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Background: In the field of medical imaging, high-resolution (HR) magnetic resonance imaging (MRI) is essential for accurate disease diagnosis and analysis. However, HR imaging is prone to artifacts and is not universally available. Consequently, low-resolution (LR) MRI images are typically acquired. Deep learning (DL)-based super-resolution (SR) techniques can transform LR images into HR quality. However, these techniques require paired HR-LR data for training the SR networks., Objective: This research aims to investigate the potential of simulated brain MRI data to train DL-based SR networks., Methods: We simulated a large set of anatomically diverse, voxel-aligned, and artifact-free brain MRI data at different resolutions. We utilized this simulated data to train four distinct DL-based SR networks and augment their training. The trained networks were then evaluated using real data from various sources., Results: With our trained networks, we produced 0.7mm SR images from standard 1mm resolution multi-source T1w brain MRI. Our experimental results demonstrate that the trained networks significantly enhance the sharpness of LR input MR images. For single-source images, the performance of networks trained solely on simulated data is slightly inferior to those trained solely on real data, with an average structural similarity index (SSIM) difference of 0.025. However, networks augmented with simulated data outperform those trained on single-source real data when evaluated across datasets from multiple sources., Conclusion: Paired HR-LR simulated brain MRI data is suitable for training and augmenting diverse brain MRI SR networks. Augmenting the training data with simulated data can enhance the generalizability of the SR networks across real datasets from multiple sources., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcel Breeuwer is an employee of Philips Medical Systems B.V. Cristian Lorenz and Jürgen Weese are employees of Philips GmbH Innovative Technologies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: As large sets of annotated MRI data are needed for training and validating deep learning based medical image analysis algorithms, the lack of sufficient annotated data is a critical problem. A possible solution is the generation of artificial data by means of physics-based simulations. Existing brain simulation data is limited in terms of anatomical models, tissue classes, fixed tissue characteristics, MR sequences and overall realism., Methods: We propose a realistic simulation framework by incorporating patient-specific phantoms and Bloch equations-based analytical solutions for fast and accurate MRI simulations. A large number of labels are derived from open-source high-resolution T1w MRI data using a fully automated brain classification tool. The brain labels are taken as ground truth (GT) on which MR images are simulated using our framework. Moreover, we demonstrate that the T1w MR images generated from our framework along with GT annotations can be utilized directly to train a 3D brain segmentation network. To evaluate our model further on larger set of real multi-source MRI data without GT, we compared our model to existing brain segmentation tools, FSL-FAST and SynthSeg., Results: Our framework generates 3D brain MRI for variable anatomy, sequence, contrast, SNR and resolution. The brain segmentation network for WM/GM/CSF trained only on T1w simulated data shows promising results on real MRI data from MRBrainS18 challenge dataset with a Dice scores of 0.818/0.832/0.828. On OASIS data, our model exhibits a close performance to FSL, both qualitatively and quantitatively with a Dice scores of 0.901/0.939/0.937., Conclusions: Our proposed simulation framework is the initial step towards achieving truly physics-based MRI image generation, providing flexibility to generate large sets of variable MRI data for desired anatomy, sequence, contrast, SNR, and resolution. Furthermore, the generated images can effectively train 3D brain segmentation networks, mitigating the reliance on real 3D annotated data., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcel Breeuwer is an employee of Philips Medical Systems B.V. Cristian Lorenz and Jürgen Weese are employees of Philips GmbH Innovative Technologies., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Accurate brain tumor segmentation is critical for diagnosis and treatment planning, whereby multi-modal magnetic resonance imaging (MRI) is typically used for analysis. However, obtaining all required sequences and expertly labeled data for training is challenging and can result in decreased quality of segmentation models developed through automated algorithms. In this work, we examine the possibility of employing a conditional generative adversarial network (GAN) approach for synthesizing multi-modal images to train deep learning-based neural networks aimed at high-grade glioma (HGG) segmentation. The proposed GAN is conditioned on auxiliary brain tissue and tumor segmentation masks, allowing us to attain better accuracy and control of tissue appearance during synthesis. To reduce the domain shift between synthetic and real MR images, we additionally adapt the low-frequency Fourier space components of synthetic data, reflecting the style of the image, to those of real data. We demonstrate the impact of Fourier domain adaptation (FDA) on the training of 3D segmentation networks and attain significant improvements in both the segmentation performance and prediction confidence. Similar outcomes are seen when such data is used as a training augmentation alongside the available real images. In fact, experiments on the BraTS2020 dataset reveal that models trained solely with synthetic data exhibit an improvement of up to 4% in Dice score when using FDA, while training with both real and FDA-processed synthetic data through augmentation results in an improvement of up to 5% in Dice compared to using real data alone. This study highlights the importance of considering image frequency in generative approaches for medical image synthesis and offers a promising approach to address data scarcity in medical imaging segmentation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasmina Al Khalil and Aymen Ayaz report financial support was provided by Marie Curie Innovative Training Networks (ITN) fellowship program under project No. 764465. Marcel Breeuwer reports a relationship with Philips Healthcare that includes: employment. Cristian Lorenz and Jürgen Weese report a relationship with Philips GmbH Innovative Technologies that includes: employment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spectral photoacoustic imaging (sPAI) is an emerging modality that allows real-time, non-invasive, and radiation-free assessment of tissue, benefiting from their optical contrast. sPAI is ideal for morphology assessment in arterial plaques, where plaque composition provides relevant information on plaque progression and its vulnerability. However, since sPAI is affected by spectral coloring, general spectroscopy unmixing techniques cannot provide reliable identification of such complicated sample composition. In this study, we employ a convolutional neural network (CNN) for the classification of plaque composition using sPAI. For this study, nine carotid endarterectomy plaques were imaged and were then annotated and validated using multiple histological staining. Our results show that a CNN can effectively differentiate constituent regions within plaques without requiring fluence or spectra correction, with the potential to eventually support vulnerability assessment in plaques., Competing Interests: 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., (© 2023 The Author(s).)

