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This paper presents a method for virtual contrast enhancement in breast MRI, offering a promising non-invasive alternative to traditional contrast agent-based DCE-MRI acquisition. Using a conditional generative adversarial network, we predict DCE-MRI images, including jointly-generated sequences of multiple corresponding DCE-MRI timepoints, from non-contrast-enhanced MRIs, enabling tumor localization and characterization without the associated health risks. Furthermore, we qualitatively and quantitatively evaluate the synthetic DCE-MRI images, proposing a multi-metric Scaled Aggregate Measure (SAMe), assessing their utility in a tumor segmentation downstream task, and conclude with an analysis of the temporal patterns in multi-sequence DCE-MRI generation. Our approach demonstrates promising results in generating realistic and useful DCE-MRI sequences, highlighting the potential of virtual contrast enhancement for improving breast cancer diagnosis and treatment, particularly for patients where contrast agent administration is contraindicated.

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.

Deep learning holds immense promise for aiding radiologists in breast cancer detection. However, achieving optimal model performance is hampered by limitations in availability and sharing of data commonly associated to patient privacy concerns. Such concerns are further exacerbated, as traditional deep learning models can inadvertently leak sensitive training information. This work addresses these challenges exploring and quantifying the utility of privacy-preserving deep learning techniques, concretely, (i) differentially private stochastic gradient descent (DP-SGD) and (ii) fully synthetic training data generated by our proposed malignancy-conditioned generative adversarial network. We assess these methods via downstream malignancy classification of mammography masses using a transformer model. Our experimental results depict that synthetic data augmentation can improve privacy-utility tradeoffs in differentially private model training. Further, model pretraining on synthetic data achieves remarkable performance, which can be further increased with DP-SGD fine-tuning across all privacy guarantees. With this first in-depth exploration of privacy-preserving deep learning in breast imaging, we address current and emerging clinical privacy requirements and pave the way towards the adoption of private high-utility deep diagnostic models. Our reproducible codebase is publicly available at https://github.com/RichardObi/mammo_dp., Comment: Early Accept at MICCAI 2024 Deep-Breath Workshop

In this work, we introduce Progressive Growing of Patch Size, a resource-efficient implicit curriculum learning approach for dense prediction tasks. Our curriculum approach is defined by growing the patch size during model training, which gradually increases the task's difficulty. We integrated our curriculum into the nnU-Net framework and evaluated the methodology on all 10 tasks of the Medical Segmentation Decathlon. With our approach, we are able to substantially reduce runtime, computational costs, and CO2 emissions of network training compared to classical constant patch size training. In our experiments, the curriculum approach resulted in improved convergence. We are able to outperform standard nnU-Net training, which is trained with constant patch size, in terms of Dice Score on 7 out of 10 MSD tasks while only spending roughly 50% of the original training runtime. To the best of our knowledge, our Progressive Growing of Patch Size is the first successful employment of a sample-length curriculum in the form of patch size in the field of computer vision. Our code is publicly available at https://github.com/compai-lab/2024-miccai-fischer., Comment: Accepted at MICCAI2024; Changes for Camera-Ready-Version for MICCAI2024 (missing in this arxiv submission): Replaced T-Test with Wilcoxon Signed Ranked Test, as DSC samples are not normally distributed => now only significant improvements and no significant decreases in performance for PGPS/PGPS+

Artificial Intelligence (AI) research in breast cancer Magnetic Resonance Imaging (MRI) faces challenges due to limited expert-labeled segmentations. To address this, we present a multicenter dataset of 1506 pre-treatment T1-weighted dynamic contrast-enhanced MRI cases, including expert annotations of primary tumors and non-mass-enhanced regions. The dataset integrates imaging data from four collections in The Cancer Imaging Archive (TCIA), where only 163 cases with expert segmentations were initially available. To facilitate the annotation process, a deep learning model was trained to produce preliminary segmentations for the remaining cases. These were subsequently corrected and verified by 16 breast cancer experts (averaging 9 years of experience), creating a fully annotated dataset. Additionally, the dataset includes 49 harmonized clinical and demographic variables, as well as pre-trained weights for a baseline nnU-Net model trained on the annotated data. This resource addresses a critical gap in publicly available breast cancer datasets, enabling the development, validation, and benchmarking of advanced deep learning models, thus driving progress in breast cancer diagnostics, treatment response prediction, and personalized care., Comment: 15 paes, 7 figures, 3 tables

Artificial Intelligence (AI) has emerged as a valuable tool for assisting radiologists in breast cancer detection and diagnosis. However, the success of AI applications in this domain is restricted by the quantity and quality of available data, posing challenges due to limited and costly data annotation procedures that often lead to annotation shifts. This study simulates, analyses and mitigates annotation shifts in cancer classification in the breast mammography domain. First, a high-accuracy cancer risk prediction model is developed, which effectively distinguishes benign from malignant lesions. Next, model performance is used to quantify the impact of annotation shift. We uncover a substantial impact of annotation shift on multiclass classification performance particularly for malignant lesions. We thus propose a training data augmentation approach based on single-image generative models for the affected class, requiring as few as four in-domain annotations to considerably mitigate annotation shift, while also addressing dataset imbalance. Lastly, we further increase performance by proposing and validating an ensemble architecture based on multiple models trained under different data augmentation regimes. Our study offers key insights into annotation shift in deep learning breast cancer classification and explores the potential of single-image generative models to overcome domain shift challenges., Comment: Preprint of paper accepted at SPIE IWBI 2024 Conference

