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Originally Published 2 December 2010
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EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration

Yoshinari Nagakane, MD, PhD, Soren Christensen, PhD, Caspar Brekenfeld, MD, Henry Ma, MBBS, Leonid Churilov, PhD, Mark W. Parsons, PhD, FRACP, Christopher R. Levi, FRACP, … Show All … , Kenneth S. Butcher, MD, PhD, Andre Peeters, MD, P. Alan Barber, PhD, Christopher F. Bladin, PhD, Deidre A. De Silva, MBBS, MRCP, FAMS, John Fink, FRACP, Thomas E. Kimber, PhD, FRACP, David W. Schultz, FRACP, Keith W. Muir, MD, Brian M. Tress, MD, FRANZCR, FRCR, Patricia M. Desmond, MD, Stephen M. Davis, MD, FRACP, and Geoffrey A. Donnan, MD, FRACP for the EPITHET InvestigatorsAuthor Info & Affiliations
Stroke
Volume 42, Number 1
https://doi.org/10.1161/STROKEAHA.110.580464
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Abstract

Background and Purpose—

The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated.

Methods—

Patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusion-weighted imaging volume ratio was >1.2 and total coregistered mismatch volume was ≥10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch.

Results—

Of 99 patients with baseline diffusion-weighted imaging and perfusion-weighted imaging, coregistration of both images was possible in 95 patients. Coregistered mismatch was present in 93% (88/95) compared to 85% (81/95) with standard volumetric mismatch. In the coregistered mismatch patients, of whom 45 received alteplase and 43 received placebo, the primary outcome measure of geometric mean infarct growth was significantly attenuated by a ratio of 0.58 with alteplase compared to placebo (1.02 vs 1.77; 95% CI, 0.33–0.99; P=0.0459).

Conclusions—

When using coregistration techniques to determine the presence of mismatch at study entry, alteplase significantly attenuated infarct growth. This highlights the necessity for a randomized, placebo-controlled, phase III clinical trial of alteplase using penumbral selection beyond 3 hours.
Reperfusion therapies including intravenous thrombolysis with recombinant tissue plasminogen activator are based on the premise that ischemic penumbral tissue is at risk for infarction but has the potential to be salvaged by reperfusion.1 With the advent of MRI techniques, the mismatch concept defined by the perfusion-weighted imaging (PWI) lesion exceeding the diffusion-weighted imaging (DWI) lesion was postulated as a penumbral marker.2 Since then, MR PWI/DWI has become a widely used imaging research technique in the assessment of acute stroke patients.3
Mismatch volume (MV) is conventionally calculated using a volumetric method in which the DWI lesion volume is simply subtracted from the PWI volume.2 This method assumes that ischemic core represented by the DWI lesion is surrounded by a hypoperfused area defined by the PWI lesion.4 However, the region of hypoperfusion fluctuates in the hours after stroke onset attributable to processes such as spontaneous reperfusion and changes in collateral blood flow.5 Early reperfusion of the infarct core may result in a component of the DWI lesion lying outside the PWI lesion.6 Coregistration of DWI and PWI images allows a more precise estimate of these spatial relationships, with simple volumetric analysis consistently underestimating the mismatch volume when compared to the coregistration method.7
The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a phase II, prospective, randomized, double-blinded, placebo-controlled, multinational trial of 101 patients treated between 3 and 6 hours after stroke onset.8 Importantly, the primary hypothesis was that patients with mismatch (defined by the standard volumetric method) who received alteplase would have attenuation of infarct growth seen on MRI. Although there was a trend toward attenuation of infarct growth, this did not reach statistical significance. Given that the mismatch assessment in EPITHET by the volumetric method may have underestimated the mismatch volume and, hence, the target population in whom the primary hypothesis was tested, we reanalyzed the dataset using coregistration of DWI/PWI images at baseline. We hypothesized that this may have increased the number of patients with eligible mismatch and that this, in turn, may have influenced the effects of alteplase on attenuation of infarct growth.

Patients and Methods

Imaging Protocol

The study design of EPITHET, including patient eligibility, treatment allocation, and imaging protocol, has been previously reported.8 Briefly, patients with acute hemispheric ischemic stroke who presented 3 to 6 hours after symptom onset were assigned to intravenous alteplase or placebo and had DWI, PWI, and MRA sequences with 1.5-T echoplanar-equipped MRI scanners before treatment and again at days 3 to 5. At day 90, T2-weighted images were obtained to measure final infarct volume.

