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Purpose: The purpose of this study was to assess the prognostic value of vascular hyperintensities on FLAIR images (VHF) at admission MRI in patients with acute ischemic stroke (AIS) achieving successful recanalization after mechanical thrombectomy., Materials and Methods: Patients with AIS treated by mechanical thrombectomy following admission MRI from the single-center HIBISCUS-STROKE cohort were assessed for eligibility. VHF were categorized using a four-scale classification and were considered poor when grade < 3 (i.e., absence of distal VHF). Recanalization was considered successful when modified thrombolysis in cerebral infarction score was ≥ 2B Functional outcome was considered poor if modified Rankin scale (mRS) at three months was > 2. Univariable and multiple variable logistic regressions were performed to identify factors associated with poor functional outcome despite successful recanalization., Results: A total of 108 patients were included. There were 65 men and 43 women with a median age of 70.5 years (interquartile range: 55.0, 81.0; age range: 22.0-93.0 years). Among them, 39 subjects (36.1%) had poor functional outcome at three months. Univariable logistic regressions indicated that poorly extended VHF (VHF grade < 3) were associated with a poor functional outcome (P = 0.008) as well as age, hypertension and diabetes, baseline National Institute of Health Stroke Scale (NIHSS) score, pre-stroke mRS, lack of intravenous thrombolysis, cerebral microangiopathy and the presence of microbleeds. Multivariable analysis confirmed that poor VHF status was independently associated with a poor functional outcome (odds ratio [OR], 4.26; 95% confidence interval [CI]: 1.55-12.99; P = 0.007) in combination with hypertension (OR, 1.25; 95% CI: 0.87-1.85; P = 0.02), baseline NIHSS score (OR, 1.09; 95% CI: 1.04-1.20; P = 0.03), pre-stroke mRS (OR, 2.05; 95% CI: 1.07-4.61; P = 0.05) and lack of intravenous thrombolysis (OR, 0.23; 95% CI: 0.08-0.61; P = 0.004)., Conclusion: Poorly extended VHF (grade <3) at admission MRI are associated with a poor functional outcome at three months despite successful recanalization by mechanical thrombectomy., (Copyright © 2023 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage., Methods: The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding., Findings: Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group., Interpretation: Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage., Funding: French Ministry of Health., Competing Interests: Declarations of interests LP-D reports speaker's honoraria and travel fees from Bioprojet, Jazz Pharmaceuticals, Roche, and UCB. SB reports speaker's honoraria and travel fees from ESAI, Livanona, UCB, and Angelini Pharma. SR reports speaker's honoraria and travel fees from UCB, ESAI, Angelini Pharma, Zogenix, and Gaoma Therapeutics. LD reports speaker's honoraria and travel fees from Alexion, Boehringer Ingelheim, Pfizer, and Servier. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT., Methods: Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0-3 or equal to pre-stroke mRS at 3 months., Results: Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36-0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83-0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32-10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08-0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization., Conclusions: Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

The purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two-photon intravital microscopy shows NanoGd internalization by activated CX3CR1-GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X-ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd-enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back-to-back with MRI. Furthermore, using a gadolinium-based rather than an iron-based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period., Methods: We conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods., Results: A total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period [55 (54.5%) vs 74 (69.2%); p = 0.03]. The volume of MT remains stable over the two periods [72 (71.3%) vs 65 (60.8%); p = 0.14], but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260]; p < 0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410]; p < 0.01)., Conclusions: Our study showed a decrease in the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.

