ORCID Profile
0000-0003-2434-1822
Current Organisation
University Medical Center Hamburg-Eppendorf
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Publisher: Cold Spring Harbor Laboratory
Date: 19-02-2023
DOI: 10.1101/2023.02.18.529076
Abstract: Changes in spontaneous brain activity at rest provide rich information about behavior and cognition. The mathematical properties of resting-state functional magnetic resonance imaging (rsfMRI) are a depiction of brain function and are frequently used to predict cognitive phenotypes. In idual characteristics such as age, gender, and total intracranial volume (TIV) play an important role in predictive modeling of rsfMRI (for ex le, as “confounders” in many cases). It is unclear, however, to what extent rsfMRI carries independent information from the in idual characteristics that is able to predict cognitive phenotypes. Here, we used predictive modeling to thoroughly examine the predictability of four cognitive phenotypes in 20,000 healthy UK Biobank subjects. We extracted common rsfMRI features of functional brain connectivity (FC) and temporal complexity (TC). We assessed the ability of these features to predict outcomes in the presence and absence of age, gender, and TIV. Additionally, we assessed the predictiveness of age, gender, and TIV only. We find TC and FC features to perform comparably with regard to predicting cognitive phenotypes. As compared to rsfMRI features, in idual characteristics provide systematically better predictions with smaller s le sizes and, to some extent, in larger cohorts. It is also consistent across different levels of inherent temporal noise in rsfMRI. Our results suggest that when the objective is to perform cognitive predictions as opposed to understanding the relationship between brain and behavior, in idual characteristics are more applicable than rsfMRI features.
Publisher: Research Square Platform LLC
Date: 08-03-2023
DOI: 10.21203/RS.3.RS-2631029/V1
Abstract: Changes in spontaneous brain activity at rest provide rich information about behavior and cognition. The mathematical properties of resting-state functional magnetic resonance imaging (rsfMRI) are a depiction of brain function and are frequently used to predict cognitive phenotypes. In idual characteristics such as age, gender, and total intracranial volume (TIV) play an important role in predictive modeling of rsfMRI (for ex le, as “confounders” in many cases). It is unclear, however, to what extent rsfMRI carries independent information from the in idual characteristics that is able to predict cognitive phenotypes. Here, we used kernel ridge regression modeling to thoroughly examine the predictability of four cognitive phenotypes in 20,000 healthy UK Biobank subjects. We extracted common rsfMRI features of functional brain connectivity (FC) and temporal complexity (TC). We assessed the ability of these features to predict outcomes in the presence and absence of age, gender, and TIV. Additionally, we assessed the predictiveness of age, gender, and TIV only. We find TC and FC features to perform comparably with regard to predicting cognitive phenotypes. As compared to rsfMRI features, in idual characteristics provide systematically better predictions with smaller s le sizes and, to some extent, in larger cohorts. It is also consistent across different levels of inherent temporal noise in rsfMRI. Our results suggest that when the objective is to perform cognitive predictions as opposed to understanding the relationship between brain and behavior, in idual characteristics outperform rsfMRI features.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2023
DOI: 10.1161/STROKEAHA.122.040247
Abstract: White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke. The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models. Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57–0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60–1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome ( P =0.443) or any hemorrhagic transformation ( P =0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19–4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80–4.81]). Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset. URL: www.clinicaltrials.gov Unique identifier: NCT01525290.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2022
DOI: 10.1161/STROKEAHA.121.036871
Abstract: Visual rating of diffusion-weighted imaging (DWI)–fluid-attenuated inversion recovery (FLAIR) mismatch can be challenging. We evaluated quantification of DWI and FLAIR to predict DWI-FLAIR mismatch status in ischemic stroke. In screened patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke), we retrospectively studied relative DWI (rDWI SI) and FLAIR signal intensity (rFLAIR SI). We defined the optimal mean rFLAIR SI and interquartile range of the rDWI SI in the DWI lesion to predict DWI-FLAIR mismatch status. We investigated agreement between each quantitative parameter and the DWI-FLAIR mismatch and the association between both quantitative parameters. We evaluated the predictive value of the quantitative parameters for excellent functional outcome by logistic regression, adjusted for DWI lesion volume, treatment, age, and National Institutes of Health Stroke Scale score. In the rFLAIR and rDWI SI analysis, 213/369 and 241/421 subjects respectively had a DWI-FLAIR mismatch. A mean rFLAIR SI cutoff of 1.09 and interquartile range rDWI SI cutoff of 0.47 were optimal to predict the DWI-FLAIR mismatch with a sensitivity and specificity of 77% (95% CI, 71%–83%) and 67% (95% CI, 59%–74%), and 76% (95% CI, 70%–81%) and 72% (95% CI, 65%–79%), respectively. For both quantitative parameters, agreement with the DWI-FLAIR mismatch was fair (73%, κ=0.44 [95% CI, 0.35–0.54] for rFLAIR and 74%, κ=0.48 [95% CI, 0.39–0.56] for rDWI). Both quantitative parameters correlated moderately (Pearson R=0.54 [95% CI, 0.46–0.61] P .001, n=367). The interquartile range rDWI SI (n=188), but not the mean rFLAIR SI (n=172), was an independent predictor of excellent functional outcome (odds ratio, 0.67 per 0.1 unit increase of interquartile range rDWI SI, 95% CI, 0.51–0.89, P =0.01). Agreement between the quantitative and qualitative approach may be insufficient to advocate DWI or FLAIR quantification as alternative for visual rating.
