Medical image synthesis presents unique challenges due to the inherent complexity and high-resolution details required in clinical contexts. Traditional generative architectures such as Generative Adversarial Networks (GANs) or Variational Auto Encoder (VAEs) have shown great promise for high-resolution image generation but struggle with preserving fine-grained details that are key for accurate diagnosis. To address this issue, we introduce Pixel Perfect MegaMed, the first vision-language foundation model to synthesize images at resolutions of 1024x1024. Our method deploys a multi-scale transformer architecture designed specifically for ultra-high resolution medical image generation, enabling the preservation of both global anatomical context and local image-level details. By leveraging vision-language alignment techniques tailored to medical terminology and imaging modalities, Pixel Perfect MegaMed bridges the gap between textual descriptions and visual representations at unprecedented resolution levels. We apply our model to the CheXpert dataset and demonstrate its ability to generate clinically faithful chest X-rays from text prompts. Beyond visual quality, these high-resolution synthetic images prove valuable for downstream tasks such as classification, showing measurable performance gains when used for data augmentation, particularly in low-data regimes. Our code is accessible through the project website - https://tehraninasab.github.io/pixelperfect-megamed.

Interpretability can improve the safety, transparency and trust of AI models, which is especially important in healthcare applications where decisions often carry significant consequences. Mechanistic interpretability, particularly through the use of sparse autoencoders (SAEs), offers a promising approach for uncovering human-interpretable features within large transformer-based models. In this study, we apply Matryoshka-SAE to the radiology-specialised multimodal large language model, MAIRA-2, to interpret its internal representations. Using large-scale automated interpretability of the SAE features, we identify a range of clinically relevant concepts - including medical devices (e.g., line and tube placements, pacemaker presence), pathologies such as pleural effusion and cardiomegaly, longitudinal changes and textual features. We further examine the influence of these features on model behaviour through steering, demonstrating directional control over generations with mixed success. Our results reveal practical and methodological challenges, yet they offer initial insights into the internal concepts learned by MAIRA-2 - marking a step toward deeper mechanistic understanding and interpretability of a radiology-adapted multimodal large language model, and paving the way for improved model transparency. We release the trained SAEs and interpretations: https://huggingface.co/microsoft/maira-2-sae.

Cortical lesions (CLs) have emerged as valuable biomarkers in multiple sclerosis (MS), offering high diagnostic specificity and prognostic relevance. However, their routine clinical integration remains limited due to subtle magnetic resonance imaging (MRI) appearance, challenges in expert annotation, and a lack of standardized automated methods. We propose a comprehensive multi-centric benchmark of CL detection and segmentation in MRI. A total of 656 MRI scans, including clinical trial and research data from four institutions, were acquired at 3T and 7T using MP2RAGE and MPRAGE sequences with expert-consensus annotations. We rely on the self-configuring nnU-Net framework, designed for medical imaging segmentation, and propose adaptations tailored to the improved CL detection. We evaluated model generalization through out-of-distribution testing, demonstrating strong lesion detection capabilities with an F1-score of 0.64 and 0.5 in and out of the domain, respectively. We also analyze internal model features and model errors for a better understanding of AI decision-making. Our study examines how data variability, lesion ambiguity, and protocol differences impact model performance, offering future recommendations to address these barriers to clinical adoption. To reinforce the reproducibility, the implementation and models will be publicly accessible and ready to use at https://github.com/Medical-Image-Analysis-Laboratory/ and https://doi.org/10.5281/zenodo.15911797.

Phrase grounding, i.e., mapping natural language phrases to specific image regions, holds significant potential for disease localization in medical imaging through clinical reports. While current state-of-the-art methods rely on discriminative, self-supervised contrastive models, we demonstrate that generative text-to-image diffusion models, leveraging cross-attention maps, can achieve superior zero-shot phrase grounding performance. Contrary to prior assumptions, we show that fine-tuning diffusion models with a frozen, domain-specific language model, such as CXR-BERT, substantially outperforms domain-agnostic counterparts. This setup achieves remarkable improvements, with mIoU scores doubling those of current discriminative methods. These findings highlight the underexplored potential of generative models for phrase grounding tasks. To further enhance performance, we introduce Bimodal Bias Merging (BBM), a novel post-processing technique that aligns text and image biases to identify regions of high certainty. BBM refines cross-attention maps, achieving even greater localization accuracy. Our results establish generative approaches as a more effective paradigm for phrase grounding in the medical imaging domain, paving the way for more robust and interpretable applications in clinical practice. The source code and model weights are available at https://github.com/Felix-012/generate_to_ground.

