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Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

The persistent challenge of medical image synthesis posed by the scarcity of annotated data and the need to synthesize `missing modalities' for multi-modal analysis, underscored the imperative development of effective synthesis methods. Recently, the combination of Low-Rank Adaptation (LoRA) with latent diffusion models (LDMs) has emerged as a viable approach for efficiently adapting pre-trained large language models, in the medical field. However, the direct application of LoRA assumes uniform ranking across all linear layers, overlooking the significance of different weight matrices, and leading to sub-optimal outcomes. Prior works on LoRA prioritize the reduction of trainable parameters, and there exists an opportunity to further tailor this adaptation process to the intricate demands of medical image synthesis. In response, we present SeLoRA, a Self-Expanding Low-Rank Adaptation Module, that dynamically expands its ranking across layers during training, strategically placing additional ranks on crucial layers, to allow the model to elevate synthesis quality where it matters most. The proposed method not only enables LDMs to fine-tune on medical data efficiently but also empowers the model to achieve improved image quality with minimal ranking. The code of our SeLoRA method is publicly available on https://anonymous.4open.science/r/SeLoRA-980D ., Comment: Project Page: https://yuchen20.github.io/SeLoRA.github.io/

Federated Learning (FL) has emerged as a promising solution to address the limitations of centralised machine learning (ML) in oncology, particularly in overcoming privacy concerns and harnessing the power of diverse, multi-center data. This systematic review synthesises current knowledge on the state-of-the-art FL in oncology, focusing on breast, lung, and prostate cancer. Distinct from previous surveys, our comprehensive review critically evaluates the real-world implementation and impact of FL on cancer care, demonstrating its effectiveness in enhancing ML generalisability, performance and data privacy in clinical settings and data. We evaluated state-of-the-art advances in FL, demonstrating its growing adoption amid tightening data privacy regulations. FL outperformed centralised ML in 15 out of the 25 studies reviewed, spanning diverse ML models and clinical applications, and facilitating integration of multi-modal information for precision medicine. Despite the current challenges identified in reproducibility, standardisation and methodology across studies, the demonstrable benefits of FL in harnessing real-world data and addressing clinical needs highlight its significant potential for advancing cancer research. We propose that future research should focus on addressing these limitations and investigating further advanced FL methods, to fully harness data diversity and realise the transformative power of cutting-edge FL in cancer care., Comment: 5 Figures, 3 Tables, 1 Supplementary Table

Immunofluorescent (IF) imaging is crucial for visualizing biomarker expressions, cell morphology and assessing the effects of drug treatments on sub-cellular components. IF imaging needs extra staining process and often requiring cell fixation, therefore it may also introduce artefects and alter endogenouous cell morphology. Some IF stains are expensive or not readily available hence hindering experiments. Recent diffusion models, which synthesise high-fidelity IF images from easy-to-acquire brightfield (BF) images, offer a promising solution but are hindered by training instability and slow inference times due to the noise diffusion process. This paper presents a novel method for the conditional synthesis of IF images directly from BF images along with cell segmentation masks. Our approach employs a Residual Diffusion process that enhances stability and significantly reduces inference time. We performed a critical evaluation against other image-to-image synthesis models, including UNets, GANs, and advanced diffusion models. Our model demonstrates significant improvements in image quality (p<0.05 in MSE, PSNR, and SSIM), inference speed (26 times faster than competing diffusion models), and accurate segmentation results for both nuclei and cell bodies (0.77 and 0.63 mean IOU for nuclei and cell true positives, respectively). This paper is a substantial advancement in the field, providing robust and efficient tools for cell image analysis.

