Intraoperative ultrasound localization microscopy of human brain tumors and arteriovenous malformations

The microvasculature and hemodynamics of human brain tumors and other lesions have remained largely unexplored in vivo due to the limited resolution of conventional imaging techniques, and may present new opportunities in biomarker identification and neurosurgeries. Ultrasound Localization Microscopy (ULM), which tracks freely circulating intravascular microbubbles used as contrast agents, overcomes these limitations and has been used to visualize vascular structures and flow. In this study, we performed intraoperative ULM during brain surgeries involving resection of brain tumors (N = 3 meningiomas, N = 3 brain metastasis, N = 3 high grade gliomas) and an arteriovenous malformation (AVM) (N = 1). ULM provided microvascular images of the human brain, resolving vessels down to 35 μm, revealing clear differences in structure and dynamics between tumor and surrounding healthy tissue. By following individual microbubbles, vessel connectivity was probed and used to identify feeding, draining, and non-tumoral vessels. In one case, a 3D ULM map of an AVM was generated with 226 μm resolution, allowing us to resolve its complex internal structure, including feeding and draining vessels. Intraoperative ULM enables visualization of human brain vasculature and hemodynamics at unprecedented resolutions, and may directly aid tumor and AVM resections by providing flow paths and speeds through compact niduses.