228 words References 43 Tables 1 JNNP 2008/168393 revision 3, Cvoro et al 2 Figures 2 (1 colour) JNNP 2008/168393 revision 3, Cvoro et al 3 ABSTRACT Background: MR diffusion and perfusion imaging are used to identify ischemic penumbra, but there are few comparisons with neuronal loss and ischaemia in vivo. We compared N-acetyl aspartate (NAA, found in intact neurons) and lactate (anaerobic metabolism) with diffusion/perfusion parameters. Methods: We prospectively recruited patients with acute

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... chemic stroke and performed MR diffusion tensor, perfusion (PWI) and proton chemical shift spectroscopic imaging (CSI). We superimposed a 0.5 cm voxel grid on the diffusion-weighted images (DWI) and classified voxels as 'definitely abnormal', 'possibly abnormal', or normal on DWI appearance, and 'mismatch' for voxels in DWI/PWI mismatch areas. We compared metabolite (NAA, lactate), perfusion and ADC values in each voxel type. Results: NAA differentiated 'definitely' from 'possibly abnormal', and 'possibly abnormal' from 'mismatch' (both comparisons p<0.01) voxels, but not 'mismatch' from 'normal' voxels. Lactate was highest in 'definitely abnormal', and progressively lower in 'possibly abnormal', 'mismatch', then 'normal' voxels (all differences p<0.01). There was no correlation between NAA and ADC or PWI values, but high lactate correlated with low ADC (Spearman ρ =-0.41, p=0.02) and prolonged MTT (Spearman ρ =0.42, p=0.02). Conclusion: ADC and MTT indicate the presence of ischemia (lactate) but not cumulative total neuronal damage (NAA) in acute ischemic stroke, suggesting that caution is required if using ADC and PWI parameters to differentiate salvageable from non-salvageable tissue. Further refinement of the DWI/PWI concept is required prior to more widespread use.