“Understanding the brain in all its complexity is impossible for any group to accomplish in isolation.”
-Arthur Toga, Director
We’ve built a diverse team of neurobiologists, mathematicians, and computer scientists, and a worldwide network of collaborators sharing data. Our goal is to increase the pace of discovery in neuroscience by better understanding how the brain works when it’s healthy and what goes wrong in disease.
Our facility houses two advanced Magnetic Resonance Imaging scanners for data acquisition: a Magnetom Prisma 3T and a Magnetom Terra 7T.Learn more
LONI’s onsite data center features state-of-the-art security technology and can store more than four petabytes of brain imaging data.Learn more
While neuroimaging is a valuable window into what happens inside the brain, it’s still an imprecise measure. Even after decades of technological advances, magnetic resonance imaging (MRI) scans still aren’t sharp enough to reveal what’s going on at the cellular level.
“By looking at brain scans, we don’t always know what mechanisms are driving a pattern of change in a given illness,” says Paul Thompson, PhD, professor of ophthalmology, neurology, psychiatry and the behavioral sciences, radiology, and engineering and associate director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute. “Researchers are left with a bit of a puzzle as to what those changes represent.”
But now, a revolutionary partnership between Thompson’s Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium—a massive data-sharing effort between scientists in 45 countries—and researchers at the University of Toronto has led to a new method that can help pin down the mechanisms behind key psychiatric and developmental disorders. It’s a powerful breakthrough that bridges the gap between imaging and genetics research to identify the specific cells and molecules at play.
The team analyzed data on cortical thickness from more than 28,000 disease patients and healthy controls, ages 2 to 89, including individuals with schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, autism spectrum disorder and attention-deficit/hyperactivity disorder. They identified a common molecular signature that spans all six disorders, publishing their findings in the journal JAMA Psychiatry in August.
The results can help pharmaceutical companies develop drug treatments that more directly address brain abnormalities, while the method developed by the team can be applied to other illnesses gain innumerable insights into the brain.
“This is a unique opportunity for science,” says Tomáš Paus, MD, PhD, professor at the University of Toronto and senior author of the paper. “ENIGMA has helped drive social innovation that allows us to move forward incredibly quickly—and to generate powerful new knowledge.”
LINKING IMAGING AND GENETICS
The new method developed by Paus and his team, known as “virtual histology,” uses atlases of gene expression to connect the dots between MRI scans and what’s happening in the brain at the cellular level. That’s possible because specific groups of genes mark certain types of cells in the brain.
For example, imaging data revealed that one cell type in particular—the pyramidal neuron—often underlies the MRI signature of the diseases studied.
“Regions that have more of these cells show a bigger difference in cortical thickness between disease cases and controls,” Paus says.
Building on this finding, Yash Patel, first author of the paper and a doctoral student in Paus’ lab, conducted a “co-expression analysis,” which identifies the genes involved in shaping those cells and plots their expression over time.
“We found two groups of genes responsible for controlling those pyramidal cells—one prenatal and one postnatal,” says Patel.
The prenatal genes control the development of axons and other infrastructure in the brain, while the postnatal genes are related to plasticity and neurotransmission. Those findings suggest that people who develop schizophrenia, bipolar disorder and the other brain diseases studied may experience common environmental influences after birth that triggers disease onset, Patel says.
By applying the virtual histology method to the massive datasets aggregated by the ENIGMA network, the study’s authors have begun to uncover the biological mechanism that links genetic vulnerability for a disorder to actual changes in the brain.
Looking forward, Paus and his team plan to conduct a similar analysis on the brain’s surface area and to apply the virtual histology method to a series of other problems, including Alzheimer’s disease, Parkinson’s disease and brain trauma.
“We can only develop practical remedies for these conditions if we know which genes, molecules and pathways to home in on,” Thompson says. “This method provides that crucial bridge for information to travel between the genetics and imaging communities.”
Researchers based at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute have conducted the largest-ever diffusion imaging study of 22q11.2 deletion syndrome (22q11DS). The genetic disorder, caused by a small segment of missing DNA on chromosome 22, is the strongest known genetic risk factor for schizophrenia.
For patients with tumors, strokes, cerebrovascular disease and other conditions, computed tomography (CT) scans can be lifesaving. But there’s a growing concern that the radiation involved is unnecessarily harmful to patients.
The USC Mark and Mary Stevens Neuroimaging and Informatics Institute (USC INI) of the Keck School of Medicine of USC has received accreditation from the American College of Radiology (ACR) for its 7Tesla Siemens Magnetom Terra magnetic resonance imaging (MRI) scanner.
Widely recognized as the “gold standard” in medical imaging, the ACR has assessed various imaging modalities, including MRI, computed tomography (CT) and ultrasound, since 1987. It uses a series of quality and safety checks to assess scanners and scanning facilities before granting accreditation. The INI’s scanner was one of the first 7T systems that have received accreditation from the ACR for neuroimaging.
“ACR accreditation provides patients and referring physicians with the assurance that we are operating our state-of-the-art equipment in a manner that reflects our commitment to quality and safety,” says Vishal Patel, MD, PhD, assistant professor of radiology at the Keck School and medical director of the INI’s Center for Image Acquisition.
The institute’s 7T MRI scanner, the first of its kind in North America, was installed in 2017. It uses advanced technology and a powerful magnetic field to collect highly detailed images of the living brain that surpass the quality of standard MRI machines. This allows researchers to see neural structures and pathways in very high resolution and to more effectively study brain tumors, epilepsy and more.
In 2018, the scanner was also approved by the FDA for clinical use, establishing it as a safe and effective instrument for diagnosing and monitoring patients with neurological diseases such as multiple sclerosis and vascular dementia.
Now, the ACR’s stamp of approval further recognizes the INI’s proficiency in operating this unique diagnostic tool for both musculoskeletal imaging and neuroimaging.
“Uniting researchers and clinicians in their efforts to study and treat brain disease is essential to our mission as an institute,” says Arthur W. Toga, PhD, provost professor of ophthalmology, neurology, psychiatry and the behavioral sciences, radiology and engineering, the Ghada Irani Chair in Neuroscience at the Keck School, and director of the INI. “We maintain instruments like the 7T scanner so we can equip leading scientists with the most powerful tools available to fuel their endeavors.”