Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment.

OBJECTIVE: Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear. METHODS: This retrospective study included 2 prospective 3.0-T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients with indications for lumbar puncture underwent 3-dimensional T1-weighted sequence (3D-T1) before and at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). In cohort 2, patients with WMH were enrolled from the CIRCLE study and had a median follow-up time of 1.4 years. WMH and CP of the lateral ventricles were automatically segmented on T2 fluid-attenuated inversion recovery (FLAIR) and 3D-T1, respectively. CP volume was expressed as a ratio to intracranial volume. Glymphatic clearance was measured as signal percentage change from baseline to 39 hours at 8 brain locations based on glymphatic MRI in the first cohort, or as noninvasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) index based on DTI in the second cohort. RESULTS: In cohort 1, a total of 52 patients were included. Higher CP volume was correlated with slower glymphatic clearance rate in all brain locations. In cohort 2, a total of 197 patients were included. Baseline CP volume was positively associated with WMH volume and its growth. Furthermore, DTI-ALPS index partially mediated the association of CP with both WMH load and growth. INTERPRETATIONS: Enlarged CP volume could be an indicator for larger growth of WMH, potentially involving impaired glymphatic clearance function. The exploration of CP may provide a novel perspective to clarify the mechanism of WMH pathogenesis, as well as other glymphatic-related disorders. ANN NEUROL 2023;94:182-195.

Effect of computed tomography vs. computed tomography perfusion on mechanical thrombectomy outcomes within 6 hours.

OBJECTIVES: It is unclear which selection strategy, plain CT vs. CT perfusion (CTP), is more powerful in predicting outcome after mechanical thrombectomy (MT). We aimed to compare the effect of plain CT and CTP in predicting outcome after MT within 6 h. METHODS: We conducted a prospective analysis of a retrospective cohort from our single-center study, which had occlusion of the internal carotid artery and middle cerebral artery up to the proximal M2 segment and received MT within 6 h. According to the Alberta Stroke Program Early CT Score (ASPECTS), patients were divided into a high-ASPECTS group (≥ 6) and a low ASPECTS group (< 6). Similarly, patients were divided into mismatch and no-mismatch groups according to the DEFUSE3 criteria for CTP. A good outcome was defined as a 90-day modified Rankin Scale (mRS) score of ≤ 3. Univariate and binary logistic regression analyses were used to investigate the association between different imaging modality and 90-day mRS score, and mortalities, respectively. RESULTS: The high ASPECTS group included 307 patients (89.2%). The mismatch group included 189 (54.9%) patients meeting the DEFUSE3 criterion. Compared to the low ASPECTS group, the high ASPECTS group had a good outcome (odds ratio (OR), 2.285; [95% confidence interval (CI) (1.106, 4.723)], p = 0.026) and lower mortality (OR, 0.350; [95% CI (0.163, 0.752)], p = 0.007). However, there were no significant differences in good outcomes and mortality between the mismatch and no-mismatch groups. CONCLUSIONS: Compared with plain CT, CTP does not provide additional benefits in the selection of patients suitable for MT within 6 h. CLINICAL RELEVANCE STATEMENT: CT perfusion is not superior to plain CT for the prediction of clinical outcomes when selecting patients for mechanical thrombectomy in the first 6 h. In that clinical setting, plain CT may be safe in the absence of perfusion data. KEY POINTS: • The advantage of CT perfusion (CTP) over CT in pre-mechanical thrombectomy (MT) screening has not been proven for patients with a large infarct core. • CTP is not better than plain CT in predicting good outcome following MT within 6 h. • Plain CT is sufficient for selecting patients suitable for MT within 6 h of large artery occlusion.

Effect of anesthesia mode during endovascular treatment on neurological functional outcomes in patients with acute posterior circulation stroke. / éº»é†‰æ–¹å¼å¯¹æ€¥æ€§åŽå¾ªçŽ¯è„‘å’ä¸­è¡€ç®¡å† æ²»ç–—æ‚£è€ ç¥žç»åŠŸèƒ½ç»“å±€çš„å½±å“.

