Towards Learning Contrast Kinetics with Multi-Condition Latent Diffusion Models

Contrast agents in dynamic contrast enhanced magnetic resonance imaging allow to localize tumors and observe their contrast kinetics, which is essential for cancer characterization and respective treatment decision-making. However, contrast agent administration is not only associated with adverse health risks, but also restricted for patients during pregnancy, and for those with kidney malfunction, or other adverse reactions. With contrast uptake as key biomarker for lesion malignancy, cancer recurrence risk, and treatment response, it becomes pivotal to reduce the dependency on intravenous contrast agent administration. To this end, we propose a multi-conditional latent diffusion model capable of acquisition time-conditioned image synthesis of DCE-MRI temporal sequences. To evaluate medical image synthesis, we additionally propose and validate the Fr\'echet radiomics distance as an image quality measure based on biomarker variability between synthetic and real imaging data. Our results demonstrate our method's ability to generate realistic multi-sequence fat-saturated breast DCE-MRI and uncover the emerging potential of deep learning based contrast kinetics simulation. We publicly share our accessible codebase at https://github.com/RichardObi/ccnet.

Pre- to Post-Contrast Breast MRI Synthesis for Enhanced Tumour Segmentation

Despite its benefits for tumour detection and treatment, the administration of contrast agents in dynamic contrast-enhanced MRI (DCE-MRI) is associated with a range of issues, including their invasiveness, bioaccumulation, and a risk of nephrogenic systemic fibrosis. This study explores the feasibility of producing synthetic contrast enhancements by translating pre-contrast T1-weighted fat-saturated breast MRI to their corresponding first DCE-MRI sequence leveraging the capabilities of a generative adversarial network (GAN). Additionally, we introduce a Scaled Aggregate Measure (SAMe) designed for quantitatively evaluating the quality of synthetic data in a principled manner and serving as a basis for selecting the optimal generative model. We assess the generated DCE-MRI data using quantitative image quality metrics and apply them to the downstream task of 3D breast tumour segmentation. Our results highlight the potential of post-contrast DCE-MRI synthesis in enhancing the robustness of breast tumour segmentation models via data augmentation. Our code is available at https://github.com/RichardObi/pre_post_synthesis.

Revisiting Skin Tone Fairness in Dermatological Lesion Classification

Addressing fairness in lesion classification from dermatological images is crucial due to variations in how skin diseases manifest across skin tones. However, the absence of skin tone labels in public datasets hinders building a fair classifier. To date, such skin tone labels have been estimated prior to fairness analysis in independent studies using the Individual Typology Angle (ITA). Briefly, ITA calculates an angle based on pixels extracted from skin images taking into account the lightness and yellow-blue tints. These angles are then categorised into skin tones that are subsequently used to analyse fairness in skin cancer classification. In this work, we review and compare four ITA-based approaches of skin tone classification on the ISIC18 dataset, a common benchmark for assessing skin cancer classification fairness in the literature. Our analyses reveal a high disagreement among previously published studies demonstrating the risks of ITA-based skin tone estimation methods. Moreover, we investigate the causes of such large discrepancy among these approaches and find that the lack of diversity in the ISIC18 dataset limits its use as a testbed for fairness analysis. Finally, we recommend further research on robust ITA estimation and diverse dataset acquisition with skin tone annotation to facilitate conclusive fairness assessments of artificial intelligence tools in dermatology. Our code is available at https://github.com/tkalbl/RevisitingSkinToneFairness.

medigan: A Python Library of Pretrained Generative Models for Enriched Data Access in Medical Imaging

