Alumnus Profile: Lei Li (PhD '19)

Lei Li (PhD '19), a newly minted assistant professor of electrical and computer engineering at Rice University, spent the years 2017-2022 as a graduate student and then a postdoctoral scholar in the lab of Lihong Wang, Bren Professor of Medical Engineering and Electrical Engineering; Andrew and Peggy Cherng Medical Engineering Leadership Chair; Executive Officer for Medical Engineering.

Li is most known for his research and advancements in photoacoustic imaging, a form of medical imaging with the potential to diagnose cancer earlier and better understand the brain. The imaging process works by using pulses of laser light to vibrate hemoglobin molecules, and then sending those vibrations through tissue and back to the surface, where they are picked up and processed by sensors. The process is similar to ultrasound imaging and can provide a clear view of structures as small as a cell.

You can hear from Li in his TED Talk on photoacoustic imaging; Li was selected as a TED fellow for his work in 2021.

ENGenuity: How would you describe what you're doing now and your professional contributions?

Lei Li: Now, I'm an assistant professor of electrical and computer engineering at Rice University. My role is to teach and mentor students, and to develop my own research field. Most of my time is focused on research—I supervise students to push the technology that we're working on to clinics. We talk with physicians or neurosurgeons almost every day to make the technology more useful and translational to clinical settings.

My main professional contribution is the development of photoacoustic technologies, specifically for imaging applications from small animals to human applications. My research is a pushing force for this technology, translating from the lab to patients.

ENGenuity: What inspired you to research photoacoustic imaging, and what initially inspired you to get into science?

Li: I had a strong interest in science and engineering when I was young. About fifteen years ago, I entered a top engineering school in China to study optics. At that time, my focus was on industry optics, like the precise measurements in the production line of a factory. When I was applying for graduate school, my grandmother died of cancer, and my grandfather died from a stroke—two very typical but hard to treat diseases at that time in China. I was thinking about how to use what I learned to help with this situation; is there anything I can do to diagnose those conditions earlier? Photoacoustic imaging was a great fit for my background in optics. Later, I found great potential for this technology; we can use it for cancer diagnosis and to better understand the brain.

ENGenuity: What is the next step in making photoacoustic imaging a more mainstream practice?

Li: I've tried to shape the photoacoustic imaging system, which is bulky and complex, into something wearable. We hope we can develop something like a watch and use that for long-term monitoring to detect tumors or other vital signs of human health. That's one direction I was focusing on before I left Caltech, and I will continue in that direction.

ENGenuity: How has your Caltech education influenced you?

Li: My Caltech education has influenced me from almost every perspective. Caltech is very open and free, and the people at Caltech are very interactive and diverse. So, I can speak to mathematicians, biologists, and chemists. I learned a lot from my lab members, my colleagues, and all my other collaborators across other departments and divisions. These interdisciplinary discussions boost technology development because nowadays, it is not a single-person job. Although you can be great in one area, you need to know electronics, mechanics, physics, mathematics, and even programming to truly push technology forward. You need to harness talent from all perspectives. Caltech is the perfect place for that.

ENGenuity: Which Caltech professor impacted you the most?

Li: I was most influenced by my principal investigator, Lihong Wang. He taught me how to do research and build a career. He's very accurate, precise, rigorous, and innovative. As an engineer working towards medical applications, we need to be very rigorous because safety is always a concern, and we have to make sure that everything we measure or image is accurate enough to truly reflect the state of the tissue or organ.

Also, I worked with Wei Gao [Assistant Professor of Medical Engineering] to develop an imaging-guided platform. He's an expert in microrobots, but his robots could not be seen in real-time inside of tissue—they essentially become invisible once they enter the body. We combined my imaging technology with his microrobots to develop an imaging-guided platform to guide the microrobots just like a GPS guides cars. We know where the robots are, where the robot should go, and when the robot reaches the destination (the targeted disease location). We use an external trigger to release the robots or release the drug, which is a much more accurate way to control the drug delivery.

ENGenuity: What aspect of Caltech do you hope never changes?

