Jianzhong Sun

Susceptibility-Diffusion Mismatch Predicts Thrombolytic Outcomes: A Retrospective Cohort Study

The benefit of thrombolytic therapy was assessed in 54 patients with a mismatch between infarct core as seen on DWI and penumbra as seen on SWI. Favorable outcomes were significantly higher in patients with DWI-SWI mismatch than in those without it. The accuracy of the DWI-SWI mismatch for predicting good outcome was higher than that for the more traditional DWI-perfusion mismatch. BACKGROUND AND PURPOSE: Asymmetric hypointensity of cerebral veins on susceptibility-weighted imaging has been shown to indirectly reflect tissue hypoxia after cerebral ischemia. We therefore investigated whether patients with prominent asymmetry of the cerebral veins on SWI and a relatively small diffusion-weighted imaging lesion (SWI-DWI mismatch), representing the presence of salvageable tissue, were more likely to benefit from thrombolytic therapy. MATERIALS AND METHODS: We conducted a retrospective study of the anterior circulation of patients with ischemic stroke with SWI/DWI acquired before thrombolysis. The asymmetry index was defined as the ratio of cerebral vein voxel count between the ischemic and normal hemisphere on the SWI phase map. We defined SWI-DWI mismatch as an asymmetry index score of ≥1.75 with a DWI lesion volume of ≤25 mL. Favorable outcome was defined as modified Rankin Scale 0–2 at 3 months. Univariate and multivariate logistic regression analyses were used to examine the association between the mismatch profile and favorable outcome. RESULTS: Fifty-four patients undergoing thrombolytic treatment were enrolled in this study. The rate of favorable outcome was significantly higher among patients with baseline SWI-DWI mismatch compared with those without (78% versus 44%; adjusted odds ratio, 6.317; 95% CI, 1.12–35.80; P = .037). Patients with SWI-DWI mismatch were also more likely to have a favorable outcome from reperfusion (91% versus 43%, P = .033) or recanalization (100% versus 40%, P = .013). The accuracy of SWI-DWI mismatch for predicting favorable outcome was higher than that of perfusion-diffusion mismatch (63% versus 48.1%). CONCLUSIONS: The presence of SWI-DWI mismatch may identify patients with ischemia who would benefit from early reperfusion therapy.

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.

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.

Prominence of Medullary Veins on Susceptibility-Weighted Images Provides Prognostic Information in Patients with Subacute Stroke

BACKGROUND AND PURPOSE: The demonstration of prominent medullary veins in the deep white matter ipsilateral to acute ischemic stroke has been shown to predict poor clinical outcome. We have investigated the prognostic implications of prominent medullary veins in patients with subacute stroke who present outside the therapeutic window for revascularization therapy. MATERIALS AND METHODS: Forty-three consecutive patients with ischemic stroke in the middle cerebral artery territory presenting within 3–7 days of ictus were enrolled. The presence of prominent medullary veins in the periventricular white matter of the ipsilateral and contralateral medullary vein hemispheres was recorded. Perfusion-weighted imaging was used to calculate differences in hemispheric CBF from corresponding areas. Clinical outcome was classified as good if the modified Rankin Scale score was <3. RESULTS: Prominent medullary veins were observed in 24/43 patients with 14 ipsilateral medullary veins and 10 contralateral medullary veins. The ipsilateral medullary vein was independently associated with poor outcome (odds ratio, 11.19; P = .046). The contralateral medullary vein was not independently predictive of outcome but was significantly more common in patients with good outcome (90.0% contralateral medullary veins). A mean 64.5% decrease and a 52.4% increase of differences in hemispheric CBF were found in ipsilateral medullary veins and contralateral medullary veins, respectively. CONCLUSIONS: The ipsilateral medullary vein was a significant predictive biomarker of poor clinical outcome after stroke and was associated with hypoperfusion. The contralateral medullary vein was associated with good clinical outcome, and we hypothesize that prominent contralateral medullary veins indirectly reflect increased CBF in the ipsilateral hemisphere due to spontaneous recanalization or collateral flow.

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.

Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.

Docosahexaenoic acid attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal cerebral ischemia in rats.

Hemorrhagic transformation (HT) is a feared complication of cerebral ischemic infarction, especially following the use of thrombolytic therapy. In this study, we examined whether docosahexaenoic acid (DHA; 22:6n-3), an omega-3 essential fatty acid family member, can protect the brain from injury and whether DHA can decrease the risk of HT enhanced by hyperglycemia after focal ischemic injury. Male Sprague-Dawley rats were injected with 50% dextrose (6ml/kg intraperitoneally) to induce hyperglycemia 10min before 1.5h of filament middle cerebral artery occlusion (MCAO) was performed. Treatment with DHA (10mg/kg) 5min before reperfusion reduced HT and further improved the 7-day neurological outcome. It also reduced infarct volume, which is consistent with the restricted DWI and T2WI hyperintensive area. Reduced Evans Blue extravasation and increased expression of collagen IV indicated the improved integrity of the blood-brain barrier (BBB) in DHA-treated rats. Moreover, DHA reduced the expression of the intercellular adhesion molecule-1 (ICAM-1) in the ischemic injured brain. Therefore, we conclude that DHA attenuated hyperglycemia-enhanced HT and improved neurological function by preserving the integrity of BBB and reducing inflammation.

Rosiglitazone attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal ischemia in rats

Hemorrhagic transformation (HT) has been claimed to represent the most feared complication of treatment with intravenous tissue plasminogen activator (t-PA) therapy. In this study, we tested the effect of rosiglitazone on HT in a rat focal cerebral ischemia model. Male Sprague-Dawley rats received an injection of 50% dextrose (6ml/kg intraperitoneally) and were subjected to middle cerebral artery occlusion (MCAO) 10 min later, with the regional cerebral blood flow monitored in vivo by laser-Doppler-flowmetry. Two groups were included: rosiglitazone treatment and vehicle group. In the treatment group, after 1.5h of ischemia, rosiglitazone (2mg/kg) was administered at the onset of reperfusion. Neurobehavioral scores, infarct volume, hemoglobin leakage, hemorrhage rate, the expression of collagen IV and glucose transporter 1 (GLUT1) were measured at 24h after ischemia. Rosiglitazone improved neurobehavioral deficits, reduced infarct volume and hemorrhage rate, and inhibited hemoglobin leakage, when compared with the vehicle group. In addition, it increased the expression of collagen IV and GLUT1 compared to the vehicle group. Our results suggest that rosiglitazone attenuated the hyperglycemia-induced HT after MCAO, possibly by preservation of GLUT1 expression.

Visualization of the internal cerebral veins on MR phase-sensitive imaging: comparison with 3D gadolinium-enhanced MR venography and fast-spoiled gradient recalled imaging.

SUMMARY: The purpose of this article is to compare the visualization quality of ICV and their tributaries on PSI-MRV, 3D CE-MRV, and 3D CE-FSPGR. PSI-MRV has been shown to delineate the ICV, TSV, SV, anterior caudate nucleus veins, and medial atrial veins effectively. Due to its advantages of no contrast material injection, acceptable examination times, and no arterial contamination, PSI-MRV should be considered in the evaluation of deep cerebral veins.

The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis.

The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626–0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820–1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke.