Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data.

OBJECTIVE: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. METHODS: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. RESULTS: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. CONCLUSIONS: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and ß-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

BACKGROUND: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. MATERIALS AND METHODS: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. RESULTS: Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). CONCLUSIONS: The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

Capillary function progressively deteriorates in prodromal Alzheimer's disease: A longitudinal MRI perfusion study.

Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream ß-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging.

BACKGROUND: This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. METHODS: In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. RESULTS: Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], -0.6 [-0.9 to -0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], -0.4[-0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. CONCLUSIONS: Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

Robust estimation of hemo-dynamic parameters in traditional DCE-MRI models.

PURPOSE: In dynamic contrast enhanced (DCE) MRI, separation of signal contributions from perfusion and leakage requires robust estimation of parameters in a pharmacokinetic model. We present and quantify the performance of a method to compute tissue hemodynamic parameters from DCE data using established pharmacokinetic models. METHODS: We propose a Bayesian scheme to obtain perfusion metrics from DCE MRI data. Initial performance is assessed through digital phantoms of the extended Tofts model (ETM) and the two-compartment exchange model (2CXM), comparing the Bayesian scheme to the standard Levenberg-Marquardt (LM) algorithm. Digital phantoms are also invoked to identify limitations in the pharmacokinetic models related to measurement conditions. Using computed maps of the extra vascular volume (ve) from 19 glioma patients, we analyze differences in the number of un-physiological high-intensity ve values for both ETM and 2CXM, using a one-tailed paired t-test assuming un-equal variance. RESULTS: The Bayesian parameter estimation scheme demonstrated superior performance over the LM technique in the digital phantom simulations. In addition, we identified limitations in parameter reliability in relation to scan duration for the 2CXM. DCE data for glioma and cervical cancer patients was analyzed with both algorithms and demonstrated improvement in image readability for the Bayesian method. The Bayesian method demonstrated significantly fewer non-physiological high-intensity ve values for the ETM (p<0.0001) and the 2CXM (p<0.0001). CONCLUSION: We have demonstrated substantial improvement of the perceptive quality of pharmacokinetic parameters from advanced compartment models using the Bayesian parameter estimation scheme as compared to the LM technique.

Acute reperfusion without recanalization: Serial assessment of collaterals within 6 h of using perfusion-weighted magnetic resonance imaging.

Acute reperfusion despite persistent arterial occlusion may occur in up to 30% of ischemic stroke patients. Recruitment of leptomeningeal collaterals may explain this phenomenon. Using dynamic susceptibility-contrast perfusion imaging (DSC-PI), we assessed acute changes in collateral flow among patients without recanalization. From a multicenter prospective database (I-KNOW), 46 patients with magnetic resonance angiography visible occlusion in whom both reperfusion and recanalization were assessed within 6 h of onset were identified. Maps of collateral flow at arterial, capillary and late venous phases were generated from DSC-PI through inter-frame registration, baseline signal subtraction and temporal summation, and graded blind to all other relevant clinical and radiological data using the Higashida scale. Flow direction and the acute evolution of collaterals were evaluated against the reperfusion status. Among patients without recanalization ( n = 33), flow direction remained retrograde. Collateral grades significantly improved between admission and acute follow-up in patients who reperfused (OR: 4.57; 95% CI: 1.1-22.7; p = 0.048), but not in those without reperfusion (OR: 1.34; 95% CI: 0.4-4.5; p = 0.623). Our study confirmed that acute reperfusion without recanalization is associated with a significant improvement of retrograde collateral flow. DSC-PI can detect acute changes in collateral flow, and may help evaluate novel treatments targeting leptomeningeal collaterals.

Stroke infarct volume estimation in fixed tissue: Comparison of diffusion kurtosis imaging to diffusion weighted imaging and histology in a rodent MCAO model.

Diffusion kurtosis imaging (DKI) is a new promising MRI technique with microstructural sensitivity superior to conventional diffusion tensor (DTI) based methods. In stroke, considerable mismatch exists between the infarct lesion outline obtained from the two methods, kurtosis and diffusion tensor derived metrics. We aim to investigate if this mismatch can be examined in fixed tissue. Our investigation is based on estimates of mean diffusivity (MD) and mean (of the) kurtosis tensor (MKT) obtained using recent fast DKI methods requiring only 19 images. At 24 hours post stroke, rat brains were fixed and prepared. The infarct was clearly visible in both MD and MKT maps. The MKT lesion volume was roughly 31% larger than the MD lesion volume. Subsequent histological analysis (hematoxylin) revealed similar lesion volumes to MD. Our study shows that structural components underlying the MD/MKT mismatch can be investigated in fixed tissue and therefore allows a more direct comparison between lesion volumes from MRI and histology. Additionally, the larger MKT infarct lesion indicates that MKT do provide increased sensitivity to microstructural changes in the lesion area compared to MD.