Background: Predictive maps of the final infarct may help therapeutic decisions in acute ischemic stroke patients. Our objectives were to assess whether integrating the reperfusion status into deep learning models would improve their performance, and to compare them to current clinical prediction methods., Methods: We trained and tested convolutional neural networks (CNNs) to predict the final infarct in acute ischemic stroke patients treated by thrombectomy in our center. When training the CNNs, non-reperfused patients from a non-thrombectomized cohort were added to the training set to increase the size of this group. Baseline diffusion and perfusion-weighted magnetic resonance imaging (MRI) were used as inputs, and the lesion segmented on day-6 MRI served as the ground truth for the final infarct. The cohort was dichotomized into two subsets, reperfused and non-reperfused patients, from which reperfusion status specific CNNs were developed and compared to one another, and to the clinically-used perfusion-diffusion mismatch model. Evaluation metrics included the Dice similarity coefficient (DSC), precision, recall, volumetric similarity, Hausdorff distance and area-under-the-curve (AUC)., Results: We analyzed 109 patients, including 35 without reperfusion. The highest DSC were achieved in both reperfused and non-reperfused patients (DSC = 0.44 ± 0.25 and 0.47 ± 0.17, respectively) when using the corresponding reperfusion status-specific CNN. CNN-based models achieved higher DSC and AUC values compared to those of perfusion-diffusion mismatch models (reperfused patients: AUC = 0.87 ± 0.13 vs 0.79 ± 0.17, P < 0.001; non-reperfused patients: AUC = 0.81 ± 0.13 vs 0.73 ± 0.14, P < 0.01, in CNN vs perfusion-diffusion mismatch models, respectively)., Conclusion: The performance of deep learning models improved when the reperfusion status was incorporated in their training. CNN-based models outperformed the clinically-used perfusion-diffusion mismatch model. Comparing the predicted infarct in case of successful vs failed reperfusion may help in estimating the treatment effect and guiding therapeutic decisions in selected patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The significance of white matter hyperintensities (WMHs) in the setting of mechanical thrombectomy (MT) remains poorly documented. We assessed whether pre-existing WMHs burden was associated with baseline clinical and imaging factors and neurological outcome in patients undergoing MT., Methods: This retrospective single-center study included consecutive acute ischemic stroke (AIS) patients with stroke due to large vessel occlusion treated with MT. WMHs were assessed on baseline T2 fluid-attenuated inversion recovery magnetic resonance imaging. Neurological outcome was assessed at day 90 by the modified Rankin Scale (mRS). We analyzed the association between WMH burden and clinical and imaging factors by univariate and multivariate logistic regression analyses., Results: Between July 2013 and June 2019, 293 patients with anterior circulation AIS met the inclusion criteria. WMHs burden was not associated to baseline NIHSS score severity (OR 0.89, 95% CI 0.54-1.49, p = 0.66), poor collateral status, Higashida score < 3 (OR 1.5 95% CI 0.62-3.56, p = 0.36), higher DWI volume (OR 0.69, 95% CI 0.41-1.15, p = 0.16) or to a lower recanalization rate, TICI 0/2a (OR 0.98 95% CI 0.56-1.69, p = 0.95). WMHs severity did not influence the risk of parenchymal hemorrhage (OR 0.97 95% 0.26-3, p = 0.96). WMHs burden was not an independent predictor of poor outcome in multivariate analysis. The rate of futile recanalization in patients with TICI grades 2b and 3 according to mRs score at 3 months was not influenced by WMHs burden., Conclusions: WMHs burden does not seem to influence clinical outcome and imaging parameters in patients treated by MT.

