Lesion Water Uptake Research Articles

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

Background and purposeIn wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after...

Automated Estimation of Quantitative Lesion Water Uptake as a Prognostic Biomarker for Patients with Ischemic Stroke and Large-Vessel Occlusion.

Net water uptake is qualified as an imaging marker of brain edema. We aimed to investigate the ability of net water uptake to predict 90-day functional outcome in patients with acute ischemic stroke and large-vessel occlusion. A total of 295 consecutive patients were retrospectively enrolled. Automated ASPECTS-net water uptake was calculated on the admission CT. The relationship between ASPECTS-net water uptake and 90-day neurologic outcome was assessed. The independent predictors of favorable outcome (mRS score ≤2) were assessed using multivariate logistic regression analysis and receiver operating characteristic curves and stratified by the ASPECTS. Favorable 90-day outcomes were observed in 156 (52.9%) patients. ASPECTS-net water uptake (OR, 0.79; 95% CI, 0.70-0.90), NIHSS scores (OR, 0.91; 95% CI, 0.87-0.96), age (OR, 0.96; 95% CI, 0.94-0.99), and vessel recanalization (OR, 7.78; 95% CI, 3.96-15.29) were independently associated with favorable outcomes at 90 days (all, P < .01). A lower ASPECTS-net water uptake independently predicted a good prognosis, even in the subgroup of patients with low ASPECTS (≤5) (P < .05). An outcome-prediction model based on these variables yielded an area under the receiver operating characteristic curve of 0.856 (95% CI, 0.814-0.899; sensitivity, 76.3%; specificity, 81.3%). ASPECTS-net water uptake could independently predict 90-day neurologic outcomes in patients with acute ischemic stroke and large-vessel occlusion. Integrating ASPECTS-net water uptake with clinical models could improve the efficiency of outcome stratification.

Simplified Assessment of Lesion Water Uptake for Identification of Patients within 4.5 Hours of Stroke Onset: An Analysis of the MissPerfeCT Study.

Background and Purpose Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether a simple method of computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours. Methods This retrospective analysis of the MissPerfeCT study (August 2009 to November 2017) includes consecutive patients with known onset of symptoms from seven tertiary stroke centers. We developed a simplified algorithm based on region of interest (ROI) measurements to quantify water uptake of the ischemic lesion and thereby quantify time of symptom onset within and beyond 4.5 hours. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in non-contrast CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. Results Of 263 patients, 204 (77.6%) had CT within 4.5 hours. Water uptake was significantly lower in patients with stroke onset within (6.7%; 95% confidence interval [CI], 6.0% to 7.4%) compared to beyond 4.5 hours (12.7%; 95% CI, 10.7% to 14.7%). The area under the curve for distinguishing these patient groups according to percentage water uptake was 0.744 with an optimal cut-off value of 9.5%. According to this cut-off the positive predictive value was 88.8%, sensitivity was 73.5%, specificity 67.8%, negative predictive value was 42.6%. Conclusions Ischemic stroke patients with unknown time of symptom onset can be identified as being within a timeframe of 4.5 hours using a ROI-based method to assess water uptake on admission non-contrast head CT.

Automated quantitative lesion water uptake in acute stroke is a predictor of malignant cerebral edema.

Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p < 0.001). This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

Quantitative Lesion Water Uptake as Stroke Imaging Biomarker: A Tool for Treatment Selection in the Extended Time Window?

Patients presenting in the extended time window may benefit from mechanical thrombectomy. However, selection for mechanical thrombectomy in this patient group has only been performed using specialized image processing platforms, which are not widely available. We hypothesized that quantitative lesion water uptake calculated in acute stroke computed tomography (CT) may serve as imaging biomarker to estimate ischemic lesion progression and predict clinical outcome in patients undergoing mechanical thrombectomy in the extended time window. All patients with ischemic anterior circulation stroke presenting within 4.5 to 24 hours after symptom onset who received initial multimodal CT between August 2014 and March 2020 and underwent mechanical thrombectomy were analyzed. Quantitative lesion net water uptake was calculated from the admission CT. Prediction of clinical outcome was assessed using univariable receiver operating characteristic curve analysis and logistic regression analyses. One hundred two patients met the inclusion criteria. In the multivariable logistic regression analysis, net water uptake (odds ratio, 0.78 [95% CI, 0.64-0.95], P=0.01), age (odds ratio, 0.94 [95% CI, 0.88-0.99]; P=0.02), and National Institutes of Health Stroke Scale (odds ratio, 0.88 [95% CI, 0.79-0.99], P=0.03) were significantly and independently associated with favorable outcome (modified Rankin Scale score ≤1), adjusted for degree of recanalization and Alberta Stroke Program Early CT Score. A multivariable predictive model including the above parameters yielded the highest diagnostic ability in the classification of functional outcome, with an area under the curve of 0.88 (sensitivity 92.3%, specificity 82.9%). The implementation of quantitative lesion water uptake as imaging biomarker in the diagnosis of patients with ischemic stroke presenting in the extended time window might improve clinical prognosis. Future studies could test this biomarker as complementary or even alternative tool to CT perfusion.