The progress in deep learning solutions for disease diagnosis and prognosis based on cardiac magnetic resonance imaging is hindered by highly imbalanced and biased training data. To address this issue, we propose a method to alleviate imbalances inherent in datasets through the generation of synthetic data based on sensitive attributes such as sex, age, body mass index, and health condition. We adopt ControlNet based on a denoising diffusion probabilistic model to condition on text assembled from patient metadata and cardiac geometry derived from segmentation masks using a large-cohort study, specifically, the UK Biobank. We assess our method by evaluating the realism of the generated images using established quantitative metrics. Furthermore, we conduct a downstream classification task aimed at debiasing a classifier by rectifying imbalances within underrepresented groups through synthetically generated samples. Our experiments demonstrate the effectiveness of the proposed approach in mitigating dataset imbalances, such as the scarcity of younger patients or individuals with normal BMI level suffering from heart failure. This work represents a major step towards the adoption of synthetic data for the development of fair and generalizable models for medical classification tasks. Notably, we conduct all our experiments using a single, consumer-level GPU to highlight the feasibility of our approach within resource-constrained environments. Our code is available at https://github.com/faildeny/debiasing-cardiac-mri.

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 and provide a user-friendly library for Fr\'echet radiomics distance calculation at https://pypi.org/project/frd-score., Comment: Early Accept at MICCAI2024

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., Comment: Accepted as oral presentation at SPIE Medical Imaging 2024 (Image Processing)

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., Comment: Accepted at 2023 MICCAI FAIMI Workshop

Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI.

Despite extensive recent advances in summary generation models, evaluation of auto-generated summaries still widely relies on single-score systems insufficient for transparent assessment and in-depth qualitative analysis. Towards bridging this gap, we propose the multifaceted interpretable summary evaluation method (MISEM), which is based on allocation of a summary's contextual token embeddings to semantic topics identified in the reference text. We further contribute an interpretability toolbox for automated summary evaluation and interactive visual analysis of summary scoring, topic identification, and token-topic allocation. MISEM achieves a promising .404 Pearson correlation with human judgment on the TAC'08 dataset., Comment: 5 pages, 3 figures

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., Comment: 32 pages, 7 figures

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 highdensity 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 highresolution mammograms. The training images were split by breast density BIRADS 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 models trained with small datasets and improved the domain generalization of the models trained with large databases. In addition, the clinical realism of the synthetic images was evaluated in a reader study involving two expert radiologists and one surgical oncologist., Comment: 9 figures, 4 tables

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., Comment: Draft accepted as oral presentation at International Workshop on Breast Imaging (IWBI) 2022. 9 pages, 3 figures

The recent advancements in artificial intelligence (AI) combined with the extensive amount of data generated by today's clinical systems, has led to the development of imaging AI solutions across the whole value chain of medical imaging, including image reconstruction, medical image segmentation, image-based diagnosis and treatment planning. Notwithstanding the successes and future potential of AI in medical imaging, many stakeholders are concerned of the potential risks and ethical implications of imaging AI solutions, which are perceived as complex, opaque, and difficult to comprehend, utilise, and trust in critical clinical applications. Addressing these concerns and risks, the FUTURE-AI framework has been proposed, which, sourced from a global multi-domain expert consensus, comprises guiding principles for increased trust, safety, and adoption for AI in healthcare. In this paper, we transform the general FUTURE-AI healthcare principles to a concise and specific AI implementation guide tailored to the needs of the medical imaging community. To this end, we carefully assess each building block of the FUTURE-AI framework consisting of (i) Fairness, (ii) Universality, (iii) Traceability, (iv) Usability, (v) Robustness and (vi) Explainability, and respectively define concrete best practices based on accumulated AI implementation experiences from five large European projects on AI in Health Imaging. We accompany our concrete step-by-step medical imaging development guide with a practical AI solution maturity checklist, thus enabling AI development teams to design, evaluate, maintain, and deploy technically, clinically and ethically trustworthy imaging AI solutions into clinical practice., Comment: Please refer to arXiv:2309.12325 for the latest FUTURE-AI framework for healthcare

Despite technological and medical advances, the detection, interpretation, and treatment of cancer based on imaging data continue to pose significant challenges. These include inter-observer variability, class imbalance, dataset shifts, inter- and intra-tumour heterogeneity, malignancy determination, and treatment effect uncertainty. Given the recent advancements in Generative Adversarial Networks (GANs), data synthesis, and adversarial training, we assess the potential of these technologies to address a number of key challenges of cancer imaging. We categorise these challenges into (a) data scarcity and imbalance, (b) data access and privacy, (c) data annotation and segmentation, (d) cancer detection and diagnosis, and (e) tumour profiling, treatment planning and monitoring. Based on our analysis of 164 publications that apply adversarial training techniques in the context of cancer imaging, we highlight multiple underexplored solutions with research potential. We further contribute the Synthesis Study Trustworthiness Test (SynTRUST), a meta-analysis framework for assessing the validation rigour of medical image synthesis studies. SynTRUST is based on 26 concrete measures of thoroughness, reproducibility, usefulness, scalability, and tenability. Based on SynTRUST, we analyse 16 of the most promising cancer imaging challenge solutions and observe a high validation rigour in general, but also several desirable improvements. 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 data synthesis and adversarial networks in the artificial intelligence community., Comment: v2, 51 pages, 15 Figures, 9 Tables, accepted for publication in Medical Image Analysis