The True Colors of Cancer--shining a new light on disease--Dr. Stephen Boppart

Cancer biopsies are scary. The patient gets tissue removed from his or her body, the sample gets sent off to the lab and then there's the agonizing wait for the results.  Dr. Stephen Boppart of the University of Illinois Urbana-Champaign, both a physician and an engineer, is working on instant biopsies that will produce results in minutes. Using laser light and artificial intelligence, Dr. Boppart and his colleagues have been able to identify cancers early and accurately. Moreover, this technique promises to identify conditions in the body that might lead to future cancers by looking at tiny vesicles, liquid-filled sacs that act as messengers.  His "Town Talk" sponsored by Telluride Science, was recorded at the Telluride Mountain Village Conference Center in Colorado.  The program was moderated by veteran broadcast journalists Judy Muller and George Lewis.

Transcript

Science Straight Up

Season 4, Episode 7

“The True Colors of Cancer”

Dr. Stephen Boppart, University of Illinois

Moderators: Judy Muller and George Lewis

GEORGE: From Telluride science, this is SCIENCE STRAIGHT UP.

STEPHEN:  What light and this field of biophotonics gives us is a view of the cellular and molecular world. And it’s that world where disease starts. Who wouldn't want to be able to understand and identify disease at its earliest stages. 

GEORGE: The true colors of cancer—seeing disease in a new light. I’m George Lewis.

JUDY: And I’m Judy Muller. Dr. Stephen Boppart is a physician and also a professor of electrical and computer engineering and bioengineering at the University of Illinois in Urbana-Champain. He’s looking at cancer and other diseases in a new light that could revolutionize medical treatment.

STEPHEN: I really appreciate the opportunity to share the research that my group has been developing and many in my field, but also research that truly is going to impact all of us.

GEORGE: Traditionally, if a patient is suspected of having some form of cancer, the doctor takes a biopsy, a sample of tissue, sends it off to the lab, where it’s stained with dyes and a pathologist examines it under a microscope, a process that can take days of anxious waiting for the patient.

STEPHEN: It's actually over 100 years old in terms of this whole process. And to us, it seems a bit archaic.

JUDY: What Dr Boppart and his colleagues have done is use laser light to examine the tissue, right on the spot where the sample is taken, then using artificial intelligence, do a quick analysis of how that tissue looks using different wavelengths of light, showing off cancerous growths in brightly-colored computer generated images. The true colors of cancer.

STEPHEN: imagine then, instead of this image that takes a day or two, we start to get all this type of these types of images in real time, basically by shining different types of light onto the tissue and collecting the light that comes back from different structures.

GEORGE: As he speaks, and I’m sorry we can’t do it justice in a podcast, Dr. Boppart shows off a series of slides, some of which resemble those spectacular NASA space telescope photos of distant stars and nebulas.

STEPHEN: one of my grad students likes to call this the tumor galaxy, because if you didn't know, we were looking at, you know, a microscopic view of tissue, you might think this was coming from the, you know, the //Webb telescope that's currently looking at all the galaxies out there. So because these images are so rich with data, we can apply this AI approach. And we can actually automate and have that algorithm identify which regions are more suspicious, and which look normal.

JUDY: What’s really exciting about all this is that laser imaging can detect activity that may lead to cancer even before malignancies start to form.

STEPHEN: With this, this type of imaging technology, we see things that people haven't seen before. And when we started imaging, this image came up and we saw these little blue dots, but no one could really figure out what we were seeing at first.

GEORGE: Those little blue dots they saw are vesicles. Microscopic sacs filled with liquid. 

STEPHEN:  Now these are a new hot topic in science because while biologists and medical scientists used to think this, this was just garbage that the cells were trying to get rid of, we now know that cells use these vesicles to signal other cells throughout the body.

GEORGE: Because those vesicles can act as messengers they may give researchers a new understanding of how cancer recurs in some patients and metastasizes, or spreads throughout the body.

