News From RSNA 2019

Imaging Reveals Pathways Behind Depression

MRI illuminates abnormalities in the brains of people with depression, potentially opening the door to new and improved treatments for the disorder, according to two studies presented at RSNA 2019. Major depressive disorder (MDD) is one of the most common and debilitating mental disorders worldwide. Symptoms include feelings of hopelessness, diminished interest in daily activities, and fatigue. Limited understanding of the brain changes associated with MDD hinders the effectiveness of treatments.

“Unfortunately, with current treatments, there is a large chance of relapse or recurrence,” according to Kenneth T. Wengler, PhD, of Columbia University in New York City, coauthor of one of the studies. “To develop new, more effective treatments, we must improve our understanding of the disorder.”

Wengler, along with colleagues at the Renaissance School of Medicine at Stony Brook University in New York, recently studied connections between MDD and disruptions in the blood-brain barrier (BBB), a network of blood vessels and tissue that protects the brain from foreign substances. Using an MRI technique they developed, intrinsic diffusivity encoding of arterial labeled spins (IDEALS), they looked at BBB water permeability, or the movement of water out of the blood vessels and into the brain tissue.

Comparison of results in 14 healthy individuals and 14 MDD patients found that less water moved from inside the blood vessels to outside in the MDD patients, representing disrupted BBB integrity. This difference was particularly large in two regions of the brain: the amygdala and the hippocampus.

“We observed disruption of the blood-brain barrier in gray matter regions known to be altered in major depressive disorder,” Wengler said. “This study helps improve our understanding of the pathophysiology of depression and can open new avenues of treatment for a disorder that affects over 100 million individuals worldwide.”

A second study looked at abnormalities in the complex brain network connections known as the connectome for their role in depression. Previous research has focused on characterizing the connections between different brain regions, but this study, from researchers at the University of North Carolina (UNC) in Chapel Hill, looked deeper within individual brain regions.

The researchers compared 66 adults with MDD and 66 matched healthy controls during wakeful rest using functional MRI and a newly developed multiscale neural model inversion framework that linked the brain’s microscopic circuitry with its larger-scale interactions. As part of the study, the researchers were able to assess excitatory or inhibitory influence between neuronal cell groups. A proper balance between excitation and inhibition is crucial to a well-functioning brain.

Patients with MDD had abnormal patterns of excitation and inhibition at the dorsal lateral prefrontal cortex, a brain area important to cognitive control functions including the regulation of the amygdala, a key region embedded deep in the brain for expression of emotion. It has long been hypothesized that malfunctioning inhibitory control over the amygdala could result in depressive symptoms.

“In our study, we found that excitation and inhibition in the brain regions in control of executive functions and emotional regulation were reduced in patients with MDD,” said study coauthor Guoshi Li, PhD, of UNC. “This suggests that control functions in MDD are impaired, which may lead to elevated responses in the amygdala, resulting in increased anxiety and other negative moods.”

In addition, the researchers found that recurrent excitation in the thalamus, an area of the central brain that is also responsible for emotional regulation, was abnormally elevated in patients with MDD. According to Li, the new approach could open the door for a deeper understanding of the mechanisms behind depression.

“Current methods of studying the brain provide a superficial understanding of connectivity,” Li said. “This method allows us to identify impaired connectivity within each brain region, making it a potentially more powerful tool to study the neuromechanism of brain disorders and develop more effective diagnosis and treatment.”

MRI Indicates Signs of Brain Damage in Obese Teens

Researchers using MRI have found signs of damage that may be related to inflammation in the brains of obese adolescents, according to a study presented at RSNA 2019. Obesity in young people has become a significant public health problem. In the United States, the percentage of children and adolescents affected by obesity has more than tripled since the 1970s, according to the Centers for Disease Control and Prevention. Data from the World Health Organization indicate that the number of overweight or obese infants and young children aged 5 years or younger increased from 32 million globally in 1990 to 41 million in 2016.

While obesity is primarily associated with weight gain, recent evidence suggests that the disease triggers inflammation in the nervous system that could damage important regions of the brain. Developments in MRI, including diffusion tensor imaging (DTI), a technique that tracks the diffusion of water along the brain’s signal-carrying white matter tracts, have enabled researchers to study this damage directly.

