New Platform Enables Ultra-Detailed Imaging of Human Brain Tissue

Researchers reveal that a novel technology allows for the simultaneous capture at many scales of neuronal projection, synapse distribution, cellular architecture, and protein expression in large-scale human brain tissues.

The method allows for unparalleled resolution and speed in the thorough imaging and analysis of massive human brain tissue samples, all while preserving the cellular architecture. The authors processed entire hemispheres of the human brain to disclose the degenerative characteristics of Alzheimer's disease tissue, demonstrating the technology's usefulness.

The authors said, “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.”

Understanding human brain function and the effects of brain disorders and traumas requires a detailed mapping of brain cells' anatomical and molecular structures and connectivity. However, existing neuroimaging technologies like functional magnetic resonance imaging do not have the spatial resolution needed to record the brain's complex anatomical, cellular, and molecular intricacies.

Juhyuk Park and colleagues developed a technology that seamlessly incorporates new mechanical, pharmacological, and computational technologies for constructing a brain-wide three-dimensional human brain cell atlas at subcellular resolution as part of the BRAIN Initiative Cell Census Network (BICCN).

The UNSLICE computational pipeline reconstructs three-dimensional axonal network connectivity across multiple tissue slabs processed by MEGAtome and mELAST. 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 known as mELAST transforms tissue samples into elastic and reversibly expandable hydrogels that facilitate high-throughput multiscale imaging.