Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization – When “tissue clock” and “time clock” are desynchronized

Nawabi, Jawed; Flottmann, Fabian; Kemmling, André; Kniep, Helge; Leischner, Hannes; Sporns, Peter; Schön, Gerhard; Hanning, Uta; Thomalla, Götz; Fiehler, Jens; Broocks, Gabriel

doi:10.1177/1747493019884522

Cited by 42 publications

(51 citation statements)

References 16 publications

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“…Our results suggest that the application of intravenous lysis in patients with wake‐up stroke with higher NWU may be associated with worse outcome, compared to patients prescirbed lysis with lower NWU, albeit major confounders cannot be controlled. This is in line with previous studies showing that the level of NWU in early infarct may mediate treatment effects and predict functional outcome 22 . Although low NWU may be a beneficial constellation for intravenous thrombolysis, high levels of NWU may suggest higher lesion progression with subsequent higher risk for malignant edema or secondary hemorrhage 17,23 …”

Section: Discussionsupporting

confidence: 89%

“…10 This patientindividual variability of NWU may imply an inherent limitation to show an accurate "time clock," however, at the same time, it may imply an advantage: NWU as an imaging biomarker of actual ischemic pathophysiology has been emphasized as a patient-specific tool to estimate the real "tissue clock" of infarct progression independent of time that directly relates to functional outcome. 17,22,23 Limitations of our study include the small number of patients as well as its retrospective design. The small number is mainly due to the fact that patients with acute stroke rarely receive both imaging modalities consecutively during triage.…”

Section: Discussionmentioning

confidence: 99%

“…This is in line with previous studies showing that the level of NWU in early infarct may mediate treatment effects and predict functional outcome. 22 Although low NWU may be a beneficial constellation for intravenous thrombolysis, high levels of NWU may suggest higher lesion progression with subsequent higher risk for malignant edema or secondary hemorrhage. 17,23 In MRI, the presence of a visible ischemic lesion on DWI combined with the absence of a clearly visible hyperintense lesion in the same region on FLAIR may predict symptom onset within 4.5 hours.…”

Section: Discussionmentioning

confidence: 99%

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Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI‐FLAIR Mismatch

Broocks

Leischner

Hanning

et al. 2020

Annals of Neurology

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In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset. Methods: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke. Results: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%). Conclusion: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI‐FLAIR Mismatch

Broocks

Leischner

Hanning

et al. 2020

Annals of Neurology

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“…Secondarily, NWU was also quantified in follow-up non-enhanced CT scans (FCT) and then NWU-NECT and NWU-FCT were compared and the differences were calculated as Δ-NWU. 9,12–16 Figure 1 provides a brief overview of NWU densitometric measurements.…”

Section: Methodsmentioning

confidence: 99%

Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: The impact of age

Meyer

Schönfeld

Bechstein

et al. 2020

J Cereb Blood Flow Metab

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The effect of age on lesion pathophysiology in the context of thrombectomy has been poorly investigated. We aimed to investigate the impact of age on ischemic lesion water homeostasis measured with net water uptake (NWU) within a multicenter cohort of patients receiving thrombectomy for anterior circulation large vessel occlusion (LVO) stroke. Lesion-NWU was quantified in multimodal CT on admission and 24 h for calculating Δ-NWU as their difference. The impact of age and procedural parameters on Δ-NWU was analyzed. Multivariable regression analysis was performed to identify significant predictors for Δ-NWU. Two hundred and four patients with anterior circulation stroke were included in the retrospective analysis. Comparison of younger and elderly patients showed no significant differences in NWU on admission but significantly higher Δ-NWU ( p = 0.005) on follow-up CT in younger patients. In multivariable regression analysis, higher age was independently associated with lowered Δ-NWU (95% confidence interval: −0.59 to −0.16, p < 0.001). Although successful recanalization (TICI ≥ 2b) significantly reduced Δ-NWU progression by 6.4% ( p < 0.001), younger age was still independently associated with higher Δ-NWU ( p < 0.001). Younger age is significantly associated with increased brain edema formation after thrombectomy for LVO stroke. Younger patients might be particularly receptive targets for future adjuvant neuroprotective drugs that influence ischemic edema formation.

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“…Specifically, patients with a large volume of early infarct and visually evident areas of hypoattenuation are potentially excluded from IT. However, the recanalization status and its influence on IP-NWU and MCE are unknown and need further investigation ( 37 , 38 ). Complete recanalization does not directly indicate a good clinical outcome ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Image Patch-Based Net Water Uptake and Radiomics Models Predict Malignant Cerebral Edema After Ischemic Stroke

Lin

et al. 2020

Front. Neurol.

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Malignant cerebral edema (MCE) after an ischemic stroke results in a poor outcome or death. Early prediction of MCE helps to identify subjects that could benefit from a surgical decompressive craniectomy. Net water uptake (NWU) in an ischemic lesion is a predictor of MCE; however, CT perfusion and lesion segmentation are required. This paper proposes a new Image Patch-based Net Water Uptake (IP-NWU) procedure that only uses non-enhanced admission CT and does not need lesion segmentation. IP-NWU is calculated by comparing the density of ischemic and contralateral normal patches selected from the middle cerebral artery (MCA) area using standard reference images. We also compared IP-NWU with the Segmented Region-based NWU (SR-NWU) procedure in which segmented ischemic regions from follow-up CT images are overlaid onto admission images. Furthermore, IP-NWU and its combination with imaging features are used to construct predictive models of MCE with a radiomics approach. In total, 116 patients with an MCA infarction (39 with MCE and 77 without MCE) were included in the study. IP-NWU was significantly higher for patients with MCE than those without MCE (p < 0.05). IP-NWU can predict MCE with an AUC of 0.86. There was no significant difference between IP-NWU and SR-NWU, nor between their predictive efficacy for MCE. The inter-reader and interoperation agreement of IP-NWU was exceptional according to the Intraclass Correlation Coefficient (ICC) analysis (inter-reader: ICC = 0.92; interoperation: ICC = 0.95). By combining IP-NWU with imaging features through a random forest classifier, the radiomics model achieved the highest AUC (0.96). In summary, IP-NWU and radiomics models that combine IP-NWU with imaging features can precisely predict MCE using only admission non-enhanced CT images scanned within 24 h from onset.

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Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization – When “tissue clock” and “time clock” are desynchronized

Cited by 42 publications

References 16 publications

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI‐FLAIR Mismatch

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI‐FLAIR Mismatch

Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: The impact of age

Image Patch-Based Net Water Uptake and Radiomics Models Predict Malignant Cerebral Edema After Ischemic Stroke

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