Integrated Platform for Multiscale Molecular Imaging and Phenotyping of the Human Brain

Overview

Journal Science

Specialty Science

Date 2024 Jun 13

PMID 38870291

Authors

Juhyuk Park

Ji Wang

Webster Guan

Lars A Gjesteby

Dylan Pollack

Lee Kamentsky

Nicholas B Evans

Jeff Stirman

Xinyi Gu

Chuanxi Zhao

Slayton Marx

Minyoung E Kim

Seo Woo Choi

Michael Snyder

David Chavez

Clover Su-Arcaro

Yuxuan Tian

Chang Sin Park

Qiangge Zhang

Dae Hee Yun

Mira Moukheiber

Guoping Feng

X William Yang

C Dirk Keene

Patrick R Hof

Satrajit S Ghosh

Matthew P Frosch

Laura J Brattain

Kwanghun Chung

Affiliations

Soon will be listed here.

Abstract

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.

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