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Predicting outcome after stroke: take a look at the other side

English title Predicting outcome after stroke: take a look at the other side
Applicant Wegener Susanne
Number 170683
Funding scheme SNSF Professorships
Research institution Neurologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Clinical Cardiovascular Research
Start/End 01.09.2017 - 31.08.2021
Approved amount 1'509'881.00
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Keywords (3)

neuroimaging; stroke; outcome prediction

Lay Summary (German)

Lead
Die Behandlung des Schlaganfalles in der Akutphase ist schwierig, da sie mit Komplikationen verbunden sein kann, Therapie-Entscheidungen aber in kurzer Zeit getroffen werden müssen. Bisherige Prädiktoren für Therapieerfolg konzentrieren sich auf die Schlaganfall-Läsion selbst (Größe, Schwere des Gewebeschadens). In dem Projekt soll untersucht werden, wieweit die Gegenseite des Gehirns über Regulation der Hirndurchblutung und Kollateralversorgung zum Schutz des betroffenen Gebietes beiträgt. Hieraus sollen neue Prädiktoren für Therapie-Erfolg entwickelt werden.
Lay summary

Inhalt und Ziele des Forschungsprojektes

Trotz weiterentwickelter Behandlungsmöglichkeiten stellt Schlaganfall weiterhin ein immenses Problem für die Betroffenen und ihre Familien dar. Zudem ist die Akutbehandlung (Thrombolyse) mit Risiken verbunden. Bildgebung des Gehirns ist ein zentraler Bestandteil der Schlaganfalldiagnostik und wird zur Entscheidung für oder gegen eine Therapie genutzt. Hierbei beurteilt der Kliniker Grösse und Schwere der Läsion zusammen mit anderen Faktoren wie Alter und Begleiterkrankungen, um eine optimale Entscheidung für den Patienten zu treffen. Dies ist aber mit den bestehenden Methoden nur ungenügend möglich. In dem aktuellen Projekt sollen neue, bessere Bildgebungsprädiktoren entwickelt werden. Aus experimentellen Schlaganfallstudien und Pilotdaten von Patienten wissen wir, dass die Gegenseite des Hirnes eine wichtige Rolle zur Unterstützung des betroffenen Gewebes spielt. In einem klinischen Projektteil sollen Bildgebungsdaten, speziell Bilder der Hirndurchblutung aus der Routinediagnostik mit neuen Methoden untersucht werden, um den Beitrag der Gegenseite zu charakterisieren. Hierbei kommen auch automatisierte Methoden («deep learning») zur Anwendung. In einem experimentellen Teil werden Mechanismen der Blutflussregulation auf der Gegenseite analysiert. Dazu wird in einem Schlaganfallmodell die Reaktion der Blutgefässe auf der Gegenseite durch optische Verfahren in vivo beurteilt.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojektes

In dem translationalen Projekt werden sich klinischer und experimenteller Forschungsteil ergänzen, um Mechanismen von Blutflussregulation bei Schlaganfall zu erforschen, und neue Bildgebungsprädiktoren zu entwickeln, die direkt in der Klinik angewandt werden können. Das Ziel ist, Therapieentscheidungen bei Schlagfall zu verbessern.

