Penumbra detection in acute stroke with perfusion magnetic resonance imaging: Validation with 15 O-positron emission tomography.

OBJECTIVE: Accurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch-based penumbra detection against full quantitative positron emission tomography (15 O-PET), the gold standard for penumbra detection in acute ischemic stroke. METHODS: Ten patients (group A) with acute and subacute ischemic stroke underwent perfusion-weighted (PW)/diffusion-weighted MRI and consecutive full quantitative 15 O-PET within 48 hours of stroke onset. Penumbra as defined by 15 O-PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time-to-maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel-based receiver-operating-characteristic curve analysis. The same validation based on penumbra as defined by quantitative 15 O-PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B). RESULTS: The PW map Tmax (area-under-the-curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%. INTERPRETATION: The performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds-based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875-886.

Is Perfusion MRI without Deconvolution Reliable for Mismatch Detection in Acute Stroke? Validation with 15O-Positron Emission Tomography.

BACKGROUND: In acute stroke, the magnetic resonance (MR) imaging-based mismatch concept is used to select patients with tissue at risk of infarction for reperfusion therapies. There is however a controversy if non-deconvolved or deconvolved perfusion weighted (PW) parameter maps perform better in tissue at risk prediction and which parameters and thresholds should be used to guide treatment decisions. METHODS: In a group of 22 acute stroke patients with consecutive MR and quantitative positron emission tomography (PET) imaging, non-deconvolved parameters were validated with the gold standard for penumbral-flow (PF) detection 15O-water PET. Performance of PW parameters was assessed by a receiver operating characteristic curve analysis to identify the accuracy of each PWI map to detect the -upper PF threshold as defined by PET cerebral blood flow <20 mL/100 g/min. RESULTS: Among normalized non-deconvolved parameters, PW-first moment without delay correction (FM without DC) > 3.6 s (area under the curve [AUC] = 0.89, interquartile range [IQR] 0.85-0.94), PW-maximum of the concentration curve (Cmax) < 0.66 (AUC = 0.92, IQR 0.84-0.96) and PW-time to peak (TTP) > 4.0 s (AUC = 0.92, IQR 0.87-0.94) perform significantly better than other non-deconvolved parameters to detect the PF threshold as defined by PET. CONCLUSIONS: Non-deconvolved parameters FM without DC, Cmax and TTP are an observer-independent alternative to established deconvolved parameters (e.g., Tmax) to guide treatment decisions in acute stroke.

Multiparametric Model for Penumbral Flow Prediction in Acute Stroke.

BACKGROUND AND PURPOSE: Identification of salvageable penumbra tissue by dynamic susceptibility contrast magnetic resonance imaging is a valuable tool for acute stroke patient stratification for treatment. However, prior studies have not attempted to combine the different perfusion maps into a predictive model. In this study, we established a multiparametric perfusion imaging model and cross-validated it using positron emission tomography perfusion for detection of penumbral flow. METHODS: In a retrospective analysis of 17 subacute stroke patients with consecutive magnetic resonance imaging and H2O15 positron emission tomography scans, perfusion maps of cerebral blood flow, cerebral blood volume, mean transit time, time-to-maximum, and time-to-peak were constructed and combined using a generalized linear model (GLM). Both the GLM maps and the single perfusion maps alone were cross-validated with positron emission tomography-cerebral blood flow scans to predict penumbral flow on a voxel-wise level. Performance was tested by receiver-operating characteristics curve analysis, that is, the area under the curve, and the models' fits were compared using the likelihood ratio test. RESULTS: The GLM demonstrated significantly improved model fit compared with each of the single perfusion maps (P<1×e-5) and demonstrated higher performance, with an area under the curve of 0.91. However, the absolute difference between the performance of GLM and the best-performing single perfusion parameter (time-to-maximum) was relatively low (area under the curve difference =0.04). CONCLUSIONS: Our results support a dynamic susceptibility contrast magnetic resonance imaging-based GLM as an improved model for penumbral flow prediction in stroke patients. With given perfusion maps, this model is a straightforward and observer-independent alternative for therapy stratification.

Clinical-Radiological Parameters Improve the Prediction of the Thrombolysis Time Window by Both MRI Signal Intensities and DWI-FLAIR Mismatch.

