OBJECTIVE: Ischemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)-based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts.
METHODS: Patients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO.
RESULTS: Seventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61-0.88] vs. MLS AUC 0.82 [95%CI 0.71-0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60-0.84] vs. MLS AUC 0.69 [95%CI 0.57-0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33).
CONCLUSIONS: EV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS.
CONCLUSIONS: Utilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome.
CONCLUSIONS: • CT densitometry-based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema. • Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent. • Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size.

Cerebral oedema following acute ischemic infarction has been correlated with poor functional outcomes and is the driving mechanism of malignant infarction. Measurements of midline shift and qualitative assessment for herniation are currently the main CT indicators for cerebral oedema but have limited sensitivity for small cortical infarcts and are typically a delayed sign. In contrast, diffusion-weighted (DWI) or T2-weighted magnetic resonance imaging (MRI) are highly sensitive but are significantly less accessible. Due to the need for early quantification of cerebral oedema, several novel imaging biomarkers have been proposed. Based on neuroanatomical shift secondary to space-occupying oedema, measures such as relative hemispheric volume and cerebrospinal fluid displacement are correlated with poor outcomes. In contrast, other imaging biometrics, such as net water uptake, T2 relaxometry and blood brain barrier permeability, reflect intrinsic tissue changes from the influx of fluid into the ischemic region. This review aims to discuss quantification of cerebral oedema using current and developing advanced imaging techniques, and their role in predicting clinical outcomes.

UNASSIGNED: To explore whether dual-energy computed tomography (DECT) angiography can provide reliable quantitative information on net water uptake (NWU) of ischemic brain to identify stroke patients within 4.5 h.
UNASSIGNED: We retrospectively reviewed 142 patients with stroke occurrence and who underwent DECT angiography between August 2016 and May 2022. DECT angiography manual drawn the ischemic area by referring to the normal area of the contralateral hemisphere and follow-up images. The NWU in the ischemic area was determined using virtual non-contrast and monoenergetic (VNC &VM) images acquired from DECT angiography. The NWU values in the ischemic area were compared between stroke patients within and beyond 4.5 h. The diagnostic performance of the NWU values derived from the VNC and VM images was assessed through receiver operating characteristic curve analysis. Additionally, Furthermore, we examined the correlation between the NWU values and the stroke onset time.
UNASSIGNED: Seventy-eight (54.93 %) stroke patients underwent DECT angiography and within 4.5 h. These patients with lower median National Institute of Health stroke scale (NIHSS) scores on admission than those beyond 4.5 h (p < 0.05). Furthermore, the group within 4.5 h had lower NWU values than did the group beyond 4.5 h on all VNC and VM images (p < 0.001). The analysis revealed that the NWU values determined using the VM (60 keV) images had the highest predictive efficiency (AUC, 0.95; sensitivity, 100 %; and specificity, 89.06 %) and showed the strongest positive correlation with stroke onset time (r-value = 0.58, p < 0.001).
UNASSIGNED: Our findings showed that DECT angiography-based quantification of NWU helps identify the stroke patients within 4.5 h with high predictive efficiency. Thus, NWU values determined using VM (60 keV) images could serve as a significant biomarker for stroke onset time.

Diagnosing recent small subcortical infarcts (RSSIs) via early computed tomography (CT) remains challenging. This study aimed to assess CT attenuation values (Hounsfield Units (HU)) and net water uptake (NWU) in RSSI and explore a postprocessing algorithm\'s potential to enhance thalamic RSSI detection. We examined non-contrast CT (NCCT) data from patients with confirmed thalamic RSSI on diffusion-weighted magnetic resonance imaging (DW-MRI) between January 2010 and October 2017. Co-registered DW-MRI and NCCT images enabled HU and NWU quantification in the infarct area compared to unaffected contralateral tissue. Results were categorized based on symptom onset to NCCT timing. Postprocessing using window optimization and frequency-selective non-linear blending (FSNLB) was applied, with interpretations by three blinded Neuroradiologists. The study included 34 patients (median age 70 years [IQR 63-76], 14 women). RSSI exhibited significantly reduced mean CT attenuation compared to unaffected thalamus (29.6 HU (±3.1) vs. 33.3 HU (±2.6); p < 0.01). Mean NWU in the infarct area increased from 6.4% (±7.2) at 0-6 h to 16.6% (±8.7) at 24-36 h post-symptom onset. Postprocessed NCCT using these HU values improved sensitivity for RSSI detection from 32% in unprocessed CT to 41% in FSNLB-optimized CT, with specificities ranging from 86% to 95%. In conclusion, CT attenuation values and NWU are discernible in thalamic RSSI up to 36 h post-symptom onset. Postprocessing techniques, particularly window optimization and FSNLB, moderately enhance RSSI detection.

