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Background: Alterations to microstructural integrity in white matter hyperintensities (WMH) in patients with severe leukoaraiosis are poorly understood. Neurite density and orientation dispersion imaging (NODDI) produce better estimates of myelin density than diffusion tensor MRI (DTI) and therefore may provide additional in vivo insight into WMH pathophysiology. Methods: NODDI was acquired in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Median values were measured in in the hemisphere contralateral to the incident stroke in regions of WMH and in normal appearing white matter (NAWM) and compared (paired Wilcoxon-exact test). Linear regression was performed to evaluate univariate predictors of log-transformed WMH volumes (log WMHv). Results: Patient characteristics were: mean±SD age 69±10 y, time-to-MRI 2.8±1.2 days, median [IQ] normalized WMHv 4.7 [2.3-9.3] and 61% men. MD, AD and RD were greater, while FA, MK, AK, RK, OD and ND were lower in WMH compared to NAWM (P Discussion: Diffusivity, kurtosis and ND and OD in acute stroke patients with moderate to severe leuokoaraiosis differed significantly between NAWM and WMH in the contralateral hemisphere. Reduced neurite density is suggestive of microstructural injury. Reduced OD is typically associated with greater organization, but might also reflect restricted extracellular space diffusivity. The association of MD, AD, AK and OD in NAWM with WMH burden suggests there is ongoing risk for developing future WMH.

Background: For cardiac arrest survivors initially comatose after restoration of spontaneous circulation (ROSC), the extent of brain injury and expected neurologic outcome are crucial for patient management decisions. Advanced diffusion imaging approaches such as neurite orientation dispersion and density imaging (NODDI) or diffusion kurtosis imaging may provide additional insight into tissue integrity and potential for recovery of consciousness complementary to standard diffusion tensor imaging (DTI). Methods: Multi-shell diffusion imaging was acquired in a prospective study of comatose cardiac arrest patients and in 5 controls. Neurite orientation dispersion (OD), intracellular volume fraction (ICVF), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were calculated. Median whole-brain values in patients with poor outcomes (no arousal recovery [AR] by discharge) were compared with those with AR and to controls (1-way ANOVA, post-hoc 1-sided Wilcoxon exact test). Results: 18 patients (mean ±SD 48±23 y, 39% men) and 5 controls (37±19 y, 40% men) were analyzed. Median (range) Glasgow Coma Scale was 3 [3-5]. 10 patients exhibited AR, 8 did not. Median [IQR] time-to-MRI was 5 [4-8] days. FA (P=0.009), MK (P=0.017), AK (P=0.026), RK (P=0.014), OD (P=0.018) and ICVF (P=0.0038) were significantly different (see Figure). FA control values were greater than AR and no AR (P Discussion: This is the first report investigating early NODDI and diffusional heterogeneity changes in post-cardiac arrest comatose patients. Patients who failed to recover arousal demonstrated greater values for all kurtosis and NODDI metrics compared to controls. Potential bias from early withdrawal of life sustaining treatment and small cohorts are limitations.

Background: Advanced diffusion imaging approaches that model intracellular and extracellular diffusion components such as neurite orientation dispersion and density imaging (NODDI) may provide additional insight into evolution of acute ischemic stroke (AIS) injury over standard diffusion tensor imaging approaches (DTI). Methods: NODDI was acquired at discharge in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Follow-up (FU) infarct volumes were drawn on discharge FLAIR. MD, AD, RD, FA, MK, AK, RK, OD and ND values were compared (1-way ANOVA) in infarct core (abnormal acute DWI), Growth (normal acute DWI, abnormal FU) and normal contralateral gray matter (nGM) and white matter (nWM). Results: Patient characteristics were: mean±SD age 69±10 y, median [IQR] initial NIH SS score 6 [3-11], time-to-acute MRI 7.3±5.3 h, time-to-FU MRI 2.8±1.2 days, acute DWI lesion 3.1 [0.5-18.8] cm 3 , FU lesion 8.1 [1.2-45.4] cm 3 and 61% men. Figure A shows examples of maps from a single subject. Core and growth values differed significantly (P Discussion: Increased OD is expected with tissue infarction due to loss of structural integrity. In contrast, increased ND in the subacute time-frame is paradoxical. One possible mechanism could be that hyperacute ischemia-induced cellular swelling increases tortuosity of water diffusion paths, imposing direction-dependent restrictions upon diffusion, increasing intracellular and extracellular diffusion.

Background and Purpose— Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Methods— Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland–Altman analyses were used to assess the reliability of CTP. Results— Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated ( R 2 =0.87 for CT-CBF; R 2 =0.83 for CT-CBV; P Conclusions— The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used.