Sparse autoencoders (SAEs) emerged as a promising tool for mechanistic interpretability of transformer-based foundation models. Very recently, SAEs were also adopted for the visual domain, enabling the discovery of visual concepts and their patch-wise attribution to tokens in the transformer model. While a growing number of foundation models emerged for medical imaging, tools for explaining their inferences are still lacking. In this work, we show the applicability of SAEs for hematology. We propose CytoSAE, a sparse autoencoder which is trained on over 40,000 peripheral blood single-cell images. CytoSAE generalizes to diverse and out-of-domain datasets, including bone marrow cytology, where it identifies morphologically relevant concepts which we validated with medical experts. Furthermore, we demonstrate scenarios in which CytoSAE can generate patient-specific and disease-specific concepts, enabling the detection of pathognomonic cells and localized cellular abnormalities at the patch level. We quantified the effect of concepts on a patient-level AML subtype classification task and show that CytoSAE concepts reach performance comparable to the state-of-the-art, while offering explainability on the sub-cellular level. Source code and model weights are available at https://github.com/dynamical-inference/cytosae.

Foundation models, pre-trained on large image datasets and capable of capturing rich feature representations, have recently shown potential for zero-shot image registration. However, their performance has mostly been tested in the context of rigid or less complex structures, such as the brain or abdominal organs, and it remains unclear whether these models can handle more challenging, deformable anatomy. Breast MRI registration is particularly difficult due to significant anatomical variation between patients, deformation caused by patient positioning, and the presence of thin and complex internal structure of fibroglandular tissue, where accurate alignment is crucial. Whether foundation model-based registration algorithms can address this level of complexity remains an open question. In this study, we provide a comprehensive evaluation of foundation model-based registration algorithms for breast MRI. We assess five pre-trained encoders, including DINO-v2, SAM, MedSAM, SSLSAM, and MedCLIP, across four key breast registration tasks that capture variations in different years and dates, sequences, modalities, and patient disease status (lesion versus no lesion). Our results show that foundation model-based algorithms such as SAM outperform traditional registration baselines for overall breast alignment, especially under large domain shifts, but struggle with capturing fine details of fibroglandular tissue. Interestingly, additional pre-training or fine-tuning on medical or breast-specific images in MedSAM and SSLSAM, does not improve registration performance and may even decrease it in some cases. Further work is needed to understand how domain-specific training influences registration and to explore targeted strategies that improve both global alignment and fine structure accuracy. We also publicly release our code at \href{https://github.com/mazurowski-lab/Foundation-based-reg}{Github}.

Computed Tomography (CT) is a widely utilized imaging modality in clinical settings. Using densely acquired rotational X-ray arrays, CT can capture 3D spatial features. However, it is confronted with challenged such as significant time consumption and high radiation exposure. CT reconstruction methods based on sparse-view X-ray images have garnered substantial attention from researchers as they present a means to mitigate costs and risks. In recent years, diffusion models, particularly the Latent Diffusion Model (LDM), have demonstrated promising potential in the domain of 3D CT reconstruction. Nonetheless, due to the substantial differences between the 2D latent representation of X-ray modalities and the 3D latent representation of CT modalities, the vanilla LDM is incapable of achieving effective alignment within the latent space. To address this issue, we propose the Consistent Latent Space Diffusion Model (CLS-DM), which incorporates cross-modal feature contrastive learning to efficiently extract latent 3D information from 2D X-ray images and achieve latent space alignment between modalities. Experimental results indicate that CLS-DM outperforms classical and state-of-the-art generative models in terms of standard voxel-level metrics (PSNR, SSIM) on the LIDC-IDRI and CTSpine1K datasets. This methodology not only aids in enhancing the effectiveness and economic viability of sparse X-ray reconstructed CT but can also be generalized to other cross-modal transformation tasks, such as text-to-image synthesis. We have made our code publicly available at https://anonymous.4open.science/r/CLS-DM-50D6/ to facilitate further research and applications in other domains.

