Daniel C. Alexander

Jason P. Lim, Stefano B. Blumberg, Neil Narayan et al.

Machine learning is a powerful approach for fitting microstructural models to diffusion MRI data. Early machine learning microstructure imaging implementations trained regressors to estimate model parameters in a supervised way, using synthetic training data with known ground truth. However, a drawback of this approach is that the choice of training data impacts fitted parameter values. Self-supervised learning is emerging as an attractive alternative to supervised learning in this context. Thus far, both supervised and self-supervised learning have typically been applied to isotropic models, such as intravoxel incoherent motion (IVIM), as opposed to models where the directionality of anisotropic structures is also estimated. In this paper, we demonstrate self-supervised machine learning model fitting for a directional microstructural model. In particular, we fit a combined T1-ball-stick model to the multidimensional diffusion (MUDI) challenge diffusion-relaxation dataset. Our self-supervised approach shows clear improvements in parameter estimation and computational time, for both simulated and in-vivo brain data, compared to standard non-linear least squares fitting. Code for the artificial neural net constructed for this study is available for public use from the following GitHub repository: https://github.com/jplte/deep-T1-ball-stick

Mona Sheikh Zeinoddin, Chiara Lena, Jiongqi Qu et al.

Robotic-assisted surgery (RAS) relies on accurate depth estimation for 3D reconstruction and visualization. While foundation models like Depth Anything Models (DAM) show promise, directly applying them to surgery often yields suboptimal results. Fully fine-tuning on limited surgical data can cause overfitting and catastrophic forgetting, compromising model robustness and generalization. Although Low-Rank Adaptation (LoRA) addresses some adaptation issues, its uniform parameter distribution neglects the inherent feature hierarchy, where earlier layers, learning more general features, require more parameters than later ones. To tackle this issue, we introduce Depth Anything in Robotic Endoscopic Surgery (DARES), a novel approach that employs a new adaptation technique, Vector Low-Rank Adaptation (Vector-LoRA) on the DAM V2 to perform self-supervised monocular depth estimation in RAS scenes. To enhance learning efficiency, we introduce Vector-LoRA by integrating more parameters in earlier layers and gradually decreasing parameters in later layers. We also design a reprojection loss based on the multi-scale SSIM error to enhance depth perception by better tailoring the foundation model to the specific requirements of the surgical environment. The proposed method is validated on the SCARED dataset and demonstrates superior performance over recent state-of-the-art self-supervised monocular depth estimation techniques, achieving an improvement of 13.3% in the absolute relative error metric. The code and pre-trained weights are available at https://github.com/mobarakol/DARES.

Hongxiang Lin, Matteo Figini, Felice D'Arco et al.

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

Sterre de Jonge, Elisabeth J. Vinke, Meike W. Vernooij et al.

Disease progression modeling provides a robust framework to identify long-term disease trajectories from short-term biomarker data. It is a valuable tool to gain a deeper understanding of diseases with a long disease trajectory, such as Alzheimer's disease. A key limitation of most disease progression models is that they are specific to a single data type (e.g., continuous data), thereby limiting their applicability to heterogeneous, real-world datasets. To address this limitation, we propose the Mixed Events model, a novel disease progression model that handles both discrete and continuous data types. This model is implemented within the Subtype and Stage Inference (SuStaIn) framework, resulting in Mixed-SuStaIn, enabling subtype and progression modeling. We demonstrate the effectiveness of Mixed-SuStaIn through simulation experiments and real-world data from the Alzheimer's Disease Neuroimaging Initiative, showing that it performs well on mixed datasets. The code is available at: https://github.com/ucl-pond/pySuStaIn.

Peirong Liu, Oula Puonti, Xiaoling Hu et al.

Recent learning-based approaches have made astonishing advances in calibrated medical imaging like computerized tomography (CT), yet they struggle to generalize in uncalibrated modalities -- notably magnetic resonance (MR) imaging, where performance is highly sensitive to the differences in MR contrast, resolution, and orientation. This prevents broad applicability to diverse real-world clinical protocols. We introduce Brain-ID, an anatomical representation learning model for brain imaging. With the proposed "mild-to-severe" intra-subject generation, Brain-ID is robust to the subject-specific brain anatomy regardless of the appearance of acquired images (e.g., contrast, deformation, resolution, artifacts). Trained entirely on synthetic data, Brain-ID readily adapts to various downstream tasks through only one layer. We present new metrics to validate the intra- and inter-subject robustness of Brain-ID features, and evaluate their performance on four downstream applications, covering contrast-independent (anatomy reconstruction/contrast synthesis, brain segmentation), and contrast-dependent (super-resolution, bias field estimation) tasks. Extensive experiments on six public datasets demonstrate that Brain-ID achieves state-of-the-art performance in all tasks on different MRI modalities and CT, and more importantly, preserves its performance on low-resolution and small datasets. Code is available at https://github.com/peirong26/Brain-ID.

Yaozhi Lu, Shahab Aslani, An Zhao et al.

In this study, we present a hybrid CNN-RNN approach to investigate long-term survival of subjects in a lung cancer screening study. Subjects who died of cardiovascular and respiratory causes were identified whereby the CNN model was used to capture imaging features in the CT scans and the RNN model was used to investigate time series and thus global information. The models were trained on subjects who underwent cardiovascular and respiratory deaths and a control cohort matched to participant age, gender, and smoking history. The combined model can achieve an AUC of 0.76 which outperforms humans at cardiovascular mortality prediction. The corresponding F1 and Matthews Correlation Coefficient are 0.63 and 0.42 respectively. The generalisability of the model is further validated on an 'external' cohort. The same models were applied to survival analysis with the Cox Proportional Hazard model. It was demonstrated that incorporating the follow-up history can lead to improvement in survival prediction. The Cox neural network can achieve an IPCW C-index of 0.75 on the internal dataset and 0.69 on an external dataset. Delineating imaging features associated with long-term survival can help focus preventative interventions appropriately, particularly for under-recognised pathologies thereby potentially reducing patient morbidity.

Stefano B. Blumberg, Hongxiang Lin, Francesco Grussu et al.

We present PROSUB: PROgressive SUBsampling, a deep learning based, automated methodology that subsamples an oversampled data set (e.g. multi-channeled 3D images) with minimal loss of information. We build upon a recent dual-network approach that won the MICCAI MUlti-DIffusion (MUDI) quantitative MRI measurement sampling-reconstruction challenge, but suffers from deep learning training instability, by subsampling with a hard decision boundary. PROSUB uses the paradigm of recursive feature elimination (RFE) and progressively subsamples measurements during deep learning training, improving optimization stability. PROSUB also integrates a neural architecture search (NAS) paradigm, allowing the network architecture hyperparameters to respond to the subsampling process. We show PROSUB outperforms the winner of the MUDI MICCAI challenge, producing large improvements >18% MSE on the MUDI challenge sub-tasks and qualitative improvements on downstream processes useful for clinical applications. We also show the benefits of incorporating NAS and analyze the effect of PROSUB's components. As our method generalizes to other problems beyond MRI measurement selection-reconstruction, our code is https://github.com/sbb-gh/PROSUB

Daniele Ravi, Frederik Barkhof, Daniel C. Alexander et al.

