Whole human-brain mapping of single cortical neurons for profiling morphological diversity and stereotypy.

Quantifying neuron morphology and distribution at the whole-brain scale is essential to understand the structure and diversity of cell types. It is exceedingly challenging to reuse recent technologies of single-cell labeling and whole-brain imaging to study human brains. We propose adaptive cell tomography (ACTomography), a low-cost, high-throughput, and high-efficacy tomography approach, based on adaptive targeting of individual cells. We established a platform to inject dyes into cortical neurons in surgical tissues of 18 patients with brain tumors or other conditions and one donated fresh postmortem brain. We collected three-dimensional images of 1746 cortical neurons, of which 852 neurons were reconstructed to quantify local dendritic morphology, and mapped to standard atlases. In our data, human neurons are more diverse across brain regions than by subject age or gender. The strong stereotypy within cohorts of brain regions allows generating a statistical tensor field of neuron morphology to characterize anatomical modularity of a human brain.

Smart imaging to empower brain-wide neuroscience at single-cell levels.

A deep understanding of the neuronal connectivity and networks with detailed cell typing across brain regions is necessary to unravel the mechanisms behind the emotional and memorial functions as well as to find the treatment of brain impairment. Brain-wide imaging with single-cell resolution provides unique advantages to access morphological features of a neuron and to investigate the connectivity of neuron networks, which has led to exciting discoveries over the past years based on animal models, such as rodents. Nonetheless, high-throughput systems are in urgent demand to support studies of neural morphologies at larger scale and more detailed level, as well as to enable research on non-human primates (NHP) and human brains. The advances in artificial intelligence (AI) and computational resources bring great opportunity to 'smart' imaging systems, i.e., to automate, speed up, optimize and upgrade the imaging systems with AI and computational strategies. In this light, we review the important computational techniques that can support smart systems in brain-wide imaging at single-cell resolution.