We assessed net water uptake changes (NWU) in regions of posttraumatic ischemia in relation to cerebral microcirculation mean transit time (MTT) at moderate-to-severe traumatic brain injury (TBI).
METHODS: 128 moderate-to-severe traumatic brain injury patients (44 women, 84 men, age: 37 ± 12 years) were stratified into 3 groups: Marshall 2-3: 48 patients, Marshall 4: 44 patients, Marshall 5: 36 patients. The groups were matched by sex and age. Patients received multiphase perfusion computed tomography (PCT) 1-5 days after admission. Net water uptake was calculated from non-contrast computed tomography. Data are shown as a median [interquartile range]. P < 0.05 was considered statistically significant.
RESULTS: Cerebral blood flow in posttraumatic ischemia foci in Marshall 4 group was significantly higher than that in the Marshall 5 group (p = 0.027). Net water uptake in posttraumatic ischemia zones was significantly higher than in zones without posttraumatic ischemia (8.1% versus 4.2%, p < 0.001). Mean transit time in posttraumatic ischemia zones was inversely and significantly correlated with higher net water uptake (R2 = 0,089, p < 0.01).
CONCLUSIONS: Delay of blood flow through the cerebral microvascular bed was significantly correlated with the increased net water uptake in posttraumatic ischemia foci. Marshall\'s classification did not predict the progression of posttraumatic ischemia.

UNASSIGNED: The study aimed to explore the association between midline shift (MLS) and net water uptake (NWU) within the ischemic penumbra in acute ischemic stroke patients.
UNASSIGNED: This was a retrospective cohort study that examined patients with anterior circulation stroke. Net water uptake within the acute ischemic core and penumbra was calculated using data from admission multimodal CT scans. The primary outcome was severe cerebral edema measured by the presence of MLS on 24 to 48 h follow-up CT scans. The presence of a significant MLS was defined by a deviation of the septum pellucidum from the midline on follow-up CT scans of at least 3 mm or greater due to the mass effect of ischemic edema. The net water uptake was compared between patients with and without MLS, followed by logistic regression analyses and receiver operating characteristics (ROCs) to assess the predictive power of net water uptake in MLS.
UNASSIGNED: A total of 133 patients were analyzed: 50 patients (37.6%) with MLS and 83 patients (62.4%) without. Compared to patients without MLS, patients with MLS had higher net water uptake within the core [6.8 (3.2-10.4) vs. 4.9 (2.2-8.1), P = 0.048] and higher net water uptake within the ischemic penumbra [2.9 (1.8-4.3) vs. 0.2 (-2.5-2.7), P < 0.001]. Penumbral net water uptake had higher predictive performance than net water uptake of the core in MLS [area under the curve: 0.708 vs. 0.603, p < 0.001]. Moreover, the penumbral net water uptake predicted MLS in the multivariate regression model, adjusting for age, sex, admission National Institutes of Health Stroke Scale (NIHSS), diabetes mellitus, atrial fibrillation, ischemic core volume, and poor collateral vessel status (OR = 1.165; 95% CI = 1.002-1.356; P = 0.047). No significant prediction was found for the net water uptake of the core in the multivariate regression model.
UNASSIGNED: Net water uptake measured acutely within the ischemic penumbra could predict severe cerebral edema at 24-48 h.

