We have shown that appropriately thresholded MTT maps, processed with both delay-sensitive and delay-insensitive deconvolution algorithms, can optimally identify “at-risk” penumbra destined to infarct, but that the specific thresholds vary with postprocessing technique.
Our results expand on and overcome several potential limitations of prior studies, including distinguishing clinically relevant ischemia from benign oligemia, use of a longer “current generation” CTP acquisition time (older 40–50 second protocols could result in time-attenuation curve truncation in patients with large vessel occlusion or atrial fibrillation, causing overestimation of the CBV and MTT lesions), and comparison between standard and delay-corrected postprocessing software (1
). In addition, although it has been reported in some studies that the CBF*CBV interaction parameter may provide more accurate prediction of penumbra destined to infarct than CBF alone in patients without recanalization, the comparison between CBF*CBV and MTT has not previously been emphasized (17
). Moreover, the CBF thresholds used in those studies were predefined rather than optimized (17
). With regard to the variability in thresholds between different postprocessing algorithms, it is noteworthy that different digital signal intensity processing approaches—even when the same deconvolution algorithm is used—can result in marked variations in CTP maps. Specifically, fixed-point processing has the advantage of speed, whereas floating point processing has higher dynamic range, better precision, and higher signal intensity to noise (19
Another important feature of our study was the heterogeneity of our stroke cohort, which included patients with both ACA and M2 segmental MCA occlusions, in addition to the ICA terminus and MCA stem occlusions of earlier studies (1
). MCA occlusive strokes can be classified into different clinical and hemodynamic subtypes depending on the level of the occlusion, which may improve the generalizability of our results (21
). For example, stroke patients with proximal MCA occlusion are more likely to present with core/penumbra mismatch and have final infarct growth into penumbra, compared with those with distal MCA occlusion, in whom the admission core lesion is a stronger predictor of final infarct size.
One prior study of CTP ischemic thresholds, by using a shorter, 60-second acquisition protocol, found that tissue with <50% reduction in CBF is likely to survive, whereas a >66% reduction is likely to infarct (22
). Although another important study in 2006 found that rMTT provided the most accurate estimate of penumbra, those results—and thresholds—might not be generalizable to different cohorts with different distributions of vascular lesions and hemodynamics (ie, misery perfusion), or to newer, longer CTP acquisition protocols with different postprocessing platforms (1
). Indeed, a recent (2011) study not only concluded that CBF maps acquired by using newer, longer scan protocols provide more accurate estimates of infarct core than do CBV maps but also that the marked variability across different postprocessing softwares limits the generalizability of parameter map thresholds between platforms (23
) Our current study extends and complements these results for “core” by distinguishing noncritical hypoperfusion (“benign oligemia”) from true critical ischemia (“at-risk” penumbra).
Potential limitations of our study include the relatively small number of patients identified with large vessel occlusion but without clinical evidence or imaging findings of reperfusion. Additionally “2-slab”—as opposed to “whole brain”—CTP coverage may have decreased our power to detect more subtle differences between the parameter maps and related threshold values, though because our analysis included only coregistered pixels that were present in the admission and follow-up images, this consideration does not negate our results. Moreover, a limitation inherent to all stroke imaging studies is that they represent a “snapshot” in time; hence, our study lacked sufficient patients to stratify by time postictus. In addition, the relatively small number of patients in our final study group (of 98 potential subjects, we were only able to identify 23 who met all inclusion criteria) precluded additional stratification according to time-to-follow-up or follow-up technique (CT versus MR imaging). Finally, although software availability precluded us from directly comparing MTT to other transit-time measures such as Tmax, a number of recent studies, many of which included xenon CT and PET reference standards, have suggested that MTT and Tmax maps—when appropriately thresholded—are largely equivalent in their assessment of penumbra, and, indeed, in some instances MTT may exceed Tmax in accuracy (10