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1. ISLES 2024: The first longitudinal multimodal multi-center real-world dataset in (sub-)acute stroke

Author

Riedel, Evamaria O., de la Rosa, Ezequiel, Baran, The Anh, Petzsche, Moritz Hernandez, Baazaoui, Hakim, Yang, Kaiyuan, Robben, David, Seia, Joaquin Oscar, Wiest, Roland, Reyes, Mauricio, Su, Ruisheng, Zimmer, Claus, Boeckh-Behrens, Tobias, Berndt, Maria, Menze, Bjoern, Wiestler, Benedikt, Wegener, Susanne, and Kirschke, Jan S.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Stroke remains a leading cause of global morbidity and mortality, placing a heavy socioeconomic burden. Over the past decade, advances in endovascular reperfusion therapy and the use of CT and MRI imaging for treatment guidance have significantly improved patient outcomes and are now standard in clinical practice. To develop machine learning algorithms that can extract meaningful and reproducible models of brain function for both clinical and research purposes from stroke images - particularly for lesion identification, brain health quantification, and prognosis - large, diverse, and well-annotated public datasets are essential. While only a few datasets with (sub-)acute stroke data were previously available, several large, high-quality datasets have recently been made publicly accessible. However, these existing datasets include only MRI data. In contrast, our dataset is the first to offer comprehensive longitudinal stroke data, including acute CT imaging with angiography and perfusion, follow-up MRI at 2-9 days, as well as acute and longitudinal clinical data up to a three-month outcome. The dataset includes a training dataset of n = 150 and a test dataset of n = 100 scans. Training data is publicly available, while test data will be used exclusively for model validation. We are making this dataset available as part of the 2024 edition of the Ischemic Stroke Lesion Segmentation (ISLES) challenge (https://www.isles-challenge.org/), which continuously aims to establish benchmark methods for acute and sub-acute ischemic stroke lesion segmentation, aiding in creating open stroke imaging datasets and evaluating cutting-edge image processing algorithms.

Published
2024

2. ISLES'24: Improving final infarct prediction in ischemic stroke using multimodal imaging and clinical data

Author

de la Rosa, Ezequiel, Su, Ruisheng, Reyes, Mauricio, Wiest, Roland, Riedel, Evamaria O., Kofler, Florian, Yang, Kaiyuan, Baazaoui, Hakim, Robben, David, Wegener, Susanne, Kirschke, Jan S., Wiestler, Benedikt, and Menze, Bjoern

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Accurate estimation of core (irreversibly damaged tissue) and penumbra (salvageable tissue) volumes is essential for ischemic stroke treatment decisions. Perfusion CT, the clinical standard, estimates these volumes but is affected by variations in deconvolution algorithms, implementations, and thresholds. Core tissue expands over time, with growth rates influenced by thrombus location, collateral circulation, and inherent patient-specific factors. Understanding this tissue growth is crucial for determining the need to transfer patients to comprehensive stroke centers, predicting the benefits of additional reperfusion attempts during mechanical thrombectomy, and forecasting final clinical outcomes. This work presents the ISLES'24 challenge, which addresses final post-treatment stroke infarct prediction from pre-interventional acute stroke imaging and clinical data. ISLES'24 establishes a unique 360-degree setting where all feasibly accessible clinical data are available for participants, including full CT acute stroke imaging, sub-acute follow-up MRI, and clinical tabular data. The contributions of this work are two-fold: first, we introduce a standardized benchmarking of final stroke infarct segmentation algorithms through the ISLES'24 challenge; second, we provide insights into infarct segmentation using multimodal imaging and clinical data strategies by identifying outperforming methods on a finely curated dataset. The outputs of this challenge are anticipated to enhance clinical decision-making and improve patient outcome predictions. All ISLES'24 materials, including data, performance evaluation scripts, and leading algorithmic strategies, are available to the research community following \url{https://isles-24.grand-challenge.org/}.

Published
2024

3. A Robust Ensemble Algorithm for Ischemic Stroke Lesion Segmentation: Generalizability and Clinical Utility Beyond the ISLES Challenge

Author

de la Rosa, Ezequiel, Reyes, Mauricio, Liew, Sook-Lei, Hutton, Alexandre, Wiest, Roland, Kaesmacher, Johannes, Hanning, Uta, Hakim, Arsany, Zubal, Richard, Valenzuela, Waldo, Robben, David, Sima, Diana M., Anania, Vincenzo, Brys, Arne, Meakin, James A., Mickan, Anne, Broocks, Gabriel, Heitkamp, Christian, Gao, Shengbo, Liang, Kongming, Zhang, Ziji, Siddiquee, Md Mahfuzur Rahman, Myronenko, Andriy, Ashtari, Pooya, Van Huffel, Sabine, Jeong, Hyun-su, Yoon, Chi-ho, Kim, Chulhong, Huo, Jiayu, Ourselin, Sebastien, Sparks, Rachel, Clèrigues, Albert, Oliver, Arnau, Lladó, Xavier, Chalcroft, Liam, Pappas, Ioannis, Bertels, Jeroen, Heylen, Ewout, Moreau, Juliette, Hatami, Nima, Frindel, Carole, Qayyum, Abdul, Mazher, Moona, Puig, Domenec, Lin, Shao-Chieh, Juan, Chun-Jung, Hu, Tianxi, Boone, Lyndon, Goubran, Maged, Liu, Yi-Jui, Wegener, Susanne, Kofler, Florian, Ezhov, Ivan, Shit, Suprosanna, Petzsche, Moritz R. Hernandez, Menze, Bjoern, Kirschke, Jan S., and Wiestler, Benedikt

