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Turning Photons into Soundwaves
Duke Biomedical Engineering professor Junjie Yao has helped pioneer the field of photoacoustic imaging, which uses light and sound to create detailed and informative biological images of everything from a single cell to an entire body.
Michaela Kane: This is Rate of Change, a podcast from Duke Engineering dedicated to the ingenious ways engineers are solving some of society’s toughest problems. I’m Michaela Kane.
When you hear the term biomedical imaging, you probably think of tools like ultrasound imaging, which allow us to see things like the growth of a fetus in a pregnant woman, an X-ray, to detect a fractured bone, or an MRI, which can spot an injury like an ACL tear other damage to your ligaments and tendons.
These tools can provide clinicians with a large, anatomical view of different parts of the human body, but they don’t easily allow researchers to zoom in on smaller details and examine things like individual cells. And these tools aren’t ideal if you’re trying to study things as they move and change, like the level of oxygen consumption in the brain, blood flow across different organ systems, or even the temperature of deep tissues.
But that’s where Junjie Yao and his imaging research come into play.
Junjie Yao: My name is Junjie Yao and I’m an assistant professor of Duke BME department. We are imaging scientists, and we develop a technology called photoacoustic imaging, and as you can tell by the name, that’s a two-part imaging technology. It has both photo, that is light, and acoustics, that is ultrasound.
Kane: Photoacoustic imaging is a hybrid of light and sound, where researchers will shoot a burst of light into a targeted tissue, and then they’ll use an ultrasound probe to read the resulting sound signals.
Yao has been working with this tool for more than a decade, and in his lab at Duke, his team is able to use photoacoustic imaging to pursue both basic research and to advance projects could eventually help patients in the clinic.
But the first step of this process involves harnessing the power of light.
Yao: It starts with, we use lasers to excite the tissues and the photons travel inside the tissue and some of them are absorbed by the molecules, like hemoglobin in the red blood cells or melanin on the skin surface or even DNA and RNA in the cell nuclei. And those molecules absorb some of the light, and the photons, they have energy. The energy of the absorbed photons is converted into heat. We call that the photothermal effect.
According to Yao, it’s basically like collecting one second’s worth of summer sunlight, and then sending it to an area the size of a single fingernail for a single nanosecond. When the laser light hits the biomaterial, the energy from these photons will cause the tissue to heat up a tiny bit and expand instantaneously. This creates an ultrasonic wave that reverberates through the tissue and is picked up by an ultrasound sensor.
Yao: The beginning of the whole story is light is absorbed, and the end of the story is that sound is generated. And then we would do a computer reconstruction. So when we receive the signal we try to find where sound wave came from, just like the GPS, where you drive around and know where you are. It’s the same story in ultrasound imaging recon, where we try to find where the soundwaves come from originally, and that becomes the imaging reconstruction. And once we have that information there is following steps like imaging processing, and data processing and deep learning is involved so we can reconstruct more information. We can convert those boring electric signals into colorful images so people can have a better understanding of what’s really going on. We love to show the oxygenation of the blood with red or blue colors, and red color means it’s really oxygenated, and blue color means it’s less oxygenated. And of course, rest assured your blood is never blue, but that’s the way we demonstrate the contrast.
When you look at an ultrasound image, you’d typically see a blurry photo that is in various shades of black and gray, making it incredibly difficult to decipher small details. But because photoacoustic imaging works with the full optical spectrum, the resulting images are incredibly colorful and make it much easier to see small details in tissues and cells.
Yao: For photoacoustic imaging we are very sensitive to the colors of the materials, you know biomaterials or inorganic materials, so we are kind of a color sensor, and that is in the more professional way it’s in the optical absorption of the light. If we have different absorption of the light then we have different colors of all the materials, and photoacoustic imaging is fundamentally sensitive to that contrast. And that is the major difference with photoacoustic imaging and other technologies.
Kane: The final images Yao and his team are left with can sometimes look more like abstract art than a visual of biological data, but they can showcase biology at an incredibly wide scale, ranging from individual organelles, cells or neurons to full muscle tissues and even organs. The imaging tool can also tell researchers about a tissue’s anatomical, functional and metabolic properties.
Although this technology seems almost futuristic, the technique’s history actually dates back to 1880 with the inventor of the telephone—Alexander Graham Bell. Bell discovered that you could modulate sunlight to create soundwaves.
He called this phenomena photoacoustic effect, so basically it’s from light to sound. He basically made up that name. And then his first response to that discovery was OK, so now we can create sound by using light. Can we make a phone call using this discovey? And he actually invented this photophone, and he used this technology to make a phone call with his associate who was 800 yards away.
Kane: To use the photophone someone would project the voice through an instrument toward a mirror. The vibrations in the voice caused similar vibrations in the mirror. Bell would then direct sunlight into the mirror, which captured and projected the mirror’s vibrations. The vibrations were then transformed back into sound at the receiving end of the projection.
The photophone functioned like the telephone, but rather than use electricity the photophone used light. Although Bell said that the photophone was his most important invention, the tool didn’t catch on like he hoped because he wasn’t ever able to develop a way to protect the light transmissions from outside interference. Things like clouds would often disrupt the light transmission.
It was only with the advent of lasers in the 1950s—and the stable light source they provided—that people began to reevaluate the potential uses of the photoacoustic effect.