Introduction and Hypothesis: Small initial DWI lesion volume (≤70 mL) is a strong predictor of favorable outcome post i IA thrombectomy and has been used for patient selection in multiple clinical trials. We sought to investigate if collateral and/or CT ASPECT scores could predict a small DWI lesion volume. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who underwent DWI within 8 hours of stroke onset. DWI lesion volumes were dichotomized to small (≤70mL) and large (>70ml). Collateral vessels were categorized to 5 groups: 0=none, 1=minimal, 2=less than 50%, 3=more than 50%, 4=equal and 5=more than the contralateral side. Logistic regression, ROC curve analyses and weighted Kappa test were performed. Results: In 130 patients, 62 female (48%), the average values (mean±SD) were: age 70±17 years, NIHSS 16±6, DWI volume 59±65 mL, time after stroke onset 4.4±1.8 hours, CT ASPECT score 6±2 and collateral score 3±1. Time, age, gender, or occlusion site (ICA vs MCA) were not independent predictors of a small DWI volume with p values all >0.05. Collateral score (OR 6.32, P Conclusion: Collateral score alone or combined with ASPECTS can predict a small DWI lesion volume with high specificity. However, sensitivity is relatively low and inter-rater agreement is fair. These findings should be considered when DWI is not available to select patients for IA therapy.

Introduction and Hypothesis: Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but < contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis. Results: In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p Conclusion: AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.

Background: In acute ischemic stroke (AIS), therapeutic decisions are increasingly being based upon the volume of likely-unsalvageable brain tissue, which is often estimated using DWI. Deep learning algorithms, e.g. convolutional neural networks (CNN), have been employed for chronic stroke lesion segmentation. Here we investigate the applicability of CNN for DWI lesion measurement in acute stroke. Methods: 50 AIS patients underwent DWI < 12h from last known well. Apparent diffusion coefficient maps, T2WI, and DWI were used as covariates in a 2D CNN (5-fold cross validation). Including convolutional, inception and fully connected dense layers, a CNN of 15 layers was trained using manually outlined DWI lesions. To avoid overfitting, statistical dropout, L1- and L2-regularization and batch-normalization were used. Automatically segmented lesion volumes (ALV) using a 50% risk threshold were compared to the manual lesion volumes (MLV) using Dice similarity index (DSI, a measure of overlap) and Spearman’s correlation coefficient. Subset analysis was performed evaluating results between small ( Results: The figure shows examples of CNN segmentation. The median [IQR] measured lesion volume and DSI were 25 [13-46] mL and 66% [35-75%], respectively. The correlation of MLV with ALV was 86% (P Discussion: Automatic DWI lesion segmentation for large lesions is feasible using CNN. CNN tended to overestimate the volumes of small lesions. Prior methods have used a priori heuristics or morphometric operations to remove artifacts. CNN methods show promise for “learning” to discriminate artifacts from real lesions.

Background and Purpose— Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. Methods— Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. Results— Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate ( R 2 =0.001). The majority of patients had DWI lesions that were 8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Conclusions— Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.

Background: Increases in FLAIR MRI signal intensity (SI) after acute ischemic stroke (AIS) have been proposed as “tissue clocks”, reflecting the degree of ischemic injury and potential for recovery in brain tissue. We hypothesize that lower SI increases will be a biomarker for less severe tissue injury and hence is potentially salvageable. To test this, we investigated patients who were treated with tPA to determine whether better outcomes were associated with lower FLAIR SI. Methods: Using our Get with the Guidelines database, we retrospectively analyzed AIS patients admitted between 2011 to 2013 who received full-dose tPA based on institutional protocols. Patients were included if they received a CT scan at our hospital before tPA therapy, and MRI performed < 1 h post CT included a usable FLAIR scan and evidence of stroke on acute DWI. SI ratio (SIR) was calculated on the FLAIR by selecting region of interests in hyperintense FLAIR areas that coincided with the acute DWI lesion and matching contralateral regions. Logistic regression analysis was performed using forward stepwise analysis to combine age, sex, admission NIHSS, SIR and onset-to-treatment (OTT) time to predict discharge outcome. Good outcome was defined as discharge to home or in-patient rehabilitation hospital. Results: There were 129 AIS patients who received tPA, and 57 met our imaging criteria. Patient characteristics were: mean±SD age 70±15 years, median [IQR] NIHSS 13 [7-18], OTT 2.1±1.1 h, time-to-MRI 2.1±1.0 h, 58% female and median SIR 1.13 [1.05-1.26]. On a univariate basis, only age (P Discussion: Controlling for age and admission NIHSS, we found that lower FLAIR SIR was a significant predictor of discharge outcome while OTT was not. This suggests that “tissue clocks” may be more accurate than “time clocks” for predicting tissue outcome, and ultimately functional outcome.