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Diffusion-weighted MRI (DWI) is essential for stroke diagnosis, treatment decisions, and prognosis. However, image and disease variability hinder the development of generalizable AI algorithms with clinical value. We address this gap by presenting a novel ensemble algorithm derived from the 2022 Ischemic Stroke Lesion Segmentation (ISLES) challenge. ISLES'22 provided 400 patient scans with ischemic stroke from various medical centers, facilitating the development of a wide range of cutting-edge segmentation algorithms by the research community. Through collaboration with leading teams, we combined top-performing algorithms into an ensemble model that overcomes the limitations of individual solutions. Our ensemble model achieved superior ischemic lesion detection and segmentation accuracy on our internal test set compared to individual algorithms. This accuracy generalized well across diverse image and disease variables. Furthermore, the model excelled in extracting clinical biomarkers. Notably, in a Turing-like test, neuroradiologists consistently preferred the algorithm's segmentations over manual expert efforts, highlighting increased comprehensiveness and precision. Validation using a real-world external dataset (N=1686) confirmed the model's generalizability. The algorithm's outputs also demonstrated strong correlations with clinical scores (admission NIHSS and 90-day mRS) on par with or exceeding expert-derived results, underlining its clinical relevance. This study offers two key findings. First, we present an ensemble algorithm (https://github.com/Tabrisrei/ISLES22_Ensemble) that detects and segments ischemic stroke lesions on DWI across diverse scenarios on par with expert (neuro)radiologists. Second, we show the potential for biomedical challenge outputs to extend beyond the challenge's initial objectives, demonstrating their real-world clinical applicability.

Published
2024

4. Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA

Author

Yang, Kaiyuan, Musio, Fabio, Ma, Yihui, Juchler, Norman, Paetzold, Johannes C., Al-Maskari, Rami, Höher, Luciano, Li, Hongwei Bran, Hamamci, Ibrahim Ethem, Sekuboyina, Anjany, Shit, Suprosanna, Huang, Houjing, Prabhakar, Chinmay, de la Rosa, Ezequiel, Waldmannstetter, Diana, Kofler, Florian, Navarro, Fernando, Menten, Martin, Ezhov, Ivan, Rueckert, Daniel, Vos, Iris, Ruigrok, Ynte, Velthuis, Birgitta, Kuijf, Hugo, Hämmerli, Julien, Wurster, Catherine, Bijlenga, Philippe, Westphal, Laura, Bisschop, Jeroen, Colombo, Elisa, Baazaoui, Hakim, Makmur, Andrew, Hallinan, James, Wiestler, Bene, Kirschke, Jan S., Wiest, Roland, Montagnon, Emmanuel, Letourneau-Guillon, Laurent, Galdran, Adrian, Galati, Francesco, Falcetta, Daniele, Zuluaga, Maria A., Lin, Chaolong, Zhao, Haoran, Zhang, Zehan, Ra, Sinyoung, Hwang, Jongyun, Park, Hyunjin, Chen, Junqiang, Wodzinski, Marek, Müller, Henning, Shi, Pengcheng, Liu, Wei, Ma, Ting, Yalçin, Cansu, Hamadache, Rachika E., Salvi, Joaquim, Llado, Xavier, Estrada, Uma Maria Lal-Trehan, Abramova, Valeriia, Giancardo, Luca, Oliver, Arnau, Liu, Jialu, Huang, Haibin, Cui, Yue, Lin, Zehang, Liu, Yusheng, Zhu, Shunzhi, Patel, Tatsat R., Tutino, Vincent M., Orouskhani, Maysam, Wang, Huayu, Mossa-Basha, Mahmud, Zhu, Chengcheng, Rokuss, Maximilian R., Kirchhoff, Yannick, Disch, Nico, Holzschuh, Julius, Isensee, Fabian, Maier-Hein, Klaus, Sato, Yuki, Hirsch, Sven, Wegener, Susanne, and Menze, Bjoern

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods, Quantitative Biology - Tissues and Organs
Abstract

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically., Comment: 24 pages, 11 figures, 9 tables. Summary Paper for the MICCAI TopCoW 2023 Challenge

Published
2023

9. Deep transformation models for functional outcome prediction after acute ischemic stroke

Author

Herzog, Lisa, Kook, Lucas, Götschi, Andrea, Petermann, Katrin, Hänsel, Martin, Hamann, Janne, Dürr, Oliver, Wegener, Susanne, and Sick, Beate

Subjects
Statistics - Applications
Abstract

In many medical applications, interpretable models with high prediction performance are sought. Often, those models are required to handle semi-structured data like tabular and image data. We show how to apply deep transformation models (DTMs) for distributional regression which fulfill these requirements. DTMs allow the data analyst to specify (deep) neural networks for different input modalities making them applicable to various research questions. Like statistical models, DTMs can provide interpretable effect estimates while achieving the state-of-the-art prediction performance of deep neural networks. In addition, the construction of ensembles of DTMs that retain model structure and interpretability allows quantifying epistemic and aleatoric uncertainty. In this study, we compare several DTMs, including baseline-adjusted models, trained on a semi-structured data set of 407 stroke patients with the aim to predict ordinal functional outcome three months after stroke. We follow statistical principles of model-building to achieve an adequate trade-off between interpretability and flexibility while assessing the relative importance of the involved data modalities. We evaluate the models for an ordinal and dichotomized version of the outcome as used in clinical practice. We show that both, tabular clinical and brain imaging data, are useful for functional outcome prediction, while models based on tabular data only outperform those based on imaging data only. There is no substantial evidence for improved prediction when combining both data modalities. Overall, we highlight that DTMs provide a powerful, interpretable approach to analyzing semi-structured data and that they have the potential to support clinical decision making., Comment: Preprint under review

