A comparative study of multi and single post labeling delay pseudocontinuous arterial spin labeling in patients with carotid artery stenosis.

PURPOSE: Arterial Spin Labeling (ASL) allows for the non-invasive visualization of brain perfusion to detect abnormalities. In unilateral carotid artery stenosis, one hemisphere is less supplied with blood which results in a lower cerebral blood flow (CBF) compared to the healthy side. ASL can be performed time-resolved using multiple post labeling delay (PLD) times after labeling or static with a single delay, the latter allowing for a faster and more robust acquisition while bearing the risk of a falsely set delay resulting in unusable images. The purpose of this study is to compare the performance of multi-PLD and single-PLD ASL in patients with unilateral carotid artery stenosis both as means of diagnosis and therapeutic follow-up examination. METHODS: ASL perfusion data of 17 patients with known unilateral carotid artery stenosis was used to compare the diagnostic performance of the multi-PLD and single-PLD approach. Comparisons were made based on the CBF values and the added benefit of arrival time maps showing slower blood flow in multi-PLD ASL which might be overlooked in the individual delay images both before and after therapy. RESULTS: Both the multi-PLD and the single-PLD data could identify the side of the stenosis with hemispheric differences in each approach (p < 0.001) and depict the normalization of CBF after therapy (p > 0.05). There were no differences between the individual methods (p > 0.05). CONCLUSION: In this work, we could show that multi-PLD ASL in patients with unilateral carotid artery stenosis is beneficial as it provides both CBF and arrival time maps, however when only a single-PLD acquisition is available, this appears sufficient in a clinical setting to investigate the presence of a unilateral stenosis.

Pre-stroke socioeconomic status predicts upper limb motor recovery after inpatient neurorehabilitation.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher mortality rates and the likelihood of receiving less evidence-based treatment after stroke. In contrast, little is known about the impact of SES on recovery after discharge from inpatient rehabilitation. The aim of this study was to investigate the influence of SES on long-term recovery after stroke. PATIENTS AND METHODS: In a prospective, observational, multicentre study, inpatients were recruited towards the end of rehabilitation. The 12-month follow-up focussed on upper limb motor recovery, measured by the Fugl-Meyer score. A clinically relevant improvement of ≥5.25 points was considered recovery. Patient-centric measures such as the Patient-reported Outcomes Measurement Information System-Physical Health (PROMIS-10 PH) provided secondary outcomes. Information on schooling, vocational training, income and occupational status pre-stroke entered a multidimensional SES index. Multivariate logistic regression models calculating odds ratios (ORs) and corresponding confidence intervals (CIs) were applied. SES was added to an initial model including age, sex and baseline neurological deficit. Additional exploratory analyses examined the association between SES and outpatient treatment. RESULTS: One hundred and seventy-six patients were enrolled of whom 98 had SES and long-term recovery data. Model comparisons showed the SES-model superior to the initial model (Akaike information criterion (AIC): 123 vs. 120, Pseudo R2: 0.09 vs. 0.13). The likelihood of motor recovery (OR = 17.12, 95%CI = 1.31; 224.18) and PROMIS-10 PH improvement (OR = 20.76, 95%CI = 1.28; 337.11) were significantly increased with higher SES, along with more frequent use of outpatient therapy (p = .02). CONCLUSIONS: Higher pre-stroke SES is associated with better long-term recovery after discharge from rehabilitation. Understanding these factors can improve outpatient long-term stroke care and lead to better recovery.KEY MESSAGEHigher pre-stroke socioeconomic status (SES) is associated with better long-term recovery after discharge from rehabilitation both in terms of motor function and self-reported health status.Higher SES is associated with significantly higher utilization of outpatient therapies.Discharge management of rehabilitation clinics should identify and address socioeconomic factors in order to detect individual needs and to improve outpatient recovery. Article registration: clinicaltrials.gov NCT04119479.

Early TICI 2b or Late TICI 3-Is Perfect the Enemy of Good?