Cell imaging assays utilizing fluorescence stains are essential for observing sub-cellular organelles and their responses to perturbations. Immunofluorescent staining process is routinely in labs, however the recent innovations in generative AI is challenging the idea of IF staining are required. This is especially true when the availability and cost of specific fluorescence dyes is a problem to some labs. Furthermore, staining process takes time and leads to inter-intra technician and hinders downstream image and data analysis, and the reusability of image data for other projects. Recent studies showed the use of generated synthetic immunofluorescence (IF) images from brightfield (BF) images using generative AI algorithms in the literature. Therefore, in this study, we benchmark and compare five models from three types of IF generation backbones, CNN, GAN, and diffusion models, using a publicly available dataset. This paper not only serves as a comparative study to determine the best-performing model but also proposes a comprehensive analysis pipeline for evaluating the efficacy of generators in IF image synthesis. We highlighted the potential of deep learning-based generators for IF image synthesis, while also discussed potential issues and future research directions. Although generative AI shows promise in simplifying cell phenotyping using only BF images with IF staining, further research and validations are needed to address the key challenges of model generalisability, batch effects, feature relevance and computational costs.

Generative AI has revolutionised visual content editing, empowering users to effortlessly modify images and videos. However, not all edits are equal. To perform realistic edits in domains such as natural image or medical imaging, modifications must respect causal relationships inherent to the data generation process. Such image editing falls into the counterfactual image generation regime. Evaluating counterfactual image generation is substantially complex: not only it lacks observable ground truths, but also requires adherence to causal constraints. Although several counterfactual image generation methods and evaluation metrics exist, a comprehensive comparison within a unified setting is lacking. We present a comparison framework to thoroughly benchmark counterfactual image generation methods. We integrate all models that have been used for the task at hand and expand them to novel datasets and causal graphs, demonstrating the superiority of Hierarchical VAEs across most datasets and metrics. Our framework is implemented in a user-friendly Python package that can be extended to incorporate additional SCMs, causal methods, generative models, and datasets for the community to build on. Code: https://github.com/gulnazaki/counterfactual-benchmark., Comment: Published as a conference paper at NeurIPS 2024 Datasets and Benchmarks Track https://openreview.net/forum?id=0T8xRFrScB Project page: https://gulnazaki.github.io/counterfactual-benchmark

Deep learning (DL) has substantially enhanced natural language processing (NLP) in healthcare research. However, the increasing complexity of DL-based NLP necessitates transparent model interpretability, or at least explainability, for reliable decision-making. This work presents a thorough scoping review of explainable and interpretable DL in healthcare NLP. The term "eXplainable and Interpretable Artificial Intelligence" (XIAI) is introduced to distinguish XAI from IAI. Different models are further categorized based on their functionality (model-, input-, output-based) and scope (local, global). Our analysis shows that attention mechanisms are the most prevalent emerging IAI technique. The use of IAI is growing, distinguishing it from XAI. The major challenges identified are that most XIAI does not explore "global" modelling processes, the lack of best practices, and the lack of systematic evaluation and benchmarks. One important opportunity is to use attention mechanisms to enhance multi-modal XIAI for personalized medicine. Additionally, combining DL with causal logic holds promise. Our discussion encourages the integration of XIAI in Large Language Models (LLMs) and domain-specific smaller models. In conclusion, XIAI adoption in healthcare requires dedicated in-house expertise. Collaboration with domain experts, end-users, and policymakers can lead to ready-to-use XIAI methods across NLP and medical tasks. While challenges exist, XIAI techniques offer a valuable foundation for interpretable NLP algorithms in healthcare., Comment: This paper has been accepted by Computational and Structural Biotechnology Journal

Clinical decision making from magnetic resonance imaging (MRI) combines complementary information from multiple MRI sequences (defined as 'modalities'). MRI image registration aims to geometrically 'pair' diagnoses from different modalities, time points and slices. Both intra- and inter-modality MRI registration are essential components in clinical MRI settings. Further, an MRI image processing pipeline that can address both afine and non-rigid registration is critical, as both types of deformations may be occuring in real MRI data scenarios. Unlike image classification, explainability is not commonly addressed in image registration deep learning (DL) methods, as it is challenging to interpet model-data behaviours against transformation fields. To properly address this, we incorporate Grad-CAM-based explainability frameworks in each major component of our unsupervised multi-modal and multi-organ image registration DL methodology. We previously demonstrated that we were able to reach superior performance (against the current standard Syn method). In this work, we show that our DL model becomes fully explainable, setting the framework to generalise our approach on further medical imaging data.

