Development and validation of a novel dementia of Alzheimer's type (DAT) score based on metabolism FDG-PET imaging

Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging based 3D topographic brain glucose metabolism patterns from normal controls (NC) and individuals with dementia of Alzheimer's type (DAT) are used to train a novel multi-scale ensemble classification model. This ensemble model outputs a FDG-PET DAT score (FPDS) between 0 and 1 denoting the probability of a subject to be clinically diagnosed with DAT based on their metabolism profile. A novel 7 group image stratification scheme is devised that groups images not only based on their associated clinical diagnosis but also on past and future trajectories of the clinical diagnoses, yielding a more continuous representation of the different stages of DAT spectrum that mimics a real-world clinical setting. The potential for using FPDS as a DAT biomarker was validated on a large number of FDG-PET images (N=2984) obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database taken across the proposed stratification, and a good classification AUC (area under the curve) of 0.78 was achieved in distinguishing between images belonging to subjects on a DAT trajectory and those images taken from subjects not progressing to a DAT diagnosis. Further, the FPDS biomarker achieved state-of-the-art performance on the mild cognitive impairment (MCI) to DAT conversion prediction task with an AUC of 0.81, 0.80, 0.77 for the 2, 3, 5 years to conversion windows respectively.

Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images

Alzheimer's Disease (AD) is a progressive neurodegenerative disease. Amnestic mild cognitive impairment (MCI) is a common first symptom before the conversion to clinical impairment where the individual becomes unable to perform activities of daily living independently. Although there is currently no treatment available, the earlier a conclusive diagnosis is made, the earlier the potential for interventions to delay or perhaps even prevent progression to full-blown AD. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo view into the structure and function (glucose metabolism) of the living brain. It is hypothesized that combining different image modalities could better characterize the change of human brain and result in a more accuracy early diagnosis of AD. In this paper, we proposed a novel framework to discriminate normal control(NC) subjects from subjects with AD pathology (AD and NC, MCI subjects convert to AD in future). Our novel approach utilizing a multimodal and multiscale deep neural network was found to deliver a 85.68\% accuracy in the prediction of subjects within 3 years to conversion. Cross validation experiments proved that it has better discrimination ability compared with results in existing published literature.