For the new study, researchers compared DTI results in 59 obese adolescents and 61 healthy adolescents, aged 12 to 16 years. From DTI, the researchers derived fractional anisotropy (FA), a measure that correlates with the condition of the brain’s white matter. A reduction in FA is indicative of increasing damage in the white matter. The results showed a reduction of FA values in the obese adolescents in regions located in the corpus callosum, a bundle of nerve fibers that connects the left and right hemispheres of the brain. Decrease of FA was also found in the middle orbitofrontal gyrus, a brain region related to emotional control and the reward circuit. None of the brain regions in obese patients showed increased FA.

“Brain changes found in obese adolescents related to important regions responsible for control of appetite, emotions, and cognitive functions,” said study coauthor Pamela Bertolazzi, a biomedical scientist and PhD student from the University of São Paulo in Brazil.

This pattern of damage correlated with some inflammatory markers such as leptin, a hormone made by fat cells that helps regulate energy levels and fat stores. In some obese people, the brain does not respond to leptin, causing them to keep eating despite adequate or excessive fat stores. This condition, known as leptin resistance, makes the fat cells produce even more leptin.

Worsening condition of the white matter was also associated with levels of insulin, a hormone produced in the pancreas that helps regulate blood sugar levels. Obese people often suffer from insulin resistance, a state in which the body is resistant to the effects of the hormone.

“Our maps showed a positive correlation between brain changes and hormones such as leptin and insulin,” Bertolazzi said. “Furthermore, we found a positive association with inflammatory markers, which leads us to believe in a process of neuroinflammation besides insulin and leptin resistance.”

Bertolazzi noted that additional studies are needed to determine whether this inflammation in young people with obesity is a consequence of the structural changes in the brain.

“In the future, we would like to repeat brain MRI in these adolescents after multiprofessional treatment for weight loss, to assess whether the brain changes are reversible,” she added.

Concussion Alters Information Transmission in the Brain

Damage from concussion alters the way information is transmitted between the two hemispheres of the brain, according to a study presented at RSNA 2019. Research has shown that the corpus callosum, a bundle of nerve fibers that carries signals between the brain’s left and right hemispheres, is vulnerable to damage from mild traumatic brain injury, commonly known as concussion. Less is known about the impact of this damage on cognitive function.

To learn more, researchers at New York University (NYU) School of Medicine in New York compared the condition of the corpus callosum in 36 patients with recent concussion with that of 27 healthy controls. They studied the participants’ brains with two new methods, including an MRI technique that uses measures of water diffusion to provide a microscopic view of the brain’s signal-carrying white matter.

“Looking at how water molecules are diffusing in the nerve fibers in the corpus callosum and within the microenvironment around the nerve fibers allows us to better understand the white matter microstructural injury that occurs,” said study coauthor Melanie Wegener, MD, a resident physician at NYU Langone Health in New York.

Wegener and colleagues combined the MRI findings with results from the study’s second advance, the Interhemispheric Speed of Processing Task, a test developed at NYU Langone that evaluates how well the two hemispheres in the brain communicate with each other. For the test, the participants were told to sit in a chair and focus their gaze on the letter X, which was displayed on a screen directly in front of them. The researchers then flashed three-letter words to the right or the left of the X and asked the participants to say those words as quickly as possible. When the researchers evaluated this reaction time in both patients with concussion and healthy controls, they noticed an interesting phenomenon.

“There is a definite and reproducible delay in reaction time to the words presented to the left of the X compared with words presented to the right visual field,” Wegener said. “This shows it takes time for information to cross the corpus callosum from one hemisphere to the other, which is measured by the difference in response time between words presented to different sides of our visual field.”

This delay is likely due to the fact that language function is most often located in the brain’s left hemisphere. This means that information presented to the left visual field is first transmitted to the right visual cortex in the brain and then has to cross over the corpus callosum to get to the left language center. In contrast, words that are presented to the right visual field do not need to cross the corpus callosum.

Performance on the test correlated with brain findings on MRI. In the healthy controls, reaction time corresponded with several diffusion measures in the splenium, an area of the corpus callosum located between the right visual cortex and the left language center. No such correlation was found in the concussion patients, suggesting microstructural changes relating to injury.

“We saw a correlation between white matter microstructure injury and the clinical status of the patient,” Wegener said. “This information could ultimately help with treatment in patients who have mild traumatic brain injury.”

For instance, according to Wegener, patients could undergo MRI immediately after a concussion to see whether they experienced any clinically important white matter injury and thus may benefit from early intervention.

“Another thing we can do is use MRI to look at patients’ brains during treatment and monitor the microstructure to see whether there is a treatment-related response,” she said.

— Source: Press materials distributed at RSNA 2019