Medical imaging is a key component in clinical diagnosis, treatment planning and clinical trial design, accounting for almost 90% of all healthcare data. CNNs achieved performance gains in medical image analysis (MIA) over the last years. CNNs can efficiently model local pixel interactions and be trained on small-scale MI data. The main disadvantage of typical CNN models is that they ignore global pixel relationships within images, which limits their generalisation ability to understand out-of-distribution data with different 'global' information. The recent progress of Artificial Intelligence gave rise to Transformers, which can learn global relationships from data. However, full Transformer models need to be trained on large-scale data and involve tremendous computational complexity. Attention and Transformer compartments (Transf/Attention) which can well maintain properties for modelling global relationships, have been proposed as lighter alternatives of full Transformers. Recently, there is an increasing trend to co-pollinate complementary local-global properties from CNN and Transf/Attention architectures, which led to a new era of hybrid models. The past years have witnessed substantial growth in hybrid CNN-Transf/Attention models across diverse MIA problems. In this systematic review, we survey existing hybrid CNN-Transf/Attention models, review and unravel key architectural designs, analyse breakthroughs, and evaluate current and future opportunities as well as challenges. We also introduced a comprehensive analysis framework on generalisation opportunities of scientific and clinical impact, based on which new data-driven domain generalisation and adaptation methods can be stimulated.

Synthetic images generated from deep generative models have the potential to address data scarcity and data privacy issues. The selection of synthesis models is mostly based on image quality measurements, and most researchers favor synthetic images that produce realistic images, i.e., images with good fidelity scores, such as low Fr\'echet Inception Distance (FID) and high Peak Signal-To-Noise Ratio (PSNR). However, the quality of synthetic images is not limited to fidelity, and a wide spectrum of metrics should be evaluated to comprehensively measure the quality of synthetic images. In addition, quality metrics are not truthful predictors of the utility of synthetic images, and the relations between these evaluation metrics are not yet clear. In this work, we have established a comprehensive set of evaluators for synthetic images, including fidelity, variety, privacy, and utility. By analyzing more than 100k chest X-ray images and their synthetic copies, we have demonstrated that there is an inevitable trade-off between synthetic image fidelity, variety, and privacy. In addition, we have empirically demonstrated that the utility score does not require images with both high fidelity and high variety. For intra- and cross-task data augmentation, mode-collapsed images and low-fidelity images can still demonstrate high utility. Finally, our experiments have also showed that it is possible to produce images with both high utility and privacy, which can provide a strong rationale for the use of deep generative models in privacy-preserving applications. Our study can shore up comprehensive guidance for the evaluation of synthetic images and elicit further developments for utility-aware deep generative models in medical image synthesis., Comment: 10 pages, 4 figures, MICCAI Early Acceptance

As a pragmatic data augmentation tool, data synthesis has generally returned dividends in performance for deep learning based medical image analysis. However, generating corresponding segmentation masks for synthetic medical images is laborious and subjective. To obtain paired synthetic medical images and segmentations, conditional generative models that use segmentation masks as synthesis conditions were proposed. However, these segmentation mask-conditioned generative models still relied on large, varied, and labeled training datasets, and they could only provide limited constraints on human anatomical structures, leading to unrealistic image features. Moreover, the invariant pixel-level conditions could reduce the variety of synthetic lesions and thus reduce the efficacy of data augmentation. To address these issues, in this work, we propose a novel strategy for medical image synthesis, namely Unsupervised Mask (UM)-guided synthesis, to obtain both synthetic images and segmentations using limited manual segmentation labels. We first develop a superpixel based algorithm to generate unsupervised structural guidance and then design a conditional generative model to synthesize images and annotations simultaneously from those unsupervised masks in a semi-supervised multi-task setting. In addition, we devise a multi-scale multi-task Fr\'echet Inception Distance (MM-FID) and multi-scale multi-task standard deviation (MM-STD) to harness both fidelity and variety evaluations of synthetic CT images. With multiple analyses on different scales, we could produce stable image quality measurements with high reproducibility. Compared with the segmentation mask guided synthesis, our UM-guided synthesis provided high-quality synthetic images with significantly higher fidelity, variety, and utility ($p<0.05$ by Wilcoxon Signed Ranked test)., Comment: 12 pages, 11 figures, accepted by IEEE TMI