Cardiac magnetic resonance (CMR) image segmentation is an integral step in the analysis of cardiac function and diagnosis of heart related diseases. While recent deep learning-based approaches in automatic segmentation have shown great promise to alleviate the need for manual segmentation, most of these are not applicable to realistic clinical scenarios. This is largely due to training on mainly homogeneous datasets, without variation in acquisition, which typically occurs in multi-vendor and multi-site settings, as well as pathological data. Such approaches frequently exhibit a degradation in prediction performance, particularly on outlier cases commonly associated with difficult pathologies, artifacts and extensive changes in tissue shape and appearance. In this work, we present a model aimed at segmenting all three cardiac structures in a multi-center, multi-disease and multi-view scenario. We propose a pipeline, addressing different challenges with segmentation of such heterogeneous data, consisting of heart region detection, augmentation through image synthesis and a late-fusion segmentation approach. Extensive experiments and analysis demonstrate the ability of the proposed approach to tackle the presence of outlier cases during both training and testing, allowing for better adaptation to unseen and difficult examples. Overall, we show that the effective reduction of segmentation failures on outlier cases has a positive impact on not only the average segmentation performance, but also on the estimation of clinical parameters, leading to a better consistency in derived metrics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcel Breeuwer is an employee of Philips Medical Systems B.V. Cristian Lorenz and Jürgen Weese are employees of Philips GmbH Innovative Technologies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms., Materials and Methods: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE = 5000/78 ms, voxel size = 2 × 2 × 2 mm 3 , 1 volume at b = 0 s/mm 2 , 32 volumes at b = 1000 s/mm 2 ). DTI, constrained spherical deconvolution, and multilevel fiber tractography-based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested., Results: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 26,485 mm 3 , 6308 mm 3 , and 4270 mm 3 )., Conclusions: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy., (© 2023 by American Journal of Neuroradiology.)

One of the limiting factors for the development and adoption of novel deep-learning (DL) based medical image analysis methods is the scarcity of labeled medical images. Medical image simulation and synthesis can provide solutions by generating ample training data with corresponding ground truth labels. Despite recent advances, generated images demonstrate limited realism and diversity. In this work, we develop a flexible framework for simulating cardiac magnetic resonance (MR) images with variable anatomical and imaging characteristics for the purpose of creating a diversified virtual population. We advance previous works on both cardiac MR image simulation and anatomical modeling to increase the realism in terms of both image appearance and underlying anatomy. To diversify the generated images, we define parameters: 1)to alter the anatomy, 2) to assign MR tissue properties to various tissue types, and 3) to manipulate the image contrast via acquisition parameters. The proposed framework is optimized to generate a substantial number of cardiac MR images with ground truth labels suitable for downstream supervised tasks. A database of virtual subjects is simulated and its usefulness for aiding a DL segmentation method is evaluated. Our experiments show that training completely with simulated images can perform comparable with a model trained with real images for heart cavity segmentation in mid-ventricular slices. Moreover, such data can be used in addition to classical augmentation for boosting the performance when training data is limited, particularly by increasing the contrast and anatomical variation, leading to better regularization and generalization. The database is publicly available at https://osf.io/bkzhm/ and the simulation code will be available at https://github.com/sinaamirrajab/CMRI.

