Destroying Tumors With Sound: Histotripsy with Dr. Zhen Xu

Can sound destroy a tumor without an incision? Dr. Zhen Xu joins Krishna Choudhary to explain histotripsy: focused ultrasound that creates tiny bubbles to mechanically break apart tissue, without relying on heat. From a noise complaint in a University of Michigan lab to the Edison system, Xu traces the unexpected discovery, the physics of cavitation, and the decades of research behind noninvasive liver-tumor treatment. We explore surprising immune effects in animal studies, the #HOPE4LIVER clinical trials, and what remains to be tested for other organs. Recorded in Washington, D. C., on September 28, 2026, before the Golden Goose Awards ceremony. Xu is a histotripsy co-inventor, HistoSonics co-founder, and U-M's Li Ka Shing Professor of Biomedical Engineering. This is the first interview in our Golden Goose series. CHAPTERS 00:00 The discovery that became histotripsy 00:50 A PhD student and a heart problem 03:42 Heat vs. sound: how histotripsy works 07:06 Gas pockets, and why not the lungs 09:06 The first paper (2004) 09:38 "Don't read any papers": Yellow Pages and pig hearts 12:29 Too loud: rethinking the ultrasound pulse 14:56 "Almost like smoke": the 2002 discovery 18:14 Building the equipment, and the Edison system 22:19 Through the skull, and controlling the bubbles 23:50 The physics: pressure waves, bubbles and cells 28:47 Ten years to understand it 32:42 Surgery keeps getting smaller: from ether to Star Trek 35:58 The surprise: an immune response 38:16 Why liver cancer, and 9 of 11 rats 47:19 #HOPE4LIVER: the clinical trial 49:59 How a treatment works 52:27 Recovery and the 20-mile-run anecdote 56:24 The future: worldwide, kidney, pancreas and brain 1:01:33 The Golden Goose Award and federal funding 1:04:31 Sign-off 1:04:41 Outro RESEARCH & FURTHER READING First tissue-erosion paper (2004): https://doi.org/10.1109/tuffc.2004.1308731 High-speed imaging of bubble clouds (2007): https://doi.org/10.1109/tuffc.2007.504 Microtripsy and precise cavitation (2014): https://doi.org/10.1109/tuffc.2014.6722611 Bubble-cloud and cancer-cell interactions (2016): https://doi.org/10.1016/j.ultrasmedbio.2016.05.018 Histotripsy through the skull (2016): https://doi.org/10.1109/tuffc.2016.2531504 Abscopal immune responses: animal research (2020): https://doi.org/10.1136/jitc-2019-000200 Partial treatment of rat liver tumors (2022): https://doi.org/10.3390/cancers14071612 #HOPE4LIVER pivotal trial (2024): https://doi.org/10.1148/radiol.233051 #HOPE4LIVER one-year follow-up (2025): https://doi.org/10.1097/sla.0000000000006720 FDA Edison De Novo review: https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN220087.pdf EDITORIAL NOTES 08:40 / 48:12: Edison received FDA De Novo authorization in 2023 for noninvasive liver-tumor destruction. This is not a general cancer-cure approval. 35:58-47:19: The cited immune-response and 9-of-11 results are animal studies, not human cure rates. 49:17: The one-year trial reported 63.4% local control on primary review and 90% on post hoc review. Technical success and durable tumor control are different measures. 53:46: The 20-mile run is an individual anecdote, not recovery advice; Dr. Xu explicitly advises against it. 55:39: The one-year #HOPE4LIVER update was published in 2025. Clinical and company updates reflect the September 2026 recording. Dr. Xu co-founded HistoSonics. WATCH & LISTEN Episode notes and research: https://ffppod.com/episodes/ep66 Golden Goose science rundown (EP59): https://ffppod.com/episodes/ep59 Watch and listen: https://ffppod.com Subscribe: https://www.youtube.com/@FromFirstPrinciplesPod?sub_confirmation=1 Support the show: https://ffppod.com/donate Follow @FFPPod on Instagram, TikTok, X and Facebook. Breaking down science news so it makes sense to curious people everywhere. #Histotripsy #GoldenGooseAward #SciencePodcast

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  And in front of me, I saw there's like, almost like a smoke coming out of the pick heart tissue, but it can't be because it's in a washer tank. And within a minute, I saw a hole through that pick heart tissue. And I thought I was dreaming. The eleven marks treated, nine of them, not only uh, the tumor didn't spread.

• 0:25Krishna Choudhary?

  Uh huh.

• 0:25Speaker 00

  The remaining tumor was just gone. We're like looking for it everywhere. We couldn't find them. This crazy patient went out and run twenty miles within the first week of her tumor treatment.

• 0:50Krishna Choudhary?

  So you've had an incredible career with histotripsy. It's something that you kind of started. Um, before we get into some of the later stages, where now you've co-founded a company and you're doing all these amazing things. You were once a grad student in the University of Michigan. So I wanted to start there because I think that's really the genesis of um, this story and also the genesis of why you're getting this award. It was in the two thousands and you were under Charles Kane at the University of Michigan. And someone had asked if there's a way to use ultrasound to make surgery-like manipulations inside tissue without actually um, doing the invasive stuff that comes with it.

• 1:35Krishna Choudhary?

  He, did he just put this on your desk one day? Or how did, how did, how did you get involved with it as a grad student?

• 1:41Speaker 00

  Yeah, so in two thousand one, I uh, came to United States uh, to do graduate study uh, in biomedical engineering. Uh, and so I was a first year PhD student. And Dr. Ahil Udomursky, so he is this pediatric cardiologist. So he just came to the lab meeting one day. Uh, and he was telling us how he was operating on patients. And they are babies, very young kids with congenital heart disease.

• 2:14Krishna Choudhary?

  Right.

• 2:14Speaker 00

  Very sick. Uh, and he had to operate on their heart. And they would die on the surgical table.

• 2:21Krishna Choudhary?

  Oh, okay.

• 2:21Speaker 00

  So that he asked that, can you invent a technology that can perform the real surgery? Without incision? And he emphasized on real surgery because there was radiation. And there was a different form of ablation technology, which means that you use uh, different energy, microwave, radio frequency, even ultrasound laser to heat up the target tissue. And the thermally

• 2:52Krishna Choudhary?

  Uh huh.

• 2:52Speaker 00

  heal the tissue, but you don't remove anything. So it's no use to him. And in order to save his patients, he need to do the real surgery. And there was no way of doing it. And he posed that as a challenge to the group. And I was a very young and naive student and I was so inspired by him. So after Dr. Udomursky left, I went to my PhD mentor, Charles Kane, and said, I wonder that to be my PhD dissertation. I had no clue how to do it.

• 3:26Krishna Choudhary?

  Yeah.

• 3:26Speaker 00

  But that just sounds so inspiring.

• 3:27Krishna Choudhary?

  Yeah, yeah, that's definitely something a first year PhD student would do.

• 3:32Speaker 00

  I had nothing to lose.

• 3:33Krishna Choudhary?

  Yeah, yeah, yeah, exactly. Like if you're like four or five years in, you're like, ah, maybe I'll just try and graduate.

• 3:40Krishna Choudhary?

  Okay. Yeah, yeah. And, and there, there were already previous technologies that used ultrasound, as you said. But this was more, but this was for ultrasound heating.

• 3:50Speaker 00

  Yes, so there was previous technology which is referred to high intensity focus ultrasound, HIFU. Uh, but it's for thermally generating heating. And then you can uh, kill the target tissue that way. So it's like cooked tissue, right? Um, but uh, there's no way at the time uh, to do mechanically uh, in a non-invasive way to remove tissue. And still, uh, even nowadays, histotripsy is the only technology that can perform mechanical

• 4:29Krishna Choudhary?