Large medical imaging data sets are becoming increasingly available, but ensuring sample quality without significant artefacts is challenging. Existing methods for identifying imperfections in medical imaging rely on data-intensive approaches, compounded by a scarcity of artefact-rich scans for training machine learning models in clinical research. To tackle this problem, we propose a framework with four main components: 1) artefact generators inspired by magnetic resonance physics to corrupt brain MRI scans and augment a training dataset, 2) abstract and engineered features to represent images compactly, 3) a feature selection process depending on the artefact class to improve classification, and 4) SVM classifiers to identify artefacts. Our contributions are threefold: first, physics-based artefact generators produce synthetic brain MRI scans with controlled artefacts for data augmentation. This will avoid the labour-intensive collection and labelling process of scans with rare artefacts. Second, we propose a pool of abstract and engineered image features to identify 9 different artefacts for structural MRI. Finally, we use an artefact-based feature selection block that, for each class of artefacts, finds the set of features providing the best classification performance. We performed validation experiments on a large data set of scans with artificially-generated artefacts, and in a multiple sclerosis clinical trial where real artefacts were identified by experts, showing that the proposed pipeline outperforms traditional methods. In particular, our data augmentation increases performance by up to 12.5 percentage points on accuracy, precision, and recall. The computational efficiency of our pipeline enables potential real-time deployment, promising high-throughput clinical applications through automated image-processing pipelines driven by quality control systems.

Lemuel Puglisi, Frederik Barkhof, Daniel C. Alexander et al.

Recent advances in MRI have led to the creation of large datasets. With the increase in data volume, it has become difficult to locate previous scans of the same patient within these datasets (a process known as re-identification). To address this issue, we propose an AI-powered medical imaging retrieval framework called DeepBrainPrint, which is designed to retrieve brain MRI scans of the same patient. Our framework is a semi-self-supervised contrastive deep learning approach with three main innovations. First, we use a combination of self-supervised and supervised paradigms to create an effective brain fingerprint from MRI scans that can be used for real-time image retrieval. Second, we use a special weighting function to guide the training and improve model convergence. Third, we introduce new imaging transformations to improve retrieval robustness in the presence of intensity variations (i.e. different scan contrasts), and to account for age and disease progression in patients. We tested DeepBrainPrint on a large dataset of T1-weighted brain MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and on a synthetic dataset designed to evaluate retrieval performance with different image modalities. Our results show that DeepBrainPrint outperforms previous methods, including simple similarity metrics and more advanced contrastive deep learning frameworks.

Wing Keung Cheung, Ashkan Pakzad, Nesrin Mogulkoc et al.

The morphology and distribution of airway tree abnormalities enables diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. In this study, we propose a data-centric deep learning technique to segment the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway trees at different scales. In terms of segmentation performance (dice similarity coefficient), our method outperforms the baseline model by 2.5% on average when a combined loss is used. Further, our proposed technique has a low GPU usage and high flexibility enabling it to be deployed on any 2D deep learning model.

Seunghoi Kim, Henry F. J. Tregidgo, Ahmed K. Eldaly et al.

Low-field (LF) MRI scanners (<1T) are still prevalent in settings with limited resources or unreliable power supply. However, they often yield images with lower spatial resolution and contrast than high-field (HF) scanners. This quality disparity can result in inaccurate clinician interpretations. Image Quality Transfer (IQT) has been developed to enhance the quality of images by learning a mapping function between low and high-quality images. Existing IQT models often fail to restore high-frequency features, leading to blurry output. In this paper, we propose a 3D conditional diffusion model to improve 3D volumetric data, specifically LF MR images. Additionally, we incorporate a cross-batch mechanism into the self-attention and padding of our network, ensuring broader contextual awareness even under small 3D patches. Experiments on the publicly available Human Connectome Project (HCP) dataset for IQT and brain parcellation demonstrate that our model outperforms existing methods both quantitatively and qualitatively. The code is publicly available at \url{https://github.com/edshkim98/DiffusionIQT}.

Christopher S. Parker, Anna Schroder, Sean C. Epstein et al.

Purpose: Previous quantitative MR imaging studies using self-supervised deep learning have reported biased parameter estimates at low SNR. Such systematic errors arise from the choice of Mean Squared Error (MSE) loss function for network training, which is incompatible with Rician-distributed MR magnitude signals. To address this issue, we introduce the negative log Rician likelihood (NLR) loss. Methods: A numerically stable and accurate implementation of the NLR loss was developed to estimate quantitative parameters of the apparent diffusion coefficient (ADC) model and intra-voxel incoherent motion (IVIM) model. Parameter estimation accuracy, precision and overall error were evaluated in terms of bias, variance and root mean squared error and compared against the MSE loss over a range of SNRs (5 - 30). Results: Networks trained with NLR loss show higher estimation accuracy than MSE for the ADC and IVIM diffusion coefficients as SNR decreases, with minimal loss of precision or total error. At high effective SNR (high SNR and small diffusion coefficients), both losses show comparable accuracy and precision for all parameters of both models. Conclusion: The proposed NLR loss is numerically stable and accurate across the full range of tested SNRs and improves parameter estimation accuracy of diffusion coefficients using self-supervised deep learning. We expect the development to benefit quantitative MR imaging techniques broadly, enabling more accurate parameter estimation from noisy data.

Stefano B. Blumberg, Paddy J. Slator, Daniel C. Alexander

This paper presents a data-driven, task-specific paradigm for experimental design, to shorten acquisition time, reduce costs, and accelerate the deployment of imaging devices. Current approaches in experimental design focus on model-parameter estimation and require specification of a particular model, whereas in imaging, other tasks may drive the design. Furthermore, such approaches often lead to intractable optimization problems in real-world imaging applications. Here we present a new paradigm for experimental design that simultaneously optimizes the design (set of image channels) and trains a machine-learning model to execute a user-specified image-analysis task. The approach obtains data densely-sampled over the measurement space (many image channels) for a small number of acquisitions, then identifies a subset of channels of prespecified size that best supports the task. We propose a method: TADRED for TAsk-DRiven Experimental Design in imaging, to identify the most informative channel-subset whilst simultaneously training a network to execute the task given the subset. Experiments demonstrate the potential of TADRED in diverse imaging applications: several clinically-relevant tasks in magnetic resonance imaging; and remote sensing and physiological applications of hyperspectral imaging. Results show substantial improvement over classical experimental design, two recent application-specific methods within the new paradigm, and state-of-the-art approaches in supervised feature selection. We anticipate further applications of our approach. Code is available: https://github.com/sbb-gh/experimental-design-multichannel

Wing Keung Cheung, Jeremy Kalindjian, Robert Bell et al.

