Light-Sheet Unlocks Speed for Whole Human Brain Microscopy

In a human brain, around 200 billion cells are working together, shaping who a person is. Grasping their complex organization, even in a single brain, remains a major challenge. Advances in tissue clearing provide a window onto cells inside of intact brains; however, imaging cleared tissues on the scale of the whole human brain presents many challenges, with conventional methods likely to require years of acquisition time per brain.

This presentation will reveal a complete imaging and analysis pipeline developed specifically to achieve high-throughput, multispectral imaging of entire, cleared and immunolabeled human brains at cellular resolution for cell-type atlasing with acquisition times of about two weeks. The human brain optimized light-sheet (HOLIS) microscopy system is a form of oblique-plane single objective light-sheet, capable of imaging 5 mm thick, optically cleared, complete coronal sections of human brain designed for highest throughput acquisition and cell type resolved atlasing with data analysis in mind.

About the presenter
Malte Johannes Casper, Ph.D., is a postdoc at Elizabeth Hillman’s lab at Columbia University. He received a bachelor’s degree in medical computer science from the University of Lübeck in 2014 and a master’s degree in medical engineering science in 2017, and his doctorate in biomedical engineering from Columbia University in 2024.

During his doctorate, he developed, based on SCAPE microscopy (Swept confocally aligned planar excitation), a high-throughput light-sheet system for large-scale imaging of optically cleared tissue.