Editorial: The human brain multiscale imaging challenge

The combination of tissue preparation techniques (Costantini et al., 2019), advanced optical microscopy (Abdelfattah et al., 2022), and big data analysis is revolutionizing the way of studying the brain anatomy (Ueda et al., 2020). These techniques already allowed mapping of cell distribution or reconstruction of neuronal circuits in whole mouse brains (BRAIN Initiative Cell Census Network, 2021; Silvestri et al., 2021). However, the analysis of the human brain is still in its infancy. Such specimens present specific challenges that need to be solved in comparison to animal models: massive dimension of the specimen (up to several cm3), geometry, variability of post-mortem fixation conditions and storage, presence of blood inside the vasculature, autofluorescence signals from lipofuscin-type pigments, and consistency of cellular labeling. In addition, alteration of antigens, due to fixation and storage conditions, may prevent reliable immunostaining (Weiss et al., 2021; Pesce et al., 2022). Various optical technologies have started to address human brain reconstruction in combination with advanced staining methods or relying on label-free detections (Axer et al., 2016; Wang et al., 2018; Menzel et al., 2020; Costantini et al., 2021a) but much remains to be done. Moreover, the capability of achieving the reconstruction of human brains has also raised the problem of creating new software platforms that enable to manage, analyze, and share TB-sized volumetric images (Tyson and Margrie, 2022). In this collection various methodologies are proposed to perform human brain study from the macro- to the microscale. These studies are summarized in the following paragraphs.