Fast Automatic Detection of Large Vessel Occlusions on CT Angiography.

Background and Purpose- Accurate and rapid detection of anterior circulation large vessel occlusion (LVO) is of paramount importance in patients with acute stroke due to the potentially rapid infarction of at-risk tissue and the limited therapeutic window for endovascular clot retrieval. Hence, the optimal threshold of a new, fully automated software-based approach for LVO detection was determined, and its diagnostic performance evaluated in a large cohort study. Methods- For this retrospective study, data were pooled from: 2 stroke trials, DEFUSE 2 (n=62; 07/08-09/11) and DEFUSE 3 (n=213; 05/17-05/18); a cohort of endovascular clot retrieval candidates (n=82; August 2, 2014-August 30, 2015) and normals (n=111; June 6, 2017-January 28, 2019) from a single quaternary center; and code stroke patients (n=501; January 1, 2017-December 31, 2018) from a single regional hospital. All CTAs were assessed by the automated algorithm. Consensus reads by 2 neuroradiologists served as the reference standard. ROC analysis was used to assess diagnostic performance of the algorithm for detection of (1) anterior circulation LVOs involving the intracranial internal carotid artery or M1 segment middle cerebral artery (M1-MCA); (2) anterior circulation LVOs and proximal M2 segment MCA (M2-MCA) occlusions; and (3) individual segment occlusions. Results- CTAs from 926 patients (median age 70 years, interquartile range: 58-80; 422 females) were analyzed. Three hundred ninety-five patients had an anterior circulation LVO or M2-MCA occlusion (National Institutes of Health Stroke Scale 14 [median], interquartile range: 9-19). Sensitivity and specificity were 97% and 74%, respectively, for LVO detection, and 95% and 79%, respectively, when M2 occlusions were included. On analysis by occlusion site, sensitivities were 90% (M2-MCA), 97% (M1-MCA), and 97% (intracranial internal carotid artery) with corresponding area-under-the-ROC-curves of 0.874 (M2), 0.962 (M1), and 0.997 (intracranial internal carotid artery). Conclusions- Intracranial anterior circulation LVOs and proximal M2 occlusions can be rapidly and reliably detected by an automated detection tool, which may facilitate intra- and inter-instutional workflows and emergent imaging triage in the care of patients with stroke.

Cerebral Blood Flow Predicts the Infarct Core: New Insights From Contemporaneous Diffusion and Perfusion Imaging.

Background and Purpose- The aim of this study is to determine the spatial and volumetric accuracy of infarct core estimates from relative cerebral blood flow (rCBF) by comparison with near-contemporaneous diffusion-weighted imaging (DWI), and evaluate whether it is sufficient for patient triage to reperfusion therapies. Methods- One hundred ninety-three patients enrolled in the DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) and SENSE 3 (Sensitivity Encoding) stroke studies were screened, and 119 who underwent acute magnetic resonance imaging with DWI and perfusion imaging within 24 hours of onset were included. Infarct core was estimated using reduced rCBF at 12 thresholds (<0.20-<0.44) and compared against DWI (apparent diffusion coefficient <620 10-6mm2/s). For each threshold, volumetric agreement between the rCBF and DWI core estimates was assessed using Bland-Altman, correlation, and linear regression analyses; spatial agreement was assessed using receiver operating characteristic analysis. Results- An rCBF threshold of 0.32 yielded the smallest mean absolute volume difference (14.7 mL), best linear regression fit (R2=0.84), and best spatial agreement (Youden index, 0.38; 95% CI, 0.34-0.41) between rCBF and DWI, with high correlation (r=0.91, P<0.05), a small mean volume difference (1.3 mL) and no fixed bias (P<0.05). At this threshold, 110 of 119 (92.4%) patients were correctly triaged when applying 70 mL as the volume limit for thrombectomy. Spatial agreement was better for prediction of large infarcts (>70 mL) than small infarcts (≤70 mL), with Youden indices of 0.53 (95% CI, 0.49-0.56) and 0.34 (95% CI, 0.30-0.37), respectively. Conclusions- Strong correlation and agreement with near-contemporaneous DWI indicate that infarct core estimates obtained using rCBF are sufficiently accurate for patient triage to reperfusion therapies. The identified optimal rCBF threshold of 0.32 closely approximates the threshold currently used in clinical practice.