STEPHEN: If this is a different paradigm, what this suggests is that when that first cancer starts to transform and become cancerous, it starts putting out these vesicles very early on. And so even before that, that tumor metastasizes and what it's doing, if you think about it, maybe that that cancer is smart in some way, it's trying to basically condition the soil, to where these metastatic cells will eventually land and hopefully grow from the perspective of the tumor. But, but so if that's the case, we have to really think about how to prevent that process and to identify, you know, are there tumor cells present, we know there's tumor cells all the time in our body, but they're, but they're, you know, removed by our immune system. But how do we stop or evaluate that spreading of these vesicles. And this is where a lot of scientists are interested in the therapeutic potential of these vesicles and intervening in this process. But there's still a lot this is the medical science that we're trying to explore. 

JUDY: Dr. Boppart says these imaging techniques have potential well beyond treating cancer.

STEPHEN: This is just opening up a huge range of different applications. We're starting to look at different tissue types other cancers, states of health and disease and just finding we're seeing things that have never been seen before. And with that comes, you know, many new ideas and many new discoveries.

GEORGE FROM TALK: You've said in previous presentations that you yourself are a cancer survivor. And I'm wondering that you, I think, were diagnosed with cancer some 30 years ago. So you’re long term survivor? What's to what degree does that inform and inspire your work? Did that motivate some of your research?

STEPHEN: It did, it did. So I was diagnosed with non Hodgkins lymphoma, stage four, so very late stage, and you didn't have your odds for survival were not good.They weren't good. It was about 30%. And I think 40% risk of just dying from the treatment, this is back when I ended up getting a bone marrow transplant and, and received marrow from my my sister, my only sister, blood related sister. And, and then a 30% chance of it just recurring, but it's been 30 years. And, and I you know, I think that technology, I like to think that, you know, engineers can't solve everything, can't fix all the problems. And, and so we have to rely, you know, on this interdisciplinary approach, and it was wonderful physicians and wonderful support from family and friends and, and of spiritual support many different types of support that come together to, you know, for this, and so it was an inspiration. It really was an inspiration, good and bad. I had bad physicians along the way too. And they inspired me just as much as the good ones. So

GEORGE: How are your vesicles?

STEPHEN: That's a good question. I actually I have not looked, you know, we have this capability. But you know, I've not looked and maybe not because I'm afraid to look, but But I think, you know, very odd case, because again, the blood circulating in me is from my sister, and all the other cells are mine. So….

JUDY FROM TALK: It's interesting as you were talking about the true colors of cancer, I couldn't get that song out of my head. Debbie Harry… Cyndi Lauper. That's gonna be there. But you know, the images, and you mentioned that a colleague said, this is like the Webb telescope. And, and it really is there's so fantastical a beautiful, you can't believe you're looking at cancer. Right. But I'm wondering, it's more than a metaphor that this is opening up horizons that you didn't know about before this, there are questions you don't even know.

STEPHEN: It is because, you know, remarkably, from a very artistic point of view, we're fascinated. These images are both beautiful, intriguing, but also on ominous as well, because we know what's behind them. We had, in fact, a story. We had a research patient coordinator involved in a lot of our clinical studies, and she was a breast cancer survivor herself, and, and was just amazed by these images. And she was an artist, a watercolor artist. And so she took one of our images. And she painted that. And it was her way of really approaching and dealing with this disease. And we've had almost all of our surgeons that we've worked with have image these images hanging in their offices, because it I think that's the power of imaging in some sense, because it it inspires it raises questions, people ask, What am I seeing? That's how I got interested in imaging, because we would see things and we wanted to know what what are they? And it really opens new worlds to us.

GEORGE FROM TALK: You talk about an interdisciplinary approach, you have background in both engineering and medicine. I covered tech for a long time the guys in Silicon Valley believe in the words of Mark Zuckerberg, “Move fast and break things.” Doctors believe in the words of Hippocrates “Do no harm.” How do you reconcile the two? 