In acute ischaemic stroke, identifying brain tissue at high risk of infarction is important for clinical decision-making. This tissue may be identified with suitable classification methods from magnetic resonance imaging data. The aim of the present study was to assess and compare the performance of five popular classification methods (adaptive boosting, logistic regression, artificial neural networks, random forest and support vector machine) in identifying tissue at high risk of infarction on human voxel-based brain imaging data. The classification methods were used with eight MRI parameters, including diffusion-weighted imaging and perfusion-weighted imaging obtained in 55 patients. The five criteria used to assess the performance of the methods were the area under the receiver operating curve (AUC roc ), the area under the precision-recall curve (AUC pr ), sensitivity, specificity and the Dice coefficient. The methods performed equally in terms of sensitivity and specificity, while the results of AUC roc and the Dice coefficient were significantly better for adaptive boosting, logistic regression, artificial neural networks and random forest. However, there was no statistically significant difference between the performances of these five classification methods regarding AUC pr , which was the main comparison metric. Machine learning methods can provide valuable prognostic information using multimodal imaging data in acute ischaemic stroke, which in turn can assist in developing personalized treatment decision for clinicians after a thorough validation of methods with an independent data set., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Purpose: Recent imaging developments have shown the potential of voxel-based models in assessing infarct growth after stroke. Many models have been proposed but their relevance in predicting the benefit of a reperfusion therapy remains unclear. We searched for a predictive model whose volumetric predictions would identify stroke patients who are to benefit from tissue plasminogen activator (t-PA)-induced reperfusion., Material and Methods: Forty-five cases were used to study retrospectively stroke progression from admission to end of follow-up. Predictive approaches based on various statistical models, predictive variables and spatial filtering methods were compared. The optimal approach was chosen according to the area under the precision-recall curve (AUPRC). The final lesion volume was then predicted assuming that the patient would or would not reperfuse. Patients, with an acute lesion of ≤50 ml and a predicted reduction in the presence of reperfusion >6 ml and >25% of the acute lesion, were classified as responders., Results: The optimal model was a logistic regression using the voxel distance to the acute lesion, the volume of the acute lesion and Gaussian-filtered MRI contrast parameters as predictive variables. The predictions gave a median AUPRC of 0.655, a median AUC of 0.976 and a median volumetric error of 8.29 ml. Nineteen patients matched the responder profile. A non-significant trend of improved reduction in NIHSS score (-42.8%, p = .09) and in lesion volume (-78.1%, p = 0.21) following reperfusion was observed for responder patients., Conclusion: Despite limited volumetric accuracy, predictive stroke models can be used to quantify the benefit of reperfusion therapies., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background and Purpose: Hemodynamic and metabolic impairment in intracranial atherosclerotic stenosis (ICAS) may promote stroke vulnerability particularly in borderzone areas. Perfusion and oxygen mapping magnetic resonance imaging (MRI) may provide useful information in this setting., Methods: In this pilot study, patients with symptomatic atherosclerotic anterior circulation stenosis ≥60%, without other sources of ischemic stroke, were included. High-resolution vessel wall MRI quantified the stenosis degree, and hemodynamic and metabolic impairment was assessed at baseline using dynamic susceptibility contrast perfusion and multiparametric quantitative blood-oxygen-level-dependent (mqBOLD) oxygenation MRI. All parameters were assessed within both hemispheres and in borderzone areas., Results: Forty-three subjects with intracranial artery narrowing were screened from November 2014 to January 2016. Eleven patients met the study criteria (mean ± standard deviation age = 64.4 ± 10.6 years, the mean degree of stenosis was 76.9 ± 23.4%). No interhemispheric differences were observed across oxygen (cerebral metabolic rate of oxygen and tissular saturation of oxygen) or perfusion (mean transit time, time to maximum, T max , normalized cerebral blood volume [nCBV], and normalized cerebral blood flow) parameters. A positive correlation was observed between the stenosis degree and ipsilateral nCBV (R = .77, P = .008). In addition, a significant increase in CBV was observed in anterior cortical borderzones ipsilateral to stenosis (nCBV = 7.20 ± 1.81 vs. 5.45 ± 1.40 mL/100 g, P = .02)., Conclusion: Symptomatic ICAS had no global impact on perfusion and oxygen mapping MRI at resting state. A significant increase in nCBV was found within anterior borderzone areas., (© 2019 by the American Society of Neuroimaging.)