Synthetic data generated by generative models can enhance the performance and capabilities of data-hungry deep learning models in medical imaging. However, there is (1) limited availability of (synthetic) datasets and (2) generative models are complex to train, which hinders their adoption in research and clinical applications. To reduce this entry barrier, we propose medigan, a one-stop shop for pretrained generative models implemented as an open-source framework-agnostic Python library. medigan allows researchers and developers to create, increase, and domain-adapt their training data in just a few lines of code. Guided by design decisions based on gathered end-user requirements, we implement medigan based on modular components for generative model (i) execution, (ii) visualisation, (iii) search & ranking, and (iv) contribution. The library's scalability and design is demonstrated by its growing number of integrated and readily-usable pretrained generative models consisting of 21 models utilising 9 different Generative Adversarial Network architectures trained on 11 datasets from 4 domains, namely, mammography, endoscopy, x-ray, and MRI. Furthermore, 3 applications of medigan are analysed in this work, which include (a) enabling community-wide sharing of restricted data, (b) investigating generative model evaluation metrics, and (c) improving clinical downstream tasks. In (b), extending on common medical image synthesis assessment and reporting standards, we show Fr\'echet Inception Distance variability based on image normalisation and radiology-specific feature extraction.

High-resolution synthesis of high-density breast mammograms: Application to improved fairness in deep learning based mass detection

Computer-aided detection systems based on deep learning have shown good performance in breast cancer detection. However, high-density breasts show poorer detection performance since dense tissues can mask or even simulate masses. Therefore, the sensitivity of mammography for breast cancer detection can be reduced by more than 20% in dense breasts. Additionally, extremely dense cases reported an increased risk of cancer compared to low-density breasts. This study aims to improve the mass detection performance in high-density breasts using synthetic high-density full-field digital mammograms (FFDM) as data augmentation during breast mass detection model training. To this end, a total of five cycle-consistent GAN (CycleGAN) models using three FFDM datasets were trained for low-to-high-density image translation in high-resolution mammograms. The training images were split by breast density BI-RADS categories, being BI-RADS A almost entirely fatty and BI-RADS D extremely dense breasts. Our results showed that the proposed data augmentation technique improved the sensitivity and precision of mass detection in high-density breasts by 2% and 6% in two different test sets and was useful as a domain adaptation technique. In addition, the clinical realism of the synthetic images was evaluated in a reader study involving two expert radiologists and one surgical oncologist.

Sharing Generative Models Instead of Private Data: A Simulation Study on Mammography Patch Classification

Early detection of breast cancer in mammography screening via deep-learning based computer-aided detection systems shows promising potential in improving the curability and mortality rates of breast cancer. However, many clinical centres are restricted in the amount and heterogeneity of available data to train such models to (i) achieve promising performance and to (ii) generalise well across acquisition protocols and domains. As sharing data between centres is restricted due to patient privacy concerns, we propose a potential solution: sharing trained generative models between centres as substitute for real patient data. In this work, we use three well known mammography datasets to simulate three different centres, where one centre receives the trained generator of Generative Adversarial Networks (GANs) from the two remaining centres in order to augment the size and heterogeneity of its training dataset. We evaluate the utility of this approach on mammography patch classification on the test set of the GAN-receiving centre using two different classification models, (a) a convolutional neural network and (b) a transformer neural network. Our experiments demonstrate that shared GANs notably increase the performance of both transformer and convolutional classification models and highlight this approach as a viable alternative to inter-centre data sharing.

Domain generalization in deep learning-based mass detection in mammography: A large-scale multi-center study

Computer-aided detection systems based on deep learning have shown great potential in breast cancer detection. However, the lack of domain generalization of artificial neural networks is an important obstacle to their deployment in changing clinical environments. In this work, we explore the domain generalization of deep learning methods for mass detection in digital mammography and analyze in-depth the sources of domain shift in a large-scale multi-center setting. To this end, we compare the performance of eight state-of-the-art detection methods, including Transformer-based models, trained in a single domain and tested in five unseen domains. Moreover, a single-source mass detection training pipeline is designed to improve the domain generalization without requiring images from the new domain. The results show that our workflow generalizes better than state-of-the-art transfer learning-based approaches in four out of five domains while reducing the domain shift caused by the different acquisition protocols and scanner manufacturers. Subsequently, an extensive analysis is performed to identify the covariate shifts with bigger effects on the detection performance, such as due to differences in patient age, breast density, mass size, and mass malignancy. Ultimately, this comprehensive study provides key insights and best practices for future research on domain generalization in deep learning-based breast cancer detection.

