P rogression to infarction after acute ischemic stroke onset is time-sensitive and has substantial intersubject variability. 1,2 Computed tomographic (CT) perfusion (CTP) measurement of brain parenchyma can be used to estimate ischemic core and penumbra and, therefore, provide immediate information for treatment decision-making. Current CTP thresholds that estimate these tissue states are generally derived either by comparison with magnetic resonance (MR) diffusion-weighted imaging (DWI), often done within an hour of CTP, or with follow-up infarction in patients who have reperfused sometime within 24 hours.3-11 Because infarcts grow over time and final tissue fate depends greatly on what happens in the minutes to hours immediately after this imaging snapshot, CTP thresholds predicting infarction are likely to depend on the time from stroke symptom onset to imaging, time from imaging to reperfusion, and the quality of reperfusion.Background and Purpose-Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Methods-Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. T max , cerebral blood flow, and cerebral blood volume derived from delayinsensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. Results-One hundred and thirty-two patients were included. T max thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL•min −1•100 g −1 were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and T max (P<0.001; r=−0.68 and −0.60 for gray and white matter, respectively) parameters. Conclusions-Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

We have previously shown that the myocardial Gd-DTPA concentration ([Gd-DTPA]t(t)) after a bolus injection of Gd-DTPA can be predicted by the Modified Kety Equation (MKE). If [Gd-DTPA]t(t) can be determined by MRI and the data fit to the MKE, then the distribution volume (lambda) of Gd-DTPA and the myocardial flow (F) times the extraction efficiency (E), i.e., the FE product, can be determined. Therefore F can only be quantified if E is known. We measured the global E in vivo in normal canine myocardium, and measured E and lambda, in vitro, locally in normal, acute ischemic (n = 5; coronary artery occlusion < 4 h), infarcted (n = 4; coronary artery occlusion, 6 days) and reperfused (n = 4; coronary artery occlusion 2 h, and reperfusion 2 h and 6 days) myocardium. Results indicate that E differs with F and with individuals and consequently, F cannot be quantified using the MKE unless the local E is also determined in vivo.

These results validate the idea that functional CT can help quantify the perfusion function of mature vessels but not changes in microvessel density in antiangiogenic therapy.