Dynamic Changes of Asymmetric Cortical Veins Relate to Neurologic Prognosis in Acute Ischemic Stroke.

Background Cerebral oxygenation is closely related to neural function in acute ischemic stroke (AIS) and can be measured noninvasively from asymmetrically prominent cortical veins (APCVs) using quantitative susceptibility mapping (QSM). Purpose To quantify venous oxygen saturation (SvO2) using brain MRI with QSM in patients with AIS, to analyze its change at 2-week follow-up, and to assess the influence of SvO2 in clinical prognosis. Materials and Methods Between 2016 and 2020, consecutive patients with AIS who underwent brain MRI within 24 hours from symptom onset and 2 weeks after treatment were retrospectively enrolled. The SvO2 of APCVs was quantified using QSM. The independent sample t test was used to compare the SvO2 between patients with and patients without APCVs. The paired sample t test was used to assess the dynamic change in SvO2. Pearson and Spearman correlation analysis was used to explore the relationship among dynamic change in SvO2 and hypoperfusion, National Institutes of Health Stroke Scale (NIHSS) score change, and 90-day modified Rankin Scale (mRS) score. The independent sample t test was used to compare the dynamic change in SvO2 between different clinical prognoses and outcome subgroups. Results APCVs were detected in 39 of 73 patients (mean age, 70 years ± 10 [standard deviation]; 49 men) at admission and disappeared in 35 patients at 2-week follow-up MRI. The mean SvO2 increased from 35.0% ± 5.8 to 64.5% ± 10.0 (P < .001) in 39 patients. For the 35 patients with APCVs that disappeared, the dynamic change in SvO2 negatively correlated with change in NIHSS score (r = -0.37, R2 = 0.19, P = .03) and 90-day mRS score (r = -0.54, R2 = 0.27, P = .001), and the dynamic change in SvO2 in the subgroup with good 90-day outcomes (n = 19) was greater than that in the subgroup with poor 90-day outcomes (n = 16) (mean, 34.5% ± 5.8 vs 29.7% ± 6.3; 95% CI: 0.6, 8.9; P = .03). Conclusion Improved oxygen saturation of asymmetric cortical veins detected using brain MRI with quantitative susceptibility mapping corresponded with better acute ischemic stroke outcomes for patients with asymmetrically prominent cortical veins that disappeared at 2-week follow-up MRI. © RSNA, 2021 Online supplemental material is available for this article.

Quantitative susceptibility-weighted imaging may be an accurate method for determining stroke hypoperfusion and hypoxia of penumbra.

OBJECTIVES: To quantitatively evaluate the volume of the ischemic penumbra using susceptibility-weighted imaging and mapping (SWIM) of asymmetrical prominent cortical veins (APCVs) in patients with acute ischemic stroke. METHODS: Eighty-five eligible patients with acute ischemic stroke on admission within 12 h from symptom onset were studied. The APCVs on SWIM were quantitatively (SWI-volume) and semi-quantitatively (SWI-Alberta Stroke Program Early CT Score, SWI-ASPECTS) evaluated to calculate mismatch. To assess the diagnostic efficacy of APCVs on SWIM, comparative analyses were performed between SWIvolume-DWI mismatch and SWIASPECTS-DWI mismatch, using PWI-DWI mismatch as a reference. Correlations were calculated between the mismatches, as well as between SWI-volume and time-to-maximum (Tmax) > 6 s volume. Additionally, each of these mismatches was correlated with the National Institute of Health Stroke Scale (NIHSS). RESULTS: The sensitivity, negative predictive value, and accuracy of SWIvolume-DWI mismatch were demonstrably higher than SWIASPECTS-DWI mismatch (100% vs. 53.7%, 100% vs. 9.5%, 97.7% vs. 54.5%, respectively). A significant positive correlation was found between SWIvolume-DWI and PWI-DWI mismatch (r = 0.691, p < 0.01), as well as between SWI-volume and Tmax > 6 s volume (r = 0.786, p < 0.001). A significant negative correlation was found between SWIvolume-DWI mismatch and NIHSS (r = - 0.360, p = 0.022), as well as between SWIASPECTS-DWI mismatch and NIHSS (r = - 0.499, p = 0.001). CONCLUSIONS: SWIvolume-DWI mismatch had higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra and showed good consistency with PWI-DWI mismatch in acute ischemic stroke. Quantitation of APCVs using SWIM provided an accurate method for determining hypoperfusion and provided a reliable method to reflect the hypoxia of penumbra. KEY POINTS: • SWIvolume-DWI mismatch has higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra. • SWIvolume-DWI mismatch shows good consistency with PWI-DWI mismatch in managing penumbra in acute ischemic stroke. • Quantitation of APCV volume using SWIM provided an accurate method for determining the hypoperfusion area and provided a reliable method to reflect the hypoxia of penumbra.

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke.

OBJECTIVE: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. METHODS: The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 µg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. RESULTS: Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 µg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). INTERPRETATION: RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 µg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.

Automatic detection of cerebral microbleeds using susceptibility weighted imaging and artificial intelligence.

Background: Efficiently and accurately detecting cerebral microbleeds (CMBs) is crucial for diagnosing dementia, stroke, and traumatic brain injury. Manual CMB detection, however, is time-consuming and error-prone. This study evaluates a novel artificial intelligence (AI) software designed for the automated detection of CMBs using susceptibility weighted imaging (SWI). Methods: The SWI data from 265 patients, 206 of whom had a history of stroke and others of whom presented a variety of other medical histories, including hypertension, diabetes, hyperlipidemia, cerebral hemorrhage, intracerebral vascular malformations, tumors, and inflammation, collected between January 2015 and December 2018, were analyzed. Two independent radiologists initially reviewed the images to identify and count the number of CMBs. Subsequently, the images were processed using an automatic CMB detection software. The generated reports were then reviewed by the radiologists. A final consensus between the two radiologists, obtained after a second review of the images, was used to compare results obtained from the initial manual detection and those of the automatic CMB detection software. The differences of detection sensitivity and precision for patients with or without CMBs and for individual CMBs between the radiologist and the automatic CMB detection software were compared using Pearson chi-squared tests. Results: A total of 1,738 CMBs were detected among 148 patients (71.4±10.7 years, 100 males) from the analyzed SWI data. While the radiologists identified 139 cases with CMBs, the automatic CMB detection software detected 145 cases. Nevertheless, there was no statistical difference in the sensitivity and specificity of the automatic CMB detection software compared to manual detection in determining patients with CMBs (P=0.656 and P=0.212, chi-square test). However, the radiologist identified 93 patients without CMBs, while the automatic CMB detection software detected 121 patients without CMBs, exhibiting a statistically significant difference (P=0.016, chi-square test). In terms of individual CMBs, the radiologists found 1,284, whereas the automatic CMB detection software detected 1,677 CMBs. The detection sensitivity for human versus the automatic CMB detection software were 75.5% and 96.5% respectively (P<0.001, chi-square test), while the precision rates were 92.2% and 86.0% (P<0.001, chi-square test), respectively. Notably, the radiologists were more likely to overlook CMBs when the number of CMBs was high (above 30). Conclusions: The automatic CMB detection software proved to be an effective tool for the detection and quantification of CMBs. It demonstrated higher sensitivity than the radiologists, especially in detecting minuscule CMBs and in cases with high CMB prevalence.