Richard I Aviv

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Publications (131)502.92 Total impact

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    ABSTRACT: RationaleIn acute stroke, time is brain: faster tissue plasminogen activator treatment improves patient outcomes. Published guidelines for door-to-scanner time are <25 minutes, and for door-to-needle time <60 minutes. These benchmarks are rarely met. Paradoxically, the earlier a stroke patient arrives to hospital, the longer treatment takes. There is an urgent need to shift focus away from the 4·5 hour time window, towards treatment times <60 minutes.AimsThe objective of the Countdown Lights to Optimize Quality in acute Stroke (CLOQS) trial is to determine whether a simple, low-cost organizational behavior intervention, a large, red stopwatch timer attached to the stretcher upon arrival, will decrease door-to-scanner and door-to-needle treatment times for tissue plasminogen activator-treated patients.DesignA multicenter, time-clustered randomized control trial. The stopwatch timers will be used in Emergency Departments for all acute stroke patients across the University of Toronto Stroke Program. The order of intervention (ON) and control (OFF) blocks will be randomly assigned in a 1:1 ratio over an 18 month period. Blocks will be weighted in a 2:1 ratio of ON/OFF using a permuted block design (ON blocks last two weeks; OFF blocks last one week).Study OutcomesThe primary end-point is percentage of patients achieving best-practice guidelines (door-to-needle treatment time <60 minutes). Secondary end-points are median time intervals for 1) door-to-scanner and 2) door-to-needle times during ON versus OFF blocks. Tertiary end-points are in-hospital mortality and time series analysis to determine change in treatment times from prior to study onset through study completion.
    International Journal of Stroke 06/2014; 9(4). · 2.75 Impact Factor
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    ABSTRACT: Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (pcorr < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (pcorr > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.
    American Journal of Neuroradiology 05/2014; · 3.17 Impact Factor
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    ABSTRACT: The "spot sign" or contrast extravasation is strongly associated with hematoma formation and growth. An animal model of contrast extravasation is important to test existing and novel therapeutic interventions to inform present and future clinical studies. The purpose of this study was to create an animal model of contrast extravasation in acute intracerebral hemorrhage. Twenty-eight hemispheres of Yorkshire male swine were insonated with an MR imaging-guided focused sonography system following lipid microsphere infusion and mean arterial pressure elevation. The rate of contrast leakage was quantified by using dynamic contrast-enhanced MR imaging and was classified as contrast extravasation or postcontrast leakage by using postcontrast T1. Hematoma volume was measured on gradient recalled-echo MR imaging performed 2 hours postprocedure. Following this procedure, sacrificed brain was subjected to histopathologic examination. Power level, burst length, and blood pressure elevation were correlated with leakage rate, hematoma size, and vessel abnormality extent. Median (intracerebral hemorrhage) contrast extravasation leakage was higher than postcontrast leakage (11.3; 6.3-23.2 versus 2.4; 1.1-3.1 mL/min/100 g; P < .001). Increasing burst length, gradient recalled-echo hematoma (ρ = 0.54; 95% CI, 0.2-0.8; P = .007), and permeability were correlated (ρ = 0.55; 95% CI, 0.1-0.8; P = .02). Median permeability (P = .02), gradient recalled-echo hematoma (P = .02), and dynamic contrast-enhanced volumes (P = .02) were greater at 1000 ms than at 10 ms. Within each burst-length subgroup, incremental contrast leakage was seen with mean arterial pressure elevation (ρ = 0.2-0.8). We describe a novel MR imaging-integrated real-time swine intracerebral hemorrhage model of acute hematoma growth and contrast extravasation.
    American Journal of Neuroradiology 04/2014; · 3.17 Impact Factor
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    ABSTRACT: Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.