  Yeah.

• 4:29Speaker 00

  non-invasive surgery. And so that is distinctively uh, something entirely new and different.

• 4:37Krishna Choudhary?

  Yeah, and, and the principle of histotripsy is you use the ultrasound, which is effectively like sound waves, like laser beams of sound waves in some sense, that is getting focused to create cavitation, right? So it's like bubbles. Now, the, the idea that sound could create bubbles, was that already um, sort of an established reality at the time?

• 5:00Speaker 00

  Yeah, so uh, so here's what just see how it works, like you said, ultrasound delivered from outside the body, focused to really precise millimeter region in the tissue, generate bubbles and the bubble uh, expand and collapse and mechanically uh, core part the cells in the target tumor, for example. And using sound to generate uh, those bubble activity, which is churned cavitation, was a known phenomenon for almost fifty years at time. But however, it was always viewed at this

• 5:43Speaker 00

  uncontrolled, random phenomenon, and that's harmful. The reason is that it was discovered and mostly in the sense where you have ultrasound imaging, right? And they generate cavitation in the lung because our lungs full of air bubbles.

• 6:01Krishna Choudhary?

  Oh.

• 6:01Speaker 00

  And then you can, you know, cause damage, unwanted damage. So uh, and, and at the time, even though it's a phenomenon known for years, the uh, conventional belief is that it cannot be controlled.

• 6:16Krishna Choudhary?

  I see.

• 6:17Speaker 00

  To do anything uh, really beneficial uh, if you don't have uh, injected uh, gas nuclei, gas bubbles already, you know, in a controlled way. Meaning that the only way to control cavitation is you actually inject bubbles. And you know, this bubble is in here with a specific number, concentration. Then that's the only way to gen- generate controlled cavitation. Uh, and when even we see control, it's still sort of uh, you know, adjustable charm, how controlled you can be. So what we're talking about histotripsy uh, in the sense that we don't inject anything.

• 6:59Speaker 00

  And we just euthanize the air pockets that we already have in our body, which we do because we're breathing air.

• 7:06Krishna Choudhary?

  Right, so there's dissolved gases in the fluid.

• 7:09Speaker 00

  But it's future by the lung. So the dissolved gas pockets in the tissue, like, you know, in our liver, in our pancreas, heart, they are nanometer gas pockets, really, really tight. Uh, and it's very hard to damage cavitation from those nanometer gas pockets because their surface tension are extremely high. We're talking about two hundred to three hundred times of the atmosphere. So they are super stabilized. And though it was just, you know, belief that you, you just can attack, you know, can possibly control the generation

• 7:51Speaker 00

  and the activity of cavitation in a human body to do things like non-invasive surgery, that was considered impossible.

• 8:00Krishna Choudhary?

  That was, okay, I see. I see the point, yeah. And like in lungs, it because the lungs have so much, such a higher, let's say, partial pressure of gases.

• 8:10Speaker 00

  Just so many large bubbles. You go in lung and use ultrasound, you're gonna explode the lung base.

• 8:16Krishna Choudhary?

  Interesting, okay.

• 8:17Speaker 00

  People don't wanna go to lung to uh, do this cavitation thing. And I also need to say that histotripsy is great, but so far we cannot treat lung cancer because lung is full of large air bubbles. But it had been used to treat other parts.

• 8:35Krishna Choudhary?

  Yeah, yeah, yeah, and it's kind of scary that the heart is right next to the lungs, so.

• 8:40Speaker 00

  There are ways that you need to do it very carefully.

• 8:45Krishna Choudhary?

  Right.

• 8:45Speaker 00

  Uh, um, but uh, the, we'll talk later, but right now uh, the clinical use of histotripsy, so far, the FDA approval is to treat liver cancer, right? And then clinical trials, pancreas and kidney and other things. So, so we are, you know, still, you know, away from them.

• 9:06Krishna Choudhary?

  That makes sense. That actually makes sense, um. Very cool. And so, you know, the first paper that you had, I believe this was in um, two thousand and four, where um, it's in the IEEE journals, I believe. And I have a few figures from there, where you show that you can cause uh tissue, you can like bore holes in tissue using this cavitation approach. And then you also use like some Doppler imaging to show that like fluids can cross these this hole and things like that. Um, but there's like some interesting stories that I've heard about this paper, about like the fact that your lab mates thought that the ultrasound was too loud. And that was maybe an impetus for you to make it quieter and maybe that.

• 9:52Speaker 00

  Yeah, so what happened is uh, uh, why, you know, basically volunteered myself, right? To to look for this uh impossible non-invasive surgery technique. Uh, and I came in uh with no background in ultrasound therapy at all. Uh, and I was like, how do I do it? And uh, I talked to Charles Kane, my mentor, and trying to get guidance. And Charles literally said, um, you know, just go ahead and explore.

• 10:23Krishna Choudhary?

  Uh huh.

• 10:23Speaker 00

  Uh, and don't read any papers. And I was like, oh, my God, why? And then he said, you're doing something entirely new. And I don't want your innovative mind to be limited by the conventional thinking. So I, you know, like, just don't read papers and I go and explore. So what I did is I started to open up the Yellow Pages. I don't know if nowadays kids even know that, but you know, it's a phone book. So I found a number from uh for a local slaughterhouse. Cause I said, I need to get some tissue to do experiments. If I, you know, I I was trained as engineer, right? So if I uh don't know anything and I just should try.

• 11:06Speaker 00

  And because uh Dr. Rudemirsky mentioned a congenial heart disease. So I said, okay, what do I get? So I called a slaughterhouse and they were slaughtering pigs every week. And I said, can I come and get some hearts from the pig? And they were not selling those. So I went, uh, you know, I would go uh every Thursday morning back then. And then then uh the owners just like take me to a huge dumpster.

• 11:34Krishna Choudhary?

  Okay.

• 11:34Speaker 00

  Uh, where they dump all the organs and he just gave me like this plastic trash bag. Just, you know, take whatever you want.

• 11:42Krishna Choudhary?

  And you got it for free?

• 11:43Speaker 00

  Um, well, they figured out very quickly. I immediately got it for free. Then it was five bucks and ten bucks.

• 11:48Krishna Choudhary?

  Okay.

• 11:49Speaker 00

  They made it out of business.

• 11:50Krishna Choudhary?

  Yeah, yeah, yeah.

• 11:51Speaker 00

  So I would get uh pig hearts by dumpster diving every week in a local slaughterhouse. And they get that, you know, trash bag back to the lab. But now do experiments uh by dissecting a heart tissue, uh, right? And and then try ultrasound parameters on those. And I tried, uh, you know, weeks and a month and for a whole year. Uh, I was, you know, I failed and failed and failed and didn't get anything. Uh, and for ultrasound therapy, a typical thing you do is uh, well, ultrasound is called ultrasound because it's beyond our hearing range.

• 12:29Krishna Choudhary?

  Right.

• 12:30Speaker 00

  Right? And our hearing range for human beings is from twenty hertz to twenty kilohertz. Uh, and uh, but ultrasound therapy is like I do bursts of ultrasound waves and use different power so that I can see if they can do anything. And the burst of this ultra, you know, burst of ultrasound now will repeat them. And the repeating of this ultrasound wave bursts are within our hearing range. And they are powerful, so so they're loud. So my lab mates are like, you're too loud. Not only you're failing and you're loud. And I was like, okay, oh, you know, I I was uh desperate. You know, I was trying everything. So uh, I thought two things.

