An MCMi Regulatory Science Profile
FDA scientist Anjuli Jain conducts an experiment validating nonclinical biomarker models for traumatic brain injury in Dr. Welle’s lab. This research will potentially help establish a regulatory pathway for the use of emerging flexible EEG technologies to rapidly detect brain injury during emergency response situations, such as explosions. (photo: FDA staff)
EEG electrodes used for brain injury biomarker investigation in FDA’s Neural Interface Laboratory. These flexible sensors have gold recording electrodes and conform to the shape of the skin. (photo: Stanley Huang, FDA)
Electrical brain function monitoring has not been studied extensively for medical countermeasures (MCM) during various scenarios involving epidemics, chemical/biological agents, or blast injury. One reason is that electrophysiological measurements of brain function, including EEG, have historically been cumbersome, subject to noise, labor-intensive and require wired connections for data processing. One approach to solving this problem is through the engineering of flexible microelectronics and wireless communications. Much of this engineering work has been accomplished by FDA collaborators at the University of California, San Diego and their colleagues who demonstrated EEG measurements from a flexible device that resembles a “stick-on tattoo.”
Cristin Welle, PhD, is a Staff Fellow in the FDA Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Physics. Dr. Welle is the Principal Investigator of the MCMi project to establish biomarkers for traumatic brain injury monitoring. In this 2012 photo, she is speaking at the FDA Science Writer’s workshop. (FDA photo by Cathy Brown, Flickr)
Principal Investigator: Cristin Welle, PhD
FDA Center: FDA Center for Devices and Radiological Health (CDRH), Office of Science and Engineering Laboratories, Division of Physics
Recent advances in flexible microelectronics that are wearable and conformable to the skin bring us closer to a future where portable electroencephalogram (EEG) technology could be used to detect brain injury in victims of traumatic events such as accidents or explosions.
To evaluate this new technology for use in humans, FDA needs a scientific knowledge base related to validated brain injury biomarkers and models. This research could help pave the way for the development of field-deployable devices that can rapidly collect and evaluate EEG signals to diagnose traumatic brain injury.
Symptoms of brain injury may not appear until days or weeks following a head injury, and CT scans—the standard for diagnosing head injuries—may not be immediately available. EEG technology has the potential to detect traumatic brain injury (TBI) rapidly and non-invasively. However, traditional EEG technology is labor- and equipment-intensive, and the development of commercially available portable devices that can collect and evaluate EEG signals for the diagnosis of TBI is still underway.
Recent innovations in flexible and portable electronics may be used to create “smart sensors” that allow emergency responders to detect EEG signals rapidly in the field environment. However, development of portable devices that can detect TBI is hindered by a lack of validated biomarkers and models of brain injury. FDA and industry use these models and biomarkers to evaluate the effectiveness of new devices for regulatory approval before such devices can be marketed.
This research will benefit the public and industry by developing useful brain injury models, identifying and validating brain injury biomarkers, and studying the potential for new EEG technologies to diagnose traumatic brain injury in the field.
This project supports several goals identified in the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) strategy and implementation plan, including establishing regulatory pathways to facilitate medical countermeasure (MCM) development and use, and address MCM gaps for all sectors of the American civilian population. The tangible results of this project will include:
- Developing a calibrated brain injury model through the use of highly reproducible, high-intensity focused ultrasound (HIFU);
- Identifying and validating the electrophysiological, anatomical, and behavioral correlates of the brain injuries produced in the calibrated brain injury model; and
- Testing how correlates observed in the electrophysiological signal might be detected by a new, rapidly developing class of non-invasive electrodes.
“Breakthrough technology can—and should—be used to improve medical devices and promote public health. Our lab hopes to contribute to this discovery process by identifying changes in brain signals following injury, and then looking for those same changes using a novel flexible electrode technology.
"We envision a day when soldiers or civilians who have experienced a blast or a head impact will be able to stick a small sensor to their forehead and know if they have sustained a brain injury. Although we may not be the ones who develop such a device, we want to contribute research that can help advance the field.”
–Cristin Welle, PhD
Cristin Welle, PhD, is the principal investigator of the Neural Implant Lab in the Division of Biomedical Physics at FDA, where she directs a team of scientists in the development of test platforms to evaluate the long-term safety and reliability of neural interface devices. The lab’s goal is to contribute to the scientific knowledge base required to speed innovative neural device development and regulatory review. Dr. Welle brings expertise in neurophysiology and cortical microcircuitry from her graduate and postdoctoral experience at the University of Pennsylvania.
This project builds on a current FDA/CDRH collaboration with the Defense Advanced Research Projects Agency (DARPA) on neuroprosthetic technology. CDRH is also collaborating on research for novel flexible EEG electronics with the University of California, San Diego, Harvard University, and Massachusetts General Hospital. The project uses and improves a nonclinical model developed by FDA and the Uniformed Services University of the Health Sciences.
- Traumatic Brain Injury (information from CDC)
- Kim TI, Chowdhury R, Ying M, Xu L, Li M, Chung HJ, Keum H, McCormich M, Liu P, Zhang YW, Omenetto FG, Huang Y, Coleman T, Rogers JA (2011) Epidermal electronics. Science. 333 (6044): 838-843.
CDRH – FDA Center for Devices and Radiological Health – CDRH facilitates medical device innovation by advancing regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the U.S.
EEG – electroencephalogram – an electroencephalogram is a test that detects electrical activity in the brain
HIFU – High-intensity focused ultrasound – HIFU pressure waves will be used to produce a defined, repeatable brain injury model
MCM – medical countermeasure (see also: What are Medical Countermeasures?)
PHEMCE – Public Health Emergency Medical Countermeasures Enterprise (PHEMCE website)