Boosted Tree Model Reforms Multimodal Magnetic Resonance Imaging Infarct Prediction in Acute Stroke.

BACKGROUND AND PURPOSE: Stroke imaging is pivotal for diagnosis and stratification of patients with acute ischemic stroke to treatment. The potential of combining multimodal information into reliable estimates of outcome learning calls for robust machine learning techniques with high flexibility and accuracy. We applied the novel extreme gradient boosting algorithm for multimodal magnetic resonance imaging-based infarct prediction. METHODS: In a retrospective analysis of 195 patients with acute ischemic stroke, fluid-attenuated inversion recovery, diffusion-weighted imaging, and 10 perfusion parameters were derived from acute magnetic resonance imaging scans. They were integrated to predict final infarct as seen on follow-up T2-fluid-attenuated inversion recovery using the extreme gradient boosting and compared with a standard generalized linear model approach using cross-validation. Submodels for recanalization and persistent occlusion were calculated and were used to identify the important imaging markers. Performance in infarct prediction was analyzed with receiver operating characteristics. Resulting areas under the curve and accuracy rates were compared using Wilcoxon signed-rank test. RESULTS: The extreme gradient boosting model demonstrated significantly higher performance in infarct prediction compared with generalized linear model in both cross-validation approaches: 5-folds (P<10e-16) and leave-one-out (P<0.015). The imaging parameters time-to-peak, mean transit time, time-to-maximum, and diffusion-weighted imaging were indicated as most valuable for infarct prediction by the systematic algorithm rating. Notably, the performance improvement was higher with 5-folds cross-validation approach than leave-one-out. CONCLUSIONS: We demonstrate extreme gradient boosting as a state-of-the-art method for clinically applicable multimodal magnetic resonance imaging infarct prediction in acute ischemic stroke. Our findings emphasize the role of perfusion parameters as important biomarkers for infarct prediction. The effect of cross-validation techniques on performance indicates that the intrapatient variability is expressed in nonlinear dynamics of the imaging modalities.

Predictors of Infarct Growth in Patients with Large Vessel Occlusion Treated with Endovascular Therapy.

INTRODUCTION: Endovascular therapy (EVT) is now evidence based in anterior circulation stroke caused by large vessel occlusion. Outcome is related to infarct size, but data on predictors of infarct growth is limited. We analyzed our cohort of EVT treated patients primarily selected by magnetic resonance imaging (MRI) to examine predictors of infarct growth and the association between infarct size and outcome. METHODS: We identified 342 patients with anterior circulation stroke from 2004 to 2014 in our prospectively collected EVT database. Baseline infarct size was available for 281 (measured by MRI) while final infarct size was available for 312 patients. Functional outcome was defined by modified Rankin Score (mRS) after 90 days and good outcome was defined as mRS 0-2. Predictors of infarct growth were examined by regression analysis. RESULTS: Successful reperfusion [odds ratio (OR) 0.17, 95% confidence interval (CI) (0.09-0.33)] was the strongest predictor of reduction of infarct growth. Receiving intravenous thrombolysis and a short time span from symptom onset to scanning also reduced infarct growth. Occlusion of the internal carotid artery (ICA) intracranially predicted infarct growth (OR = 7.29, 95% CI: 2.36-22.53). EVT under general anesthesia and having a NIHSS between 10 and 15 were also associated with infarct growth. DISCUSSION: Failure of reperfusion resulted in an average infarct growth of approximately 50 ml. Lack of reperfusion generally results in a poor outcome likely due to infarct growth. Occlusion of the intracranial ICA and EVT under general anesthesia predicted infarct growth, while successful reperfusion, getting intraveneous thrombolysis, and a short time span from onset to scan protected against growth. A median infarct size of 52 ml best discriminates between a good and a bad outcome.

Automatic thalamus and hippocampus segmentation from MP2RAGE: comparison of publicly available methods and implications for DTI quantification.

