Distinguishing Healthy Ageing from Dementia: a Biomechanical Simulation of Brain Atrophy using Deep Networks

Biomechanical modeling of tissue deformation can be used to simulate different scenarios of longitudinal brain evolution. In this work,we present a deep learning framework for hyper-elastic strain modelling of brain atrophy, during healthy ageing and in Alzheimer's Disease. The framework directly models the effects of age, disease status, and scan interval to regress regional patterns of atrophy, from which a strain-based model estimates deformations. This model is trained and validated using 3D structural magnetic resonance imaging data from the ADNI cohort. Results show that the framework can estimate realistic deformations, following the known course of Alzheimer's disease, that clearly differentiate between healthy and demented patterns of ageing. This suggests the framework has potential to be incorporated into explainable models of disease, for the exploration of interventions and counterfactual examples.

ICAM-reg: Interpretable Classification and Regression with Feature Attribution for Mapping Neurological Phenotypes in Individual Scans

An important goal of medical imaging is to be able to precisely detect patterns of disease specific to individual scans; however, this is challenged in brain imaging by the degree of heterogeneity of shape and appearance. Traditional methods, based on image registration to a global template, historically fail to detect variable features of disease, as they utilise population-based analyses, suited primarily to studying group-average effects. In this paper we therefore take advantage of recent developments in generative deep learning to develop a method for simultaneous classification, or regression, and feature attribution (FA). Specifically, we explore the use of a VAE-GAN translation network called ICAM, to explicitly disentangle class relevant features from background confounds for improved interpretability and regression of neurological phenotypes. We validate our method on the tasks of Mini-Mental State Examination (MMSE) cognitive test score prediction for the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, as well as brain age prediction, for both neurodevelopment and neurodegeneration, using the developing Human Connectome Project (dHCP) and UK Biobank datasets. We show that the generated FA maps can be used to explain outlier predictions and demonstrate that the inclusion of a regression module improves the disentanglement of the latent space. Our code is freely available on Github https://github.com/CherBass/ICAM.

Biomechanical modelling of brain atrophy through deep learning

We present a proof-of-concept, deep learning (DL) based, differentiable biomechanical model of realistic brain deformations. Using prescribed maps of local atrophy and growth as input, the network learns to deform images according to a Neo-Hookean model of tissue deformation. The tool is validated using longitudinal brain atrophy data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and we demonstrate that the trained model is capable of rapidly simulating new brain deformations with minimal residuals. This method has the potential to be used in data augmentation or for the exploration of different causal hypotheses reflecting brain growth and atrophy.

ICAM: Interpretable Classification via Disentangled Representations and Feature Attribution Mapping

Feature attribution (FA), or the assignment of class-relevance to different locations in an image, is important for many classification problems but is particularly crucial within the neuroscience domain, where accurate mechanistic models of behaviours, or disease, require knowledge of all features discriminative of a trait. At the same time, predicting class relevance from brain images is challenging as phenotypes are typically heterogeneous, and changes occur against a background of significant natural variation. Here, we present a novel framework for creating class specific FA maps through image-to-image translation. We propose the use of a VAE-GAN to explicitly disentangle class relevance from background features for improved interpretability properties, which results in meaningful FA maps. We validate our method on 2D and 3D brain image datasets of dementia (ADNI dataset), ageing (UK Biobank), and (simulated) lesion detection. We show that FA maps generated by our method outperform baseline FA methods when validated against ground truth. More significantly, our approach is the first to use latent space sampling to support exploration of phenotype variation. Our code will be available online at https://github.com/CherBass/ICAM.