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Objectives: The aim of the present study was to assess the association between collateral status and DWI-FLAIR mismatch in patients with acute ischemic stroke within the 4.5 h time-window., Methods: We analysed DWI, FLAIR, and PWI data in patients within 4.5 h after symptom onset from the I-KNOW European database. Collateral flow maps were graded by analyzing contrast 'staining' extent over the early, mid and late perfusion phases. ADC values, DWI lesion volume, and normalised perfusion parameters (CBV,Tmax) within DWI lesions were determined. Visibility of parenchymal hyperintensivty on FLAIR was evaluated ("FLAIR positive"), and DWI-FLAIR mismatch was assessed. Spontaneously reperfused regions were defined as voxels with Tmax <6 s within the DWI lesion. Final infarct size was assessed on day-30 FLAIR images., Results: Of the 168 patients included in I-KNOW database, 87 were eligible for this study. DWI-FLAIR mismatch was present in 69 patients. There was no difference between poor and good collaterals status according to age, sex, baseline NIHSS score, time to MRI and DWI lesion volume. Collateral status was significantly better in the FLAIR positive group (p = .001). Patients with poor collaterals had significantly increased Tmax (p = .005). Baseline DWI lesion volume and final lesion volume were significantly smaller in patients with good collateral status (p < .001 and 0.01, respectively)., Conclusions: We found that patients with early FLAIR lesion visibility have a better collateral status. This finding has implications for the management of stroke patients with unknown time-of-onset, and more widely should be considered in the current context of extending the therapeutic window., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Brain atrophy has shown a protective effect on the risk of early neurological deterioration (END) related to malignant edema in patients with hemispheric infarction but could be deleterious on the outcome., Aims: We aimed to assess whether brain atrophy has an impact on the risk of END and on the outcome in severe ischemic strokes after intravenous (IV) thrombolysis., Methods: From a prospective thrombolysis registry, 137 patients who had a National Institutes of Health Stroke Scale (NIHSS) ≥15, MRI at admission, and IV thrombolysis were included. Relative cerebral volume was calculated. END was defined as a ≥2-points deterioration 72-h NIHSS and a good outcome as a modified Rankin Scale (mRS) ≤2 at 3 months. A multiple logistic regression analysis with a stepwise backward procedure was performed., Results: END and a good outcome were observed, respectively, in 20 (14.6%) and 48 (37.5%) patients. In univariate analysis, predictors of END included age (p = 0.049), diabetes (p = 0.041), and parenchymal hemorrhage (p = 0.039). In multivariate analysis, age (p = 0.018) was significantly associated with END. Brain atrophy was not associated with END even in subgroup analysis according to the baseline infarct size. In univariate analysis, age (p = 0.003), prestroke mRS (p = 0.002), hypertension (p = 0.006), baseline NIHSS (p = 0.002), END (p = 0.002), proximal occlusion (p = 0.006), and recanalization at 24 h (p < 0.001) were associated with a good outcome. Only baseline NIHSS (p = 0.006) was associated with a good outcome after adjustment., Conclusions: We did not find any impact of brain atrophy on the risk of END and the outcome at 3 months in severe ischemic strokes after IV thrombolysis., (© 2018 S. Karger AG, Basel.)

High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

Background and Purpose: We sought to identify MRI factors associated with BBB changes at the acute stage of ischemic stroke., Methods: We analyzed BBB changes on admission and within 3 hours after the first scan. BBB changes was defined as the presence of leptomeningeal and parenchymal contrast enhancement on T1-weighted imaging. Tmax , CBV, and DWI lesion volume were assessed on baseline MRI. Clinical and MRI factors associated with BBB changes were assessed by univariate and multivariate logistic regressions analyses., Results: Forty-four patients were included. BBB changes on baseline MRI was observed in 2 of 44 patients (3%). BBB disruption on H3-MRI was present in 19 of 44 patients (43%). Hemodynamic status and baseline ischemic core size were not different between patients with or without BBB changes. BBB alteration on H3 MRI was strongly associated with FLAIR MRI sequence positivity, 16/19 patients (83%) P = .001., Conclusion: BBB changes are exceptional during the first 3 hours after stroke onset. Delayed BBB alteration was associated with FLAIR positivity mainly reflecting vasogenic edema., (Copyright © 2015 by the American Society of Neuroimaging.)

Background and Purpose: Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion criteria that predicts clinical outcome in ischemic stroke., Methods: Early reperfusion was assessed voxel-wise in 57 patients within 6 hours of symptom onset. The performance of the time to peak (TTP), the mean transit time (MTT), and the time to maximum of residue function (Tmax ) at various delays thresholds in predicting the neurological response (based on the National Institutes of Health Stroke Scale) and the functional outcome (modified Rankin scale ≤1) at 1 month were compared. A receiver operating characteristics (ROC) analysis determined the optimal extent of reperfusion. A novel unsupervised classification of reperfusion using group-based trajectory modeling (GBTM) was evaluated., Results: MTT had a lower performance than TTP and Tmax in predicting the neurological response (P = .008 vs. TTP and P = .006 vs. Tmax ) or the functional outcome (P = .0006 vs. TTP; P = .002 vs. Tmax ). No delay threshold had a significantly higher predictive value than another. The optimal percentage of reperfusion was dependent on the outcome scale (P < .001). The GBTM-based classification of reperfusion was closely associated with the clinical outcome and had a similar accuracy compared to ROC-based classification., Conclusions: TTP and Tmax should be preferred to MTT in defining early reperfusion. GBTM provided a clinically relevant reperfusion classification that does not require prespecified delay thresholds or clinical outcomes., (Copyright © 2015 by the American Society of Neuroimaging.)