Magnetic Resonance Imaging (MRI) typically recruits multiple sequences (defined here as "modalities"). As each modality is designed to offer different anatomical and functional clinical information, there are evident disparities in the imaging content across modalities. Inter- and intra-modality affine and non-rigid image registration is an essential medical image analysis process in clinical imaging, as for example before imaging biomarkers need to be derived and clinically evaluated across different MRI modalities, time phases and slices. Although commonly needed in real clinical scenarios, affine and non-rigid image registration is not extensively investigated using a single unsupervised model architecture. In our work, we present an un-supervised deep learning registration methodology which can accurately model affine and non-rigid trans-formations, simultaneously. Moreover, inverse-consistency is a fundamental inter-modality registration property that is not considered in deep learning registration algorithms. To address inverse-consistency, our methodology performs bi-directional cross-modality image synthesis to learn modality-invariant latent rep-resentations, while involves two factorised transformation networks and an inverse-consistency loss to learn topology-preserving anatomical transformations. Overall, our model (named "FIRE") shows improved performances against the reference standard baseline method on multi-modality brain 2D and 3D MRI and intra-modality cardiac 4D MRI data experiments., Comment: 38 pages, 7 figures, will be published in Sensors journal by MDPI

Automated pathology segmentation remains a valuable diagnostic tool in clinical practice. However, collecting training data is challenging. Semi-supervised approaches by combining labelled and unlabelled data can offer a solution to data scarcity. An approach to semi-supervised learning relies on reconstruction objectives (as self-supervision objectives) that learns in a joint fashion suitable representations for the task. Here, we propose Anatomy-Pathology Disentanglement Network (APD-Net), a pathology segmentation model that attempts to learn jointly for the first time: disentanglement of anatomy, modality, and pathology. The model is trained in a semi-supervised fashion with new reconstruction losses directly aiming to improve pathology segmentation with limited annotations. In addition, a joint optimization strategy is proposed to fully take advantage of the available annotations. We evaluate our methods with two private cardiac infarction segmentation datasets with LGE-MRI scans. APD-Net can perform pathology segmentation with few annotations, maintain performance with different amounts of supervision, and outperform related deep learning methods., Comment: 12 Pages, 4 figures

Magnetic resonance (MR) protocols rely on several sequences to assess pathology and organ status properly. Despite advances in image analysis, we tend to treat each sequence, here termed modality, in isolation. Taking advantage of the common information shared between modalities (an organ's anatomy) is beneficial for multi-modality processing and learning. However, we must overcome inherent anatomical misregistrations and disparities in signal intensity across the modalities to obtain this benefit. We present a method that offers improved segmentation accuracy of the modality of interest (over a single input model), by learning to leverage information present in other modalities, even if few (semi-supervised) or no (unsupervised) annotations are available for this specific modality. Core to our method is learning a disentangled decomposition into anatomical and imaging factors. Shared anatomical factors from the different inputs are jointly processed and fused to extract more accurate segmentation masks. Image misregistrations are corrected with a Spatial Transformer Network, which non-linearly aligns the anatomical factors. The imaging factor captures signal intensity characteristics across different modality data and is used for image reconstruction, enabling semi-supervised learning. Temporal and slice pairing between inputs are learned dynamically. We demonstrate applications in Late Gadolinium Enhanced (LGE) and Blood Oxygenation Level Dependent (BOLD) cardiac segmentation, as well as in T2 abdominal segmentation. Code is available at https://github.com/vios-s/multimodal_segmentation.