BACKGROUND AND PURPOSE: A Thrombolysis in Cerebral Infarction (TICI) score of 3 has been established as therapeutic goal in endovascular therapy (EVT) for acute ischemic stroke; however, in the case of early TICI2b reperfusion, the question remains whether to stop the procedure or to continue in the pursuit of perfection (i.e., TICI 2c/3). METHODS: A total of 6635 patients were screened from the German Stroke Registry. Patients who underwent EVT for occlusion of the middle cerebral artery (M1 segment), with final TICI score of 2b/3 were included. Multivariable logistic regression was performed with functional independence (modified Rankin Scale, mRS at day 90 of 0-2) as the dependent variable. RESULTS: Of 1497 patients, 586 (39.1%) met inclusion criteria with a final TICI score of 2b and 911 (60.9%) with a TICI score of 3. Patients who achieved first-pass TICI3 showed highest odds of functional independence (Odds ratio [OR] 1.71, 95% confidence interval [95% CI] 1.18-2.47). Patients who achieved TICI2b with the second pass (OR 0.53, 95% CI 0.31-0.89) or with three or more passes (OR 0.44, 95% CI 0.27-0.70) had significantly worse clinical outcomes compared to first-pass TICI2b. TICI3 at the second pass was by trend better than first-pass TICI2b (OR 1.55, 95% CI 0.98-2.45), but TICI3 after 3 or more passes (OR 0.93, 95% CI 0.57-1.50) was not significantly different from first-pass TICI2b. CONCLUSION: First-pass TICI2b was superior to TICI2b after ≥ 2 retrievals and comparable to TICI3 at ≥ 3 retrievals. The potential benefit in outcome after achieving TICI3 following further retrieval attempts after first-pass TICI2b need to be weighed against the risks.

More Retrieval Attempts are Associated with Poorer Functional Outcome After Unsuccessful Thrombectomy.

PURPOSE: In mechanical thrombectomy, it has been hypothesized that multiple retrieval attempts might the improve reperfusion rate but not the clinical outcome. In order to assess a potential harmful effect of a mechanical thrombectomy on patient outcome, the number of retrieval attempts was analyzed. Only patients with a thrombolysis in cerebral infarction (TICI) score of 0 were reviewed to exclude the impact of eventual successful reperfusion on the mechanical hazardousness of repeated retrievals. METHODS: In this study 6635 patients who underwent endovascular thrombectomy (EVT) for acute large vessel occlusion (LVO) from the prospectively administered multicenter German Stroke Registry were screened. Insufficient reperfusion was defined as no reperfusion (TICI score of 0), whereas a primary outcome was defined as functional independence (modified Rankin scale [mRS] 0-2 at day 90). Propensity score matching and multivariable logistic regressions were then performed to adjust for confounders. RESULTS: A total of 377 patients (7.8%) had a final TICI score of 0 and were included in the study. After propensity score matching functional independence was found to be significantly more frequent in patients who underwent ≤ 2 retrieval attempts (14%), compared to patients with > 2 retrieval attempts (3.9%, OR 0.29, 95% CI 0.07-0.73, p = 0.009). After adjusting for age, sex, admission NIHSS score, and location of occlusion, more than two retrieval attempts remained significantly associated with lower odds of functional independence at 90 days (OR 0.2, 95% CI 0.07-0.52, p = 0.002). CONCLUSION: In patients with failure of reperfusion, more than two retrieval attempts were associated with a worse clinical outcome, therefore indicating a possible harmful effect of multiple retrieval attempts.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Health-related quality of life 90 days after stroke assessed by the International Consortium for Health Outcome Measurement standard set.

BACKGROUND AND PURPOSE: Stroke has detrimental effects in multiple health domains not captured by routine scales. The International Consortium for Health Outcome Measurement has developed a standardized set for self-reported assessment to overcome this limitation. The aim was to assess this set in acute stroke care. METHODS: Consecutive patients with acute ischaemic stroke, transient ischaemic attack or intracerebral hemorrhage were enrolled. Demographics, living situation and cardiovascular risk factors were collected from medical records and interviews. The Patient-reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) and the Patient Health Questionnaire-4 (PHQ-4) were conducted 90 days after admission. Linear and logistic regression analyses were used to identify predictors of outcome. The study is registered at ClinicalTrials.gov, NCT03795948. RESULTS: In all, 1064 patients were enrolled; mean age was 71.6 years, 51% were female, and median National Institutes of Health Stroke Scale (NIHSS) on admission was 3. Diagnosis was acute ischaemic stroke in 74%, transient ischaemic attack in 20% and intracerebral hemorrhage in 6%. 673 patients were available for outcome evaluation at 90 days; of these 90 (13%) had died. In survivors, t scores of PROMIS-10 physical and mental health were 40.3 ± 6.17 and 44.3 ± 8.63, compared to 50 ± 10 in healthy populations. 16% reported symptoms indicating depression or anxiety on the PHQ-4. Higher NIHSS, prior stroke and requiring help pre-stroke predicted lower values in physical and mental health scores. Higher NIHSS and diabetes were associated with anxiety or depression. CONCLUSIONS: Integrated in the routine of acute stroke care, systematic assessment of patient-reported outcomes reveals impairments in physical and mental health. Main predictors are severity of stroke symptoms and comorbidities such as hypertension and diabetes.