Published
2022
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11. Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization

Author

Binder, Nadine Felizitas, El Amki, Mohamad, Glück, Chaim, Middleham, William, Reuss, Anna Maria, Bertolo, Adrien, Thurner, Patrick, Deffieux, Thomas, Lambride, Chryso, Epp, Robert, Handelsmann, Hannah-Lea, Baumgartner, Philipp, Orset, Cyrille, Bethge, Philipp, Kulcsar, Zsolt, Aguzzi, Adriano, Tanter, Mickael, Schmid, Franca, Vivien, Denis, Wyss, Matthias Tasso, Luft, Andreas, Weller, Michael, Weber, Bruno, and Wegener, Susanne

Published
2024
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14. Sex Differences in Outcomes of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Preadmission Use of Antiplatelets

Author

Noseda, Roberta, Rea, Federico, Pagnamenta, Alberto, Agazzi, Pamela, Bianco, Giovanni, Sihabdeen, Shairin, Seiffge, David, Michel, Patrik, Nedeltchev, Krassen, Bonati, Leo, Kägi, Georg, Niederhauser, Julien, Nyffeler, Thomas, Luft, Andreas, Wegener, Susanne, Schelosky, Ludwig, Medlin, Friedrich, Rodic, Biljana, Peters, Nils, Renaud, Susanne, Mono, Marie-Luise, Carrera, Emmanuel, Fischer, Urs, Ceschi, Alessandro, and Cereda, Carlo Walter

Published
2023
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15. Effect of Asymptomatic and Symptomatic COVID-19 on Acute Ischemic Stroke Revascularization Outcomes

