FUNCTIONAL ULTRASOUND IMAGING OF BRAIN-WIDE NEURONAL ACTIVITY

A team of scientists led by Alan Urban and Gabriel Montaldo developed a new volumetric functional ultrasound imaging (vfUSI) platform based on ultrasound to unravel brain function at unprecedented spatial and temporal resolution. The ease of use, reliability, and affordability of vfUSI the technology make it an excellent candidate for driving future brain-wide neuroimaging research.

Ultrasound is the first clinical modality for soft tissues and deep organ imaging, such as the heart, lungs, bladder, etc. It is routinely used in the hospital thanks to its real-time capabilities, safety, and low cost.

Over the past ten years, the Urban lab has contributed to the development of innovative brain ultrasound hardware and software solutions in collaboration with several academic and industrial partners. This culminated in the use of functional ultrasound imaging (fUSI) to visualize neural activity by mapping local changes in cerebral blood flow based on the Doppler effect—the shift in frequency of an emitted wave due to the motion of red blood cell relative to the ultrasound transducer.

Initially restricted to cross-sectional 2D imaging with a small field of view, visualizing the whole brain using fUSI required stepping the transducer across multiple positions, involving long acquisition times and repetitive stimulus presentation (which may trigger habituation).

A versatile imaging platform

To overcome these problems, a team of scientists led by Alan Urban developed volumetric fUSI (vfUSI) based on a 2D-array transducer matrix array multiplexing to enable 3D imaging with only a 256 channels ultrasound electronics. The team also developed a high-performance computing workstation and a standardized software pipeline, ensuring reliable registration, segmentation and data analysis across experimental sessions based on the broadly accepted Allen Mouse Common Coordinate Framework.

“We wanted not only to release the most advanced functional ultrasound imaging platform for neuroscience research but also to simplify its integration into routine experiments,” says Clément Brunner, co-first author on the study.

“For the first time, it is possible to quickly gain access to the spatiotemporal dynamics of brain-wide activity during behavior, directly at the bench,” adds Micheline Grillet, the other co-first author.

In collaboration with researchers from the laboratory of Karl Farrow (also at NERF) and with Emilie Mace from the Max Planck Institute of Neurobiology in Germany, the team demonstrated the high sensitivity of vfUSI under multiple experimental conditions. Moreover, they revealed the sequential activation of sensory-motor cortical and subcortical regions during a grasping water droplet task as never seen before with other imaging techniques, including fMRI.

Ready for the clinics

The monitoring of newborns and adults with critical neurologic illness has expanded significantly over several decades. Still, it relies on frequent clinical examinations to detect neurologic deterioration, which is cumbersome. Available neuromonitoring devices are relatively low resolution, not user-friendly, and cannot provide objective measurements. Data interpretation is often limited by the availability of highly trained clinicians and nursing staff. Additionally, the interventions taken to treat these conditions (such as induced coma, profound sedation, or brain cooling) could further mask the clinical signs necessary for detecting an acute change.