OBJECTIVES: To compare the effect of anesthesia mode on the neurological functional outcomes in patients undergoing endovascular treatment for acute posterior circulation ischemic stroke. METHODS: Clinical data of 656 patients undergoing intravascular therapy for acute posterior circulation ischemic stroke registered in online Acute Stroke Patients for Stroke Management Quality Evaluation Database from January 2017 to December 2022 were retrospectively analyzed. The data included 163 cases with conscious sedation and 493 cases with general anesthesia during the procedure. After propensity score matching, 428 patients were included in the analysis, including 155 cases in the conscious sedation group and 273 cases in the general anesthesia group. The differences of operation mode, etiology type, vascular recanalization, hemorrhagic transformation at 24 h, modified Rankin Scale (mRS) score at 3 months and mortality within 3 months were compared between the two groups. Binary logistic regression was used to explore the effect of different anesthesia mode on neurological functional outcomes. RESULTS: There was a significant difference in operation mode between the two groups (P<0.01), while there were no significant differences in etiology type, vascular recanalization, hemorrhagic transformation at 24 h, mRS score at 3 months or mortality within 3 months (all P>0.05). Binary logistic regression analysis revealed that anesthesia modes were not significantly associated with functional outcomes of patients (OR=1.151, 95%CI: 0.751-1.765, P>0.05). CONCLUSIONS: Anesthesia mode (conscious sedation or general anesthesia) will not affect the neurological functional outcomes in patients with acute posterior circulation ischemic stroke undergoing endovascular treatment.

Older age and the presence of intrameniscal signs are risk factors for nonsurgical treatment failure of symptomatic intact discoid lateral meniscus.

PURPOSE: The treatment for symptomatic intact discoid lateral meniscus (DLM) is controversial and the long-term clinical outcome remains unknown. The purpose of this study was to analyze the overall failure rate of nonsurgical treatment for symptomatic intact DLM and identify the risk factors for nonoperative management failure. METHODS: Consecutive patients who underwent nonsurgical treatment for symptomatic intact DLM at our hospital from 2014 to 2017 were retrospectively reviewed. Patients were divided into Group A (failure group) and Group B (nonfailure group) based on overall failure criteria: conversion to surgery, progression of a tear on MRI re-examination, or severely abnormal International Knee Documentation Committee (IKDC) scores. Statistical analyses between the two groups were performed for demographic and radiographic characteristics. Multivariate regression analysis was used to determine the risk factors associated with worse outcomes. RESULTS: One-hundred and four knees in 96 patients were included in this study. After a mean follow-up of 76.9 ± 11.1 months, 25 knees (24.0%) met the overall failure criteria. Multivariate regression analysis demonstrated that age and the presence of intrameniscus signals increased the risk of nonoperative management failure. The clinical criterion of age > 37.5 years combined with the imaging criterion of the presence of intrameniscal signals predicted conservative treatment failure of symptomatic intact DLM with a sensitivity of 0.87 and a specificity of 0.91. CONCLUSION: Twenty-five (24.0%) knees that underwent nonsurgical treatment met the overall failure criteria after a mean follow-up of 76.9 months. With increased age and the presence of intrameniscal signals, the nonoperative results become worse. LEVEL OF EVIDENCE: III.

Stroke outcome of early antiplatelet in post-thrombolysis haemorrhagic infarction.

BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.

Pose tracking method using magnetic excitations with frequency division for robotic endoscopic capsules.

