Thomas P. DeRamus

Alex Fedorov, Eloy Geenjaar, Lei Wu et al.

Recent neuroimaging studies that focus on predicting brain disorders via modern machine learning approaches commonly include a single modality and rely on supervised over-parameterized models.However, a single modality provides only a limited view of the highly complex brain. Critically, supervised models in clinical settings lack accurate diagnostic labels for training. Coarse labels do not capture the long-tailed spectrum of brain disorder phenotypes, which leads to a loss of generalizability of the model that makes them less useful in diagnostic settings. This work presents a novel multi-scale coordinated framework for learning multiple representations from multimodal neuroimaging data. We propose a general taxonomy of informative inductive biases to capture unique and joint information in multimodal self-supervised fusion. The taxonomy forms a family of decoder-free models with reduced computational complexity and a propensity to capture multi-scale relationships between local and global representations of the multimodal inputs. We conduct a comprehensive evaluation of the taxonomy using functional and structural magnetic resonance imaging (MRI) data across a spectrum of Alzheimer's disease phenotypes and show that self-supervised models reveal disorder-relevant brain regions and multimodal links without access to the labels during pre-training. The proposed multimodal self-supervised learning yields representations with improved classification performance for both modalities. The concomitant rich and flexible unsupervised deep learning framework captures complex multimodal relationships and provides predictive performance that meets or exceeds that of a more narrow supervised classification analysis. We present elaborate quantitative evidence of how this framework can significantly advance our search for missing links in complex brain disorders.

Alex Fedorov, Eloy Geenjaar, Lei Wu et al.

Self-supervised learning has enabled significant improvements on natural image benchmarks. However, there is less work in the medical imaging domain in this area. The optimal models have not yet been determined among the various options. Moreover, little work has evaluated the current applicability limits of novel self-supervised methods. In this paper, we evaluate a range of current contrastive self-supervised methods on out-of-distribution generalization in order to evaluate their applicability to medical imaging. We show that self-supervised models are not as robust as expected based on their results in natural imaging benchmarks and can be outperformed by supervised learning with dropout. We also show that this behavior can be countered with extensive augmentation. Our results highlight the need for out-of-distribution generalization standards and benchmarks to adopt the self-supervised methods in the medical imaging community.

Alex Fedorov, Tristan Sylvain, Eloy Geenjaar et al.

Sensory input from multiple sources is crucial for robust and coherent human perception. Different sources contribute complementary explanatory factors. Similarly, research studies often collect multimodal imaging data, each of which can provide shared and unique information. This observation motivated the design of powerful multimodal self-supervised representation-learning algorithms. In this paper, we unify recent work on multimodal self-supervised learning under a single framework. Observing that most self-supervised methods optimize similarity metrics between a set of model components, we propose a taxonomy of all reasonable ways to organize this process. We first evaluate models on toy multimodal MNIST datasets and then apply them to a multimodal neuroimaging dataset with Alzheimer's disease patients. We find that (1) multimodal contrastive learning has significant benefits over its unimodal counterpart, (2) the specific composition of multiple contrastive objectives is critical to performance on a downstream task, (3) maximization of the similarity between representations has a regularizing effect on a neural network, which can sometimes lead to reduced downstream performance but still reveal multimodal relations. Results show that the proposed approach outperforms previous self-supervised encoder-decoder methods based on canonical correlation analysis (CCA) or the mixture-of-experts multimodal variational autoEncoder (MMVAE) on various datasets with a linear evaluation protocol. Importantly, we find a promising solution to uncover connections between modalities through a jointly shared subspace that can help advance work in our search for neuroimaging biomarkers.

Alex Fedorov, Lei Wu, Tristan Sylvain et al.

Introspection of deep supervised predictive models trained on functional and structural brain imaging may uncover novel markers of Alzheimer's disease (AD). However, supervised training is prone to learning from spurious features (shortcut learning) impairing its value in the discovery process. Deep unsupervised and, recently, contrastive self-supervised approaches, not biased to classification, are better candidates for the task. Their multimodal options specifically offer additional regularization via modality interactions. In this paper, we introduce a way to exhaustively consider multimodal architectures for contrastive self-supervised fusion of fMRI and MRI of AD patients and controls. We show that this multimodal fusion results in representations that improve the results of the downstream classification for both modalities. We investigate the fused self-supervised features projected into the brain space and introduce a numerically stable way to do so.