New Technology Enables 3D Subcellular Imaging of Whole Human Brain Hemispheres

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Three-Dimensional Imaging of Whole Human Brains

The new study does not present a comprehensive map or atlas of the entire brain, where every cell, circuit, and protein is identified and analyzed. Instead, the research provides a proof of concept by demonstrating an integrated pipeline of three technologies for whole hemispheric imaging, according to the source article. The innovations allow scientists to view sweeping landscapes of thousands of neurons within whole brain regions, diverse forests of cells in individual detail, and tufts of subcellular structures nestled among extracellular molecules.

According to the source article, the importance of imaging whole hemispheres of human brains intact down to the resolution of individual synapses serves a twofold purpose in understanding the brain in health and disease. It allows scientists to conduct integrated explorations using the same brain rather than constructing composite pictures from varying samples, and it maintains tissue durability for repeated labeling.

Three Key Innovations Driving the Pipeline

The development of the technology pipeline relies on three major innovations created by researchers on the team, as reported by the source article. Ji Wang developed a mechanical device called the Megatome to slice intact human brain hemispheres finely without causing tissue damage. Juhyuk Park created a chemistry technology known as mELAST, which makes each brain slice clear, flexible, durable, expandable, and quickly, evenly, and repeatedly labelable. The mELAST technology makes the samples extremely durable and repeatedly re-labelable to highlight different cells or molecules over potentially years of study. The research team demonstrated the use of 20 different antibody labels to highlight specific cells and proteins, with plans to expand to a hundred or more.

Scalability and Future Research Applications

Imaging a whole brain hemisphere once prepared takes 100 hours rather than many months, offering high scalability and throughput, according to the source article. This speed allows researchers to create many samples representing different sexes, ages, and disease states for robust statistical comparisons.

We need to be able to see all these different functional components — cells, their morphology and their connectivity, subcellular architectures, and their individual synaptic connections — ideally within the same brain, considering the high individual variabilities in the human brain and considering the precious nature of human brain samples, Chung said, as reported by the source article. This technology pipeline really enables us to extract all these important features from the same brain in a fully integrated manner.

The researchers also presented a rich variety of quantitative analytical comparisons focused on a chosen region within Alzheimer’s and non-Alzheimer’s hemispheres. Chung envisions establishing a brain bank of fully imaged specimens that scientists can analyze and re-label for future studies, according to the source article.