Background and Purpose— Admission infarct core lesion size is an important determinant of management and outcome in acute ( Methods— We evaluated 48 consecutive cases with vessel occlusion and admission CT perfusion and diffusion-weighted imaging within 3 hours of each other. CT perfusion was acquired with a “second-generation” 66-second biphasic cine protocol and postprocessed using “standard” (from 2 vendors, “A-std” and “B-std”) and “delay-corrected” (from 1 vendor, “A-dc”) commercial software. Receiver operating characteristic curve analysis was performed comparing each CT perfusion parameter—both absolute and normalized to the contralateral uninvolved hemisphere—between infarcted and noninfarcted regions as defined by coregistered diffusion-weighted imaging. Results— Cerebral blood flow had the highest accuracy (receiver operating characteristic area under the curve) for all 3 platforms ( P P Conclusions— Admission absolute and normalized “second-generation” cine acquired CT cerebral blood flow lesion volumes correlate more closely with diffusion-weighted imaging-defined infarct core than do those of CT cerebral blood volume or mean transit time. Although limited availability of diffusion-weighted imaging for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification among different postprocessing software limits generalizability of parameter map thresholds between platforms.

Background and Purpose— To characterize the spatial pattern of cerebral ischemic vulnerability to hypoperfusion in stroke patients. Methods— We included 90 patients who underwent admission CT perfusion and MRI within 12 hours of ischemic stroke onset. Infarcted brain lesions (“core”) were segmented from admission diffusion-weighted imaging and, along with the CT perfusion parameter maps, coregistered onto MNI-152 brain space, which was parcellated into 125 mirror cortical and subcortical regions per hemisphere. We tested the hypothesis that the percent infarction increment per unit of relative cerebral blood flow (rCBF) reduction differs statistically between regions using regression analysis to assess the interaction between regional rCBF and region variables. Next, for each patient, a “vulnerability index” map was constructed with voxel values equaling the product of that voxel's rCBF and infarction probability (derived from the MNI-152–transformed, binary, segmented, diffusion-weighted imaging lesions). Voxel-based rCBF threshold for core was determined within the upper 20 th percentile of vulnerability index map voxel values. Results— Different regions had different percent infarction increase per unit rCBF reduction ( P =0.001). The caudate body, putamen, insular ribbon, paracentral lobule, and precentral, middle, and inferior frontal gyri had the highest ischemic vulnerability to hypoperfusion. A voxel-based rCBF threshold of Conclusions— We demonstrated regional ischemic vulnerability of the brain to hypoperfusion in acute stroke patients. Location-specific, rather than whole-brain, rCBF thresholds may provide a more accurate metric for estimating infarct core using CT perfusion maps.

Background and Purpose— The spot sign score is a potent predictor of hematoma expansion in patients with primary intracerebral hemorrhage (ICH). We aim to determine the accuracy of this scoring system for the prediction of in-hospital mortality and poor outcome among survivors in patients with primary ICH. Methods— Three neuroradiologists retrospectively reviewed CT angiograms (CTAs) performed in 573 consecutive patients who presented to our Emergency Department with primary ICH over a 9-year period to determine the presence and scoring of spot signs according to strict criteria. Baseline ICH and intraventricular hemorrhage volumes were independently determined by computer-assisted volumetric analysis. Medical records were independently reviewed for baseline clinical characteristics and modified Rankin Scale (mRS) at hospital discharge and 3-month follow-up. Poor outcome among survivors was defined as a mRS ≥4 at 3-month follow-up. Results— We identified spot signs in 133 of 573 CTAs (23.2%), 11 of which were delayed spot signs (8.3%). The presence of any spot sign increased the risk of in-hospital mortality (55.6%, OR 4.0, 95% CI 2.6 to 5.9, P P P P Conclusion— The spot sign score is an independent predictor of in-hospital mortality and poor outcome among survivors in primary ICH.

Background and Purpose— Acute ischemic stroke due to large vessel occlusion (LVO)—vertebral, basilar, carotid terminus, middle and anterior cerebral arteries—likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. Methods— The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Results— Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P P Conclusion— Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.

Background and Purpose— The presence of active contrast extravasation (the spot sign) on computed tomography (CT) angiography has been recognized as a predictor of hematoma expansion in patients with intracerebral hemorrhage. We aim to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. Methods— We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis. Results— We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P Conclusion— The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy.

Background and Purpose— Rarely, acute ischemic stroke (AIS) patients have pretreatment CT-CBV abnormalities larger than final infarct volumes. We sought to determine: (1) the prevalence of CT-CBV “reversibility” in AIS patients treated with thrombolytic therapy, and (2) whether the presumed tissue salvage of these CT-CBV lesions depends on the CTP software. Methods— We reviewed the admission CT-CBV maps (calculated with an algorithm sensitive to tracer arrival time) and follow-up images of 148 AIS patients who received thrombolytic therapy. When the follow-up infarct appeared smaller than the admission CT-CBV lesion, the CTP source images were reprocessed using “delay-correction” software (GE, CTP 4). Original and “delay-corrected” CT-CBV ischemic lesion volumes were compared to each other and follow-up infarct volumes using the Student t test. Results— 11/148 (7.4%) patients had admission CT-CBV larger than follow-up lesions (mean difference −69.5 cc, range −146.0 to −14.0 cc; P P Conclusion— True “reversibility” of CT-CBV “core” lesions in AIS patients after thrombolytic therapy is rare, with small volumes of “salvaged” tissue. Pseudoreversibility of core lesions in standard CT-CBV maps can be avoided by using specific algorithmically optimized delay-correction software. Further investigation is warranted to determine whether this finding applies to algorithms provided by other vendors.