Objectives: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size., Methods: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis., Results: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009)., Conclusions: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization., Classification of Evidence: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone., (© 2015 American Academy of Neurology.)

Background and Purpose: This study examines whether lesion shape documented on magnetic resonance diffusion-weighted imaging during acute stroke improves the prediction of the final infarct volume compared with lesion volume only., Methods: Diffusion-weighted imaging data and clinical information were retrospectively reviewed in 110 consecutive patients who underwent (n=67) or not (n=43) thrombolytic therapy for acute ischemic stroke. Three-dimensional shape analysis was performed on admission diffusion-weighted imaging data and 5 shape descriptors were developed. Final infarct volume was measured on T2-fluid-attenuated inversion recovery imaging data performed 30 days after stroke., Results: Shape analysis of acute ischemic lesion and more specifically the ratio of the bounding box volume to the lesion volume before thrombolytic treatment improved the prediction of the final infarct for patients undergoing thrombolysis (R(2)=0.86 in model with volume; R(2)=0.98 in model with volume and shape)., Conclusions: Our findings suggest that lesion shape contains important predictive information and reflects important environmental factors that might determine the progression of ischemia from the core., (© 2015 American Heart Association, Inc.)

Background and Purpose: Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization., Methods: The volume of cerebral tissue with CBV≤2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI., Results: Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score (P=0.002), acute diffusion-weighted imaging lesion volume (P=0.02), and thrombolysis (P=0.03), but not very low CBV (P=0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH (P=0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH., Conclusion: Very low CBV was the only independent predictor of PH in patients with acute stroke.

Objectives: This study sought to evaluate whether the therapeutic effects of an anti-inflammatory drug such as minocycline could be monitored by serial ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI in experimental stroke., Methods: Mice received a three-dose minocycline treatment (n = 12) or vehicle (n = 12) after permanent middle cerebral artery occlusion. USPIOs were administered 5 h post-surgery. MRI was performed before, 24 h and 48 h post-USPIO administration. MRI endpoints were the extent of signal abnormalities on R2 maps (=1/T2) and quantitative R2 changes over time (∆R2). Post-mortem brains were prepared either for immunohistology (n = 16) or for iron dosage (n = 8)., Results: As expected, treatment with minocycline significantly reduced infarct size, blood-brain barrier permeability and F4/80 immunostaining for microglia/macrophages. Areas of R2 maps > 35 ms(-1) also appeared significantly decreased in minocycline-treated mice (ANOVA for repeated measures, P = 0.017). There was a fair correlation between these areas and the amount of iron in the brain (R(2) = 0.69, P = 0.010), but no significant difference in ∆R2 was found between the two groups., Conclusions: This study showed that the extent of signal abnormalities on R2 maps can be used as a surrogate marker to detect minocycline effects in a murine experimental model of stroke.

Introduction: The value of perfusion MRI for identifying the tissue at risk has been questioned. Our objective was to assess baseline perfusion-weighted imaging parameters within infarct progression areas., Methods: Patients with anterior circulation stroke without early reperfusion were included from a prospective MRI database. Sequential MRI examinations were performed on admission, 2-3 h (H2), 2-3 days (D2), and between 15 and 30 days after the initial MRI. Maps of baseline time-to-peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were calculated. Lesion extension areas were defined as pixels showing de novo lesions between each MRI and were generated by subtracting successive lesion masks: V(0), baseline diffusion-weighted imaging (DWI) lesion; V(1), lesion extension between baseline and H2 DWI; V(2), lesion extension from H2 to D2 DWI; and V(3), lesion extension from D2 DWI to final FLAIR. Repeated measures analysis was used to compare hemodynamic parameters within the baseline diffusion lesion and subsequent lesion extension areas., Results: Thirty-two patients were included. Baseline perfusion parameters were significantly more impaired within the acute DWI lesion compared to lesion extension areas (TTP, p < 0.0001; MTT, p < 0.0001; CBF p < 0.0001; CBV, p < 0.0001). A significant decrease in MTT (p = 0.01) and TTP (p = 0.01) was found within successive lesion growth areas., Conclusion: A decreasing gradient of severity for TTP and MTT was observed within successive infarct growth areas.

