To test whether the relationship between acute ischemic infarct size on concurrent computed tomographic (CT) angiography source images and diffusion-weighted (DW) magnetic resonance images is dependent on the parameters of CT angiography acquisition protocols.This retrospective study had institutional review board approval, and all records were HIPAA compliant. Data in 100 patients with anterior-circulation acute ischemic stroke and large vessel occlusion who underwent concurrent CT angiography and DW imaging within 9 hours of symptom onset were analyzed. Measured areas of hyperintensity at acute DW imaging were used as the standard of reference for infarct size. Information regarding lesion volumes and CT angiography protocol parameters was collected for each patient. For analysis, patients were divided into two groups on the basis of CT angiography protocol differences (patients in group 1 were imaged with the older, slower protocol). Intermethod agreement for infarct size was evaluated by using the Wilcoxon signed rank test, as well as by using Spearman correlation and Bland-Altman analysis. Multivariate analysis was performed to identify predictors of marked (≥20%) overestimation of infarct size on CT angiography source images.In group 1 (n=35), median hypoattenuation volumes on CT angiography source images were slightly underestimated compared with DW imaging hyperintensity volumes (33.0 vs 41.6 mL, P=.01; ratio=0.83), with high correlation (ρ=0.91). In group 2 (n=65), median volume on CT angiography source images was much larger than that on DW images (94.8 vs 17.8 mL, P<.0001; ratio=3.5), with poor correlation (ρ=0.49). This overestimation on CT angiography source images would have inappropriately excluded from reperfusion therapy 44.4% or 90.3% of patients eligible according to DW imaging criteria on the basis of a 100-mL absolute threshold or a 20% or greater mismatch threshold, respectively. Atrial fibrillation and shorter time from contrast material injection to image acquisition were independent predictors of marked (≥20%) infarct size overestimation on CT angiography source images.CT angiography protocol changes designed to speed imaging and optimize arterial opacification are associated with significant overestimation of infarct size on CT angiography source images.
Aberrant innate immune response drives the pathophysiology of many diseases.Myeloperoxidase (MPO) is a highly oxidative enzyme secreted by activated myeloid pro-inflammatory immune cells such as neutrophils and macrophages, and is a key mediator of the damaging innate immune response.Current technologies for detecting MPO activity in living organisms are sparse and suffer from any combination of low specificity, low tissue penetration, or low spatial resolution.We describe a versatile imaging platform to detect MPO activity using an activatable construct conjugated to a biotin moiety (MPO-activatable biotinylated sensor, MABS) that allows monitoring the innate immune response and its modulation at different scales and settings.Methods: We designed and synthesized MABS that contains MPO-specific and biotin moieties, and validated its specificity and sensitivity combining with streptavidin-labeled fluorescent agent and gold nanoparticles imaging in vitro and in vivo in multiple mouse models of inflammation and infection, including Matrigel implant, dermatitis, cellulitis, cerebritis and complete Fraud's adjuvant (CFA)-induced inflammation.Results: MABS MPO imaging non-invasively detected varying MPO concentrations, MPO inhibition, and MPO deficiency in vivo with high sensitivity and specificity.MABS can be used to obtain not only a fluorescence imaging agent, but also a CT imaging agent, conferring molecular activity information to a structural imaging modality.Importantly, using this method on tissue-sections, we found that MPO enzymatic activity does not always co-localize with MPO protein detected with conventional techniques (e.g., immunohistochemistry), underscoring the importance of monitoring enzymatic activity.Conclusion: By choosing from different available secondary probes, MABS can be used to create systems suitable to investigate and image MPO activity at different scales and settings.
Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo.
Introduction: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (mRS 0-2). Secondary outcomes included excellent functional outcome at 90 days (mRS 0-1), mortality, and day-one post-MT NIHSS score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1,354 patients, 150 were on pre-stroke low-dose aspirin. Aspirin use was associated with significantly better functional outcomes (mRS 0-2: OR = 2.12, 95% CI, 1.29 to 3.49; mRS 0-1: OR = 1.87, 95% CI, 1.12 to 3.14;) and lower 90-day mortality (OR = 0.53, 95% CI, 0.30 to 0.95). The aspirin group had lower NIHSS scores on day one (β = -2.0, 95% CI, -3.3 to -0.70). The rate of sICH was not significantly different between the groups (OR = 0.98, 95% CI, 0.56 to 1.72). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.
Introduction: Isolated anterior cerebral artery occlusions (iACAo) in acute ischemic stroke (AIS) patients present significant challenges due to their rarity and complex symptomatology. The efficacy of endovascular therapy (EVT) versus best medical management (BMM) for iACAo remains unclear. In light of context we aim in this investigation to assess the outcomes of these treatments. Methods: This multinational, multicenter study analyzed data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry. We included 108 patients with iACAo, who underwent either EVT or BMM. Data were collected retrospectively from 37 sites across North America, Asia, and Europe. Inverse Probability of Treatment Weighting (IPTW) was applied to balance confounding variables between treatment groups. The primary outcome was functional independence at 90 days. Secondary outcomes included excellent outcomes (mRS 0-1), mortality, and NIHSS score on day one post-EVT. Safety outcomes assessed hemorrhagic complications. Results: Of the 108 patients, 36 received BMM and 72 underwent EVT. The median age was 75 years (IQR 67-87), with 60 (56%) male patients overall. The primary outcome of 90-day mRS 0-2 was achieved in 40% of the cohort, with no significant difference between the EVT and BMM groups (38% vs. 45%, p=0.46). Procedural success (TICI 2b-3) was high in EVT patients at 91%, with a low sICH rate of 2.9%. The IPTW-adjusted analysis showed no significant association between EVT and improved functional outcomes (OR 1.17, 95% CI 0.23-6.02, p=0.85) or reduced mortality (23% overall; 25% EVT vs. 21% BMM, p=0.71). However, EVT was associated with higher NIHSS scores on day one post-stroke in crude analyses (OR 4.8, 95% CI 1.2-8.5, p=0.012), though this was not significant in the IPTW model (OR 2.2, 95% CI -0.51 to 4.8, p=0.11). Conclusions: In this propensity score-weighted analysis, EVT did not demonstrate superior functional outcomes compared to BMM in patients with iACAo. Nonetheless, EVT achieved high procedural success and low rates of symptomatic hemorrhage, indicating its safety. These findings highlight the need for randomized controlled trials to further explore EVT's potential role as a first-line or rescue therapy in iACAo patients, especially given the low recanalization rates with IV thrombolysis alone.