Li: At Caltech, there is an open platform for collaboration. People can easily exchange their ideas and concepts. For instance, inside the Keck Laboratory kitchen, there is always a whiteboard. No matter what type of discussion we had during lunch or a coffee break, we could always write things down. That's a small thing, but it reflects the environment Caltech provides for their researchers, students, and faculty.

As a student, Caltech is unique in that all my classes were very small. I had enough time to interact with my lecturer no matter if they were a new faculty, a fellow in the National Academy of Sciences, or a Nobel Prize winner. In the Caltech classroom, the lecturer taught me about the state-of-the-art technology they were developing, but I also had time to interact with them and get real-time feedback.

ENGenuity: What do you think could make the Caltech experience more impactful?

Li: Because the classes are small, we don't necessarily need to constrain the students and teacher in the format of a classroom. Maybe we can have more roundtables to facilitate even more interaction.

ENGenuity: What advice would you give to the next generation of Caltech students and alumni?

Li: You have the best resources, so don't limit yourself. Always aim high, and always believe in yourself. I never thought I could develop technology, make people interested in that technology, and sell it. Never underestimate yourself, the sky is the limit!

Also, if you have questions about something specific, talk to people who have more experience or more knowledge on that subject. It might not always be necessary to figure everything out by yourself. Take advantage of the resources you have at hand.

ENGenuity: What is your favorite story?

Li: I don't think I have a favorite story, but I did watch The Big Bang Theory a lot, which took place at Caltech. Although it's a great show, it's far away from real life at Caltech. The people at Caltech are not that nerdy. Not everybody is like Leonard or Sheldon. People here are real; they are much closer to normal people. We are hardworking, and we have a strong interest in research, but we are not always that nerdy.

ENGenuity: What is your favorite destination?

Li: One is Monterey Bay in California. That's a beautiful place I've been to a few times. It's very close to the sea and quiet. Me and my wife and family like to go there to rest. The weather there is beautiful, it's not as hot as southern California. It rains more often there, so the humidity is better. It's very quiet. We can be at the beach, and we avoid the crowd.

Before we had our daughters, my wife and I liked to go on cruises, because they're all-inclusive. We don't have to worry about everything.

ENGenuity: Is there a project that you're most proud of?

Li: The one I developed for small animal imaging; we call it single impulse panoramic photoacoustic computed tomography. Before I started that, people always thought photoacoustic imaging had good potential, but nobody could produce a standalone system to deliver the performance you expected. I wanted to develop and optimize the system as much as I could from every perspective. The ultimate outcome was that we were able to build a single, standalone system capable of very high spatiotemporal resolution, functional information, molecular contrast and deep penetration. This system generated a lot of exciting images. The whole field was excited by that piece of work. We really raised the bar of the image quality. People saw cloudy or blurry images before, but now they see very clear organs inside the tissue. We can perform tumor diagnosis, drug tests, and even fundamental research like brain activity or some other dynamics inside the whole organism. It's a very powerful system, and I'm very happy and proud of it.

ENGenuity: What gives you the most satisfaction in your work?

Li: There is a company that commercialized photoacoustic imaging before, and the image quality that we provided was orders of magnitude better than theirs. I met one of their executives at a conference, and people were showing my paper to them. A few years later, that company could also produce similar, high-quality images. This shows the positive impact of my work on the entire field of photoacoustic imaging.

ENGenuity: What keeps you up at night?

Li: Most of the time, I get to sleep quite easily because I did a lot of work during the day. Usually, when I can't get to sleep, it is because something is wrong with my experiment—something happened that was unexpected. I stay awake wondering if something is wrong with my theory or if I didn't do something correctly.

ENGenuity: What gets you up in the morning?

Li: Sometimes you know there is an unsolved problem or an unfixed issue, that's for sure. More importantly, I might have something in mind to deliver better performance than what I delivered before. Or maybe there is some demonstration I really want to achieve using the system. We really want to show people how we can see inside the brain using photoacoustic imaging or how we can make the photoacoustic wearable that people are always talking about. All those projects are things that I'm chasing every day. We always have an unsolved problem at hand in which we can improve performance to increase the benefits of medical applications.