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Alzheimer’s disease (AD) is characterized by the progressive alterations seen in brain images which give rise to the onset of various sets of symptoms. The variability in the dynamics of changes in both brain images and cognitive impairments remains poorly understood. This paper introduces AD Course Map a spatiotemporal atlas of Alzheimer’s disease progression. It summarizes the variability in the progression of a series of neuropsychological assessments, the propagation of hypometabolism and cortical thinning across brain regions and the deformation of the shape of the hippocampus. The analysis of these variations highlights strong genetic determinants for the progression, like possible compensatory mechanisms at play during disease progression. AD Course Map also predicts the patient’s cognitive decline with a better accuracy than the 56 methods benchmarked in the open challenge TADPOLE. Finally, AD Course Map is used to simulate cohorts of virtual patients developing Alzheimer’s disease. AD Course Map offers therefore new tools for exploring the progression of AD and personalizing patients care.

Studying anatomical shape progression over time is of utmost importance to refine our understanding of clinically relevant processes. These include vascular remodeling, such as aortic dilation, which is particularly important in some congenital heart defects (CHD). A novel methodological framework for three-dimensional shape analysis has been applied for the first time in a CHD scenario, i.e., bicuspid aortic valve (BAV) disease, the most common CHD. Three-dimensional aortic shapes (n = 94) reconstructed from cardiovascular magnetic resonance imaging (MRI) data as surface meshes represented the input for a longitudinal atlas model, using multiple scans over time (n = 2–4 per patient). This model relies on diffeomorphism transformations in the absence of point-to-point correspondence, and on the right combination of initialization, estimation and registration parameters. We computed the shape trajectory of an average disease progression in our cohort, as well as time-dependent parameters, geometric variations and the average shape of the population. Results cover a spatiotemporal spectrum of visual and numerical information that can be further used to run clinical associations. This proof-of-concept study demonstrates the feasibility of applying advanced statistical shape models to track disease progression and stratify patients with CHD. [Display omitted] •Modeling longitudinal 3D shape data to study growth in a congenital heart disease scenario.•Exploring the spatiotemporal shape trajectory of disease progression.•Separating the analysis of temporal and spatial warps to show clinical potential.

We propose a scalable and data-driven approach to learn shape distributions from large databases of healthy organs. To do so, volumetric segmentation masks are embedded into a common probabilistic shape space that is learned with a variational auto-encoding network. The resulting latent shape representations are leveraged to derive zeroshot and few-shot methods for abnormal shape detection. The proposed distribution learning approach is illustrated on a large database of 1200 healthy pancreas shapes. Downstream qualitative and quantitative experiments are conducted on a separate test set of 224 pancreas from patients with mixed conditions. The abnormal pancreas detection AUC reached up to 65.41% in the zero-shot configuration, and 78.97% in the few-shot configuration with as few as 15 abnormal examples, outperforming a baseline approach based on the sole volume.

Large medical imaging datasets can be cheaply and quickly annotated with low-confidence, weak labels (e.g., radiological scores). Access to high-confidence labels, such as histology-based diagnoses, is rare and costly. Pretraining strategies, like contrastive learning (CL) methods, can leverage unlabeled or weakly-annotated datasets. These methods typically require large batch sizes, which poses a difficulty in the case of large 3D images at full resolution, due to limited GPU memory. Nevertheless, volumetric positional information about the spatial context of each 2D slice can be very important for some medical applications. In this work, we propose an efficient weakly-supervised positional (WSP) contrastive learning strategy where we integrate both the spatial context of each 2D slice and a weak label via a generic kernel-based loss function. We illustrate our method on cirrhosis prediction using a large volume of weakly-labeled images, namely radiological low-confidence annotations, and small strongly-labeled (i.e., high-confidence) datasets. The proposed model improves the classification AUC by 5% with respect to a baseline model on our internal dataset, and by 26% on the public LIHC dataset from the Cancer Genome Atlas. The code is available at: https://github.com/Guerbet-AI/wsp-contrastive.

The analysis of manifold-valued data requires efficient tools from Riemannian geometry to cope with the computational complexity at stake. This complexity arises from the always-increasing dimension of the data, and the absence of closed-form expressions to basic operations such as the Riemannian logarithm. In this paper, we adapt a generic numerical scheme recently introduced for computing parallel transport along geodesics in a Riemannian manifold to finite-dimensional manifolds of diffeomorphisms. We provide a qualitative and quantitative analysis of its behavior on high-dimensional manifolds, and investigate an application with the prediction of brain structures progression.

