The Long Game
By Beth W. Orenstein
Radiology Today
Vol. 26 No. 7 P. 22

A multimodality study aims to define healthy aging.

The University of Texas at Arlington (UTA) has begun enrolling participants in its healthy aging study, in which advanced imaging will play ta key role. The Arlington Study of Healthy Aging (ASHA) will evaluate tar600 older adults to examine how aging impacts heart, brain, and muscle health as well as identify factors that promote healthy aging. The researchers are using not only advanced imaging but also genetics and multiomics, exercise science, neuroscience, and remote monitoring to investigate age-related declines in health.

The data they collect will be used to help individuals and health care practitioners prevent the effects of disease on older adults, says Michael Nelson, PhD, the lead investigator and director of UTA’s Center for Healthy Living and Longevity. “My role as director for the Center for Healthy Living and Longevity is making sure that we identify and understand ways to age successfully,” Nelson says.

The research team hopes to enroll volunteers who are between the ages of 50 and 85. Volunteers must live in Tarrant County, Texas, which is the third largest county in the state with a population of more than 2.2 million, according to the United States Census Bureau. The county is about 70% white, 20% Black, and nearly 6% Asian, and has smaller percentages of Native Americans, Native Hawaiians or Pacific Islanders, and other multiracial populations.

The researchers expect it will take about four years to enroll everyone. “We’re trying to understand exactly who is in our community, how they are aging successfully and unsuccessfully, and trying to understand the mechanisms that are driving both of those pathways,” Nelson says. “We’re not looking for the fittest 80-year-olds in Texas, for example, but we want to avoid those who have overt health conditions like heart failure.”

What’s unique about this study, Nelson says, is that it focuses on the entire person. Generally, scientific studies tend to focus on a specific part of the body, such as the heart, lungs, or brain. However, Nelson says, his team is employing a fully encompassing approach: “We are looking across the entire body from head to toe.”

Multiple Tests
All volunteers undergo two days of testing at UTA. One day is devoted to a full-body MRI at UTA’s Clinical Imaging Research Center, which provides images of the brain, heart, and skeletal muscle. The second day, volunteers undergo tests that measure blood vessel function, memory, and physical performance. None of the imaging involves contrast or ionizing radiation so participants don’t have to worry about being exposed, Nelson notes. Blood samples are also acquired.

“As we grow this large database,” Nelson says, “our faculty and students will have the ability to answer or ask their own specific questions about aging and/ or human physiology.”

Having started enrolling participants in January, within six months the researchers had enrolled 30-plus subjects. Originally, they were doing two to three scans a week, but now they are able to complete roughly four scans per week.

The generated data represent a single point in time. “Our goal—and one of my jobs—is to make sure that we secure funding so that we can follow these individuals over time,” Nelson says. “We would love to bring them back in five, 10, 15 years, for example, and look at their progression.” However, that is still a future goal, and funding for that aspect is not yet secured.

Once the data is acquired, it will be reviewed by faculty, staff, and students from across the campus. UTA’s next-generation gene sequencer, the first of its kind in North Texas, will be used to help analyze the results. The newly acquired $1 million instrument— housed in the Science and Engineering Innovation and Research building on campus—will allow researchers to study genetic links between health and disease at a large scale.

The whole-body MRI for participants differs from the imaging center’s standard diagnostic MRIs. “We’re allowed to have more time to get better quality, higher resolution imaging,” says Chase Johnson, RT (R), (MR), lead MRI technologist on the research team. “It’s really great to be able to stretch out the imaging session, in order to get really great images and so much more information.”

The cardiac scan takes about 75 minutes, which is extensive. “We do lots of volumetric data that you would do in a normal scan but also some more advanced things like multiparametric mapping, tissue tagging, and 4D Flow,” Johnson says. The most interesting scans, he adds, are highly specific, such as spectroscopy in the heart, which requires both respiratory gating and cardiac gating. “It’s very exciting,” Johnson says.

More Than Diagnostic Imaging
Also, the sequences are not the same as those typically used for diagnostic imaging, Johnson says. “There are multiple things we look at in the brain and heart,” he says. “For example, one of the things we look for is fat in the heart muscle itself.” These scans provide valuable information about aging, he adds, and the researchers are hoping to correlate such information with healthy aging.

The brain scans include various structural and functional imaging techniques to measure anatomy and map activity. The anatomical scans will give the researchers information on cortical volume and thickness, as well as the health and integrity of white matter tracts. Participants are given tasks to do while being scanned to look for changes in blood flow that might indicate how well their brains are functioning. These range from basic to more complex processes important in aging, such as motor and language ability.

