Digital Atlases to Unlock the Potential of Brain Biorepository Tissues for Interdisciplinary Research

Abstract

Human brain tissue preserved in biorepositories is foundational for the structural, cellular, and biomolecular research necessary for a mechanistic understanding of neurological diseases. Realizing the research potential of these valuable resources requires well-characterized research-relevant tissue that can be efficiently identified by investigators and incorporated into the conceptual and computational frameworks of interdisciplinary research. Several large-scale efforts to improve research reliability and reproducibility have sought to characterize and annotate the processes by which these samples are collected, yet limited progress has been made on standardizing spatial information for these samples. Biorepositories systematically collect brain tissue according to a brain sampling protocol (BSP) that differs between institutions, yet explicit spatial information regarding the samples may not be documented in standard operating procedures (SOPs). The amount of anatomical location details available to investigators are inconsistent across biorepositories and typically lack sufficient anatomical precision to ensure correspondence with samples from other biorepositories or research relevant brain regions specified by neuroimaging, functional, or disease-susceptibility criteria. Here, we introduce a pipeline for developing a Spatial Atlas for Mapping Protocol Locations of Ex vivo Samples (SAMPLES), which uses a neuroimaging framework to create a 3D representation of a BSP through a metrically precise digital instantiation of the procedures for brain extraction, segmentation, slicing, and sampling on a modern digital brain template. SAMPLES incorporates modern neuroinformatics conventions to create explicit 3D labels of BSP-defined samples that can be interactively visualized with freely available neuroimaging software. We illustrate the pipeline by developing an atlas for the protocol from the University of Washington BioRepository and Integrated Neuropathology laboratory (UW BRaIN SAMPLES). By providing an explicit, computable reference, SAMPLES atlases can support the efficient identification, referencing, and utilization of postmortem samples for interdisciplinary research. These capabilities enable biorepository workflows, data harmonization across biorepositories, and integration with antemortem neuroimaging.