Evaluating generative models for synthetic medical imaging is crucial yet challenging, especially given the high standards of fidelity, anatomical accuracy, and safety required for clinical applications. Standard evaluation of generated images often relies on no-reference image quality metrics when ground truth images are unavailable, but their reliability in this complex domain is not well established. This study comprehensively assesses commonly used no-reference image quality metrics using brain MRI data, including tumour and vascular images, providing a representative exemplar for the field. We systematically evaluate metric sensitivity to a range of challenges, including noise, distribution shifts, and, critically, localised morphological alterations designed to mimic clinically relevant inaccuracies. We then compare these metric scores against model performance on a relevant downstream segmentation task, analysing results across both controlled image perturbations and outputs from different generative model architectures. Our findings reveal significant limitations: many widely-used no-reference image quality metrics correlate poorly with downstream task suitability and exhibit a profound insensitivity to localised anatomical details crucial for clinical validity. Furthermore, these metrics can yield misleading scores regarding distribution shifts, e.g. data memorisation. This reveals the risk of misjudging model readiness, potentially leading to the deployment of flawed tools that could compromise patient safety. We conclude that ensuring generative models are truly fit for clinical purpose requires a multifaceted validation framework, integrating performance on relevant downstream tasks with the cautious interpretation of carefully selected no-reference image quality metrics.
This study presents Latent Diffusion Autoencoder (LDAE), a novel encoder-decoder diffusion-based framework for efficient and meaningful unsupervised learning in medical imaging, focusing on Alzheimer disease (AD) using brain MR from the ADNI database as a case study. Unlike conventional diffusion autoencoders operating in image space, LDAE applies the diffusion process in a compressed latent representation, improving computational efficiency and making 3D medical imaging representation learning tractable. To validate the proposed approach, we explore two key hypotheses: (i) LDAE effectively captures meaningful semantic representations on 3D brain MR associated with AD and ageing, and (ii) LDAE achieves high-quality image generation and reconstruction while being computationally efficient. Experimental results support both hypotheses: (i) linear-probe evaluations demonstrate promising diagnostic performance for AD (ROC-AUC: 90%, ACC: 84%) and age prediction (MAE: 4.1 years, RMSE: 5.2 years); (ii) the learned semantic representations enable attribute manipulation, yielding anatomically plausible modifications; (iii) semantic interpolation experiments show strong reconstruction of missing scans, with SSIM of 0.969 (MSE: 0.0019) for a 6-month gap. Even for longer gaps (24 months), the model maintains robust performance (SSIM > 0.93, MSE < 0.004), indicating an ability to capture temporal progression trends; (iv) compared to conventional diffusion autoencoders, LDAE significantly increases inference throughput (20x faster) while also enhancing reconstruction quality. These findings position LDAE as a promising framework for scalable medical imaging applications, with the potential to serve as a foundation model for medical image analysis. Code available at https://github.com/GabrieleLozupone/LDAE
Despite the potential of synthetic medical data for augmenting and improving the generalizability of deep learning models, memorization in generative models can lead to unintended leakage of sensitive patient information and limit model utility. Thus, the use of memorizing generative models in the medical domain can jeopardize patient privacy. We propose a framework for identifying replicas, i.e. nearly identical copies of the training data, in synthetic medical image datasets. Our REpLIca deteCTion (RELICT) framework for medical image generative models evaluates image similarity using three complementary approaches: (1) voxel-level analysis, (2) feature-level analysis by a pretrained medical foundation model, and (3) segmentation-level analysis. Two clinically relevant 3D generative modelling use cases were investigated: non-contrast head CT with intracerebral hemorrhage (N=774) and time-of-flight MR angiography of the Circle of Willis (N=1,782). Expert visual scoring was used as the reference standard to assess the presence of replicas. We report the balanced accuracy at the optimal threshold to assess replica classification performance. The reference visual rating identified 45 of 50 and 5 of 50 generated images as replicas for the NCCT and TOF-MRA use cases, respectively. Image-level and feature-level measures perfectly classified replicas with a balanced accuracy of 1 when an optimal threshold was selected for the NCCT use case. A perfect classification of replicas for the TOF-MRA case was not possible at any threshold, with the segmentation-level analysis achieving a balanced accuracy of 0.79. Replica detection is a crucial but neglected validation step for the development of generative models in medical imaging. The proposed RELICT framework provides a standardized, easy-to-use tool for replica detection and aims to facilitate responsible and ethical medical image synthesis.