• 13:13Speaker 00

  One is as engineer, uh, you know, if a hammer doesn't work, I try a bigger hammer, right? So I just increase the power. Secondly is uh, if he thinks I'm too loud, then I will make it quieter by repeating those bursts beyond our hearing range, twenty kilohertz.

• 13:31Krishna Choudhary?

  Ah, okay, so so the ultrasound is like really fast?

• 13:34Speaker 00

  And I'm using, you know, like a beyond, you know, uh, uh, I was using a frequency that's seven hundred kilohertz, five megahertz, and those way high.

• 13:43Krishna Choudhary?

  Those are okay.

• 13:44Speaker 00

  But the bursts of the waves were within our hearing range. So in order to make it quieter, I made it so that it's twenty kilohertz. But in order to do that, which means I have to make those bursts really, really short.

• 14:00Krishna Choudhary?

  Yeah.

• 14:00Speaker 00

  So twenty kilohertz meaning that I'm repeating every fifty microseconds. So my bursts have to be a few microseconds, which should.

• 14:09Krishna Choudhary?

  Fit enough.

• 14:10Speaker 00

  Should fit enough, right? But which is a stupid thing to do because like ringing a bell, it take time to ring up to the full power. Ultrasound is the same way. You need to have enough of the length in order for the ultrasound wave to reach its high power. So I'm basically cutting my ultrasound wave pressure way down by doing this short microseconds ultrasound pulse while I think I should go, you know, bigger hammer, right? But I was like, okay, I will humor him because nothing worked anyway. Uh, and so I tried the microseconds ultrasound pulse at as high a power or pressure as I possibly can get.

• 14:54Speaker 00

  And I repeat them really fast. And I remember I had that piece of pig heart tissue in the water tank. And in front of me, I saw, there's like, almost like a smoke coming out of the pig heart tissue. But it can't be because it's in a washer tank. And within a minute, I saw a hole through that pig heart tissue. And I thought I was straining, right? Cause it's like I trimmed it so many times. Um, and I was like, this is can be true. This just can be true.

• 15:27Krishna Choudhary?

  Yeah.

• 15:27Speaker 00

  So I repeat it second time and I repeat it again. And my rule of thumb is that if we repeat three times, it must be true. And that's why I started running to Charles' office and I like, Charles, Charles, you need to come over. Something really special just happened. And that was in two thousand and two when I first discovered Histo Trips.

• 15:46Krishna Choudhary?

  That is such a cool story. So from dumpster diving, you went from dumpster diving for pig hearts to like this eureka moment.

• 15:54Speaker 00

  My, my side, you know, special silent hall sequence. And then the funny thing is, uh, even though it was occurring supposedly repeating beyond our hearing range. But when cavitation occurred, it make this crackling sound. So it's still not really quiet. But but that was a serendipity that led to the discovery. And honestly speaking, at the time, I had no clue what was the underlying mechanism. I had no clue how it worked, why it worked. So I first discovered this specialized parameter set, this magic parameter set. Uh, then I had to go back.

• 16:36Speaker 00

  Uh, it was really funny because uh, you know, this big discovery, I was so proud of it.

• 16:42Krishna Choudhary?

  Uh huh.

• 16:42Speaker 00

  And um, literally within a month later, uh, I went to Charles' office again. And I said, Charles, there's a good news and bad news. And Charles is like, what? I was like, good news is I was able to repeat it.

• 16:57Krishna Choudhary?

  Uh huh.

• 16:57Speaker 00

  So it's true.

• 16:58Krishna Choudhary?

  That's true, yeah.

• 16:59Speaker 00

  The bad news is, I I just broke the most expensive piece of equipment in the lab. And I'm too poor, I can't pay for it. Um, but I realized at the time that Histo Trips required a very different set of equipment. And and it was, it just couldn't be produced even with the best commercial ultrasound equipment at the time. So then, you know, that's why I, why after I uh published that paper and presented to the uh scientific peers, they all came back, said it's impossible.

• 17:39Krishna Choudhary?

  Uh huh.

• 17:39Speaker 00

  Why is the parameters you talk about cannot be produced by any commercially ultrasound equipment, even the best one? Secondly is that nobody had a clue how it worked, right? Like you, we think it's cavitation, but how do you possibly control cavitation to do this? So it's impossible. If no equipment, no mechanism. So it was a eureka moment followed by a long period of time where I had to really figure out, you know, give up our own equipment and really understand the mechanism.

• 18:16Krishna Choudhary?

  Yeah, actually, one of the, one of the things I wanted to talk to you about was like, you know, the grad students in your lab today, because Histo Trips has become such a flourishing field, there's probably like custom equipment that now manufacturers build specifically for these types of experiments, right? But at the time, as you were saying, like, you you had to build custom ultrasound equipment. Was it the power? And like the the fact that these waveform, you had to like fit the waveforms into this Gaussian envelope that repeats every whatever?

• 18:48Speaker 00

  It was actually turned out, it was that uh, you know, because we need required microseconds, very short courses, at a really high instantaneous pressure. Um, just for that microseconds pulse. Like I said, that you can even ring up to the full amplitude. But you couldn't wait for a long time for the next pulse to come. So the cumulative power is actually low. We actually intentionally make it low so that we can avoid heating.

• 19:18Krishna Choudhary?

  Ah.

• 19:18Speaker 00

  But we wanna maximize the cavitation effects and also control it. So we need to build a specialized ultrasound equipment to produce microseconds ultrasound pulse, like a imaging system. But with like hundred times higher power, uh higher pressure. So that's kind of the challenge because nobody had a need for that before. And it's a new kind of needs. That's why a specialized equipment have to be developed for that special purposes. And then now even nowadays, there is a commercial hisochipsy clinical system, which is this Edison system uh produced by Hisasonics for patient treatment.

• 20:02Krishna Choudhary?

  Okay.

• 20:02Speaker 00

  But the research equipment are still in a build and developing in our own lab. And that's why it's harder for other researchers to do this uh research. And that's why recently I established this hisochipsy center at University of Michigan. Uh and to really enable the researchers to do hisochipsy work by opening up uh and provide access to those equipment that we build uh and also technical expertise entirely for. So uh you know, people who wanna investigate hisochipsy for new disease treatment or combined with drugs.

• 20:44Speaker 00

  They can just come in and use equipment uh for free.

• 20:48Krishna Choudhary?

  Wow.

• 20:48Speaker 00

  We can even ship a system out to other people to do those work also for free.

• 20:55Krishna Choudhary?

  Yeah, that's that's pretty incredible, actually. Um you could have made a a nice buck with that, if you didn't do it for free.

• 21:03Speaker 00

  Well, my intention, uh you know, research uh is a solid foundation to enable more uh clinical translation, like commercialization. And my intention is that I have seen hisochipsy is a platform technology that can be used to treat many new disease, including different type of cancer and even brain disease. So we can actually treat through the skull to do precise non-invasive during surgery. Uh so it's really incredible and I have received emails from patients every single day. And they ask, why can not, can I actually get the treatment?

• 21:48Speaker 00

  I have, you know, all different diseases.

• 21:50Krishna Choudhary?

  Well.

• 21:50Speaker 00

  So so my hope is by opening up to uh, you know, enable thousands of researchers to do this. We can quickly uh get more results to enable clinical translation. So they, that we can help as many patients as fast as possible. And that's the impact I wanna make, uh rather than just, you know, trying to sell the system to the researchers, you know, I wanna mobilize and just get this, go to patients.

• 22:20Krishna Choudhary?

  Yeah, yeah, um actually, we covered your uh, the the transcranial paper in our, in our rundown episode.