Incomplete or failed thrombectomy in acute stroke patients with Alberta Stroke Program Early Computed Tomography Score 0-5 - how harmful is trying?

BACKGROUND AND PURPOSE: It is currently unknown whether mechanical thrombectomy (MT) for ischaemic stroke patients with low initial Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is clinically beneficial or even harmful. The purpose of this study was to investigate whether failed or incomplete MT in acute large vessel occlusion stroke with an initial ASPECTS ≤ 5 is associated with worse clinical outcome compared to patients not undergoing MT. METHODS: This observational cohort study included a consecutive sample of patients with anterior circulation stroke and initial ASPECTS ≤ 5 admitted between March 2015 and August 2019. Failed recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) score 0-2a, and incomplete recanalization as TICI 2b. Clinical outcome was assessed using the modified Rankin Scale (mRS) at 90 days defining very poor clinical outcome as mRS > 4. RESULTS: One hundred and seventy patients were included. Ninety-nine patients underwent MT and 71 patients received best medical treatment only. Clinical outcome after failed or incomplete MT (TICI 0-2b) was significantly better compared to patients with medical treatment only (median mRS 5, interquartile range 4-6 vs 5-6, P = 0.03). In multivariable logistic regression analysis, failed or incomplete MT (TICI 0-2b) showed a significantly reduced likelihood for very poor outcome (odds ratio 0.39, 95% confidence interval 0.19-0.83, P = 0.01). Failed MT (TICI 0-2a) was not associated with a worse outcome compared to best medical treatment. CONCLUSIONS: Patients with failed or incomplete recanalization results (TICI 0-2b) showed a reduced likelihood for very poor outcome compared with those who did not receive MT. Evidence from randomized trials is needed to confirm that even failed or incomplete MT is not harmful in these patients.

Effect of intravenous alteplase on ischaemic lesion water homeostasis.

BACKGROUND AND PURPOSE: Intravenous (IV) lysis with alteplase is known to increase biomarkers of blood-brain barrier breakdown and has therefore been associated with secondary injuries such as hemorrhagic transformation. The impact of alteplase on brain edema formation, however, has not been investigated yet. The purpose was to examine the effects of IV alteplase on ischaemic lesion water homeostasis differentiated from final tissue infarct in patients with and without successful endovascular therapy (sET). METHODS: In all, 232 middle cerebral artery stroke patients were analyzed. 147 patients received IV alteplase, of whom 106 patients received subsequent sET. Out of 85 patients without IV alteplase, 50 received sET. Ischaemic brain edema was quantified at admission and follow-up computed tomography using quantitative lesion net water uptake (NWU) and its difference was calculated (ΔNWU). The relationship of alteplase on ΔNWU and edema-corrected final infarct volume was analyzed using univariate and multivariate linear regression models. RESULTS: The mean ΔNWU was 11.8% (SD 7.9) in patients with alteplase and 11.5% (SD 8.3) in patients without alteplase (P = 0.8). Alteplase was not associated with lowered ΔNWU whilst being associated with reduced edema-corrected tissue infarct volume [-27.4 ml, 95% confidence interval (CI) -49.4 to -5.4 ml; P = 0.02], adjusted for the Alberta Stroke Program Early Computed Tomography Score and recanalization status. In patients with sET, ΔNWU was 10.5% (95% CI 6.3%-10.5%) for patients with IV alteplase and 8.4% (95% CI 9.1%-12.0%) for patients without IV alteplase. CONCLUSION: The application of IV alteplase did not significantly alter ischaemic lesion water homeostasis but was associated with reduced edema-corrected tissue infarct volume, which might be directly linked to improved functional outcome.

