4D Ultrasound Localization Microscopy of Deep Cerebral Perforating Arteries for Intraoperative Neurosurgical Guidance

The human cerebral microvasculature is both essential for brain function and highly vulnerable, yet its in-vivo structure and local hemodynamics remain largely unexplored due to the lack of imaging techniques capable of resolving deep microvascular flow in humans. This limitation not only constrains fundamental neurovascular research, but poses life-altering risks during neurosurgery, where damage to small perforating arteries can have devastating neurological consequences. Specifically, the deep cerebral perforators, branching from the major trunks of the Circle of Willis, supply essential regions of the cerebral central core but remain beyond the resolution of current intraoperative imaging modalities. Here, we report a first in-human cohort study (10 patients) demonstrating the use of 4-dimensional ultrasound localization microscopy (4D-ULM) for the intraoperative visualization of cerebral microvascular anatomy and hemodynamics. In eight patients, 4D-ULM enabled volumetric mapping of deep perforators with sub-millimeter spatial resolution ([~]140 {micro}m) at depths reaching 7 cm. This approach revealed detailed flow patterns within the previously inaccessible deep vascular networks of the human brain. Our results open new opportunities for studying microvascular physiology and could enhance intraoperative decision-making by providing high-resolution hemodynamic data, paving the way for improved microsurgical precision in neurosurgical procedures.