Background and Purpose— Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm 3 predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts 3 , we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. Methods— We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess differences in clinical and imaging outcomes. Good clinical outcome was defined as a 3-month modified Rankin Scale score ≤2. Results— Among patients with initial infarcts >70 cm 3 , all had poor outcomes despite a 50% recanalization rate with mean infarct growth of 114 cm 3 . These patients also had the largest mean transit time volumes ( P 3 who recanalized early had the best clinical outcomes ( P P 3 . Conclusion— This study supports the use of an acute diffusion-weighted imaging lesion volume threshold as an imaging selection criterion for intra-arterial therapy. It also confirms the importance of early reperfusion in selected patients.

Background and Purpose— Our purpose was to determine (1) the correlation between quantitative CT and MR measurements of infarct core, penumbra, and mismatch; and (2) whether the difference between these measurements would alter patient selection for stroke clinical trials. Methods— We studied 45 patients with acute middle cerebral artery stroke imaged a mean of 3.8 hours after onset (range, 0.48 to 8.35 hours) who underwent CT perfusion and MR diffusion (DWI)/perfusion imaging within 3 hours of each other. The DWI and MR-mean transit time (MTT) abnormalities were visually segmented using a semiautomated commercial analysis program. The CT-cerebral blood volume) and CT-MTT lesions were automatically segmented using a relative cerebral blood volume threshold of 0.56 and a relative MTT threshold of 1.50 on commercially available software. Percent mismatch was defined as [(MTT−DWI)/DWI volume]×100. Pearson correlation coefficients were calculated. Results— There were significant correlations for DWI versus CT-cerebral blood volume lesion volumes ( r 2 =0.88, P r 2 =0.86, P r 2 =0.81, P 2 cm diameter in 42 of 45 (93.3%); (3) mismatch < versus >20% in 41 of 45 (91.1%); and (4) inclusion versus exclusion from trial enrollment in 38 of 45 (84.4%) patients. Six of 7 disagreements were due to inadequate CT coverage. Conclusion— Advanced MR and CT perfusion imaging measurements of core/penumbra mismatch for patient selection in stroke trials are highly correlated when CT perfusion coverage is sufficient to include most of the ischemic region. Although MR is currently the preferred imaging method for determining core and penumbra, CT perfusion is comparable and potentially more available.

Background and Purpose— Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. Methods— Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Results— Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. Conclusions— Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies.

Background: In acute ischemic stroke (AIS) patients, multi-parametric MRI-based predictive algorithms have shown promise in identifying tissue at risk of infarction, but do not consider the intrinsic variations of normal or pathological tissue. We hypothesized that extending MRI-based algorithms to take into consideration tissue type will improve predictions of tissue outcome. Methods: We retrospectively analyzed AIS patients who received neither revascularization nor experimental interventional treatment, who underwent MRI within 12 h from the time since they were last known well and who had follow-up imaging >4 days. Perfusion- and diffusion-parametric maps were combined to predict tissue outcome using 2 models: 1) a generalized linear model (GLM) trained with data from the whole ipsilateral hemisphere (sGLM), irrespective of tissue type, or 2) an anatomically-weighted GLM (aGLM) that was calculated using a weighted average to combine results from models generated using entire white or gray matter regions only. Both methods were evaluated using jack-knifing and predicted and follow-up regions were compared in terms of accuracy (measured as area under the receiver operator characteristic curve, AUC), Dice similarity index (DSI) and root mean square error (RMSE). Results: Results from 109 patients (65% male, median 68 y IQR [55-77], NIHSS 14 [9-25]) showed that, compared to sGLM, aGLM’s predictions had higher DSI (0.48 [0.19-0.59], P Discussion: We showed that anatomically-weighted algorithms may better capture differences in tissue vulnerability in acute ischemic stroke, contributing to improved MRI-based tissue outcome predictions.

Background: There is increasing interest in using oxygen challenges during MRI to image metabolic dysfunction in acute ischemic stroke. Methods: Subjects enrolled in a prospective MRI study of patients imaged within 48 h of stroke onset underwent arterial spin labeling (ASL) MRI for 10-12 min, while receiving a transient normobaric oxygen (NBO) challenge, according to this protocol: (1) Room air (RA) for 2-5 min; (2) NBO at 10-12 L/min via nonrebreather mask for 4 min; (3) RA for 2-4 min. ASL data were motion corrected and used to calculate CBF. Changes of blood-oxygen level dependent (BOLD) and perfusion MRI signal intensities during NBO were calculated (along with Z-scores) using FEAT. Mean changes within the DWI lesion (Core), ipsilateral normal tissue (IPS) and contralesional hemisphere (CNL) were compared. Results: Patient characteristics (N=19) were age 62±13 years, median admission NIHSS 12 [IQR 3-12], time-to-MRI 33±13 h, median Core volume 31.2 [IQR 14.3-68] cc. 6 patients were imaged after tPA therapy. One subject’s CBF data were unusable due to artifacts. Both hyperemia (N=8) and hypoperfusion (N=12) were observed in areas in and around the DWI lesion. Baseline CBF in Core was significantly higher than in CNL (P=0.01) and IPS (P=0.03), indicative of hyperemia. No significant difference was found for perfusion change in response to NBO (mean Z-score < 1.1 for all regions). In contrast, strong positive and negative BOLD responses were found both ipsilaterally and contralaterally. Negative BOLD responses were significantly smaller (P Discussion: Our results confirm previous reports in both human and experimental stroke models of strong increases in BOLD signal in response to NBO challenges. In addition, we found negative BOLD responses both ipsilesionally and contralesionally, often in conjunction with hyperemia, perhaps suggesting a steal effect. Future research may further elucidate the complexities of oxygen metabolism in stroke, perhaps encouraging the development of novel therapies.

