Quantifying microstructural changes in Alzheimer's disease using Restriction Spectrum Imaging

Project Summary/Abstract The overall goal of this project is to deliver an automated diffusion image analysis tool to be used in a clinical setting that quickly evaluates the diffusion images in conjunction with MR volumetric images and reports diffusion-based microstructural parameters derived from segmented anatomical locations to determine Alzheimer’s disease status of patients. Alzheimer’s disease is characterized with β-amyloid deposits and neurofibrillary tangles preceding neuronal loss and cognitive decline. Hence quantitative volumetry and measures of neuronal function have been studied extensively as potential bioimaging markers. There has been increasing evidence of microstructural alterations in Alzheimer’s patients’ brains in addition to the volume and functional changes in neuronal bodies. While diffusion imaging has been used effectively in diseases involving specific white matter pathways, the recent advances in the diffusion imaging techniques particularly multi-compartmental models for successfully quantifying microstructural changes now enables the effective use of diffusion imaging in Alzheimer’s disease. Restriction Spectrum Imaging (RSI) is an advanced diffusion imaging method and currently can be used in MR scanners from major manufactures which have the capability to acquire multi-shell diffusion imaging. Recent studies of Alzheimer’s disease patients with diffusion techniques reported decreased diffusion anisotropy in multiple white matter tracts as well as increased diffusion in gray matter structures. Microstructural changes due to axonal and dendritic pathology, would reflect in diffusional measures. Advanced diffusion methods that are sensitive to neurite density and orientation are best qualified for elucidating the neuropathological changes preceding the cognitive decline in Alzheimer’s patients. Indeed, strong correlations between tau deposits measured by PET studies and neurite density index measured by advanced diffusion techniques were reported. There was also evidence of higher neurite dispersion in Alzheimer affected brain regions in addition to diffusion tensor imaging findings. Correlations with cognitive measures and diffusion parameters were also reported in a group of Alzheimer patients. Recent studies showed abnormal CSF measures of β-amyloid and tau levels associated with widespread alterations in white matter microstructures throughout the Alzheimer’s patients’ brains. Since CSF measures are well established biomarkers for AD pathology, in vivo and non-invasive determined diffusion parameters may convey AD related brain changes and predict future cognitive decline.