The poses of robotic endoscopic capsules are indispensable for further follow-up examinations, potential targeted drug delivery, and closed-loop controlling of active locomotion. A novel tracking method using the multiple magnetic excitations with frequency division has been investigated. The multiple excitation coils can simultaneously work at different frequency to improve real-time tracking. A novel model between the magnetic flux density and the capsule's pose has been derived, which shows a nonlinear equation group with multiple local extremum. Then, a Back-Propagation (BP) neural network algorithm combined with the mother wavelet is investigated to solve the pose. To reduce the volume and power consumption, the wireless magnetic sensing module uses digital signal processing as the core framework, which is beneficial to be miniaturized to integrate with the capsule. The functional prototype of the tracking system has been developed, which consists of a wireless magnetic sensing module mounted in the capsule, a magnetic excitation module with frequency division, a wireless receiver and data interface, an excitation coil array and a platform for pose solving. The experimental results show that the mean errors are 0.0098 m in x-component, 0.0122 m in y-component, 0.0077 m in z-component, 0.187 rad in α-component and 0.161 rad in ß-component, respectively. The real-time performance of the tracking system is improved.

Impairment of the Glymphatic Pathway and Putative Meningeal Lymphatic Vessels in the Aging Human.

OBJECTIVE: Aging is a major risk factor for numerous neurological disorders, and the mechanisms underlying brain aging remain elusive. Recent animal studies demonstrated a tight relationship between impairment of the glymphatic pathway, meningeal lymphatic vessels, and aging. However, the relationship in the human brain remains uncertain. METHODS: In this observational cohort study, patients underwent magnetic resonance imaging before and at multiple time points after intrathecal administration of a contrast agent. Head T1-weighted imaging was performed to assess the function of the glymphatic pathway and head high-resolution T2-fluid attenuated inversion recovery imaging to visualize putative meningeal lymphatic vessels (pMLVs). We measured the signal unit ratio (SUR) of 6 locations in the glymphatic pathway and pMLVs, defined the percentage change in SUR from baseline to 39 hours as the clearance of the glymphatic pathway and pMLVs, and then analyzed their relationships with aging. RESULTS: In all patients (N = 35), the SUR of the glymphatic pathway and pMLVs changed significantly after intrathecal injection of the contrast agent. The clearance of both the glymphatic pathway and pMLVs was related to aging (all p < 0.05). The clearance of pMLVs was significantly related to the clearance of the glymphatic pathway (all p < 0.05), and the clearance of the glymphatic pathway was significantly faster in patients with early filling of pMLVs than those with late filling (all p < 0.05). INTERPRETATION: We revealed that both the glymphatic pathway and pMLVs might be impaired in the aging human brain through the novel, clinically available method to simultaneously visualize their clearance. Our findings also support that in humans, pMLVs are the downstream of the glymphatic pathway. Ann Neurol 2020;87:357-369.

A novel and reproducible release mechanism for a drug-delivery system in the gastrointestinal tract.

To establish a reliable, reproducible and accurate release of the drug in the gastrointestinal tract, a novel release mechanism for a controllable drug-delivery system has been investigated. The release mechanism, consisting of a one-way valve for drug release, a drug chamber, two axially magnetized cylindrical permanent magnets and a multi-layer solenoid coil, is hosted in the capsule-shaped shell with diameter 11 mm and length 30 mm. To actuate the coil piston, the two static magnetic fields produced by the two magnets are aligned along the same axis, having the same magnitude, but opposite directions. Based on the principle of the electromagnetic force and the Bernoulli equation, the actuating force can be expressed as a function of the coil stroke and the excitation current, which was modeled and experimentally verified. Thus the actuating force can be controlled by adjusting the activated period and intensity of the coil, resulting in the reproducible release with different doses and mean rates. Then, a prototype of the drug-delivery system has been developed, which consists of a drug-delivery capsule, a radio frequency transmission module, an interface circuit, and an instruction setting and triggering platform. All the drug release parameters, including the release mode, times, dose and mean flow rate, can be set by the platform. The experiment verifies that the drug-delivery capsule can deliver a predetermined dose with different flow rates and dip angles of the capsule. The relative error of the releasing dose becomes larger with increasing releasing rate and decreasing releasing dose.