Direct link to Lay Summary Last update: 04.07.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Intravenous thrombolysis for suspected ischemic stroke with seizure at onset
Polymeris Alexandros A., Curtze Sami, Erdur Hebun, Hametner Christian, Heldner Mirjam R., Groot Adrien E., Zini Andrea, Béjot Yannick, Dietrich Annina, Martinez‐Majander Nicolas, von Rennenberg Regina, Gumbinger Christoph, Schaedelin Sabine, De Marchis Gian Marco, Thilemann Sebastian, Traenka Christopher, Lyrer Philippe A., Bonati Leo H., Wegener Susanne, Ringleb Peter A., Tatlisumak Turgut, Nolte Christian H., Scheitz Jan F., Arnold Marcel, et al. (2019), Intravenous thrombolysis for suspected ischemic stroke with seizure at onset, in Annals of Neurology, ana.25582-ana.25582.
Sensorimotor stroke alters hippocampo-thalamic network activity
Baumgartner Philipp, El Amki Mohamad, Bracko Oliver, Luft Andreas R., Wegener Susanne (2018), Sensorimotor stroke alters hippocampo-thalamic network activity, in Scientific Reports, 8(1), 15770-15770.
Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration.
(2018), Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration., in BMJ Open, e023265-e023265.
Ischemic stroke across sexes: What is the status quo?
Liberale Luca, Carbone Federico, Montecucco Fabrizio, Gebhard Cathérine, Lüscher Thomas F., Wegener Susanne, Camici Giovanni G. (2018), Ischemic stroke across sexes: What is the status quo?, in Frontiers in Neuroendocrinology, 50, 3-17.
Impact of Smoking on Clinical Outcome and Recanalization After Intravenous Thrombolysis for StrokeMulticenter Cohort Study
Kurmann Rebekka, Engelter Stefan T., Michel Patrik, Luft Andreas R., Wegener Susanne, Branscheidt Meret, Eskioglou Elissavet, Sirimarco Gaia, Lyrer Philippe A., Gensicke Henrik, Horvath Thomas, Fischer Urs, Arnold Marcel, Sarikaya Hakan (2018), Impact of Smoking on Clinical Outcome and Recanalization After Intravenous Thrombolysis for StrokeMulticenter Cohort Study, in Stroke, 49(5), 1170-1175.
Getting the First Grant
Wegener Susanne, Katan Mira (2017), Getting the First Grant, in Stroke, 49(1), e7-e9.
Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke
El AmkiMohamad, WegenerSusanne (2017), Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke, in International Journal of Molecular Sciences, 18(12), 2669-2669.
Contraceptive drugs mitigate experimental stroke-induced brain injury
El AmkiMohamad, BinderNAdine, Steffen Riccardo, SchneiderHannah, LuftAndreas, WellerMichael, ImthurnBruno, Merki-FeldGabriele, WegenerSusanne, Contraceptive drugs mitigate experimental stroke-induced brain injury, in Cardiovascular Research.

Collaboration

Group / person Country
Types of collaboration
Prof. James Faber UNC Chapel Hill United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Prof. D. Razansky/INstitute of Pharmacology and Toxicology UZH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Valavanis/Dept. of Neuroradiology USZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Prof. Sick/ Institute of Epidemiology, Biostatistics and Prevention Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Menze/TU Munich Informatics Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Gralla and Prof. Wiest/Neuroradiology Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. B. Weber/Institute of Pharmacology and Toxicology UZH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Hoehn/MPI for Metabolism Research Cologne Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Arnold/ Neurology Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Buxton and Prof. Wong/ UCSD CFMRI United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Symposium Neurointensivmedizin Talk given at a conference Der instabile Patient mit akuutem Schlaganfall 10.10.2019 Zürich, Switzerland Wegener Susanne;
Mismatch Symposium Neurochirurgie Talk given at a conference Das Mismatch in MRT und CT 20.03.2019 Zürich, Switzerland Wegener Susanne;
Fortbildung Anästhesie/ Intensivmedizin USZ Talk given at a conference TICH-NOAC Studie 09.01.2019 Zürich, Switzerland Wegener Susanne;
Seniorenuniverstät Zürich Talk given at a conference Neues aus der personalisierten Schlaganfalltherapie 29.11.2018 Zürich, Switzerland Wegener Susanne;
Seniorenuniversität Winterthur Individual talk Neue Ansätze zur personalisierten Schlaganfalltherapie 14.11.2018 Winterthur ZHAW, Switzerland Wegener Susanne;
Swiss Neurological Society Annual Conference Talk given at a conference Women in Neurology 27.09.2018 Montreux, Switzerland Wegener Susanne; El Amki Mohamad; Herzog Lisa;
ZNZ Annual Symposium Poster 2 posters: Stroke detection using deep learning approaches/ The impact of collaterals on reperfusion in stroke 13.09.2018 Zürich, Switzerland El Amki Mohamad; Wegener Susanne; Herzog Lisa;
Europen Stroke Conference Poster 3Posters: Crossed cerebellar diaschisis after stroke/ Quantitative Susceptibility Mapping in Ischemic stroke patients/Anticipating intracranial hypertension before it can harm: Optic nerve sonography to monitor intracranial pressure aftzer stroke 16.05.2018 Gotheborg, Sweden Wegener Susanne;
30+1 Years of In-vivo-NMR Symposium Talk given at a conference The other side of stroke 27.04.2018 Köln, Germany Wegener Susanne;


