Shenqiang Yan

Extensive cerebral microbleeds predict parenchymal haemorrhage and poor outcome after intravenous thrombolysis

Purpose Thrombolysis-related haemorrhagic transformation (HT) subtypes may have different prognostic implications. We aimed to analyse the impact of cerebral microbleeds (CMBs) burden on HT subtypes and outcome after intravenous thrombolysis. Methods We retrospectively examined clinical and radiological data from 333 consecutive patients with acute ischaemic stroke who underwent susceptibility-weighted imaging before intravenous thrombolysis. Logistic regression analysis was used to determine the impact of CMBs on HT subtypes and neurological outcome. Results We observed 596 CMBs in 119 (39.7%) patients on initial gradient-recalled echo scans. HT occurred in 88 (29.3%) patients, among which 62 were haemorrhagic infarction and 26 were parenchymal haemorrhage (PH). Logistic regression analysis indicated that the presence of extensive (≥3) CMBs was independently associated with PH (OR 6.704; 95% CI 2.054 to 21.883; p=0.002) and poor clinical outcome (OR 2.281; 95% CI 1.022 to 5.093; p=0.044). Conclusions The presence of extensive (≥3) CMBs increased the risk of PH 24 h after intravenous thrombolysis, and predicted poor clinical outcome independently.

Thrombus Length Estimation on Delayed Gadolinium–Enhanced T1

Background and Purpose— Previous studies revealed a close relationship between thrombus length and recanalization rate after intravenous thrombolysis (IVT). As a novel approach, we prospectively adjusted the order of sequence acquisition to obtain delayed gadolinium–enhanced T1 (dGE-T1) and thereby assess thrombus length on dGE-T1 to evaluate its predictive value for recanalization after IVT. Methods— We reviewed prospectively collected clinical and imaging data from acute ischemic stroke patients with middle cerebral artery occlusion who underwent multimodal magnetic resonance imaging before and 24 hours after IVT. Perfusion-weighted imaging was performed followed by conventional T1. We measured thrombus length on dGE-T1 and examined its association with middle cerebral artery recanalization. Results— Of the included 74 patients, the median age was 66 years and 28 (37.8%) were women. Thrombus length was 8.18±4.56 mm on dGE-T1, which was an acceptable predictor for no recanalization (odds ratio, 1.196; 95% confidence interval, 1.015–1.409; P=0.033), with a receiver–operator characteristic of 0.732 (95% confidence interval, 0.619–0.845; P=0.001). The optimal cut-off point was identified at 6.77 mm, which yielded a sensitivity of 77.8%, a specificity of 57.9%, and an odds ratio of 4.81 (95% confidence interval, 1.742–13.292; P=0.002). Moreover, no one achieved recanalization after IVT when length of thrombus exceeded 14 mm on dGE-T1. Conclusions— The dGE-T1, obtained by simply adjusting scanning order in multimodal magnetic resonance imaging protocol, is a useful tool for thrombus length estimation and middle cerebral artery recanalization prediction after IVT.

New Microbleeds After Thrombolysis: Contiguous Thin-Slice 3T MRI

AbstractWe aimed to determine the frequency of new microbleeds after intravenous thrombolysis using contiguous thin-slice 3T magnetic resonance imaging. We retrospectively examined clinical and imaging data from 121 consecutive acute ischemic stroke patients who underwent magnetic resonance imaging before and 24 hours after intravenous thrombolysis. Of the included patients, 44 (36.4%) were women, with a median age of 69 years (range, 35–94 years). A total of 363 baseline microbleeds were observed in 57 patients and 8 new microbleeds in 6 patients. Multiple regression analysis indicated that baseline infarct volume (odds ratio, 1.556/10 mL; 95% CI, 1.017–2.379; P = 0.04) and systolic blood pressure (odds ratio, 1.956/10 mm Hg; 95% CI, 1.056–3.622; P = 0.03), but not the presence of baseline microbleeds, were independently associated with new microbleeds. The frequency of neither symptomatic intracranial hemorrhage nor remote hemorrhage or any hemorrhagic transformation was different between patients with and without new microbleeds (0.0% vs 1.7%, P > 0.99; 0.0% vs 1.7%, P > 0.99; 50.0% vs 28.7%, P =0.36). New microbleeds developed rapidly 24 hours after intravenous thrombolysis. The significance of these new microbleeds and their effect on cognitive and functional outcome merits further investigation.

Brain iron deposition in white matter hyperintensities: a 3-T MRI study

Iron accumulation has been implicated in the pathogenesis of demyelinating diseases. Therefore, we hypothesized that abnormal high cerebral iron deposition may be involved in the development of white matter hyperintensities (WMHs). We used R2* relaxometry to assess whether iron levels in different brain regions correlate with the severity of WMHs. This technique has been recently validated in a postmortem study to demonstrate in vivo brain iron accumulation in a quantitative manner. Fifty-two consecutive WMH patients and 30 healthy controls with 3-T magnetic resonance imaging (MRI) were reviewed in this study. We measured WMH volume (as a marker of the severity of WMHs) on MRI, and the transverse relaxation rate R2*, as an estimate of iron content in seven brain regions. We found that R2* in globus pallidus was associated with WMH volume after adjusting for sociodemographic variables (partial correlation coefficient = 0.521, P < 0.001) and in a multivariate analysis adjusted for common vascular risk factors (partial correlation coefficient = 0.572, P = 0.033). Regional R2* in globus pallidus was also significantly higher in WMHs than in controls (P = 0.042). Iron content in globus pallidus, as assessed by R2* relaxometry, is independently linked to the severity of WMHs in our cohort of patients, suggesting that iron deposition in the brain may play a role in the pathogenesis of WMHs. This may provide prognostic information on patients with WMHs and may have implications for therapeutic interventions in WMHs.