Background and Purpose —Better measures of cerebral tissue perfusion and earlier detection of ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia and early ischemic injury with combined diffusion-weighted (DW) and hemodynamically weighted (HW) MRI in patients with vasospasm after SAH. Methods —Combined DW and HW imaging was used to study 6 patients with clinical and angiographic vasospasm, 1 patient without clinical signs of vasospasm but with severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis of the passage of an intravenous contrast bolus through brain was used to construct multislice maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize that large HW imaging (HWI) abnormalities would be present in treated patients at the time they develop neurological deficit due to vasospasm without matching DW imaging (DWI) abnormalities. Results —Small, sometimes multiple, ischemic lesions on DWI were seen encircled by a large area of decreased rCBF and increased tMTT in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent. MRI hemodynamic abnormalities occurred in regions supplied by vessels with angiographic vasospasm or in their watershed territories. All patients with neurological deficit showed an area of abnormal tMTT much larger than the area of DWI abnormality. MRI images were normal in the asymptomatic patient with angiographic vasospasm and the patient with normal angiogram and no clinical signs of vasospasm. Conclusions —We conclude that DW/HW MRI in symptomatic vasospasm can detect widespread changes in tissue hemodynamics that encircle early foci of ischemic injury. With additional study, the technique could become a useful tool in the clinical management of patients with SAH.

Background and Purpose— The aim of this study was to correlate CT angiography-source image (CTA-SI) parenchymal hypoattenuation with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis. Methods— In 16 patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis, we graded CTA-SI parenchymal hypoattenuation in the medulla, pons, midbrain, thalamus, cerebellum, occipital lobe, inferior parietal lobe, and medial temporal lobe. The grading scale was: 0, no hypoattenuation; 1, 50% hypoattenuation. On CTA, we assessed clot location and length and collaterals. Outcome was measured with modified Rankin score. Results— Mean patient age was 68.3 years (range, 47 to 86 years), National Institutes of Health Stroke Scale was 28 (range, 11 to 40), time to CTA was 5.2 hours (range, 0.69 to 15.32), and time from CTA to intra-arterial thrombolysis was 5 hours (range, 2.25 to 10.38 hours). There were 4 basilar, 2 vertebral, and 10 combined occlusions. Eleven patients had near complete, 4 had partial, and one had no recanalization. Independent outcome predictors measured as modified Rankin score at 3 months were CTA-SI pons and midbrain scores(cumulative r =0.81, P P =0.0037) was the only independent predictor. Conclusion— Hypoattenuation in the pons and midbrain on pretreatment CTA-SI correlates highly with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis.

Background and Purpose —We sought to characterize the evolution of acute ischemic stroke by MRI and its relationship to patients’ neurological outcome. Methods —Fourteen patients with acute ischemic stroke underwent MRI within 13 hours of symptom onset (mean, 7.4±3 hours) and underwent repeated imaging and concurrent neurological examination at 8, 24, 36, and 48 hours and 7 days and >42 days after first imaging. Results —Diffusion-weighted imaging (DWI) lesion volumes increased between the first and second scans in 10 of 14 patients; scans with maximum DWI lesion volume occurred at a mean of 70.4 hours. Initial DWI lesion volume correlated with the largest T2 lesion volume ( r =0.97; P r =0.67; P =0.01) and maximum T2 lesion volume ( r =0.77; P r =−0.64; P P Conclusions —Serial MRI demonstrates the dynamic nature of progressive ischemic injury in acute stroke patients developing over hours to days, and it suggests that both primary and secondary pathophysiological processes can be valuable targets for neuroprotective interventions.