Author

Strambo, Davide, Marto, João Pedro, Ntaios, George, Nguyen, Thanh N., Michel, Patrik, Herzig, Roman, Członkowksa, Anna, Demeestere, Jelle, Yassin Mansour, Ossama, Georgiopoulos, Georgios, Nogueira, Raul G., Salerno, Alexander, Wegener, Susanne, Baumgartner, Philipp, Cereda, Carlo W., Bianco, Giovanni, Beyeler, Morin, Arnold, Marcel, Carrera, Emmanuel, Machi, Paolo, Altersberger, Valerian, Bonati, Leo, Gensicke, Henrik, Bolognese, Manuel, Peters, Nils, Wetzel, Stephan, Magriço, Marta, Nuno Ramos, João, Sargento-Freitas, João, Machado, Rita, Maia, Carolina, Machado, Egídio, Paiva-Nunes, Ana, Ferreira, Patrícia, Pinho-e-Melo, Teresa, Carvalho-Dias, Mariana, Paula, André, Alberto Correia, Manuel, Castro, Pedro, Azevedo, Elsa, Albuquerque, Luís, Nuno-Alves, José, Ferreira-Pinto, Joana, Meira, Torcato, Pereira, Liliana, Rodrigues, Miguel, Araújo, André, Rodrigues, Marta, Rocha, Mariana, Pereira-Fonseca, Ângelo, Ribeiro, Luís, Varela, Ricardo, Cappellari, Manuel, Zivelonghi, Cecilia, Sajeva, Giulia, Zini, Andrea, Gentile, Mauro, Forlivesi, Stefano, Migliaccio, Ludovica, Sessa, Maria, Pezzini, Alessandro, Sangalli, Davide, Zedde, Marialuisa, Pascarella, Rosario, Diamanti, Susanna, Beretta, Simone, Schwarz, Ghil, Frisullo, Giovanni, Marcheselli, Simona, Seners, Pierre, Sabben, Candice, Escalard, Simon, Piotin, Michel, Maier, Benjamin, Charbonnier, Guillaume, Vuillier, Fabrice, Legris, Loic, Cuisenier, Pauline, Vodret, Francesca R., Marnat, Gaultier, Liegey, Jean-Sebastien, Sibon, Igor, Flottmann, Fabian, Broocks, Gabriel, Gloyer, Nils-Ole, Bohmann, Ferdinand O., Hendrik Schaefer, Jan, Nolte, Christian H., Audebert, Heinrich, Siebert, Eberhard, Sykora, Marek, Lang, Wilfried, Ferrari, Julia, Mayer-Suess, Lukas, Knoflach, Michael, Gizewski, Elke-Ruth, Stolp, Jeffrey, Stolze, Lotte J., Coutinho, Jonathan M., Nederkoorn, Paul J., van-den-Wijngaard, Ido, de Meris, Joke, Lemmens, Robin, De Raedt, Sylvie, Vandervorst, Fenne, Pierre Rutgers, Matthieu, Guilmot, Antoine, Dusart, Anne, Bellante, Flavio, Calleja-Castaño, Patricia, Ostos, Fernando, Gonzalez-Ortega, Guillermo, Martín-Jiménez, Paloma, García-Madrona, Sebastian, Cruz-Culebras, Antonio, Vera, Rocio, Matute, Maria-Consuelo, Fuentes, Blanca, Alonso-de-Leciñana, María, Rigual, Ricardo, Díez-Tejedor, Exuperio, Pérez-Sánchez, Soledad, Montaner, Joan, Díaz-Otero, Fernando, Perez de la Ossa, Natalia, Flores-Pina, Belén, Muñoz-Narbona, Lucia, Chamorro, Angel, Rodríguez-Vázquez, Alejandro, Renú, Arturo, Ayo-Martin, Oscar, Hernandez-Fernandez, Francisco, Segura, Tomas, Tejada-Meza, Herbert, Hlaing, Thant, See, Isaiah, Simister, Robert, Werring, David J., Saxhaug Kristoffersen, Espen, Nordanstig, Annika, Jood, Katarina, Rentzos, Alexandros, Šimůnek, Libor, Krajíčková, Dagmar, Krajina, Antonín, Mikulík, Robert, Cviková, Martina, Vinklárek, Jan, Školoudík, David, Roubec, Martin, Hurtikova, Eva, Hrubý, Rostislav, Ostry, Svatopluk, Skoda, Ondrej, Pernicka, Marek, Kočí, Lubomír, Eichlová, Zuzana, Jíra, Martin, Kovář, Martin, Panský, Michal, Mencl, Pavel, Paloušková, Hana, Tomek, Aleš, Janský, Petr, Olšerová, Anna, Šrámek, Martin, Havlíček, Roman, Malý, Petr, Trakal, Lukáš, Fiksa, Jan, Slovák, Matěj, Karliński, Michał, Nowak, Maciej, Sienkiewicz-Jarosz, Halina, Bochynska, Anna, Wrona, Pawel, Homa, Tomasz, Sawczynska, Katarzyna, Slowik, Agnieszka, Wlodarczyk, Ewa, Wiącek, Marcin, Tomaszewska-Lampart, Izabella, Sieczkowski, Bartosz, Bartosik-Psujek, Halina, Bilik, Marta, Bandzarewicz, Anna, Dorobek, Malgorzata, Zielińska-Turek, Justyna, Nowakowska-Kotas, Marta, Obara, Krystian, Urbanowski, Paweł, Budrewicz, Sławomir, Guziński, Maciej, Świtońska, Milena, Rutkowska, Iwona, Sobieszak-Skura, Paulina, Łabuz-Roszak, Beata, Dębiec, Aleksander, Staszewski, Jacek, Stępień, Adam, Zwiernik, Jacek, Wasilewski, Grzegorz, Tiu, Cristina, Terecoasă, Elena-Oana, Radu, Razvan-Alexandru, Negrila, Anca, Dorobat, Bogdan, Panea, Cristina, Tiu, Vlad, Petrescu, Simona, Özcan-Özdemir, Atilla, Mahmoud, Mostafa, El-Samahy, Hussam, Abdelkhalek, Hazem, Al-Hashel, Jasem, Ibrahim Ismail, Ismail, Salmeen, Athari, Ghoreishi, Abdoreza, Sabetay, Sergiu, Gross, Hana, Klein, Piers, Abdalkader, Mohamad, Jabbour, Pascal, El Naamani, Kareem, Tjoumakaris, Stavropoula, Abbas, Rawad, Mohamed, Ghada-A., Chebl, Alex, Min, Jiangyong, Hovingh, Majesta, Tsai, Jenny, Khan, Muhib-A., Nalleballe, Krishna, Onteddu, Sanjeeva, Masoud, Hesham E., Michael, Mina, Kaur, Navreet, Maali, Laith, Abraham, Michael, Khandelwal, Priyank, Bach, Ivo, Ong, Melody, Babici, Denis, Khawaja, Ayaz-M., Hakemi, Maryam, Rajamani, Kumar, Cano-Nigenda, Vanessa, Arauz, Antonio, Amaya, Pablo, Llanos, Natalia, Arango, Akemi, Vences, Miguel A., Barrientos, José-Domingo, Caetano, Rayllene, Targa, Rodrigo, Scollo, Sergio, Yalung, Patrick, Nagendra, Shashank, Gaikwad, Abhijit, and Seo, Kwon-Duk

Published
2024
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17. Integrating uncertainty in deep neural networks for MRI based stroke analysis

Author

Herzog, Lisa, Murina, Elvis, Dürr, Oliver, Wegener, Susanne, and Sick, Beate

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods, Statistics - Machine Learning
Abstract

At present, the majority of the proposed Deep Learning (DL) methods provide point predictions without quantifying the models uncertainty. However, a quantification of the reliability of automated image analysis is essential, in particular in medicine when physicians rely on the results for making critical treatment decisions. In this work, we provide an entire framework to diagnose ischemic stroke patients incorporating Bayesian uncertainty into the analysis procedure. We present a Bayesian Convolutional Neural Network (CNN) yielding a probability for a stroke lesion on 2D Magnetic Resonance (MR) images with corresponding uncertainty information about the reliability of the prediction. For patient-level diagnoses, different aggregation methods are proposed and evaluated, which combine the single image-level predictions. Those methods take advantage of the uncertainty in image predictions and report model uncertainty at the patient-level. In a cohort of 511 patients, our Bayesian CNN achieved an accuracy of 95.33% at the image-level representing a significant improvement of 2% over a non-Bayesian counterpart. The best patient aggregation method yielded 95.89% of accuracy. Integrating uncertainty information about image predictions in aggregation models resulted in higher uncertainty measures to false patient classifications, which enabled to filter critical patient diagnoses that are supposed to be closer examined by a medical doctor. We therefore recommend using Bayesian approaches not only for improved image-level prediction and uncertainty estimation but also for the detection of uncertain aggregations at the patient-level., Comment: 21 pages, 13 figures