Automated Detection of Intracranial Large Vessel Occlusions on Computed Tomography Angiography: A Single Center Experience.

Background and Purpose- Endovascular thrombectomy is highly effective in acute ischemic stroke patients with an anterior circulation large vessel occlusion (LVO), decreasing morbidity and mortality. Accurate and prompt identification of LVOs is imperative because these patients have large volumes of tissue that are at risk of infarction without timely reperfusion, and the treatment window is limited to 24 hours. We assessed the accuracy and speed of a commercially available fully automated LVO-detection tool in a cohort of patients presenting to a regional hospital with suspected stroke. Methods- Consecutive patients who underwent multimodal computed tomography with thin-slice computed tomography angiography between January 1, 2017 and December 31, 2018 for suspected acute ischemic stroke within 24 hours of onset were retrospectively identified. The multimodal computed tomographies were assessed by 2 neuroradiologists in consensus for the presence of an intracranial anterior circulation LVO or M2-segment middle cerebral artery occlusion (the reference standard). The patients' computed tomography angiographies were then processed using an automated LVO-detection algorithm (RAPID CTA). Receiver-operating characteristic analysis was used to determine sensitivity, specificity, and negative predictive value of the algorithm for detection of (1) an LVO and (2) either an LVO or M2-segment middle cerebral artery occlusion. Results- CTAs from 477 patients were analyzed (271 men and 206 women; median age, 71; IQR, 60-80). Median processing time was 158 seconds (IQR, 150-167 seconds). Seventy-eight patients had an anterior circulation LVO, and 28 had an isolated M2-segment middle cerebral artery occlusion. The sensitivity, negative predictive value, and specificity were 0.94, 0.98, and 0.76, respectively for detection of an intracranial LVO and 0.92, 0.97, and 0.81, respectively for detection of either an intracranial LVO or M2-segment middle cerebral artery occlusion. Conclusions- The fully automated algorithm had very high sensitivity and negative predictive value for LVO detection with fast processing times, suggesting that it can be used in the emergent setting as a screening tool to alert radiologists and expedite formal diagnosis.

Automated Calculation of Alberta Stroke Program Early CT Score: Validation in Patients With Large Hemispheric Infarct.

Background and Purpose- We compared the Alberta Stroke Program Early CT Score (ASPECTS), calculated using a machine learning-based automatic software tool, RAPID ASPECTS, as well as the median score from 4 experienced readers, with the diffusion-weighted imaging (DWI) ASPECTS obtained following the baseline computed tomography (CT) in patients with large hemispheric infarcts. Methods- CT and magnetic resonance imaging scans from the GAMES-RP study, which enrolled patients with large hemispheric infarctions (82-300 mL) documented on DWI-magnetic resonance imaging, were evaluated by blinded experienced readers to determine both CT and DWI ASPECTS. The CT scans were also evaluated by an automated software program (RAPID ASPECTS). Using the DWI ASPECTS as a reference standard, the median CT ASPECTS of the clinicians and the automated score were compared using the interclass correlation coefficient. Results- The median CT ASPECTS for the clinicians was 5 (interquartile range, 4-7), for RAPID ASPECTS 3 (interquartile range, 1-6), and for DWI ASPECTS 3 (2-4). Median error for RAPID ASPECTS was 1 (interquartile range, -1 to 3) versus 3 (interquartile range, 1-4) for clinicians (P<0.001). The automated score had a higher level of agreement with the median of the DWI ASPECTS, both for the full scale and when dichotomized at <6 versus 6 or more (difference in intraclass correlation coefficient, P=0.001). Conclusions- RAPID ASPECTS was more accurate than experienced clinicians in identifying early evidence of brain ischemia as documented by DWI.

Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke.

BACKGROUND AND PURPOSE: This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. METHODS: We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5. RESULTS: Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001). CONCLUSIONS: Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke.

OBJECTIVE: To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS: We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging. RESULTS: Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140). INTERPRETATION: The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes.

BACKGROUND AND PURPOSE: The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature. METHODS: We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time. RESULTS: We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R2=0.49). CONCLUSIONS: This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended.

Reperfusion of very low cerebral blood volume lesion predicts parenchymal hematoma after endovascular therapy.