Background and Purpose —We sought to map early regional ischemia and infarction in patients with middle cerebral artery (MCA) stroke and compare them with final infarct size using advanced MRI techniques. MRI can now delineate very early infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by perfusion-weighted imaging (PWI). Methods —Seventeen patients seen within 12 hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI MRI. PWI maps were generated by analysis of the passage of intravenous contrast bolus through the brain. Cerebral blood volume (CBV) was determined after quantitative analysis of PWI data. Volumes of the initial DWI and PWI lesion were calculated and compared with a final infarct volume from a follow-up imaging study (CT scan or MRI). Results —Group 1 (10 patients) had MCA stem (M1) occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of CBV abnormality. In 7 patients the final stroke volume was larger or the same, and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the initial DWI lesion matched the initial CBV abnormality and the final infarct. Conclusions —Most patients with M1 occlusion showed progression of infarction into the region of abnormal perfusion. In contrast, patients with open M1 had strokes consistent with distal branch occlusion and had maximal extent of injury on DWI at initial presentation. Application of these MRI techniques should improve definition of different acute stroke syndromes and facilitate clinical decision making.

Background: Increases in oxygen extraction fraction (OEF) are postulated to be a marker of tissue at risk of infarction in acute ischemic stroke patients. R2’, a parameter that can be measured rapidly using an asymmetric spin echo MRI sequence (ASE), can be considered an OEF-weighted MRI metric, being a combination of both OEF and venous cerebral blood volume. We investigated the feasibility and utility of OEF-weighted MRI in acute stroke. Methods: Adult ischemic stroke patients were prospectively enrolled in a 3T MRI study of patients imaged within 48 hours of stroke onset. Only the subset of patients whose MRI included ASE and whose DWI was positive for acute infarction was analyzed. Acquisition time for ASE was 1.5 min. R2’ maps was calculated from ASE data on a voxel-wise basis after motion correction and smoothing. DWI and follow-up images (FU), when available, were co-registered to the ASE. Mean R2’ values and coefficient of variance (mean/SD) within the lesion, ipsilateral DWI-normal (IPS) and contralesional hemisphere (CNL) were calculated and compared. Results: Fifteen subjects met the inclusion criteria with mean±SD age 64±14 years, median admission NIHSS 12 [IQR 7-15] and time from onset to MRI 39±30 h. Eleven patients were imaged after tPA therapy. Both elevated and decreased R2’ were observed within DWI and FU lesions. Mean R2’ values in the DWI lesion (6.0±1.5 Hz) were significantly lower than CNL (7.2±0.6 Hz, P=0.02) and IPS (7.2±0.7 Hz, P=0.01). Coefficient of variance in R2’ values in the DWI lesion were also significantly lower than IPS (P=0.03) or CNL (P=0.05). For the 12 subjects with follow-up imaging, mean R2’ in tissue that eventually infarcted (5.7±1.8 Hz) was significantly lower (P=0.02) than in ipsilateral tissue surrounding the eventually infarcted lesion (7.3±0.6 Hz) but not significantly lower than DWI lesion values (6.1±1.6 Hz). Discussion: In this study using ASE, decreased OEF-weighted MRI values can potentially reflect tissue that is destined for infarction since OEF is proportional to cerebral oxygen metabolic rate. Increased OEF-weighted MRI values may be a sign of tissue that is at risk of infarction. Studies including measures of CBF and CBV will allow for better discrimination of tissue status.

Background and Purpose— Pretreatment infarct volume appears to predict clinical outcome after intra-arterial therapy. To confirm the importance of infarct size in patients undergoing intra-arterial therapy, we sought to characterize the relationship between final infarct volume (FIV) and long-term functional outcome in a prospective cohort of endovascularly treated patients. Methods— From our prospective intra-arterial therapy database, we identified 107 patients with acute ischemic stroke with anterior circulation proximal artery occlusions who underwent final infarct imaging and had 3-month modified Rankin Scale scores. Clinical, imaging, treatment, and outcome data were analyzed. Results— Mean age was 66.6 years. Median admission National Institutes of Health Stroke Scale score was 17. Reperfusion (Thrombolysis In Cerebral Infarction 2A–3) was achieved in 78 (72.9%) patients. Twenty-seven (25.2%) patients achieved a 3-month good outcome (modified Rankin Scale 0–2), and 30 (28.0%) died. Median FIV was 71.4 cm 3 . FIV independently correlated with functional outcome across the entire modified Rankin Scale. In receiver operating characteristic analysis, it was the best discriminator of both good outcome (area under the curve=0.857) and mortality (area under the curve=0.772). A FIV of approximately 50 cm 3 demonstrated the greatest accuracy for distinguishing good versus poor outcome, and a FIV of approximately 90 cm 3 was highly specific for a poor outcome. The interaction term between FIV and age was the only independent predictor of good outcome ( P Conclusions— Among patients with anterior circulation acute ischemic stroke who undergo intra-arterial therapy, final infarct volume is a critical determinant of 3-month functional outcome and appears suitable as a surrogate biomarker in proof-of-concept intra-arterial therapy trials.

