Maps of Time to Maximum and Time to Peak for Mismatch Definition in Clinical Stroke Studies Validated With Positron Emission Tomography

Abstract

Background and Purpose-Perfusion-weighted imaging-derived maps of time-to-maximum (Tmax) are increasingly used to identify the tissue at risk in clinical stroke studies (eg, DEFUSE and EPITHET). Using quantitative positron emission tomography (PET), we evaluated Tmax to define the penumbral flow threshold in stroke patients and compared its performance to nondeconvolved time-to-peak (TTP) maps. Methods-Comparative perfusion-weighted imaging and quantitative 15O-water PET images of acute stroke patients were analyzed using cortical regions of interest. A receiver-operating characteristic curve analysis described the threshold independent performance of Tmax (area under the curve) and identified the best threshold (equal sensitivity and specificity threshold) to identify penumbral flow (Ͻ20 mL/100 g/min on PET cerebral blood flow). The results were compared with nondeconvolved TTP and other current perfusion-weighted imaging maps using the Mann-Whitney rank-sum test. Results-In 26 patients (time delay between MRI and PET, 65 minutes), the best threshold for penumbral flow was 5.5 seconds for Tmax (median; interquartile range, 3.9 -6.6; sensitivity/specificity, 88%/89%

Heterogeneity in the penumbra

“…Similarly, in EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial), both the size and the severity of PWI lesions correlated with clinical outcomes (Parsons et al, 2010). Recent data have suggested a B90% sensitivity and specificity for Tmax > 5.5 seconds to identify the PET-defined penumbra rCBF threshold of 20 mL/100 g per min (Zaro-Weber et al, 2010). These results suggest that quantification of the severity of PWI lesions can improve accuracy for identification of tissue that is in the penumbra.…”

“…More advanced PWI techniques, including deconvolution sequences that account for differences in arterial input to vessels with normal flow, appear to produce more accurate estimates of the regions of hypoperfusion that define the outer boundaries of the penumbra. Although PWI provides a number of parameters including mean transit time and cerebral blood volume, recently there has been focus on the maximum of the tissue residue function (Tmax) obtained by deconvolution (Zaro-Weber et al, 2010). Although the physiologic interpretation of Tmax is complex, it reflects the degree of lag between the arterial input and the tissue response, as well as dispersion and mean transit time (Calamante et al, 2010).…”

Comparison of 10 TTP and Tmax Estimation Techniques for MR Perfusion-Diffusion Mismatch Quantification in Acute Stroke

“…So far, only 1 study has been conducted comparing direct TTP and deconvolution-based Tmax estimation. 13 With PET as a criterion standard, it was concluded that deconvoluted Tmax does not perform significantly better than the direct TTP estimation. Moreover, the optimal TTP delay threshold was estimated at 4.2 seconds, while the optimal Tmax threshold was determined at 5.5 seconds in this study.…”

“…However, the findings of these studies are ambiguous, with identified optimal delay thresholds ranging from 4 to 6 seconds, depending on the applied methods and validations. 4,12,13 Several factors may influence the PWI analysis, such as the use and localization of the arterial input function. 14,15 Apart from this, there is another important aspect of PWI analysis that has not attracted much attention; that is the method for computation of TTP or Tmax parameter maps.…”

Failure of Collateral Blood Flow is Associated with Infarct Growth in Ischemic Stroke

“…However, subsequent research has demonstrated that much of the Tmax2-6 seconds region is 'benign oligemia'-unlikely to infarct even in the absence of reperfusion. [12][13][14] Hence Tmax46 seconds is now the preferred perfusion threshold, and we therefore also examined the mean Tmax within the Tmax46 seconds region and a modified ratio of Tmax 414 seconds to Tmax46 seconds to provide a similar index to the original 'hypoperfusion intensity ratio'.…”