Generative models trained on multi-institutional datasets can provide an enriched understanding through diverse data distributions. However, training the models on medical images is often challenging due to hospitals' reluctance to share data for privacy reasons. Federated learning(FL) has emerged as a privacy-preserving solution for training distributed datasets across data centers by aggregating model weights from multiple clients instead of sharing raw data. Previous research has explored the adaptation of FL to generative models, yet effective aggregation algorithms specifically tailored for generative models remain unexplored. We hereby propose a novel algorithm aimed at improving the performance of generative models within FL. Our approach adaptively re-weights the contribution of each client, resulting in well-trained shared parameters. In each round, the server side measures the distribution distance between fake images generated by clients instead of directly comparing the Fr\'echet Inception Distance per client, thereby enhancing efficiency of the learning. Experimental results on three public chest X-ray datasets show superior performance in medical image generation, outperforming both centralized learning and conventional FL algorithms. Our code is available at https://github.com/danny0628/FedCAR.
Medical image segmentation has recently demonstrated impressive progress with deep neural networks, yet the heterogeneous modalities and scarcity of mask annotations limit the development of segmentation models on unannotated modalities. This paper investigates a new paradigm for leveraging generative models in medical applications: controllably synthesizing data for unannotated modalities, without requiring registered data pairs. Specifically, we make the following contributions in this paper: (i) we collect and curate a large-scale radiology image-text dataset, MedGen-1M, comprising modality labels, attributes, region, and organ information, along with a subset of organ mask annotations, to support research in controllable medical image generation; (ii) we propose a diffusion-based data engine, termed MRGen, which enables generation conditioned on text prompts and masks, synthesizing MR images for diverse modalities lacking mask annotations, to train segmentation models on unannotated modalities; (iii) we conduct extensive experiments across various modalities, illustrating that our data engine can effectively synthesize training samples and extend MRI segmentation towards unannotated modalities.
In the realm of medical image analysis, self-supervised learning (SSL) techniques have emerged to alleviate labeling demands, while still facing the challenge of training data scarcity owing to escalating resource requirements and privacy constraints. Numerous efforts employ generative models to generate high-fidelity, unlabeled 3D volumes across diverse modalities and anatomical regions. However, the intricate and indistinguishable anatomical structures within the abdomen pose a unique challenge to abdominal CT volume generation compared to other anatomical regions. To address the overlooked challenge, we introduce the Locality-Aware Diffusion (Lad), a novel method tailored for exquisite 3D abdominal CT volume generation. We design a locality loss to refine crucial anatomical regions and devise a condition extractor to integrate abdominal priori into generation, thereby enabling the generation of large quantities of high-quality abdominal CT volumes essential for SSL tasks without the need for additional data such as labels or radiology reports. Volumes generated through our method demonstrate remarkable fidelity in reproducing abdominal structures, achieving a decrease in FID score from 0.0034 to 0.0002 on AbdomenCT-1K dataset, closely mirroring authentic data and surpassing current methods. Extensive experiments demonstrate the effectiveness of our method in self-supervised organ segmentation tasks, resulting in an improvement in mean Dice scores on two abdominal datasets effectively. These results underscore the potential of synthetic data to advance self-supervised learning in medical image analysis.
