title: CT perfusion analysis by nonlinear regression for predicting hemorrhagic transformation in ischemic stroke.
abstract: OBJECTIVE
  Intravenous thrombolysis can improve clinical outcome in acute ischemic stroke patients but increases the risk of hemorrhagic transformation (HT). Blood-brain barrier damage, which can be quantified by the vascular permeability for contrast agents, is a potential predictor for HT. This study aimed to assess whether this prediction can be improved by measuring vascular permeability using a novel fast nonlinear regression (NLR) method instead of Patlak analysis.
  
  
  METHODS
  From a prospective ischemic stroke multicenter cohort study, 20 patients with HT on follow-up imaging and 40 patients without HT were selected. The permeability transfer constant K(trans) was measured in three ways; using standard Patlak analysis, Patlak analysis with a fixed offset, and the NLR method. In addition, the permeability-surface (PS) area product and the conventional perfusion parameters (blood volume, flow, and mean transit time) were measured using the NLR method. Relative values were calculated in two ways, i.e., by dividing the average in the infarct core by the average in the contralateral hemisphere, and by dividing the average in the ipsilateral hemisphere by the average in the contralateral hemisphere. Mann-Whitney U tests and receiver operating characteristic (ROC) analyses were performed to assess the discriminative power of each of the relative parameters.
  
  
  RESULTS
  Both the infarct-core and whole-hemisphere averaged relative K(trans) (rK(trans)) values, measured with the NLR method, were significantly higher in the patients who developed HT as compared with those who did not. The rK(trans) measured with standard Patlak analysis was not significantly different. The relative PS (rPS), measured with NLR, had the highest discriminative power (P = 0.002). ROC analysis of rPS showed an area under the curve (AUC) of 0.75 (95% confidence interval: 0.62-0.89) and a sensitivity of 0.75 at a specificity of 0.75. The AUCs of the Patlak rK(trans), the Patlak rK(trans) with fixed offset, and the NLR rK(trans) were 0.58, 0.66, and 0.67, respectively.
  
  
  CONCLUSIONS
  CT perfusion analysis may aid in predicting HT, but standard Patlak analysis did not provide estimates for rK(trans) that were significantly higher in the HT group. The rPS, measured in the infarct core with NLR, had superior discriminative power compared with K(trans) measured with either Patlak analysis with a fixed offset or NLR, and conventional perfusion parameters.
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands and Image Sciences Institute, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Bennink
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Horsch
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Dankbaar
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Birgitta K
authors.initials: BK
authors.lastname: Velthuis
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Max A
authors.initials: MA
authors.lastname: Viergever
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands and Image Sciences Institute, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
authors.forename: Hugo W A M
authors.initials: HW
authors.lastname: de Jong
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D002545:Brain Ischemia / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002199:Capillary Permeability; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020300:Intracranial Hemorrhages / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D017711:Nonlinear Dynamics; D055420:Perfusion Imaging / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D020521:Stroke / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed / Q000379:methods*