BACKGROUND: The influence of cerebral edema and resultant secondary complications on the clinical outcome of traumatic brain injury (TBI) is well known. Clinical studies of brain water homeostasis dynamics in TBI are limited, which determines the relevance of our work. The purpose is to study changes in brain water homeostasis after TBI of varying severity compared to corresponding cerebral microcirculation parameters.
METHODS: This non-randomized retrospective single-center study complies with the Helsinki Declaration for patient\'s studies. The study included 128 patients with posttraumatic ischemia (PCI) after moderate-to-severe TBI in the middle cerebral artery territory who were admitted to the hospital between July 2015 and February 2022. PCI was evaluated by perfusion computed tomography (CT), and brain edema was determined using net water uptake (NWU) on baseline CT images. The patients were allocated according to Marshall\'s classification. Multivariate linear regression models were performed to analyze data.
RESULTS: NWU in PCI areas were significantly higher than in patients with its absence (8.1% vs. 4.2%, accordingly; p < 0.001). In the multivariable regression analysis, the mean transit time increase was significantly and independently associated with higher NWU (R2 = 0.089, p < 0.01). In the PCI zone, cerebral blood flow, cerebral blood volume, and time to peak were not significantly associated with NWU values (p > 0.05). No significant differences were observed between the NWU values in PCI foci in different Marshall groups (p = 0.308).
CONCLUSIONS: Marshall\'s classification does not predict the progression of posttraumatic ischemia. The blood passage delays through the cerebral microvascular bed is associated with brain tissue water content increase in the PCI focus.

UNASSIGNED: Following reperfusion treatment in ischemic stroke, computed tomography (CT) imaging at 24 h is widely used to assess radiological outcomes. Even without visible hyperattenuation, occult angiographic contrast may persist in the brain and confound Hounsfield unit-based imaging metrics, such as net water uptake (NWU).
UNASSIGNED: We aimed to assess the presence and factors associated with retained contrast post-thrombectomy on 24-h imaging using dual-energy CT (DECT), and its impact on the accuracy of NWU as a measure of cerebral edema.
UNASSIGNED: Consecutive patients with anterior circulation large vessel occlusion who had post-thrombectomy DECT performed 24-h post-treatment from two thrombectomy stroke centers were retrospectively studied. NWU was calculated by interside comparison of HUs of the infarct lesion and its mirror homolog. Retained contrast was quantified by the difference in NWU values with and without adjustment for iodine. Patients with visible hyperdensities from hemorrhagic transformation or visible contrast retention and bilateral infarcts were excluded. Cerebral edema was measured by relative hemispheric volume (rHV) and midline shift (MLS).
UNASSIGNED: Of 125 patients analyzed (median age 71 (IQR = 61-80), baseline National Institutes of Health Stroke Scale (NIHSS) 16 (IQR = 9.75-21)), reperfusion (defined as extended-Thrombolysis-In-Cerebral-Infarction 2b-3) was achieved in 113 patients (90.4%). Iodine-subtracted NWU was significantly higher than unadjusted NWU (17.1% vs 10.8%, p < 0.001). In multivariable median regression analysis, increased age (p = 0.024), number of passes (p = 0.006), final infarct volume (p = 0.023), and study site (p = 0.021) were independently associated with amount of retained contrast. Iodine-subtracted NWU correlated with rHV (rho = 0.154, p = 0.043) and MLS (rho = 0.165, p = 0.033) but unadjusted NWU did not (rHV rho = -0.035, p = 0.35; MLS rho = 0.035, p = 0.347).
UNASSIGNED: Angiographic iodine contrast is retained in brain parenchyma 24-h post-thrombectomy, even without visually obvious hyperdensities on CT, and significantly affects NWU measurements. Adjustment for retained iodine using DECT is required for accurate NWU measurements post-thrombectomy. Future quantitative studies analyzing CT after thrombectomy should consider occult contrast retention.