BACKGROUND AND PURPOSE: Ischemic stroke patients with regional very low cerebral blood volume (VLCBV) on baseline imaging have increased risk of parenchymal hemorrhage (PH) after intravenous alteplase-induced reperfusion. We developed a method for automated detection of VLCBV and examined whether patients with reperfused-VLCBV are at increased risk of PH after endovascular reperfusion therapy. METHODS: Receiver operating characteristic analysis was performed to optimize a relative CBV threshold associated with PH in patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study. Regional reperfused-VLCBV was defined as regions with low relative CBV on baseline imaging that demonstrated normal perfusion (Tmax <6 s) on coregistered early follow-up magnetic resonance imaging. The association between VLCBV, regional reperfused-VLCBV and PH was assessed in univariate and multivariate analyses. RESULTS: In 91 patients, the greatest area under the curve for predicting PH occurred at an relative CBV threshold of <0.42 (area under the curve, 0.77). At this threshold, VLCBV lesion volume ≥3.55 mL optimally predicted PH with 94% sensitivity and 63% specificity. Reperfused-VLCBV lesion volume was more specific (0.74) and equally sensitive (0.94). In total, 18 patients developed PH, of whom 17 presented with VLCBV (39% versus 2%; P=0.001), all of them had regional reperfusion (47% versus 0%; P=0.01), and 71% received intravenous alteplase. VLCBV lesion (odds ratio, 33) and bridging with intravenous alteplase (odds ratio, 3.8) were independently associated with PH. In a separate model, reperfused-VLCBV remained the single independent predictor of PH (odds ratio, 53). CONCLUSIONS: These results suggest that VLCBV can be used for risk stratification of patients scheduled to undergo endovascular therapy in trials and routine clinical practice.

Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy.

BACKGROUND AND PURPOSE: The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion. METHODS: Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status. RESULTS: A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion<50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria. CONCLUSIONS: The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset.

BACKGROUND AND PURPOSE: The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient. METHODS: MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed. RESULTS: A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion. CONCLUSIONS: Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

Hypoperfusion intensity ratio predicts infarct progression and functional outcome in the DEFUSE 2 Cohort.

BACKGROUND AND PURPOSE: We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2). METHODS: Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days. RESULTS: Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014. CONCLUSIONS: HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke. METHODS: Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90. RESULTS: Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06). CONCLUSIONS: Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

Advanced imaging improves prediction of hemorrhage after stroke thrombolysis.

OBJECTIVE: Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. METHODS: The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging. RESULTS: In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. INTERPRETATION: VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion.

Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE 2.

BACKGROUND AND PURPOSE: It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume. METHODS: This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes. RESULTS: Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2). CONCLUSIONS: Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies.

BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSION: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

Impact of diffusion-weighted imaging lesion volume on the success of endovascular reperfusion therapy.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. METHODS: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005). CONCLUSIONS: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study.

BACKGROUND AND PURPOSE: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. METHODS: The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. RESULTS: From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups. CONCLUSIONS: The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.

Prospective optical motion correction for 3D time-of-flight angiography.

Magnetic resonance angiograms are often nondiagnostic due to patient motion. In clinical practice, the available time to repeat motion-corrupted scans is very limited--especially in patients who suffer from acute cerebrovascular conditions. Here, the feasibility of an optical motion correction system to prospectively correct patient motion for 3D time-of-flight magnetic resonance angiography was investigated. Experiments were performed on five subjects with and without parallel imaging (SENSE R=2) on a 1.5 T unit. Two human readers assessed the data and were in good agreement (kappa: 0.77). The results from this study indicate that the optical motion correction system greatly reduces motion artifacts when motion was present and did not impair the image quality in the absence of motion. Statistical analysis showed no significant difference between the (vendor-provided) SENSE and the nonaccelerated acquisitions. In conclusion, the optical motion correction system tested in this study has the potential to greatly improve 3D time-of-flight angiograms regardless of whether it is used with or without SENSE.

Insula-specific H magnetic resonance spectroscopy reactions in heavy smokers under acute nicotine withdrawal and after oral nicotine substitution.

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.

Patients with the malignant profile within 3 hours of symptom onset have very poor outcomes after intravenous tissue-type plasminogen activator therapy.

BACKGROUND AND PURPOSE: The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset. METHODS: The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6). RESULTS: Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74±14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001). CONCLUSIONS: The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.