Integrated platform for multiscale molecular imaging and phenotyping of the human brain.
Juhyuk ParkJi WangWebster GuanLars A GjestebyDylan PollackLee KamentskyNicholas B EvansJeff StirmanXinyi GuChuanxi ZhaoSlayton MarxMinyoung E KimSeo Woo ChoiMichael SnyderDavid ChavezClover Su-ArcaroYuxuan TianChang Sin ParkQiangge ZhangDae Hee YunMira MoukheiberGuoping FengXiangdong William YangC Dirk KeenePatrick R HofSatrajit S GhoshMatthew P FroschLaura J BrattainKwanghun ChungPublished in: Science (New York, N.Y.) (2024)
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.
Keyphrases
- resting state
- functional connectivity
- white matter
- endothelial cells
- high throughput
- high resolution
- induced pluripotent stem cells
- multiple sclerosis
- induced apoptosis
- cell proliferation
- healthcare
- drug delivery
- photodynamic therapy
- high density
- cell death
- health information
- cell cycle arrest
- single cell
- data analysis
- pi k akt
- cerebral ischemia