BACKGROUND: With regard to acute stroke, patients with unknown time from stroke onset are not eligible for thrombolysis. Quantitative diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) MRI relative signal intensity (rSI) biomarkers have been introduced to predict eligibility for thrombolysis, but have shown heterogeneous results in the past. In the present work, we investigated whether the inclusion of easily obtainable clinical-radiological parameters would improve the prediction of the thrombolysis time window by rSIs and compared their performance to the visual DWI-FLAIR mismatch. METHODS: In a retrospective study, patients from 2 centers with proven stroke with onset <12 h were included. The DWI lesion was segmented and overlaid on ADC and FLAIR images. rSI mean and SD, were calculated as follows: (mean ROI value/mean value of the unaffected hemisphere). Additionally, the visual DWI-FLAIR mismatch was evaluated. Prediction of the thrombolysis time window was evaluated by the area-under-the-curve (AUC) derived from receiver operating characteristic (ROC) curve analysis. Factors such as the association of age, National Institutes of Health Stroke Scale, MRI field strength, lesion size, vessel occlusion and Wahlund-Score with rSI were investigated and the models were adjusted and stratified accordingly. RESULTS: In 82 patients, the unadjusted rSI measures DWI-mean and -SD showed the highest AUCs (AUC 0.86-0.87). Adjustment for clinical-radiological covariates significantly improved the performance of FLAIR-mean (0.91) and DWI-SD (0.91). The best prediction results based on the AUC were found for the final stratified and adjusted models of DWI-SD (0.94) and FLAIR-mean (0.96) and a multivariable DWI-FLAIR model (0.95). The adjusted visual DWI-FLAIR mismatch did not perform in a significantly worse manner (0.89). ADC-rSIs showed fair performance in all models. CONCLUSIONS: Quantitative DWI and FLAIR MRI biomarkers as well as the visual DWI-FLAIR mismatch provide excellent prediction of eligibility for thrombolysis in acute stroke, when easily obtainable clinical-radiological parameters are included in the prediction models.

Comparison of the 2 Most Popular Deconvolution Techniques for the Detection of Penumbral Flow in Acute Stroke.

BACKGROUND AND PURPOSE: Dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance imaging (MRI) is used to identify the tissue-at-risk in acute stroke, but the choice of optimal DSC postprocessing in the clinical setting remains a matter of debate. Using 15O-water positron emission tomography (PET), we validated the performance of 2 common deconvolution methods for DSC-MRI. METHODS: In (sub)acute stroke patients with consecutive MRI and PET imaging, DSC maps were calculated applying 2 deconvolution methods, standard and block-circulant single value decomposition. We used 2 standardized analysis methods, a region of interest-based and a voxel-based analysis, where PET cerebral blood flow masks of <20 mL/100 g per minute (penumbral flow) and gray matter masks were overlaid on DSC parameter maps. For both methods, receiver operating characteristic curve analysis was performed to identify the accuracy of each DSC-MR map for the detection of PET penumbral flow. RESULTS: In 18 data sets (median time after stroke onset: 18 hours; median time PET to MRI: 101 minutes), block-circulant single value decomposition showed significantly better performance to detect PET penumbral flow only for mean transit time maps. Time-to-maximum (Tmax) had the highest performance independent of the deconvolution method. CONCLUSIONS: Block-circulant single value decomposition seems only significantly beneficial for mean transit time maps in (sub)acute stroke. Tmax is likely the most stable deconvolved parameter for the detection of tissue-at-risk using DSC-MRI.

Influence of the arterial input function on absolute and relative perfusion-weighted imaging penumbral flow detection: a validation with ¹5O-water positron emission tomography.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging maps are used to identify critical hypoperfusion in acute stroke. However, quantification of perfusion may depend on the choice of the arterial input function (AIF). Using quantitative positron emission tomography we evaluated the influence of the AIF location on maps of absolute and relative perfusion-weighted imaging to detect penumbral flow (PF; <20 mL/100 g/min on positron emission tomography(CBF)) in acute stroke. METHODS: In 22 patients with acute stroke the AIF was placed at 7 sites (M1, M2, M3 ipsi- and contralateral and internal carotid artery-M1 contralateral to the infarct). Comparative (15)O-water positron emission tomography and AIF-dependent perfusion-weighted imaging (cerebral blood flow, cerebral blood volume, mean transit time, and time to maximum) were performed. A receiver operating characteristic curve analysis described the threshold independent performance (area under the curve) of the perfusion-weighted maps for all 7 AIF locations and identified the best AIF-dependent absolute and relative thresholds to identify PF. These results were compared with AIF-independent time-to-peak maps. RESULTS: Quantitative perfusion-weighted imaging maps of cerebral blood flow and time to maximum performed best. For PF detection, AIF placement did significantly influence absolute PF thresholds. However, AIF placement did not influence (1) the threshold independent performance; and (2) the relative PF thresholds. AIF placement in the proximal segment of the contralateral middle cerebral artery (cM1) was preferable for quantification. CONCLUSIONS: AIF-based maps of cerebral blood flow and time to maximum were most accurate to detect the PF threshold. The AIF placement significantly altered absolute PF thresholds and showed best agreement with positron emission tomography for the cM1 segment. The performance of relative PF thresholds, however, was not AIF location-dependent and might be along with AIF-independent time-to-peak maps, more suitable than absolute PF thresholds in acute stroke if detailed postprocessing is not feasible.