Inter-modality image registration is an critical preprocessing step for many applications within the routine clinical pathway. This paper presents an unsupervised deep inter-modality registration network that can learn the optimal affine and non-rigid transformations simultaneously. Inverse-consistency is an important property commonly ignored in recent deep learning based inter-modality registration algorithms. We address this issue through the proposed multi-task architecture and the new comprehensive transformation network. Specifically, the proposed model learns a modality-independent latent representation to perform cycle-consistent cross-modality synthesis, and use an inverse-consistent loss to learn a pair of transformations to align the synthesized image with the target. We name this proposed framework as FIRE due to the shape of its structure. Our method shows comparable and better performances with the popular baseline method in experiments on multi-sequence brain MR data and intra-modality 4D cardiac Cine-MR data., Comment: We submitted this paper to a top medical imaging conference, srebuttal responded by the meta-reviewer. We were told that this work is not important and will not have big impact as the "reviewers were not enthusiastic". Here I publish the paper online for an open discussion. I will publish the code, the pre-trained model, the results, especially the reviews, and the meta reviews on github

Typically, a medical image offers spatial information on the anatomy (and pathology) modulated by imaging specific characteristics. Many imaging modalities including Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) can be interpreted in this way. We can venture further and consider that a medical image naturally factors into some spatial factors depicting anatomy and factors that denote the imaging characteristics. Here, we explicitly learn this decomposed (disentangled) representation of imaging data, focusing in particular on cardiac images. We propose Spatial Decomposition Network (SDNet), which factorises 2D medical images into spatial anatomical factors and non-spatial modality factors. We demonstrate that this high-level representation is ideally suited for several medical image analysis tasks, such as semi-supervised segmentation, multi-task segmentation and regression, and image-to-image synthesis. Specifically, we show that our model can match the performance of fully supervised segmentation models, using only a fraction of the labelled images. Critically, we show that our factorised representation also benefits from supervision obtained either when we use auxiliary tasks to train the model in a multi-task setting (e.g. regressing to known cardiac indices), or when aggregating multimodal data from different sources (e.g. pooling together MRI and CT data). To explore the properties of the learned factorisation, we perform latent-space arithmetic and show that we can synthesise CT from MR and vice versa, by swapping the modality factors. We also demonstrate that the factor holding image specific information can be used to predict the input modality with high accuracy. Code will be made available at https://github.com/agis85/anatomy_modality_decomposition.

Recently, the cycle-consistent generative adversarial networks (CycleGAN) has been widely used for synthesis of multi-domain medical images. The domain-specific nonlinear deformations captured by CycleGAN make the synthesized images difficult to be used for some applications, for example, generating pseudo-CT for PET-MR attenuation correction. This paper presents a deformation-invariant CycleGAN (DicycleGAN) method using deformable convolutional layers and new cycle-consistency losses. Its robustness dealing with data that suffer from domain-specific nonlinear deformations has been evaluated through comparison experiments performed on a multi-sequence brain MR dataset and a multi-modality abdominal dataset. Our method has displayed its ability to generate synthesized data that is aligned with the source while maintaining a proper quality of signal compared to CycleGAN-generated data. The proposed model also obtained comparable performance with CycleGAN when data from the source and target domains are alignable through simple affine transformations.

The success and generalisation of deep learning algorithms heavily depend on learning good feature representations. In medical imaging this entails representing anatomical information, as well as properties related to the specific imaging setting. Anatomical information is required to perform further analysis, whereas imaging information is key to disentangle scanner variability and potential artefacts. The ability to factorise these would allow for training algorithms only on the relevant information according to the task. To date, such factorisation has not been attempted. In this paper, we propose a methodology of latent space factorisation relying on the cycle-consistency principle. As an example application, we consider cardiac MR segmentation, where we separate information related to the myocardium from other features related to imaging and surrounding substructures. We demonstrate the proposed method's utility in a semi-supervised setting: we use very few labelled images together with many unlabelled images to train a myocardium segmentation neural network. Specifically, we achieve comparable performance to fully supervised networks using a fraction of labelled images in experiments on ACDC and a dataset from Edinburgh Imaging Facility QMRI. Code will be made available at https://github.com/agis85/spatial_factorisation., Comment: Accepted in MICCAI 2018