Inferior Frontal Sulcal Hyperintensity on Fluid-Attenuated Inversion Recovery Is Related to Cerebrospinal Fluid Clearance via Putative Meningeal Lymphatics.

Inferior frontal sulcal hyperintensity (IFSH) on FLAIR sequence may indicate elevated cerebrospinal fluid (CSF) wastes. The objective of this study was to investigate its association with the clearance function of putative meningeal lymphatic vessels (mLVs). We included patients who underwent FLAIR sequence and dynamic contrast MRI with intrathecal administration of contrast agent. The visibility of IFSH was quantitatively assessed by measuring the mean signal intensity of inferior frontal sulci on 2D FLAIR. The clearance function of putative mLVs was defined as the percentage change of signal unite ratio in the parasagittal dura from baseline to 4.5, 15 and 39 hours after intrathecal injection on dynamic contrast MRI. Additionally, imaging markers of cerebral small vessel disease, including white matter hyperintensities and enlarged perivascular spaces, were measured. Correlation analysis and linear regression were employed to verify the association of IFSH with the clearance function of mLVs. A total of 76 patients were included in the study. The visibility of IFSH was found to be associated with the percentage change of signal unite ratio in parasagittal dura from baseline to 15 and 39 hours in adjusted analyses. Furthermore, the visibility of IFSH was positively related to the age, scores of both periventricular and deep white matter hyperintensities, and the grade of enlarged perivascular spaces in centrum semiovale. These findings suggest that the visibility of IFSH on 2D FLAIR may serve as an indicator of clearance dysfunction of mLVs and may be implicated in the development of cerebral small vessel disease.

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Cut-off point of mature oocyte for routine clinical application of rescue IVM: a retrospective cohort study.

BACKGROUND: The rescue in vitro mature(Rescue IVM) technique allows the use of immature oocytes collected in conventional COH to obtain more mature oocytes for fertilization through in vitro maturation. Some studies have shown that Rescue IVM could improve clinical outcomes in patients undergoing IVF/ICSI, but the effectiveness and the indications for the clinical application of this technique remain controversial. It remains to be studied whether Rescue IVM should be universally applied in all conventional IVF/ICSI cycles. METHOD: This is a large retrospective cohort study that included a total of 22,135 female patients undergoing their first IVF treatment cycles. The effect of the number of mature oocytes(metaphaseII[MII]) on the cumulative live birth rate was investigated in a population with routine IVF/ICSI first. The receiver operating characteristic curve(ROC) analysis was used to explore the cut-off point of the number of MII affecting CLBR. Secondly, Patients undergoing ICSI with Rescue IVM were included in the analysis with those who underwent ICSI only during the same period, grouped according to the MII cut-off values. Multi-factor binary logistic regression and inverse probability weighting (IPW) were used to investigate whether Rescue IVM influenced the final cumulative live birth rate(CLBR). RESULTS: The CLBR increased with the number of MIIoocytes (P < 0.001). The ROC analysis showed the cut-off point for the number of MIIoocytes to have a significant effect on CLBR was 9 (sensitivity 0.715, specificity 0.656). Furthermore, 912 patients who underwent ICSI with Rescue IVM were included and compared to those who underwent ICSI only during the same period, and found Rescue IVM significantly increased the number of available MIIoocytes. For patients with MII numbers < 9, Rescue IVM significantly improves their clinical pregnancy rate(55.6% vs. 46.7%, P = 0.001) and CLBR(65.4% vs. 48.1%, P < 0.001), but not for those patients with MII numbers ≥ 9. CONCLUSION: This study further clarifies the candidates for the application of Rescue IVM technique: patients with an MII oocytes < 9 in a conventional IVF/ICSI cycle. In contrast, it is not necessary for patients who already have sufficient mature oocytes(≥ 9), to avoid over-medication.

