This paper presents a comprehensive systematic review of generative models (GANs, VAEs, DMs, and LLMs) used to synthesize various medical data types, including imaging (dermoscopic, mammographic, ultrasound, CT, MRI, and X-ray), text, time-series, and tabular data (EHR). Unlike previous narrowly focused reviews, our study encompasses a broad array of medical data modalities and explores various generative models. Our aim is to offer insights into their current and future applications in medical research, particularly in the context of synthesis applications, generation techniques, and evaluation methods, as well as providing a GitHub repository as a dynamic resource for ongoing collaboration and innovation. Our search strategy queries databases such as Scopus, PubMed, and ArXiv, focusing on recent works from January 2021 to November 2023, excluding reviews and perspectives. This period emphasizes recent advancements beyond GANs, which have been extensively covered in previous reviews. The survey also emphasizes the aspect of conditional generation, which is not focused on in similar work. Key contributions include a broad, multi-modality scope that identifies cross-modality insights and opportunities unavailable in single-modality surveys. While core generative techniques are transferable, we find that synthesis methods often lack sufficient integration of patient-specific context, clinical knowledge, and modality-specific requirements tailored to the unique characteristics of medical data. Conditional models leveraging textual conditioning and multimodal synthesis remain underexplored but offer promising directions for innovation. Our findings are structured around three themes: (1) Synthesis applications, highlighting clinically valid synthesis applications and significant gaps in using synthetic data beyond augmentation, such as for validation and evaluation; (2) Generation techniques, identifying gaps in personalization and cross-modality innovation; and (3) Evaluation methods, revealing the absence of standardized benchmarks, the need for large-scale validation, and the importance of privacy-aware, clinically relevant evaluation frameworks. These findings emphasize the need for benchmarking and comparative studies to promote openness and collaboration.

• It is feasible to perform tracer-kinetic modelling and parameter inference with physics-informed neural networks. • This framework gives a high degree of flexibility for improving the parameter estimation performance. • The models learn purely from the observed data and are constrained by the physics of the problem, avoiding the need for a large training set.

Objective diagnosis and prognosis in major depressive disorder (MDD) remains a challenge due to the absence of biomarkers based on physiological parameters or medical tests. Numerous studies have been conducted to identify functional magnetic resonance imaging‐based biomarkers of depression that either objectively differentiate patients with depression from healthy subjects, predict personalized treatment outcome, or characterize biological subtypes of depression. While there are some findings of consistent functional biomarkers, there is still lack of robust data acquisition and analysis methodology. According to current findings, primarily, the anterior cingulate cortex, prefrontal cortex, and default mode network play a crucial role in MDD. Yet, there are also less consistent results and the involvement of other regions or networks remains ambiguous. We further discuss image acquisition, processing, and analysis limitations that might underlie these inconsistencies. Finally, the current review aims to address and discuss possible remedies and future opportunities that could improve the search for consistent functional imaging biomarkers of depression. Novel acquisition techniques, such as multiband and multiecho imaging, and neural network‐based cleaning approaches can enhance the signal quality in limbic and frontal regions. More comprehensive analyses, such as directed or dynamic functional features or the identification of biological depression subtypes, can improve objective diagnosis or treatment outcome prediction and mitigate the heterogeneity of MDD. Overall, these improvements in functional MRI imaging techniques, processing, and analysis could advance the search for biomarkers and ultimately aid patients with MDD and their treatment course.

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.

Kinetic parameter values, such as myocardial perfusion, can be quantified from dynamic contrast-enhanced magnetic resonance imaging data using tracer-kinetic modeling. However, respiratory motion affects the accuracy of this process. Motion compensation of the image series is difficult due to the rapid local signal enhancement caused by the passing of the gadolinium-based contrast agent. This contrast enhancement invalidates the assumptions of the (global) cost functions traditionally used in intensity-based registrations. The algorithms are unable to distinguish whether the differences in signal intensity between frames are caused by the spatial motion artifacts or the local contrast enhancement. In order to address this problem, a fully automated motion compensation scheme is proposed, which consists of two stages. The first of which uses robust principal component analysis (PCA) to separate the local signal enhancement from the baseline signal, before a refinement stage which uses the traditional PCA to construct a synthetic reference series that is free from motion but preserves the signal enhancement. Validation is performed on 18 subjects acquired in free-breathing and 5 clinical subjects acquired with a breath-hold. The validation assesses the visual quality, the temporal smoothness of tissue curves, and the clinically relevant quantitative perfusion values. The expert observers score the visual quality increased by a mean of 1.58/5 after motion compensation and improvement over the previously published methods. The proposed motion compensation scheme also leads to the improved quantitative performance of motion compensated free-breathing image series [30% reduction in the coefficient of variation across quantitative perfusion maps and 53% reduction in temporal variations (p <; 0.001)].

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.