: NCT02580097.