Epidemiologic studies report cardiovascular protection conferred by omega-3 fatty acids, in particular docosahexaenoic acid (DHA). However, few experimental studies have addressed its potential in acute stroke treatment. The present study used multimodal MRI to assess in vivo the neuroprotection conferred by DHA and by a brain-targeting form of DHA-containing lysophosphatidylcholine (AceDoPC) in experimental stroke. Rats underwent intraluminal middle cerebral artery occlusion (MCAO) and were treated at reperfusion by intravenous injection of i) saline, ii) plasma from donor rats, iii) DHA or iv) AceDoPC, both solubilized in plasma. Twenty-four hours after reperfusion, animals underwent behavioral tests and were sacrificed. Multiparametric MRI (MRA, DWI, PWI, T2-WI) was performed at H0, during occlusion, and at H24, before sacrifice. Brain tissue was used for assay of F(2)-isoprostanes as lipid peroxidation markers. Initial lesion size and PWI/DWI mismatch were comparable in the four groups. Between H0 and H24, lesion size increased in the saline group (mean ± s.d.: +18% ± 20%), was stable in the plasma group (-3% ± 29%), and decreased in the DHA (-17% ± 15%, P=0.001 compared to saline) and AceDoPC (-34% ± 27%, P=0.001 compared to saline) groups. Neuroscores in the AceDoPC group tended to be lower than in the other groups (P=0.07). Treatments (pooled DHA and AceDoPC groups) significantly decreased lipid peroxidation as compared to controls (pooled saline and vehicle) (P=0.03). MRI-based assessment demonstrated the neuroprotective effect of DHA in the MCAO model. Results further highlighted the therapeutic potential of engineered brain-targeting forms of omega-3 fatty acids for acute stroke treatment., (© 2011 Bentham Science Publishers Ltd.)

Stroke is the third leading cause of death, after myocardial infarction and cancer, and the leading cause of permanent disability in Western countries. Although anti-inflammatory drugs have shown very promising results in preclinical rodent studies, they appeared to be ineffective against stroke in clinical trials. In this context, non-invasive detection of inflammatory cells after brain ischemia could be helpful (i) to select patients who may benefit from anti-inflammatory treatment, and/or (ii) to target an adequate individualized therapeutic time window. Magnetic resonance imaging (MRI) coupled with injection of iron oxide nanoparticles, a contrast agent taken up by macrophages ex vivo and in vivo, appears to be a promising tool for this purpose. This review focuses on the use of this technique to image inflammation in pre-clinical and clinical studies of stroke. Despite current limitations, MRI of inflammation may become an important tool for the investigation of novel ischemic stroke therapeutics targeting inflammation.

Background and Purpose: The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume., Methods: We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests., Results: The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test (P=0.39) or Spearman test (P=0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement., Conclusions: USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Background and Purpose: A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice., Methods: Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours., Results: We here present the first MRI data showing in vivo phagocyte-labeling obtained in mice with focal cerebral ischemia. USPIO-enhanced MRI kinetic analysis disclosed an inflammatory response surrounding the ischemic lesion and in the contralateral hemisphere via the corpus callosum. The imaging data collected during the first 36 hours postinjury suggested a spread of USPIO-related signal from ipsi- to contralateral hemisphere. Imaging data correlated with histochemical analysis showing inflammation remote from the lesion and ingestion of nanoparticles by microglia/macrophages., Conclusions: The present study shows that MR-tracking of phagocyte cells is feasible in mice, which may have critical therapeutic implications given the potential neurotoxicity of activated microglia/macrophages in central nervous system disorders.

Magnetic resonance imaging (MRI) of inflammation is based on the in vivo magnetic labelling of macrophages, the most abundant cells involved in the post-ischemic inflammatory response, by nanoparticles of iron oxides. Such approach has been successfully applied to study experimental rodent models of focal cerebral ischemia and has proved feasible in pioneer clinical studies. Despite current limitations, MRI of inflammation may become an important tool for the investigation of novel ischemic stroke therapeutics targeted at inflammation.