Background: We investigated whether MRI-based algorithms combining acute DWI & PWI can be used to identify patients likely to experience lesion expansion. Methods: We analyzed MRI from 181 unilateral stroke patients who underwent DWI & PWI ≤ 12h from last seen well and had follow-up imaging (F/u) ≥4 days with lesions ≥ 1 cm 3 . Apparent diffusion coefficient, T2, DWI, CBF, CBV, MTT and Tmax (time of peak of deconvolved residue function) maps were co-registered, normalized and used as covariates in a model that produced infarction risk maps. Coefficients were calculated from 111 non-lysed patients and applied to 70 patients who received mechanical or drug lysis. Area under generated receiver operating characteristic curves (AUC) were calculated. Regional analyses were performed comparing mean risk values in Core (acute DWI), Growth (F/u - Core), Reverse (Core - F/u) and Normal (ipsilesional hemisphere - F/u) regions. Predicted lesion volumes (PLV) using a 50% risk threshold and post-hoc artifact removal for classifying infarcted tissue were correlated with the measured lesion volumes (MLV) on F/u. Values are median [IQR] or mean±SD. Results: The thrombolysis-treated group differed significantly from the non-lysis group in admission NIH Stroke Scale scores (12 [9-16] vs 6 [3-13]; P3 ; P=0.02) and F/u lesion volumes (39 [12-72] vs 17 [6-56] cm 3 ; P=0.02). No significant difference was found between age (67±15 vs 65±17 years old), male sex (59% vs 67%) and time to F/u (15 [6-47] vs 10 [6-46] days). Significant differences in predicted risk between the 4 regions were found for both lysed (Core: 0.72±0.15; Growth: 0.41±0.13; Reverse: 0.64±0.16; Normal: 0.25±0.06; P Conclusion: Mismatch in PLV and core can be used to identify patients most likely to experience lesion expansion if not given reperfusion therapy. The performance of the models was reduced in thrombolysed patients, which we propose is due to salvage of tissue that would have otherwise infarcted. MRI-based algorithms may identify patients who are not candidates for thrombolysis, yet have tissue to salvage. This may be useful as imaging selection criteria for future investigational trials of reperfusion therapy in extended time windows or for patients with unclear onsets.

Background and Purpose— The purpose of this study was to determine whether acute diffusion-weighted imaging (DWI) and mean transit time (MTT) lesion volumes and presenting National Institutes of Health Stroke Scale (NIHSS) can identify patients with acute ischemic stroke who will have a high probability of good and poor outcomes. Methods— Fifty-four patients with acute ischemic stroke who had MRI within 9 hours of symptom onset and 3-month follow-up with modified Rankin scale were evaluated. Acute DWI and MTT lesion volumes and baseline NIHSS scores were calculated. Clinical outcomes were considered good if the modified Rankin Scale was 0 to 2. Results— The 33 of 54 (61%) patients with good outcomes had significantly smaller DWI lesion volumes ( P =0.0001), smaller MTT lesion volumes ( P P 72 mL (13 of 54) and an NIHSS score >20 (6 of 54) had poor outcomes. All patients with an MTT volume of P =0.01). Conclusions— Combining quantitative DWI and MTT with NIHSS predicts good and poor outcomes with high probability and is superior to NIHSS alone.

Background and Purpose— The degree of internal carotid artery (ICA) stenosis is an established primary risk factor for embolic stroke. Recent publications suggest that inflammatory features may also play an important role. Our purpose was to correlate acute neurological symptoms with either carotid artery wall enhancement or plaque calcification, on axial CT angiographic source images (CTA-SI) of patients with severe (≥70%) ICA stenosis. Methods— 75 consecutive patients with ≥70% ICA stenosis on CTA-SI were identified. Each case was classified as symptomatic (n=37) or asymptomatic (n=38), and as having either calcified or noncalcified plaque. The latter group was stratified into those with versus without arterial wall enhancement, measured in absolute and relative Hounsfield Units (HU). Results— Calcified plaque was present in 39% (15/38) of the symptomatic patients and in 62% (23/37) of the asymptomatic patients ( P =0.065). Of the 37 patients without calcified plaque, carotid wall enhancement was observed in 83% (19/23) of the symptomatic, but only in 57% (8/14) of the asymptomatic patients ( P =0.041). When the “calcified plaque” and “no carotid wall enhancement” groups were pooled, versus the “carotid wall enhancement” group, enhancement was more likely in symptomatic patients (OR 3.625, CI 95% 1.3229 to 9.93, P =0.01 Fisher Exact test). Conclusions— In patients with severe ICA stenosis, additional stratification of stroke risk may be possible based on the presence of carotid wall enhancement on CTA-SI. Patients with carotid wall enhancement are more likely to be symptomatic, compared to those with either calcified plaque or no enhancement.

