Jochen B Fiebach

Charité Universitätsmedizin Berlin | Charité · Center for Stroke Research Berlin

Mobile computed tomography (CT) scanning in specialized ambulances has recently become feasible. Two randomized trials have used mobile CTs for prehospital thrombolysis. This short review summarizes the available literature on this topic and provides an outlook on potential future developments. Mobile CT in acute suspected stoke is feasible and hel...

Importance The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the golden hour.Objective To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome.Desi...

Background and purpose: Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a mal...

"Lone" atrial fibrillation (AF) is generally used to refer to patients with AF in the absence of structural heart disease. When the decision for oral anticoagulation is discussed, "lone" AF refers to patients who do not have established stroke risk factors. Imaging is often used to rule out structural heart disease, e.g. coronary artery disease, pe...

Background and purpose: Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Methods: Between 2008 and...

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....

Vasogenic edema and sulcal effusions detected with Magnetic Resonance Imaging (MRI), known as Amyloid‐Related Imaging Abnormalities‐Edema (ARIA‐E), are manageable side effects of anti‐amyloid immunotherapies. Periodic MRI scans with severity assessment of ARIA‐E are used in clinical trials or to guide practice with these therapies. Several scales w...

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 tim...

Brain arteries are routinely imaged in the clinical setting by various modalities, e.g., time-of-flight magnetic resonance angiography (TOF-MRA). These imaging techniques have great potential for the diagnosis of cerebrovascular disease, disease progression, and response to treatment. Currently, however, only qualitative assessment is implemented i...

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 analysi...

Background Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods Patients with an acut...

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...

Introduction Higher white blood cell (WBC) count is associated with poor functional outcome in acute ischemic stroke (AIS). However, little is known about whether the association is modified by treatment with intravenous alteplase. Methods WAKE-UP was a randomized controlled trial of the efficacy and safety of magnetic resonance imaging [MRI]-base...

Objectives Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict...

Sharing labeled data is crucial to acquire large datasets for various Deep Learning applications. In medical imaging, this is often not feasible due to privacy regulations. Whereas anonymization would be a solution, standard techniques have been shown to be partially reversible. Here, synthetic data using a Generative Adversarial Network (GAN) with...

Background and purpose To determine the frequency and distribution pattern of acute DWI lesions outside the hippocampus in patients clinically presenting with Transient Global Amnesia (TGA). Methods Consecutive patients clinically presenting with TGA between January 2010 and January 2017 admitted to our hospital were retrospectively evaluated. All...

Purpose Cerebral neoplasms of various histological origins may show comparable appearances on conventional Magnetic Resonance Imaging (MRI). Vessel size imaging (VSI) is an MRI technique that enables noninvasive assessment of microvasculature by providing quantitative estimates of microvessel size and density. In this study, we evaluated the potent...

Background: To assess the prevalence of magnetic resonance imaging (MRI) detected ischemic brain lesions and their association with cognitive function 3-months after first-time ablation using continuous oral anticoagulation in patients with paroxysmal atrial fibrillation (AF). Methods: Pre-specified analysis of the Anticoagulation using the direct...

Background 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. Methods In screened patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thro...

Deep learning requires large labeled datasets that are difficult to gather in medical imaging due to data privacy issues and time-consuming manual labeling. Generative Adversarial Networks (GANs) can alleviate these challenges enabling synthesis of shareable data. While 2D GANs have been used to generate 2D images with their corresponding labels, t...

Background and Purpose The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume chan...

Introduction: Various chronic pain conditions go along with functional and structural brain changes. This study aimed to investigate functional and structural brain changes by magnetic resonance imaging (MRI) in inflammatory bowel disease (IBD) patients with chronic abdominal pain. Methods: Sixty-four subjects were included in the final analysis...

Background: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure. Aims: The aim of this stu...

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate t...

Background 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. Aims Estimating symptom onset during night-sleep in patients from the WAK...

Background and Objectives Cerebral microbleeds (CMBs) are common in acute ischemic stroke patients and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown. Methods We performed a pre-specified analysis of the prospective randomized...