PURPOSE: In both structural and functional MRI, there is a need for accurate and reliable automatic segmentation of brain regions. Inconsistent segmentation reduces sensitivity and may bias results in clinical studies. The current study compares the performance of publicly available segmentation tools and their impact on diffusion quantification, emphasizing the importance of using recently developed segmentation algorithms and imaging techniques. METHODS: Four publicly available, automatic segmentation methods (volBrain, FSL, FreeSurfer and SPM) are compared to manual segmentation of the thalamus and hippocampus imaged with a recently proposed T1-weighted MRI sequence (MP2RAGE). We evaluate morphometric accuracy on 22 healthy subjects and impact on diffusivity measurements obtained from aligned diffusion-weighted images on a subset of 10 subjects. RESULTS: Compared to manual segmentation, the highest Dice similarity index of the thalamus is obtained with volBrain using a local library ([Formula: see text], [Formula: see text]) followed by volBrain using an external library ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). The same order is found for hippocampus with volBrain local ([Formula: see text], [Formula: see text]), volBrain external ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). For diffusivity measurements, volBrain provides values closest to those obtained from manual segmentations. volBrain is the only method where FA values do not differ significantly from manual segmentation of the thalamus. CONCLUSIONS: Overall we find that volBrain is superior in thalamus and hippocampus segmentation compared to FSL, FreeSurfer and SPM. Furthermore, the choice of segmentation technique and training library affects quantitative results from diffusivity measures in thalamus and hippocampus.

Early neurological deterioration after thrombolysis: Clinical and imaging predictors.

BACKGROUND: National Institutes of Health Stroke Scale is the most common scale used in stroke patients. An increase of four points or more within 24 h signifies early neurological deterioration. We aimed to establish how often early neurological deterioration occurs in a cohort selected by magnetic resonance imaging and which factors predicted early neurological deterioration. METHODS: In this single-center study, we collected epidemiological, imaging and outcome data on 569 consecutive patients undergoing reperfusion therapy after magnetic resonance imaging selection. RESULTS: Of these, 33 (5.8%) experienced early neurological deterioration. Seven were due to a symptomatic intracerebral hemorrhage, 23 were caused by extension of ischemia on follow-up imaging and three were due to progression on the basis of small vessel disease. Early neurological deterioration was predicted by a larger perfusion lesion, higher blood glucose and presence of large vessel disease. Penumbra occurred in 34% of patients but only 9% of patients with penumbra experienced early neurological deterioration, thus eroding the value of penumbra as an imaging marker. Early neurological deterioration was a poor prognostic sign. Odds ratio for disability or death was 14.9 (95% confidence interval: 6.5-34.0). CONCLUSION: Early neurological deterioration is rare. It originates mainly from ischemic infarct growth rather than from hemorrhage. Concern should be highest in patients with elevated blood glucose, larger perfusion lesions and large vessel disease. Prior aspirin use increases risk of symptomatic intracerebral hemorrhage.

Sensitivity of diffusion- and perfusion-weighted imaging for diagnosing acute ischemic stroke is 97.5%.

BACKGROUND AND PURPOSE: MRI using diffusion-weighted imaging (DWI) is the most sensitive diagnostic imaging modality for early detection of ischemia, but how accurate is it and how much does perfusion-weighted imaging (PWI) add to the sensitivity have to be known. METHODS: In this single-center study, we collected epidemiological, imaging, and outcome data on all patients with stroke undergoing MRI-based treatment with intravenous tissue-type plasminogen activator at our center from 2004 to 2010. The DWI negative patients were identified, and we calculated the sensitivity and specificity of DWI and additional PWI for diagnosing acute ischemic stroke. We compared DWI positive and negative patients to identify characteristics associated with DWI negativity. RESULTS: Five hundred sixty-nine consecutive patients were treated with intravenous tissue-type plasminogen activator on the basis of an acute MRI. A DWI lesion was evident in 518 patients. Forty-seven patients were DWI negative; however, a relevant PWI lesion was found in 33 of these patients. Four stroke mimics were treated with intravenous tissue-type plasminogen activator and 1 of these patients had a DWI lesion. Thus, 8% of all patients with stroke were DWI negative. The combination of DWI and PWI resulted in a sensitivity of 97.5% for the ischemic stroke diagnosis. DWI negativity was associated with less severe strokes, location in the posterior circulation, a longer time from onset to scan, and an improved 90-day outcome. The cause of small-vessel disease was more likely to be DWI negative. CONCLUSIONS: The combination of DWI and PWI before intravenous tissue-type plasminogen activator confirms the diagnosis in 97.5% of all ischemic strokes.

Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury.

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.

MRI before intraarterial therapy in ischemic stroke: feasibility, impact, and safety.