Early detection and diagnosis of coronary artery disease (CAD) could save lives and reduce healthcare costs. The current clinical practice is to perform CAD diagnosis through analysing medical images from computed tomography coronary angiography (CTCA). Most current approaches utilise deep learning methods but require centerline extraction and multi-planar reconstruction. These indirect methods are not designed in a clinician-friendly manner, and they complicate the interventional procedure. Furthermore, the current deep learning methods do not provide exact explainability and limit the usefulness of these methods to be deployed in clinical settings. In this study, we first propose a 3D Resnet-50 deep learning model to directly classify normal subjects and CAD patients on CTCA images, then we demonstrate a 2D modified U-Net model can be subsequently employed to segment the coronary arteries. Our proposed approach outperforms the state-of-the-art models by 21.43% in terms of classification accuracy. The classification model with focal loss provides a better and more focused heat map, and the segmentation model provides better explainability than the classification-only model. The proposed holistic approach not only provides a simpler and clinician-friendly solution but also good classification accuracy and exact explainability for CAD diagnosis.

Mou-Cheng Xu, Yu-Kun Zhou, Chen Jin et al.

We propose MisMatch, a novel consistency-driven semi-supervised segmentation framework which produces predictions that are invariant to learnt feature perturbations. MisMatch consists of an encoder and a two-head decoders. One decoder learns positive attention to the foreground regions of interest (RoI) on unlabelled images thereby generating dilated features. The other decoder learns negative attention to the foreground on the same unlabelled images thereby generating eroded features. We then apply a consistency regularisation on the paired predictions. MisMatch outperforms state-of-the-art semi-supervised methods on a CT-based pulmonary vessel segmentation task and a MRI-based brain tumour segmentation task. In addition, we show that the effectiveness of MisMatch comes from better model calibration than its supervised learning counterpart.

Mou-Cheng Xu, Yukun Zhou, Chen Jin et al.

This paper concerns pseudo labelling in segmentation. Our contribution is fourfold. Firstly, we present a new formulation of pseudo-labelling as an Expectation-Maximization (EM) algorithm for clear statistical interpretation. Secondly, we propose a semi-supervised medical image segmentation method purely based on the original pseudo labelling, namely SegPL. We demonstrate SegPL is a competitive approach against state-of-the-art consistency regularisation based methods on semi-supervised segmentation on a 2D multi-class MRI brain tumour segmentation task and a 3D binary CT lung vessel segmentation task. The simplicity of SegPL allows less computational cost comparing to prior methods. Thirdly, we demonstrate that the effectiveness of SegPL may originate from its robustness against out-of-distribution noises and adversarial attacks. Lastly, under the EM framework, we introduce a probabilistic generalisation of SegPL via variational inference, which learns a dynamic threshold for pseudo labelling during the training. We show that SegPL with variational inference can perform uncertainty estimation on par with the gold-standard method Deep Ensemble.

Yukun Zhou, Moucheng Xu, Yipeng Hu et al.

Estimating clinically-relevant vascular features following vessel segmentation is a standard pipeline for retinal vessel analysis, which provides potential ocular biomarkers for both ophthalmic disease and systemic disease. In this work, we integrate these clinical features into a novel vascular feature optimised loss function (VAFO-Loss), in order to regularise networks to produce segmentation maps, with which more accurate vascular features can be derived. Two common vascular features, vessel density and fractal dimension, are identified to be sensitive to intra-segment misclassification, which is a well-recognised problem in multi-class artery/vein segmentation particularly hindering the estimation of these vascular features. Thus we encode these two features into VAFO-Loss. We first show that incorporating our end-to-end VAFO-Loss in standard segmentation networks indeed improves vascular feature estimation, yielding quantitative improvement in stroke incidence prediction, a clinical downstream task. We also report a technically interesting finding that the trained segmentation network, albeit biased by the feature optimised loss VAFO-Loss, shows statistically significant improvement in segmentation metrics, compared to those trained with other state-of-the-art segmentation losses.

Stefano B. Blumberg, Daniele Raví, Mou-Cheng Xu et al.

Transposed convolution is crucial for generating high-resolution outputs, yet has received little attention compared to convolution layers. In this work we revisit transposed convolution and introduce a novel layer that allows us to place information in the image selectively and choose the `stroke breadth' at which the image is synthesized, whilst incurring a small additional parameter cost. For this we introduce three ideas: firstly, we regress offsets to the positions where the transpose convolution results are placed; secondly we broadcast the offset weight locations over a learnable neighborhood; and thirdly we use a compact parametrization to share weights and restrict offsets. We show that simply substituting upsampling operators with our novel layer produces substantial improvements across tasks as diverse as instance segmentation, object detection, semantic segmentation, generative image modeling, and 3D magnetic resonance image enhancement, while outperforming all existing variants of transposed convolutions. Our novel layer can be used as a drop-in replacement for 2D and 3D upsampling operators and the code will be publicly available.

Yipei Wang, Yinsong Xu, Weixi Yi et al.

Many diagnostic and therapeutic clinical tasks for prostate cancer increasingly rely on multi-parametric MRI. Automating these tasks is challenging because they necessitate expert interpretations, which are difficult to scale to capitalise on modern deep learning. Although modern automated systems achieve expert-level performance in isolated tasks, their general clinical utility remains limited by the requirement of large task-specific labelled datasets. In this paper, we present ProFound, a domain-specialised vision foundation model for volumetric prostate mpMRI. ProFound is pre-trained using several variants of self-supervised approaches on a diverse, multi-institutional collection of 5,000 patients, with a total of over 22,000 unique 3D MRI volumes (over 1,800,000 2D image slices). We conducted a systematic evaluation of ProFound across a broad spectrum of $11$ downstream clinical tasks on over 3,000 independent patients, including prostate cancer detection, Gleason grading, lesion localisation, gland volume estimation, zonal and surrounding structure segmentation. Experimental results demonstrate that finetuned ProFound consistently outperforms or remains competitive with state-of-the-art specialised models and existing medical vision foundation models trained/finetuned on the same data.

Ahmed H. Shahin, Joseph Jacob, Daniel C. Alexander et al.

Idiopathic Pulmonary Fibrosis (IPF) is an inexorably progressive fibrotic lung disease with a variable and unpredictable rate of progression. CT scans of the lungs inform clinical assessment of IPF patients and contain pertinent information related to disease progression. In this work, we propose a multi-modal method that uses neural networks and memory banks to predict the survival of IPF patients using clinical and imaging data. The majority of clinical IPF patient records have missing data (e.g. missing lung function tests). To this end, we propose a probabilistic model that captures the dependencies between the observed clinical variables and imputes missing ones. This principled approach to missing data imputation can be naturally combined with a deep survival analysis model. We show that the proposed framework yields significantly better survival analysis results than baselines in terms of concordance index and integrated Brier score. Our work also provides insights into novel image-based biomarkers that are linked to mortality.