Combined interventional stroke therapy using intracranial stent and local intraarterial thrombolysis (LIT).

INTRODUCTION: Supported by results of the ECASS III study, intravenous rt-PA thrombolysis is considered a standard therapy for acute stroke within 4.5 h. Still under debate is the use of a more aggressive treatment as that of local intraarterial thrombolysis (LIT) or combining intravenous administration of recombinant tissue plasminogen activator (rt-PA) followed by LIT (bridging concept). Mechanical thrombus removal devices and effective flow achievement by stenting are reported to increase the recanalization rate and patient outcome. Newer reports showed the use of intracranial stents as the latest trend-setting technique. A combined approach hereby appears to achieve the best results consisting of pharmacologic thrombolysis, manual aspiration devices and stenting. We employed a novel removable stent as a new approach in acute stroke, aiming to make the intraarterial thrombolysis through an enhanced thrombus contact surface more effective and to reduce the effective revascularisation time with the possibility of stent removal after re-opening the occluded vessel. METHODS: We describe four cases with acute stroke in the anterior and posterior circulation using a newer self-expandable removable stent (Solitaire™ AB) combined with LIT performed in the 'bridging technique', occasionally supported by additional thrombus aspiration. RESULTS: In all cases, we directly achieved after stenting an effective revascularization with fast recanalization time when using stent implantation first. Stenting was always technically successful without complications. CONCLUSION: The easy handling of a removable stent in stent-assisted revascularization combined with thrombolysis (i.v./i.a.) is a newly described technique for acute stroke treatment, which join immediate mechanical recanalization, postulated improved thrombolysis and the possibility of stent removing.

A simple positron emission tomography-based calibration for perfusion-weighted magnetic resonance maps to optimize penumbral flow detection in acute stroke.

BACKGROUND AND PURPOSE: Perfusion-weighted (PW) MRI is increasingly used to identify the tissue at risk. The adequate PW-MRI map and threshold remain controversial due to a considerable individual variation of values. By comparative positron emission tomography, we evaluated a simple MR-based and positron emission tomography-validated calibration of PW maps. METHODS: PW-MRI and quantitative positron emission tomography (15O-water) of patients with acute stroke were used to calculate averaged as well as individual thresholds of penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100 g/min) for maps of time to peak, mean transit time, cerebral blood flow, and cerebral blood volume. A linear regression analysis studied the variability of the individual thresholds using 3 different PW reference regions (hemispheric, white matter, gray matter). The best model was used for volumetric analysis to compare averaged and scaled individual thresholds and to calculate look-up tables for PW maps. RESULTS: In 26 patients, the averaged thresholds were (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32); cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2 (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large individual variability was best explained by the mean value of the hemispheric reference derived from a region of interest on a level with the basal ganglia of the unaffected hemisphere (R(2): cerebral blood flow 0.76, cerebral blood volume 0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected thresholds clearly improved the detection of penumbral flow. Look-up tables were calculated to identify the individual thresholds according to the hemispheric reference value. CONCLUSIONS: The individual variation of PW values, even if calculated by deconvolution, remains a major obstacle in quantitative PW imaging and can be significantly improved by a simple MR-based calibration. Easily applicable look-up tables identify the individual best threshold for each PW map to optimize mismatch detection.