Intraarterial therapy (IAT) in acute ischemic stroke is effective for opening occlusions of major extracranial or intracranial vessels. Clinical efficacy data are lacking pointing to a need for proper patient selection. We examined feasibility, clinical impact, and safety profile of magnetic resonance imaging (MRI) for patient selection before IAT. In this single-center study, we collected epidemiologic, imaging, and outcome data on all intraarterial-treated patients presenting with anterior circulation occlusions at our center from 2004 to 2011. Magnetic resonance imaging was the first imaging choice. Computer tomography (CT) was performed in the presence of a contraindication. We treated 138 patients. Mean age was 64 years and median National Institutes of Health Stroke Scale (NIHSS) was 17. Major reperfusion (thrombolysis in cerebral infarction (TICI) 2b+3) was achieved in 52% and good outcome defined as modified Rankin Scale (mRS) score 0 to 2 at 90 days was achieved in 41%. Mortality at 90 days was 10%. There was only one symptomatic hemorrhage. Recanalization, age, and stroke severity were associated with outcome. Preprocedure MRI was obtained in 83%. Good outcome was significantly associated with smaller diffusion-weighted imaging (DWI) lesion size at presentation and not with the size of the perfusion lesion. It is feasible to triage patients for IAT using MRI with acceptable rates of poor outcome and symptomatic hemorrhage.

Cerebral perfusion measured by dynamic susceptibility contrast MRI is reduced in patients with idiopathic normal pressure hydrocephalus.

PURPOSE: To demonstrate in idiopathic normal pressure hydrocephalus (iNPH) patients by dynamic susceptibility contrast MRI a reduced preoperative cerebral blood flow (CBF) which correlates with the severity of clinical symptoms and predicts shunt outcome. MATERIALS AND METHODS: In cortical, subcortical, periventricular regions and along peri-and paraventricular profiles absolute perfusion values were estimated by multi-slice DSC MRI in 21 iNPH patients and 16 age-matched healthy individuals (HI). Relative CBF (rCBF), calculated with the occipital cortex as internal reference, was used for comparison between groups and for correlation analysis between regional rCBF and symptoms or outcome. RESULTS: iNPH patients showed significantly decreased rCBF in the basal medial frontal cortex, hippocampus, lentiform nucleus, periventricular white matter (PVWM), central grey matter and the global parenchyma as compared to HI. iNPH patients with higher preoperative rCBF in the PVWM performed better in clinical tests. A lower overall preoperative function resulted in a more obvious recovery after shunt insertion. Shunt-responders had higher rCBF values in the basal medial frontal cortex than non-responders. CONCLUSION: DSC MRI perfusion is a potentially useful diagnostic tool in iNPH and perfusion based criteria might be possible predictors of shunt response.

Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial.

BACKGROUND AND PURPOSE: Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. METHODS: Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month. RESULTS: Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003). CONCLUSIONS: Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.

Analysis of partial volume effects on arterial input functions using gradient echo: a simulation study.

Absolute blood flow and blood volume measurements using perfusion weighted MRI require an accurately measured arterial input function (AIF). Because of limited spatial resolution of MR images, AIF voxels cannot be placed completely within a feeding artery. We present a two-compartment model of an AIF voxel including the relaxation properties of blood and tissue. Artery orientations parallel and perpendicular to the main magnetic field were investigated and AIF voxels were modeled to either include or be situated close to a large artery. The impact of partial volume effects on quantitative perfusion metrics was investigated for the gradient echo pulse sequence at 1.5 T and 3.0 T. It is shown that the tissue contribution broadens and introduces fluctuations in the AIF. Furthermore, partial volume effects bias perfusion metrics in a nonlinear fashion, compromising quantitative perfusion estimates and profoundly effecting local AIF selection.

Absolute quantification of cerebral blood flow in neurologically normal volunteers: dynamic-susceptibility contrast MRI-perfusion compared with computed tomography (CT)-perfusion.

To improve the reproducibility of arterial input function (AIF) registration and absolute cerebral blood flow (CBF) quantification in dynamic-susceptibility MRI-perfusion (MRP) at 1.5T, we rescaled the AIF by use of a venous output function (VOF). We compared CBF estimates of 20 healthy, elderly volunteers, obtained by computed tomography (CT)-perfusion (CTP) and MRP on two consecutive days. MRP, calculated without the AIF correction, did not result in any significant correlation with CTP. The rescaled MRP showed fair to moderate correlation with CTP for the central gray matter (GM) and the whole brain. Our results indicate that the method used for correction of partial volume effects (PVEs) improves MRP experiments by reducing AIF-introduced variance at 1.5T.