Pretreatment blood-brain barrier damage and post-treatment intracranial hemorrhage in patients receiving intravenous tissue-type plasminogen activator

Abstract

Background and purpose: Early blood-brain barrier damage after acute ischemic stroke has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of blood-brain barrier damage evident on pre-tissue-type plasminogen activator MRI scans was related to the degree of post-tissue-type plasminogen activator ICH in patients with acute ischemic stroke.

Methods: Analysis was performed on a database of patients with acute ischemic stroke provided by the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) Imaging Investigators. Patients with perfusion-weighted imaging lesions>10 mL and negative gradient-recalled echo imaging before intravenous tissue-type plasminogen activator were included. Postprocessing of the perfusion-weighted imaging source images was performed to estimate changes in blood-brain barrier permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up gradient-recalled echo images were reviewed for evidence of ICH and divided into 3 groups according to European Cooperative Acute Stroke Study (ECASS) criteria: no hemorrhage, hemorrhagic infarction, and parenchymal hematoma.

Results: Seventy-five patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as hemorrhagic infarction and 9 were classified as parenchymal hematoma. The mean permeability (±SDs), expressed as an index of contrast leakage, was 17.0±8.8% in the no hemorrhage group, 19.4±4.0% in the hemorrhagic infarction group, and 24.6±4.5% in the parenchymal hematoma group. Permeability was significantly correlated with ICH grade in univariate (P=0.007) and multivariate (P=0.008) linear regression modeling.

Conclusions: A perfusion-weighted imaging-derived index of blood-brain barrier damage measured before intravenous tissue-type plasminogen activator is given is associated with the severity of ICH after treatment in patients with acute ischemic stroke.

Keywords: blood–brain barrier; magnetic resonance imaging; stroke.

Figure 1

Example of mean permeability ROI: The TTP map (A) is thresholded (B) and overlain on the permeability map (C).

Figure 2

Example images for a patient who suffered parenchymal hematoma after tPA are shown. Panel A: pre-treatment DWI. Panel B: pre-treatment GRE. Panel C: pre-treatment permeability image. Panel D: post-treatment GRE demonstrating ICH.

Figure 3

Panel A shows the mean permeability derangement for each group with 95% confidence intervals. The red line demonstrates a threshold that separates parenchymal hematoma from all other patients with 95% accuracy. Panel B shows box plots for the mean permeability derangement of each group; the central mark is the median, the edges of the box are the 25th and 75th percentiles, the bars extend to the most extreme data points not considered outliers, and outliers are plotted individually.