Moving Beyond a Single Perfusion Threshold to Define Penumbra

Abstract

Background and Purpose— The mismatch lesion volumes defined by perfusion-weighted imaging exceeding diffusion-weighted imaging have been used as a marker of ischemic penumbral tissue. Defining the perfusion lesion by thresholding has shown promise as a practical tool; several positron emission tomography studies have indicated a more probabilistic relationship between perfusion and infarction. Here, we used a randomized controlled trial dataset of tissue-type plasminogen activator 3 to 6 hours after stroke to: (1) quantify the relationship between severity of hypoperfusion (measured by Tmax) and risk of infarction; (2) exploit this relationship to present a novel definition of mismatch based on infarct probabilities rather than dichotomies; and (3) examine the treatment response in the subgroup of patients with mismatch by the new definition. Methods— Patients from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) were included. Baseline perfusion-weighted imaging and 90-day T2-weighted imaging were coregistered. Perfusion-weighted imaging lesion volumes were divided into 10 Tmax delay strata, and infarct risk was defined as the fraction of the tissue at a given Tmax strata that progressed to infarction by day 90. Results— Sixty-two patients were studied. Infarct risk was an increasing function of Tmax for all subgroups, including the whole cohort. The probabilistic approach outperformed all Tmax thresholds, with exception of the Tmax ≥10 threshold, for which it was only favored by a trend. Conclusions— Infarct risk and treatment effect increased with severity of perfusion abnormalities. This suggests that a severity-weighted mismatch definition may define penumbral tissue more accurately.

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

“…A more probabilistic approach has demonstrated increasing infarction risk with increasing degrees of Tmax delay. 3 This appears to improve prediction of final infarct volume, although it cannot easily be applied to a spatial prediction. We hypothesize that increasing Tmax delay indicates tissue further down the collateral flow pathway with greater vulnerability to any reduction in collateral flow as a result.…”

“…2 However, it is evident in clinical practice that infarct growth does not always progress to the full extent of the involved vascular territory, even in the absence of reperfusion. 3 This variability in outcome may well relate to the persistence or failure of collateral vessels over time.…”

Predictive Value of the Velocity of Collateral Filling in Patients with Acute Ischemic Stroke

“…Nagakane et al 29 showed that the risk of subsequent infarction increases if Tmax increases and that this probabilistic approach allowed a better prediction of the final infarction volume than single cutoff values. 29 It is likely that in patients with a longer collateral filling time there is an increased proportion of tissue-atrisk with higher Tmax values.…”

“…29 It is likely that in patients with a longer collateral filling time there is an increased proportion of tissue-atrisk with higher Tmax values. Assuming an increased likelihood of infarction for this tissue as suggested by Nagakane et al, this may explain the observed association between collateral filling time and infarct growth.…”

Recanalization with Stent-Retriever Devices in Patients with Wake-Up Stroke

“…At admission, the median NIHSS score was 17 (IQR, [15][16][17][18][19][20]. Eleven patients had leftsided strokes with concomitant aphasic symptoms.…”