Deep Learning (DL) in neuroimaging has become increasingly relevant for detecting neurological conditions and neurodegenerative disorders. One of the most predominant biomarkers in neuroimaging is represented by brain age, which has been shown to be a good indicator for different conditions, such as Alzheimer's Disease. Using brain age for pretraining DL models in transfer learning settings has also recently shown promising results, especially when dealing with data scarcity of different conditions. On the other hand, anatomical information of brain MRIs (e.g. cortical thickness) can provide important information for learning good representations that can be transferred to many downstream tasks. In this work, we propose AnatCL, an anatomical foundation model for brain MRIs that i.) leverages anatomical information with a weakly contrastive learning approach and ii.) achieves state-of-the-art performances in many different downstream tasks. To validate our approach we consider 12 different downstream tasks for diagnosis classification, and prediction of 10 different clinical assessment scores.

Contrastive Analysis VAE (CA-VAEs) is a family of Variational auto-encoders (VAEs) that aims at separating the common factors of variation between a background dataset (BG) (i.e., healthy subjects) and a target dataset (TG) (i.e., patients) from the ones that only exist in the target dataset. To do so, these methods separate the latent space into a set of salient features (i.e., proper to the target dataset) and a set of common features (i.e., exist in both datasets). Currently, all models fail to prevent the sharing of information between latent spaces effectively and to capture all salient factors of variation. To this end, we introduce two crucial regularization losses: a disentangling term between common and salient representations and a classification term between background and target samples in the salient space. We show a better performance than previous CA-VAEs methods on three medical applications and a natural images dataset (CelebA). Code and datasets are available on GitHub https://github.com/neurospin-projects/2023_rlouiset_sepvae.

Many datasets are biased, namely they contain easy-to-learn features that are highly correlated with the target class only in the dataset but not in the true underlying distribution of the data. For this reason, learning unbiased models from biased data has become a very relevant research topic in the last years. In this work, we tackle the problem of learning representations that are robust to biases. We first present a margin-based theoretical framework that allows us to clarify why recent contrastive losses (InfoNCE, SupCon, etc.) can fail when dealing with biased data. Based on that, we derive a novel formulation of the supervised contrastive loss (epsilon-SupInfoNCE), providing more accurate control of the minimal distance between positive and negative samples. Furthermore, thanks to our theoretical framework, we also propose FairKL, a new debiasing regularization loss, that works well even with extremely biased data. We validate the proposed losses on standard vision datasets including CIFAR10, CIFAR100, and ImageNet, and we assess the debiasing capability of FairKL with epsilon-SupInfoNCE, reaching state-of-the-art performance on a number of biased datasets, including real instances of biases in the wild.

Deep Learning (DL) and specifically CNN models have become a de facto method for a wide range of vision tasks, outperforming traditional machine learning (ML) methods. Consequently, they drew a lot of attention in the neuroimaging field in particular for phenotype prediction or computer-aided diagnosis. However, most of the current studies often deal with small single-site cohorts, along with a specific pre-processing pipeline and custom CNN architectures, which make them difficult to compare to. We propose an extensive benchmark of recent state-of-the-art (SOTA) 3D CNN, evaluating also the benefits of data augmentation and deep ensemble learning, on both Voxel-Based Morphometry (VBM) pre-processing and quasi-raw images. Experiments were conducted on a large multi-site 3D brain anatomical MRI data-set comprising N=10k scans on 3 challenging tasks: age prediction, sex classification, and schizophrenia diagnosis. We found that all models provide significantly better predictions with VBM images than quasi-raw data. This finding evolved as the training set approaches 10k samples where quasi-raw data almost reach the performance of VBM. Moreover, we showed that linear models perform comparably with SOTA CNN on VBM data. We also demonstrated that DenseNet and tiny-DenseNet, a lighter version that we proposed, provide a good compromise in terms of performance in all data regime. Therefore, we suggest to employ them as the architectures by default. Critically, we also showed that current CNN are still very biased towards the acquisition site, even when trained with N=10k multi-site images. In this context, VBM pre-processing provides an efficient way to limit this site effect. Surprisingly, we did not find any clear benefit from data augmentation techniques. Finally, we proved that deep ensemble learning is well suited to re-calibrate big CNN models without sacrificing performance.

Building accurate Deep Learning (DL) models for brain age prediction is a very relevant topic in neuroimaging, as it could help better understand neurodegenerative disorders and find new biomarkers. To estimate accurate and generalizable models, large datasets have been collected, which are often multi-site and multi-scanner. This large heterogeneity negatively affects the generalization performance of DL models since they are prone to overfit site-related noise. Recently, contrastive learning approaches have been shown to be more robust against noise in data or labels. For this reason, we propose a novel contrastive learning regression loss for robust brain age prediction using MRI scans. Our method achieves state-of-the-art performance on the OpenBHB challenge, yielding the best generalization capability and robustness to site-related noise.

Subtype Discovery consists in finding interpretable and consistent sub-parts of a dataset, which are also relevant to a certain supervised task. From a mathematical point of view, this can be defined as a clustering task driven by supervised learning in order to uncover subgroups in line with the supervised prediction. In this paper, we propose a general Expectation-Maximization ensemble framework entitled UCSL (Unsupervised Clustering driven by Supervised Learning). Our method is generic, it can integrate any clustering method and can be driven by both binary classification and regression. We propose to construct a non-linear model by merging multiple linear estimators, one per cluster. Each hyperplane is estimated so that it correctly discriminates - or predict - only one cluster. We use SVC or Logistic Regression for classification and SVR for regression. Furthermore, to perform cluster analysis within a more suitable space, we also propose a dimension-reduction algorithm that projects the data onto an orthonormal space relevant to the supervised task. We analyze the robustness and generalization capability of our algorithm using synthetic and experimental datasets. In particular, we validate its ability to identify suitable consistent sub-types by conducting a psychiatric-diseases cluster analysis with known ground-truth labels. The gain of the proposed method over previous state-of-the-art techniques is about +1.9 points in terms of balanced accuracy. Finally, we make codes and examples available in a scikit-learn-compatible Python package at https://github.com/neurospin-projects/2021_rlouiset_ucsl

Traditional supervised learning with deep neural networks requires a tremendous amount of labelled data to converge to a good solution. For 3D medical images, it is often impractical to build a large homogeneous annotated dataset for a specific pathology. Self-supervised methods offer a new way to learn a representation of the images in an unsupervised manner with a neural network. In particular, contrastive learning has shown great promises by (almost) matching the performance of fully-supervised CNN on vision tasks. Nonetheless, this method does not take advantage of available meta-data, such as participant's age, viewed as prior knowledge. Here, we propose to leverage continuous proxy metadata, in the contrastive learning framework, by introducing a new loss called y-Aware InfoNCE loss. Specifically, we improve the positive sampling during pre-training by adding more positive examples with similar proxy meta-data with the anchor, assuming they share similar discriminative semantic features.With our method, a 3D CNN model pre-trained on $10^4$ multi-site healthy brain MRI scans can extract relevant features for three classification tasks: schizophrenia, bipolar diagnosis and Alzheimer's detection. When fine-tuned, it also outperforms 3D CNN trained from scratch on these tasks, as well as state-of-the-art self-supervised methods. Our code is made publicly available here.