The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke

 Successful reperfusion doesn't solve the neuronal cascade of death problem. My god, you don't understand one goddamn thing about stroke do you?

The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke

Maria Marburg^1†Linda F. Rudolf^2†Christine Matthis³Alexander Neumann²Constantin Schareck⁴Hannes Schacht²Robert Schulz⁵Björn Machner⁶Peter Schramm²Georg Royl^1,7Philipp J. Koch^1,7*

• ¹Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany
• ²Department of Neuroradiology, University Hospital Schleswig-Holstein, Lübeck, Germany
• ³Department of Social Medicine and Epidemiology, University Hospital Schleswig-Holstein, Lübeck, Germany
• ⁴Department of Radiology, University Hospital Schleswig-Holstein, Lübeck, Germany
• ⁵Department of Neurology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
• ⁶Department of Neurology, Schoen Clinic Neustadt, Neustadt in Holstein, Germany
• ⁷Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany

Introduction: Despite profitable group effects on functional outcomes after mechanical thrombectomy (MT) in large vessel occlusion (LVO), many patients with successful reperfusion show a non-favorable long-term outcome, highlighting the necessity to identify potential biomarkers predicting outcome variability. In this regard, the role of perfusion mismatch imaging for outcome variability in the early time window within 6 h after symptom onset is a matter of debate. We attempted to investigate under which conditions early perfusion mismatch imaging accounts for variability in functional outcomes after mechanical thrombectomy.

Patients and methods: In a retrospective single-center study, we examined 190 consecutive patients with LVO who were admitted to the Medical Center Lübeck within 6 h after symptom onset, all of whom underwent MT. Perfusion mismatch was quantified by applying the Alberta Stroke Program Early CT score (ASPECTS) on CT-measured cerebral blood flow (CBF-ASPECTS) and subtracting it from an ASPECTS application on cerebral blood volume (CBV-ASPECTS), i.e., ASPECTS mismatch. Using multivariate ordinal regression models, associations between ASPECTS mismatch and modified Rankin Scale (mRS) after 90 days were assessed. Furthermore, the interaction between ASPECTS mismatch and the core lesion volume was calculated to evaluate conditional associations.

Results: ASPECTS mismatch did not correlate with functional outcomes when corrected for multiple influencing covariables. However, interactions between ASPECTS mismatch and CBV-ASPECTS [OR: 1.12 (1.06–1.18), p-value < 0.001], as well as NCCT-ASPECTS [OR: 1.15 (1.06–1.25), p-value < 0.001], did show a significant association with functional outcomes. Model comparisons revealed that, profoundly, in patients with large core lesion volumes (CBV-ASPECTS < 6 or NCCT-ASPECTS < 6), perfusion mismatch showed a negative correlation with the mRS.

Discussion and conclusion: Perfusion mismatch imaging within the first 6 h of symptom onset provides valuable insights into the outcome variability of LVO stroke patients receiving thrombectomy but only in patients with large ischemic core lesions.

Introduction

In recent years, the selection of patients with anterior circulation large vessel occlusion (LVO) for mechanical thrombectomy (MT) has been continuously extended. Profitable outcomes have been shown until 24 h after symptom onset (1, 2), and most recently, randomized controlled trials (RCT) have shown a group benefit of MT for patients even with large core lesion volume (1–4). However, there are a significant number of patients with futile recanalization, i.e., poor outcomes despite successful MT. This highlights the urgent need to identify biomarkers that most likely predict a beneficial outcome and therapeutic gain for individual patients after mechanical thrombectomy. In patients presenting with anterior circulation LVO within 6 h after symptom onset, early diagnostics used in most RCT trials includes non-contrast CT (NCCT) and demonstration of the LVO using angiography to select patients for further endovascular treatment (5–7). CT-perfusion (CTP) imaging allows the quantification of irreversibly damaged and potentially salvageable brain tissue, i.e., the mismatch between definite infarction and tissue with reduced perfusion (8–11). Perfusion imaging is not commonly used in early diagnostics within the first 6 h since its primary usage is for penumbra imaging, which, for various reasons like RCT designs, starts at 6 h when considering patients with LVO and stroke. Therefore, it has not been systematically investigated in its relevance for functional outcome variability but instead used to increase the sensitivity depending on the healthcare system (12). Being widely accessible and still essential for patient selection for MT in the extended or unknown time window by estimating targeted mismatch (13), it may add valuable information for patient outcome variability within the first 6 h after symptom onset. By comparing MT patients with a historical cohort without MT, it has been shown that in patients with large ischemic core lesions within the first 6 h of symptom onset, the prevalence of CTP mismatch might distinguish patients who benefit from MT from those who do not (14). Reperfusion in patients with targeted CTP mismatch was associated with better outcomes in patients within 6 h after symptom onset (15) and patients after 6 h of onset, suggesting the potential role of CTP mismatch for clinical decision-making in the early time window (16). On the contrary, a comprehensive meta-analysis evaluated cohort studies within the first 6 h after symptom onset and did not see any association between functional outcomes and initial mismatch, but rather with lesion core volume (17). The perfusion mismatch is most commonly defined on validated cutoffs on specific perfusion maps (e.g., CBF < 30%, Tmax > 6 s) (11). However, its determination relies heavily on post-processing procedures, including smoothing and signal deconvolution typically integrated into commercial software (e.g., RAPID, VizAI) (18), which restricts its applicability in resource-limited settings. We introduce an alternative region-based approach to describe the extent of perfusion mismatch by applying the Alberta Stroke Program Early CT score (ASPECTS) on perfusion imaging maps. It further implies the potential advantage of weighting the perfusion mismatch or extent of the core lesion depending on the specific anatomical region involved compared to a solely volume-based approach. The core lesion was defined based on the CBV for its high correlation with MRI CBV maps within 6 h after onset (19). Tissue at risk was defined based on reduced CBF.