Imaging Analysis

Baseline DWI was registered to the baseline PWI using MINC software (The McConnell Brain Imaging Centre) by 1 investigator (Y.N.) blinded to treatment assignment but not to time point. First, automatic registration was applied to register baseline DWI to the PWI frame. Second, manual landmark-based registration was used to initialize another automatic registration in cases in which automatic coregistration failed on the first attempt. The quality of coregistration was reviewed by a second investigator (S.C.).
Using these coregistration techniques, the baseline DWI lesion was divided into 2 regions: DWI within and DWI outside of the PWI volume (Figure 1). Regions of interest on DWI and T2-weighted images, Tmax map, and MRA ratings were unaltered from the original trial. Similarly, hypoperfusion volumes were defined using a Tmax delay of ≥2 seconds as previously described. For patients who died or who could not be studied at day 90, the last results at days 3 to 5 were carried forward as a measure of imaging outcome.
Figure 1. A, Coregistration of perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) allows the DWI lesion to be divided into 2 regions: DWI within (wDWI; yellow) and DWI lying outside the PWI lesion (oDWI; red). Using the volumetric technique, the mismatch volume (MV) is PWI−(wDWI+oDWI), whereas the coregistered MV (green) is defined as PWI−wDWI. An 82-year-old woman with baseline MRI performed 325 minutes after stroke onset. The baseline DWI lesion volume was 65.3 mL (B) and PWI lesion volume was 68.8 mL (C; green areas indicate PWI abnormalities of Tmax 2 seconds or more). In EPITHET using the volumetric technique, she was classified as having no mismatch (3.5 mL); however, while coregistered (D), she was classified as having mismatch (26.2 mL; wDWI in yellow, oDWI in red, and coregistered mismatch areas in green).

Definitions

All definitions were as in the main EPITHET study except for the addition of coregistered mismatch (Table 1).8
Table 1. Definitions
Coregistered mismatch: PWI÷wDWI volume >1.2, and PWI−wDWI volume ≥10 mL
Volumetric mismatch: PWI÷DWI volume >1.2, and PWI−DWI volume ≥10 mL
Infarct growth: expansion between baseline DWI and day-90 T2-weighted lesion
    Geometric mean: exponential of mean log relative growth
    Relative growth: final lesion volume÷baseline DWI lesion volume
    Absolute growth: final lesion volume−baseline DWI lesion volume
    Difference in cube root volumes: (final lesion volume)1/3−(baseline DWI lesion volume)1/3
    Any growth: relative growth >0%
Malignant profile: DWI volume and/or PWI volume with Tmax ≥8 seconds ≥100 mL
Reperfusion: >90% reduction between baseline and day-3 PWI volumes
Recanalization: improvement from baseline to day 3 to 5 in arterial obstruction by ≥2 points, based on an adaptation of the thrombolysis in myocardial infarction grading on MRA (0=complete occlusion, 1=severe stenosis, 2=mild to moderate stenosis, and 3=normal arterial caliber)
Symptomatic ICH: ICH with significant clinical deterioration of ≥4 NIHSS points within 36 hours of treatment and parenchymal hemorrhage of grade 2 on CT (blood clots in >30% of the infarcted area with substantial space-occupying effect) adjudicated by a blinded committee (SITS-MOST definition)9
Good neurological outcome: NIHSS at day 90 of 0 or 1 or improvement ≥8 from baseline
Good functional outcome: modified Rankin scale at day 90 of 0 to 2
DWI indicates diffusion-weighted imaging; ICH, intracerebral hemorrhage; PWI, perfusion-weighted imaging; wDWI, diffusion-weighted imaging within the perfusion-weighted imaging lesion.

Outcome Measures

The primary outcome measure was infarct growth attenuation in coregistered mismatch patients between alteplase and placebo, primarily analyzed by geometric mean and secondarily by relative growth, absolute growth, and difference in cube root lesion volumes. Secondary end points included reperfusion, clinical outcomes, recanalization, and symptomatic intracerebral hemorrhage.