Lemuel Puglisi, Daniel C. Alexander, Daniele Ravì

The growing availability of longitudinal Magnetic Resonance Imaging (MRI) datasets has facilitated Artificial Intelligence (AI)-driven modeling of disease progression, making it possible to predict future medical scans for individual patients. However, despite significant advancements in AI, current methods continue to face challenges including achieving patient-specific individualization, ensuring spatiotemporal consistency, efficiently utilizing longitudinal data, and managing the substantial memory demands of 3D scans. To address these challenges, we propose Brain Latent Progression (BrLP), a novel spatiotemporal model designed to predict individual-level disease progression in 3D brain MRIs. The key contributions in BrLP are fourfold: (i) it operates in a small latent space, mitigating the computational challenges posed by high-dimensional imaging data; (ii) it explicitly integrates subject metadata to enhance the individualization of predictions; (iii) it incorporates prior knowledge of disease dynamics through an auxiliary model, facilitating the integration of longitudinal data; and (iv) it introduces the Latent Average Stabilization (LAS) algorithm, which (a) enforces spatiotemporal consistency in the predicted progression at inference time and (b) allows us to derive a measure of the uncertainty for the prediction at the global and voxel level. We train and evaluate BrLP on 11,730 T1-weighted (T1w) brain MRIs from 2,805 subjects and validate its generalizability on an external test set comprising 2,257 MRIs from 962 subjects. Our experiments compare BrLP-generated MRI scans with real follow-up MRIs, demonstrating state-of-the-art accuracy compared to existing methods. The code is publicly available at: https://github.com/LemuelPuglisi/BrLP.

Ahmed Karam Eldaly, Matteo Figini, Daniel C. Alexander

We propose a novel framework for joint magnetic resonance image reconstruction and uncertainty quantification using under-sampled k-space measurements. The problem is formulated as a Bayesian linear inverse problem, where prior distributions are assigned to the unknown model parameters. Specifically, we assume the target image is sparse in its spatial gradient and impose a total variation prior model. A Markov chain Monte Carlo (MCMC) method, based on a split-and-augmented Gibbs sampler, is then used to sample from the resulting joint posterior distribution of the unknown parameters. Experiments conducted using single- and multi-coil datasets demonstrate the superior performance of the proposed framework over optimisation-based compressed sensing algorithms. Additionally, our framework effectively quantifies uncertainty, showing strong correlation with error maps computed from reconstructed and ground-truth images.

Shahab Aslani, Mehran Azimbagirad, Daryl Cheng et al.

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening populations remains unclear. We investigated whether longitudinal change in PPFE quantified on low dose CT independently associates with mortality and respiratory morbidity. Methods: We analysed longitudinal low-dose CT scans and clinical data from two lung cancer screening studies: the National Lung Screening Trial (NLST; n=7980) and the SUMMIT study (n=8561). An automated algorithm quantified PPFE volume on baseline and follow up scans. Annualised change in PPFE (dPPFE) was derived and dichotomised using a distribution based threshold to define progressive PPFE. Associations between dPPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In the SUMMIT cohort, dPPFE was also examined in relation to clinical outcomes. Findings: dPPFE independently associated with mortality in both cohorts (NLST: HR 1.25, 95% CI 1.01-1.56, p=0.042; SUMMIT: HR 3.14, 95% CI 1.66-5.97, p<0.001). Kaplan-Meier curves showed reduced survival among participants with progressive PPFE in both cohorts. In SUMMIT, dPPFE was associated with higher respiratory admissions (IRR 2.79, p<0.001), increased antibiotic and steroid use (IRR 1.55, p=0.010), and a trend towards higher mMRC scores (OR 1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large lung cancer screening cohorts and with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker for identifying individuals at increased respiratory risk within screening programmes.

Tiantian He, An Zhao, Elinor Thompson et al.

Understanding the interactions between biomarkers among brain regions during neurodegenerative disease is essential for unravelling the mechanisms underlying disease progression. For example, pathophysiological models of Alzheimer's Disease (AD) typically describe how variables, such as regional levels of toxic proteins, interact spatiotemporally within a dynamical system driven by an underlying biological substrate, often based on brain connectivity. However, current methods grossly oversimplify the complex relationship between brain connectivity by assuming a single-modality brain connectome as the disease-spreading substrate. This leads to inaccurate predictions of pathology spread, especially during the long-term progression period. Meanhwile, other methods of learning such a graph in a purely data-driven way face the identifiability issue due to lack of proper constraint. We thus present a novel framework that uses Large Language Models (LLMs) as expert guides on the interaction of regional variables to enhance learning of disease progression from irregularly sampled longitudinal patient data. By leveraging LLMs' ability to synthesize multi-modal relationships and incorporate diverse disease-driving mechanisms, our method simultaneously optimizes 1) the construction of long-term disease trajectories from individual-level observations and 2) the biologically-constrained graph structure that captures interactions among brain regions with better identifiability. We demonstrate the new approach by estimating the pathology propagation using tau-PET imaging data from an Alzheimer's disease cohort. The new framework demonstrates superior prediction accuracy and interpretability compared to traditional approaches while revealing additional disease-driving factors beyond conventional connectivity measures.

Seunghoi Kim, Chen Jin, Henry F. J. Tregidgo et al.

Zero-shot MRI reconstruction relies on generative priors, but single-modality unconditional priors produce hallucinations under severe ill-posedness. In many clinical workflows, complementary MRI acquisitions (e.g. high-quality structural scans) are routinely available, yet existing reconstruction methods lack mechanisms to leverage this additional information. We propose MPFlow, a zero-shot multi-modal reconstruction framework built on rectified flow that incorporates auxiliary MRI modalities at inference time without retraining the generative prior to improve anatomical fidelity. Cross-modal guidance is enabled by our proposed self-supervised pretraining strategy, Patch-level Multi-modal MR Image Pretraining (PAMRI), which learns shared representations across modalities. Sampling is jointly guided by data consistency and cross-modal feature alignment using pre-trained PAMRI, systematically suppressing intrinsic and extrinsic hallucinations. Extensive experiments on HCP and BraTS show that MPFlow matches diffusion baselines on image quality using only 20% of sampling steps while reducing tumor hallucinations by more than 15% (segmentation dice score). This demonstrates that cross-modal guidance enables more reliable and efficient zero-shot MRI reconstruction.

Peirong Liu, Oula Puonti, Xiaoling Hu et al.

Recent learning-based approaches have made astonishing advances in calibrated medical imaging like computerized tomography (CT), yet they struggle to generalize in uncalibrated modalities -- notably magnetic resonance (MR) imaging, where performance is highly sensitive to the differences in MR contrast, resolution, and orientation. This prevents broad applicability to diverse real-world clinical protocols. Here we introduce BrainFM, a modality-agnostic, multi-task vision foundation model for human brain imaging. With the proposed "mild-to-severe" intra-subject generation and "real-synth" mix-up training strategy, BrainFM is resilient to the appearance of acquired images (e.g., modality, contrast, deformation, resolution, artifacts), and can be directly applied to five fundamental brain imaging tasks, including image synthesis for CT and T1w/T2w/FLAIR MRI, anatomy segmentation, scalp-to-cortical distance, bias field estimation, and registration. We evaluate the efficacy of BrainFM on eleven public datasets, and demonstrate its robustness and effectiveness across all tasks and input modalities. Code is available at https://github.com/jhuldr/BrainFM.

Alec Sargood, Lemuel Puglisi, James H. Cole et al.