Transformers have revolutionized medical image restoration, but the quadratic complexity still poses limitations for their application to high-resolution medical images. The recent advent of the Receptance Weighted Key Value (RWKV) model in the natural language processing field has attracted much attention due to its ability to process long sequences efficiently. To leverage its advanced design, we propose Restore-RWKV, the first RWKV-based model for medical image restoration. Since the original RWKV model is designed for 1D sequences, we make two necessary modifications for modeling spatial relations in 2D medical images. First, we present a recurrent WKV (Re-WKV) attention mechanism that captures global dependencies with linear computational complexity. Re-WKV incorporates bidirectional attention as basic for a global 16 receptive field and recurrent attention to effectively model 2D dependencies from various scan directions. Second, we develop an omnidirectional token shift (Omni-Shift) layer that enhances local dependencies by shifting tokens from all directions and across a wide context range. These adaptations make the proposed Restore-RWKV an efficient and effective model for medical image restoration. Even a lightweight variant of Restore-RWKV, with only 1.16 million parameters, achieves comparable or even superior results compared to existing state-of-the-art (SOTA) methods. Extensive experiments demonstrate that the resulting Restore-RWKV achieves SOTA performance across a range of medical image restoration tasks, including PET image synthesis, CT image denoising, MRI image superresolution, and all-in-one medical image restoration. Code is available at: https://github.com/Yaziwel/Restore-RWKV.

High-quality 3D fetal brain MRI reconstruction from motion-corrupted 2D slices is crucial for precise clinical diagnosis and advancing our understanding of fetal brain development. This necessitates reliable slice-to-volume registration (SVR) for motion correction and super-resolution reconstruction (SRR) techniques. Traditional approaches have their limitations, but deep learning (DL) offers the potential in enhancing SVR and SRR. However, most of DL methods require large-scale external 3D high-resolution (HR) training datasets, which is challenging in clinical fetal MRI. To address this issue, we propose an unsupervised iterative joint SVR and SRR DL framework for 3D isotropic HR volume reconstruction. Specifically, our method conceptualizes SVR as a function that maps a 2D slice and a 3D target volume to a rigid transformation matrix, aligning the slice to the underlying location within the target volume. This function is parameterized by a convolutional neural network, which is trained by minimizing the difference between the volume slicing at the predicted position and the actual input slice. For SRR, a decoding network embedded within a deep image prior framework, coupled with a comprehensive image degradation model, is used to produce the HR volume. The deep image prior framework offers a local consistency prior to guide the reconstruction of HR volumes. By performing a forward degradation model, the HR volume is optimized by minimizing the loss between the predicted slices and the acquired slices. Experiments on both large-magnitude motion-corrupted simulation data and clinical data have shown that our proposed method outperforms current state-of-the-art fetal brain reconstruction methods. The source code is available at https://github.com/DeepBMI/SUFFICIENT.

Effective treatment for rectal cancer relies on accurate lymph node metastasis (LNM) staging. However, radiological criteria based on lymph node (LN) size, shape and texture morphology have limited diagnostic accuracy. In this work, we investigate applying a Variational Autoencoder (VAE) as a feature encoder model to replace the large pre-trained Convolutional Neural Network (CNN) used in existing approaches. The motivation for using a VAE is that the generative model aims to reconstruct the images, so it directly encodes visual features and meaningful patterns across the data. This leads to a disentangled and structured latent space which can be more interpretable than a CNN. Models are deployed on an in-house MRI dataset with 168 patients who did not undergo neo-adjuvant treatment. The post-operative pathological N stage was used as the ground truth to evaluate model predictions. Our proposed model 'VAE-MLP' achieved state-of-the-art performance on the MRI dataset, with cross-validated metrics of AUC 0.86 +/- 0.05, Sensitivity 0.79 +/- 0.06, and Specificity 0.85 +/- 0.05. Code is available at: https://github.com/benkeel/Lymph_Node_Classification_MIUA.