Deep learning-based segmentation methods provide an effective and automated way for assessing the structure and function of the heart in cardiac magnetic resonance (CMR) images. However, despite their state-of-the-art performance on images acquired from the same source (same scanner or scanner vendor) as images used during training, their performance degrades significantly on images coming from different domains. A straightforward approach to tackle this issue consists of acquiring large quantities of multi-site and multi-vendor data, which is practically infeasible. Generative adversarial networks (GANs) for image synthesis present a promising solution for tackling data limitations in medical imaging and addressing the generalization capability of segmentation models. In this work, we explore the usability of synthesized short-axis CMR images generated using a segmentation-informed conditional GAN, to improve the robustness of heart cavity segmentation models in a variety of different settings. The GAN is trained on paired real images and corresponding segmentation maps belonging to both the heart and the surrounding tissue, reinforcing the synthesis of semantically-consistent and realistic images. First, we evaluate the segmentation performance of a model trained solely with synthetic data and show that it only slightly underperforms compared to the baseline trained with real data. By further combining real with synthetic data during training, we observe a substantial improvement in segmentation performance (up to 4% and 40% in terms of Dice score and Hausdorff distance) across multiple data-sets collected from various sites and scanner. This is additionally demonstrated across state-of-the-art 2D and 3D segmentation networks, whereby the obtained results demonstrate the potential of the proposed method in tackling the presence of the domain shift in medical data. Finally, we thoroughly analyze the quality of synthetic data and its ability to replace real MR images during training, as well as provide an insight into important aspects of utilizing synthetic images for segmentation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcel Breeuwer is an employee of Philips Medical Systems B.V. Cristan LorenZ and Jürgen Weese are employees of Philips GmbH Innovative Technologies., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Synthesis of a large set of high-quality medical images with variability in anatomical representation and image appearance has the potential to provide solutions for tackling the scarcity of properly annotated data in medical image analysis research. In this paper, we propose a novel framework consisting of image segmentation and synthesis based on mask-conditional GANs for generating high-fidelity and diverse Cardiac Magnetic Resonance (CMR) images. The framework consists of two modules: i) a segmentation module trained using a physics-based simulated database of CMR images to provide multi-tissue labels on real CMR images, and ii) a synthesis module trained using pairs of real CMR images and corresponding multi-tissue labels, to translate input segmentation masks to realistic-looking cardiac images. The anatomy of synthesized images is based on labels, whereas the appearance is learned from the training images. We investigate the effects of the number of tissue labels, quantity of training data, and multi-vendor data on the quality of the synthesized images. Furthermore, we evaluate the effectiveness and usability of the synthetic data for a downstream task of training a deep-learning model for cardiac cavity segmentation in the scenarios of data replacement and augmentation. The results of the replacement study indicate that segmentation models trained with only synthetic data can achieve comparable performance to the baseline model trained with real data, indicating that the synthetic data captures the essential characteristics of its real counterpart. Furthermore, we demonstrate that augmenting real with synthetic data during training can significantly improve both the Dice score (maximum increase of 4%) and Hausdorff Distance (maximum reduction of 40%) for cavity segmentation, suggesting a good potential to aid in tackling medical data scarcity., Competing Interests: Declaration of Competing Interest One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.compmedimag.2022.102123. Marcel Breeuwer is an employee of Philips Medical Systems B.V. Cristian Lorenz and Jürgen Weese are employees of Philips GmbH Innovative Technologies., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods., 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 © 2022. Published by Elsevier Inc.)

One of the most common types of cancer in men is prostate cancer (PCa). Biopsies guided by bi-parametric magnetic resonance imaging (MRI) can aid PCa diagnosis. Previous works have mostly focused on either detection or classification of PCa from MRI. In this work, however, we present a neural network that simultaneously detects and grades cancer tissue in an end-to-end fashion. This is more clinically relevant than the classification goal of the ProstateX-2 challenge. We used the dataset of this challenge for training and testing. We use a 2D U-Net with MRI slices as input and lesion segmentation maps that encode the Gleason Grade Group (GGG), a measure for cancer aggressiveness, as output. We propose a method for encoding the GGG in the model target that takes advantage of the fact that the classes are ordinal. Furthermore, we evaluate methods for incorporating prostate zone segmentations as prior information, and ensembling techniques. The model scored a voxel-wise weighted kappa of 0.446 ±0.082 and a Dice similarity coefficient for segmenting clinically significant cancer of 0.370 ±0.046, obtained using 5-fold cross-validation. The lesion-wise weighted kappa on the ProstateX-2 challenge test set was 0.13 ±0.27. We show that our proposed model target outperforms standard multiclass classification and multi-label ordinal regression. Additionally, we present a comparison of methods for further improvement of the model performance.

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research., (© 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.)