STEPHEN: Yeah,good question. Right. I mean, medicine and engineering, they're very different cultures, and they approach problems in a very different way. You know, medicine, very conservative, rightly so. You know, very thorough systematic, wanting to make sure things are, are proven safe, right before being used. So they're not so creative, and they're not necessarily risk takers. Whereas engineering engineers, and scientists tend to ask questions tend to, you know, solve problems tend to break things. Love complexity. And, and so these are a bit in contrast, and so we've, in fact, at the University of Illinois, we've created a new medical school that is about train training future physician innovators. So we bring in engineers, we teach them we train them through a medical curriculum, but we train them to, to, to care for patients in very compassionate and caring ways. But, but to really think about innovative solutions to their problems, to not necessarily stop at the status quo. But are there technological solutions to this, their problems and, and so I think what we're trying to do is really bridge these cultures. And that's important. That's the essence of interdisciplinarity is trying to, to bring two cultures or fields together, encourage them to communicate in new ways. And I do truly believe that all the the next great enter inventions and ideas and innovations are going to come at these boundaries between disciplines,

GEORGE FROM TALK: Do you see one of your goals as developing an early warning system for cancer that we'll be able to detect cancers even earlier than we can?

STEPHEN: It is, it is. So you know, in fact, these vesicles that we're looking at, I showed you a number of examples from tissue, but they're also in our urine and in our blood. And so we've been actually collecting them from from urine, from human subjects, those with breast cancer, those healthy subjects, it's a bit more complicated those optical signals, because, again, we don't know how other diseases might impact those. But we're starting to see evidence that maybe this could be also a screening modality much like, you get screened // with mammography or colonoscopy, or pap smears. You know, maybe you know, everyone has to pee. So that's…

JUDY FROM TALK: The question I wanted to ask, you had told us, or at an earlier conversation that this is about five to seven years out from seeing it clinics and hospitals, right? 

STEPHEN: Well, we hope so. 

JUDY: Okay. So let's assume that's true. What would that mean to a woman who's going in for her regular breast exam? For mammography or MRIs? Yeah. How does that change?

STEPHEN: Yeah, I think that before we kind of get to the, you know, that patient, that level, the screening level, I think that this, these technologies are going to have greater impacts on, say, pathology as a field. So, again, this whole idea of digital pathology, being able to capture these images, and do that rapidly, I think that's going to have a more of an impact. So first, so we're going to be able to see new markers of disease, we're going to be able to get those results earlier, maybe even at the bedside, you know when you know, the doctor sees that patient. So I think that's going to happen soon. And not just my work, but there's a lot of in our community, our you know, in our bio photonics community that are working on this problem.

JUDY: But I interrupted you, because you were saying everybody has to pee. Keep that going?

STEPHEN Yes, yes. So, you know, I think there's lots of ways that we can think about how to non-invasively sample this, there's a lot of work going on looking at other markers for cancer in the blood. And I think that's going to be coming as well. // And I think we're going to shift we're going to see a shift those will be used when we're trying to find the cancer that we know exists. And we're going to be using blood markers or urine markers to tell us there's a cancer present. And we've got to figure out where it is.

GEORGE: You’ve reduced your laser imaging equipment to a cart that can be wheeled around a hospital, you come from a small town in Illinois, Harvard, Illinois population, what 5000 at last count? How soon do you think that rural communities like yours or ours here in Colorado will have access to this technology?

STEPHEN: Yeah, I think that's, you know, one of the goals for a lot of the biomedical engineers these days, is they're trying with their their innovations to make technology, you know, better, more sensitive, but also more widely accessible, and lower cost. And so we understand that those engineering challenges are important to make it to make the bring those systems to the rural communities or globally, you know, to to underserved populations. And, and so that that is something we're all thinking about, and, and, you know, I come back to this comparison between medicine and engineering. You know, as engineers, we love complexity, right? We love labs that are full of equipment and wires and knobs and, and the more the better, but in medicine, the simpler the better, right? If there's one metric that can be measured, that would tell the doctor is this you know, disease or normal. That's really kind of what we have to channel our, our technologies to. So while we have a very complex laser system, we're also looking for ways that maybe just with a simple LED or a laser pointer, we can identify a marker that will tell us if something is wrong.

JUDY: You mentioned artificial intelligence in your end, AI sometimes now brings up fear about big AI…

STEPHEN: Yeah..

JUDY: But in this case, how is that going to be? How is it really a key for you?

