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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. To improve accuracy and availability of the mismatch concept, deep learning might be able to augment human rating and support decision-making in these cases., Methods: We used unprocessed DWI and coregistered FLAIR imaging data to train a deep learning model to predict dichotomized time since ischemic stroke onset. We analyzed the performance of Group Convolutional Neural Networks compared to other deep learning methods. Unlabeled imaging data was used for pre-training. Prediction performance of the best deep learning model was compared to the performance of four independent junior and senior raters. Additionally, in cases deemed indeterminable by human raters, model ratings were used to augment human performance. Post-hoc gradient-based explanations were analyzed to gain insights into model predictions., Results: Our best predictive model performed comparably to human raters. Using model ratings in cases deemed indeterminable by human raters improved rating accuracy and interrater agreement for junior and senior ratings. Post-hoc explainability analyses showed that the model localized stroke lesions to derive predictions., Discussion: Our analysis shows that deep learning based clinical decision support has the potential to improve the accessibility of the DWI-FLAIR mismatch concept by supporting patient stratification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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, they cannot capture the volumetric information of 3D medical imaging. 3D GANs are more suitable for this and have been used to generate 3D volumes but not their corresponding labels. One reason might be that synthesizing 3D volumes is challenging owing to computational limitations. In this work, we present 3D GANs for the generation of 3D medical image volumes with corresponding labels applying mixed precision to alleviate computational constraints. We generated 3D Time-of-Flight Magnetic Resonance Angiography (TOF-MRA) patches with their corresponding brain blood vessel segmentation labels. We used four variants of 3D Wasserstein GAN (WGAN) with: 1) gradient penalty (GP), 2) GP with spectral normalization (SN), 3) SN with mixed precision (SN-MP), and 4) SN-MP with double filters per layer (c-SN-MP). The generated patches were quantitatively evaluated using the Fréchet Inception Distance (FID) and Precision and Recall of Distributions (PRD). Further, 3D U-Nets were trained with patch-label pairs from different WGAN models and their performance was compared to the performance of a benchmark U-Net trained on real data. The segmentation performance of all U-Net models was assessed using Dice Similarity Coefficient (DSC) and balanced Average Hausdorff Distance (bAVD) for a) all vessels, and b) intracranial vessels only. Our results show that patches generated with WGAN models using mixed precision (SN-MP and c-SN-MP) yielded the lowest FID scores and the best PRD curves. Among the 3D U-Nets trained with synthetic patch-label pairs, c-SN-MP pairs achieved the highest DSC (0.841) and lowest bAVD (0.508) compared to the benchmark U-Net trained on real data (DSC 0.901; bAVD 0.294) for intracranial vessels. In conclusion, our solution generates realistic 3D TOF-MRA patches and labels for brain vessel segmentation. We demonstrate the benefit of using mixed precision for computational efficiency resulting in the best-performing GAN-architecture. Our work paves the way towards sharing of labeled 3D medical data which would increase generalizability of deep learning models for clinical use., Competing Interests: Declaration of Competing Interest All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript The following authors have affiliations with organizations with direct or indirect financial interest in the subject matter discussed in the manuscript: None of the authors have direct or indirect financial interest in the subject matter discussed in the manuscript. However, the following disclosures unrelated to the current work is as follows: Pooja Subramaniam reported receiving personal fees from ai4medicine outside the submitted work. Tabea Kossen reported receiving personal fees from ai4medicine outside the submitted work. Dr Madai reported receiving personal fees from ai4medicine outside the submitted work. Adam Hilbert reported receiving personal fees from ai4medicine outside the submitted work. Dr Frey reported receiving grants from the European Commission, reported receiving personal fees from and holding an equity interest in ai4medicine outside the submitted work. There is no connection, commercial exploitation, transfer or association between the projects of ai4medicine and the results presented in this work. While not related to this work, Dr Sobesky reports receipt of speakers honoraria from Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. Furthermore, Dr Fiebach has received consulting and advisory board fees from BioClinica, Cerevast, Artemida, Brainomix, Biogen, BMS, EISAI, and Guerbet., (Copyright © 2022. Published by Elsevier B.V.)

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 potential to provide anonymous images while preserving predictive properties. Analyzing brain vessel segmentation, we trained 3 GANs on time-of-flight (TOF) magnetic resonance angiography (MRA) patches for image-label generation: 1) Deep convolutional GAN, 2) Wasserstein-GAN with gradient penalty (WGAN-GP) and 3) WGAN-GP with spectral normalization (WGAN-GP-SN). The generated image-labels from each GAN were used to train a U-net for segmentation and tested on real data. Moreover, we applied our synthetic patches using transfer learning on a second dataset. For an increasing number of up to 15 patients we evaluated the model performance on real data with and without pre-training. The performance for all models was assessed by the Dice Similarity Coefficient (DSC) and the 95th percentile of the Hausdorff Distance (95HD). Comparing the 3 GANs, the U-net trained on synthetic data generated by the WGAN-GP-SN showed the highest performance to predict vessels (DSC/95HD 0.85/30.00) benchmarked by the U-net trained on real data (0.89/26.57). The transfer learning approach showed superior performance for the same GAN compared to no pre-training, especially for one patient only (0.91/24.66 vs. 0.84/27.36). In this work, synthetic image-label pairs retained generalizable information and showed good performance for vessel segmentation. Besides, we showed that synthetic patches can be used in a transfer learning approach with independent data. This paves the way to overcome the challenges of scarce data and anonymization in medical imaging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)