Registration and resampling of large-scale 3 D mosaic images

Determining the detailed structure of intact organs such as the mammalian brain requires submicron (~0.1 μm voxel size) imaging of large tissue volumes often hundreds of mm. Due to limitations in imaging technologies, large numbers of smaller images, each representing a subset of the full sample, are acquired and assembled into a continuous whole using image registration techniques. The full mouse brain requires approximately 10 teravoxels for a complete representation at diffraction-limited resolution. However, relatively few tools exist for processing biological datasets of this magnitude. Here, we describe a procedure for the registration and resampling of large-scale imaging data that can be employed for assembling tens of thousands of individual image volumes tiling complete organs in three dimensions.