Visualizing Alzheimer's disease progression in low dimensional manifolds.

While tomographic neuroimaging data is information rich, objective, and with high sensitivity in the study of brain diseases such as Alzheimer's disease (AD), its direct use in clinical practice and in regulated clinical trial (CT) still has many challenges. Taking CT as an example, unless the relevant policy and the perception of the primary outcome measures change, the need to construct univariate indices (out of the 3-D imaging data) to serve as CT's primary outcome measures will remain the focus of active research. More relevant to this current study, an overall global index that summarizes multiple complicated features from neuroimages should be developed in order to provide high diagnostic accuracy and sensitivity in tracking AD progression over time in clinical setting. Such index should also be practically intuitive and logically explainable to patients and their families. In this research, we propose a new visualization tool, derived from the manifold-based nonlinear dimension reduction of brain MRI features, to track AD progression over time. In specific, we investigate the locally linear embedding (LLE) method using a dataset from Alzheimer's Disease Neuroimaging Initiative (ADNI), which includes the longitudinal MRIs from 562 subjects. About 20% of them progressed to the next stage of dementia. Using only the baseline data of cognitively unimpaired (CU) and AD subjects, LLE reduces the feature dimension to two and a subject's AD progression path can be plotted in this low dimensional LLE feature space. In addition, the likelihood of being categorized to AD is indicated by color. This LLE map is a new data visualization tool that can assist in tracking AD progression over time.