• 22:27Speaker 00

  Yeah.

• 22:28Krishna Choudhary?

  Oh yeah, we started with this two thousand four one. And then um, but that was one of the ones that we covered where you had a, like a, you had a, a human skull that they were like shooting stuff through to make sure that even the, it would go through a human skull as well, which I thought was pretty incredible. So I wanted to get back to, you know, people said that it would be, okay, so now you've done cavitation. Let's say, let's say you've performed um controlled cavitation using ultrasounds, fine. How do you control it? That's the next big thing. It's impossible to control. Um and so I have, I wanted to talk to you about two figures from one, some, one of your papers that um, that I, as a physicist, I really liked.

• 23:11Krishna Choudhary?

  Um especially, so this first one is about the nonlinear nature of cavitation probability with respect to pressure. It's kind of like a switch that allows you to control the, the location on top of the pressure wave itself. And like you're kind of beating the diffraction limit in some sense, which, which I thought was kind of cool.

• 23:35Speaker 00

  Yeah, so what happens is that we all breathing air, like I mentioned. So we have nanometer gas pockets in tissue filtered by the lung. And um it's a super stabilized with this really high surface tension. What happens is that ultrasound is a mechanical wave. So it propagates by vibrating particles in the media, right? And uh when you actually compress the particles, it creates a positive pressure. Now, when you kind of pull particles apart, it creates a negative pressure. And if you imagine there's a balloon, uh and you wanna make the balloon to grow.

• 24:15Speaker 00

  What you do is that you wanna make the pressure outside actually lower than the inside of the balloon so that you can overcome the surface tension of the balloon. So the nanometer gas pockets, what happens is the surface tension is two hundred to three hundred times of the atmosphere if it's in a water molecule environment, right? And we as human are seventy percent of us are just water based. Uh and so most tissue are water based, uh then you, the rest will be fat and you have bone, right? So if you have this water based tissue and the gas pockets in there is two to three hundred times of the atmosphere as a surface tension.

• 24:59Speaker 00

  Then supposedly what you need to do is within really short duration, uh instantaneously make the pressure outside and lower than the inside, meaning that I need to achieve two hundred to three hundred times of the negative pressure

• 25:17Krishna Choudhary?

  Mm-hmm.

• 25:18Speaker 00

  within microseconds region. Now I can explode that nanometer gas pockets to really large, right? And that's the trick. So we're uh producing a, a pulse wave with two to three hundred times a negative pressure within microseconds. Expand a nanometer gas pockets to, from nanometer to a hundred micro. Then you take that pressure away, then we will just collapse. So don't keep it going, literally, microseconds, expand, then take it away, then let it collapse. Then that is almost like a micro, micro bond.

• 25:56Krishna Choudhary?

  Mm-hmm.

• 25:56Speaker 00

  Right? So you will produce this mechanical stress to the cells when the bubble expand, it crush the cells, squeeze it. When you collapse, you pull cells apart. So it's mechanically toing cells apart. And um because we, you know, the water molecule surface tension is so consistent. Therefore, it's a threshold, you have to cross that threshold with your ultrasound pressure, then you generate bubbles. And if it's lower than the threshold, you don't generate. So even though the ultrasound focus uh for transducer typically is, you know, like a couple of millimeter.

• 26:33Krishna Choudhary?

  Right.

• 26:34Speaker 00

  If you make it so that your region that above that exceeding the pressure threshold, the limit to generate cavitation, uh and that's the region that measures. So that's the region where you can generate cavitation and it can be even less than millimeter, right? And you know, beating the diffraction limit. And the lower you don't have any activity, which is really poor and very helpful because uh if you think about using heating as a mechanism, heating is always heating. You can have high heating, low heating. So higher energy give you a high heating, lower energy give you a low heating.

• 27:12Krishna Choudhary?

  It's a linear kind of.

• 27:13Speaker 00

  It's a linear thing and there's a confusion too.

• 27:15Krishna Choudhary?

  Yeah, yeah, there's diffusion from just, yeah.

• 27:17Speaker 00

  Yeah, so you, your accuracy is low because you, you can't just say, hey, I heat this region and everywhere else I don't heat. It's a continual thing, you're treating everything. Radiation is the same thing. You have radiation, high dose, low dose in the beam pathway. So uh but with hisochipsy, the beautiful thing about here is that it's a threshold phenomenon. So either within the focus exceeding that threshold, you have cavitation, you have damage. And outside, you have no damage. So really it's a very highly accurate treatment.

• 27:55Krishna Choudhary?

  Mm-hmm.

• 27:55Speaker 00

  Uh and because the threshold phenomenon, on top of that, it's a mechanical damage. So it really be charming by the mechanical property of target tissue. And naturally, our uh major blood vessels, nerves, bile ducts, those structures have high mechanical strength and are more resistant to mechanical damage. So we actually uh have been able to preserve those critical structures. Uh because they just, you know, they, they are naturally designed to resist positive blood flow, that kind of thing. So we are able to go in, treat tumor without damaging the vessel

• 28:37Speaker 00

  and treating inoperable, surgically inoperable tumors sandwiched between two vessels where vessels remain intact. This is really incredible.

• 28:47Krishna Choudhary?

  Yeah, yeah, okay, that, that makes total sense. And like when you, when you were going about trying to figure out this non-linearity, like what is the, this, this was part of like you discovering what is the mechanism by which cavitation happens, right? Um how much of it was like in the dark, just shooting around?

• 29:03Speaker 00

  It is pretty much all in the dark. We, we actually spend, um it, after my initial discovery in two thousand two. Uh literally, uh we went back and spent almost ten years developing the equipment and the investigation mechanism. And by uh wanting to investigate mechanism, we had to uh use ultra-high speed camera, uh because we're talking about micro bubble happening within microseconds. So, so really we're looking for this tiny little thing happening within very short amount of time and it, you know, you were talking about um during, doing treatment for minutes.

• 29:45Speaker 00

  Uh but really what's really happening is within microseconds. So, so you really have to go in and really test it out and trying to get, capture the precise timing uh with of this really fast events and also tiny events.

• 30:01Krishna Choudhary?

  Yeah.

• 30:01Speaker 00

  So microscope, high speed camera, uh and, and do experiments day in and the day out and hoping you can capture that moment. And this, honest speaking, that no same person will give you money to do, right? Like the companies or uh, you know, investors would never give you any money to do this kind of work. Uh so it was so fundamental and so, you know, really looking in the dark and turning impossible to possible, that kind of thing. Uh, and and we, you know, federal funding was so helpful here. We were able to get uh funding from National Institute of Health, saying, this is worth looking into and go and figure out to the mechanism, on the right mechanism.

• 30:46Speaker 00

  So we really spent ten years in and out, just trying to figure out how it works. And on this, only by understanding how it works, then we can optimize and design our parameters to do the best non-invasive surgery for human patients.

• 31:02Krishna Choudhary?

  Yeah, I mean, as you said, this is two thousand four, and then this is twenty fourteen. So there's ten years in between first discovering it and really having some sense of how to control the thing and what's actually happening.

• 31:14Speaker 00

  Yeah.

• 31:14Krishna Choudhary?

  Um, so for those ten years, like, did you ever, um, was there ever a time where you were like, uh, maybe I need to go do something else? You know, because that's, that's a long time.

• 31:25Speaker 00

  Yeah, it's a ten years, but before people realized that I, you know, the FDA approval was twenty twenty three. I initially discovered two thousand two, so it was twenty one years. And then that people always ask me, like, have you thought about, you know, that doing something else, really, right? Because it's like, not just ten years, it was more than twenty years before I even had any real impact on humans, right?

