JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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RNN-based longitudinal analysis for diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with progressive impairment of memory and other mental functions. Magnetic resonance images (MRI) have been widely used as an important imaging modality of brain for AD diagnosis and monitoring the disease progression. The longitudinal analysis of sequential MRIs is important to model and measure the progression of the disease along the time axis for more accurate diagnosis. Most existing methods extracted the features capturing the morphological abnormalities of brain and their longitudinal changes using MRIs and then designed a classifier to discriminate different groups. However, these methods have several limitations. First, since the feature extraction and classifier model are independent, the extracted features may not capture the full characteristics of brain abnormalities related to AD. Second, longitudinal MR images may be missing at some time points for some subjects, which results in difficulties for extraction of consistent features for longitudinal analysis. In this paper, we present a classification framework based on combination of convolutional and recurrent neural networks for longitudinal analysis of structural MR images in AD diagnosis. First, Convolutional Neural Networks (CNN) is constructed to learn the spatial features of MR images for the classification task. After that, recurrent Neural Networks (RNN) with cascaded three bidirectional gated recurrent units (BGRU) layers is constructed on the outputs of CNN at multiple time points for extracting the longitudinal features for AD classification. Instead of independently performing feature extraction and classifier training, the proposed method jointly learns the spatial and longitudinal features and disease classifier, which can achieve optimal performance. In addition, the proposed method can model the longitudinal analysis using RNN from the imaging data at various time points. Our method is evaluated with the longitudinal T1-weighted MR images of 830 participants including 198 AD, 403 mild cognitive impairment (MCI), and 229 normal controls (NC) subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results show that the proposed method achieves classification accuracy of 91.33% for AD vs. NC and 71.71% for pMCI vs. sMCI, demonstrating the promising performance for longitudinal MR image analysis.

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