Synthesizing amyloid PET scans from the more widely available and accessible structural MRI modality offers a promising, cost-effective approach for large-scale Alzheimer's Disease (AD) screening. This is motivated by evidence that, while MRI does not directly detect amyloid pathology, it may nonetheless encode information correlated with amyloid deposition that can be uncovered through advanced modeling. However, the high dimensionality and structural complexity of 3D neuroimaging data pose significant challenges for existing MRI-to-PET translation methods. Modeling the cross-modality relationship in a lower-dimensional latent space can simplify the learning task and enable more effective translation. As such, we present CoCoLIT (ControlNet-Conditioned Latent Image Translation), a diffusion-based latent generative framework that incorporates three main innovations: (1) a novel Weighted Image Space Loss (WISL) that improves latent representation learning and synthesis quality; (2) a theoretical and empirical analysis of Latent Average Stabilization (LAS), an existing technique used in similar generative models to enhance inference consistency; and (3) the introduction of ControlNet-based conditioning for MRI-to-PET translation. We evaluate CoCoLIT's performance on publicly available datasets and find that our model significantly outperforms state-of-the-art methods on both image-based and amyloid-related metrics. Notably, in amyloid-positivity classification, CoCoLIT outperforms the second-best method with improvements of +10.5% on the internal dataset and +23.7% on the external dataset. The code and models of our approach are available at https://github.com/brAIn-science/CoCoLIT.

Seunghoi Kim, Henry F. J. Tregidgo, Chen Jin et al.

Generative models are prone to hallucinations: plausible but incorrect structures absent in the ground truth. This issue is problematic in image restoration for safety-critical domains such as medical imaging, industrial inspection, and remote sensing, where such errors undermine reliability and trust. For example, in low-field MRI, widely used in resource-limited settings, restoration models are essential for enhancing low-quality scans, yet hallucinations can lead to serious diagnostic errors. Progress has been hindered by a circular dependency: evaluating hallucinations requires labeled data, yet such labels are costly and subjective. We introduce HalluGen, a diffusion-based framework that synthesizes realistic hallucinations with controllable type, location, and severity, producing perceptually realistic but semantically incorrect outputs (segmentation IoU drops from 0.86 to 0.36). Using HalluGen, we construct the first large-scale hallucination dataset comprising 4,350 annotated images derived from 1,450 brain MR images for low-field enhancement, enabling systematic evaluation of hallucination detection and mitigation. We demonstrate its utility in two applications: (1) benchmarking image quality metrics and developing Semantic Hallucination Assessment via Feature Evaluation (SHAFE), a feature-based metric with soft-attention pooling that improves hallucination sensitivity over traditional metrics; and (2) training reference-free hallucination detectors that generalize to real restoration failures. Together, HalluGen and its open dataset establish the first scalable foundation for evaluating hallucinations in safety-critical image restoration.

Tianshu Zheng, Zican Wang, Timothy Bray et al.

Quantitative magnetic resonance imaging (qMRI) is increasingly investigated for use in a variety of clinical tasks from diagnosis, through staging, to treatment monitoring. However, experiment design in qMRI, the identification of the optimal acquisition protocols, has been focused on obtaining the most precise parameter estimations, with no regard for the specific requirements of downstream tasks. Here we propose SCREENER: A general framework for task-specific experiment design in quantitative MRI. SCREENER incorporates a task-specific objective and seeks the optimal protocol with a deep-reinforcement-learning (DRL) based optimization strategy. To illustrate this framework, we employ a task of classifying the inflammation status of bone marrow using diffusion MRI data with intravoxel incoherent motion (IVIM) modelling. Results demonstrate SCREENER outperforms previous ad hoc and optimized protocols under clinical signal-to-noise ratio (SNR) conditions, achieving significant improvement, both in binary classification tasks, e.g. from 67% to 89%, and in a multi-class classification task, from 46% to 59%. Additionally, we show this improvement is robust to the SNR. Lastly, we demonstrate the advantage of DRL-based optimization strategy, enabling zero-shot discovery of near-optimal protocols for a range of SNRs not used in training. In conclusion, SCREENER has the potential to enable wider uptake of qMRI in the clinic.

Junkai Liu, Nay Aung, Theodoros N. Arvanitis et al.

Missing data problems, such as missing modalities in multi-modal brain MRI and missing slices in cardiac MRI, pose significant challenges in clinical practice. Existing methods rely on external guidance to supply detailed missing state for instructing generative models to synthesize missing MRIs. However, manual indicators are not always available or reliable in real-world scenarios due to the unpredictable nature of clinical environments. Moreover, these explicit masks are not informative enough to provide guidance for improving semantic consistency. In this work, we argue that generative models should infer and recognize missing states in a self-perceptive manner, enabling them to better capture subtle anatomical and pathological variations. Towards this goal, we propose CoPeDiT, a general-purpose latent diffusion model equipped with completeness perception for unified synthesis of 3D MRIs. Specifically, we incorporate dedicated pretext tasks into our tokenizer, CoPeVAE, empowering it to learn completeness-aware discriminative prompts, and design MDiT3D, a specialized diffusion transformer architecture for 3D MRI synthesis, that effectively uses the learned prompts as guidance to enhance semantic consistency in 3D space. Comprehensive evaluations on three large-scale MRI datasets demonstrate that CoPeDiT significantly outperforms state-of-the-art methods, achieving superior robustness, generalizability, and flexibility. The code is available at https://github.com/JK-Liu7/CoPeDiT .

Yucheng Tang, Yunguan Fu, Weixi Yi et al.

Multimodal large language models (MLLMs) can process and integrate information from multimodality sources, such as text and images. However, interrelationship among input modalities, uncertainties due to individual uni-modal data and potential clinical applications following such an uncertainty decomposition are yet fully understood in the context of large-scale MLLMs. In this work, we propose a multimodal uncertainty propagation model (MUPM) based on uncertainty propagation, to characterise the relationship among the uncertainties arising from image-only, text-only, and joint image-text variations in MLLM inputs. Using real clinical data consisting of cardiac MR scans and digital health records, we describe that MUPMs can be optimised robustly with a few samples. We then show that the fitted MUPMs are generalisable across different input data distributions and, perhaps surprisingly, across different downstream tasks. Such a transferability may be explained by the shared pretraining, comparatively light MLLM fine-tuning, along with the low-dimensional nature of the MUPMs. More importantly, this learned transferability, quantifying the relationship between these uncertainties, led to direct clinical applications in which uncertainties may be estimated and thus analysed robustly for varying data or even a novel set of cardiac disease prediction tasks. In addition, we show experimentally the efficiency in multimodal data required for estimating the overall uncertainty and its ability to identify redundant factors, both of which are considered practical yet clinically useful applications with the proposed MUPMs. Codes are available at https://github.com/yucheng722/MUPM.

Niccolò McConnell, Pardeep Vasudev, Daisuke Yamada et al.