We introduce Kvasir-VQA, an extended dataset derived from the HyperKvasir and Kvasir-Instrument datasets, augmented with question-and-answer annotations to facilitate advanced machine learning tasks in Gastrointestinal (GI) diagnostics. This dataset comprises 6,500 annotated images spanning various GI tract conditions and surgical instruments, and it supports multiple question types including yes/no, choice, location, and numerical count. The dataset is intended for applications such as image captioning, Visual Question Answering (VQA), text-based generation of synthetic medical images, object detection, and classification. Our experiments demonstrate the dataset's effectiveness in training models for three selected tasks, showcasing significant applications in medical image analysis and diagnostics. We also present evaluation metrics for each task, highlighting the usability and versatility of our dataset. The dataset and supporting artifacts are available at https://datasets.simula.no/kvasir-vqa.
Generally, the small size of public medical imaging datasets coupled with stringent privacy concerns, hampers the advancement of data-hungry deep learning models in medical imaging. This study addresses these challenges for 3D cardiac MRI images in the short-axis view. We propose Latent Diffusion Models that generate synthetic images conditioned on medical attributes, while ensuring patient privacy through differentially private model training. To our knowledge, this is the first work to apply and quantify differential privacy in 3D medical image generation. We pre-train our models on public data and finetune them with differential privacy on the UK Biobank dataset. Our experiments reveal that pre-training significantly improves model performance, achieving a Fr\'echet Inception Distance (FID) of 26.77 at $\epsilon=10$, compared to 92.52 for models without pre-training. Additionally, we explore the trade-off between privacy constraints and image quality, investigating how tighter privacy budgets affect output controllability and may lead to degraded performance. Our results demonstrate that proper consideration during training with differential privacy can substantially improve the quality of synthetic cardiac MRI images, but there are still notable challenges in achieving consistent medical realism.
Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are the predominant modalities utilized in the field of medical imaging. Although MRI capture the complexity of anatomical structures with greater detail than CT, it entails a higher financial costs and requires longer image acquisition times. In this study, we aim to train latent diffusion model for CT to MRI conversion, replacing the commonly-used U-Net or Transformer backbone with a State-Space Model (SSM) called Mamba that operates on latent patches. First, we noted critical oversights in the scan scheme of most Mamba-based vision methods, including inadequate attention to the spatial continuity of patch tokens and the lack of consideration for their varying importance to the target task. Secondly, extending from this insight, we introduce Diffusion Mamba (DiffMa), employing soft masked to integrate Cross-Sequence Attention into Mamba and conducting selective scan in a spiral manner. Lastly, extensive experiments demonstrate impressive performance by DiffMa in medical image generation tasks, with notable advantages in input scaling efficiency over existing benchmark models. The code and models are available at https://github.com/wongzbb/DiffMa-Diffusion-Mamba
Generative adversarial networks (GANs) are machine learning models that are used to estimate the underlying statistical structure of a given dataset and as a result can be used for a variety of tasks such as image generation or anomaly detection. Despite their initial simplicity, designing an effective loss function for training GANs remains challenging, and various loss functions have been proposed aiming to improve the performance and stability of the generative models. In this study, loss function design for GANs is presented as an optimization problem solved using the genetic programming (GP) approach. Initial experiments were carried out using small Deep Convolutional GAN (DCGAN) model and the MNIST dataset, in order to search experimentally for an improved loss function. The functions found were evaluated on CIFAR10, with the best function, named GANetic loss, showing exceptionally better performance and stability compared to the losses commonly used for GAN training. To further evalute its general applicability on more challenging problems, GANetic loss was applied for two medical applications: image generation and anomaly detection. Experiments were performed with histopathological, gastrointestinal or glaucoma images to evaluate the GANetic loss in medical image generation, resulting in improved image quality compared to the baseline models. The GANetic Loss used for polyp and glaucoma images showed a strong improvement in the detection of anomalies. In summary, the GANetic loss function was evaluated on multiple datasets and applications where it consistently outperforms alternative loss functions. Moreover, GANetic loss leads to stable training and reproducible results, a known weak spot of GANs.
