In collaboration with researchers from the University of Southern California, a Caltech professor has for the first time demonstrated a new technology for imaging the human brain with laser light and ultrasound waves.
The technology, known as Photoacoustic Computed Tomography or PACT, was developed by developed Lihong Wang, Bren Professor of Medical Technology and Electrical Engineering, as a method for mapping tissues and organs. Earlier versions of PACT technology were shown to be able to map the internal structures of a rat’s body; PACT is also able to detect tumors in the human breast, making it a possible alternative to mammography.
Now Wang has further improved the technology that makes it so precise and sensitive that it can detect even tiny changes in the amount of blood flowing through very small blood vessels and the oxygen levels in that blood. Because blood flow increases in certain areas of the brain during cognitive tasks – blood flow to the visual cortex increases while watching a movie, for example – a device that shows changes in blood concentration and oxygen supply can help researchers and medical professionals monitor brain activity. This is called functional imaging.
“With breast imaging, you only want to see blood vessels because they can reveal the presence of a tumor [tumors secrete chemicals that stimulate blood vessel formation]”Says Wang. “But the functional change in the mapped brain activity is only a change in the baseline signal of a few percent. That is more than an order of magnitude harder to measure. “
To date, this type of imaging has only been done with functional magnetic resonance imaging (fMRI), which use radio waves and magnetic fields 100,000 times stronger than the Earth’s magnetic field to monitor blood oxygen levels. The machines work well and are a mature technology, but they have some drawbacks. For one thing, they’re very expensive, costing a few million dollars each. Another disadvantage is that the strong magnetic fields generated by the machine require special precautionary measures as ferrous objects such as some medical tools and surgical implants can be pulled from the machine with great force Imaging is placed in a narrow tube, which can be uncomfortable for people with claustrophobia.
In contrast, Wang’s technology is much simpler, cheaper, and more compact, and doesn’t require the patient to be placed in the device.
It works by shining a pulse of laser light into the head. When the light shines through the scalp and skull, it is scattered by the brain and absorbed by oxygen-carrying hemoglobin molecules in the patient’s red blood cells. The energy that the hemoglobin molecules absorb from light causes them to vibrate with ultrasound. These vibrations travel back through the tissue and are detected by a series of 1,024 tiny ultrasonic sensors attached to the outside of the head. The data from these sensors is then combined by a computer algorithm into a 3D map of the blood flow and oxygen supply throughout the brain.
To test the technology in humans, Wang worked with Jonathan Russin, assistant professor of clinical neurological surgery at the Keck School and assistant director of the USC Neurorestoration Center; Danny J Wang, professor at the USC Institute for Neuroimaging and Informatics; and Charles Liu, professor of clinical neurological surgery at the Keck School and director of the USC Neurorestoration Center.
After severe traumatic brain injury, some patients undergo decompressive hemicraniectomy, a life-saving procedure that involves removing a large portion of the skull to control pressure from the swelling of the brain. Liu and Russin work with many of these patients at Rancho Los Amigos National Rehabilitation Center in Downey, California, where Liu is the director of innovation and research. After recovery from an acute injury, but prior to skull reconstruction, selected patients participated in this study to determine how well the imaging technology was performing.
“One hurdle that we still have to overcome is the skull,” says Wang. “It’s an acoustic lens, but it’s a bad one, so it also distorts our signal with attenuation. It’s like looking outside through a wavy window, ”he says. “But they have a population of patients who have had a hemicraniectomy. They are missing a part of their skull so that we can imagine them. “
“Neuroimaging is central to the development of new treatment paradigms, and this demonstration is a very important step in developing a powerful new tool that complements current approaches such as MRI-based techniques,” says Russin.
Liu agrees, adding that “Many of the most exciting therapeutic approaches to functional restoration involve neuromodulation strategies that cannot be explored in the MRI environment, and we look forward to using this new technology to better understand our treatments and refine. Many of the participants in this study may eventually need new treatments, so this is an excellent opportunity to develop a tool that will ultimately benefit them. “
To image a patient, the research team shaves their head (a step they want to eliminate, according to Wang) so the laser light can illuminate their scalp. The patient then lies down on a table with their head partially resting in a bowl that contains the laser source, ultrasound sensors, and water. The water acts as a “mediator” by acoustically coupling the sensors to the surface of the scalp and allowing them to pick up signals efficiently, says Wang. It is analogous to the gel that is applied to the skin when a patient is given an ultrasound.
Wang says future research needs to focus on solving the problems caused by the hair and skull. He said it might be possible to avoid shaving a patient’s head if optical fibers could be used to transmit the pulses of laser light between hair follicles on the scalp. And he also hopes to be able to use the technology in patients with intact skulls at some point.
“We need a way to counteract the distortion caused by the skull,” he says, adding that such a corrective “lens” will most likely be a more powerful computing algorithm that can compensate for the distortion when composing an image.
A paper describing the technology entitled “Massively parallel functional photoacoustic computed tomography of the human brain“Appears in the May 31st issue of May magazine Nature Biomedical Engineering. Caltech’s co-authors are postdoctoral researchers Shuai Na and Li Lin (PhD ’20); Medical technology student Peng Hu; Konstantin Maslov, research fellow at the Andrew and Peggy Cherng Department of Medical Engineering; Junhui Shi, former postdoctoral fellow now at Zhijiang Laboratories; and Xiaoyun Yuan, former visiting scholar, now at Tsinghua University in Beijing. USC co-authors are Jonathan Russin, Charles Y. Liu, Kay Jann, Lirong Yan, and Danny Wang.
The research was funded by the National Institutes of Health.