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An MIT-based research team has unveiled a breakthrough in neuroscience: a technology pipeline that enables high-resolution, rapid imaging of whole human brain hemispheres. This digital technology has allowed the team to process, label, and image the brains of two donors – one with Alzheimer’s disease and one without – revealing unprecedented detail and opening new avenues for brain research.
“We performed holistic imaging of human brain tissues at multiple resolutions, from single synapses to whole brain hemispheres, and we have made that data available,” says Kwanghun Chung, Associate Professor at MIT and Senior Author of the study. “This technology pipeline enables us to analyse the human brain at multiple scales. Potentially, this pipeline can be used for fully mapping human brains.”
The study showcases an integrated suite of three innovative technologies forming the pipeline. These technologies include the “Megatome” for precise slicing of brain hemispheres, “mELAST” for making brain tissue clear and durable, and “UNSLICE” for computationally reconstructing the brain in three dimensions. This integrated approach allows for comprehensive and detailed imaging, from large brain regions to individual synapses.
The first key innovation, the Megatome, developed by Ji Wang, ensures that human brain hemispheres are sliced finely without damage. This advanced slicer can cut through brain tissue rapidly and accurately, preserving anatomical information and allowing for faster processing times.
Juhyuk Park, the mind behind mELAST, engineered a hydrogel that infuses brain tissue, making it clear, flexible, and virtually indestructible. This innovation allows the brain slices to be labelled with multiple antibodies quickly and repeatedly, enabling detailed imaging of various cells and proteins.
The final puzzle piece, UNSLICE, created by Webster Guan, is a computational system that stitches the brain slices back together into a cohesive 3D model. This technology ensures precise alignment and integration of the brain’s intricate structures, providing a seamless and comprehensive view of the brain’s anatomy.
This technology pipeline represents a significant leap forward for neuroscience. By enabling detailed imaging and analysis of whole brain hemispheres, researchers can now conduct integrated explorations of brain functions and diseases using the same brain, reducing variability and enhancing the reliability of their findings.
Kwanghun and his team have demonstrated the pipeline’s potential with a series of detailed investigations into the brains of donors with and without Alzheimer’s disease. Their findings, such as the concentrated synapse loss in areas with amyloid plaques, highlight the pipeline’s capability to uncover critical insights into neurological conditions.
Moreover, the scalability and throughput of the pipeline mean that many brain samples can be processed and analysed, paving the way for extensive comparative studies across different demographics and disease states. This could create a brain bank of fully imaged brains, accessible for future research and re-labelling as new questions arise.
While the current focus is on the human brain, the technology has broader applications. The pipeline can be adapted to study other tissues in the body, potentially advancing our understanding of various organ functions and disease mechanisms.
“We envision that this scalable technology platform will advance our understanding of human organ functions and disease mechanisms to spur the development of new therapies,” the authors conclude.
This revolutionary digital technology transforms our ability to study the human brain. It holds promise for a wide range of biomedical research, marking a new era in the quest to understand and treat human diseases.