Diffusion models excel in generating images that closely resemble their training data but are also susceptible to data memorization, raising privacy, ethical, and legal concerns, particularly in sensitive domains such as medical imaging. We hypothesize that this memorization stems from the overparameterization of deep models and propose that regularizing model capacity during fine-tuning can mitigate this issue. Firstly, we empirically show that regulating the model capacity via Parameter-efficient fine-tuning (PEFT) mitigates memorization to some extent, however, it further requires the identification of the exact parameter subsets to be fine-tuned for high-quality generation. To identify these subsets, we introduce a bi-level optimization framework, MemControl, that automates parameter selection using memorization and generation quality metrics as rewards during fine-tuning. The parameter subsets discovered through MemControl achieve a superior tradeoff between generation quality and memorization. For the task of medical image generation, our approach outperforms existing state-of-the-art memorization mitigation strategies by fine-tuning as few as 0.019% of model parameters. Moreover, we demonstrate that the discovered parameter subsets are transferable to non-medical domains. Our framework is scalable to large datasets, agnostic to reward functions, and can be integrated with existing approaches for further memorization mitigation. To the best of our knowledge, this is the first study to empirically evaluate memorization in medical images and propose a targeted yet universal mitigation strategy. The code is available at https://github.com/Raman1121/Diffusion_Memorization_HPO
Fundus photography, in combination with the ultra-wide-angle fundus (UWF) techniques, becomes an indispensable diagnostic tool in clinical settings by offering a more comprehensive view of the retina. Nonetheless, UWF fluorescein angiography (UWF-FA) necessitates the administration of a fluorescent dye via injection into the patient's hand or elbow unlike UWF scanning laser ophthalmoscopy (UWF-SLO). To mitigate potential adverse effects associated with injections, researchers have proposed the development of cross-modality medical image generation algorithms capable of converting UWF-SLO images into their UWF-FA counterparts. Current image generation techniques applied to fundus photography encounter difficulties in producing high-resolution retinal images, particularly in capturing minute vascular lesions. To address these issues, we introduce a novel conditional generative adversarial network (UWAFA-GAN) to synthesize UWF-FA from UWF-SLO. This approach employs multi-scale generators and an attention transmit module to efficiently extract both global structures and local lesions. Additionally, to counteract the image blurriness issue that arises from training with misaligned data, a registration module is integrated within this framework. Our method performs non-trivially on inception scores and details generation. Clinical user studies further indicate that the UWF-FA images generated by UWAFA-GAN are clinically comparable to authentic images in terms of diagnostic reliability. Empirical evaluations on our proprietary UWF image datasets elucidate that UWAFA-GAN outperforms extant methodologies. The code is accessible at https://github.com/Tinysqua/UWAFA-GAN.
4D medical images, which represent 3D images with temporal information, are crucial in clinical practice for capturing dynamic changes and monitoring long-term disease progression. However, acquiring 4D medical images poses challenges due to factors such as radiation exposure and imaging duration, necessitating a balance between achieving high temporal resolution and minimizing adverse effects. Given these circumstances, not only is data acquisition challenging, but increasing the frame rate for each dataset also proves difficult. To address this challenge, this paper proposes a simple yet effective Unsupervised Volumetric Interpolation framework, UVI-Net. This framework facilitates temporal interpolation without the need for any intermediate frames, distinguishing it from the majority of other existing unsupervised methods. Experiments on benchmark datasets demonstrate significant improvements across diverse evaluation metrics compared to unsupervised and supervised baselines. Remarkably, our approach achieves this superior performance even when trained with a dataset as small as one, highlighting its exceptional robustness and efficiency in scenarios with sparse supervision. This positions UVI-Net as a compelling alternative for 4D medical imaging, particularly in settings where data availability is limited. The source code is available at https://github.com/jungeun122333/UVI-Net.