    Technology in cancer research & treatment 04/2014; · 1.94 Impact Factor
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    ABSTRACT: This study reviews the quality of economic evaluations of imaging after acute stroke and identifies areas for improvement. We performed full-text searches of electronic databases that included Medline, Econlit, the National Health Service Economic Evaluation Database, and the Tufts Cost Effectiveness Analysis Registry through July 2012. Search strategy terms included the following: stroke*; cost*; or cost-benefit analysis*; and imag*. Inclusion criteria were empirical studies published in any language that reported the results of economic evaluations of imaging interventions for patients with stroke symptoms. Study quality was assessed by a commonly used checklist (with a score range of 0% to 100%). Of 568 unique potential articles identified, 5 were included in the review. Four of 5 articles were explicit in their analysis perspectives, which included healthcare system payers, hospitals, and stroke services. Two studies reported results during a 5-year time horizon, and 3 studies reported lifetime results. All included the modified Rankin Scale score as an outcome measure. The median quality score was 84.4% (range=71.9%-93.5%). Most studies did not consider the possibility that patients could not tolerate contrast media or could incur contrast-induced nephropathy. Three studies compared perfusion computed tomography with unenhanced computed tomography but assumed that outcomes guided by the results of perfusion computed tomography were equivalent to outcomes guided by the results of magnetic resonance imaging or noncontrast computed tomography. Economic evaluations of imaging modalities after acute ischemic stroke were generally of high methodological quality. However, important radiology-specific clinical components were missing from all of these analyses.
    Stroke 02/2014; · 6.16 Impact Factor
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    ABSTRACT: Variability in computed tomography angiography (CTA) acquisitions may be one explanation for the modest accuracy of the spot sign for predicting intracerebral hemorrhage expansion detected in the multicenter Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study. This study aimed to determine the frequency of the spot sign in intracerebral hemorrhage and its relationship with hematoma expansion depending on the phase of image acquisition. PREDICT study was a prospective observational cohort study of patients with intracerebral hemorrhage presenting within 6 hours from onset. A post hoc analysis of the Hounsfield units of an artery and venous structure were measured on CTA source images of the entire PREDICT cohort in a core laboratory. Each CTA study was classified into arterial or venous phase and into 1 of 5 specific image acquisition phases. Significant hematoma expansion and total hematoma enlargement were recorded at 24 hours. Overall (n=371), 77.9% of CTA were acquired in arterial phase. The spot sign, present in 29.9% of patients, was more frequently seen in venous phase as compared with arterial phase (39% versus 27.3%; P=0.041) and the later the phase of image acquisition (P=0.095). Significant hematoma expansion (P=0.253) and higher total hematoma enlargement (P=0.019) were observed more frequently among spot sign-positive patients with earlier phases of image acquisition. Later image acquisition of CTA improves the frequency of spot sign detection. However, spot signs identified in earlier phases may be associated with greater absolute enlargement. A multiphase CTA including arterial and venous acquisitions could be optimal in patients with intracerebral hemorrhage.
    Stroke 01/2014; 45(3):734-9. · 6.16 Impact Factor
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    ABSTRACT: Standard (static) CT angiography is used to identify the intracerebral hemorrhage (ICH) spot sign. We used dynamic CT-angiography to describe spot sign characteristics and measurement parameters over 60-seconds of image acquisition. We prospectively identified consecutive patients presenting with acute ICH within 4.5 hours of symptom onset, and collected whole brain dynamic CT-angiography (dCTA). Spot parameters (earliest appearance, duration, maximum Hounsfield unit (HU), time to maximum HU, time to spot diagnostic definition, spot volume and hematoma volumes) were measured using volumetric analysis software. We enrolled 34 patients: three were excluded due to secondary causes of ICH. Of the remaining 31 patients there were 18 females (58%) with median age 70 (range 47-86) and baseline hematoma volume 33 ml (range 0.7-103 ml). Positive dCTA spot sign was present in 13 patients (42%) visualized as an expanding 3-dimensional structure temporally evolving its morphology over the scan period. Median time to spot appearance was 21 s (range 15-35 seconds). This method allowed tracking of spots evolution until the end of venous phase (active extravasation) with median duration of 39 s (range 25-45 seconds). The average density and time to maximum density was 204HU and 30.8 s (range 23-31 s) respectively. Median time to spot diagnosis was 20.8 s using either 100 or 120HU definitions. Dynamic CTA allows a 3-dimensional assessment of spot sign formation during acute ICH, and captured higher spot sign prevalence than previously reported. This is the first study to describe and quantify spot sign characteristics using dCTA; these can be used in ongoing and upcoming ICH studies.