Non-porous thrombi are less pervious and easier to be retrieved: implication from scanning electron microscopy study.

BACKGROUND: Scanning electron microscopy (SEM) studies found that the porosity of thrombi might vary among individuals. However, its relationship with the clinical presentation and efficacy of mechanical thrombectomy (MT) remains unknown. We aimed to characterize the ultrastructure of thrombi and explore its association with the complexity of MT and clot perviousness. METHODS: SEM was used to observe the morphological features of different components of thrombi obtained from patients with anterior circulation large vessel occlusion undergoing MT and to determine the porosity of thrombi by semi-quantitative analysis. Non-porous thrombi were defined as thrombi with porosity <2%. Clot perviousness was also evaluated using thrombus attenuation increase on CT perfusion (TAIctp). We assessed the complexity of MT by attempts of retrieval >3 and procedural duration >60 min, defined as the time interval between groin puncture and recanalization. RESULTS: A total of 49 thrombi were analyzed and 31 (63.3%) were classified as non-porous thrombi. The presence of non-porous thrombi was negatively associated with procedure >60 min (OR 0.152, 95% CI 0.031 to 0.734, p=0.019) and attempts >3 (OR 0.194, 95% CI 0.046 to 0.822, p=0.026) after adjustment. Additionally, receiver operating characteristic curve analysis indicated that TAIctp <17.9 Hounsfield units could predict the presence of non-porous thrombi with an area under the curve of 0.915. CONCLUSIONS: Non-porous thrombi on SEM are easier to be retrieved during MT and could be identified as less pervious clots on CT images.

Impaired intracranial venous outflow profiles are associated with poor outcome in stroke after reperfusion therapy: A hypoperfusion-matched intracranial venous scale.

PURPOSE: Arterial blood flow provided prognostic information in acute ischemic stroke (AIS). However, part of the patients with favorable arterial blood flow still suffered from poor outcomes after reperfusion therapy. We aimed to verify the hypothesis that intracranial venous outflow profiles (both cortical and deep) within the hypoperfusion area were associated with clinical outcome in AIS patients who received reperfusion therapy. METHOD: We performed a retrospective analysis of prospectively collected data from anterior circulation AIS patients. All patients underwent pretreatment CTP and received reperfusion therapy. We constructed a 5-point hypoperfusion-matched Intracranial Venous Scale (hypo-IVS) from the sum of the contrast enhancement degree (1, attenuated contrast enhancement; 0, complete contrast enhancement) of 4 typical veins (superficial middle cerebral vein, vein of Labbé, vein of Trolard, and internal cerebral vein) whose outflow territories had matched hypoperfusion. Logistic and ordinal regression were used to analyze the association between hypo-IVS and clinical outcome. RESULTS: A total of 751 patients were included. Higher Hypo-IVS was significantly associated with poor outcome (3-month mRS of >2; OR = 1.194; 95 % CI: 1.014-1.407; p = 0.033). The adjusted ORs for poor outcome and high 24-hour NIHSS were 1.172 (95 %CI: 1.035-1.328; p = 0.012) and 1.176 (95 %CI: 1.030-1.330; p = 0.010) in ordinal regression, respectively. Hypo-IVS > 2 was an independent risk factor of poor outcome (75.2 % vs 40.8 %; OR = 1.932; 95 %CI: 1.158-3.224; p = 0.012). CONCLUSIONS: Intracranial venous outflow profiles deliver prognostic information in AIS and the hypo-IVS is a helpful tool to predict clinical outcomes after reperfusion therapy.

Low-density lipoprotein cholesterol, statin therapy, and cerebral microbleeds: The CIRCLE study.

