Revolutionary platform unveils detailed human brain architecture at multiple scales

American Association for the Advancement of Science (AAAS)Jun 13 2024

A new platform enables simultaneous capture of protein expression, cellular morphology, neural projection, and synapse distribution in large-scale human brain tissues at multiple scales, researchers report. The system ensures the preservation of cellular architecture while enabling detailed imaging and analysis of large human brain tissue samples at unprecedented resolution and speed. The authors demonstrated its utility by processing whole human brain hemispheres to reveal pathological features of Alzheimer's disease tissue. "We envision that this scalable technology platform will advance our understanding of the human organ functions and disease mechanisms to spur development of new therapies," say the authors.

Detailed mapping of the anatomical and molecular architectures of brain cells and their connectivity is crucial for understanding human brain function and the impact of brain injuries and diseases. However, current neuroimaging technologies, such as functional magnetic resonance imaging, lack the spatial resolution required to capture the brain's intricate structural, cellular, and molecular details. As part of the BRAIN initiative cell census network (BICCN), Juhyuk Park and colleagues developed a platform that seamlessly combines new mechanical, chemical, and computational tools for creating a brain-wide three-dimensional human brain cell atlas at subcellular resolution.

Park et al.'s novel platform integrates three core elements to enable slicing, processing, and imaging of human-organ scale brain tissues; the MEGAtome – a vibrating microtome – enables ultra-precision tissue slicing without loss of cellular connectivity; a tissue-gel technology termed mELAST transforms tissue samples into elastic and reversibly expandable hydrogels that facilitate high-throughput multiscale imaging; and the UNSLICE computational pipeline reconstructs three-dimensional axonal network connectivity across multiple tissue slabs processed by MEGAtome and mELAST.