Maps of time to maximum and time to peak for mismatch definition in clinical stroke studies validated with positron emission tomography.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging-derived maps of time-to-maximum (Tmax) are increasingly used to identify the tissue at risk in clinical stroke studies (eg, DEFUSE and EPITHET). Using quantitative positron emission tomography (PET), we evaluated Tmax to define the penumbral flow threshold in stroke patients and compared its performance to nondeconvolved time-to-peak (TTP) maps. METHODS: Comparative perfusion-weighted imaging and quantitative 15O-water PET images of acute stroke patients were analyzed using cortical regions of interest. A receiver-operating characteristic curve analysis described the threshold independent performance of Tmax (area under the curve) and identified the best threshold (equal sensitivity and specificity threshold) to identify penumbral flow (< 20 mL/100 g/min on PET cerebral blood flow). The results were compared with nondeconvolved TTP and other current perfusion-weighted imaging maps using the Mann-Whitney rank-sum test. RESULTS: In 26 patients (time delay between MRI and PET, 65 minutes), the best threshold for penumbral flow was 5.5 seconds for Tmax (median; interquartile range, 3.9-6.6; sensitivity/specificity, 88%/89%). The area under the curve value was 0.95 (median; interquartile range, 0.93-0.97). Deconvolved Tmax did not perform significantly better than TTP (P = 0.34). CONCLUSIONS: Maps of Tmax detected penumbral flow but did not perform better than the easy-to-obtain maps of nondeconvolved TTP. Thus, "simple" TTP maps still remain suitable for clinical stroke studies if detailed postprocessing is not feasible.

MRI perfusion maps in acute stroke validated with 15O-water positron emission tomography.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging maps are used to identify hypoperfusion in acute ischemic stroke. We evaluated maps of cerebral blood flow (CBF), cerebral blood volume, mean transit time, and time to peak (TTP) in acute stroke by comparison with positron emission tomography. METHODS: Perfusion-weighted imaging and positron emission tomography were performed in 26 patients with acute ischemic stroke (median 18.5 hours after stroke onset, 65 minutes between MRI and positron emission tomography). The perfusion-weighted imaging-derived maps of CBF, cerebral blood volume, mean transit time, and TTP delay were compared with quantitative positron emission tomography CBF. A receiver-operating characteristic curve analysis identified the best perfusion-weighted imaging map and threshold to identify hypoperfusion <20 mL/100 g/min, a widely used measure of penumbral flow. RESULTS: Individual regression analysis of positron emission tomography CBF and perfusion-weighted imaging values were strong for CBF and TTP delay and weaker for mean transit time and cerebral blood volume, but the pooled analysis showed a large variance. Receiver-operating characteristic curve analysis identified TTP and CBF maps as most predictive (median area under the curve=0.94 and 0.93). Penumbral flow thresholds were <21.7 mL/100 g/min (CBF), <1.5 mL/100 g (cerebral blood volume), >5.3 seconds (mean transit time), and >4.2 seconds (TTP). TTP and CBF maps reached sensitivity/specificity values of 91%/82% and 89%/87%. CONCLUSIONS: In our sample, maps of CBF, TTP, and mean transit time yielded a good estimate of penumbral flow. The performance of TTP maps was equivalent to deconvolution techniques using an arterial input function. For all maps, the application of a predefined threshold is mandatory and calibration studies will enhance their use in acute stroke therapy as well as in clinical stroke trials.

Sequential escalation of therapy in "malignant" cerebral venous and sinus thrombosis.

BACKGROUND: The best treatment of fulminant or progressive cerebral venous and sinus thrombosis (CVST) despite dose-adjusted heparin remains controversial. Local thrombolysis has been successfully performed in several cases. In cases of impending herniation hemicraniectomy has been suggested as ultima ratio. We describe sequential escalation of therapy in "malignant" CVST. METHODS: Case report. RESULTS: We report a case of fulminant CVST in whom sequential escalation of therapy with intravenous heparin, local thrombolysis, and hemicraniectomy was necessitated by the progressive clinical course. The patient survived with a relatively good outcome. CONCLUSIONS: This first description on the combined treatment with local thrombolysis and hemicraniectomy illustrates that even in severely affected individuals, therapeutic nihilism is unwarranted and that all available therapeutic options including local thrombolysis and hemicraniectomy should be taken into consideration.

The performance of MRI-based cerebral blood flow measurements in acute and subacute stroke compared with 15O-water positron emission tomography: identification of penumbral flow.

