Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study

Background In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators. Objective To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres. Methods We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography. Results Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1–30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively). Conclusion Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

[1]  W. Hacke,et al.  Mismatch-Based Delayed Thrombolysis: A Meta-Analysis , 2010, Stroke.

[2]  P Sandercock,et al.  Magnetic resonance perfusion diffusion mismatch and thrombolysis in acute ischaemic stroke: a systematic review of the evidence to date , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[3]  Max Wintermark,et al.  MR and CT Monitoring of Recanalization, Reperfusion, and Penumbra Salvage: Everything That Recanalizes Does Not Necessarily Reperfuse! , 2009, Stroke.

[4]  G. Schroth,et al.  Recanalisation of middle cerebral artery occlusion after intra-arterial thrombolysis: different recanalisation grading systems and clinical functional outcome , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[5]  Jeffrey L Saver,et al.  The Impact of Recanalization on Ischemic Stroke Outcome: A Meta-Analysis , 2007, Stroke.

[6]  Geoffrey A. Donnan,et al.  Acute Stroke Imaging Research Roadmap , 2008, Stroke.

[7]  B. Rosen,et al.  Tracer arrival timing‐insensitive technique for estimating flow in MR perfusion‐weighted imaging using singular value decomposition with a block‐circulant deconvolution matrix , 2003, Magnetic resonance in medicine.

[8]  Francesca M Chappell,et al.  Apparent diffusion coefficient thresholds and diffusion lesion volume in acute stroke. , 2013, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[9]  P. Barber,et al.  Assessing Reperfusion and Recanalization as Markers of Clinical Outcomes After Intravenous Thrombolysis in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) , 2009, Stroke.

[10]  R Frayne,et al.  Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[11]  H. S. Mueller,et al.  The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. , 1985, The New England journal of medicine.

[12]  W. Ganz,et al.  The thrombolysis in myocardial infarction (TIMI) trial. , 1985, The New England journal of medicine.

[13]  J. Wardlaw,et al.  A simple practical classification of cerebral infarcts on CT and its interobserver reliability. , 1994, AJNR. American journal of neuroradiology.

[14]  A. Demchuk,et al.  Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy , 2000, The Lancet.

[15]  S. Warach,et al.  Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion–diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study , 2009, The Lancet Neurology.

[16]  P. Koudstaal,et al.  Grading white matter lesions on CT and MRI: a simple scale. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[17]  M. Bastin,et al.  DSC perfusion MRI—Quantification and reduction of systematic errors arising in areas of reduced cerebral blood flow , 2006, Magnetic resonance in medicine.

[18]  K. Lee Disappearing hyperdense middle cerebral artery sign in ischaemic stroke patients treated with intravenous thrombolysis: clinical course and prognostic significance , 2010 .

[19]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[20]  P. Sandercock,et al.  Protocol for the Perfusion and Angiography Imaging Sub-Study of the Third International Stroke Trial (IST-3) of Alteplase Treatment within Six-Hours of Acute Ischemic Stroke , 2015, International journal of stroke : official journal of the International Stroke Society.

[21]  P. Barber,et al.  Expediting MRI-Based Proof-of-Concept Stroke Trials Using an Earlier Imaging End Point , 2009, Stroke.

[22]  Geoffrey A. Donnan,et al.  RAPID Automated Patient Selection for Reperfusion Therapy: A Pooled Analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study , 2011, Stroke.

[23]  J. Wardlaw,et al.  An open source toolkit for medical imaging de-identification , 2010, European Radiology.

[24]  M. Luby,et al.  Visual Perfusion–Diffusion Mismatch Is Equivalent to Quantitative Mismatch , 2011, Stroke.

[25]  A. Demchuk,et al.  The Alberta Stroke Program Early CT Score in Clinical Practice: What have We Learned? , 2009, International journal of stroke : official journal of the International Stroke Society.

[26]  Jan Potter,et al.  Reliability of the Modified Rankin Scale Across Multiple Raters: Benefits of a Structured Interview , 2005, Stroke.

[27]  P. A. Armitage,et al.  Development and initial testing of normal reference MR images for the brain at ages 65–70 and 75–80 years , 2008, European Radiology.

[28]  Ernst Klotz,et al.  MOSAIC: Multimodal Stroke Assessment Using Computed Tomography: Novel Diagnostic Approach for the Prediction of Infarction Size and Clinical Outcome , 2002, Stroke.

[29]  Geoff Cohen,et al.  The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial , 2012, The Lancet.

[30]  Kirsten Shuler,et al.  Computed tomography and magnetic resonance perfusion imaging in ischemic stroke: Definitions and thresholds , 2011, Annals of neurology.

[31]  P. Barber,et al.  Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch , 2010, Neurology.

[32]  J. Wardlaw,et al.  Disappearing hyperdense middle cerebral artery sign in ischaemic stroke patients treated with intravenous thrombolysis: clinical course and prognostic significance , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[33]  Keith Muir,et al.  Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial , 2008, The Lancet Neurology.

[34]  M. Luby,et al.  Acute Stroke Imaging Research Roadmap II , 2008, Stroke.

[35]  J. Wardlaw,et al.  Systematic Review of Perfusion Imaging With Computed Tomography and Magnetic Resonance in Acute Ischemic Stroke: Heterogeneity of Acquisition and Postprocessing Parameters A Translational Medicine Research Collaboration Multicentre Acute Stroke Imaging Study , 2012, Stroke.

[36]  A. Yamadori,et al.  Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke , 1992, Neurology.

[37]  A. Demchuk,et al.  Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. , 2000, Lancet.

[38]  Joanna M. Wardlaw,et al.  A Large Web-Based Observer Reliability Study of Early Ischaemic Signs on Computed Tomography. The Acute Cerebral CT Evaluation of Stroke Study (ACCESS) , 2010, PloS one.

[39]  P. Sandercock,et al.  Comparison of 10 Different Magnetic Resonance Perfusion Imaging Processing Methods in Acute Ischemic Stroke: Effect on Lesion Size, Proportion of Patients With Diffusion/Perfusion Mismatch, Clinical Scores, and Radiologic Outcomes , 2007, Stroke.

[40]  Jane C Khoury,et al.  Revascularization End Points in Stroke Interventional Trials: Recanalization Versus Reperfusion in IMS-I , 2005, Stroke.