Functional ultrasound imaging of the human brain activity: An intraoperative pilot study for cortical functional mapping

A wide spectrum of methods is used to image brain activation in vivo, such as functional MRI (fMRI) or positron emission tomography. Both techniques have excellent depth penetration but do not provide good spatial nor temporal resolution. By contrast, ultrasound imaging achieves good spatiotemporal resolution in depth, but until now its poor sensitivity has limited its use to the imaging of major vessels. Functional ultrasound (fUS) derived from the key concept of ultrafast imaging (up to 20 000 frames/s) overcomes this limitation. fUS enables high spatiotemporal resolution imaging of microvasculature dynamics in response to brain activation and was previously validated in rodents. We aim to demonstrate that fUS could find activation maps accurately during brain surgery in humans without requiring electrocortical stimulation mapping (ESM). A clinical study including 10 patients with brain lesion is undertaken, with both fMRI and ESM as gold standard. Patients underwent fMRI before surgery, data were intraoperatively used for ultrasound probe positioning on a targeted functional area using a neuronavigation system (Brainlab AG, Feldkirchen, Germany) and probe location was also confirmed by ESM. A sterilized linear probe driven by an ultrafast ultrasound scanner (Aixplorer, Supersonic Imagine, France) was placed directly on the brain after skull opening. Patients, awake during this part of their surgery, were asked to perform a specific task (motor, sensory or language). fUS imaging with a 6000 Hz frame rate determines regions of brain activity based on the cerebral blood volume (CBV) increase due to neurovascular coupling. This first pilot study demonstrates the ability of fUS imaging to map with a high signal-to-noise ratio (SNR) the stimulus-based neuronal activation in depth in real time during brain surgery. Such technique could be extremely useful for neurosurgeons to improve their surgery and therefore patient quality of life.