Publisher: Wiley
Date: 14-09-2022
DOI: 10.1002/HBM.26073
Abstract: The symptoms of acute ischemic stroke can be attributed to disruption of the brain network architecture. Systemic thrombolysis is an effective treatment that preserves structural connectivity in the first days after the event. Its effect on the evolution of global network organisation is, however, not well understood. We present a secondary analysis of 269 patients from the randomized WAKE‐UP trial, comparing 127 imaging‐selected patients treated with alteplase with 142 controls who received placebo. We used indirect network mapping to quantify the impact of ischemic lesions on structural brain network organisation in terms of both global parameters of segregation and integration, and local disruption of in idual connections. Network damage was estimated before randomization and again 22 to 36 h after administration of either alteplase or placebo. Evolution of structural network organisation was characterised by a loss in integration and gain in segregation, and this trajectory was attenuated by the administration of alteplase. Preserved brain network organization was associated with excellent functional outcome. Furthermore, the protective effect of alteplase was spatio‐topologically nonuniform, concentrating on a subnetwork of high centrality supported in the salvageable white matter surrounding the ischemic cores. This interplay between the location of the lesion, the pathophysiology of the ischemic penumbra, and the spatial embedding of the brain network explains the observed potential of thrombolysis to attenuate topological network damage early after stroke. Our findings might, in the future, lead to new brain network‐informed imaging biomarkers and improved prognostication in ischemic stroke.
Publisher: SAGE Publications
Date: 18-11-2022
DOI: 10.1177/17474930211059608
Abstract: Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases. Estimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study). FLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep. FLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age ( Nocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2021
DOI: 10.1038/S41467-021-22786-W
Abstract: Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI 95% [−8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI 95% [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2023
DOI: 10.1161/STROKEAHA.122.041505
Abstract: Reversibility of the diffusion-weighted imaging (DWI) lesion means that not all of the DWI lesion represents permanently injured tissue. We investigated DWI reversibility and the association with thrombolysis, reperfusion and functional outcome in patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging–Based Thrombolysis in Wake-Up Stroke). In this retrospective analysis of WAKE-UP, a randomized controlled trial (RCT) between September 2012 and June 2017 in Belgium, Denmark, France, Germany, Spain and United Kingdom, a convolutional neural network segmented the DWI lesions (b=1000 s/mm 2 ) at baseline and follow-up (24 hours). We calculated absolute and relative DWI reversibility in 2 ways: first, a volumetric (baseline volume−24-hour volume ) and second, a voxel-based (part of baseline lesion not overlapping with 24-hour lesion) approach. We additionally defined relative voxel-based DWI-reversibility % to account for coregistration inaccuracies. We calculated the odds ratio for reversibility according to treatment arm. We analyzed the association of reversibility with excellent functional outcome (modified Rankin Scale score of 0–1), in a multivariable model. In 363 patients, the median DWI volume was 3 (1–10) mL at baseline and 6 (2–20) mL at follow-up. Volumetric DWI reversibility was present in 19% (69/363) with a median absolute reversible volume of 1 mL (0–2) or 28% (14–50) relatively. Voxel-based DWI reversibility was present in 358/363 (99%) with a median absolute volume of 1 mL (0–2), or 22% (9–38) relatively. In 18% of the patients (67/363), relative voxel-based DWI reversibility % was present. Volumetric DWI reversibility and relative voxel-based DWI reversibility % was more frequent in patients treated with alteplase versus placebo (OR, 1.86 [95% CI, 1.09–3.17] and OR, 2.03 [95% CI, 1.18–3.50], respectively). Relative voxel-based DWI reversibility % was associated with excellent functional outcome (OR, 2.30 [95% CI, 1.17–4.51]). Small absolute volumes of DWI reversibility were present in a large proportion of randomized patients in the WAKE-UP trial. Reversibility was more often present after thrombolysis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2021
DOI: 10.1161/STROKEAHA.120.033071
Abstract: We aimed to investigate fluid-attenuated inversion recovery changes in the penumbra. We determined core and perfusion lesions in subjects from the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) and AXIS 2 trial (Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke) with perfusion- and diffusion-weighted imaging at baseline. Only subjects with a mismatch volume mL and ratio .2 were included. We created voxel-based relative fluid-attenuated inversion recovery signal intensity (rFLAIR SI) maps at baseline and follow-up. We studied rFLAIR SI in 2 regions of interest: baseline penumbra (baseline perfusion lesion−[core lesion+voxels with apparent diffusion coefficient 10 −6 mm 2 /s]) and noninfarcted penumbra (baseline perfusion lesion−follow-up fluid-attenuated inversion recovery lesion) at 24 hours (WAKE-UP) or 30 days (AXIS 2). We analyzed the association between rFLAIR SI and severity of hypoperfusion, defined as time to maximum of the residue function. In the baseline penumbra, rFLAIR SI was elevated (ratio, 1.04 P =1.7×10 − 13 n=126) and correlated with severity of hypoperfusion (Pearson r, 0.03 P .0×10 − 4 n=126). In WAKE-UP, imaging at 24 hours revealed a further increase of rFLAIR SI in the noninfarcted penumbra (ratio, 1.05 at 24 hours versus 1.03 at baseline P =7.1×10 −3 n=43). In AXIS 2, imaging at 30 days identified reversibility of the rFLAIR SI (ratio, 1.02 at 30 days versus 1.04 at baseline P =1.5×10 −3 n=26) since it was no longer different from 1 (ratio, 1.01 at 30 days P =0.099 n=26). Penumbral rFLAIR SI increases appear early after stroke onset, correlate with severity of hypoperfusion, further increase at 24 hours, and are reversible by 30 days. URL: clinicaltrials.gov Unique identifier: NCT01525290. URL: clinicaltrials.gov Unique identifier: NCT00927836.
No related grants have been discovered for Bastian Cheng.