Published
2020
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20. Thrombolysis in stroke patients with elevated inflammatory markers

Author

Altersberger, Valerian L., Enz, Lukas S., Sibolt, Gerli, Hametner, Christian, Nannoni, Stefania, Heldner, Mirjam R., Stolp, Jeffrey, Jovanovic, Dejana R., Zini, Andrea, Pezzini, Alessandro, Wegener, Susanne, Cereda, Carlo W., Ntaios, George, Räty, Silja, Gumbinger, Christoph, Heyse, Miriam, Polymeris, Alexandros A., Zietz, Annaelle, Schaufelbuehl, Anna, Strambo, Davide, Padlina, Giovanna, Slavova, Nedelina, Tiainen, Marjaana, Valkonen, Kati, Velzen, Twan J. van, Bigliardi, Guido, Stanarcevic, Predrag, Magoni, Mauro, Luft, Andreas, Bejot, Yannick, Vandelli, Laura, Padjen, Visnja, Nederkoorn, Paul J., Arnold, Marcel, Michel, Patrik, Ringleb, Peter A., Curtze, Sami, Engelter, Stefan T., and Gensicke, Henrik

Published
2022
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22. Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial

Author

Polymeris, Alexandros A., Karwacki, Grzegorz M., Siepen, Bernhard M., Schaedelin, Sabine, Tsakiris, Dimitrios A., Stippich, Christoph, Guzman, Raphael, Nickel, Christian H., Sprigg, Nikola, Kägi, Georg, Vehoff, Jochen, Barinka, Filip, Thilemann, Sebastian, Maurer, Marina, Wagner, Benjamin, Traenka, Christopher, Gensicke, Henrik, De Marchis, Gian Marco, Bonati, Leo H., Fischer, Urs, Z’Graggen, Werner J., Nedeltchev, Krassen, Wegener, Susanne, Baumgartner, Philipp, Engelter, Stefan T., Seiffge, David J., Peters, Nils, Lyrer, Philippe A., Clarke, Sandra, Falcao, Martina, Avramiotis, Nikolaos S, Dittrich, Tolga, Fisch, Urs, Fladt, Joachim, Hert, Lisa, Schneider, Iris, Wiegert, Martina, Zietz, Annaelle, Beyeler, Morin, Goeldlin, Martina, Kormann, Marianne, Maamari, Basel, McEvoy, Liselotte, Meinel, Thomas R, Müller, Madlaina, Vynckier, Jan, Ardila, Elena, Feuerstein, Ingrid, Gantenbein, Claudine, Müller, Anna, Seljmani, Vjosa, Wagner, Benedikt, Anders, Bettina, Backhaus, Roland, Paliantonis, Asterios, Taheri, Shadi, Thumm, Dennis, van Duinen, Jannie, and Von Bieberstein, Lita

Published
2023
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25. The volume of steal phenomenon is associated with neurological deterioration in patients with large-vessel occlusion minor stroke not eligible for thrombectomy

Author

Bellomo, Jacopo, primary, Sebök, Martina, additional, van Niftrik, Christiaan HB, additional, Stumpo, Vittorio, additional, Schubert, Tilman, additional, Madjidyar, Jawid, additional, Thurner, Patrick, additional, Globas, Christoph, additional, Wegener, Susanne, additional, Luft, Andreas R, additional, Kulcsár, Zsolt, additional, Regli, Luca, additional, and Fierstra, Jorn, additional

Published
2024
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26. Imaging of the brain–heart axis: prognostic value in a European setting

Author

Mikail, Nidaa, primary, Sager, Dominik F, additional, Gebert, Pimrapat, additional, Haider, Ahmed, additional, Todorov, Atanas, additional, Bengs, Susan, additional, Sablonier, Noemi, additional, Glarner, Isabelle, additional, Vinzens, Adriana, additional, Sang Bastian, Nastaran, additional, Epprecht, Gioia, additional, Sütsch, Claudia, additional, Delcò, Alessia, additional, Fiechter, Michael, additional, Portmann, Angela, additional, Treyer, Valerie, additional, Wegener, Susanne, additional, Gräni, Christoph, additional, Pazhenkottil, Aju, additional, Gebhard, Caroline E, additional, Regitz-Zagrosek, Vera, additional, Tanner, Felix C, additional, Kaufmann, Philipp A, additional, Buechel, Ronny R, additional, Rossi, Alexia, additional, and Gebhard, Catherine, additional

Published
2024
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31. Absent leptomeningeal collateralization is associated with greatest benefit from mechanical thrombectomy in the 6-24 hour time window.

Author

Dittrich, Tolga D, von Streng, Tennessee, Toebak, Anna M, Zietz, Annaelle, Wagner, Benjamin, Hänsel, Martin, Sutter, Raoul, Katan, Mira, Peters, Nils, Michels, Lars, Kulcsár, Zsolt, Karwacki, Grzegorz M, Pileggi, Marco, Cereda, Carlo W, Wegener, Susanne, Bonati, Leo H, Psychogios, Marios, and De Marchis, Gian Marco

Published
2024
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32. BOLD Cerebrovascular Reactivity and NOVA Quantitative MR Angiography in Adult Patients with Moyamoya Vasculopathy Undergoing Cerebral Bypass Surgery.