BACKGROUND: Current evidence suggests a potential association between cerebral microbleeds (CMBs), low-density lipoprotein cholesterol (LDL-C) levels, and statin use, but the exact relationship remains unclear. This study aims to prospectively examine these relationships in a stroke-free population. METHODS: From January 2010 to January 2020, we enrolled stroke-free individuals with at least one cerebral small vessel disease imaging marker from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734). Participants underwent baseline and 1-year follow-up susceptibility-weighted imaging (SWI), and baseline LDL-C testing. New CMBs were categorized as strictly lobar and deep CMBs based on location. RESULTS: A total of 209 individuals were included. Baseline serum LDL-C levels were divided into quartiles: Q1 (≤1.76 mmol/L), Q2 (1.77-2.36 mmol/L), Q3 (2.37-2.93 mmol/L), and Q4 (>2.93 mmol/L). The incidence of new deep CMBs was 30.0%, 11.1%, 10.9%, 8.2% in Q1, Q2, Q3, Q4, respectively. Multivariate logistic model revealed that only LDL-C in Q1 was associated with increased incidence of new deep CMBs (OR = 4.256; 95% CI: 1.156-15.666; p = 0.029). In a subset of 169 participants without prior statin use, the use of atorvastatin was associated with reduced occurrence of new deep CMBs (OR = 0.181; 95% CI: 0.035-0.928; p = 0.040), while it was not found with rosuvastatin (OR = 0.808; 95% CI: 0.174-3.741; p = 0.785). CONCLUSIONS: While lower LDL-C levels were associated with higher CMB development, statin therapy did not increase the risk of new CMBs. Atorvastatin even demonstrated a protective effect.

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours (HOPE): protocol for a randomised, controlled, multicentre study.

BACKGROUND: While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke (AIS) within 4.5 hours of symptom onset, there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic window. AIM: To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5-24 hours after stroke onset (for stroke with unknown onset time, the midpoint of the time last known to be well and symptom recognition time; for wake-up stroke, the midpoint of the time last known to be well or sleep onset and wake up time) will benefit from intravenous thrombolysis. DESIGN: HOPE is a prospective, multicentre, randomised, open-label blinded endpoint trial with the stage of phase III. The treatment allocation employs 1:1 randomisation. The treatment arm under investigation is alteplase with standard therapy, the control arm is standard therapy. Eligibility imaging criteria include ischaemic core volume ≤70 mL, penumbra ≥10 mL and mismatch ≥20%. STUDY OUTCOMES: The primary outcome is non-disabled functional outcome (assessed as modified Rankin Scale score of 0-1 at 90 days). DISCUSSION: HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5-24 hours, which has the potential to extend time window and expand eligible population for thrombolysis therapy.

Multi-Mode Imaging Scale for Endovascular Therapy in Patients with Acute Ischemic Stroke (META).

Background: With the guidance of multi-mode imaging, the time window for endovascular thrombectomy (EVT) has been expanded to 24 h. However, poor clinical outcomes are still not uncommon. We aimed to develop a multi-mode imaging scale for endovascular therapy in patients with acute ischemic stroke (META) to predict the neurological outcome in patients receiving endovascular thrombectomy (EVT). Methods: We included consecutive acute ischemic stroke patients with occlusion of middle cerebral artery and/or internal carotid artery who underwent EVT. Poor outcome was defined as modified Rankin Scale (mRS) score of 3−6 at 3 months. A five-point META score was constructed based on clot burden score, multi-segment clot, the Alberta Stroke Program early computed tomography score of cerebral blood volume (CBV-ASPECTS), and collateral status. We evaluated the META score performance using area under the curve (AUC) calculations. Results: A total of 259 patients were included. A higher META score was independently correlated with poor outcomes at 3 months (odds ratio, 1.690, 95% CI, 1.340 to 2.132, p < 0.001) after adjusting for age, hypertension, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose. Patients with a META score ≥ 2 were less likely to benefit from EVT (mRS 3−6: 60.8% vs. 29.2%, p < 0.001). The META score predicted poor outcomes with an AUC of 0.714, higher than the Pittsburgh Response to Endovascular therapy (PRE) score, the totaled health risks in vascular events (THRIVE) score (AUC: 0.566, 0.706), and the single imaging marker in the scale. Conclusions: The novel META score could refine the predictive accuracy of prognosis after EVT, which might provide a promising avenue for future automatic imaging analysis to help decision making.