• 31:50Krishna Choudhary?

  Yeah, but at least, but I, I would say after twenty fourteen, it's like, okay, I've got a good handle on this, right? But like, between two, two thousand four and twenty fourteen, that's ten years. You're like grad school, early career postdoc.

• 32:02Speaker 00

  Right, and, and assistant professor.

• 32:04Krishna Choudhary?

  Yeah, so, you know, ten years on your mind.

• 32:06Speaker 00

  Right, right.

• 32:07Krishna Choudhary?

  Ten year, the, the, the professor tenure, not the ten years, but kind of, yeah, you know, like.

• 32:12Speaker 00

  I, I think, I think two things. One is scientists are programmed differently in our brain, right? Uh, to most people, it can be frustrating that in the dark. To me, uh, I was curious, and, and this potential excitement that this is unexplored, right? Nobody knew. And that's why it's so cool to me that I can make a discovery that can potentially have a big impact, right? And, and also it's associated with a real application, uh, this potential non-invasive surgery. And, and if you actually are looking at how medicine is practiced, right?

• 32:57Speaker 00

  And it's, it's there, there has been, we have been going from Stone Age, only just a hundred years ago, to now where we are, and it's all fueled by medical innovation. So in eighteen sixty, when anesthesia was invented, that's when people first time could do real surgery, right? Other, before, it's like you get something, you die.

• 33:21Krishna Choudhary?

  Yeah.

• 33:21Speaker 00

  Right? And that happened, then in nineteen hundred, Marie Curie discovered radiation, and that, uh, basically resulting in this whole radiation oncology thing, and we take radiation treatment so grateful brighter, but it's really started even not to that, you know, like a hundred years of. And then, um, nineteen sixty were the optical people discovered that the optical fiber can made it so small and still light and without burning things, and optical lens can made it so small, so that lead to what's called endoscopic surgery, right?

• 34:02Speaker 00

  So they can put a small optical camera and go in to do mini surgery, so you don't have to just cut open the big thing.

• 34:09Krishna Choudhary?

  Mm-hmm.

• 34:10Speaker 00

  So I had my gallbladder removed with endoscopic surgery with four little holes. My father had it removed with a thirteen centimeter incision, right?

• 34:19Krishna Choudhary?

  Yeah, yeah, yeah, yeah.

• 34:19Speaker 00

  So everything is moving, medicine has, in, you know, from, uh, in less and less invasive and less as toxic. And I saw this opportunity that I was looking for something that's entirely non-invasive and non-toxic. And I really thought, even though I was way ahead of curve and the people thought I was crazy, but I thought the Stargate thing where you have people going in and you can, you know, sit in there and Star Trek, right? Like you, you just said, perform the, uh, Star Trek, and you can perform the non-invasive surgery, then you come out.

• 34:54Krishna Choudhary?

  Yeah, just scans you and then you're like, fine, yeah.

• 34:56Speaker 00

  You scan you, you're fine.

• 34:57Krishna Choudhary?

  Yeah.

• 34:58Speaker 00

  I really thought that could be a reality, and I was working towards that. So it, it's a ten-year-long road, but a, a scientific discovery, they can be entirely new and a potential non-invasive surgery that, you know, maybe I will, it, it's possible I would not be the one who actually make it happen, and, and I'm lucky that I made it happen, but someone will make it happen. But if I have, you know, may do something to contribute towards that, uh, you know, some future thing, I still thought that could be a very impactful thing. And I couldn't think of anything better to do for my career anyway, so, so I thought, why not, right?

• 35:41Krishna Choudhary?

  Yeah, yeah. And fair enough. I mean, it's kind of your baby because you started it in two thousand two, two thousand four, right? So there's always like that belief that, okay, if I like found it, I'm gonna, I'm gonna be the one that like, if, if I don't do this, this is just gonna become lost in scientific literature.

• 35:56Speaker 00

  Right.

• 35:56Krishna Choudhary?

  In some sense, right?

• 35:57Speaker 00

  Right.

• 35:58Krishna Choudhary?

  Yeah, that totally makes sense. Um, yeah, that's an incredible story. And, you know, one of the, one of the things I wanted to ask you about, you know, I was, as, as we were doing the deep dives into some of your papers, um, one thing that struck me was how histotripsy doesn't just, doesn't just accomplish its goal of using mechanical degradation to take out tumors. It also somehow supercharges the immune system. So you've got this paper here where, um, we have, um, I believe.

• 36:35Speaker 00

  Yeah, it's a mouse, a tumor model, uh, and what we did is, uh, there's a primary tumor, it's a melanoma, so it's dark, you can see it. And also the mouse had an injection of the tumor cells to form tumors in the lungs, it's a pulmonary metastasis. What happened is that, uh, we had treated the tumor, primary tumor, uh, and found that there not only is a substantial increase in the immune response measured by the CDH plus T cells,

• 37:09Krishna Choudhary?

  Mm-hmm.

• 37:09Speaker 00

  but very, very, uh, you know, this kind of astounding effect is the, after primary tumor treatment, the lung metastases, the tumors substantially shrunk. And it can only be explained by histotripsy actually stimulates the immune system, and the immune system attack the tumor we didn't even treat and make it shrinking. And, and this is, you know, basically what you're expecting new therapy to do, but we are not even injecting any drugs.

• 37:41Krishna Choudhary?

  Right.

• 37:42Speaker 00

  Uh, so.

• 37:42Krishna Choudhary?

  I mean, it's so striking. It's like an action at a distance.

• 37:45Speaker 00

  Yeah.

• 37:45Krishna Choudhary?

  Um.

• 37:47Speaker 00

  So, so, yeah, so, so this is actually another surprising finding.

• 37:51Krishna Choudhary?

  Yeah, that's what I was gonna ask. Like, there's no way this was planned.

• 37:53Speaker 00

  No, so what hap, so what happened is that when we, uh, you know, were doing the clinical translation, uh, and, uh, e- eventually decided to attack the liver cancer. Uh, uh, and it was a long story, and the liver cancer eventually determined to be, uh, this, uh, uh, clinical trial they were gonna go down to. And, and also another, uh, just a little quick thing, uh, that people, most people don't know. The reason we started liver cancer was because my former PhD student, uh, Eli Wasafish, and, uh, he's actually now a professor at Virginia Tech. He was doing PhD with me, and we're doing histotripsy.

• 38:36Speaker 00

  He came into my office, uh, uh, when, after he came in as a new student, and he said, I have to do liver cancer as my PhD dissertation, uh, because my mother died of liver cancer when I was a little kid, and this is, you know, I, I, I just have to do it. And I, I, I was like, yes, absolutely, right? You know, how, how can you, how can you decline that kind of request? So, so, so we started doing liver cancer work, and then the whole field is like, okay, first, you crazy woman wanna do non-invasive surgery. Now you wanna use a mechanical, non-invasive way to treat cancer.

• 39:19Speaker 00

  Everybody was freaking out because what if you disrupt cancer cells, tumor cells, and you just help spread the tumor and the cancer everywhere?

• 39:27Krishna Choudhary?

  Yeah, yeah, yeah. You're just like, you're, you're like stirring it up, and then, and then it goes everywhere.

