Multiscale detection and analysis of the senile plaques of Alzheimer's disease

Senile plaques (SP) are one of the characteristic neuropathologic lesions of Alzheimer's Disease (AD), and studies of SP cortical distribution, density (number of SP/mm2), and morphology are expected to lead to new information about the mechanism and pathogenesis of AD. We describe a digital image analysis procedure to detect SP, and to measure SP size, shape, and total fractional area in digital micrographs of silver-stained tissue sections. This histology is nonspecific so the program detects all the significant stained objects and a classifier sorts the SP from other tissue elements. SP vary greatly in size and form, and detection is based on multiscale template correlation. Three independent comparisons of computed versus expert-determined SP densities produced correlation coefficients greater than 0.8. The program found 94,000 SP in 2800 digital images of tissue sections from 42 postmortem cases including healthy aged controls and severely demented subjects.