In a proof-of-concept study, researchers from the Keck School of Medicine of USC and the California Institute of Technology (Caltech) have developed and implanted a transparent window in a patient’s skull and utilized functional ultrasound imaging (fUSI) to gather high-resolution brain imaging data through the window. Their initial findings indicate that this non-invasive method could revolutionize patient monitoring, clinical research, and our understanding of brain function.
“This is the first time anyone had applied functional ultrasound imaging through a skull replacement in an awake, behaving human performing a task,” said Charles Liu, MD, PhD, a professor of clinical neurological surgery, urology, and surgery at the Keck School of Medicine and director of the USC Neurorestoration Center. “The ability to extract this type of information noninvasively through a window is pretty significant, particularly since many of the patients who require skull repair have or will develop neurological disabilities. In addition, ‘windows’ can be surgically implanted in patients with intact skulls if functional information can help with diagnosis and treatment.”
After a skateboarding accident in 2019, a research participant, 39-year-old Jared Hager, suffered a traumatic brain injury (TBI). He underwent emergency surgery, which involved the removal of half of his skull to alleviate pressure on his brain, resulting in a portion of his brain being only covered by skin and connective tissue. Due to the pandemic, he had to wait for over two years to receive a prosthetic replacement for his skull.
During this period, Hager participated in earlier research involving a new form of brain imaging known as fPACT, conducted by Liu, Jonathan Russin, MD, associate surgical director of the USC Neurorestoration Center, and another Caltech team.
The experimental technique had been used on soft tissue but could only be tried on the brain in patients such as Hager, who had a portion of their skull missing. When it was time to implant the prosthesis, Hager willingly collaborated with Liu and his team to create a customized skull implant to study the effectiveness of fUSI. This innovative approach allowed them to study brain activity while repairing Hager’s injury.
Prior to the reconstructive surgery, the research team meticulously tested and fine-tuned fUSI parameters for brain imaging using both phantom and animal models. Subsequently, they gathered fUSI data from Hager as he performed various tasks before and after the transparent implant’s installation. These experiments revealed that the transparent implant provided an efficient means of measuring brain activity.
Functional brain imaging is crucial for understanding brain function in both healthy individuals and those with neurological conditions. However, current methods like fMRI and EEG have limitations such as low resolution and invasiveness. A promising alternative, fUSI, may overcome these challenges by offering a sensitive and precise solution.
Liu has worked closely with Mikhail Shapiro, PhD, and Richard Andersen, PhD, of Caltech, to develop advanced ultrasound sequences for measuring brain function and optimizing brain-computer interface technology. Collaborating with a neurotechnology company, they tested transparent skull implants on rats and found that a thin window made from polymethyl methacrylate (PMMA) provided the clearest imaging results. They then proceeded to build a custom implant for Hager.
Before surgery, fUSI data was collected while Hager performed tasks on a computer and played the guitar. After the implant was installed, they compared the results to evaluate the accuracy and usefulness of fUSI imaging data.
“The fidelity, of course, decreased, but importantly, our research showed that it’s still high enough to be useful,” Liu said. “And unlike other brain-computer interface platforms, which require electrodes to be implanted in the brain, this has far less barriers to adoption.”
Functional ultrasound imaging (fUSI) offers significant advantages over other methods, such as fMRI and intracranial EEG. It eliminates the need for implanted electrodes, making it less invasive and more cost-effective. This technology provides a clear window for easy monitoring of potential complications such as blood clots, thus improving patient outcomes. Moreover, it has the potential to offer valuable insights into traumatic brain injury and other neurological conditions while also contributing to a better understanding of the healthy brain’s functions.
“What our findings show is that we can extract useful functional information with this method,” Liu said. “The next step is: What specific functional information do we want, and what can we use it for?”
The use of fUSI and the clear implant remains experimental until they undergo clinical trials. The research team is currently focused on enhancing their fUSI protocols to improve image resolution. Additionally, future research should aim to expand on this initial proof-of-concept study by including more participants to better establish the correlation between fUSI data and specific brain functions, according to the researchers.
Journal reference:
- Claire Rabut, Sumner L. Norman, Whitney S. Griggs, Jonathan J. Russin, Kay Jann, Vasileios Christopoulos, Charles Liu, Richard A. Andersen, Mikhail G. Shapiro. Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window. Science Translational Medicine, 2024; DOI: 10.1126/scitranslmed.adj3143