• 39:32Speaker 00

  Yeah, so there, everybody had this huge concern that histotripsy will actually increase the chance of metastasis because it's mechanically break up tissue. But what happened is, it's not mechanically breaking up tissue, histotripsy is mechanically breaking up the tumor cells. But regardless, there was this big concern, so we have to go and do experiments. So what did is that we actually, uh, had a rodent model, and, uh, the first actually set of study was in, uh, in rats where they had a liver tumor in, um, and we intentionally treat fifty to seventy-five percent of the tumor

• 40:14Speaker 00

  and say, okay, in the worst case scenario, not only break up the tumor, we left something behind. Now we follow them long term to see if we increase the metastasis rate, right? Like, look for any kind of cancer, uh, within the lung at different locations and outs, uh, within the liver in different location and outside the liver. And it was, uh, uh, and we started that experiments, I still remember, we had two batch, one is control mice, and one is, you know, treated by histotripsy, eleven in each batch. Control mice all died within two to three weeks. It's a super aggressive, uh, uh, type of liver, uh,

• 40:54Speaker 00

  HCC, the hepatocellular carcinoma, primary liver tumor, um, after tumor inoculation. The eleven mice treated, nine of them, not only, uh, the tumor didn't spread.

• 41:08Krishna Choudhary?

  Mm-hmm.

• 41:09Speaker 00

  The remaining tumor was just gone. We're like looking for it everywhere, we couldn't find it, and we're like, what happened? Why, why did the residual tumor go away? Because we didn't treat that.

• 41:19Krishna Choudhary?

  And that was, that was completely.

• 41:21Speaker 00

  That was a completely surprising.

• 41:22Krishna Choudhary?

  Surprising.

• 41:23Speaker 00

  Finding. We were all shocked. And where I guess something must be going on, so we uh so then I uh uh you know, reach out to Cliff Cho, who is this uh clinical scientist, surgeon and cancer immunologist. Now we did this study that you just talked about that paper, and he helped us looking to measuring all kind of immune response. So it turned out that um cancer uh it does two thing very well. And again, I'm I'm I'm ultrasound engineer, so I'm doing this really basic chart. So why is that cancer uh hides, right? Uh and that's why, you know, you have uh the patients with cancer,

• 42:07Speaker 00

  uh supposedly a foreign thing coming, our body should kill it.

• 42:10Krishna Choudhary?

  Yeah.

• 42:11Speaker 00

  But uh for so cancer, especially surgeon cancer, like pancreatic cancer, brain cancer, you don't even find them until it's very late stage.

• 42:19Krishna Choudhary?

  Yeah.

• 42:19Speaker 00

  Cause it hides so well.

• 42:20Krishna Choudhary?

  Yeah, it like suppresses the immune response around it.

• 42:23Speaker 00

  Right, and and then you also escapes the pathway that body kill it, right? So uh what happens with histotripsy is that we disrupt the tumor cells with bubbles and open up the cell membrane, allow the tumor engine to come out. And that's the first step, and the body uh and that uh histotripsy, actually, uh you know, if you look at textures, literally liquefy this tumor into this acetic debris, then the body absorb it, absorb it uh through metabolism process. So it doesn't stay there, go to bloodstream, right? So it it tumor energy come out, and then the body start looking for things.

• 42:59Krishna Choudhary?

  Yeah.

• 43:00Speaker 00

  And not only just the uh at the location of the treatment, because it's circulating in the body.

• 43:05Krishna Choudhary?

  The immune system's everywhere.

• 43:06Speaker 00

  So immune system is just circulating and looking for tumor everywhere. Uh and also, we trigger this immunological cell dead. So really uh start this whole immune cycle. And then the body is helping now uh really stimulate this immune response and use our immune response to attack the other tumors as well. And and it uh of course, the process can vary a lot uh from tumor to tumor, patient to patients. And also with histotripsy parameters you use uh can be different. We do uh we do see in small fraction of the patients that we treat one tumor, other tumor shrinking.

• 43:51Speaker 00

  And we're in the process of studying how do we really optimize our treatment parameter to maximize the immune response for that patient and combine with drugs too, so that we expand this non-invasive focal surgery to eventually systemic cancer treatment. And only at that time, we can talk about potential cure, right?

• 44:17Krishna Choudhary?

  Yeah.

• 44:18Speaker 00

  And especially for advanced cancer stage.

• 44:20Krishna Choudhary?

  Yeah, yeah, I mean, it it was it was absolutely incredible when I was reading this. And yeah, as you said, I mean, you're a ultrasound engineer by heart. Um and so you you called up a collaborator.

• 44:33Speaker 00

  Yeah.

• 44:33Krishna Choudhary?

  Mention his name again?

• 44:34Speaker 00

  Cliff Cho.

• 44:35Krishna Choudhary?

  Yeah, so he, so you know, you he, how how how was that conversation like? Was he at first like, there's no way?

• 44:42Speaker 00

  Um well, see.

• 44:43Krishna Choudhary?

  Or was he immediately like, I can maybe guess that mechanism?

• 44:47Speaker 00

  Well, he doesn't know the mechanism, but he was very open minded. Uh he was doing uh looking at immune response induced by other forms of treatment, the surgery, you know, potentially other radiation. And so he was like, okay, you know, let's take a look at least, right? Uh but I think it just kind of show you how uh you know, my career was a series of serendipity uh leading to surprising uh scientific discovery. And also, uh I started with ultrasound engineer, but along the way, I learned so much. It was a continuous learning process over my whole career

• 45:30Speaker 00

  by working with many, many different collaborators and educating me uh and keep advancing this and and and and that's, you know, even though I had been working on only one thing for my entire career so far. Uh but it has been all extremely interesting. Uh you and and I think that's kind of how the scientific discovery, uh at least in my case, goes. It is like you you find uh things um and and and then you lead to new things. Uh and and and I never uh just kind of, you know, ditch away any potential question or anything. I always trying to, you know, keep open mind.

• 46:14Krishna Choudhary?

  Yeah.

• 46:15Speaker 00

  Trying to address it, and if I don't understand, I trying to look for and find someone who potentially can help me understand it. And and I keep and then that's how things get pushed forward.

• 46:27Krishna Choudhary?

  Yeah, and was he also at University of Michigan?

• 46:29Speaker 00

  Yeah, he was, I was introduced to him because he he uh was at University of Michigan and and moved from Wisconsin, and I had some friends from Wisconsin. And then also uh uh and then he also uh knew someone from his sonics company I co-funded. So so really just a kind of different connections and yeah, and yeah. And now there are more cancer immunologists working on it. So it's really, really becoming this new field and really uh a lot of unanswered question right now is a kind of this new field with a lot of unknown. Uh then like we can really go in and explore.

• 47:08Krishna Choudhary?

  Yeah, I mean, this is pretty recent, this is twenty twenty, so you know.

• 47:11Speaker 00

  Yeah, and that's the first first paper.

• 47:13Krishna Choudhary?

  Yeah, so so.

• 47:14Speaker 00

  So it's really uh really this is a really new field, and I invite everybody to come in.

• 47:18Krishna Choudhary?

  Yeah, yeah, I mean, it's an incredible paper. And then finally, the last sort of visual that I wanted to talk to you about was um the recent hashtag Hope For Liver twenty twenty four paper. Um this, what we're looking at is uh hepatocellular carcinoma on an MRI scan. There's a before and immediately after histotripsy, and then I think this is uh thirty days after histotripsy.

• 47:45Speaker 00

  And you're missing one year.

• 47:46Krishna Choudhary?

  Yeah, yeah, well.

• 47:48Speaker 00

  There is a, there is a one year.

• 47:49Krishna Choudhary?

  Oh, there is a one year follow up? Okay, so I I I think I got this from.

• 47:54Speaker 00

  Newer paper, it's even newer.

• 47:55Krishna Choudhary?

  Oh, it's an it's an even newer paper, okay, yeah. Um I think this was the the first one, and maybe maybe it was there, but I got like the free version on NCBI website.

