Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial.

Background And Objectives: Data from randomized trials on the treatment effect of pure thrombolysis in patients with vessel occlusion are lacking. We examined data from a corresponding subsample of patients from the multicenter, randomized, placebo-controlled WAKE-UP trial to determine whether MRI-guided IV thrombolysis with alteplase in unknown-onset ischemic stroke benefits patients presenting with vessel occlusion.

Methods: Patients with an acute ischemic lesion visible on MRI diffusion-weighted imaging but no marked parenchymal hyperintensity on fluid-attenuated inversion recovery images were randomized to treatment with IV alteplase or placebo.

Non-invasive Assessment of Cerebral Hemodynamics Using Resting-State Functional Magnetic Resonance Imaging in Multiple Sclerosis and Age-Related White Matter Lesions.

Perfusion changes in white matter (WM) lesions and normal-appearing brain regions play an important pathophysiological role in multiple sclerosis (MS). However, most perfusion imaging methods require exogenous contrast agents, the repeated use of which is discouraged. Using resting-state functional MRI (rs-fMRI), we aimed to investigate differences in perfusion between white matter lesions and normal-appearing brain regions in MS and healthy participants.

Generative adversarial network-based reconstruction of healthy anatomy for anomaly detection in brain CT scans.

Purpose: To help radiologists examine the growing number of computed tomography (CT) scans, automatic anomaly detection is an ongoing focus of medical imaging research. Radiologists must analyze a CT scan by searching for any deviation from normal healthy anatomy. We propose an approach to detecting abnormalities in axial 2D CT slice images of the brain.

Assessing blood-brain barrier dysfunction and its association with Alzheimer's pathology, cognitive impairment and neuroinflammation.

Background: Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability.

Validation of a simple clinical tool for screening of acute lacunar stroke-A substudy of the WAKE-UP trial.

Introduction: Lacunar stroke represents around a quarter of all ischemic strokes; however, their identification with computed tomography in the hyperacute setting is challenging. We aimed to validate a clinical score to identify lacunar stroke in the acute setting, independently, with data from the WAKE-UP trial using magnetic resonance imaging.

Methods: We analyzed data from the WAKE-UP trial and extracted Oxfordshire Community Stroke Project (OCSP) classification.

Validation of 3- and 5-point severity scales to assess ARIA-E.

Introduction: Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) offer the promise of disease modification and are emerging treatment options in Alzheimer's disease. Anti-Aβ mAbs require brain magnetic resonance imaging (MRI) examinations to detect anti-amyloid-induced amyloid-related imaging abnormalities (ARIA), important adverse drug reactions associated with some anti-Aβ mAbs currently available in the United States and in clinical development. We present a simple rating system for ARIA-edema (ARIA-E) that can assess severity on a 3- or 5-point scale based upon a single linear measurement of the largest area of lesion, and dissemination in space, termed the 3-point Severity Scale of ARIA-E (SSAE-3) and the 5-point Severity Scale of ARIA-E (SSAE-5), respectively.

A deep learning analysis of stroke onset time prediction and comparison to DWI-FLAIR mismatch.

Introduction: When time since stroke onset is unknown, DWI-FLAIR mismatch rating is an established technique for patient stratification. A visible DWI lesion without corresponding parenchymal hyperintensity on FLAIR suggests time since onset of under 4.5 h and thus a potential benefit from intravenous thrombolysis.

Imaging of Amyloid-Related Imaging Abnormalities (ARIA).

Patients with Alzheimer's disease (AD) can now be treated with monoclonal antibodies aiming at clearing amyloid plaques from the brain parenchyma. Weeks after initiation of this drug therapy, patients may develop so-called amyloid-related imaging abnormalities (ARIA) on MRI. ARIA comprise vasogenic edema and leptomeningeal effusions (ARIA-E) as well as microbleeds and superficial hemosiderosis (ARIA-H).

Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds.

Purpose: Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions.

Methods: Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.

Deep learning-based segmentation of brain parenchyma and ventricular system in CT scans in the presence of anomalies.

Introduction: The automatic segmentation of brain parenchyma and cerebrospinal fluid-filled spaces such as the ventricular system is the first step for quantitative and qualitative analysis of brain CT data. For clinical practice and especially for diagnostics, it is crucial that such a method is robust to anatomical variability and pathological changes such as (hemorrhagic or neoplastic) lesions and chronic defects. This study investigates the increase in overall robustness of a deep learning algorithm that is gained by adding hemorrhage training data to an otherwise normal training cohort.

Enhanced diagnostic workup increases pathological findings in patients with acute ischaemic stroke: results of the prospective HEBRAS study.

Background: Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital.

Methods: Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany.

Reversibility of Diffusion-Weighted Imaging Lesions in Patients With Ischemic Stroke in the WAKE-UP Trial.

Background: 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).

Methods: 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) at baseline and follow-up (24 hours).

Exploring the ATN classification system using brain morphology.

Background: The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+. Here we assess the evidence for monotonic brain volume decline for this particular (amyloid-conversion first, tau-conversion second, N-conversion last) and alternative progressions using voxel-based morphometry (VBM) in a large cross-sectional MRI cohort.

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study.

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis.

Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital.

Reproducibility of cerebral perfusion measurements using BOLD delay.

BOLD delay is an emerging, noninvasive method for assessing cerebral perfusion that does not require the use of intravenous contrast agents and is thus particularly suited for longitudinal monitoring. In this study, we assess the reproducibility of BOLD delay using data from 136 subjects with normal cerebral perfusion scanned on two separate occasions with scanners, sequence parameters, and intervals between scans varying between subjects. The effects of various factors on the reproducibility of BOLD delay, defined here as the differences in BOLD delay values between the scanning sessions, were investigated using a linear mixed model.

New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.

Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System.

Comparing ARIA-E severity scales and effects of treatment management thresholds.

Introduction: Amyloid-related imaging abnormalities-edema (ARIA-E) is associated with anti-amyloid beta monoclonal antibody treatment. ARIA-E severity may be assessed using the Barkhof Grand Total Scale (BGTS) or the 3- or 5-point Severity Scales of ARIA-E (SSAE-3/SSAE-5). We assessed inter- and intra-reader correlations between SSAE-3/5 and BGTS.

Sex differences in imaging and clinical characteristics of patients from the WAKE-UP trial.

Background And Purpose: Sex-based differences in acute ischemic stroke are a well-known phenomenon. We aimed to explore these differences between women and men in the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial.

Methods: We compared baseline demographic and imaging characteristics (visual fluid-attenuated inversion recovery [FLAIR] positivity, relative FLAIR signal intensity, collateral status) between women and men in all screened patients.

Anatomical labeling of intracranial arteries with deep learning in patients with cerebrovascular disease.

Brain arteries are routinely imaged in the clinical setting by various modalities, e.g., time-of-flight magnetic resonance angiography (TOF-MRA).

Patient-Reported Quality of Life After Intravenous Alteplase for Stroke in the WAKE-UP Trial.

Background And Objectives: Intravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL).

Methods: WAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time.