Current models of Alzheimer's disease suggest significant hanges in structural and chemical distribution of cellular components within the brain. This includes microvascular changes, as well as the formation of neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques. However, the broad effects of these changes across the entire brain are impossible to quantify using traditional imaging, and currently form a critical gap in our understanding of Alzheimer's disease. Three-dimensional (3D) tissue imaging also requires expensive optical systems with data throughput rates that are too slow to be practical in a histological or clinical environment. Finally, the currently available optical imaging techniques, including confocal and light-sheet microscopy, are limited to samples less than 100μm thick. We propose the development of a novel tissue imaging system that provides practical data rates at low cost while alleviating the depth constraints inherent in existing optical imaging methods. The proposed technique, which we term surface ablation lathe tomography (SALT), performs block-face imaging of embedded samples on a rotary stage followed by serial ablation of the tissue using an ultramicrotome blade. The central objective of this technique are to make whole-organ 3D imaging practical by (a) significantly increasing the acquisition speed of 3D images and (b) eliminating depth constraints inherent in existing imaging methods.