Neurological diseases such as ischemic stroke and dementia are associated with compromised blood-brain barrier (BBB) permeability. Knowledge about the time course of BBB leakage may have impact on therapeutic interventions and diagnostic measures such as testing for blood biomarkers. However, reports on the timeline and pattern of this leakage are...

Background and Purpose: In the setting of acute ischemic stroke, increased blood-brain barrier permeability (BBBP) as a sign of injury is believed to be associated with increased risk of poor outcome. Pre-clinical studies show that selected serum biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα)...

Background and Purpose During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors o...

Background and purpose: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-contro...

Background Arterial brain vessel segmentation allows utilising clinically relevant information contained within the cerebral vascular tree. Currently, however, no standardised performance measure is available to evaluate the quality of cerebral vessel segmentations. Thus, we developed a performance measure selection framework based on manual visual...

Individualized treatment of acute stroke depends on the timely detection of ischemia and potentially salvageable tissue in the brain. Using functional MRI (fMRI), it is possible to characterize cerebral blood flow from blood‐oxygen‐level‐dependent (BOLD) signals without the administration of exogenous contrast agents. In this study, we applied spat...

Objectives Patients waking up with stroke symptoms are often excluded from intravenous thrombolysis with alteplase (IV-tpa). The WAKE-UP trial, a European multicenter randomized controlled trial, proved the clinical effectiveness of magnetic resonance imaging-guided IV-tpa for these patients. This analysis aimed to assess the cost-effectiveness of...

Lesion analysis is a fundamental and classical approach for inferring the causal contributions of brain regions to brain function. However, many studies have been limited by the shortcomings of methodology or clinical data. Aiming to overcome these limitations, we here use an objective multivariate approach based on game theory, Multi-perturbation...

Stroke has a deleterious impact on quality of life. However, it is less well known if stroke lesions in different brain regions are associated with reduced quality of life (QoL). We therefore investigated this association by multivariate lesion-symptom mapping. We analyzed magnetic resonance imaging and clinical data from the WAKE-UP trial. Europea...

Cognitive dysfunction in Parkinson’s disease (PD) is associated with increased expression of the PD cognition-related pattern (PDCP), which overlaps with the normal default mode network (DMN). Here, we sought to determine the degree to which the former network represents loss of the latter as a manifestation of the disease process. To address this,...

Introduction Hyperintense acute reperfusion marker (HARM) is an indicator of early disruption of the blood-brain-barrier. Our aim was to investigate the incidence of HARM in patients with a diffusion weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch and determine the association between this marker and hemorrhagic compli...

The development of reperfusion therapies has profoundly impacted stroke care, initially with the advent of IV thrombolytic (IVT) treatment and, more recently, with the development and refinement of endovascular treatment (EVT). Progress in neuroimaging has supported the paradigm shift of stroke care, and advanced neuroimaging now has a fundamental...

Introduction To assess the association between 24 h blood pressure variability (BPV) on functional outcome and treatment effect of intravenous alteplase in acute ischaemic stroke. Patients and methods In all patients with acute ischaemic stroke of unknown onset randomised in the WAKE-UP (Efficacy and Safety of magnetic resonance imaging [MRI]-base...

Background The smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis. Methods The primary endpoin...

Background and Purpose We aimed to investigate fluid-attenuated inversion recovery changes in the penumbra. Methods 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 Str...

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...

MRI-based vessel size imaging (VSI) allows for in-vivo assessment of cerebral microvasculature and perfusion. This exploratory analysis of vessel size (VS) and density (Q; both assessed via VSI) in the subacute phase of ischemic stroke involved sixty-two patients from the BAPTISe cohort (‘Biomarkers And Perfusion--Training-Induced changes after Str...

Background: To study the effect of intravenous alteplase on development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. Methods: This post-hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT0152...

In ischemic stroke, the study of edema, measurable as fluid attenuated inversion recovery (FLAIR) signal increase, has mainly focused on the ischemic core and less on the surrounding penumbra. To the naked eye, no FLAIR changes are present in the penumbra. However, changes in perfusion status could induce physiological changes resulting in subtle p...