High-quality, large-scale data is essential for robust deep learning models in medical applications, particularly ultrasound image analysis. Diffusion models facilitate high-fidelity medical image generation, reducing the costs associated with acquiring and annotating new images. This paper utilizes recent vision-language models to produce diverse and realistic synthetic echocardiography image data, preserving key features of the original images guided by textual and semantic label maps. Specifically, we investigate three potential avenues: unconditional generation, generation guided by text, and a hybrid approach incorporating both textual and semantic supervision. We show that the rich contextual information present in the synthesized data potentially enhances the accuracy and interpretability of downstream tasks, such as echocardiography segmentation and classification with improved metrics and faster convergence. Our implementation with checkpoints, prompts, and the created synthetic dataset will be publicly available at \href{https://github.com/Pooria90/DiffEcho}{GitHub}.
Due to the three-dimensional nature of CT- or MR-scans, generative modeling of medical images is a particularly challenging task. Existing approaches mostly apply patch-wise, slice-wise, or cascaded generation techniques to fit the high-dimensional data into the limited GPU memory. However, these approaches may introduce artifacts and potentially restrict the model's applicability for certain downstream tasks. This work presents WDM, a wavelet-based medical image synthesis framework that applies a diffusion model on wavelet decomposed images. The presented approach is a simple yet effective way of scaling 3D diffusion models to high resolutions and can be trained on a single \SI{40}{\giga\byte} GPU. Experimental results on BraTS and LIDC-IDRI unconditional image generation at a resolution of $128 \times 128 \times 128$ demonstrate state-of-the-art image fidelity (FID) and sample diversity (MS-SSIM) scores compared to recent GANs, Diffusion Models, and Latent Diffusion Models. Our proposed method is the only one capable of generating high-quality images at a resolution of $256 \times 256 \times 256$, outperforming all comparing methods.
Diffusion models have enabled remarkably high-quality medical image generation, yet it is challenging to enforce anatomical constraints in generated images. To this end, we propose a diffusion model-based method that supports anatomically-controllable medical image generation, by following a multi-class anatomical segmentation mask at each sampling step. We additionally introduce a random mask ablation training algorithm to enable conditioning on a selected combination of anatomical constraints while allowing flexibility in other anatomical areas. We compare our method ("SegGuidedDiff") to existing methods on breast MRI and abdominal/neck-to-pelvis CT datasets with a wide range of anatomical objects. Results show that our method reaches a new state-of-the-art in the faithfulness of generated images to input anatomical masks on both datasets, and is on par for general anatomical realism. Finally, our model also enjoys the extra benefit of being able to adjust the anatomical similarity of generated images to real images of choice through interpolation in its latent space. SegGuidedDiff has many applications, including cross-modality translation, and the generation of paired or counterfactual data. Our code is available at https://github.com/mazurowski-lab/segmentation-guided-diffusion.
Fr\'echet Inception Distance (FID) is a widely used metric for assessing synthetic image quality. It relies on an ImageNet-based feature extractor, making its applicability to medical imaging unclear. A recent trend is to adapt FID to medical imaging through feature extractors trained on medical images. Our study challenges this practice by demonstrating that ImageNet-based extractors are more consistent and aligned with human judgment than their RadImageNet counterparts. We evaluated sixteen StyleGAN2 networks across four medical imaging modalities and four data augmentation techniques with Fr\'echet distances (FDs) computed using eleven ImageNet or RadImageNet-trained feature extractors. Comparison with human judgment via visual Turing tests revealed that ImageNet-based extractors produced rankings consistent with human judgment, with the FD derived from the ImageNet-trained SwAV extractor significantly correlating with expert evaluations. In contrast, RadImageNet-based rankings were volatile and inconsistent with human judgment. Our findings challenge prevailing assumptions, providing novel evidence that medical image-trained feature extractors do not inherently improve FDs and can even compromise their reliability. Our code is available at https://github.com/mckellwoodland/fid-med-eval.