BACKGROUND AND PURPOSE: Perfusion-weighted MRI-based maps of cerebral blood flow (CBF(MRI)) are considered a good MRI measure of penumbral flow in acute ischemic stroke but are seldom used in clinical routine due to methodical issues. We validated CBF(MRI) on quantitative CBF measurement by 15O-water positron emission tomography (CBF(PET)). MATERIAL AND METHODS: Comparative CBF(MRI) and CBF(PET) were performed in patients with acute and subacute stroke. In a voxel-based seed-growing technique, predefined CBF(MRI) thresholds (<40, <30, <20, <10 mL/100 g/min) were applied and the resulting volumes were compared with the hypoperfusion volume detected by the penumbral threshold (<20 mL/100 g/min) on CBF(PET). The volumetric comparison was expressed as the C-ratio (volume CBF(MRI)/volume CBF(PET)) to identify the best MRI threshold. The influence of vessel pathology, hypoperfusion size, and time point of imaging was described. The proportion of voxels correctly classified as hypoperfused and the proportion of voxel correctly classified as nonhypoperfused of the best CBF(MRI) threshold was calculated and a Bland-Altman plot illustrated the method-specific differences. RESULTS: In 24 patients (median time MRI to PET: 68 minutes; 16 patients imaged within 24 hours after stroke), the median volume of hypoperfusion <20 mL/100 g/min (CBF(PET)) was 78.5 cm(3). Median hypoperfusion volume on CBF(MRI) ranged from 245.9 cm(3) (<40 mL/100 g/min) to 35.5 cm(3) (<10 mL/10 g/min). On visual inspection, an excellent qualitative congruence was found. The quantitative congruence was best for the MRI-CBF threshold <20 mL/100 g/min (median C-ratio: 1.0), reaching a proportion of voxels correctly classified as hypoperfused of 76% and a proportion of voxel correctly classified as nonhypoperfused of 96%, but a wide interindividual range (C-ratio 0.3 to 3.5) was found. Ipsilateral vessel pathology, time point of imaging, and size of hypoperfusion did not significantly influence the C-ratio. The Bland-Altman analysis for the volumetric difference of CBF(MRI) and CBF(PET) found a good overall agreement but a large SD. CONCLUSIONS: Hypoperfusion areas below the CBF(PET) penumbral threshold can be well identified by the CBF(MRI) threshold <20 mL/10 g/min at a group level, but a large individual variance (exceeding 20% of volume in nearly half of the patients) could not be explained. Our results support a prudent use of MRI-based quantitative CBF measurement in clinical routine.

MRI-based mismatch detection in acute ischemic stroke: Optimal PWI maps and thresholds validated with PET.

Perfusion-weighted (PW) magnetic resonance imaging (MRI) is used to detect penumbral tissue in acute stroke, but the selection of optimal PW-maps and thresholds for tissue at risk detection remains a matter of debate. We validated the performance of PW-maps with 15O-water-positron emission tomography (PET) in a large comparative PET-MR cohort of acute stroke patients. In acute and subacute stroke patients with back-to-back MRI and PET imaging, PW-maps were validated with 15O-water-PET. We pooled two different cerebral blood flow (CBF) PET-maps to define the critical flow (CF) threshold, (i) quantitative (q)CBF-PET with the CF threshold <20 ml/100 g/min and (ii) normalized non-quantitative (nq)CBF-PET with a CF threshold of <70% (corresponding to <20 ml/100 g/min according to a previously published normogram). A receiver operating characteristic (ROC) curve analysis was performed to specify the accuracy and the optimal critical flow threshold of each PW-map as defined by PET. In 53 patients, (stroke to imaging: 9.8 h; PET to MRI: 52 min) PW-time-to-maximum (Tmax) with a threshold >6.1 s (AUC = 0.94) and non-deconvolved PW-time-to-peak (TTP) >4.8 s (AUC = 0.93) showed the best performance to detect the CF threshold as defined by PET. PW-Tmax with a threshold >6.1 s and TTP with a threshold >4.8 s are the most predictive in detecting the CF threshold for MR-based mismatch definition.

A PET-Guided Framework Supports a Multiple Arterial Input Functions Approach in DSC-MRI in Acute Stroke.

