Patterns and Predictors of Blood–Brain Barrier Permeability Derangements in Acute Ischemic Stroke

Background and Purpose— MRI permeability imaging is a promising approach to identify patients with acute ischemic stroke with an increased propensity for hemorrhagic transformation (HT). Permeability imaging provides direct visualization of blood–brain barrier derangements in ischemic fields. Methods— We retrospectively analyzed clinical and MRI data on patients with acute cerebral ischemia within the middle cerebral artery territory to identify the frequency, patterns, and predictors of permeability derangements and their association with HT types. Results— A total of 179 permeability scans was obtained in 127 patients (59 men; mean age, 66.8 years). Among 179 image sets (82 pre-/no treatment and 97 posttreatment), permeability derangements were present in 29 images, frequently at the basal ganglia (n=23) and rarely at the juxta-cortical area (n=6). After adjusting for covariates, diastolic pressure (OR, 1.12, per 1-mm Hg increase; 95% CI, 1.02 to 1.22) and s-glucose (OR, 1.04, per 1-mg/dL increase; 95% CI, 1.01 to 1.07) were independently associated with pretreatment permeability derangements, whereas low-density lipoprotein cholesterol (OR, 0.97, per 1-mg/dL increase; 95% CI, 0.94 to 0.99), malignant MRI profile (OR, 24.84; 95% CI, 1.50 to 412.93), and time from onset to recanalization therapy (OR, 1.47, per 1-hour increase; 95% CI, 1.10 to 1.96) were independently associated with permeability derangements after recanalization therapy. Types of HT varied among the patients with permeability derangements (no HT, 4; hemorrhagic infarct type, 12; and parenchymal hematoma, 13) and transient derangements (without subsequent HT) and normalization of derangements (in the presence of HT) on permeability images was observed in several cases. Conclusions— Permeability derangements, a dynamic process associated with ischemic stroke pathophysiology and recanalization therapy, vary in pattern and evolution toward HT. Several prognostic and therapeutic predictors for HT are independently associated with pre- and posttreatment permeability derangements.

[1]  T. Neumann-Haefelin,et al.  Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. , 2006, Stroke.

[2]  Steven Warach,et al.  Early blood–brain barrier disruption in human focal brain ischemia , 2004, Annals of neurology.

[3]  R. Higashida,et al.  Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke , 2001, Neurology.

[4]  A. Sorensen,et al.  Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging. , 2002, AJR. American journal of roentgenology.

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

[6]  W. Hacke,et al.  Hemorrhagic Transformation of Ischemic Brain Tissue: Asymptomatic or Symptomatic? , 2001, Stroke.

[7]  T. N. t-P. S. S. Group,et al.  Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. , 1997, Stroke.

[8]  Ims Study Investigators.  Hemorrhage in the Interventional Management of Stroke Study , 2006, Stroke.

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

[10]  Jeffry R Alger,et al.  Prediction of hemorrhagic transformation after recanalization therapy using T2*‐permeability magnetic resonance imaging , 2007, Annals of neurology.

[11]  A. Demchuk,et al.  Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. , 1999, Stroke.

[12]  W P Dillon,et al.  Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors. , 2001, Academic radiology.

[13]  Dong Gyu Na,et al.  Prediction of hemorrhagic transformation in acute ischemic stroke: role of diffusion-weighted imaging and early parenchymal enhancement. , 2005, AJNR. American journal of neuroradiology.

[14]  V Larrue,et al.  Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. , 1997, Stroke.

[15]  Werner Hacke,et al.  MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study , 2006, The Lancet Neurology.

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

[17]  Erich Bluhmki,et al.  Risk Factors for Severe Hemorrhagic Transformation in Ischemic Stroke Patients Treated With Recombinant Tissue Plasminogen Activator: A Secondary Analysis of the European-Australasian Acute Stroke Study (ECASS II) , 2001, Stroke.

[18]  B. Rosen,et al.  High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis , 1996, Magnetic resonance in medicine.

[19]  G. Schlaug,et al.  Markedly Reduced Apparent Blood Volume on Bolus Contrast Magnetic Resonance Imaging as a Predictor of Hemorrhage After Thrombolytic Therapy for Acute Ischemic Stroke , 2005, Stroke.

[20]  R. Bammer,et al.  Risk Factors of Symptomatic Intracerebral Hemorrhage After tPA Therapy for Acute Stroke , 2007, Stroke.

[21]  Gottfried Schlaug,et al.  Predictors of Hemorrhagic Transformation After Intravenous Recombinant Tissue Plasminogen Activator: Prognostic Value of the Initial Apparent Diffusion Coefficient and Diffusion-Weighted Lesion Volume , 2002, Stroke.

[22]  Andrea Kassner,et al.  Prediction of hemorrhage in acute ischemic stroke using permeability MR imaging. , 2005, AJNR. American journal of neuroradiology.

[23]  G Johnson,et al.  Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas. , 2006, AJNR. American journal of neuroradiology.

[24]  J. Babb,et al.  Measuring Elevated Microvascular Permeability and Predicting Hemorrhagic Transformation in Acute Ischemic Stroke Using First-Pass Dynamic Perfusion CT Imaging , 2007, American Journal of Neuroradiology.

[25]  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.

[26]  D. Kent,et al.  Are Some Patients Likely to Benefit From Recombinant Tissue-Type Plasminogen Activator for Acute Ischemic Stroke Even Beyond 3 Hours From Symptom Onset? , 2003, Stroke.