title: Relative recirculation: a fast, model-free surrogate for the measurement of blood-brain barrier permeability and the prediction of hemorrhagic transformation in acute ischemic stroke.
abstract: OBJECTIVE
  To retrospectively evaluate the prognostic performance of a dynamic susceptibility contrast (DSC) MRI metric for permeability (relative recirculation or rR) for the prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). To compare rR with dynamic contrast-enhanced (DCE) MRI estimates of blood-brain barrier permeability (KPS).
  
  
  METHODS
  Data obtained from 26 patients (age: 27-89 years) with a working diagnosis of AIS were examined retrospectively. Patients were examined within a mean of 3.5 hours of symptom onset. Eleven patients received intravenous recombinant tissue-plasminogen activator (rt-PA). HT was determined by follow-up computed tomography and/or magnetic resonance imaging 24 to 72 hours after initial imaging. Permeability (DCE) always preceded DSC imaging and consisted of a 3D gradient-recalled echo scan acquired in 4 minutes 48 s. DSC imaging consisted of a T2*-weighted single shot EPI scan acquired in 43 to 86 seconds. Gadodiamide (0.1 mmol/kg) was injected as a bolus for each scan. Permeability (KPS) and rR were calculated offline for regions of interest (ROI) defined within the core of the infarct, as well as within the homologous location in the contralateral hemisphere. The relationship between KPS and rR was investigated using linear regression and receiver operating characteristic (ROC) curves were computed for predicting HT from either rR or KPS.
  
  
  RESULTS
  Eleven patients proceeded to HT (including 5 treated with rt-PA). Mean KPS values were significantly elevated in infarct relative to contralateral areas (0.84 +/- 0.57 vs. 0.42 +/- 0.34 mL/100 g/min; P = 0.0003). For infarct ROIs, KPS values were significantly greater in patients with HT compared with non-HT patients (1.25 +/- 0.63 vs. 0.53 +/- 0.23 mL/100 g/min; P = 0.0015). KPS values were higher in patients who received rt-PA than in untreated patients (1.09 +/- 0.61 vs. 0.65 +/- 0.47 mL/100 g/min; P = 0.0497). ROC analysis indicated a KPS threshold value of 0.67 mL/100 g/min for providing an optimal sensitivity and specificity for predicting HT of 91% and 80%, respectively. Mean rR values for infarct ROIs were significantly higher than those determined for contralateral regions (0.17 +/- 0.06 vs. 0.09 +/- 0.03; P < 0.0001). The mean rR for the HT group was significantly greater than for the non-HT group (0.22 +/- 0.05 vs. 0.14 +/- 0.05; P = 0.0002). As with KPS, the mean rR for patients who were treated with rt-PA was significantly greater than for untreated patients (0.21 +/- 0.07 vs. 0.15 +/- 0.05; P = 0.0112). ROC analysis indicated a threshold value of 0.17 for providing optimal sensitivity and specificity for predicting HT of 91% and 87%, respectively. There was a significant correlation between rR and KPS for infarct ROIs (r = 0.67; P < 0.001).
  
  
  CONCLUSIONS
  Both KPS and rR are significantly elevated in infarcted, relative to uninfarcted tissue in the same AIS patient. Both parameters were also significantly elevated in HT, relative to non-HT infarcts. The strong correlation between rR and KPS, coupled with the high sensitivity and specificity of rR for the prediction of HT suggest that rR is related to blood-brain barrier integrity in AIS and may prove valuable in the prediction of HT.
authors.affiliation: Division of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Shengping
authors.initials: S
authors.lastname: Wu
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Thornhill
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Wael
authors.initials: W
authors.lastname: Rammo
authors.forename: David J
authors.initials: DJ
authors.lastname: Mikulis
authors.forename: Andrea
authors.initials: A
authors.lastname: Kassner
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis*; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010539:Permeability; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020521:Stroke / Q000150:complications / Q000175:diagnosis*