STEPHEN: It really is key. And in fact, I think the medical community doesn't always refer to it as artificial intelligence. We'd like to think our intelligence isn't necessarily artificial, but that it's augmented intelligence. And they truly see these algorithms and these approaches as augmenting their practice, right? That rather than looking at, you know, hundreds or 1000s of images to see if there's something wrong, let let an algorithm let let you know computer do that. And simply be able to flag is something normal or abnormal, it's a whole lot easier to be able to determine is this a normal or an abnormal than it is to say that that's a specific disease type? And so let the let the specialist determine what that specific disease type is. But let an algorithm say Is this normal or abnormal?

GEORGE: I've heard your technology compared to sonograms only you're using light instead of ultrasound. Can it be as non-invasive as a sonogram? Can you can you shine light through layers of skin without making incisions?

STEPHEN: Yeah, so that's one of our challenges, too. And I think if you look all across Biomedical Imaging, you'll see that there's a trade off we make. So MRI is great can image all the way through the body, but it doesn't have the resolution to be able to see a single cell, right or sub cellular, with light, we can see those cells, but we can't see those cells throughout the whole body. So we've done a lot of engineering of different beam delivery systems. So fibers, you know about the size of one of your hairs, optical fibers to deliver light into the body. Or obviously, wherever the light can, can get to so skin, for instance, through the eye. Typically, we can image just about a millimeter deep through tissue with with light and get these types of images. But But yeah, there's ways we can get that light into the body in different ways.

JUDY: So following up on that, are there other diseases besides cancer, where this optical imaging will be a great boon to diagnosis..

STEPHEN:  There is a lot. And in fact, a lot of the technologies because our eyes are optical instruments, there's been a lot of technologies that will look at the eye, look at the retina, look at the blood flow and circulation in the retina. Look at the skin in the vessels, you know, within our skin. There's many other ways that we can use light to do that. And I gave some examples during surgery. So in surgery, you naturally have an opportunity to expose tissue to image with light. And if you think about it, we there are a lot of optical instruments already in practice. So that colonoscopy that you have or the bronchoscopy or you go into primary care, and they'll use an optical instrument to look into your eye or your ear. So just simply looking at those optical instruments and adding some of the the new advanced optical imaging as possible, too.

JUDY So, you're not saying colonoscopies are going away. (laughter)

STEPHEN: We’re thingking about that.

GEORGE: You're going to be generating mounds and mounds of data with all this technology. Does managing that data where you do things like drowning in too much data, bother you maintaining confidentiality, making sure nobody accesses the files who shouldn't?

STEPHEN: Yeah, so those are a couple of questions there first, first, the volume of data, right with, with this multimodal imaging, and just the the high dimensionality that we see, we get terabytes of data, and it is just huge, enormous amounts of data. But fortunately, you know, the computing power has really kept pace to so the computers, the processing, that's possible, the AI algorithms that can help sort through all this data, those have really kept pace. So we love data, the more data, the more information that there is present, and we just have to sort that out. Now, the privacy issue is another fact too. And that's certainly that's of interest and, and concern for all of us as well. I think in general, people recognize that, that we have to have those protection systems in place to preserve confidentiality. And and that too, is advancing with with the data that we collect.

JUDY: Just Just one more question before we go to the audience. Is this going to put pathologists out of business or do they have to go back to school? I mean, what was happening?

STEPHEN: Yeah, no, I don't think anyone in the medical community should be afraid of these advances. They should really look to them as augmenting you know what they can do. But I think the pathologists are probably the most concerned at at risk. You know, we've we've we've shared these images and we've made this this proposition, you know, to pathologist say that, you know, we can we think we can do better. And about half of the pathologist will say, you know, I need that HD image to be able to make my diagnosis the other half say point your you know, these are look really interesting. And I can see the potential here. And usually it's the color of their hair that side is that is on. And so, you know, I think we're starting to see this information. And again, this digital pathology, it these types of changes, when you change the culture of a field, culture of medicine, it takes a generation. And so a lot of what we're focusing on, again, is training the next generation of physician innovators to think differently, when they embrace us don't have another chance.

JUDY: Okay, well we want to leave time for questions from our audience.// Yes.