Background and purpose: Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke. Methods: We retros...

Objective: The timing of brain atrophy after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI dat...

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombo...

Anonymization and data sharing are crucial for privacy protection and acquisition of large datasets for medical image analysis. This is a big challenge, especially for neuroimaging. Here, the brain’s unique structure allows for re-identification and thus requires non-conventional anonymization. Generative adversarial networks (GANs) have the potent...

Background and Purpose Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke. Methods We retrosp...

Average Hausdorff distance is a widely used performance measure to calculate the distance between two point sets. In medical image segmentation, it is used to compare ground truth images with segmentations allowing their ranking. We identified, however, ranking errors of average Hausdorff distance making it less suitable for applications in segment...

The importance of vascular integrity in the context of neurodegeneration and specifically Alzheimer’s disease (AD) is increasingly recognized. It has been shown that Blood‐brain barrier (BBB) breakdown in the hippocampus correlates with functional impairment independent of AD pathology. The aim of this study is to investigate BBB permeability in ea...

Background: We compared two simple and rapid diameter-based methods (ABC/2, od-value) in terms of their accuracy in predicting lesion volume >70 ml and >100 ml. Methods: In 238 DWI images of ischemic stroke patients from the AXIS2 trial, maximum lesion diameter and corresponding maximum orthogonal diameter were measured. Estimation of infarct vo...

Background One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. Methods WAKE-UP was a multicenter, randomized, double-blind...

Background Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods We did a systematic review and meta-analysis of individual pati...

Background and purpose: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. Methods: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided...

Introduction: Arterial brain vessel assessment is crucial for the diagnostic process in patients with cerebrovascular disease. Non-invasive neuroimaging techniques, such as time-of-flight (TOF) magnetic resonance angiography (MRA) imaging are applied in the clinical routine to depict arteries. They are, however, only visually assessed. Fully automa...

Objective: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA). Methods: We performed a post hoc anal...

Anonymization and data sharing are crucial for privacy protection and acquisition of large datasets for medical image analysis. This is a big challenge, especially for neuroimaging. Here, the brain's unique structure allows for re-identification and thus requires non-conventional anonymization. Generative adversarial networks (GANs) have the potent...

BACKGROUND Elevated cardiac troponin (cTn) indicating cardiomyocyte injury is common after acute ischemic stroke (AIS) and associated with poor functional outcome. Myocardial injury is part of a broad spectrum of cardiac complications that may occur after AIS. Previous studies have shown that in most patients the underlying mechanism of stroke-asso...

Background: Elevated cardiac troponin, which indicates cardiomyocyte injury, is common after acute ischemic stroke and is associated with poor functional outcome. Myocardial injury is part of a broad spectrum of cardiac complications that may occur after acute ischemic stroke. Previous studies have shown that in most patients, the underlying mecha...

Purpose Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of p...

Average Hausdorff Distance (AVD) is a widely used performance measure to calculate the distance between two point sets. In medical image segmentation, AVD is used to compare ground truth images with segmentation results allowing their ranking. We identified, however, a ranking bias of AVD making it less suitable for segmentation ranking. To mitigat...

Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associ...

Background: The anatomical distribution of acute lacunar infarcts has mainly been studied for supratentorial lesions. In addition, little is known about the association with distinct stroke symptoms, not summarized as classical lacunar syndromes. We aimed to describe the spatial lesion distribution of acute supra- and infratentorial lacunar infarc...

Objective To identify, characterize, and automatically classify hypoperfusion-related changes in the blood oxygenation level dependent (BOLD) signal in acute stroke using spatial independent component analysis of resting-state functional MRI data. Methods We applied spatial independent component analysis to resting-state functional MRI data of 37...

Aims Heart failure (HF) is frequent in patients with acute ischaemic stroke (AIS) and associated with higher morbidity and mortality. Assessment of cardiac function in AIS patients using cardiovascular MRI (CMR) may help to detect HF. We report the rate of systolic and diastolic dysfunction in a cohort of patients with AIS using CMR and compare cin...