Brain-Wide Transcranial Ultrasound Localization Microscopy of the Non-Human Primate.

Transcranial ultrasound localization microscopy (t-ULM) faces significant challenges for broader clinical and research applications, particularly in addressing image quality degradation caused by skull. Research on non-human primate (NHP) models, with their human-like cranial characteristics, offers crucial insights for technical innovations and neuroscience applications of t-ULM. In this study, we developed a systematic pipeline for t-ULM of NHP, incorporating low-frequency diverging wave emission, phase aberration correction and microbubble detection equalization. We also explored the contrast agent strategies and imaging plane selection. We achieved an optimal spatial resolution of 93 μm in the coronal section and 105 μm in the sagittal section at an emission frequency of 2.23 MHz, while both maintaining 5-8 cm penetration depth and 6 cm lateral field of view. We also obtained the hemodynamic mapping with a wide dynamic range up to 40 cm/s at 1000 Hz compounded frame rate. This work validates the feasibility of t-ULM in the NHP, and provides important tools and references for further neuroscience applications of t-ULM.