Impact of different white matter hyperintensities patterns on cognition: A cross-sectional and longitudinal study.

OBJECTIVES: White matter hyperintensities (WMH) are highly prevalent in older adults and considered to be a contributor to cognition impairment. However, the strategic WMH lesion distribution related to cognitive impairment is still debated. The aim of this study was to characterize the spatial patterns of WMH associated with cognitive impairment and explore its risk factors. METHODS: We retrospectively analyzed patients who underwent T2 fluid attenuated inversion recovery (FLAIR) and mini-mental state examination (MMSE) in two centers. WHM was classified into four patterns based on T2 FLAIR as follows: (1) multiple subcortical spots (multi-spots); (2) peri-basal ganglia (peri-BG); (3) anterior subcortical patches (anterior SC patches); and (4) posterior subcortical patches (posterior SC patches). We cross-sectionally and longitudinally estimated associations between different WMH patterns and all-cause dementia and cognitive decline. Multivariable logistic regression analysis was followed to identify risk factors of WMH patterns related to cognitive impairment. RESULTS: A total of 442 patients with WMH were enrolled, with average age of 71.6 ± 11.3 years, and MMSE score of 24.1 ± 5.4. Among them, 281 (63.6%), 66 (14.9%), 163 (36.9%) and 197 (44.6%) patients presented multi-spots, peri-BG, anterior SC patches and posterior SC patches, respectively. Patients with anterior SC patches were more likely to have all-cause dementia in cross-sectional study (OR 2.002; 95% CI 1.098-3.649; p = 0.024), and have cognitive decline in longitudinal analysis (OR 3.029; 95% CI 1.270-7.223; p = 0.012). Four patterns of WMH referred to different cognitive domains, and anterior SC patches had the most significant and extensive impact on cognition after Bonferroni multiple comparison correction (all p < 0.0125). In addition, older age (OR 1.054; 95% CI 1.027-1.082; p < 0.001), hypertension (OR 1.956; 95% CI 1.145-3.341; p = 0.014), higher percentage of neutrophils (OR 1.046; 95% CI 1.014-1.080; p = 0.005) and lower concentration of hemoglobin (OR 0.983; 95% CI 0.967-1.000; p = 0.044) were risk factors for the presence of anterior SC patches. CONCLUSIONS: Different patterns of subcortical leukoaraiosis visually identified on MRI might have different impacts on cognitive impairment. Further studies should be undertaken to validate this simple visual classification of WMH in different population.

Impaired peri-olfactory cerebrospinal fluid clearance is associated with ageing, cognitive decline and dyssomnia.

BACKGROUND: Animal experiments have demonstrated the dependency of cerebrospinal fluid clearance function on age and sleep, which partially underlay the cognitive decline in the elderly. However, human evidence is lacking, which could be mainly attributed to the limited methods of cerebrospinal fluid clearance function assessment. METHOD: Serial T1-weighted and T2-fluid attenuated inversion recovery imaging were performed in 92 patients before and at multiple time points including 4.5 h, 15 h and 39 h after intrathecal injection of contrast agent to visualize the putative meningeal lymphatic pathway, peri-olfactory nerve pathway, and peri-optic nerve pathway. We defined the clearance function as the percentage change in signal unit ratio of critical locations in these pathways from baseline to 39 h after intrathecal injection, and further analysed their relationships with age, sleep, and cognitive function. FINDINGS: Cerebrospinal fluid clearance through the putative meningeal lymphatic and perineural pathways were clearly visualized. The clearance function of putative meningeal lymphatic and perineural pathways were impaired with ageing (all P < 0.05). The clearance function through peri-olfactory nerve pathway in inferior turbinate was positively correlated with sleep quality and cognitive function (both P < 0.05), and mediated the association of sleep quality with cognitive function (percent change in ß [bootstrap 95% CI]: 33% [-0.220, -0.007]). INTERPRETATION: The impaired clearance through putative peri-olfactory nerve pathway may explain the cognitive decline in patients with sleep disturbance. The study shows a promising method to assess cerebrospinal fluid clearance function of putative peri-neural pathways via dynamic magnetic resonance imaging with intrathecal injection of contrast agent. FUNDING: This work was supported by the National Natural Science Foundation of China (81971101, 82171276 and 82101365).