Low-dose computed tomography (LDCT) imaging employed in lung cancer screening (LCS) programs is increasing in uptake worldwide. LCS programs herald a generational opportunity to simultaneously detect cancer and non-cancer-related early-stage lung disease. Yet these efforts are hampered by a shortage of radiologists to interpret scans at scale. Here, we present TANGERINE, a computationally frugal, open-source vision foundation model for volumetric LDCT analysis. Designed for broad accessibility and rapid adaptation, TANGERINE can be fine-tuned off the shelf for a wide range of disease-specific tasks with limited computational resources and training data. Relative to models trained from scratch, TANGERINE demonstrates fast convergence during fine-tuning, thereby requiring significantly fewer GPU hours, and displays strong label efficiency, achieving comparable or superior performance with a fraction of fine-tuning data. Pretrained using self-supervised learning on over 98,000 thoracic LDCTs, including the UK's largest LCS initiative to date and 27 public datasets, TANGERINE achieves state-of-the-art performance across 14 disease classification tasks, including lung cancer and multiple respiratory diseases, while generalising robustly across diverse clinical centres. By extending a masked autoencoder framework to 3D imaging, TANGERINE offers a scalable solution for LDCT analysis, departing from recent closed, resource-intensive models by combining architectural simplicity, public availability, and modest computational requirements. Its accessible, open-source lightweight design lays the foundation for rapid integration into next-generation medical imaging tools that could transform LCS initiatives, allowing them to pivot from a singular focus on lung cancer detection to comprehensive respiratory disease management in high-risk populations.

Lemuel Puglisi, Daniel C. Alexander, Daniele Ravì

In this work, we introduce Brain Latent Progression (BrLP), a novel spatiotemporal disease progression model based on latent diffusion. BrLP is designed to predict the evolution of diseases at the individual level on 3D brain MRIs. Existing deep generative models developed for this task are primarily data-driven and face challenges in learning disease progressions. BrLP addresses these challenges by incorporating prior knowledge from disease models to enhance the accuracy of predictions. To implement this, we propose to integrate an auxiliary model that infers volumetric changes in various brain regions. Additionally, we introduce Latent Average Stabilization (LAS), a novel technique to improve spatiotemporal consistency of the predicted progression. BrLP is trained and evaluated on a large dataset comprising 11,730 T1-weighted brain MRIs from 2,805 subjects, collected from three publicly available, longitudinal Alzheimer's Disease (AD) studies. In our experiments, we compare the MRI scans generated by BrLP with the actual follow-up MRIs available from the subjects, in both cross-sectional and longitudinal settings. BrLP demonstrates significant improvements over existing methods, with an increase of 22% in volumetric accuracy across AD-related brain regions and 43% in image similarity to the ground-truth scans. The ability of BrLP to generate conditioned 3D scans at the subject level, along with the novelty of integrating prior knowledge to enhance accuracy, represents a significant advancement in disease progression modeling, opening new avenues for precision medicine. The code of BrLP is available at the following link: https://github.com/LemuelPuglisi/BrLP.

Ahmed H. Shahin, An Zhao, Alexander C. Whitehead et al.

Survival analysis is a valuable tool for estimating the time until specific events, such as death or cancer recurrence, based on baseline observations. This is particularly useful in healthcare to prognostically predict clinically important events based on patient data. However, existing approaches often have limitations; some focus only on ranking patients by survivability, neglecting to estimate the actual event time, while others treat the problem as a classification task, ignoring the inherent time-ordered structure of the events. Furthermore, the effective utilization of censored samples - training data points where the exact event time is unknown - is essential for improving the predictive accuracy of the model. In this paper, we introduce CenTime, a novel approach to survival analysis that directly estimates the time to event. Our method features an innovative event-conditional censoring mechanism that performs robustly even when uncensored data is scarce. We demonstrate that our approach forms a consistent estimator for the event model parameters, even in the absence of uncensored data. Furthermore, CenTime is easily integrated with deep learning models with no restrictions on batch size or the number of uncensored samples. We compare our approach with standard survival analysis methods, including the Cox proportional-hazard model and DeepHit. Our results indicate that CenTime offers state-of-the-art performance in predicting time-to-death while maintaining comparable ranking performance. Our implementation is publicly available at https://github.com/ahmedhshahin/CenTime.

Moucheng Xu, Yukun Zhou, Chen Jin et al.

In this paper, we study pseudo-labelling. Pseudo-labelling employs raw inferences on unlabelled data as pseudo-labels for self-training. We elucidate the empirical successes of pseudo-labelling by establishing a link between this technique and the Expectation Maximisation algorithm. Through this, we realise that the original pseudo-labelling serves as an empirical estimation of its more comprehensive underlying formulation. Following this insight, we present a full generalisation of pseudo-labels under Bayes' theorem, termed Bayesian Pseudo Labels. Subsequently, we introduce a variational approach to generate these Bayesian Pseudo Labels, involving the learning of a threshold to automatically select high-quality pseudo labels. In the remainder of the paper, we showcase the applications of pseudo-labelling and its generalised form, Bayesian Pseudo-Labelling, in the semi-supervised segmentation of medical images. Specifically, we focus on: 1) 3D binary segmentation of lung vessels from CT volumes; 2) 2D multi-class segmentation of brain tumours from MRI volumes; 3) 3D binary segmentation of whole brain tumours from MRI volumes; and 4) 3D binary segmentation of prostate from MRI volumes. We further demonstrate that pseudo-labels can enhance the robustness of the learned representations. The code is released in the following GitHub repository: https://github.com/moucheng2017/EMSSL

Ashkan Pakzad, Wing Keung Cheung, Kin Quan et al.

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

Yukun Zhou, Moucheng Xu, Yipeng Hu et al.

Accurate multi-class segmentation is a long-standing challenge in medical imaging, especially in scenarios where classes share strong similarity. Segmenting retinal blood vessels in retinal photographs is one such scenario, in which arteries and veins need to be identified and differentiated from each other and from the background. Intra-segment misclassification, i.e. veins classified as arteries or vice versa, frequently occurs when arteries and veins intersect, whereas in binary retinal vessel segmentation, error rates are much lower. We thus propose a new approach that decomposes multi-class segmentation into multiple binary, followed by a binary-to-multi-class fusion network. The network merges representations of artery, vein, and multi-class feature maps, each of which are supervised by expert vessel annotation in adversarial training. A skip-connection based merging process explicitly maintains class-specific gradients to avoid gradient vanishing in deep layers, to favor the discriminative features. The results show that, our model respectively improves F1-score by 4.4\%, 5.1\%, and 4.2\% compared with three state-of-the-art deep learning based methods on DRIVE-AV, LES-AV, and HRF-AV data sets. Code: https://github.com/rmaphoh/Learning-AVSegmentation

Loic Peter, Daniel C. Alexander, Caroline Magnain et al.

