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Abstract BackgroundIn Alzheimer’s Diseases (AD) research, multimodal imaging analysis can unveil complementary information from multiple imaging modalities and further our understanding of the disease. One application is to discover disease subtypes using unsupervised clustering. However, existing clustering methods are often applied to input features directly, and could suffer from the curse of dimensionality with high-dimensional multimodal data. The purpose of our study is to identify multimodal imaging-driven subtypes in Mild Cognitive Impairment (MCI) participants using a multiview learning framework based on Deep Generalized Canonical Correlation Analysis (DGCCA), to learn shared latent representation with low dimensions from 3 neuroimaging modalities. ResultsDGCCA applies non-linear transformation to input views using neural networks and is able to learn correlated embeddings with low dimensions that capture more variance than its linear counterpart, generalized CCA (GCCA). We designed experiments to compare DGCCA embeddings with single modality features and GCCA embeddings by generating 2 subtypes from each feature set using unsupervised clustering. In our validation studies, we found that amyloid PET imaging has the most discriminative features compared with structural MRI and FDG PET which DGCCA learns from but not GCCA. DGCCA subtypes show differential measures in 5 cognitive assessments, 6 brain volume measures, and conversion to AD patterns. In addition, DGCCA MCI subtypes confirmed AD genetic markers with strong signals that existing late MCI group did not identify. ConclusionOverall, DGCCA is able to learn effective low dimensional embeddings from multimodal data by learning non-linear projections. MCI subtypes generated from DGCCA embeddings are different from existing early and late MCI groups and show most similarity with those identified by amyloid PET features. In our validation studies, DGCCA subtypes show distinct patterns in cognitive measures, brain volumes, and are able to identify AD genetic markers. These findings indicate the promise of the imaging-driven subtypes and their power in revealing disease structures beyond early and late stage MCI.
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Disentangled Representation of Longitudinal Β-Amyloid for AD Via Sequential Graph Variational Autoencoder with Supervision
The emergence of Positron Emission Tomography (PET) imaging allows us to quantify the burden of amyloid plaques in-vivo, which is one of the hallmarks of Alzheimer’s disease (AD). However, the invasive exposure to radiation and high imaging cost significantly restrict the application of PET in characterizing the evolution of pathology burden which often requires longitudinal PET image sequences. In this regard, we propose a proof-of-concept solution to generate the complete trajectory of pathological events throughout the brain based on very limited number of PET scans. We present a novel variational autoencoder model to learn a latent population-level representation of neurodegeneration process based on the longitudinal β-amyloid measurements at each brain region and longitudinal diagnostic stages. As the propagation of pathological burdens follow the topology of brain connectome, we further cast our neural network into a supervised sequential graph VAE, where we use the brain network to guide the representation learning. Experiments show that the disentangled representation can capture disease-related dynamics of amyloid and forecast the level of amyloid depositions at future time points.
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- Award ID(s):
- 1948510
- PAR ID:
- 10349984
- Date Published:
- Journal Name:
- International Symposium on Biomedical Imaging (ISBI)
- Page Range / eLocation ID:
- 1 to 5
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1109/ISBI52829.2022.9761588