A Review of Generative Adversarial Networks in Cancer Imaging: New Applications, New Solutions

Despite technological and medical advances, the detection, interpretation, and treatment of cancer based on imaging data continue to pose significant challenges. These include high inter-observer variability, difficulty of small-sized lesion detection, nodule interpretation and malignancy determination, inter- and intra-tumour heterogeneity, class imbalance, segmentation inaccuracies, and treatment effect uncertainty. The recent advancements in Generative Adversarial Networks (GANs) in computer vision as well as in medical imaging may provide a basis for enhanced capabilities in cancer detection and analysis. In this review, we assess the potential of GANs to address a number of key challenges of cancer imaging, including data scarcity and imbalance, domain and dataset shifts, data access and privacy, data annotation and quantification, as well as cancer detection, tumour profiling and treatment planning. We provide a critical appraisal of the existing literature of GANs applied to cancer imagery, together with suggestions on future research directions to address these challenges. We analyse and discuss 163 papers that apply adversarial training techniques in the context of cancer imaging and elaborate their methodologies, advantages and limitations. With this work, we strive to bridge the gap between the needs of the clinical cancer imaging community and the current and prospective research on GANs in the artificial intelligence community.

Deep learning reconstruction of digital breast tomosynthesis images for accurate breast density and patient-specific radiation dose estimation

The two-dimensional nature of mammography makes estimation of the overall breast density challenging, and estimation of the true patient-specific radiation dose impossible. Digital breast tomosynthesis (DBT), a pseudo-3D technique, is now commonly used in breast cancer screening and diagnostics. Still, the severely limited 3rd dimension information in DBT has not been used, until now, to estimate the true breast density or the patient-specific dose. In this study, we propose a reconstruction algorithm for DBT based on deep learning specifically optimized for these tasks. The algorithm, which we name DBToR, is based on unrolling a proximal primal-dual optimization method, where the proximal operators are replaced with convolutional neural networks and prior knowledge is included in the model. This extends previous work on a deep learning based reconstruction model by providing both the primal and the dual blocks with breast thickness information, which is available in DBT. Training and testing of the model were performed using virtual patient phantoms from two different sources. Reconstruction performance, as well as accuracy in estimation of breast density and radiation dose, was estimated, showing high accuracy (density density < +/-3%; dose < +/-20%), without bias, significantly improving on the current state-of-the-art. This work also lays the groundwork for developing a deep learning-based reconstruction algorithm for the task of image interpretation by radiologists.

Quality analysis of DCGAN-generated mammography lesions

Medical image synthesis has gained a great focus recently, especially after the introduction of Generative Adversarial Networks (GANs). GANs have been used widely to provide anatomically-plausible and diverse samples for augmentation and other applications, including segmentation and super resolution. In our previous work, Deep Convolutional GANs were used to generate synthetic mammogram lesions, masses mainly, that could enhance the classification performance in imbalanced datasets. In this new work, a deeper investigation was carried out to explore other aspects of the generated images evaluation, i.e., realism, feature space distribution, and observers studies. t-Stochastic Neighbor Embedding (t-SNE) was used to reduce the dimensionality of real and fake images to enable 2D visualisations. Additionally, two expert radiologists performed a realism-evaluation study. Visualisations showed that the generated images have a similar feature distribution of the real ones, avoiding outliers. Moreover, Receiver Operating Characteristic (ROC) curve showed that the radiologists could not, in many cases, distinguish between synthetic and real lesions, giving 48% and 61% accuracies in a balanced sample set.