We propose a method to predict the subject-specific longitudinal progression of brain structures extracted from baseline MRI, and evaluate its performance on Alzheimer's disease data. The disease progression is modeled as a trajectory on a group of diffeomorphisms in the context of large deformation diffeomorphic metric mapping (LDDMM). We first exhibit the limited predictive abilities of geodesic regression extrapolation on this group. Building on the recent concept of parallel curves in shape manifolds, we then introduce a second predictive protocol which personalizes previously learned trajectories to new subjects, and investigate the relative performances of two parallel shifting paradigms. This design only requires the baseline imaging data. Finally, coefficients encoding the disease dynamics are obtained from longitudinal cognitive measurements for each subject, and exploited to refine our methodology which is demonstrated to successfully predict the follow-up visits.

We address the problem of learning Deep Learning Radiomics (DLR) that are not redundant with Hand-Crafted Radiomics (HCR). To do so, we extract DLR features using a VAE while enforcing their independence with HCR features by minimizing their mutual information. The resulting DLR features can be combined with hand-crafted ones and leveraged by a classifier to predict early markers of cancer. We illustrate our method on four early markers of pancreatic cancer and validate it on a large independent test set. Our results highlight the value of combining non-redundant DLR and HCR features, as evidenced by an improvement in the Area Under the Curve compared to baseline methods that do not address redundancy or solely rely on HCR features.

We propose a method to learn a distribution of shape trajectories from longitudinal data, i.e. the collection of individual objects repeatedly observed at multiple time-points. The method allows to compute an average spatiotemporal trajectory of shape changes at the group level, and the individual variations of this trajectory both in terms of geometry and time dynamics. First, we formulate a non-linear mixed-effects statistical model as the combination of a generic statistical model for manifold-valued longitudinal data, a deformation model defining shape trajectories via the action of a finite-dimensional set of diffeomorphisms with a manifold structure, and an efficient numerical scheme to compute parallel transport on this manifold. Second, we introduce a MCMC-SAEM algorithm with a specific approach to shape sampling, an adaptive scheme for proposal variances, and a log-likelihood tempering strategy to estimate our model. Third, we validate our algorithm on 2D simulated data, and then estimate a scenario of alteration of the shape of the hippocampus 3D brain structure during the course of Alzheimer's disease. The method shows for instance that hippocampal atrophy progresses more quickly in female subjects, and occurs earlier in APOE4 mutation carriers. We finally illustrate the potential of our method for classifying pathological trajectories versus normal ageing.

Identifying cirrhosis is key to correctly assess the health of the liver. However, the gold standard diagnosis of the cirrhosis needs a medical intervention to obtain the histological confirmation, e.g. the METAVIR score, as the radiological presentation can be equivocal. In this work, we propose to leverage transfer learning from large datasets annotated by radiologists, which we consider as a weak annotation, to predict the histological score available on a small annex dataset. To this end, we propose to compare different pretraining methods, namely weakly-supervised and self-supervised ones, to improve the prediction of the cirrhosis. Finally, we introduce a loss function combining both supervised and self-supervised frameworks for pretraining. This method outperforms the baseline classification of the METAVIR score, reaching an AUC of 0.84 and a balanced accuracy of 0.75, compared to 0.77 and 0.72 for a baseline classifier.

Surgical resections are the most prevalent curative treatment for primary liver cancer. Tumors located in critical positions are known to complexify liver resections (LR). While experienced surgeons in specialized medical centers may have the necessary expertise to accurately anticipate LR complexity, and prepare accordingly, an objective method able to reproduce this behavior would have the potential to improve the standard routine of care, and avoid intra- and postoperative complications. In this article, we propose CoRe, an automated medical image processing pipeline for the prediction of postoperative LR complexity from preoperative CT scans, using imaging biomarkers. The CoRe pipeline first segments the liver, lesions, and vessels with two deep learning networks. The liver vasculature is then pruned based on a topological criterion to define the hepatic central zone (HCZ), a convex volume circumscribing the major liver vessels, from which a new imaging biomarker, BHCZ is derived. Additional biomarkers are extracted and leveraged to train and evaluate a LR complexity prediction model. An ablation study shows the HCZ-based biomarker as the central feature in predicting LR complexity. The best predictive model reaches an accuracy, F1, and AUC of 77.3, 75.4, and 84.1% respectively.