• 48:04Speaker 00

  You had, there's a thirty day follow up paper, then there's a year follow up paper. So year follow up paper is very recent.

• 48:11Krishna Choudhary?

  Oh, it's very recent.

• 48:12Speaker 00

  Yeah, very recent, uh and and it's uh uh so this is uh the multi-sanctuary clinical trial that led to the AP approval for non-invasive histotripsy treatment of tumors in the liver. Uh and showing uh that why is safe? So the side uh the adverse events rate is very, very low. And the second is that uh you can see on the MRI uh scan that the the tumor, they treat, the reason the radiation zone is large is because uh clinician always want to treat with a margin, right? Yeah, cause there's always cancer cells you can't see.

• 48:51Krishna Choudhary?

  Yeah, like it did chop in that.

• 48:52Speaker 00

  You can show my, so they want to really make sure you you treat everything. But that histotripsy treatment region uh like this kind of acetic liquid get absorbed by the body pretty fast. So if you see thirty days already shrinking substantially in one year, it's like the tumor is surgically reset, basically, it's it's gone.

• 49:14Krishna Choudhary?

  Oh, so so I would imagine there it's like, it looks like normal liver tissue.

• 49:17Speaker 00

  Yeah, pretty much.

• 49:18Krishna Choudhary?

  Wow.

• 49:19Speaker 00

  So uh so at the uh thirty days follow up, the technical success rate on imaging, meaning that the clinician can confirm on imaging that this is a region uh and that I treated this region uh successfully is like ninety six percent. Uh and at one year follow up, the local tumor control rate, meaning that you actually, you know, you killed it, uh is ninety percent. So which is a uh very good result.

• 49:48Krishna Choudhary?

  I mean, that's, yeah, incredible.

• 49:49Speaker 00

  Yeah, is so so really, another thing about this is that because it's non-invasive, so it's like not like surgeon going can cut it and see everything directly with their own eyes. So it's relying on imaging. So it's, you still see it, so it's image guided. Uh and if you actually looking at a treatment, is uh the the clinician going on image, they outline where the tumor is. Uh then there is this software program, create a path for the robot arm. So the treatment head is controlled by a robot arm.

• 50:24Krishna Choudhary?

  Right, okay.

• 50:24Speaker 00

  Uh and so it's create a treatment scan path for the robot to scan through uh to make sure the tumor is covered with a margin, then the treatment itself is automated. So after the uh clinician pan out and confirm everything is okay, they click a go button. Then literally uh the treat, the uh robot arm just scanning it through uh the region uh and and you know, cover that region and doing the treatment, you can still see what's going on. So there's actually this real time image guidance and monitoring, because those bubble generated.

• 51:02Speaker 00

  Our natural contrast agent for ultrasound imaging, so we can see them. So even though you don't open the patient up, there's no incision. You actually can visualize what's going on to maintain a high treatment accuracy, safety and efficacy.

• 51:20Krishna Choudhary?

  Yeah, that makes sense. And like, the fact that it's imaging along with automation and robotics, I mean, I can imagine there's a lot of space for artificial intelligence and the technologies that are being developed today in robotics to expand this further. Have you been doing work exploring those options?

• 51:39Speaker 00

  Definitely. So there is a room for AI to assist in many aspects of this whole treatment planning, uh, treatment, uh, delivery and the treatment follow-up thing. But however, because we actually recently had a meeting with clinicians on this too, and they asked, however, uh, I assure clinicians that we still need a clinician to be responsible, right? And to say, this is the part I want to treat. And to be there to make sure that's really the part you treated, right? Uh, and, and if there is, you know, because, you know, God forbid, something may happen. You, you know, there's all, not always a hundred percent to be there if something

• 52:23Speaker 00

  unexpected happens and they can deal with it right away. So, uh, our hope is we're using all the advanced technology to make the clinicians' jobs easier.

• 52:36Krishna Choudhary?

  Yeah.

• 52:36Speaker 00

  And make the experience for the patients better, because our patients after treatment, they return home, al- almost all of them immediately after procedure. There's no hospitalization.

• 52:48Krishna Choudhary?

  Wow.

• 52:49Speaker 00

  Um, because you're not.

• 52:50Krishna Choudhary?

  Oh, it's not, there's no surgery, really?

• 52:52Speaker 00

  Yeah, that's funny, because patient recover, you know, some patient when we recover is like, are you sure you did something to me? Because you know, you, you, you don't have the incision, right?

• 53:01Krishna Choudhary?

  Yeah, yeah, there's no.

• 53:02Speaker 00

  Therefore, you don't feel it.

• 53:03Krishna Choudhary?

  Right.

• 53:04Speaker 00

  But then they go home and they have supper at home, they return to, you know, at normal activity a second day. We had a crazy patient. Okay, she had her tumor and, and she was a runner. So she couldn't run because her tumor pressing on the nerves for few years. So she couldn't run, uh, uh, because of the pain, right? And she had the tumor treated by hysterectomy. Because even though absorption of this by the body take, can take, uh, you know, month, it's still pretty fast. But the tumor is liquefied right away.

• 53:38Krishna Choudhary?

  Oh, so there's no mechanical stress anymore?

• 53:40Speaker 00

  So yeah, so the, it's basically liquefies the soft gel, so she immediately, the, the pain disappear. So this crazy patient went out and run twenty miles within the first week of her tumor treatment. I, I don't add, you know, I, I would not advise any.

• 53:58Krishna Choudhary?

  I bet, I bet, I bet her clinicians were not happy about that.

• 54:01Speaker 00

  But she was like, she was so, uh, excited to have her like that. Right? And, and, and, um, I, I think that it's not just about curing patient or treating patients, it's also about the quality of life.

• 54:14Krishna Choudhary?

  Mm-hmm.

• 54:15Speaker 00

  Right? You can get the cancer treatment and cancer treatment is, uh, cancer is awful. The, the, the, the things that people don't think about is the cancer treatment is really, really awful, right? You talk about surgery painful, you talk about chemotherapy. It's horrible, like you're getting all kinds of side effects, not just the hair falling out. It, it like lack of appetite, right? And then you, you're just feeling your body aching. Even your teeth, you know, loosen up and all, it's cra- you know, it's just really, uh, a lot of bad effects. Radiation is also toxic.

• 54:51Krishna Choudhary?

  Yeah.

• 54:51Speaker 00

  So this is a way to give patients, not only, you know, a potential treatment um, for patients who run out of options, you know, don't have anywhere to go. But also for patients who have options, but they view this as a way to, uh, get cancer treated, but still maintain that quality of life. Therefore, give that hope. So it's not just awful, awful, awful, right? Like there's a hope that you can do treatment and still can have your normal activity.

• 55:23Krishna Choudhary?

  Yeah.

• 55:23Speaker 00

  Uh, so that's why, uh, the non-invasive treatment, I think in the future would be the way to go.

• 55:30Krishna Choudhary?

  Yeah. Wow. And this is twenty twenty-four, and so the recent paper that's, uh, that follows it for a year is, this is like very recent cutting-edge stuff, I guess.

• 55:39Speaker 00

  Yeah, very, very. So the recent paper, uh, is part, I think it's actually twenty twenty-six, probably this year.

• 55:45Krishna Choudhary?

  Yeah, I probably, I, I probably didn't see it. Yeah, I, I, because I think I ranked like by citations.

• 55:50Speaker 00

  Yeah.

• 55:50Krishna Choudhary?

  And that, you know, just because it's more recent, doesn't have as many citations as this one. So then I just thought like.