“The brain is an organ that cannot store oxygen or sugar, so it draws these elements from the blood,” says Crystal Cooper, PhD, an assistant professor of psychology at UTA and an ASHA investigator. “We track oxygenation changes to identify which brain regions are more active during tasks and which are more active while resting.”

The MRI scanners are like those used for clinical purposes but have been outfitted for the research, Cooper notes. One test involves the participants holding their breath while in the scanner. “When you’re holding your breath, carbon dioxide accumulates in your body, which is a powerful vasodilator of the blood vessels,” she says. “The extent of vasodilation provides valuable insight into the health of the blood vessels in the brain, without requiring exogenous contrast agents or medications.”

Cooper and fellow ASHA investigators plan to correlate the brain imaging with data from a battery of memory and other cognitive tests participants undergo, as well. “We can look at what we’re seeing on the brain scans and how that relates to what the participants are doing,” Cooper says. “Are they struggling with certain types of tasks? Are they having trouble problem- solving or remembering things?”

Multimodality Screening
The participants are screened for dementia and given a score based on these cognitive function tests. “If there’s a concern, they can follow up with their doctor, but we are not concerned if their results fall within a certain range,” says Cooper, who has been involved in other research on aging in adults and children. She says this study also will look for signs of depression and how that applies to aging and the health of the participants.

Because the researchers hope to enroll a rather large number of participants, it will take a couple of years before the study generates results, Cooper says. However, she says, “in the meantime, we have things that we are specifically going to be looking at that are more targeted, and we could probably do with smaller cohorts and don’t have to wait to have the full cohort.”

Cooper notes that the size of this aging study and its focus on many different modalities and cross-organ dimensionality is unique. “What I mean by that,” she says, “is that there are people who do brain imaging and bring a lot of people into a brain health study, but they miss the whole picture, the whole person. Our study is multifaceted, with a lot of different specialty fields.”

Amil Madhukar Shah, MD, MPH, a cardiologist, echocardiographer, and clinician-scientist at UT Southwestern Medical Center in Dallas, has participated in and seen a number of studies on cardiovascular disease and its role in aging. “I feel like I have a decent sense of the landscape of phenotyping that’s been done in larger cohort studies similar in design to the ASHA study,” Shah says. “What impresses me about this study is the level of detail of the phenotyping being done.”

“For the cardiac imaging,” Shah says, “MRI is the gold standard assessment of structure and ejection fraction. I am an echocardiographer, but these measures are more precise than we what we do with echo.” He also notes, “Importantly, they will be able to assess function beyond ejection fraction. For example, they are also going to be able to assess diastolic filling patterns and characterize the myocardial tissue.”

Shah is personally most interested in understanding why people develop heart failure. He will be especially curious to see if the study provides deeper insights into the role of metabolic dysfunction in the development of heart failure.

As for the brain imaging, Shah says, it’s impressive, as well. “The brain MRI includes not only structural data, but also functional data with provoked tasks. I think their findings are going to be very important and help our understanding of healthy aging.”

Unique Insights
The whole-body MRI should also provide important information on body composition, including fat and skeletal muscle mass distribution. For example, Shah says, “Fat tends to live in different places in the body and, in certain places, it tends to be more dysfunctional in terms of promoting prediabetes, diabetes, and other adverse outcomes. There will be a lot of interest in using this data to better understand how different fat depots in the body relate to risk of different health outcomes.” He adds, “It’s this combination of studies that makes it one of the deepest and most informative.”

While the imaging is a vitally important part of the work, the researchers are also developing a biobank to store blood so they can measure new factors as the technology becomes available. In addition, they are taking a comprehensive medical history of participants.

“I think with all of this, ASHA will offer a lot of unique insights,” Shah says.

Nelson, too, is hopeful that the comprehensive data collected will produce meaningful results that will help health care providers to approach age-related health challenges. He says the team has been actively promoting the study in Tarrant County, which includes major cities like Fort Worth, the county seat; Arlington; and Grand Prairie, as well as smaller municipalities. Nelson does not anticipate having trouble enrolling and evaluating enough participants. Volunteering for the study, he says, is a great way for participants to learn about their health and wellness. Should the imaging studies reveal any incidental findings that need follow- up, participants will be encouraged to speak with their health care providers.

“That could be an advantage to participating in a research study like this because at least you found out you have something that needs medical attention on your own accord, as opposed to waiting for symptoms,” he says.

— Beth W. Orenstein, of Northampton, Pennsylvania, is a freelance medical writer and a regular contributor to Radiology Today.