Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC are forging ahead with their research programs, even in the face of ongoing closures and distancing orders. In addition to creating COVID-ARC, a shared data repository to house imaging, clinical and other data collected from COVID-19 patients, the faculty has received several new awards that build upon the institute’s life-changing studies of the aging brain.

“This spring, in spite of the impact that COVID-19 has had on all of us, the institute has made it a priority to maintain high levels of research productivity,” said Arthur W. Toga, PhD, Provost Professor at the Keck School and director of the institute. “We know that these studies can ultimately improve prevention and care for neurodegenerative diseases and other conditions, so our faculty has remained focused on collecting and analyzing data and publishing new findings.  In addition, we continue to develop new funding proposals and have some good news lately with exciting new awards.”

Exercising in virtual reality

Judy Pa, PhD, associate professor of neurology at the Keck School, received a five-year, $7 million grant from the National Institute on Aging to launch a phase 2 clinical trial of a virtual reality-based intervention for Alzheimer’s disease. NeuroRiderVR, a 16-week program for older adults with concerns about Alzheimer’s disease, combines physical and cognitive exercise to improve brain function in an effort to reduce the risk of developing the debilitating disease. Though both cognitive and physical exercise can be effective in managing Alzheimer’s, few studies have tested a hybrid intervention that combines the two approaches.

Pa and her team will recruit 150 adults, ages 50 to 85, and start by testing cognitive function and the volume and activity of the hippocampus, a brain region associated with memory and one of the first areas affected by Alzheimer’s disease. The participants will then complete the NeuroRiderVR intervention, which involves navigating a VR obstacle course on a stationary exercise bike, and then undergo the cognitive and imaging tests again. The researchers will continue to follow up and test participants for the duration of the five-year study to learn about how the intervention changes the course of risk for Alzheimer’s disease.

“There are arguably nine modifiable lifestyle factors for Alzheimer’s prevention,” Pa said. “Our goal is to step through these factors to identify what combination most effectively reduces risk and for whom.”

Functional imaging of Alzheimer’s disease

Kay Jann, PhD, assistant professor of research at the Keck School, and Danny JJ Wang, PhD, professor of neurology and radiology and director of imaging technology innovation at the Keck School, have received a five-year grant of more than $3.2 million from the National Institute on Aging to apply advanced functional magnetic resonance imaging technology to the study of Alzheimer’s disease. Hosung Kim, PhD, assistant professor of neurology at the Keck School, is a co-investigator on the grant.

Biological markers that allow clinicians to identify Alzheimer’s disease before symptoms occur are a key part of developing effective prevention strategies. Positron emission tomography imaging is the current standard for early tracking of Alzheimer’s disease, but PET scans are expensive and clinicians need to inject patients with a radioactive compound. This study aims to develop a safer and more affordable alternative — a biomarker for Alzheimer’s disease identified by the complexity of fMRI signals. To that end, Jann, Wang and their team are working to develop advanced software and machine learning techniques to evaluate fMRI data on mild cognitive impairment and Alzheimer’s.

“The successful completion of this project will hopefully lead to a noninvasive, economical imaging biomarker of neuronal injury in MCI and Alzheimer’s with relevant tools ready to be deployed in clinical research and care,” Jann said.

Ultra-high-field vascular imaging

Lirong Yan, PhD, assistant professor of neurology at the Keck School, received $300,000 from the BrightFocus Foundation, a nonprofit organization that supports research on brain and eye diseases, to study the role of cerebrovascular diseases in Alzheimer’s, as well as vascular cognitive impairment and dementia.

Yan will use the institute’s ultra-high field 7Tesla MRI scanner to collect detailed images of very small blood vessels in the brain that are difficult to see with lower-resolution scanners. She and her team will develop imaging protocols and post-processing tools to optimize the collection of that data, then study how damage to blood vessels in the brain relates to the cognitive impairment that occurs in Alzheimer’s disease and vascular cognitive impairment and dementia.

“The microvasculature is barely visible on 1.5T and 3T scanners because the spatial resolution is relatively low as a result of limited signal-to-noise ratio,” Yan said. “Using the ultra-high field 7T scanner allows us to get a much clearer picture of cerebral arteries.”

Brain health and stroke recovery

Sook-Lei Liew, PhD, assistant professor of neurology at the Keck School with joint appointments in occcupational science and occupational therapy; biokinesiology and physical therapy; neurology; and biomedical engineering, received nearly $3.1 million from the National Institute of Neurological Disorders and Stroke to study how patients regain motor and sensory function following a stroke.

The study will look at global measures of brain health, which quantify deterioration of systems across the entire brain, in order to understand what role those factors play in a person’s ability to regain brain and body function after suffering a stroke.

“We’re looking at the overall health and integrity of the brain — not just the area damaged by a stroke — to see whether and how global brain health impacts stroke recovery,” Liew said.

She and her team will analyze existing data from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery Working Group, which has collected the world’s largest retrospective data collection of stroke brain scans and sensorimotor behavior. They will also study new data collected at two separate times within the three months following a stroke — when a majority of recovery is thought to occur — by researchers at USC, Emory University, New York University and the University of Melbourne.

— Zara Greenbaum