Nearly 300,000 soldiers have returned from service in Iraq and Afghanistan with symptoms of traumatic brain injuries due to blast shockwaves. Such injuries often go untreated because they are undetected by brain scans despite the symptoms' presence.
Michael Cho, professor and chair of The University of Texas at Arlington's Bioengineering Department, is leading a collaborative team with researchers at Old Dominion University, Purdue University and the UTA Research Institute to determine for the first time in real time the mechanisms that cause these symptoms.
The work is funded by a new three-year, $1.24 million grant from the Office of Naval Research Warfighter Performance Department and will change the way doctors look for brain injuries suffered in battle. Cho credited Timothy Bentley of the Office of Naval Research with providing insight that helped secure the award for UTA.
Cho joined UTA in March 2015 as the Alfred R. and Janet H. Potvin Endowed Chair in Bioengineering, following a distinguished career in research at Harvard Medical School and the University of Illinois, Chicago. He is a Fellow of the American Institute for Medical and Biological Engineering. He previously was awarded a $1 million grant from the ONR to investigate similar causes of traumatic brain injury.
Duane Dimos, UTA vice president for research, said Cho is a leader in the University's increasing focus on health science innovation and research that advances health and the human condition, a core theme of the Strategic Plan 2020: Bold Solutions | Global Impact. The University also recently appointed Jon Weidanz, an immunologist with expertise in cancer diagnostic and treatment products, as associate vice president for research and professor of biology to strengthen its health science thrust.
"UTA has long had a reputation for excellence in bioengineering and the health sciences, and our faculty members have shown an increasing interest in brain studies. Dr. Cho's collaborative work with other outstanding institutions is the latest outstanding example of our leadership in research in this critical area," Dimos said. "Our new $70-million Science, Engineering Innovation and Research Building is being planned and designed to accommodate and encourage this kind of multi-disciplinary collaboration and lead to new discoveries."
For his most recent project, Cho explained that shockwaves travel faster than the speed of sound, and a soldier who is physically well protected from shrapnel in a blast is not protected from the shockwave. The brain is particularly susceptible to damage from shockwaves, he said.
Scientists suspect that brain injury from shockwaves could be caused by microcavitation. Like the bubbles that form when a submarine's propeller spins -- known as cavitation -- shockwaves form tiny bubbles, or microcavitation, in the brain. These pressurized bubbles create tremendous force when they collapse, which can damage the brain tissue in which they are contained.
When such bubbles form in the brain, they also likely appear in brain blood vessels and potentially affect the blood-brain barrier. The semi-permeable barrier of tightly packed endothelial cells within the capillaries allows some molecules to cross from the bloodstream to the brain but blocks the transfer of many others.
If the blood-brain-barrier is damaged by microcavitation, the mechanical and structural integrity of the blood brain barrier is likely compromised, which may be one of the most critical mechanisms by which brain injuries occur.
Experimental evidence indicates that damage caused by microcavitation measures less than 1 millimeter across, which is outside limits of current in vivo imaging capabilities, so typical brain scans may not detect the damage.
Cho will use microcavitation systems developed by Shu Xiao at ODU as well as multi-modal imaging methods and microfabrication technology to monitor cellular and sub-cellular responses induced by shockwaves and microcavitation in tissue-engineered models of brain tissue and the blood-brain-barrier in real time.
"Micro bubbles have been observed in a phantom model of the head, but never in a real brain. Because this is an individual system that we can follow in real time, we can follow the effects of microcavitation and study the molecular mechanisms that are responsible for causing damage to brain cells," Cho said.
"We know the symptoms are there, but they're not being addressed because we don't know the cause. If we can see that the blood-brain-barrier is damaged, we can perhaps begin contemplating clinical strategies to treat the cause."
UTARI's Vinay Abhyankar will create a microfabricated, biomimetic blood vessel that will mimic the blood-brain-barrier to test and validate the hypothesis that microcavitation may be causing leakage there.
Abhyankar will be able to check leakage in the biomimetic blood vessel, as well as the types of molecules that can pass through. Cho will use different models to see if the blood-brain-barrier is damaged, then send his research to Jeff Varner at Purdue for computational studies to predict activation of potential molecular signaling pathways.
In addition to mechanism studies of blunt force brain tissue injuries, Cho's research focuses on stem cell tissue engineering and cellular biomechanics.
Cho's total funding as a principal investigator is more than $8 million from agencies such as the National Institutes of Health, the U.S. Department of Energy and the Office of Naval Research. He has been funded for more than $1.2 million as co-PI for several other grants, including a five-year, $4 million award from the National Heart, Lung and Blood Institute. He has published more than 200 journal papers, conference proceedings and abstracts.
Khosrow Behbehani, dean of UTA's College of Engineering, lauded Cho's pioneering study of the causes of traumatic brain injuries. "Dr. Cho has a proven track record in performing groundbreaking research. He is at the forefront of the study of combat-related brain injuries, and his work will help the development of more effective treatments for our wounded soldiers," Behbehani said.
Study finds dysfunction of key brain systems in people with psychosis