    PLoS ONE 01/2014; 9(3):e90431. · 3.53 Impact Factor
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    ABSTRACT: Purpose To investigate whether early relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and permeability (Ktrans2) measurements may serve as magnetic resonance imaging (MRI) biomarkers of radiation response or progression for brain metastases. Materials and methods Seventy brain metastases in 44 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged with dynamic susceptibility and dynamic contrast enhancement MRI at baseline, 1 week and 1 month after treatment. The final response status was determined according to volume criteria derived from a 1 year post-treatment MRI or last available follow-up MRI. Tumours were characterised as responders, non-responders, progressors and non-progressors and compared for Ktrans2, rCBF and rCBV differences. Uni- and multivariate analysis evaluated factors associated with tumour response and progression at 1 week and 1 month. A generalised estimating equations (GEE) model accounted for multiple tumours per subject. Receiver operator characteristic (ROC) analysis identified optimal cut-off values, sensitivity and specificity for response or progression. Results Tumour responders showed lower Ktrans2 and reduced rCBF at 1 week (P < 0.05 each). Progressive disease showed lower rCBF and reduced rCBV at 1 month (P < 0.05 each). GEE and multivariate analysis revealed lower Ktrans2 at 1 week, an absence of prior radiation predicted response. At 1 month only lower rCBV predicted progressive disease on GEE and multivariate analysis. Optimal cut-off points for Ktrans2 and rCBV were 1.37 and 2.03 with sensitivity and specificity of 61.5 and 81.1% and 73.9 and 81.8%, respectively. Conclusion Lower Ktrans2 at 1 week and rCBV at 1 month discriminated responders and progressive disease, respectively.
    Clinical Oncology. 01/2014;
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    ABSTRACT: To determine the optimal imaging strategy for ICH incorporating CTA or DSA with and without a NCCT risk stratification algorithm. A Markov model included costs, outcomes, prevalence of a vascular lesion, and the sensitivity and specificity of a risk stratification algorithm from the literature. The four imaging strategies were: (a) CTA screening of the entire cohort; (b) CTA only in those where NCCT suggested a high or indeterminate likelihood of a lesion; (c) DSA screening of the entire cohort and (d) DSA only for those with a high or indeterminate suspicion of a lesion following NCCT. Branch d was the comparator. Age of the cohort and the probability of an underlying lesion influenced the choice of optimal imaging strategy. With a low suspicion for a lesion (<12%), branch (a) was the optimal strategy for a willingness-to-pay of $100,000/QALY. Branch (a) remained the optimal strategy in younger people (<35 years) with a risk below 15%. If the probability of a lesion was >15%, branch (b) became preferred strategy. The probabilistic sensitivity analysis showed that branch (b) was the optimal choice 70-72% of the time over varying willingness-to-pay values. CTA has a clear role in the evaluation of people presenting with ICH, though the choice of CTA everyone or CTA using risk stratification depends on age and likelihood of finding a lesion.
    PLoS ONE 01/2014; 9(5):e96496. · 3.53 Impact Factor
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    ABSTRACT: Background Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). Methods We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. Results Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P=0.01). Conclusions Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924 .).
    New England Journal of Medicine 01/2014; 370:2467. · 51.66 Impact Factor
  • Thien J Huynh, Sean P Symons, Richard I Aviv
    Imaging in medicine 12/2013; 5(6):539-551.
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    ABSTRACT: Rapid, accurate, and reliable identification of the computed tomography angiography spot sign is required to identify patients with intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to assess the accuracy and interobserver agreement for spot sign identification. A total of 131 neurology, emergency medicine, and neuroradiology staff and fellows underwent imaging certification for spot sign identification before enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for evaluation of spot sign presence, number, and mimics. True spot positivity was determined by consensus of 2 experienced neuroradiologists. Diagnostic performance, agreement, and differences by training level were analyzed. Mean accuracy, sensitivity, and specificity for spot sign identification were 87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity (P<0.001) because of true spot signs incorrectly perceived as spot mimics. Interobserver agreement for spot sign presence was moderate (k=0.60). When true spots were correctly identified, 81% correctly identified the presence of single or multiple spots. Median time needed to evaluate the presence of a spot sign was 1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance, interobserver agreement, and time needed for spot sign evaluation were similar among staff physicians and fellows. Accuracy for spot identification is high with opportunity for improvement in spot interpretation sensitivity and interobserver agreement particularly through greater reliance on computed tomography angiography source data and awareness of limitations of multiplanar images. Further prospective study is needed.