Statistical Analysis

Statistical analyses were performed using Stata/IC 10 (StataCorp). The comparisons between volumetric and coregistration methods were made with Wilcoxon signed-rank test for continuous variables and with McNemar exact test for categorical variables. The agreement between the original DWI volumes and the coregistered DWI volumes was assessed by Lin's concordance coefficient and intraclass correlation coefficient. As per the original protocol of EPITHET, the difference in means of log-relative growth between patients treated with alteplase and with placebo was tested by t test. The 2-sample Wilcoxon rank-sum test was used for the comparison of relative growth, absolute growth, and the difference of cube root transformed volume change. Hodges-Lehman shift parameter was used to estimate effect sizes for the comparisons when the Wilcoxon rank-sum test was used. Fisher exact test was used to compare patients treated with alteplase and with placebo in respect to the presence or absence of growth (any), reperfusion, and recanalization status, as well as for clinical outcomes. As per the original EPITHET analysis, no adjustments for multiple comparisons were made.

Results

Ninety-nine of 101 patients enrolled in EPITHET had baseline DWI and PWI and were included in this study. Automatic coregistration of baseline DWI and PWI succeeded in 95 of 99 patients, with 5 patients requiring initialization by manual landmarks. Coregistration failed in 4 (4%) patients because of artifact (3 had severe ghost artifacts of PWI and 1 had DWI motion artifacts), and these patients were excluded from subsequent analysis.
Table 2 shows baseline imaging variables for the 95 patients. Transformation of DWI into PWI space during the coregistration process resulted in baseline DWI volume increasing slightly from 20 mL (range, 0–197) to 21 mL (range, 0–204), and the agreement on the DWI volumes between original and after coregistration was confirmed by both intraclass correlation coefficient of 1.00 (95% CI, 0.98–1.00) and Lin concordance coefficient of 0.996 (0.995–0.998). After coregistration, median baseline DWI within and DWI outside the PWI lesion volumes were 13 mL (range, 0–152) and 5 mL (range, 0–119), respectively. Median baseline coregistered MV was significantly larger than baseline volumetric MV (128 mL vs 118 mL), with median difference of 5 mL (interquartile range, 3–12; 95% CI, 4–6; P<0.0001). Because 7 patients with no mismatch by the volumetric method had mismatch by the coregistration method (Figure 1B), the prevalence of mismatch increased from 85% (81/95) by the volumetric method to 93% (88/95) by the coregistration method (P=0.0156).
Table 2. Baseline Imaging Variables for 95 Patients
 Alteplase (n=49)Placebo (n=46)
Median baseline DWI volume (mL)20 (0–188)21 (0–204)
Median baseline wDWI volume (mL)10 (0–152)16 (0–150)
Median baseline PWI volume (mL)142 (0–558)192 (0–428)
Median baseline mismatch volume (mL)  
    Volumetric method95 (−10–455)136 (−93–422)
    Coregistration method99 (0–466)152 (0–422)
Mismatch  
    Volumetric method40 (82)41 (89)
    Coregistration method45 (92)43 (93)
DWI indicates diffusion-weighted imaging; PWI, perfusion-weighted imaging; wDWI, diffusion-weighted imaging within the perfusion-weighted imaging lesion.
Data are median (range) or N (%) of patients.
Figure 2 shows the study profile and Table 3 shows baseline characteristics for mismatch patients with valid imaging outcomes. Of the 101 enrolled patients, 91 patients had baseline PWI and DWI with a day-90 T2-weighted image or with a surrogate day-3 to day-5 DWI for the final lesion. Because of coregistration failure in 4 patients (2 each in the alteplase and placebo groups), 87 patients were assessed for mismatch between PWI and DWI and 80 had mismatch (38 received alteplase and 42 received placebo). Baseline variables of patients with mismatch did not significantly differ (P≥0.1) between alteplase and placebo groups (Table 3), and no statistical correction was needed.
Figure 2. Trial profile. *Last observation carried forward (LOCF) data were used in 11 patients. †LOCF data were used in 7 patients.
Table 3. Baseline Characteristics for Patients With Coregistered Mismatch
 Alteplase (n=38)Placebo (n=42)P
Age (y)  0.7835
    Mean71.7 (14.1)71.3 (13.6) 
    Median75 (23–87)74 (39–92) 
Male15 (39%)20 (48%)0.505
Hypertension29 (76%)27 (64%)0.329
Diabetes mellitus9 (24%)10 (24%)>0.999
Hyperlipidemia18 (47%)14 (33%)0.255
Atrial fibrillation17 (45%)15 (36%)0.495
Current or past smoker11 (29%)19 (45%)0.168
Median NIHSS at presentation13 (4–23)11 (5–25)0.4778
Time to treatment (min)  0.9041
    Mean296 (44)294 (49) 
    Median303 (187–365)306 (195–365) 
Median baseline DWI volume (mL)21 (2–188)21 (0–204)0.8059
Median baseline PWI volume (mL)147 (13–558)199 (40–428)0.3353
Median baseline mismatch volume (mL)   
    Volumetric method105 (−10–455)157 (−93–422)0.3702
    Coregistration method110 (11–466)162 (26–422)0.3163
Malignant profile*12 (32%)16 (38%)0.641