Author

Garbani Nerini, Loris, Bellomo, Jacopo, Höbner, Lara Maria, Stumpo, Vittorio, Colombo, Elisa, van Niftrik, Christiaan Hendrik Bas, Schubert, Tilman, Kulcsár, Zsolt, Wegener, Susanne, Luft, Andreas, Regli, Luca, Fierstra, Jorn, Sebök, Martina, and Esposito, Giuseppe

Subjects
MAGNETIC resonance angiography, CEREBRAL revascularization, REVASCULARIZATION (Surgery), CEREBRAL hemispheres, PATIENT selection, CEREBRAL angiography
Abstract

Revascularization surgery for the symptomatic hemisphere with hemodynamic impairment is effective for Moyamoya vasculopathy patients. However, careful patient selection is crucial and ideally supported by advanced quantitative hemodynamic imaging. Recently, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and quantitative magnetic resonance angiography with non-invasive optimal vessel analysis (qMRA-NOVA) have gained prominence in assessing these patients. This study aims to present the results of BOLD-CVR and qMRA-NOVA imaging along with the changes in cerebral hemodynamics and flow status following flow augmentation with superficial temporal artery–middle cerebral artery (STA-MCA) bypass in our Moyamoya vasculopathy patient cohort. Symptomatic patients with Moyamoya vasculopathy treated at the Clinical Neuroscience Center of the University Hospital Zurich who underwent hemodynamic and flow imaging (BOLD-CVR and qMRA-NOVA) before and after bypass were included in the analysis. Reduced hemispheric volume flow rates, as well as impaired BOLD-CVR, were measured in all 12 patients with Moyamoya vasculopathy before STA-MCA bypass surgery. Following the surgical procedure, post-operative BOLD-CVR demonstrated a non-significant increase in BOLD-CVR values within the revascularized, symptomatic middle cerebral artery territory and cerebral hemisphere. The results of the statistical tests should be viewed as indicative due to the small sample size. Additionally, post-operative qMRA-NOVA revealed a significant improvement in the hemispheric volume flow rate of the affected hemisphere due to the additional bypass flow rate. Our findings affirm the presence of hemodynamic and flow impairments in the symptomatic hemisphere of the Moyamoya vasculopathy patients. Bypass surgery proves effective in improving both BOLD-CVR impairment and the hemispheric volume flow rate in our patient cohort. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Pia-FLOW: Deciphering hemodynamic maps of the pial vascular connectome and its response to arterial occlusion.

Author

Glück, Chaim, Quanyu Zhou, Droux, Jeanne, Zhenyue Chen, Glandorf, Lukas, Wegener, Susanne, Razansky, Daniel, Weber, Bruno, and El Amki, Mohamad

Subjects
ARTERIAL occlusions, HEMODYNAMICS, FLUID dynamics, FLOW velocity, BONE marrow
Abstract

The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Dynamic Perviousness Has Predictive Value for Clot Fibrin Content in Acute Ischemic Stroke.

Author

Anagnostakou, Vania, Toth, Daniel, Bertalan, Gergely, Müller, Susanne, Reimann, Regina R., Epshtein, Mark, Madjidyar, Jawid, Thurner, Patrick, Schubert, Tilman, Wegener, Susanne, and Kulcsar, Zsolt

Subjects
PEARSON correlation (Statistics), ISCHEMIC stroke, THROMBOSIS, ERYTHROCYTES, COMPUTED tomography
Abstract

Dynamic perviousness is a novel imaging biomarker, with clot density measurements at multiple timepoints to allow longer contrast to thrombus interaction. We investigated the correlations between dynamic perviousness and clot composition in the setting of acute ischemic stroke. Thirty-nine patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) were analyzed. Patients received a three-phase CT imaging pre-thrombectomy and histopathological analysis of retrieved clots. Clot densities for every phase and change in densities between phases were calculated, leading to four patterns of dynamic perviousness: no contrast uptake, early contrast uptake with and without washout and late uptake. Clots were categorized into three groups based on dominant histologic composition: red blood cell (RBC)-rich, fibrin/platelet-rich and mixed. Clot composition was correlated with dynamic perviousness using the Kruskal–Wallis test and Pearson's correlation analysis. The dynamic perviousness categories showed a significant difference between fibrin-rich clots when compared to RBC-rich plus mixed groups. The uptake without washout category had significantly fewer fibrin clots compared to the uptake with washout (p = 0.036), and nearly significantly fewer fibrin clots when compared to the no uptake category (p = 0.057). Contrast uptake with different patterns of contrast washout showed significant differences of the likelihood for fibrin-rich clots. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Circadian functional changes of pain‐processing brainstem nuclei and implications for cluster headache: A 7 Tesla imaging study.