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients., Methods: 48 consecutive patients with hemispheric stroke were given intravenous tPA within seven hours of symptom onset, after computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Baseline diffusion weighted (DWI) and perfusion weighted (PWI) imaging volumes, time to peak, mean transit time, regional cerebral blood flow index, and regional cerebral blood volume were evaluated. The distribution of apparent diffusion coefficient (ADC) values was determined within each DWI lesion., Results: The symptomatic ICH rate was 8.3% (four of 48); the rate for any ICH was 43.8% (21 of 48). Univariate analysis showed that age, weight, history of hyperlipidaemia, baseline NIHSS score, glucose level, red blood cell count, and lacunar state on MRI were associated with ICH. However, mean 24 hour systolic blood pressure and a hyperdense artery sign on pretreatment CT were the only independent predictors of ICH. Patients with a hyperdense artery sign had larger pretreatment PWI and DWI lesion volumes and a higher NIHSS score. Analysis of the distribution of ADC values within DWI lesions showed that a greater percentage of pixels had lower ADCs (< 400 x 10(-6) mm(2)/s) in patients who experienced ICH than in those who did not., Conclusion: Key clinical and biological variables, pretreatment CT signs, and MRI indices are associated with tPA related intracerebral haemorrhage.

In this prospective MRI study, we evaluated the impact of the site of occlusion on multiple baseline perfusion parameters and subsequent recanalization in 49 stroke patients who were given intravenous tissue plasminogen activator (tPA). Pretreatment magnetic resonance angiography (MRA) revealed an arterial occlusion in 47 patients: (1) internal carotid artery (ICA) + M1 middle cerebral artery (MCA) occlusion (n=12); (2) M1 MCA occlusion (n=19); (3) M2 MCA, distal branches of the MCA and anterior cerebral artery (ACA) occlusion (n=16). Patients with ICA occlusion had significantly larger DWI, PWI and mismatch lesion volume on pretreatment MRI compared to patients with other sites of occlusion. The differences in cerebral blood flow (CBF) and peak height were significantly higher in patients with ICA occlusion compared to patients with other sites of occlusion (P=0.03 and P=0.04, respectively). Day 1 MRA showed recanalization in 28 patients (60%). The rate of recanalization was significantly different depending on the site of occlusion: 33% in ICA + M1 MCA occlusion, 63% in M1 MCA occlusion and 81% in either M2 MCA, distal branches of the MCA or ACA occlusion (P=0.002). Our data suggest that CBF and peak height are the most relevant MRI parameters to assess the severity of hemodynamic impairment in regard to the site of occlusion.

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Purpose: Effective collateral blood flow seem to be an important factor associated with a small infarct volume and a good clinical outcome. We aimed to assess leptomeningeal collateral blood flow on source perfusion-weighted images in patients with acute stroke., Materials and Methods: 29 patients with proximal middle cerebral artery occlusion (MCA alone, n=17; MCA + internal carotid artery [ICA] occlusion, n=12) were evaluated with MRI at baseline before thrombolytic therapy, and at day 60. Clinical evaluation was performed at days 0 and 60 with the National Institutes of Health Stroke Scale (NIHSS) score, and at day 60 with the modified Rankin score. We assessed (on source images of the dynamic contrast-enhanced T2*-weighted perfusion [PWI] sequence) the presence of a hypointensity consistent with delayed contrast arrival within the global perfusion deficit (delayed perfusion sign). We analyzed the extent of the area demonstrating such delayed perfusion (DP area) on source images of the PWI sequence, and compared it with the global perfusion (GP) abnormality shown by time-to-peak maps. We calculated the Spearman rank correlation coefficient between the DP/GP ratio and: 1. age; 2. clinical scores; 3. site of occlusion [MCA alone versus ICA+MCA occlusion]; 4. DWI lesion size at day 0, and T2WI lesion size at day 60; 5. PWI-derived parameters (time-to-peak [TTP], relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and peak height). All tests were bilateral and a p value<0.05 was considered as significant., Results: Delayed perfusion areas of various size were found within the global perfusion deficit in all patients. High DP/GP ratio values were significantly correlated with: 1. better clinical scores at day 0 and day 60 (all p<=0.04); 2. smaller lesions at day 0 DWI and at day 60 T2WI (all p<=0.004); 3. ICA patency (r=0.49, p=0.01); 4. lower TTP delays, and higher values of rCBV, rCBF, and peak height., Conclusion: These preliminary data suggest that a delayed contrast filling observed on native perfusion-weighted images may be a marker of leptomeningeal collateral blood flow, and may lead to better clinical and morphological outcomes in acute ischemic stroke.