DWI indicates diffusion-weighted imaging; PWI, perfusion-weighted imaging.
Data are mean (SD), median (range), or N (%) of patients.
*
DWI volume ≥100 mL, PWI volume ≥100 mL, or both, with Tmax delay ≥8 sec.
For the primary outcome measure using the originally prespecified analytic method (geometric mean growth), the coregistered mismatch patients showed significant infarct growth attenuation with alteplase compared to placebo (1.02 vs 1.77; ratio, 0.58; 95% CI, 0.33–0.99; P=0.0459; Table 4). When the geometric mean growth was compared among the volumetric mismatch patients without coregistration, infarct growth attenuation did not differ between the treatment groups (1.06 vs 1.79; ratio, 0.59; 95% CI, 0.32–1.06; P=0.0779). This was confirmed by significant attenuation in infarct growth by the secondary analytical methods: relative growth (P=0.0139), absolute growth (P=0.0332), and difference in cube root lesion volume (P=0.0204). Further additional analytical methods including the proportion of patients who had any growth (P=0.0216), ratio of geometric mean (P=0.0113), and median relative growth (P=0.0038) in patients with a baseline lesion of >5 mL (33 patients in the alteplase group and 36 in the placebo group) also showed a positive effect of alteplase compared to placebo.
Table 4. Trial Outcomes for Patients With Coregistered Mismatch
 AlteplasePlaceboDifference or Ratio (95% CI)*P
Infarct growthn=38n=42  
Primary analytical method    
    Geometric mean1.021.770.58† (0.33–0.99)0.0459
Secondary analytical methods    
    Median relative growth1.00 (0.50–1.80)1.70 (1.00–3.10)0.57† (0.36–0.88)0.0139
    Median absolute growth (mL)−0.2 (−5.7–32.1)27.4 (−0.2–55.6)−12.2‡ (−31.8–0.7)0.0332
    Mean difference in cube root volumes (cm)0.27 (1.19)0.71 (1.06)−0.43 (−0.94–0.06)0.0855
    Median difference in cube root volumes (cm)0.0 (−0.4–0.7)0.5 (0.0–1.2)−0.5‡ (−0.9 to −0.1)0.0204
Additional analytical methods    
    Growth >0%18 (47%)31 (74%)−26% (−47% to −6%)0.0216
Baseline DWI lesions >5 mL    
    Geometric mean growth§1.042.010.52† (0.31–0.86)0.0113
    Median relative growth§1.00 (0.50–1.80)1.85 (1.30–3.20)0.53† (0.33–0.77)0.0038
    Reperfusion assessedn=34n=42  
    Reperfusion ≥90%20 (59%)11 (26%)33% (11%–54%)0.0052
    Median percentage reperfusion93% (68–100)53% (16 to 93)18% (3%–53%)0.0088
    Recanalization assessedn=17n=26  
    Recanalization13 (76%)14 (54%)22% (−5%–50%)0.1994
    Clinical outcomesn=45n=43  
    Good neurological outcome23 (51%)16 (37%)14% (−7%–34%)0.2056
    mRS 0–220 (44%)17 (40%)5% (−16%–26%)0.6712
    mRS 0–116 (36%)9 (21%)15% (−4%–33%)0.1591
DWI indicates diffusion-weighted imaging; mRS, modified Rankin Scale.
Data are mean (SD), N (%) of patients, or median (interquartile range).
*
Difference of average or percentage for alteplase minus that for placebo, unless indicated as a ratio or median difference.
†
Ratios.
‡
Median difference estimated by Hodges-Lehman shift parameter (95% CI).
§
Data for patients with baseline lesion >5 mL: 33 (87%) in the alteplase group and 36 (86%) in the placebo group.
For secondary outcome measures, 76 of the 88 coregistered mismatch patients had a valid PWI volume at days 3 to 5 to assess reperfusion, and all 88 had assessment of clinical outcome (Tables 4 and the online-only supplemental Table, available at http://stroke.ahajournals.org). Both the incidence of reperfusion (≥90%) and the median percentage of reperfusion were significantly higher in patients with coregistered mismatch who received alteplase. Reperfusion was significantly associated with infarct growth attenuation, good neurological outcome, and good functional outcome in patients with coregistered mismatch. As with the original EPITHET analysis, which was not powered for a clinical outcome, the difference in good neurological and functional outcomes between the alteplase and placebo groups was not significant in patients with coregistered mismatch. Recanalization could be assessed with adequate MRA scans in 43 patients with coregistered mismatch, and it occurred in 27 (63%) of these patients (Table 4). The proportion of recanalization did not differ between treatment arms.
Symptomatic intracerebral hemorrhage was seen in 8.0% (4/50) of patients treated with alteplase. All patients had mismatch by the coregistration method, whereas 3 out of 4 had mismatch by the volumetric method. Median baseline DWI volume did not differ between patients with symptomatic intracerebral hemorrhage (43 mL; interquartile range, 31–101) and those without symptomatic intracerebral hemorrhage (15 mL; interquartile range, 7–37; P=0.058).
Primary outcome could be assessed in 7 patients without coregistered mismatch. Infarct growth did not differ significantly between the alteplase and placebo groups (geometric mean growth 0.93 vs 1.03; ratio, 0.91; 95% CI, 0.31–2.66; P=0.8283). Between mismatch and nonmismatch patients in the alteplase group, infarct growth, reperfusion rate, and clinical outcomes did not differ significantly.