Yao: Then slowly this technology evolves with better and better light sources, better and better ultrasound detectors, and more powerful computers and more mathematicians joined. They developed imaging reconstruction and then many people are working together, like chemistry people and engineers, and here we are.
Kane: Now, more than 100 years after the technology was first developed, Yao and his team are exploring ways in which they can improve photoacoustic imaging for the next generation of scientists.
Yao: I try to summarize the work we’re doing is to try to make photoacoustic imaging faster, smaller and more colorful. In terms of faster, we want it to be faster so we can capture the dynamics and study different biological processes, and without worrying about motion artifacts. We also want the system to be smaller, and that doesn’t mean as small as an iPhone, we just want it to be more portable so it can be applied not just for applications in the lab, we can move it around, so for example to a patient bedside and to monitor freely moving animals. We’d also like to make it smaller to insert it into the body to do endoscopy studies and things like that.
And more colorful, whatever we do we want to gather more information about the tissue and that information can be the oxygenation of the blood or the temperature of the tissue or the neuroactivity in the brain. So that information can be extracted from the photoacoustic signals. How can we do that? What kind of contrast do we use, and how do we process the data, and how do we combine them together to provide more information? In terms of how we apply those technologies for different studies? In addition to these studies, we have many ongoing projects in the lab.
Kane: The first of these exciting projects involves exploring how the brain responds to stroke.
Yao: People are working on stroke studies for years, but there is a lack of information about how the blood vessels in the brain respond to the stroke at different levels, for example—, how do the small vessels respond, how do the big vessels respond, and how does age play a role in this process. Old people, young people, so we’re studying this micro-vessel response to stroke in both young animals and aged animals. We’re really finding different responses in terms of the vessels impairment and restoration and functions. That’s one study we’re working on, and another study we’re working on is actually quite relevant to the clinical management of cardiac arrest.
Kane: In this project, Yao is exploring the impact that epinephrine has on brain function. Epinephrine is a drug that is commonly given to patients who have experienced cardiac arrest, as it increases blood pressure by constricting blood vessels throughout the body and helps give the heart a boost.
Yao: It’s widely used in hospitals and everywhere, but there is not much study about how the drug impacts brain functions. We know it can save the heart, but how about the brain? And we know that can become a very interesting question to ask so we can see how it actually changes the brains function. And we find it’s very dramatic. The heart can be revived but damage can be done to the brain just by the drug.
Kane: Already, the team has used photoacoustic imaging to see that the use of epinephrine in animal models reduces oxygen levels in certain sections of the brain. The team is hopeful that they can use photoacoustic imaging to explore how the drug can be optimized to save the heart without causing any further damage to the brain.
Yao: Before we look at this question, there was no technology that could do the same job. They were either too slow or they do not look at the micro vessels with enough resolution, so they don’t know what happens, which is really important.
Kane: Beyond these projects that can be applied to the clinic, Yao and his lab are also working with a research subject that’s a bit out of the ordinary.
Yao: Another project, which is very cool and it’s not about humans, it’s about a frog. So that’s on the very fundamental side and it tries to address a very fundamental question. Some frogs are naturally transparent. We’re not talking about Harry Potter potter’s invisible cloak. These kinds of frogs have their own capability to keep themselves safe. And they aren’t transparent all the time, they can be transparent sometimes. SO it’s always a mystery why they are transparent and why they keep transparent.
Kane: In this collaborative effort, Yao and his team will use photoacoustic imaging study how these frogs are able to turn themselves transparent without damaging their organs.
Yao: We’re working with our collaborators, and we’ve used photoacoustic imaging, and it’s totally noninvasive and quiet, and also you don’t have to inject anything into the frog and the frog can be totally in its natural status, and we found out they have a totally unique way to keep their transparency, and this can be significant because, again, you see we are very sensitive to colors, and the photoacoustic imaging is sensing their optical absorption. When it’s transparent that means the absorption of the light is minimized. IF you’re minimized in terms of absorption you’re transparent as well. So the frogs do have that mechanism to make themselves transparent by reducing the absorption of the light as it goes through the body, and they do this by basically rearranging their organs and to filter their blood to make themselves transparent. Humans have to rearrange their blood inside the body for example when there is bleeding, where the blood has to be arranged in the system to compensate for that loss. But that’s not so easy for humans, where if you concentrate too much blood in the system you could have clots that block the vessels. But these animals they don’t.
Kane: Although this work is in its fundamental stages, Yao and his collaborators are curious to learn how the frogs are able to reorganize their blood flow and organs as they become transparent.
Understanding these basic questions, Yao says, could help them address clinical questions down the road.
Yao: I believe photoacoustic imaging can be a powerful tool for fundamental work, and I hope we can find more like this very cool, crazy research.
Kane: Yao is thrilled that this technology allows him freedom to pursue different projects, and he’s excited about the prospect of improving the technology for imaging scientists and patients alike.
Yao: The more I work on this technology the more I love it, and it is quite comprehensive, where you have to learn a lot about light and sound, but because of that it has a lot of flexibility, where you can really work on different aspects of the technology and just be as creative as you want. So I stay on this path and I believe I will stay on this path for the next tens of years.
Kane: Thanks for tuning into this week’s episode of Rate of Change. Remember to follow us on social media for updates and be sure to subscribe. Thanks for listening!