Background and Purpose— Leukoaraiosis (LA) is associated with structural and functional vascular changes that may compromise tissue perfusion at the microvascular level. We hypothesized that the volume of LA correlated with the proportion of initially ischemic but eventually infarcted tissue in acute human stroke. Methods— We studied 61 consecutive patients with diffusion-weighted imaging–mean transit time mismatch. All patients were scanned twice within 12 hours of symptom onset and between days 4 and 30. We explored the relationship between the volume of white matter regions with LA on acute images and the proportion of diffusion-weighted imaging–mean transit time mismatch tissue that progressed to infarction (percentage mismatch lost). Results— Bivariate analyses showed a statistically significant correlation between percentage mismatch lost and LA volume ( r =0.33, P P =0.04). The adjusted percentage mismatch lost in the highest quartile of LA volume was 1.9-fold (95% CI: 1.2 to 3.1) greater than the percentage mismatch lost in the lowest quartile. Conclusion— LA volume at the time of acute ischemic stroke is a predictor infarct growth. Because LA is associated with factors that modulate tissue perfusion as well as tissue capacity for handling of ischemia, LA volume appears to be a composite predictive marker for the fate of acutely ischemic tissue.

Background and Purpose— Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods— We randomized patients with acute stroke ( Results— Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (±SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8±22% versus 149.1±41%; P =0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline “ischemic” to 4-hour “non-ischemic” values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These “during-therapy” benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls ( P =0.6). Conclusions— High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Background and Purpose —Small infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions. Methods —Sixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission. Results —DWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem lesion in a penetrator territory that accounted for the clinical syndrome (“index lesion”) was found in all. DWI-hyperintense lesions other than the index lesion (“subsidiary infarctions”) were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently ( P Conclusions —Almost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI. This DWI finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention.

Background The pathophysiology of eclampsia remains unclear. While the majority of patients develop reversible T2 hyperintense signal abnormalities on MR scans and reversible neurological deficits, some patients do develop infarctions (permanent T2 hyperintense abnormalities) and permanent neurological impairment. Routine MRI cannot prospectively differentiate between these two patient groups. Echo-planar diffusion-weighted imaging, however, is a new technique that clearly differentiates between cytotoxic and vasogenic edema. Case Description A 30-year-old woman developed symptoms consistent with eclampsia 24 hours after delivering premature twins. An MRI demonstrated extensive, diffuse T2 hyperintense signal abnormalities involving subcortical white matter and adjacent gray matter with a posterior predominance, consistent with either infarction or hypertensive ischemic encephalopathy. Diffusion-weighted images demonstrated increased diffusion, consistent with vasogenic edema and hypertensive ischemic encephalopathy. Conclusions Unlike routine MRI, diffusion-weighted imaging reliably differentiates between vasogenic edema and cytotoxic edema. Consequently, in eclamptic patients diffusion-weighted imaging can afford clear differentiation between hypertensive ischemic encephalopathy and infarction, two very different entities with very different treatment protocols. Diffusion-weighted imaging should be performed in all eclamptic patients and should greatly affect their management.

To the Editor: We read with interest the recent article by Bandera and colleagues reporting their systematic review of cerebral blood flow (CBF) thresholds for ischemic penumbra and infarct core in acute ischemic stroke.1 Although we agree with the conclusion that further work is indeed required, before the use of CBF thresholds can become clinically routine, there are a number of important points not covered in this article that deserve further discussion. First and most important, this review is already dated in that there is …

P25 Purpose: To assess the utility of diffusion weighted imaging, cerebral blood volume, cerebral blood flow and mean transit time mapping in predicting final infarct volume in 81 patients with acute ischemic stroke. Methods: DWI, CBV, CBF and MTT images were obtained in 81 patients within 53 hours of stroke onset. Follow-up CT or T2 weighted MR images were obtained at 1 day to 4 months. Ischemic region volumes were measured on all images. An analysis of covariance with the variables of age, sex, treatment, time from stroke onset to imaging, and lesion type was performed. Linear regressions of DWI, CBV, CBF and MTT versus final infarct volume were obtained. A mismatch was determined if there was greater than 20% difference in volume between the diffusion and perfusion images. Results: Analysis of covariance demonstrated that DWI best predicts final infarct volume and that CBV alone of the other variables significantly improves the DWI prediction of final infarct volume. Linear regression analysis yielded an R 2 of 0.90, slope of 1.24 for DWI versus follow-up, R 2 of 0.84, slope of 1.22 for CBV versus follow-up, R 2 of 0.37, slope of 0.44 for CBF versus follow-up and R 2 of 0.25, slope of 0.33 for MTT versus follow-up. 13/81 patients had a DWI - CBV mismatch with mean lesion growth of 121 % while 68/81 patients had a DWI - CBV match with mean lesion growth of 15%. 36/81 had a DWI - CBF mismatch with mean lesion growth of 56% while 45/81 had a DWI - CBF match with mean lesion growth of 13%. 43/81 had a DWI - MTT mismatch with mean lesion growth of 47%. 38/81 had a DWI - MTT match with mean lesion growth of 16%. Conclusions: Both DWI and CBV are very good predictors of final infarct volume. CBF and MTT maps identify tissue at risk of infarction not identified on DWI or CBV maps. Since this tissue does not always infarct, these maps greatly overestimate final infarct size.The identification of a DWI - CBV, DWI - CBF or DWI - MTT mismatch predicts much more lesion growth compared with a diffusion perfusion match. This is most dramatic for DWI - CBV mismatches. This information may be valuable in the assessment of new therapeutic strategies.