Multiparametric MRI and CT Models of Infarct Core and Favorable Penumbral Imaging Patterns in Acute Ischemic Stroke

Background and Purpose— Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were (1) to develop magnetic resonance imaging (MRI) and computed tomography (CT) multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and (2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization. Methods— An analysis of imaging and clinical data was performed on 2 cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified. Results— The MRI and CT models were developed and validated from 34 and 32 patients, using 943 320 and 1 236 917 voxels, respectively. The derivation MRI and 2-branch CT models had an overall accuracy of 74% and 80%, respectively, and were independently validated with an accuracy of 71% and 79%, respectively. The imaging criteria of (1) predicted infarct core ⩽90 mL and (2) ratio of predicted infarct tissue within the at-risk region ⩽70% identified patients as having a favorable penumbral pattern with 78% to 100% accuracy. Conclusions— Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.

[1]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[2]  Leif Østergaard,et al.  How Reliable Is Perfusion MR in Acute Stroke?: Validation and Determination of the Penumbra Threshold Against Quantitative PET , 2008, Stroke.

[3]  F. Buonanno,et al.  Predicting Tissue Outcome in Acute Human Cerebral Ischemia Using Combined Diffusion- and Perfusion-Weighted MR Imaging , 2001, Stroke.

[4]  M Fisher,et al.  Characterizing the target of acute stroke therapy. , 1997, Stroke.

[5]  Gregory W Albers,et al.  Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials , 2010, The Lancet.

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

[7]  G. Albers,et al.  Applications of diffusion–perfusion magnetic resonance imaging in acute ischemic stroke , 1999, Neurology.

[8]  Scott Hamilton,et al.  Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study , 2006, Annals of neurology.

[9]  W. Heiss,et al.  Does the Mismatch Match the Penumbra?: Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke , 2005, Stroke.

[10]  J. Alger,et al.  Beyond Mismatch: Evolving Paradigms in Imaging the Ischemic Penumbra With Multimodal Magnetic Resonance Imaging , 2003, Stroke.

[11]  D. Darby,et al.  Results from the pilot phase of the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) , 2002 .

[12]  Jeffry R Alger,et al.  Perfusion-Weighted Magnetic Resonance Imaging Thresholds Identifying Core, Irreversibly Infarcted Tissue , 2003, Stroke.

[13]  G. Schlaug,et al.  Enlargement of human cerebral ischemic lesion volumes measured by diffusion‐weighted magnetic resonance imaging , 1997, Annals of neurology.

[14]  P. Adeleine,et al.  Baseline Magnetic Resonance Imaging Parameters and Stroke Outcome in Patients Treated by Intravenous Tissue Plasminogen Activator , 2003, Stroke.

[15]  R. Gonzalez,et al.  MRI-Based Selection for Intra-Arterial Stroke Therapy: Value of Pretreatment Diffusion-Weighted Imaging Lesion Volume in Selecting Patients With Acute Stroke Who Will Benefit From Early Recanalization , 2009, Stroke.

[16]  Ting-Yim Lee,et al.  White matter thresholds for ischemic penumbra and infarct core in patients with acute stroke: CT perfusion study. , 2008, Radiology.

[17]  G. Albers,et al.  Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection. , 1999, Stroke.

[18]  M. Moseley,et al.  Optimal Definition for PWI/DWI Mismatch in Acute Ischemic Stroke Patients , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  H Soltanian-Zadeh,et al.  A Model for Multiparametric MRI Tissue Characterization in Experimental Cerebral Ischemia With Histological Validation in Rat: Part 1 , 2001, Stroke.

[20]  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.

[21]  Gary A. Ford,et al.  Multivariable Analysis of Outcome Predictors and Adjustment of Main Outcome Results to Baseline Data Profile in Randomized Controlled Trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) , 2008, Stroke.

[22]  E. Kanal,et al.  The Cortical Ischemic Core and Not the Consistently Present Penumbra Is a Determinant of Clinical Outcome in Acute Middle Cerebral Artery Occlusion , 2003, Stroke.

[23]  T. J. Schaewe,et al.  Design and Rationale of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial , 2014, International journal of stroke : official journal of the International Stroke Society.

[24]  Christopher Putman,et al.  Utility of Perfusion-Weighted CT Imaging in Acute Middle Cerebral Artery Stroke Treated With Intra-Arterial Thrombolysis:: Prediction of Final Infarct Volume and Clinical Outcome , 2001, Stroke.

[25]  G. Schlaug,et al.  The ischemic penumbra: operationally defined by diffusion and perfusion MRI. , 1999, Neurology.

[26]  Gary Duckwiler,et al.  Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging , 2000, Annals of neurology.

[27]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[28]  M. Kaste,et al.  Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. , 2008, The New England journal of medicine.

[29]  Koroshetz Wj,et al.  Tissue plasminogen activator for acute ischemic stroke. , 1996, The New England journal of medicine.

[30]  V Hachinski,et al.  Identification of Penumbra and Infarct in Acute Ischemic Stroke Using Computed Tomography Perfusion–Derived Blood Flow and Blood Volume Measurements , 2006, Stroke.

[31]  P. S. Jones,et al.  The Diffusion-Weighted Lesion in Acute Stroke: Heterogeneous Patterns of Flow/Metabolism Uncoupling as Assessed by Quantitative Positron Emission Tomography , 2005, Cerebrovascular Diseases.

[32]  Reto Meuli,et al.  Perfusion-CT Assessment of Infarct Core and Penumbra: Receiver Operating Characteristic Curve Analysis in 130 Patients Suspected of Acute Hemispheric Stroke , 2006, Stroke.

[33]  M. Chopp,et al.  Multiparametric MRI Tissue Characterization in Clinical Stroke With Correlation to Clinical Outcome: Part 2 , 2001, Stroke.

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

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

[36]  A. Padovani,et al.  Perfusion CT in Patients with Acute Ischemic Stroke Treated with Intra-Arterial Thrombolysis: Predictive Value of Infarct Core Size on Clinical Outcome , 2009, American Journal of Neuroradiology.

[37]  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.

[38]  G Marchal,et al.  Voxel-based mapping of irreversible ischaemic damage with PET in acute stroke. , 1999, Brain : a journal of neurology.