Jonathan Lindner, MD, is the M. Lowell Edwards Professor of Medicine and the Chief of the Oregon National Primate Research Center’s Division of Cardiometabolic Health. An expert in cardiovascular imaging and blood vessel diseases, Dr. Lindner has received several grants from the NIH and NASA. He pioneered the use of advanced non-invasive imaging with nanotechnology for early detection of disease.
In your presentation about cardiovascular imaging at OHSU, you talked about some really exciting ways that OHSU’s cardiologists are detecting and treating heart conditions. Tell us how microbubbles are helping you detect serious heart problems.
Lindner: Cardiologists are known for plumbing the larger vessels of the heart. But many diseases originate in the smallest vessels of the body – the microcirculation – which can be detected using microbubbles.
We can engineer these bubbles to be smaller than red blood cells, which allows us to evaluate the integrity of the small vessels in conditions that affect humans. We can also put targeting molecules onto the surface to make the microbubbles “smart,” which opens up a very large portfolio of conditions that have been extremely difficult to diagnose. While these smart bubbles are just now starting to be trialed in patients, they have been used for a decade to help us understand disease and develop new drugs in animals such as mice.
In your talk, you compared two heart attack survivors who had received the same clot busting medication, but your imaging revealed two very different situations. Tell us more about that.
Lindner: Imaging allowed us to see that with one patient, the heart muscle was very dark, which meant that microbubbles were not entering into the microcirculation. It made it clear right away that this was an emergency and we needed to get the patient to the cath lab immediately to restore blood flow to the heart and save heart muscle.
“OHSU is one of the few institutions in the world that can diagnose MVD with microbubbles. This safe, rapid, and bedside method makes it so that patients do not need to undergo to a prolonged cardiac catheterization procedure that carries a risk of serious complications like stroke.”
For the second patient, the area of the heart that was affected by a heart attack had really vigorous blood flow, evidenced by a very bright signal from microbubbles flowing through the microcirculation. This made it very clear that the clot busting medication the patient received 45 minutes earlier had worked. That patient didn’t need emergent interventions.
We’re using innovations like these to rapidly diagnose diseases that are otherwise difficult to detect, and doing so with greater ease, greater reliability and less cost.
What are other heart conditions that have benefited from microbubble imaging?
Lindner: Microvascular dysfunction, or MVD, is a syndrome that is much more prevalent in middle aged women. It’s not a mild condition – it’s every bit as bad as if you have a severe limiting blockage in the big vessels of your heart. But it’s very difficult to diagnose, and no two patients respond the same way.
The small vessels in the heart muscle are the gatekeepers that determine how much blood flow and nourishment the heart receives. With MVD the vessels spasm and red blood cells just struggle to get through to the constantly working heart, causing both symptoms and indolent heart injury.
OHSU is one of the few institutions in the world that can diagnose MVD with microbubbles. We do this by using microbubbles as a marker for how efficiently blood cells are entering the heart muscle during a provocative test. This safe, rapid, and bedside method makes it so that patients do not need to undergo to a prolonged cardiac catheterization procedure that carries a risk of serious complications like stroke. We are pleased to offer this much better option.
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We can also use microbubble techniques to diagnose transplant vasculopathy, when a transplant patient’s body is rejecting the blood vessels that feed the transplanted heart. Before microbubbles, that would be diagnosed in hours in a cath lab, but now we can evaluate for this serious condition in 10 to 15 minutes, non-invasively. It’s safe, there’s no radiation, and we can do it on a yearly basis to monitor transplant patients.
How is your research being used by NASA?
Lindner: NASA is interested in what happens to blood vessels, especially the small vessels, in astronauts on long duration missions such as to Mars. There are many stresses on the blood vessels of the heart and other organs from space travel, including microgravity (weightlessness) and stress of confinement which releases certain biochemical signatures that can make blood vessels unhappy. Even the gut bacteria that change when you eat a certain diet can change blood vessel health. But the biggest threat to vessel health is space radiation, which injures the small vessels of the heart so they are either dysfunctional, or large vessels of the heart which develop blockages. Our studies are starting with studying astronauts before and after long-duration missions on the International Space Station.
“We need this information to be able to monitor astronauts on the long deep-space missions.”
When you get to deeper space, the radiation problem becomes even more significant because the radiation exposure becomes much higher when you’re out of earth’s magnetosphere which protects us groundlings. Accordingly, our studies with NASA astronauts will extend beyond the International Space Station and include the Cis-lunar orbitals, the Artemis and Gateway missions, where astronauts will be in deeper space. We need this information to be able to monitor astronauts on the long deep-space missions and be able to develop mitigation strategies so we can study the impact of a drug or supplement or something else to prevent vascular radiation injury.