Enhancing Spatiotemporal Disease Progression Models via Latent Diffusion and Prior Knowledge

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.

Tackling Structural Hallucination in Image Translation with Local Diffusion

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.

Brain-ID: Learning Robust Feature Representations for Brain Imaging

Recent learning-based approaches have made astonishing advances in calibrated medical imaging like computerized tomography, yet they struggle to generalize in uncalibrated modalities -- notoriously magnetic resonance imaging (MRI), where performance is highly sensitive to the differences in MR contrast, resolution, and orientation between the training and testing data. This prevents broad applicability to the diverse clinical acquisition protocols in the real world. We introduce Brain-ID, a robust feature representation learning strategy for brain imaging, which is contrast-agnostic, and robust to the brain anatomy of each subject regardless of the appearance of acquired images (i.e., deformation, contrast, resolution, orientation, artifacts, etc). Brain-ID is trained entirely on synthetic data, and easily adapts to downstream tasks with our proposed simple one-layer solution. We validate the robustness of Brain-ID features, and evaluate their performance in a variety of downstream applications, including both contrast-independent (anatomy reconstruction/contrast synthesis, brain segmentation), and contrast-dependent (super-resolution, bias field estimation) tasks. Extensive experiments on 6 public datasets demonstrate that Brain-ID achieves state-of-the-art performance in all tasks, and more importantly, preserves its performance when only limited training data is available.

A 3D Conditional Diffusion Model for Image Quality Transfer -- An Application to Low-Field MRI

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}.

CenTime: Event-Conditional Modelling of Censoring in Survival Analysis

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.

A data-centric deep learning approach to airway segmentation

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.

A 3D deep learning classifier and its explainability when assessing coronary artery disease

Early detection and diagnosis of coronary artery disease (CAD) could save lives and reduce healthcare costs. In this study, we propose a 3D Resnet-50 deep learning model to directly classify normal subjects and CAD patients on computed tomography coronary angiography images. Our proposed method outperforms a 2D Resnet-50 model by 23.65%. Explainability is also provided by using a Grad-GAM. Furthermore, we link the 3D CAD classification to a 2D two-class semantic segmentation for improved explainability and accurate abnormality localisation.

Rician likelihood loss for quantitative MRI using self-supervised deep learning

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.

Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.

Expectation Maximization Pseudo Labelling for Segmentation with Limited Annotations

We study pseudo labelling and its generalisation for semi-supervised segmentation of medical images. Pseudo labelling has achieved great empirical successes in semi-supervised learning, by utilising raw inferences on unlabelled data as pseudo labels for self-training. In our paper, we build a connection between pseudo labelling and the Expectation Maximization algorithm which partially explains its empirical successes. We thereby realise that the original pseudo labelling is an empirical estimation of its underlying full formulation. Following this insight, we demonstrate the full generalisation of pseudo labels under Bayes' principle, called Bayesian Pseudo Labels. We then provide a variational approach to learn to approximate Bayesian Pseudo Labels, by learning a threshold to select good quality pseudo labels. In the rest of the paper, we demonstrate the applications of Pseudo Labelling and its generalisation Bayesian Psuedo Labelling in semi-supervised segmentation of medical images 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 brain tumours from MRI volumes. We also show that pseudo labels can enhance the robustness of the learnt representations.