Brain Advance Access originally published online on August 3, 2006
Brain 2006 129(9):2384-2393; doi:10.1093/brain/awl183
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Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI
1 Center for Functionally Integrative Neuroscience, Department of Neuroradiology Århus University Hospital, Århus C, Denmark 2 Image Sciences Institute, University Medical Center Utrecht Utrecht, The Netherlands 3 Departments of Neuroradiology, University Medical Center Hamburg-Eppendorf Hamburg, Germany 4 Departments of Neurology, University Medical Center Hamburg-Eppendorf Hamburg, Germany
Correspondence to: Ona Wu, PhD, Center for Functionally Integrative Neuroscience, Århus University Hospital, Building 30, Nørrebrogade 44, 8000 Århus C, Denmark E-mail: ona{at}pet.auh.dk
Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging 
5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.
Key Words: mathematical modelling; cerebral ischaemia; magnetic resonance imaging; thrombolytic therapy; outcome measures
Abbreviations: ADC, apparent diffusion coefficient; AUC, area under the ROC curve; CBF, cerebral blood flow; CBV, cerebral blood volume; DELAY, tracer arrival delay; DWI, diffusion-weighted MRI; GLM, generalized linear model; iDWI, isotropic DWI; IQR, interquartile range; MLV, measured lesion volume; MTT, mean transit time; NIHSSS, National Institutes of Health Stroke Scale Score; PI, prediction interval; PLV, predicted lesion volume; PWI, perfusion-weighted MRI; ROC, receiver operating characteristic; rt-PA, recombinant tissue plasminogen activator; T2 EPI, T2-weighted image; TIMI, thrombolysis in myocardial infarction; WM, white matter
Received January 14, 2006. Revised June 2, 2006. Accepted June 9, 2006.
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