Self-organised

Title Date Place
CRPP kick-off Symposium 03.10.2019 Zürich, Switzerland
Workshop: The interplay of microcirculation and plasticity after ischemic stroke 12.09.2019 Zürich, Switzerland
KNZ Research Day 22.08.2019 Zürich, Switzerland
Symposium Hot techniques in neuroimaging of cerebrovascular disease 05.07.2019 Yokohama, Japan
NKO (Neuro-Kopf) Research Day 17.06.2019 Zürich, Switzerland
KNZ Research day 05.09.2018 Zürich, Switzerland
Kontroversen in der Schlaganfalltherapie 09.11.2017 Zürich, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Seniorenuniversität German-speaking Switzerland 2019
Talks/events/exhibitions 100 ways of thinking/Kunsthalle UZH German-speaking Switzerland 2018

Associated projects

Number Title Start Funding scheme
189776 SAFIR - From the Prototype to the Full-Scale Scanner 01.09.2020 R'EQUIP

Abstract

Despite improvements in primary prophylaxis and acute recanalization treatments, stroke remains one of the leading causes of death and disability worldwide. In order to achieve the best outcome possible for the individual patient, therapies have to be administered rapidly. However, the longer the time from symptom onset, the lower the efficacy and the higher the risk of treatment side effects. Although brain imaging is the mainstay of acute stroke diagnostics, current imaging strategies that aim to predict therapeutic success or failure in acute stroke patients remain insufficient. Here, we propose a novel prediction approach that is based on immediate and long-term vascular adaptations affecting the contralateral side of stroke. From data obtained through animal models of stroke and imaging in patients with proximal vessel occlusions, contralateral cerebral blood flow (CBF) appears to be particularly suited to predict clinical benefit from recanalization therapies. Contralateral CBF and related perfusion parameters may indicate the ability of the individual to withstand longer durations of ischemia. In the experimental part of the project, we will use a thrombin-injection stroke model that does not artificially impact collateral supply. Reperfusion will be achieved through intravenous injection of recombinant tissue plasminogen activator (rtPA). To assess CBF and ischemic tissue damage, repeated magnetic resonance imaging (MRI) combined with positron emission tomography (PET) will be performed during ischemia, after reperfusion and in the chronic phase of stroke along with behavioral assessments. In the same stroke model, processes influencing CBF on the microvascular level will be directly observed using advanced optical imaging methods. Structural adaptations of the microvascular bed as well as gene and protein expression profiles contralateral to stroke will be analyzed in brain samples. In the clinical part of the project, we will analyze stroke patient imaging data in relation to clinical outcome. In addition to a traditional region-of interest (ROI) based analysis we will apply a novel, “unbiased” machine learning algorithm to extract relevant outcome predictors from patient imaging data.Using a translational approach we aim for a mechanistic characterization of the concept of contralateral flow changes in stroke, and will generate and apply imaging predictors to clinical patient data. With the multidisciplinary study proposed here, I envision i) to deepen the understanding of the basic mechanisms regulating brain perfusion after ischemic stroke, and ii) to improve therapeutic decision-making in acute stroke patients.
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