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

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 Added by Cher Bass
 Publication date 2021
and research's language is English




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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 Alzheimers 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.



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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.
As our population ages, neurological impairments and degeneration of the musculoskeletal system yield gait abnormalities, which can significantly reduce quality of life. Gait rehabilitative therapy has been widely adopted to help patients maximize community participation and living independence. To further improve the precision and efficiency of rehabilitative therapy, more objective methods need to be developed based on sensory data. In this paper, an algorithmic framework is proposed to provide classification of gait disorders caused by two common neurological diseases, stroke and Parkinsons Disease (PD), from ground contact force (GCF) data. An advanced machine learning method, multi-task feature learning (MTFL), is used to jointly train classification models of a subjects gait in three classes, post-stroke, PD and healthy gait. Gait parameters related to mobility, balance, strength and rhythm are used as features for the classification. Out of all the features used, the MTFL models capture the more important ones per disease, which will help provide better objective assessment and therapy progress tracking. To evaluate the proposed methodology we use data from a human participant study, which includes five PD patients, three post-stroke patients, and three healthy subjects. Despite the diversity of abnormalities, the evaluation shows that the proposed approach can successfully distinguish post-stroke and PD gait from healthy gait, as well as post-stroke from PD gait, with Area Under the Curve (AUC) score of at least 0.96. Moreover, the methodology helps select important gait features to better understand the key characteristics that distinguish abnormal gaits and design personalized treatment.
Nonlinear inter-modality registration is often challenging due to the lack of objective functions that are good proxies for alignment. Here we propose a synthesis-by-registration method to convert this problem into an easier intra-modality task. We introduce a registration loss for weakly supervised image translation between domains that does not require perfectly aligned training data. This loss capitalises on a registration U-Net with frozen weights, to drive a synthesis CNN towards the desired translation. We complement this loss with a structure preserving constraint based on contrastive learning, which prevents blurring and content shifts due to overfitting. We apply this method to the registration of histological sections to MRI slices, a key step in 3D histology reconstruction. Results on two different public datasets show improvements over registration based on mutual information (13% reduction in landmark error) and synthesis-based algorithms such as CycleGAN (11% reduction), and are comparable to a registration CNN with label supervision.
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