    Stroke 11/2013; · 6.16 Impact Factor
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11/2013; 40(6):873-874. · 1.33 Impact Factor
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11/2013; 40(6):870-872. · 1.33 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:Multiple patient-specific clinical and radiologic parameters impact traditional perfusion thresholds used to classify/determine tissue outcome. We sought to determine whether modified baseline perfusion thresholds calculated by integrating baseline perfusion and clinical factors better predict tissue fate and clinical outcome.MATERIALS AND METHODS:CTP within 4.5 hours of acute anterior circulation stroke onset and 5- to 7-day MR imaging were performed for 203 patients with stroke, divided into derivation (n = 114) and validation (n = 89) data bases. Affected regions were operationally classified as infarct and noninfarct according to baseline CTP and follow-up FLAIR imaging. Perfusion thresholds were derived for each of the infarct and noninfarct regions, without and with transformation by baseline clinical and radiologic variables by using a general linear mixed model. Performance of transformed and nontransformed perfusion thresholds for tissue fate and 90-day clinical outcome prediction was then tested in the derivation data base. Reproducibility of models was verified by using bootstrapping and validated in an independent cohort.RESULTS:Perfusion threshold transformation by clinical and radiologic baseline parameters significantly improved tissue fate prediction for both gray matter and white matter (P < .001). Transformed thresholds improved the 90-day outcome prediction for CBF and time-to-maximum (P < .001). Transformed relative CBF and absolute time-to-maximum values demonstrated maximal GM and WM accuracies in the derivation and validation cohorts (relative CBF GM: 91%, 86%; WM: 86%, 83%; absolute time-to-maximum 88%, 79%, and 80%, 76% respectively).CONCLUSIONS:Transformation of baseline perfusion parameters by patient-specific clinical and radiologic parameters significantly improves the accuracy of tissue fate and clinical outcome prediction.
    American Journal of Neuroradiology 10/2013; · 3.17 Impact Factor
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    ABSTRACT: Background: The outcomes of pregnancy and subsequent delivery of healthy neonates in women who have undergone previous near total hemispherectomy for Sturge-Weber syndrome (SWS) have rarely been reported. Case: A woman with SWS had two successful and uncomplicated pregnancies and deliveries under epidural anaesthesia after undergoing a near total hemispherectomy with subsequent unilateral cerebral palsy. Non-contrast MRI of the brain revealed post hemispherectomy changes with no residual meningeal angiomatosis. Conclusion: As more women who undergo surgical resection for underlying SWS grow into the child-bearing years, additional reports of pregnancy and delivery outcomes in this patient population can be expected and will be valuable.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 10/2013; 35(10):917-9.
  • Stroke. 10/2013;
  • Neurology 09/2013; 81(13):1181. · 8.25 Impact Factor
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    ABSTRACT: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth - AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.
    International Journal of Stroke 08/2013; · 2.75 Impact Factor
  • Stroke 08/2013; · 6.16 Impact Factor

Publication Stats

1k Citations
502.92 Total Impact Points

Institutions

  • 2007–2014
    • Sunnybrook Health Sciences Centre
      • • Department of Medical Imaging
      • • Division of Neurology
      Toronto, Ontario, Canada
  • 2007–2013
    • SickKids
      • Division of Neurology
      Toronto, Ontario, Canada
    • University of Toronto
      • Division of Neuroradiology
      Toronto, Ontario, Canada
  • 2012
    • The University of Calgary
      • Department of Clinical Neurosciences
      Calgary, Alberta, Canada
  • 2008–2012
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 2011
    • The University of Western Ontario
      London, Ontario, Canada
  • 2005
    • Women's College Hospital
      Toronto, Ontario, Canada