Author

Pohl, Heiko, Neumeier, Maria S., Gantenbein, Andreas R., Wegener, Susanne, Rosio, Michael, Hennel, Franciszek, Sandor, Peter S., Weller, Michael, and Michels, Lars

Subjects
BRAIN stem anatomy, THALAMUS physiology, RESEARCH funding, ACADEMIC medical centers, DIAGNOSTIC imaging, SCIENTIFIC observation, NEURAL pathways, PAIN threshold, DESCRIPTIVE statistics, MAGNETIC resonance imaging, CIRCADIAN rhythms, BRAIN stem, CLUSTER headache, PSYCHOLOGICAL tests, TIME
Abstract

Background: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. Objective: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. Methods: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high‐field (7 Tesla) and high‐resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region‐of‐interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region‐of‐interest. Results: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A‐delta‐mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = −40.79). Conclusion: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A‐delta‐mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks. Plain Language Summary: We wanted to find out if cluster headache attacks occur primarily at night because even healthy persons are more likely to feel pain at that time. Our sample of healthy participants did not have lower pain thresholds in the evening than at noon, and brain imaging suggested that the measurements were accurate. Thus, we could not prove our idea. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study

Author

Dittrich, Tolga D., Sporns, Peter B., Kriemler, Lilian F., Rudin, Salome, Nguyen, Anh, Zietz, Annaelle, Polymeris, Alexandros A., Tränka, Christopher, Thilemann, Sebastian, Wagner, Benjamin, Altersberger, Valerian L., Piot, Ines, Barinka, Filip, Müller, Susanne, Hänsel, Martin, Gensicke, Henrik, Engelter, Stefan T., Lyrer, Philippe A., Sutter, Raoul, Nickel, Christian H., Katan, Mira, Peters, Nils, Kulcsár, Zsolt, Karwacki, Grzegorz M., Pileggi, Marco, Cereda, Carlo, Wegener, Susanne, Bonati, Leo H., Fischer, Urs, Psychogios, Marios, and De Marchis, Gian Marco

Published
2023
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38. Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity

Author

van Niftrik, Christiaan H.B., primary, Sebök, Martina, additional, Germans, Menno R., additional, Halter, Matthias, additional, Pokorny, Thomas, additional, Stumpo, Vittorio, additional, Bellomo, Jacopo, additional, Piccirelli, Marco, additional, Pangalu, Athina, additional, Katan, Mira, additional, Wegener, Susanne, additional, Tymianski, Michael, additional, Kulcsár, Zsolt, additional, Luft, Andreas R., additional, Fisher, Joseph A., additional, Mikulis, David J., additional, Regli, Luca, additional, and Fierstra, Jorn, additional

Published
2024
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39. Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke

Author

Wueger, Patrizia, primary, Noseda, Roberta, additional, Pagnamenta, Alberto, additional, Bianco, Giovanni, additional, Seiffge, David, additional, Michel, Patrik, additional, Nedeltchev, Krassen, additional, Bonati, Leo, additional, Kägi, Georg, additional, Niederhauser, Julien, additional, Nyffeler, Thomas, additional, Luft, Andreas, additional, Wegener, Susanne, additional, Schelosky, Ludwig, additional, Medlin, Friedrich, additional, Rodic, Biljana, additional, Peters, Nils, additional, Renaud, Susanne, additional, Mono, Marie Luise, additional, Carrera, Emmanuel, additional, Fischer, Urs, additional, De Marchis, Gian Marco, additional, and Cereda, Carlo W., additional

Published
2024
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42. Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data

Author

Sebök, Martina, primary, Höbner, Lara Maria, additional, Fierstra, Jorn, additional, Schubert, Tilman, additional, Wegener, Susanne, additional, Kulcsár, Zsolt, additional, Luft, Andreas R., additional, Regli, Luca, additional, and Esposito, Giuseppe, additional

Published
2024
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43. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial

Author

Kahles, Timo, Nedeltchev, Krassen, Altersberger, Valerian, Bonati, Leo H, Brehm, Alex, Bruni, Nicole, De Marchis, Gian Marco, Engelter, Stefan T, Fabbro, Thomas, Fisch, Urs, Fladt, Joachim, Gensicke, Henrik, Hert, Lisa, Lyrer, Philippe A, Maurer, Marina, Peters, Nils, Polymeris, Alexandros, Psychogios, Marios-Nikos, Schaedelin, Sabine, Stippich, Christoph, Thilemann, Sebastian, Traenka, Christopher, Wagner, Benjamin, Arnold, Marcel, Fischer, Urs, Goeggel Simonetti, Barbara, Gralla, Jan, Heldner, Mirjam, Jung, Simon, Leib, Stephen L, Seiffge, David J, Mueller, Hubertus, Sveikata, Lukas, Sztajzel, Roman, Correia, Pamela, Eskandari, Ashraf, Meyer, Ivo, Michel, Patrik, Nannoni, Stefania, Remillard, Suzette, Sirimarco, Gaia, Zachariadis, Alexandros, Kaegi, Georg, Mueller, Anna, Vehoff, Jochen, Hamann, Janne, Luft, Andreas R, Steiner, Levke, Wegener, Susanne, Erdur, Hebun J, Nolte, Christian H, von Rennenberg, Regina, Scheitz, Jan F, Feil, Katharina, Kellert, Lars, Christensen, Hanne, Rosenbaum, Sverre, Schaedelin, Sabine A, Simonetti, Barbara Goeggel, Kägi, Georg, Seiffge, David, Polymeris, Alexandros A, and Lyrer, Philippe

Published
2021
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44. Hemodynamic Evaluation of Paradoxical Blood Oxygenation Level-Dependent Cerebrovascular Reactivity with Transcranial Doppler and MR Perfusion in Patients with Symptomatic Cerebrovascular Steno-occlusive Disease

Author

van Niftrik, Christiaan Hendrik Bas, primary, Sebök, Martina, additional, Muscas, Giovanni, additional, Hiller, Aimée, additional, Halter, Matthias, additional, Wegener, Susanne, additional, Regli, Luca, additional, and Fierstra, Jorn, additional

Published
2021
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46. Use of levamisole-adulterated cocaine is associated with increased load of white matter lesions

Author

Conrad, Florian, Hirsiger, Sarah, Winklhofer, Sebastian, Baumgartner, Markus R., Stampfli, Philipp, Seifritz, Erich, Wegener, Susanne, and Quednow, Boris B.

