Functional ultrasound imaging (fUSI)
An anatomical MRI scan alongside the functional ultrasound imaging plane. [Credit: Rabut, Norman, Griggs et al., Sci. Trans. Med, 16, eadj3143 (2024)]

Scientists have inserted a “window” into a patient’s skull to monitor their brain activity in real-time. An individual’s brain activity could be observed outside of the operating room with the help of a custom-made, ultrasound-transparent cranial window implant, which was given to an adult patient undergoing skull reconstruction surgery after a traumatic brain injury. While the patient was playing a video game and strumming a guitar, ultrasound was used to record brain activity, which was then mapped to specific cortical responses. This research establishes a foundation for future work toward using ultrasonic imaging through transparent skull replacement materials to understand better how the human brain works.

The research article “Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window” was published in Science Translational Medicine.

The brain imaging resolution-invasiveness tradeoff

Measurement of brain function in adults is crucial for diagnosing, tracking, treating, and studying neurological and psychiatric diseases. Still, the present methods of recording brain activity have many compromises related to invasiveness, participant mobility, coverage area, and sensitivity.

Noninvasive methods like functional magnetic resonance imaging (fMRI) allow whole-brain imaging but have low sensitivity, spatiotemporal resolution, and restricted participant movement. Although portable, scalp electroencephalography and functional near-infrared spectroscopy (fNIRS) have variable signal quality and cannot accurately measure deep brain function. Electrocorticography and intracranial electroencephalogram have superior resolution but require electrode insertion beneath the skull or into the brain, limiting their scalability and functional lifetime.

Creating a window into the brain for ultrasound

A new method for imaging the brain called functional ultrasound imaging (fUSI) measures changes in the amount of blood in the brain by picking up backscattered echoes from red blood cells. It can do this over a field of view of several centimeters. These changes in cerebral blood volume are linked to single-neuron activity and local field potentials through neurovascular coupling. With a framerate of up to 10 Hz and a spatial precision of 100 μm, fUSI can detect the function of small populations of neurons. 

Most importantly, this imaging modality is non-toxic, portable, radiation-free, and proven in rodents, ferrets, birds, nonhuman primates, and humans. Brain imaging using fUSI does not necessitate the utilization of contrast agents or the implantation of electrodes. The imaging equipment is positioned externally to the brain’s protective dura mater. However, in the case of large animals with excessively thick skulls, fUSI necessitates the removal of a section of the skull. This is necessary because ultrasound waves are unable to effectively penetrate these thick skulls, which is crucial for high-resolution imaging techniques.

Functional recording and decoding of live human brain signals

Scientists from the lab of Mikhail G. Shapiro (Caltech’s Max Delbrück professor of chemical and medical engineering and an investigator at HHMI) set out to create a skull replacement window that would allow for the noninvasive performance of fUSI in an awake adult human. That would necessitate the use of an ultrasound-transparent “acoustic window” during a decompressive hemi-cranial resection, which involves replacing part of the patient’s skull.

The team, led by Claire Rabut, PhD, Sumner L. Norman, PhD, and MD-PhD student Whitney S. Griggs, initially assessed the appropriateness of two FDA-approved materials (PMMA and titanium mesh) for fUSI. They utilized a life-sized model of the cerebral vasculature, referred to as an in vitro cerebrovascular phantom, to conduct this evaluation. Subsequently, the team compared the signal and contrast properties of these materials using an in vivo rat cranial defect model.

The Caltech team proceeded to develop a PMMA acoustic window with the intention of including it in a skull reconstruction for human patients. They showed that functional brain signals could be recorded and decoded through this PMMA window while our human subject conducted visuomotor tasks, such as playing a guitar and playing a video game, outside of the operating room, in an ambulatory setting. This development in fUSI-based state decoding of brain waves paves the way for future human ultrasonic brain-machine interfaces and has significant research and clinical implications.

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