BACKGROUND AND PURPOSE: In acute stroke, arterial-input-function (AIF) determination is essential for obtaining perfusion estimates with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging (DSC-MRI). Standard DSC-MRI postprocessing applies single AIF selection, ie, global AIF. Physiological considerations, however, suggest that a multiple AIFs selection method would improve perfusion estimates to detect penumbral flow. In this study, we developed a framework based on comparable DSC-MRI and positron emission tomography (PET) images to compare the two AIF selection approaches and assess their performance in penumbral flow detection in acute stroke. METHODS: In a retrospective analysis of 17 sub(acute) stroke patients with consecutive MRI and PET scans, voxel-wise optimized AIFs were calculated based on the kinetic model as derived from both imaging modalities. Perfusion maps were calculated based on the optimized-AIF using two methodologies: (1) Global AIF and (2) multiple AIFs as identified by cluster analysis. Performance of penumbral-flow detection was tested by receiver-operating characteristics (ROC) curve analysis, ie, the area under the curve (AUC). RESULTS: Large variation of optimized AIFs across brain voxels demonstrated that there is no optimal single AIF. Subsequently, the multiple-AIF method (AUC range over all maps: .82-.90) outperformed the global AIF methodology (AUC .72-.85) significantly. CONCLUSIONS: We provide PET imaging-based evidence that a multiple AIF methodology is beneficial for penumbral flow detection in comparison with the standard global AIF methodology in acute stroke.

Bilateral vertebral artery disease: transcranial Doppler assessment of the hemodynamic vulnerability to changes in posture.

Posture changes may cause hemodynamic ischemic events, particularly in severe vertebrobasilar artery disease. It may be difficult and not without risk to prove this vulnerability to changes in posture during angiography. Therefore, TCD monitoring with passive tilting (PT) was used to evaluate cerebral hemodynamics distally to severe bilateral vertebral artery disease (BVAD). PCA flow velocity changes and dynamic cerebral autoregulation (DCA) were analyzed in supine and upright position. Despite a significant autoregulatory deficit distally to BVAD, the posterior cerebral blood supply seemed to be sufficiently maintained as long as systemic blood pressure changes were within normal limits. Posterior cerebral flow velocities, however, were significantly diminished when PT detected a systemic hypotension in upright position. This study proves the feasibility to combine PT and TCD monitoring of the PCA in patients with BVAD. In vertebrobasilar artery disease, the examination of spontaneous and tilt-induced autoregulatory responses could support the evaluation of a risk for hemodynamic ischemia.

Proton magnetic resonance spectroscopy in ecstasy (MDMA) users.

The popular recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has well-recognized neurotoxic effects upon central serotonergic systems in animal studies. In humans, the use of MDMA has been linked to cognitive problems, particularly to deficits in long-term memory and learning. Recent studies with proton magnetic resonance spectroscopy (1H MRS) have reported relatively low levels of the neuronal marker N-acetylaspartate (NAA) in MDMA users, however, these results have been ambiguous. Moreover, the only available 1H MRS study of the hippocampus reported normal findings in a small sample of five MDMA users. In the present study, we compared 13 polyvalent ecstasy users with 13 matched controls. We found no differences between the NAA/creatine/phosphocreatine (Cr) ratios of users and controls in neocortical regions, and only a tendency towards lower NAA/Cr ratios in the left hippocampus of MDMA users. Thus, compared with cognitive deficits, 1H MRS appears to be a less sensitive marker of potential neurotoxic damage in ecstasy users.

DWI intensity values predict FLAIR lesions in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset. METHODS: In a retrospective, dual-center MR-imaging study we included patients with acute stroke and time-from-stroke-onset ≤12 hours (group A: n = 49, 1.5T; group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion extent in DWI defined the slice for further analysis. FLAIR-lesions were identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on the DW-images. Circular ROIs were placed within the DWI-lesion and labeled according to the FLAIR-pattern (FLAIR+ or FLAIR-). ROI-values were normalized to the unaffected hemisphere. Adjusted and nonadjusted receiver-operating-characteristics (ROC) curve analysis on patient level was performed to analyze the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR-lesions. Spearman correlation and adjusted linear regression analysis was performed to assess the relationship between DWI-intensity and time-from-stroke-onset. RESULTS: DWI-rSI performed well in predicting lesions in FLAIR-imaging (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior performance of DWI-rSI. Correlation coefficents and linear regression showed a good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI. CONCLUSION: An easily assessable DWI-rSI threshold identifies the presence of lesions in FLAIR-imaging with good accuracy and is associated with time-from-stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI threshold as a marker of lesion age.