Fundus photography is an essential examination for clinical and differential diagnosis of fundus diseases. Recently, Ultra-Wide-angle Fundus (UWF) techniques, UWF Fluorescein Angiography (UWF-FA) and UWF Scanning Laser Ophthalmoscopy (UWF-SLO) have been gradually put into use. However, Fluorescein Angiography (FA) and UWF-FA require injecting sodium fluorescein which may have detrimental influences. To avoid negative impacts, cross-modality medical image generation algorithms have been proposed. Nevertheless, current methods in fundus imaging could not produce high-resolution images and are unable to capture tiny vascular lesion areas. This paper proposes a novel conditional generative adversarial network (UWAT-GAN) to synthesize UWF-FA from UWF-SLO. Using multi-scale generators and a fusion module patch to better extract global and local information, our model can generate high-resolution images. Moreover, an attention transmit module is proposed to help the decoder learn effectively. Besides, a supervised approach is used to train the network using multiple new weighted losses on different scales of data. Experiments on an in-house UWF image dataset demonstrate the superiority of the UWAT-GAN over the state-of-the-art methods. The source code is available at: https://github.com/Tinysqua/UWAT-GAN.
GenerateCT, the first approach to generating 3D medical imaging conditioned on free-form medical text prompts, incorporates a text encoder and three key components: a novel causal vision transformer for encoding 3D CT volumes, a text-image transformer for aligning CT and text tokens, and a text-conditional super-resolution diffusion model. Without directly comparable methods in 3D medical imaging, we benchmarked GenerateCT against cutting-edge methods, demonstrating its superiority across all key metrics. Importantly, we evaluated GenerateCT's clinical applications in a multi-abnormality classification task. First, we established a baseline by training a multi-abnormality classifier on our real dataset. To further assess the model's generalization to external data and performance with unseen prompts in a zero-shot scenario, we employed an external set to train the classifier, setting an additional benchmark. We conducted two experiments in which we doubled the training datasets by synthesizing an equal number of volumes for each set using GenerateCT. The first experiment demonstrated an 11% improvement in the AP score when training the classifier jointly on real and generated volumes. The second experiment showed a 7% improvement when training on both real and generated volumes based on unseen prompts. Moreover, GenerateCT enables the scaling of synthetic training datasets to arbitrary sizes. As an example, we generated 100,000 3D CTs, fivefold the number in our real set, and trained the classifier exclusively on these synthetic CTs. Impressively, this classifier surpassed the performance of the one trained on all available real data by a margin of 8%. Last, domain experts evaluated the generated volumes, confirming a high degree of alignment with the text prompt. Access our code, model weights, training data, and generated data at https://github.com/ibrahimethemhamamci/GenerateCT
Diffusion models for text-to-image generation, known for their efficiency, accessibility, and quality, have gained popularity. While inference with these systems on consumer-grade GPUs is increasingly feasible, training from scratch requires large captioned datasets and significant computational resources. In medical image generation, the limited availability of large, publicly accessible datasets with text reports poses challenges due to legal and ethical concerns. This work shows that adapting pre-trained Stable Diffusion models to medical imaging modalities is achievable by training text embeddings using Textual Inversion. In this study, we experimented with small medical datasets (100 samples each from three modalities) and trained within hours to generate diagnostically accurate images, as judged by an expert radiologist. Experiments with Textual Inversion training and inference parameters reveal the necessity of larger embeddings and more examples in the medical domain. Classification experiments show an increase in diagnostic accuracy (AUC) for detecting prostate cancer on MRI, from 0.78 to 0.80. Further experiments demonstrate embedding flexibility through disease interpolation, combining pathologies, and inpainting for precise disease appearance control. The trained embeddings are compact (less than 1 MB), enabling easy data sharing with reduced privacy concerns.