Discussion

The efficacy analysis in EPITHET, although negative on the prespecified primary outcome, provided strong support for further investigation of the use of PWI/DWI mismatch in the identification of favorable reperfusion outcomes with alteplase. By applying the coregistration method to assess MV at study entry, we found that the prevalence of mismatch patients was increased and resulted in a positive outcome of EPITHET for the primary end point of infarct growth attenuation with alteplase in mismatch patients. As in EPITHET, we also found a strongly positive relationship between reperfusion and both attenuation of infarct growth and good clinical outcome in the coregistered mismatch group. These results emphasize the concept that selecting patients with PWI/DWI mismatch beyond 3 hours might be a useful approach to extend the time window for thrombolytic therapy.10,11 Our findings can now be put in the context of EPITHET, in which there was a borderline significant attenuation in relative infarct growth with alteplase in patients with standard volumetric mismatch. Interestingly, the coregistered mismatch definition appears to be a more sensitive selection criterion, with all measures of infarct growth showing significant attenuation with alteplase in patients included in EPITHET using this approach.
The great advantage of coregistration of PWI and DWI is that it allows a more precise estimate of the spatial relationship between these imaging modalities to occur and, hence, a better understanding of the dynamic nature of the evolving ischemia and reperfusion process. In particular, it becomes clear that portions of the DWI lesions have already reperfused at the time of imaging and, under these circumstances, the volumetric method does underestimate the true proportion of mismatch.7 This is illustrated in Figure 1A, in which the coregistered MV is greater than the volumetric MV by the amount of the DWI outside volume (the volume of the DWI portion lying outside the PWI lesion). Already reperfused DWI tissue has previously been labeled by reversible acute diffusion lesion already reperfused.6 This particular region is most likely to recover if reperfusion occurs within 6 hours of symptom onset. Overall, in the current study, MV calculated by the coregistration method was a median of 5 mL (95% CI, 4–6) larger than that calculated by the volumetric method.
Interestingly, using a higher Tmax threshold instead of Tmax 2-second delay may cause an even larger difference between volumetric and coregistered MV. For example, when using Tmax 6-second threshold, PWI lesion volumes were smaller than those using Tmax 2 seconds (median, 82 vs 162 mL); this made DWI within smaller (10 vs 13 mL) and DWI outside larger (8 vs 5 mL). Although median MV were 48 mL and the prevalence of mismatch was 76% (72/95) by the volumetric method, median MV were 63 mL and the prevalence of mismatch was 85% (81/95) by the coregistration method. In other words, this confirms that the differences between the volumetric and coregistration methods were greater when using Tmax 6 seconds rather than Tmax 2 seconds. It is worth noting that the same central processing and data analysis techniques as the original EPITHET were used, apart from the addition of the coregistration components.
There are some limitations to this study. First, some patients were excluded from the analysis because of coregistration failure, mainly attributable to inadequate imaging quality. Therefore, the altered trial results cannot be attributed exclusively to the inclusion of additional patients. There is a constant improvement occurring in the quality of DWI and PWI imaging techniques with software and MR hardware developments. In the clinical trial setting, imaging quality is better-controlled and may allow the support of successful coregistration procedures (including manual adjustment when required), whereas in a clinical setting, volumetric mismatch would seem to be a realistic “fall-back“ option in cases in which registration fails. Second, the coregistration method here was only used to select patients and not to assess infarct growth, which requires the presence of follow-up MR images. Coregistration is possible but less reliable at later time points because of the structural changes associated with later infarct volumes, hemorrhagic transformation, and shrinkage. Although it seems likely that automated coregistration software without manual quality control may become a reality in the near future, its clinical use is likely to be restricted to the acute assessment only as it was in the current study. Third, this study was a post hoc analysis and, therefore, does not provide any change in interpretation of the original results of EPITHET. Despite these limitations, this study provided a more ideal mismatch analysis approach for selecting eligible candidates for thrombolytic therapy beyond the 3-hour time window. This suggests that there is a need to develop appropriate software to provide rapid coregistered image analysis.

