The gold standard in functional brain imaging for over two decades, functional magnetic resonance imaging (fMRI) has transformed the landscape of research and clinical care. Yet, because of its cost and functional limitations, scientists have continued to look for new ways to see into the human brain.
Researchers from the Keck School of Medicine of USC and the California Institute of Technology (Caltech), with the help of patients recovering from traumatic brain injury, have now demonstrated an alternative way to produce highly detailed images of the human brain. Their work, published in Nature Biomedical Engineering, yielded the first pictures of human brain function ever produced using functional photoacoustic computerized tomography (fPACT) - a landmark in the history of functional brain imaging.
Technology meets technique
Imaging with fPACT works by emitting a beam of laser light into the area being imaged. The light is absorbed by oxygen-carrying hemoglobin molecules in the patient's red blood cells causing them to vibrate ultrasonically. The vibrations can then be scanned by sensors. Lihong Wang, PhD the Bren professor of medical and electrical engineering at the Andrew and Peggy Cherng Department of Medical Engineering at Caltech is a leader in the field of photoacoustic imaging.
The technology has previously been successful in animal and some human tissue models, but there are hurdles to applying it to the brain.
The human skull is an acoustic lens, but it distorts and attenuates our signals. It's like looking outside through a wavy window. The barrier impacts the clarity of the image rendered, a challenge our field is working to overcome."
Lihong Wang, PhD, Bren Professor of Medical and Electrical Engineering at Andrew and Peggy Cherng Department of Medical Engineering, Caltech
Despite the challenges, this research collaboration has shown proof of concept that fPACT can be used for brain imaging. To establish the technology's effectiveness, Charles Liu, MD, PhD, director of the USC Neurorestoration Center and professor of clinical neurological surgery, and Jonathan Russin, MD, an associate director of the USC Neurorestoration Center and assistant professor of clinical neurological surgery, enlisted the aid of traumatic brain injury patients in the USC Neurorestoration Center.
"Our study subjects had undergone hemicraniectomy [the temporary removal of a large portion of the skull], which enabled us to test the technology without interference in fully awake humans prior to skull reconstruction surgery. Thanks to their participation, we discovered fPACT is capable of creating functional brain images that are superior in some ways to 7T fMRI," Liu says. "This may be something that will change neuroimaging forever."
The study subjects were recruited from Rancho Los Amigos National Rehabilitation Center where a large number of cranial reconstruction surgeries are performed. "It is terrific to work with patients to develop transformative tools to better understand how to treat their neurological disabilities", adds Liu, who also serves as chair of neurosurgery and orthopedics and chief of innovation and research at Rancho.
The benefits could be enormous. "fPACT costs less than MRI, is potentially portable, is accessible to patients with implants and eliminates the claustrophobic/magnetic MRI environment," Russin notes. "This study is a first for functional human brain imaging - and, we believe, a critical step forward in advancing the field."
Reactions to results
In order to complete the study, Liu, Russin and Wang solicited critical input from the USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, which provided expertise and resources including access to a state-of-the-art 7-Tesla MRI. "To understand the potential of fPACT, the research team needed to compare it to the best current functional brain imaging," says Danny J.J. Wang, PhD, professor of neurology and radiology. "After reviewing the data, it seems clear that fPACT could have immense impact in neuroscience, with applications ranging from vessel and tumor imaging to localization of function and seizures."
Results from the study highlight fPACT's ability to produce accurate 3D maps of blood flow. Since blood flow increases to specific areas of the brain during cognitive tasks, a device that shows blood concentration and oxygenation changes can help researchers and medical professionals monitor brain activity. This is known as functional imaging.
The study offers key insight into fPACT's long-term potential. Today, Liu, Russin and their team are partnering with Caltech to develop workarounds to skull interference to further investigate the possibilities of fPACT technology.
Na, S., et al. (2021) Massively parallel functional photoacoustic computed tomography of the human brain. Nature Biomedical Engineering. doi.org/10.1038/s41551-021-00735-8.