Integrated platform for multiscale molecular imaging and phenotyping of the human brain

Key findings

A new integrated platform combines an ultraprecision vibrating microtome (MEGAtome), a hydrogel-based multiplexed imaging method (mELAST), and a 3-D reconstruction pipeline (UNSLICE) to extract spatial, molecular, morphological, and connectivity information from the same human brain, applied to multiscale analysis of Alzheimer's disease pathology.

Abstract

Source: pubmed

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer's disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

Topics

neuroimaging-methods
connectomics-circuits

Preprint precursor

Earlier versions of this work that have been superseded by the published record above.

bioRxiv (Cold Spring Harbor Laboratory) 2022 10.1101/2022.03.13.484171

Lab authors

Satrajit S Ghosh