Clinical relevance of asymptomatic intracerebral hemorrhage post thrombectomy depends on angiographic collateral score.

Asymptomatic intracerebral hemorrhage (aICH) is a common phenomenon in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (ET). However, the impact of aICH on the functional outcome remains widely unclear. In this study, we aimed at identifying predictors for aICH and analyzing its impact on functional outcome. Patients with AIS due to large artery occlusion in the anterior circulation treated with successful ET were enrolled in a tertiary stroke center. Patients with aICH or without intracerebral hemorrhage were included according to post-treatment CT performed within 72 h; 100 consecutive patients fulfilled the inclusion criteria and 30% classified with aICH. In logistic regression analysis, lower collateral score (OR 0.24; 95% CI 0.12-0.46, p < 0.0001) was significantly associated with aICH. Less patients with aICH achieved an independent outcome (mRS 0-2, 16.7% vs. 44.3%, p = 0.007). Poor outcome (mRS 4-6) was significantly higher in patients with aICH (41.4% vs. 70%, p = 0.021). Patients with aICH had a lower ratio of independent outcome (OR 0.23, 95% CI 0.05-0.1.05, p = 0.041) than without ICH. There were no differences concerning poor outcome (p = 0.5). Lower collateral status was a strong independent predictor for aICH. aICH after successful ET may decrease the likelihood of an independent functional outcome without influencing poor outcome.

Emergency Conversion to General Anesthesia Is a Tolerable Risk in Patients Undergoing Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy for acute ischemic stroke is performed with the patient under local anesthesia, conscious sedation, or general anesthesia. According to recent trials, up to 16% of patients require emergency conversion to general anesthesia during mechanical thrombectomy. This study investigated the procedural and clinical outcomes after emergency conversion in comparison with local anesthesia, conscious sedation, and general anesthesia. MATERIALS AND METHODS: This retrospective study included 254 patients undergoing mechanical thrombectomy for acute large-vessel occlusion. The procedure was started with the patient either under local anesthesia, conscious sedation, or general anesthesia. Emergency conversion was defined as induction of general anesthesia during mechanical thrombectomy. The primary outcomes were successful reperfusion (TICI 2b/3) and functional independence (mRS at 90 days, ≤2). RESULTS: Twenty-five patients (9.8%) required emergency conversion to general anesthesia. The time from admission to flow restoration was increased under general anesthesia (median, 137 minutes) and emergency conversion (median, 138 minutes) compared with local anesthesia (median 110 minutes). After adjustment for confounders, emergency conversion to general anesthesia and primary general anesthesia had comparable chances of successful reperfusion (OR = 1.28; 95% CI, 0.31-5.25). Patients with emergency conversion had a tendency toward higher chances of functional independence (OR = 4.48; 95% CI, 0.49-40.86) compared with primary general anesthesia, but not compared with local anesthesia (OR = 0.86; 95% CI, 0.14-5.11) and conscious sedation (OR = 1.07; 95% CI, 0.17-6.53). CONCLUSIONS: Patients with emergency conversion did not have lower chances of successful reperfusion or functional independence compared those with primary general anesthesia, and time to flow restoration was also similar. We found no evidence supporting the primary induction of general anesthesia in patients at risk for emergency conversion.

Parietofrontal network upregulation after motor stroke.

Objective: Motor recovery after stroke shows a high inter-subject variability. The brain's potential to form new connections determines individual levels of recovery of motor function. Most of our daily activities require visuomotor integration, which engages parietal areas. Compared to the frontal motor system, less is known about the parietal motor system's reconfiguration related to stroke recovery. Here, we tested if functional connectivity among parietal and frontal motor areas undergoes plastic changes after stroke and assessed the behavioral relevance for motor function after stroke. Methods: We investigated stroke lesion-induced changes in functional connectivity by measuring high-density electroencephalography (EEG) and assessing task-related changes in coherence during a visually guided grip task with the paretic hand in 30 chronic stroke patients with variable motor deficits and 19 healthy control subjects. Quantitative changes in task-related coherence in sensorimotor rhythms were compared to the residual motor deficit. Results: Parietofrontal coupling was significantly stronger in patients compared to controls. Whereas motor network coupling generally increased during the task in both groups, the task-related coherence between the parietal and primary motor cortex in the stroke lesioned hemisphere showed increased connectivity across a broad range of sensorimotor rhythms. Particularly the parietofrontal task-induced coupling pattern was significantly and positively related to residual impairment in the Nine-Hole Peg Test performance and grip force. Interpretation: These results demonstrate that parietofrontal motor system integration during visually guided movements is stronger in the stroke-lesioned brain. The correlation with the residual motor deficit could either indicate an unspecific marker of motor network damage or it might indicate that upregulated parietofrontal connectivity has some impact on post-stroke motor function.