Increased visibility of deep medullary veins in leukoaraiosis: a 3-T MRI study

Cerebral venous collagenosis has been implicated in leading to white matter hyperintensities (WMHs) via venous ischemia. We sought to determine whether cerebral venous dilation or ischemia correlate with the severity of WMHs by quantitative in vivo imaging techniques. This was an investigator-initiated prospective single-center study. We reviewed clinical, laboratory data from 158 consecutive WMHs patients and 50 controls, and measured the number of voxels of deep medullary veins (DMVs) on susceptibility-weighted image and assessed the WMH volume (as a marker of the severity of WMHs) on a 3-T magnetic resonance system. We then performed the logistic-regression analysis and partial Pearson’s correlation analysis to examine the association between the venous voxel count and WMH volume. The number of voxels of DMVs was significantly higher in WMHs than in controls. Increased number of voxels of DMVs was independently associated with both WMH volume of the whole brain and coregistered regional WMH volume after adjusting for age and number of lacunes. Our study indicates that cerebral deep venous insufficiency or ischemia play a role in the pathogenesis of WMHs, which may provide prognostic information on patients with WMHs and may have implications for therapeutic interventions.

Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion

Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden’s Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Phenotypic and mutational spectrum in patients from mainland China

Aims: To analyze the NOTCH3 gene mutations in patients from mainland China clinically suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and evaluate large intracranial arteries in CADASIL patients. Methods: We performed clinical, neuroimaging and NOTCH3 gene (exons 2–23) examinations in 47 subjects from 34 families. Large intracranial arteries were assessed using magnetic resonance angiography (MRA) in 19 cases with NOTCH3 gene variants. Results: Screening of exons 3 and 4 identified six different known mutations in eight families and two novel mutations in two families. Further screening of the remaining exons identified p.R1175W, a variant of unknown significance. The incidence of NOTCH3 mutations was 29.4% (10/34). Five cases with NOTCH3 mutations showed intracranial atherosclerosis. One patient developed cerebral infarction due to left middle cerebral artery occlusion (M2 segment). Conclusions: The NOTCH3 mutation spectrum in our group was diverse and consistent with those in Caucasians but differed from those in Korea and Taiwan. The screening strategy used in Caucasian populations can be applied to mainland Chinese patients. Atherosclerosis of the large intracranial arteries involvement does not exclude CADASIL diagnosis.

Morphology of Susceptibility Vessel Sign Predicts Middle Cerebral Artery Recanalization After Intravenous Thrombolysis

Background and Purpose— We aimed to evaluate the predictive value of susceptibility vessel sign (SVS) burden and morphology in middle cerebral artery recanalization. Methods— We retrospectively examined clinical and imaging data from 72 consecutive patients with acute ischemic stroke with middle cerebral artery occlusion and examined the association of recanalization with SVS length and shape. Results— None of the patients with a middle cerebral artery SVS >20 mm in length achieved recanalization. For patients with a relatively short SVS (length <20 mm), irregular shape was a strong independent predictor for no recanalization (odds ratio, 6.891; 95% confidence interval, 1.441–32.950; P=0.016). Conclusions— Irregular shape and long length (>20 mm) of SVS decrease the potential to recanalize the occluded middle cerebral artery with intravenous thrombolysis.

Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause.

Background and Purpose— The extent of blooming artifact may reflect the amount of paramagnetic material. We thus assessed the overestimation ratio of susceptibility vessel sign (SVS) on susceptibility-weighted imaging, defined as the extent of SVS width beyond the lumen and examined its value for predicting the stroke cause in acute ischemic stroke patients. Methods— We included consecutive acute ischemic stroke patients with proximal large artery occlusion who underwent both susceptibility-weighted imaging and time-of-flight magnetic resonance angiography within 8 hours poststroke onset. We calculated the length, width, and overestimation ratio of SVS on susceptibility-weighted imaging and then investigated their values for predicting the stroke cause, respectively. Results— One-hundred eleven consecutive patients (72 female; mean age, 66.6±13.4 years) were enrolled, among whom 39 (35.1%) were diagnosed with cardiogenic embolism, 43 (38.7%) with large artery atherosclerosis, and 29 (26.1%) with undetermined cause. The presence, length, width, and overestimation ratio of SVS were all independently associated with the cause of cardiogenic embolism after adjusting for baseline National Institute of Health Stroke Scale and infarct volume. After excluded patients with undetermined cause, the sensitivity and specificity of overestimation ratio of SVS for cardiogenic embolism were 0.971 and 0.913; for the length of SVS, they were 0.629 and 0.739; for the width of SVS, they were 0.829 and 0.826, respectively. Conclusions— The overestimation ratio of SVS can predict cardiogenic embolism, with both high sensitivity and specificity, which can be helpful for the management of acute ischemic stroke patients in hyperacute stage.

Optimal Magnetic Resonance Perfusion Thresholds Identifying Ischemic Penumbra and Infarct Core: A Chinese Population-based Study

To validate whether the optimal magnetic resonance perfusion (MRP) thresholds for ischemic penumbra and infarct core, between voxel and volume‐based analysis, are varied greatly among Chinese acute ischemic stroke patients.