• 55:55Speaker 00

  Yeah, it literally just came up.

• 55:57Krishna Choudhary?

  That's, you know, that's a lesson for me, future Krishna. When you're looking for papers, don't just, don't just order by citations.

• 56:03Speaker 00

  But no, no, but that's really new though.

• 56:05Krishna Choudhary?

  Yeah.

• 56:05Speaker 00

  If you are now within the field, it's very hard for you to actually, you know, being able to get. So I'm actually impressed how you were able to pick out, you know, kind of the paper representing, uh, I would say the game-changing moments of the technology development.

• 56:21Krishna Choudhary?

  Yeah.

• 56:21Speaker 00

  So it's actually very nice, uh, selection that you have here.

• 56:24Krishna Choudhary?

  All right, thank you. Yeah, I'll, um, that's, that, that's a great compliment. Um, I wanted to ask you about the future. So I mean, as you said, this is like happening now, right? Um, how do we expedite this thing?

• 56:39Speaker 00

  Yeah.

• 56:40Krishna Choudhary?

  Because this needs to like be in every hospital, if this is like how great it is.

• 56:44Speaker 00

  So, so give you a status of the current, is, uh, so far, uh, five thousand patients have been treated.

• 56:52Krishna Choudhary?

  Whoa, okay.

• 56:53Speaker 00

  Even though it's only like five, uh, three years after FDA approval, so it's pretty fast though.

• 56:58Krishna Choudhary?

  Okay, so yeah, that's great.

• 57:00Speaker 00

  So, so, uh.

• 57:01Krishna Choudhary?

  And it's all liver?

• 57:02Speaker 00

  So, uh, it's, uh, so it's proof of liver tumor. But we have seen, uh, some clinician doing off-label treatment to, uh, thing other organs within abdominal region, but primarily is liver, in the liver. And that, uh, it come from two hundred sites, clinical sites, uh, uh, mostly within United States, but there are, uh, patients also treated in Hong Kong, Taiwan. Uh, there are also clinical trial, or we also have the CE mark, uh, which is the equivalent of FDA approval in Europe. So that also approved and also their approval in UK.

• 57:44Speaker 00

  Uh, there's also clinical trials in Australia, uh, Japan, um, and yeah, so this is kind of.

• 57:53Krishna Choudhary?

  Okay, it's becoming a global thing.

• 57:54Speaker 00

  Pretty global thing. Uh, and, um, there are clinical trials, uh, uh, for tumors in the kidney. Uh, and actually that trial have already been completed and submitted to FDA. And there's a, a ongoing trial for tumor in the pancreas. Uh, so, so that's kind of current status already pretty, pretty big. Uh, and, um, but it is a platform technology that can be used for many, many things, anything you can think of that a non-invasive removal of tissue can be beneficial for the patients, uh, that it can be potentially useful. And we are currently looking at different type of cancer

• 58:37Speaker 00

  such as, you know, beyond liver, kidney, pancreas, also breast, uh, prostate, uh, thyroid, uh, and you know, like, uh, sarcoma, which is tumor come, coming from muscle and, uh, fat, uh, even skin, just, you know, different type of cancer. Uh, also again, um, brain, I think is something I really want to push for because our neurons cannot be regenerated.

• 59:04Krishna Choudhary?

  Right.

• 59:04Speaker 00

  Right? You, when you do surgery in the brain and, and the neuron even, you know, only a few, if you damage and if they are functional neurons can, you know, cause patient to even paralyzed, right? Lose functions. So I think.

• 59:18Krishna Choudhary?

  Oh, and like, and like to get to the spot, you have to, you have to kill all the neurons like on the way down.

• 59:24Speaker 00

  Right, right.

• 59:25Krishna Choudhary?

  Right, okay, yeah.

• 59:26Speaker 00

  Uh, so, so non-invasive, uh, so like a brain surgery, uh, you know, you shouldn't treat it, uh, really, uh, largely because, and neurosurgeons are fully aware that, uh, you know, they can basically damage functions, right? And so, um, so I think this is where hysterectomy can also be super high impactful because we can treat a target tissue without damaging those neurons in a way. Uh, and we're not looking at just cancer, we're looking at stroke.

• 59:56Krishna Choudhary?

  Mm-hmm.

• 59:57Speaker 00

  We're looking at, uh, searching brain tumor, but we're looking at like functional disease such as epilepsy, right? Things that you can possibly, uh, you know, treat with a solution. But beyond that, we are also combining hysterectomy with drug delivery. And, and we have ultrasound ways that can improve the drug delivery, that we can incorporate into the same system. There's also, we are, uh, now we have an all-in-one system where I can use the same system to treat through the skull, to do non-invasive brain surgery, but also doing neural modulation, modulation of neurons.

• 1:00:37Krishna Choudhary?

  Okay.

• 1:00:37Speaker 00

  Doing, uh, drug delivery through the brain barriers, all those combined together. So I think in the future, by doing a multimodal thing combined, further enhance the treatment therapy, uh, is a way to go to really bring a maximum benefits to the patients. And, and I actually don't think this is a science fiction. Uh, uh, it's actually can happen in the near future. Uh, and that's why I'm really, again, doing this hysterectomy center to mobilize as many scientists as I can possibly push.

• 1:01:15Krishna Choudhary?

  Yeah.

• 1:01:15Speaker 00

  To, to fund this together. Uh, so I think the, uh, uh, future is, and I'm making announcement here, that.

• 1:01:26Speaker 00

  We are entering a new era of non-invasive surgery, and it's already starting.

• 1:01:34Krishna Choudhary?

  That's amazing. So the Star Trek hospital pod is actually becoming a reality. Well, I mean, I could talk to you about this um for several more, at least at least a few hours more, but I know that you are a very busy person because today you have won the Golden Goose Awards of 2026. So congratulations on that. I don't want to keep you any longer, but um it's it's really incredible some of the work that you do. Congratulations.

• 1:02:03Speaker 00

  Thank you. And then I do want the audience to know the triple S Golden Goose Award. Uh, the one big thing is to uh to really emphasize how federal funding is impacting the research and and not just research, but research that produces a big impact on our society. And and I do want to note that uh for the history, it's just an example of the research that had been heavily funded by uh the federal funding. And in my case, uh more than ninety percent of my research was has been funded by National Institute of Health, NIH.

• 1:02:45Speaker 00

  And especially at the beginning, when no investor, no company would be willing to put a penny into this at the early stage of the discovery, where the uh government step up, NIH step up, and said, we will, you know, fund you to do very innovative work. And that funding, over the twenty years, uh federal funding, NIH funded uh about like forty million dollars. But it has resulted in FDA approval, more than five thousand patients treated, and his sonics is valued at three point seven five billion dollars. With a B. With a B.

• 1:03:29Krishna Choudhary?

  Yeah.

• 1:03:30Speaker 00

  And five hundred employees and the value is really climbing up. Uh, and his sonics uh was named this year by Time uh as one of the top ten uh influential companies in life science and uh healthcare. And you know, I'm I was named by Time a hundred uh global healthcare leaders, but but that's that's a different, but I just, you know, this is showing that um the the government funding for research uh really produces uh the, you know, big impact on healthcare and our society economy. And this is precisely the reason

• 1:04:16Speaker 00

  that United States is leading the technological innovation. And if we want to keep doing so and keeping being the leader and and this is the biggest driver of the economy going, we need to support federal funding for research.

• 1:04:31Krishna Choudhary?

  Yeah. Like, I don't think I could have said it any better myself. Thank you so much. And uh we'll see you later this evening at the Library of Congress for your awards.

• 1:04:40Speaker 00

  Thank you.