Effect of thrombectomy on oedema progression and clinical outcome in patients with a poor collateral profile

Background and purposeThe impact of the cerebral collateral circulation on lesion progression and clinical outcome in ischaemic stroke is well established. Moreover, collateral status modifies the effect of endovascular treatment...

Early Prediction of Malignant Cerebellar Edema in Posterior Circulation Stroke Using Quantitative Lesion Water Uptake.

Malignant cerebellar edema (MCE) is a life-threatening complication of ischemic posterior circulation stroke that requires timely diagnosis and management. Yet, there is no established imaging biomarker that may serve as predictor of MCE. Early edematous water uptake can be determined using quantitative lesion water uptake, but this biomarker has only been applied in anterior circulation strokes. To test the hypothesis that lesion water uptake in early posterior circulation stroke predicts MCE. A total 179 patients with posterior circulation stroke and multimodal admission CT were included. A total of 35 (19.5%) patients developed MCE defined by using an established 10-point scale in follow-up CT, of which ≥4 points are considered malignant. Posterior circulation net water uptake (pcNWU) was quantified in admission CT based on CT densitometry and compared with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) as predictor of MCE using receiver operating curve (ROC) analysis and logistic regression analysis. Acute pcNWU within the early ischemic lesion was 24.6% (±8.4) for malignant and 7.2% (±7.4) for nonmalignant infarctions, respectively (P<.0001). Based on ROC analysis, pcNWU above 14.9% identified MCE with high discriminative power (area under the curve: 0.94; 95% CI: 0.89-0.97). Early pcNWU (odds ratio [OR]: 1.28; 95% CI: 1.15-1.42, P<.0001) and pc-ASPECTS (OR: 0.71, 95% CI: 0.53-0.95, P=.02) were associated with MCE, adjusted for age and recanalization status. Quantitative pcNWU in early posterior circulation stroke is an important marker for MCE. Besides pc-ASPECTS, lesion water uptake measurements may further support identifying patients at risk for MCE at an early stage indicating stricter monitoring and consideration for further therapeutic measures.

Patients with low Alberta Stroke Program Early CT Score (ASPECTS) but good collaterals benefit from endovascular recanalization

BackgroundBenefit of thrombectomy in patients with a low initial Alberta Stroke Program Early CT Score (ASPECTS) is still uncertain. We hypothesized that, despite low ASPECTS, patients may benefit from endovascular...

Computed Tomography Angiography Collateral Profile Is Directly Linked to Early Edema Progression Rate in Acute Ischemic Stroke.

Background and Purpose- Poor collateral flow is associated with poor clinical outcome in acute ischemic stroke and may indicate futile recanalization after successful thrombectomy. Pronounced early formation of cerebral ischemic edema may be the link between poor collateral status and declined functional outcome, but this relationship has not been investigated yet. We hypothesized that collateral status is associated with early lesion water uptake as quantitative marker for edema progression. Methods- One hundred seventy-six patients with middle cerebral artery stroke who underwent mechanical thrombectomy were analyzed. Status of cerebral collateral circulation (collaterals status [CS]) was derived using an established 5-point scoring system in admission computed tomography angiography, and good collaterals were defined as CS 3 to 4. Ischemic brain edema dynamics were quantified using early edema progression rate (EPR). EPR was derived from quantitative lesion water uptake in admission computed tomography divided by time from symptom onset to imaging. Good clinical outcome was defined as modified Rankin Scale score 0 to 2 after 90 days. Results- The median EPR was 1.4% per hour (interquartile range, 0.5-3.5%) in patients with good collaterals, which was lower than the median EPR in patients with poor collaterals of 5.8% per hour (interquartile range, 2.1-5.9%; P<0.0001). In multivariable regression analysis, lower CS was significantly and independently associated with higher EPR (1.6% EPR per 1-point CS; P=0.002). A higher EPR was associated with reduced likelihood of good clinical outcome: odds ratio 0.87; (95% CI, 0.76-0.99; P=0.03). Conclusions- Patients with poor CS had significantly higher EPR, which was associated with worse clinical outcome. These patients might benefit from adjuvant antiedematous treatment.

Elevated blood glucose is associated with aggravated brain edema in acute stroke.

