During brain surgery, healthy and diseased brain regions are marked with sterile papers to define the margins for a safe operation. These margins are defined through communication between the neurosurgeon and a team of electrophysiologists located in a different part of the operating area. Adding further difficulty, the electrode grids that are used to measure brain activity and identify the boundaries between pathological and functional brain regions have low resolution and limited conformity to the brain surface. To enable more efficient monitoring of brain surface activity during surgery, a scientific team led by professor Shadi Dayeh at the University of California San Diego, comprising engineers and physicians from UC San Diego and Massachusetts General Hospital (MGH), developed a microLED display that produces a visual representation of the brain’s activity in real time. The intracranial electroencephalogram (iEEG)-microdisplay could improve the way neurosurgeons observe brain states while performing surgical interventions to remove tumors and epileptic tissue. Each LED in the device mirrors the activity of a few thousand neurons. In a series of proof-of-concept experiments in rodents and large non-primate mammals, researchers showed that the device can track and display neural activity in the brain corresponding to different areas of the body. In this case, the LEDs developed by the team light up red in the areas that need to be removed by the surgeon. Surrounding areas that control critical functions and should be avoided show up in green. Courtesy of University of California San Diego. The iEEG-microdisplays consist of freestanding arrays of gallium nitride LEDs laminated on the back of micro-electrocorticography electrode grids. Each LED in the microdisplay mirrors the activity of a few thousand neurons. When an iEEG-microdisplay is laminated on the brain surface, it can record and display cortical activities according to spatially corresponding light patterns on the surface of the brain in the surgical field. The microdisplays measure 5 x 5 sq mm and 32 x 32 sq mm and include either 1024 or 2048 LEDs. The device also provides acquisition and control electronics and software drivers to analyze and project cortical activity directly from the surface of the brain. A special manufacturing technique was developed to produce high-efficiency LEDs that do not heat up when illuminated. “These gallium nitride-based, inorganic microLEDs, substantially brighter and more power-efficient than organic LEDs, can maintain clear visibility under surgical lights that may exceed the brightness of direct sunlight,” said Youngbin Tchoe, formerly a researcher in the Dayeh group and now a professor at Ulsan National Institute of Science and Technology. “The iEEG-microdisplay, just a few tens of microns thick, captures brain activity at 20,000 samples per second across thousands of channels and visualizes it at a video rate of 40 Hz. This enables precise and real-time displays of cortical dynamics during critical surgical interventions,” Tchoe said. To make the visual representation of brain activity patterns more precise, the researchers printed indium phosphide quantum dot color conversion ink on the surface of the LEDs. The quantum dot ink can convert the LED blue light to multiple colors, allowing normal brain activity to be displayed in one color and abnormal brain activity in another. “This enables richer and more nuanced visual representation of neural activity patterns,” Dayeh said. The iEEG device displays the boundaries between healthy and diseased brain areas with sub-mm resolution. In contrast, current approaches to monitoring brain activity during surgery do not produce detailed data, so surgeons must maintain a large resection margin of 5-7 mm around the diseased region. MGH researcher Angelique Paulk, a co-inventor of the iEEG-microdisplay, said that existing methods of communicating critical information during a procedure are inefficient and can impact surgical outcomes. Researchers at UC San Diego embedded thousands of LEDs in flexible films and released them from the substrate in the form of a flexible display panel. The researchers then used inkjet printing to deposit quantum dot inks on the surface of the LEDs to convert their blue light to other colors. Courtesy of University of California San Diego. The detail provided by the iEEG-microdisplay could shrink the resection margin for surgery to less than 1 mm, increasing the likelihood of a successful outcome. “We invented the brain microdisplay to display, with precision, critical cortical boundaries and to guide neurosurgery in a cost-effective device that simplifies and reduces the time of brain mapping procedures,” Dayeh said. In a series of proof-of-concept experiments in pigs and rats, the iEEG-microsdisplay enabled visualization of spontaneous and elicited cortical activity and functional cortical boundaries on the surface of the brain. The LEDs displayed red in the diseased areas, while the surrounding areas that controlled critical brain functions displayed a green light. The researchers also showed that the microdisplay could visualize the onset and map the propagation of an epileptic seizure on the surface of the brain. This capability could be used to isolate the parts of the brain that are involved in epilepsy. “Neurosurgeons could see and stop a seizure before it spreads, view what brain areas are involved in different cognitive processes, and visualize the functional extent of tumor spread,” Daniel Cleary, MD, formerly a researcher at UC San Diego and now a neurosurgeon and professor at Oregon Health and Science University, said. “This work will provide a powerful tool for the difficult task of removing a tumor from the most sensitive brain areas.” The team is now at work on a microdisplay that will include 100,000 LEDs, with a resolution equivalent to that of a smartphone screen. Each LED in the microdisplay will reflect the activity of a few hundred neurons. The cost of the microdisplay will be a fraction of the cost of a high-end smartphone. These LEDs are part of a grid that is 5 square millimeters. The display in this small version includes 1048 LEDs. The researchers used their expertise in working with gallium nitride to develop a manufacturing technique for high-efficiency LEDs that do not heat up when they light up and do not damage brain tissues. Courtesy of University of California San Diego. The prospective microdisplay will include a foldable portion. Surgeons will be able to operate within the foldable portion of the display and monitor the impact of the procedure with the unfolded portion, which will show the status of the brain in real time. The team also plans to build customized hardware to change the frequency of the pulses that turn on the LEDs, to make it easier to screen out irrelevant signals caused by the proximity of the LED sensors to the grids. The iEEG-microdisplay promises to improve the monitoring of pathological brain activity in clinical settings. “The brain iEEG-microdisplay can impressively both record the activity of the brain to a very fine degree and display this activity for a neurosurgeon to use in the course of surgery,” said Jimmy Yang, a neurosurgeon and professor at Ohio State University. “We hope that this device will ultimately lead to better clinical outcomes for patients, with its ability to both reveal and communicate the detailed activity of the underlying brain during surgery.” The research was published in Science Translational Medicine (www.doi.org/10.1126/scitranslmed.adj7257).