Supplemental Material

File (580464datasupp.pdf)
File (nagakane_59.pdf)
File (nagakone_59.pdf)

Sources of Funding

National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; and Heart Foundation of Australia.

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On the cover: The illustration is taken from an article in this issue “Critical Roles of Macrophages in the Formation of Intracranial Aneurysm” by Kanematsu et al (Stroke. 2011;42:173–178).

Stroke
Volume 42 • Number 1 • January 2011
Pages: 59 - 64
PubMed: 21127303

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© 2010 American Heart Association, Inc.

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History

Received: 4 February 2010
Accepted: 29 July 2010
Published online: 2 December 2010
Published in print: January 2011

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Keywords

  1. magnetic resonance imaging
  2. mismatch
  3. penumbra
  4. tissue plasminogen activator

Subjects

  1. Computerized Tomography (CT)

Authors

Affiliations

Yoshinari Nagakane, MD, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Soren Christensen, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Caspar Brekenfeld, MD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Henry Ma, MBBS
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Leonid Churilov, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Mark W. Parsons, PhD, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Christopher R. Levi, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Kenneth S. Butcher, MD, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Andre Peeters, MD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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P. Alan Barber, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Christopher F. Bladin, PhD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Deidre A. De Silva, MBBS, MRCP, FAMS
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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John Fink, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Thomas E. Kimber, PhD, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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David W. Schultz, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Keith W. Muir, MD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Brian M. Tress, MD, FRANZCR, FRCR
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Patricia M. Desmond, MD
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Stephen M. Davis, MD, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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Geoffrey A. Donnan, MD, FRACP
From the National Stroke Research Institute (Y.N., C.B., H.M., L.C., G.A.D.), Florey Neuroscience Institutes, Austin Health, University of Melbourne, Australia; Department of Neurology (S.C., D.A.D.S., S.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia; Institute of Interventional and Diagnostic Neuroradiology (C.B.), University of Bern, Switzerland; Department of Mathematics and Statistics (L.C.), University of Melbourne, Australia; Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; Department of Neurology (K.S.B.), University of Alberta, Edmonton, Alberta, Canada; University Hospital St Luc (A.P.), Brussels, Belgium; Neurology Department (P.A.B.), Auckland City Hospital, Grafton, Auckland, New Zealand; Eastern Melbourne Neurosciences (C.F.B.), Melbourne, Australia; Department of Neurology (D.A.D.S.), Singapore General Hospital campus, National Neuroscience Institute, Singapore; Department of Neurology (J.F.), Christchurch Hospital, Christchurch, New Zealand; Royal Adelaide Hospital (T.E.K.), Adelaide, Australia; Department of Neurology (D.W.S.), Flinders Medical Centre, Bedford Park, Australia; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, UK; Department of Radiology (B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Australia.
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for the EPITHET Investigators

Notes

The online-only Data Supplement is available at http://stroke.ahajournals.org/cgi/content/full/STROKEAHA.110.580464/DC1.
Correspondence to Geoffrey A. Donnan, Florey Neuroscience Institutes, University of Melbourne, Level 2 Alan Gilbert Building, 161 Barry Street, Carlton South Victoria 3053, Australia. E-mail [email protected]

Disclosures

None.

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