In patients with acute ischemic stroke, early recanalization may save tissue at risk for ischemic infarction, thus resulting in smaller infarcts and better clinical outcome. The hypothesis that clinical and diffusion- and perfusion-weighted imaging (DWI, PWI) parameters may have a predictive value for early recanalization and final infarct size was assessed. Twenty-nine patients were prospectively enrolled and underwent sequential magnetic resonance imaging (1) within 6 hours from hemispheric stroke onset, before thrombolytic therapy; (2) at day 1; and (3) at day 60. Late infarct volume was assessed by T2 -weighted imaging. At each time, clinical status was assessed by the National Institutes of Health Stroke Scale (NIHSS). Twenty-eight patients had arterial occlusion at day 0 magnetic resonance angiography (MRA). They were classified into two groups according to day 1 MRA: recanalization (n = 18) versus persistent occlusion (n = 10). Any significant differences between these groups were assessed regarding (1) PWI and DWI abnormality volumes, (2) relative and absolute time-to-peak (TTP) and apparent diffusion coefficient within the lesion on DWI; and (3) day 60 lesion volume on T2 -weighted imaging. Univariate and multivariate logistic regression analysis showed that the most powerful predictive factors for recanalization were lower baseline NIHSS score and lower baseline absolute TTP within the lesion on DWI. The best predictors of late infarct size were day 0 lesion volume on DWI and day 1 recanalization. Early PWI and DWI studies and day 1 MRA provide relevant predictive information on stroke outcome.

Background and Purpose: We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA)., Methods: Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion- (DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion., Results: Twenty-nine patients (16 men and 13 women; mean+/-SD age, 65+/-14 years) underwent MRI; the mean time from symptom onset to treatment was 255+/-62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7+/-5.4 if recanalization had occurred and 14+/-2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved (r=-0.68, P=0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume: r=0.51, P=0.006, TTP: r=0.35, P=0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score (r=0.58, P=0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 (P=0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score (P=0.03)., Conclusions: Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke.

The use of T2*-weighted sequences has been advocated for early differentiation between hematoma and ischemia in patients with acute stroke. Early hemorrhagic transformation of ischemic stroke is an adverse event which may occur under treatment and may impair the prognosis: our aim is to evaluate the ability of T2*-weighted gradient-echo sequence (T2* GRE) to detect post-ischemic cerebral hemorrhage. The imaging procedure included: (1) baseline CT scan at admission. (2) MRI performed within 24 h of therapy onset including: (a) dual fast spin echo T2 sequence, (b) axial isotropic echoplanar diffusion-weighted imaging sequence, (c) conventional T2* GRE, and (d) 3D TOF turbo MRA. Post-ischemic cerebral hemorrhage was diagnosed if T2* GRE detected a focal intraparenchymal area of signal loss. The diameter of this lesion had to be more than 5 mm in order to eliminate past microbleeds. (3) Patients who showed an early suspicion of bleeding on MRI promptly had a second CT scan, and, if this one was negative for bleeding, another CT scan was performed 1 day later. All the other patients had a control CT scan during the first week. Forty-five consecutive patients have been included. T2* GRE showed intracranial bleeding in seven. The diagnosis of post-ischemic cerebral bleeding was confirmed by CT in all patients. Control CT scans did not reveal any post-ischemic cerebral hemorrhage in patients with negative MRI. In one case, hemorrhage was seen earlier on MRI than on CT scan. In conclusion, T2* GRE appeared to be at least as efficient as CT scan in the detection of early post-ischemic cerebral hemorrhage.

Background Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke. Contribution We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects. Conclusion This review presents the contribution of the collaborative research project under the “TecSan” grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. [ABSTRACT FROM AUTHOR]

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