U-net Models Based on Computed Tomography Perfusion Predict Tissue Outcome in Patients with Different Reperfusion Patterns.

Evaluation of cerebral perfusion is important for treatment selection in patients with acute large vessel occlusion (LVO). To assess ischemic core and tissue at risk more accurately, we developed a deep learning model named U-net using computed tomography perfusion (CTP) images. A total of 110 acute ischemic stroke patients undergoing endovascular treatment with major reperfusion (≥ 80%) or minimal reperfusion (≤ 20%) were included. Using baseline CTP, we developed two U-net models: one model in major reperfusion group to identify infarct core; the other in minimal reperfusion group to identify tissue at risk. The performance of fixed-thresholding methods was compared with that of U-net models. In the major reperfusion group, the model estimated infarct core with a Dice score coefficient (DSC) of 0.61 and an area under the curve (AUC) of 0.92, while fixed-thresholding methods had a DSC of 0.52. In the minimal reperfusion group, the model estimated tissue at risk with a DSC of 0.67 and an AUC of 0.93, while fixed-thresholding methods had a DSC of 0.51. In both groups, excellent volumetric consistency (intraclass correlation coefficient was 0.951 in major reperfusion and 0.746 in minimal reperfusion) was achieved between the estimated lesion and the actual lesion volume. Thus, in patients with anterior LVO, the CTP-based U-net models were able to identify infarct core and tissue at risk on baseline CTP superior to fixed-thresholding methods, providing individualized prediction of final lesion in patients with different reperfusion patterns.

Iodinated Contrast Agents Reduce the Efficacy of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients: a Multicenter Cohort Study.

This study aimed to investigate whether the application of iodinated contrast agents before intravenous (IV) recombinant tissue plasminogen activator (rt-PA) reduces the efficacy in acute ischemic stroke (AIS) patients. To determine whether the application of iodinated contrast agents before intravenous rt-PA reduces the efficacy in AIS patients. We analyzed our prospectively collected data of consecutive AIS patients receiving IV rt-PA treatment in the MISSION CHINA study. Clinical outcome at 3 months was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0-2) and poor outcome (3-6). Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24-h. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of iodinated contrast agents before IV rt-PA on poor outcome and sICH, respectively. A total of 3593 patients were finally included, and iodinated contrast agents were used before IV rt-PA among 859 (23.9%) patients. Patients in the iodinated contrast group were more likely to result in poor outcome (39.9% vs 33.4%, P = 0.001) and sICH (3.4% vs 1.5%, P < 0.001), compared with non-contrast group. Binary logistic regression analysis revealed that the application of iodinated contrast agents was independently associated with poor outcome (OR 1.342; 95% CI 1.103-1.631; P = 0.003) and sICH (OR 1.929; 95% CI 1.153-3.230; P = 0.012), respectively. After propensity score matching, the application of iodinated contrast agents was still independently associated with poor outcome (OR 1.246; 95% CI 1.016-1.531; P = 0.034) and sICH (OR 1.965; 95% CI 1.118-3.456; P = 0.019). Applying iodinated contrast agents before IV rt-PA may reduce the thrombolytic efficacy in AIS patients. Further benefit-risk analysis might be needed when iodinated contrast-used imaging is considered before intravenous thrombolysis.