UNASSIGNED: We hypothesized that quantitative net water uptake (NWU), a novel neuroimaging marker of early brain edema, can predict symptomatic intracranial hemorrhage (sICH) after acute ischemic stroke (AIS).
UNASSIGNED: We enrolled patients with AIS who completed admission multimodal computed tomography (CT) within 24 h after stroke onset. NWU within the ischemic core and penumbra was calculated based on admission CT, namely NWU-core and NWU-penumbra. sICH was defined as the presence of ICH in the infarct area within 7 days after stroke onset, accompanied by clinical deterioration. The predictive value of NWU-core and NWU-penumbra on sICH was evaluated by logistic regression analyses and the receiver operating characteristic (ROC) curve. A pure neuroimaging prediction model was built considering imaging markers, which has the potential to be automatically quantified with an artificial algorithm on image workstation.
UNASSIGNED: 154 patients were included, of which 93 underwent mechanical thrombectomy (MT). The median time from symptom onset to admission CT was 262 min (interquartile range, 198-368). In patients with MT, NWU-penumbra (OR =1.442; 95% CI = 1.177-1.766; P < 0.001) and NWU-core (OR = 1.155; 95% CI = 1.027-1.299; P = 0.016) were independently associated with sICH with adjustments for age, sex, time from symptom onset to CT, hypertension, lesion volume, and admission National Institutes of Health Stroke Scale (NIHSS) score. ROC curve showed that NWU-penumbra had better predictive performance than NWU-core on sICH [area under the curve (AUC): 0.773 vs. 0.673]. The diagnostic efficiency of the predictive model was improved with the containing of NWU-penumbra (AUC: 0.853 vs. 0.760). A pure imaging model also presented stable predictive power (AUC = 0.812). In patients without MT, however, only admission NIHSS score (OR = 1.440; 95% CI = 1.055-1.965; P = 0.022) showed significance in predicting sICH in multivariate analyses.
UNASSIGNED: NWU-penumbra may have better predictive performance than NWU-core on sICH after MT. A pure imaging model showed potential value to automatically screen patients with sICH risk by image recognition, which may optimize treatment strategy.

UNASSIGNED: To investigate the difference in early edema, quantified by net water uptake (NWU) based on computed tomography (CT) between ischemic core and penumbra and to explore predictors of NWU and test its predictive power for clinical outcome.
UNASSIGNED: Retrospective analysis was conducted on patients admitted to Ningbo First Hospital with anterior circulation stroke and multi-modal CT. In 154 included patients, NWU of the ischemic core and penumbra were calculated and compared by Mann-Whitney U test. Correlations between NWU and variables including age, infarct time (time from symptom onset to imaging), volume of ischemic core, collateral status, and National Institutes of Health Stroke Scale (NIHSS) scores were investigated by Spearman\'s correlation analyses. Clinical outcome was defined using the modified Rankin Scale (mRS) at 90 days. Logistic regression and receiver operating characteristic analyses were performed to test the predictive value of NWU. Summary statistics are presented as median (interquartile range), mean (standard deviation) or estimates (95% confidence interval).
UNASSIGNED: The NWU within the ischemic core [6.1% (2.9-9.2%)] was significantly higher than that of the penumbra [1.8% (-0.8-4.0%)]. The only significant predictor of NWU within the ischemic core was infarct time (p = 0.004). The NWU within the ischemic core [odds ratio = 1.23 (1.10-1.39)], the volume of ischemic core [1.04, (1.02-1.06)], age [1.09 (1.01-1.17)], and admission NHISS score [1.05 (1.01-1.09)] were associated with the outcome of patients adjusted for sex and treatment. The predictive power for the outcome of the model was significantly higher when NWU was included (area under the curve 0.875 vs. 0.813, p < 0.05 by Delong test).
UNASSIGNED: Early edema quantified by NWU is relatively limited in the ischemic core and develops in a time-dependent manner. NWU estimates within the ischemic core may help to predict clinical outcomes of patients with acute ischemic stroke.