Landmark correspondences are a widely used type of gold standard in image registration. However, the manual placement of corresponding points is subject to high inter-user variability in the chosen annotated locations and in the interpretation of visual ambiguities. In this paper, we introduce a principled strategy for the construction of a gold standard in deformable registration. Our framework: (i) iteratively suggests the most informative location to annotate next, taking into account its redundancy with previous annotations; (ii) extends traditional pointwise annotations by accounting for the spatial uncertainty of each annotation, which can either be directly specified by the user, or aggregated from pointwise annotations from multiple experts; and (iii) naturally provides a new strategy for the evaluation of deformable registration algorithms. Our approach is validated on four different registration tasks. The experimental results show the efficacy of suggesting annotations according to their informativeness, and an improved capacity to assess the quality of the outputs of registration algorithms. In addition, our approach yields, from sparse annotations only, a dense visualization of the errors made by a registration method. The source code of our approach supporting both 2D and 3D data is publicly available at https://github.com/LoicPeter/evaluation-deformable-registration.

Juan Eugenio Iglesias, Benjamin Billot, Yael Balbastre et al.

Most existing algorithms for automatic 3D morphometry of human brain MRI scans are designed for data with near-isotropic voxels at approximately 1 mm resolution, and frequently have contrast constraints as well - typically requiring T1 scans (e.g., MP-RAGE). This limitation prevents the analysis of millions of MRI scans acquired with large inter-slice spacing ("thick slice") in clinical settings every year. The inability to quantitatively analyze these scans hinders the adoption of quantitative neuroimaging in healthcare, and precludes research studies that could attain huge sample sizes and hence greatly improve our understanding of the human brain. Recent advances in CNNs are producing outstanding results in super-resolution and contrast synthesis of MRI. However, these approaches are very sensitive to the contrast, resolution and orientation of the input images, and thus do not generalize to diverse clinical acquisition protocols - even within sites. Here we present SynthSR, a method to train a CNN that receives one or more thick-slice scans with different contrast, resolution and orientation, and produces an isotropic scan of canonical contrast (typically a 1 mm MP-RAGE). The presented method does not require any preprocessing, e.g., skull stripping or bias field correction. Crucially, SynthSR trains on synthetic input images generated from 3D segmentations, and can thus be used to train CNNs for any combination of contrasts, resolutions and orientations without high-resolution training data. We test the images generated with SynthSR in an array of common downstream analyses, and show that they can be reliably used for subcortical segmentation and volumetry, image registration (e.g., for tensor-based morphometry), and, if some image quality requirements are met, even cortical thickness morphometry. The source code is publicly available at github.com/BBillot/SynthSR.

Yunguan Fu, Nina Montaña Brown, Shaheer U. Saeed et al.

DeepReg (https://github.com/DeepRegNet/DeepReg) is a community-supported open-source toolkit for research and education in medical image registration using deep learning.

Chen Jin, Ryutaro Tanno, Moucheng Xu et al.

Segmentation of ultra-high resolution images is challenging because of their enormous size, consisting of millions or even billions of pixels. Typical solutions include dividing input images into patches of fixed size and/or down-sampling to meet memory constraints. Such operations incur information loss in the field-of-view (FoV) i.e., spatial coverage and the image resolution. The impact on segmentation performance is, however, as yet understudied. In this work, we start with a motivational experiment which demonstrates that the trade-off between FoV and resolution affects the segmentation performance on ultra-high resolution images---and furthermore, its influence also varies spatially according to the local patterns in different areas. We then introduce foveation module, a learnable "dataloader" which, for a given ultra-high resolution image, adaptively chooses the appropriate configuration (FoV/resolution trade-off) of the input patch to feed to the downstream segmentation model at each spatial location of the image. The foveation module is jointly trained with the segmentation network to maximise the task performance. We demonstrate on three publicly available high-resolution image datasets that the foveation module consistently improves segmentation performance over the cases trained with patches of fixed FoV/resolution trade-off. Our approach achieves the SoTA performance on the DeepGlobe aerial image dataset. On the Gleason2019 histopathology dataset, our model achieves better segmentation accuracy for the two most clinically important and ambiguous classes (Gleason Grade 3 and 4) than the top performers in the challenge by 13.1% and 7.5%, and improves on the average performance of 6 human experts by 6.5% and 7.5%. Our code and trained models are available at $\text{https://github.com/lxasqjc/Foveation-Segmentation}$.

Stefano B. Blumberg, Marco Palombo, Can Son Khoo et al.

In this paper, we introduce multi-task learning (MTL) to data harmonization (DH); where we aim to harmonize images across different acquisition platforms and sites. This allows us to integrate information from multiple acquisitions and improve the predictive performance and learning efficiency of the harmonization model. Specifically, we introduce the Multi Stage Prediction (MSP) Network, a MTL framework that incorporates neural networks of potentially disparate architectures, trained for different individual acquisition platforms, into a larger architecture that is refined in unison. The MSP utilizes high-level features of single networks for individual tasks, as inputs of additional neural networks to inform the final prediction, therefore exploiting redundancy across tasks to make the most of limited training data. We validate our methods on a dMRI harmonization challenge dataset, where we predict three modern platform types, from one obtained from an old scanner. We show how MTL architectures, such as the MSP, produce around 20\% improvement of patch-based mean-squared error over current state-of-the-art methods and that our MSP outperforms off-the-shelf MTL networks. Our code is available https://github.com/sbb-gh/ .

Razvan V. Marinescu, Arman Eshaghi, Marco Lorenzi et al.

Here we present DIVE: Data-driven Inference of Vertexwise Evolution. DIVE is an image-based disease progression model with single-vertex resolution, designed to reconstruct long-term patterns of brain pathology from short-term longitudinal data sets. DIVE clusters vertex-wise biomarker measurements on the cortical surface that have similar temporal dynamics across a patient population, and concurrently estimates an average trajectory of vertex measurements in each cluster. DIVE uniquely outputs a parcellation of the cortex into areas with common progression patterns, leading to a new signature for individual diseases. DIVE further estimates the disease stage and progression speed for every visit of every subject, potentially enhancing stratification for clinical trials or management. On simulated data, DIVE can recover ground truth clusters and their underlying trajectory, provided the average trajectories are sufficiently different between clusters. We demonstrate DIVE on data from two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Dementia Research Centre (DRC), UK, containing patients with Posterior Cortical Atrophy (PCA) as well as typical Alzheimer's disease (tAD). DIVE finds similar spatial patterns of atrophy for tAD subjects in the two independent datasets (ADNI and DRC), and further reveals distinct patterns of pathology in different diseases (tAD vs PCA) and for distinct types of biomarker data: cortical thickness from Magnetic Resonance Imaging (MRI) vs amyloid load from Positron Emission Tomography (PET). Finally, DIVE can be used to estimate a fine-grained spatial distribution of pathology in the brain using any kind of voxelwise or vertexwise measures including Jacobian compression maps, fractional anisotropy (FA) maps from diffusion imaging or other PET measures. DIVE source code is available online: https://github.com/mrazvan22/dive

Razvan V. Marinescu, Marco Lorenzi, Stefano B. Blumberg et al.

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.

Nicholas C. Firth, Emma Harding, Mary Pat Sullivan et al.

