A functional ultrasound brain GPS for automatic vascular-based neuronavigation.

Recent advances in ultrasound imaging triggered by transmission of ultrafast plane waves have rendered functional ultrasound (fUS) imaging a valuable neuroimaging modality capable of mapping cerebral vascular networks, but also for the indirect capture of neuronal activity with high sensitivity thanks to the neurovascular coupling. However, the expansion of fUS imaging is still limited by the difficulty to identify cerebral structures during experiments based solely on the Doppler images and the shape of the vessels. In order to tackle this challenge, this study introduces the vascular brain positioning system (BPS), a GPS of the brain. The BPS is a whole-brain neuronavigation system based on the on-the-fly automatic alignment of ultrafast ultrasensitive transcranial Power Doppler volumic images to common templates such as the Allen Mouse Brain Common Coordinates Framework. This method relies on the online registration of the complex cerebral vascular fingerprint of the studied animal to a pre-aligned reference vascular atlas, thus allowing rapid matching and identification of brain structures. We quantified the accuracy of the automatic registration using super-resolution vascular images obtained at the microscopic scale using Ultrasound Localization Microscopy and found a positioning error of 44 µm and 96 µm for intra-animal and inter-animal vascular registration, respectively. The proposed BPS approach outperforms the manual vascular landmark recognition performed by expert neuroscientists (inter-annotator errors of 215 µm and 259 µm). Using the online BPS approach coupled with the Allen Atlas, we demonstrated the capability of the system to position itself automatically over chosen anatomical structures and to obtain corresponding functional activation maps even in complex oblique planes. Finally, we show that the system can be used to acquire and estimate functional connectivity matrices automatically. The proposed functional ultrasound on-the-fly neuronavigation approach allows automatic brain navigation and could become a key asset to ensure standardized experiments and protocols for non-expert and expert researchers.

Functional ultrasound imaging reveals different odor-evoked patterns of vascular activity in the main olfactory bulb and the anterior piriform cortex.

Topographic representation of the outside world is a key feature of sensory systems, but so far it has been difficult to define how the activity pattern of the olfactory information is distributed at successive stages in the olfactory system. We studied odor-evoked activation patterns in the main olfactory bulb and the anterior piriform cortex of rats using functional ultrasound (fUS) imaging. fUS imaging is based on the use of ultrafast ultrasound scanners and detects variations in the local blood volume during brain activation. It makes deep brain imaging of ventral structures, such as the piriform cortex, possible. Stimulation with two different odors (hexanal and pentylacetate) induced the activation of odor-specific zones that were spatially segregated in the main olfactory bulb. Interestingly, the same odorants triggered the activation of the entire anterior piriform cortex, in all layers, with no distinguishable odor-specific areas detected in the power Doppler images. These fUS imaging results confirm the spatial distribution of odor-evoked activity in the main olfactory bulb, and furthermore, they reveal the absence of such a distribution in the anterior piriform cortex at the macroscopic scale in vivo.