QUESTION FROM AUDIENCE: Yes. So just curious, when you're thinking about the types of cancer, are there certain cancers that lend themselves better to your early research than others? Are there some that are tricky from a therapeutic perspective? //

STEPHEN:  Yeah, yeah, we think that what we're seeing here and with these vesicles is really universal across all cancer types. Now, we do know certain cancers will put out more of these vesicles and, and change in different ways. So brain tumors, breast cancers, tend to be more produce more of these vesicles than others. But, you know, there's certain again, I think, we think all cancer cells will use this mechanism to send information and signals out to the body and just trying to decode what that information is, is a challenge for the for the scientists. There's other diseases too. So we're looking at Alzheimer's, neurodegenerative diseases. Just even an exercise when you you know, exercise if you're at altitude. If you injure a muscle, your muscle cells will will put out these, these vesicles, as it probably a way of informing the rest of the body that something's injured, and we need to repair something as well, my wife, she's a professor as well at at Illinois. And she studies some of these vesicles in, in the, in the area of aging and senescence. And she really thinks that these vesicles as we age, these vesicles are what tells the whole body to age? And and is there a way of understanding that language and slowing it down or processing it. So the point is that there's there's a lot of information, the cells use different mechanisms to spread this information. And this is really new to a lot of us scientists.

QUESTION FROM AUDIENCE:  Is it possible that vesicles are not negative, that they are doing a positive thing?

STEPHEN: They are. True. So even in states of health, right, they're naturally signaling other cells, you know, that we have to engage? Think about it how, you know, how does one cell in one part of the body just kind of recruit the rest of the body, the physiology of the whole body to just start, you know, repairing injuries or treating disease, removing something. So there is a whole level of coordination here. And that's a very positive thing that that these vesicles are doing.

QUESTION FROM AUDIENCE: If you were to look at a transplant, organ, or tissue or whatever, and when the body is starting to reject it, to go in and look at the tissue to see what's happening, and then use that it in a way to use that information to correlate getting the body to use something like that to then reject a tumor. 

STEPHEN: Yeah, absolutely. And it's great that you're, you know, you're already thinking about, you know, other areas, other ways to use this information. Right. And that's a question in transplant, organ transplant, you know, how is that that organ been rejected? You know, is it being accepted at how functional is it? Is it you know, getting better or getting worse. And a lot of that comes down to metabolism and cell function and cell dynamics. And, and so, exactly some of these, these methods can be used to assess that functional state of different tissues. Now, it's a challenge, if that's, you know, if it's a liver transplant, accessibility is a challenge, but, but if you can, you know, look at biopsies or even, you know, with a fiber assess that that transplanted organ, you might be able to tell those differences as well. So that's an area to think about cancer and how it spreads.

GEORGE: That's about all the time we have for this evening. If you want to hear this presentation again, or if you want to share it with a friend. Once again, we encourage you to check out our podcast science straight up wherever you get your podcasts, and may all your vesicles be good ones. (laughter)

JUDY: George and I want to thank Telluride science for the privilege of moderating these amazing and informative talks again this summer, and let's all thank Dr. Steven Boppart for a great evening. (applause)

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GEORGE (new track) 

 That’s it for this edition of Science Straight up. If you want to look at one of Dr. Boppart’s images that made the cover of the Proceedings of the National Academy of Sciences here’s a nerdy way to find it.  Use a search engine like Google or Bing or whatever…search for P-N-A-S November 2019. It’s well worth the effort.

JUDY: Our program was recorded at the Telluride Conference Center in Mountain Village, Colorado and Dean Rolley of Dragonfire productions was our superb audio engineer.  

GEORGE: A big thanks to our sponsors, Alpine Bank and the Telluride Mountain Village Homeowners Association. The executive director of Telluride science is Mark ˚Kozak and Cindy Fusting is managing director. 

JUDY: Annie Carlson runs donor relations and Sara Friedberg is lodging and operations manager. For more information, to hear all our podcasts, and if you want to donate to the cause, go to telluride science-dot-o.r.g.  I’m Judy Muller.

JUDY: And I’m George Lewis, inviting you to join us next time on Science Straight Up.

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