Smart devices have become common place in many homes, and these devices can be utilized to provide support for people with mental or physical deficits. Voice-controlled assistants are a class of smart device that collect a large amount of data in the home. In this work we present Echo SCraper and ClAssifier of Persons (ESCAPE), an open source software for the extraction of Amazon Echo interaction data, and speaker recognition on that data. We show that ESCAPE is able to extract data from a voice-controlled assistant and classify with accuracy who is talking, based on a small number of labeled audio data. Using ESCAPE to extract interactions recorded over 3 months in the first author's home yields a rich dataset of transcribed audio recordings. Our results demonstrate that using this software the Amazon Echo can be used to study participants in a naturalistic setting with minimal intrusion. We also discuss the potential for usage of voice-controlled devices together with ESCAPE to understand how diseases affect individuals, and how these data can be used to monitor disease processes in general.

Seunghoi Kim, Chen Jin, Tom Diethe et al.

Recent developments in diffusion models have advanced conditioned image generation, yet they struggle with reconstructing out-of-distribution (OOD) images, such as unseen tumors in medical images, causing "image hallucination" and risking misdiagnosis. We hypothesize such hallucinations result from local OOD regions in the conditional images. We verify that partitioning the OOD region and conducting separate image generations alleviates hallucinations in several applications. From this, we propose a training-free diffusion framework that reduces hallucination with multiple Local Diffusion processes. Our approach involves OOD estimation followed by two modules: a "branching" module generates locally both within and outside OOD regions, and a "fusion" module integrates these predictions into one. Our evaluation shows our method mitigates hallucination over baseline models quantitatively and qualitatively, reducing misdiagnosis by 40% and 25% in the real-world medical and natural image datasets, respectively. It also demonstrates compatibility with various pre-trained diffusion models.

Seunghoi Kim, Henry F. J. Tregidgo, Matteo Figini et al.

Hallucinations are spurious structures not present in the ground truth, posing a critical challenge in medical image reconstruction, especially for data-driven conditional models. We hypothesize that combining an unconditional diffusion model with data consistency, trained on a diverse dataset, can reduce these hallucinations. Based on this, we propose DynamicDPS, a diffusion-based framework that integrates conditional and unconditional diffusion models to enhance low-quality medical images while systematically reducing hallucinations. Our approach first generates an initial reconstruction using a conditional model, then refines it with an adaptive diffusion-based inverse problem solver. DynamicDPS skips early stage in the reverse process by selecting an optimal starting time point per sample and applies Wolfe's line search for adaptive step sizes, improving both efficiency and image fidelity. Using diffusion priors and data consistency, our method effectively reduces hallucinations from any conditional model output. We validate its effectiveness in Image Quality Transfer for low-field MRI enhancement. Extensive evaluations on synthetic and real MR scans, including a downstream task for tissue volume estimation, show that DynamicDPS reduces hallucinations, improving relative volume estimation by over 15% for critical tissues while using only 5% of the sampling steps required by baseline diffusion models. As a model-agnostic and fine-tuning-free approach, DynamicDPS offers a robust solution for hallucination reduction in medical imaging. The code will be made publicly available upon publication.

An Zhao, Moucheng Xu, Ahmed H. Shahin et al.

Understanding the progression trajectories of diseases is crucial for early diagnosis and effective treatment planning. This is especially vital for life-threatening conditions such as Idiopathic Pulmonary Fibrosis (IPF), a chronic, progressive lung disease with a prognosis comparable to many cancers. Computed tomography (CT) imaging has been established as a reliable diagnostic tool for IPF. Accurately predicting future CT scans of early-stage IPF patients can aid in developing better treatment strategies, thereby improving survival outcomes. In this paper, we propose 4D Vector Quantised Generative Adversarial Networks (4D-VQ-GAN), a model capable of generating realistic CT volumes of IPF patients at any time point. The model is trained using a two-stage approach. In the first stage, a 3D-VQ-GAN is trained to reconstruct CT volumes. In the second stage, a Neural Ordinary Differential Equation (ODE) based temporal model is trained to capture the temporal dynamics of the quantised embeddings generated by the encoder in the first stage. We evaluate different configurations of our model for generating longitudinal CT scans and compare the results against ground truth data, both quantitatively and qualitatively. For validation, we conduct survival analysis using imaging biomarkers derived from generated CT scans and achieve a C-index comparable to that of biomarkers derived from the real CT scans. The survival analysis results demonstrate the potential clinical utility inherent to generated longitudinal CT scans, showing that they can reliably predict survival outcomes.

Ahmed Karam Eldaly, Matteo Figini, Daniel C. Alexander

Image Quality Transfer (IQT) aims to enhance the contrast and resolution of low-quality medical images, e.g. obtained from low-power devices, with rich information learned from higher quality images. In contrast to existing IQT methods which adopt supervised learning frameworks, in this work, we propose two novel formulations of the IQT problem. The first approach uses an unsupervised learning framework, whereas the second is a combination of both supervised and unsupervised learning. The unsupervised learning approach considers a sparse representation (SRep) and dictionary learning model, which we call IQT-SRep, whereas the combination of supervised and unsupervised learning approach is based on deep dictionary learning (DDL), which we call IQT-DDL. The IQT-SRep approach trains two dictionaries using a SRep model using pairs of low- and high-quality volumes. Subsequently, the SRep of a low-quality block, in terms of the low-quality dictionary, can be directly used to recover the corresponding high-quality block using the high-quality dictionary. On the other hand, the IQT-DDL approach explicitly learns a high-resolution dictionary to upscale the input volume, while the entire network, including high dictionary generator, is simultaneously optimised to take full advantage of deep learning methods. The two models are evaluated using a low-field magnetic resonance imaging (MRI) application aiming to recover high-quality images akin to those obtained from high-field scanners. Experiments comparing the proposed approaches against state-of-the-art supervised deep learning IQT method (IQT-DL) identify that the two novel formulations of the IQT problem can avoid bias associated with supervised methods when tested using out-of-distribution data that differs from the distribution of the data the model was trained on. This highlights the potential benefit of these novel paradigms for IQT.

Alec Sargood, Lemuel Puglisi, Elinor Thompson et al.

Tractography is the process of inferring the trajectories of white-matter pathways in the brain from diffusion magnetic resonance imaging (dMRI). Local tractography methods, which construct streamlines by following local fiber orientation estimates stepwise through an image, are prone to error accumulation and high false positive rates, particularly on noisy or low-resolution data. In contrast, global methods, which attempt to optimize a collection of streamlines to maximize compatibility with underlying fiber orientation estimates, are computationally expensive. To address these challenges, we introduce GenTract, the first generative model for global tractography. We frame tractography as a generative task, learning a direct mapping from dMRI to complete, anatomically plausible streamlines. We compare both diffusion-based and flow matching paradigms and evaluate GenTract's performance against state-of-the-art baselines. Notably, GenTract achieves precision 2.1x higher than the next-best method, TractOracle. This advantage becomes even more pronounced in challenging low-resolution and noisy settings, where it outperforms the closest competitor by an order of magnitude. By producing tractograms with high precision on research-grade data while also maintaining reliability on imperfect, lower-resolution data, GenTract represents a promising solution for global tractography.