Clinical outcome after endovascular thrombectomy in patients with acute ischemic stroke still varies significantly. Higher blood glucose levels (BGL) have been associated with worse clinical outcome, but the pathophysiological causes are not yet understood. We hypothesized that higher levels of BGL are associated with more pronounced ischemic brain edema and worse clinical outcome mediated by cerebral collateral circulation. 178 acute ischemic stroke patients who underwent mechanical thrombectomy were included. Early ischemic brain edema was determined using quantitative lesion water uptake on initial computed tomography (CT) and collateral status was assessed with an established 5-point scoring system in CT-angiography. Good clinical outcome was defined as functional independence (modified Rankin Scale [mRS] score 0-2). Multivariable logistic regression analysis was performed to predict functional independence and linear regression analyses to investigate the impact of BGL and collateral status on water uptake. The mean BGL at admission was significantly lower in patients with good outcome at 90days (116.5 versus 138.5mg/dl; p < 0.001) and early water uptake was lower (6.3% versus 9.6%; p < 0.001). The likelihood for good outcome declined with increasing BGL (odds ratio [OR] per 100mg/dl BGL increase: 0.15; 95% CI 0.02-0.86; p = 0.039). Worse collaterals (1% water uptake per point, 95% CI 0.4-1.7%) and higher BGL (0.6% per 10mg/dl BGL, 95% CI 0.3-0.8%) were significantly associated with increased water uptake. Elevated admission BGL were associated with increased early brain edema and poor clinical outcome mediated by collateral status. Patients with higher BGL might be targeted by adjuvant anti-edematous treatment.

Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization - When "tissue clock" and "time clock" are desynchronized.

Ischemic water uptake in acute stroke is a reliable indicator of lesion age. Nevertheless, inter-individually varying edema progression has been observed and elevated water uptake has recently been described as predictor of malignant infarction. We hypothesized that early-elevated lesion water uptake indicates accelerated "tissue clock" desynchronized with "time clock" and therefore predicts poor clinical outcome despite successful recanalization. Acute middle cerebral artery stroke patients with multimodal admission-CT who received successful thrombectomy (TICI 2b/3) were analyzed. Net water uptake (NWU), a quantitative imaging biomarker of ischemic edema, was determined in admission-CT and tested as predictor of clinical outcome using modified Rankin Scale (mRS) after 90 days. A binary outcome was defined for mRS 0-4 and mRS 5-6. Seventy-two patients were included. The mean NWU (SD) in patients with mRS 0-4 was lower compared to patients with mRS 5-6 (5.0% vs. 12.1%; p < 0.001) with similar time from symptom onset to imaging (2.6 h vs. 2.4 h; p = 0.7). Based on receiver operating curve analysis, NWU above 10% identified patients with very poor outcome with high discriminative power (AUC 0.85), followed by Alberta Stroke Program Early CT Score (ASPECTS) (AUC: 0.72) and National Institutes of Health Stroke Scale (NIHSS) (AUC: 0.72). Quantitative NWU may serve as an indicator of "tissue clock" and pronounced early brain edema with elevated NWU might suggest a desynchronized "tissue clock" with real "time clock" and therefore predict futile recanalization with poor clinical outcome.

Ischemic Lesion Water Uptake in Acute Stroke: Is Blood Glucose Related to Cause and Effect?

Ischemic Lesion Water Uptake in Acute Stroke: Is Blood Glucose Related to Cause and Effect?

Futile Recanalization With Poor Clinical Outcome Is Associated With Increased Edema Volume After Ischemic Stroke.

Futile recanalization with poor clinical outcome after endovascular treatment of acute ischemic stroke is poorly understood. Recently, vessel recanalization has been associated with reduced ischemic brain edema in patients with good clinical outcome. As edema volume (EV) may be quantified in computed tomography (CT), we hypothesized that higher EV after revascularization predicts futile recanalization with poor outcome. In this observational study, 67 ischemic stroke patients with M1 middle cerebral artery occlusion fulfilled all inclusion criteria and were analyzed. All patients received successful endovascular recanalization (thrombolysis in cerebral infarction scale 2b/3) and subsequent follow-up CT 24 hours later. Edema volume within the infarct lesion was calculated in follow-up CT applying lesion water uptake quantification and was used to predict clinical outcome (Modified Rankin Scale [mRS] after 90 days) compared with infarct volume. The median EV after thrombectomy was 1.6 mL (interquartile range, 0.2-4.2 mL) in patients with mRS 0 to 4 and 8.6 mL (interquartile range, 2.0-49.8 mL) in patients with mRS 5 to 6 (P = 0.0008). In regression analysis, an EV increase of 1 mL was associated with an 8.0% increased likelihood of poor outcome (95% confidence interval, 2.8%-15.4%; P = 0.008). Based on univariate receiver operating characteristic curve analysis, absolute EV over 4.2 mL predicted poor outcome (mRS 5-6) with good discriminative power (area under curve, 0.74; 95% confidence interval, 0.62-0.84; specificity, 77%; sensitivity, 68%). In comparison, the area under curve for infarct volume was 0.68. Elevated EV after endovascular thrombectomy was associated with poor clinical outcome and may indicate futile recanalization.

Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P < 0.0001; mean ± SD difference, -0.29% ± 0.39%, not different from 0, P < 0.0001). In the study cohort, the mean ± SD uptake of water within infarct measured by volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001). Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging of water uptake depicts lesion pathophysiology and could serve as a quantitative imaging biomarker of acute infarct lesions.

Computed tomography–based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study

Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval = 0.996-1.000, p < 0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Ann Neurol 2016;80:924-934.