Neural correlates of visuospatial bias in patients with left hemisphere stroke: a causal functional contribution analysis based on game theory.

Stroke patients frequently display spatial neglect, an inability to report, or respond to, relevant stimuli in the contralesional space. Although this syndrome is widely considered to result from the dysfunction of a large-scale attention network, the individual contributions of damaged grey and white matter regions to neglect are still being disputed. Moreover, while the neuroanatomy of neglect in right hemispheric lesions is well studied, the contributions of left hemispheric brain regions to visuospatial processing are less well understood. To address this question, 128 left hemisphere acute stroke patients were investigated with respect to left- and rightward spatial biases measured as severity of deviation in the line bisection test and as Center of Cancellation (CoC) in the Bells Test. Causal functional contributions and interactions of nine predefined grey and white matter regions of interest in visuospatial processing were assessed using Multi-perturbation Shapley value Analysis (MSA). MSA, an inference approach based on game theory, constitutes a robust and exact multivariate mathematical method for inferring functional contributions from multi-lesion patterns. According to the analysis of performance in the Bells test, leftward attentional bias (contralesional deficit) was associated with contributions of the left superior temporal gyrus and rightward attentional bias with contributions of the left inferior parietal lobe, whereas the arcuate fascicle was contributed to both contra- and ipsilesional bias. Leftward and rightward deviations in the line bisection test were related to contributions of the superior longitudinal fascicle and the inferior parietal lobe, correspondingly. Thus, Bells test and line bisection tests, as well as ipsi- and contralesional attentional biases in these tests, have distinct neural correlates. Our findings demonstrate the contribution of different grey and white matter structures to contra- and ipsilesional spatial biases as revealed by left hemisphere stroke. The results provide new insights into the role of the left hemisphere in visuospatial processing.

Altered topology of structural brain networks in patients with Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by tics. Abnormal neuronal circuits in a wide-spread structural and functional network involved in planning, execution and control of motor functions are thought to represent the underlying pathology. We therefore studied changes of structural brain networks in 13 adult GTS patients reconstructed by diffusion tensor imaging and probabilistic tractography. Structural connectivity and network topology were characterized by graph theoretical measures and compared to 13 age-matched controls. In GTS patients, significantly reduced connectivity was detected in right hemispheric networks. These were furthermore characterized by significantly reduced local graph parameters (local clustering, efficiency and strength) indicating decreased structural segregation of local subnetworks. Contrasting these results, whole brain and right hemispheric networks of GTS patients showed significantly increased normalized global efficiency indicating an overall increase of structural integration among distributed areas. Higher global efficiency was associated with tic severity (R = 0.63, p = 0.022) suggesting the clinical relevance of altered network topology. Our findings reflect an imbalance between structural integration and segregation in right hemispheric structural connectome of patients with GTS. These changes might be related to an underlying pathology of impaired neuronal development, but could also indicate potential adaptive plasticity.

[Endovascular stroke treatment following recent positive clinical trials]. / Endovaskuläre Schlaganfallbehandlung vor dem Hintergrund der aktuellen positiven klinischen Studien.

Recently, five independent randomized controlled clinical trials demonstrated the efficacy and safety of endovascular stroke treatment in stroke patients with occlusion of proximal intracranial arteries. The five trials MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME and REVASCAT randomized a total of 1287 stroke patients to either standard treatment, which in the majority of patients consisted of intravenous thrombolysis within 4.5 h of symptom onset or additional endovascular stroke treatment. In all the studies endovascular treatment resulted in a better clinical outcome with an odds ratio for a better clinical outcome 90 days after stroke ranging between 1.7 and 3.1 and an absolute increase in the proportion of patients with functionally independent outcome between 14% and 31%. The overwhelming benefit of endovascular treatment mainly results from mechanical thrombectomy using stent retriever devices and starting endovascular treatment within 6 h of symptom onset in stroke patients.