Subjects
Levamisole -- Health aspects, Brain diseases -- Risk factors, Cocaine -- Health aspects, Health, Psychology and mental health
Abstract

Background: Cocaine use has been associated with vascular pathologies, including cerebral white matter hyperintensities. Street cocaine is most often adulterated with levamisole, an anthelminthic drug that may also be associated with vascular toxicity. However, whether I evamisole exposure from cocaine consumption further accelerates the development of white matter lesions remains unknown. Methods: We investigated the association of cocaine and levamisole exposure with white matter hyperintensities in 35 chronic cocaine users and 34 healthy controls. We measured cocaine and levamisole concentrations in hair samples, which reflected exposure up to 6 months previously. We assessed the number and total surface area of the white matter hyperintensities using structural MRI (FLAIR sequence). Using generalized linear models, we analyzed the contributions of cocaine and levamisole to the number and area of white matter hyperintensities, accounting for several confounding factors. Results: Analysis using generalized linear models revealed that cocaine users had more white matter hyperintensities in terms of total surface area, but not in terms of number. Further generalized linear models that included cocaine and levamisole hair concentrations (instead of group) as predictors indicated that levamisole exposure was strongly associated with more and larger white matter hyperintensities, suggesting that the elevated white matter hyperintensities in cocaine users were driven mainly by levamisole exposure. Finally, white matter hyperintensities in levamisole-exposed cocaine users were located primarily in the periventricular and juxtacortical white matter. Limitations: The sample size was moderate, and blood pressure was not systematically assessed. Conclusion: As an adulterant of cocaine, levamisole appears to increase the risk of white matter injury., Introduction Cocaine is the second most consumed illicit drug in Europe and North America, after cannabis. In 2018, cocaine use was estimated to be 1.2% in the European Union (3.9 [...]

Published
2021
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48. Comparison of Aneurysmal and Non-Aneurysmal Spontaneous Cervical Artery Dissections in a Large Multicenter Cohort.

Author

Steinsiepe, Valentin K., Sarikaya, Hakan, Mordasini, Pasquale R., Wegener, Susanne, Inauen, Corinne, Baumgartner, Philipp, Jung, Simon, Antonenko, Kateryna, Fischer, Urs, Gralla, Jan, Umarova, Roza M., Goeggel Simonetti, Barbara, van Laarhoven, Constance J. H. C. M., de Borst, Gert J., Chabriat, Hugues, Heldner, Mirjam R., and Arnold, Marcel

Subjects
DISSECTING aneurysms, UNIVERSITY hospitals, MAGNETIC resonance angiography, VERTEBRAL artery, FOLLOW-up studies (Medicine)
Abstract

Dissecting aneurysms in patients with spontaneous cervical artery dissections have, so far, been reported as "benign", but more specific information is scarce. We aimed to elucidate (1) vascular risk factors, (2) local and ischemic symptoms, and (3) long-term prognosis compared to non-aneurysmal dissections. This case–control study included consecutive patients with spontaneous cervical artery dissection from three university hospitals in Switzerland and France, evaluated at baseline and at 3 months. In addition, further follow-ups were performed at the discretion of the treating physician. Dissecting aneurysms were diagnosed with duplex sonography, magnetic resonance angiography, and/or digital subtraction angiography. Of 1012 patients, 151 (14.9%) presented with 167 dissecting aneurysms at baseline (n = 103) or follow-up (n = 64). The median follow-up was 24.9 months (IQR: 6.8–60.8). Compared to patients without a dissecting aneurysm there were no significant differences in the vascular risk factors or local symptoms (91.4 vs. 89.8%). Ischemic strokes at baseline were less common (29.1% vs. 54.4%; OR: 0.41; 95% CI: 0.28–0.60) in patients with a dissecting aneurysm, even after correction for the degree of stenosis of the dissected arteries (OR: 0.53; 95% CI: 0.34–0.81). Patients with a dissecting aneurysm more often had a favorable clinical outcome (modified Rankin Scale Score of 0–1) at 3 months (80.6% vs. 54.5%). There was no significant difference in recurrent cerebrovascular events at 3 months or overall. The lower rate of ischemic strokes at baseline may reflect a different pathogenic mechanism, such as a smaller initial tear in the vessel wall or an increased vessel caliber from an early or primary intramural hematoma with a different shape. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis.

Author

Kaufmann, Josefin E., Harshfield, Eric L., Gensicke, Henrik, Wegener, Susanne, Michel, Patrik, Kägi, Georg, Nedeltchev, Krassen, Kellert, Lars, Rosenbaum, Sverre, Nolte, Christian H., Christensen, Hanne, Arnold, Marcel, Lyrer, Philippe, Levi, Christopher, Bath, Philip M., Engelter, Stefan T., Traenka, Christopher, and Markus, Hugh S.

Published
2024
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