Human cerebral arterial morphogenesis explored by 3D microscopic imaging of cleared embryos: Bridging the gap between embryonic and adult anatomy.

The anatomy of cerebral arteries impacts cerebrovascular diseases, their management, and their prognosis. Postnatal cerebrovascular anatomy can be understood only through detailed knowledge of the developmental events leading to mature cerebral vessels. Current knowledge about human embryology relies on data collected in the first half of the 20th century using traditional histological methods. In this study, we provide a narrative description of human embryonic cerebral arterial development based on whole-mount immunostaining, tissue clearing, three-dimensional (3D) light sheet microscopy imaging, and anatomically informed virtual segmentation of human embryos. The findings are compared with adult radiological anatomy explored by magnetic resonance imaging and 3D digital subtraction angiography. We provide a detailed account of the development of cerebral arteries including the circle of Willis and its major branches, the vertebrobasilar circulation, the ophthalmic artery, and related vessels. Explanations for several anatomical variants are provided. Pediatric and adult anatomy in the context of brain arteriovenous and vein of Galen malformations is compared with embryological data. Finally, we provide a direct comparison of embryonic and adult anatomical nomenclatures and clarify the identity of homonymous arterial segments. These data shed new light on both embryonic development of cerebral arteries and postnatal anatomy.