[Imaging-based indications for interventional treatment of stroke]. / Bildgebungsbasierte Indikationsstellung für die interventionelle Schlaganfallbehandlung.

The indications for mechanical thrombectomy are based on a proximal vessel occlusion in the absence of extensive ischemic damage in the corresponding dependent vascular territory. The maximum extent of early ischemic edema for which endovascular treatment is still useful is not clear from the studies. A benefit of mechanical thrombectomy can be safely assumed with an ASPECT score of 6-10, possibly also with lower scores. A more complex imaging with assessment of the status of collateral vessels or perfusion abnormality is scientifically interesting but usually not necessary for clinical decision-making for endovascular stroke treatment within the first 6 h after symptom onset.

Prediction of infarction and reperfusion in stroke by flow- and volume-weighted collateral signal in MR angiography.

BACKGROUND AND PURPOSE: In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion. MATERIALS AND METHODS: Consecutively (2009-2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved. RESULTS: Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001). CONCLUSIONS: Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.

ANTONIA perfusion and stroke. A software tool for the multi-purpose analysis of MR perfusion-weighted datasets and quantitative ischemic stroke assessment.

OBJECTIVES: The objective of this work is to present the software tool ANTONIA, which has been developed to facilitate a quantitative analysis of perfusion-weighted MRI (PWI) datasets in general as well as the subsequent multi-parametric analysis of additional datasets for the specific purpose of acute ischemic stroke patient dataset evaluation. METHODS: Three different methods for the analysis of DSC or DCE PWI datasets are currently implemented in ANTONIA, which can be case-specifically selected based on the study protocol. These methods comprise a curve fitting method as well as a deconvolution-based and deconvolution-free method integrating a previously defined arterial input function. The perfusion analysis is extended for the purpose of acute ischemic stroke analysis by additional methods that enable an automatic atlas-based selection of the arterial input function, an analysis of the perfusion-diffusion and DWI-FLAIR mismatch as well as segmentation-based volumetric analyses. RESULTS: For reliability evaluation, the described software tool was used by two observers for quantitative analysis of 15 datasets from acute ischemic stroke patients to extract the acute lesion core volume, FLAIR ratio, perfusion-diffusion mismatch volume with manually as well as automatically selected arterial input functions, and follow-up lesion volume. The results of this evaluation revealed that the described software tool leads to highly reproducible results for all parameters if the automatic arterial input function selection method is used. CONCLUSION: Due to the broad selection of processing methods that are available in the software tool, ANTONIA is especially helpful to support image-based perfusion and acute ischemic stroke research projects.

Comparison of 10 TTP and Tmax estimation techniques for MR perfusion-diffusion mismatch quantification in acute stroke.

BACKGROUND AND PURPOSE: The mismatch between lesions identified in perfusion- and diffusion-weighted MR imaging is typically used to identify tissue at risk of infarction in acute stroke. The purpose of this study was to analyze the variability of mismatch volumes resulting from different time-to-peak or time-to-maximum estimation techniques used for hypoperfused tissue definition. MATERIALS AND METHODS: Data of 50 patients with middle cerebral artery stroke and intracranial vessel occlusion imaged within 6 hours of symptom onset were analyzed. Therefore, 10 different TTP/Tmax techniques and delay thresholds between +2 and +12 seconds were used for calculation of perfusion lesions. Diffusion lesions were semiautomatically segmented and used for mismatch quantification after registration. RESULTS: Mean volumetric differences up to 40 and 100 mL in individual patients were found between the mismatch volumes calculated by the 10 TTP/Tmax estimation techniques for typically used delay thresholds. The application of typical criteria for the identification of patients with a clinically relevant mismatch volume resulted in different mismatch classifications in ≤24% of all cases, depending on the TTP/Tmax estimation method used. CONCLUSIONS: High variations of tissue-at-risk volumes have to be expected when using different TTP/Tmax estimation techniques. An adaption of different techniques by using correction formulas may enable more comparable study results until a standard has been established by agreement.

Early infarct FLAIR hyperintensity is associated with increased hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. METHODS: Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. RESULTS: Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). CONCLUSIONS: Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.