Although still a busy consultant in the field, Lawrence A. Crum, PhD, recently retired as a Research Professor of Bioengineering and Electrical Engineering at the University of Washington (UW). He has also retired from his posts as Principal Physicist in UW's Applied Physics Laboratory and as Founder/Past Director of the Center for Industrial and Medical Ultrasound, a translational research enterprise that builds collaboration between industry, research, and academia for the development of technology.

To capture the history and work of this focused ultrasound visionary, the Foundation's Chief Scientific Officer, Jessica Foley, PhD, interviewed Dr. Crum. She first met him almost 20 years ago, when she arrived at the University of Washington to begin her PhD work. Although Shahram Vaezy, PhD, was her direct advisor, Dr. Crum encouraged her to pursue focused ultrasound research, served on her dissertation committee, and supported her work then – and throughout her career.

You completed your education through the doctoral level at Ohio University in the 1960s (BS in Mathematics, MS in Physics, and PhD in Physics). What was that like?
I grew up on a farm in a small town in Appalachia and then first attended the US Naval Academy, which changed my life because I was introduced to a level of academics that I had not previously known, including a course in physics. I was looking for a job in mathematics when I discovered the physics department at Ohio University, and they actually offered me an assistantship to do graduate work in physics. With only having sophomore physics, the graduate courses were difficult, but I soon caught up and learned to love acoustics, the subject of my dissertation.

How did you get to the University of Washington? What is your current status?
After earning my PhD, the academic life led me to various appointments, including time at Harvard University and the University of Mississippi. I "officially retired" in 2017, but I go in occasionally and work with my group. I am also traveling a lot for my consulting work. I've been to Europe several times since retiring, and I have some upcoming travel to Europe and China. I'm still working on some grants – it's difficult to retire.

How did you become interested in focused ultrasound?
I was interested in cavitation, the subject of my postdoctoral work at Harvard. In 1994, I was asked to consult with "Focus Surgery," which led to the development of US HIFU and eventually SonaCare Medical. Early on, they were treating patients with benign prostatic hyperplasia (BPH), and I observed a patient treatment where I heard a loud popping sound. After a while, I decided that they were heating the prostate so fast that there was superheated boiling occurring right in the prostate. When the initial company dissolved, Naren Sanghvi brought a Japanese investor to a lecture that I gave in Indianapolis about the future of focused ultrasound for patient care. The investor bought the company and hired Naren to run it. That was the beginning of SonaCare, and Naren always said to me, "You saved my company."

Later I noticed that applying high-intensity focused ultrasound to a bleeding site led to hemostasis, so I wrote a proposal to the Defense Advanced Research Projects Agency (DARPA) for $10 million to use HIFU to treat combat casualties by controlling bleeding. Over the next 15 years, more than $80 million was spent on acoustic hemostasis, and we were successful in detecting occult bleeding in less than a minute and in stopping that bleeding in less than 40 seconds. But the device was quite complicated – and large and expensive – and so the military never followed through with a commercial device.

Given your long and illustrious career in physics, in particular acoustics, what are some of the key highlights and accomplishments of which you are proudest?
Probably the co-founding of the International Society for Therapeutic Ultrasound – ISTU. I was invited to a meeting in Chongqing in 2001, and the Chinese were treating patients with HIFU. So, in 2002, I invited everyone I knew to come to Seattle and called it the Second International Symposium on Therapeutic Ultrasound. A few years later, I wrote the by-laws for the Society, and for 19 years we have had more and more successful meetings.

CrumBubbleAs a "bubble expert," when did you realize the therapeutic potential of cavitation?
When I first heard the prostate popping in an early treatment. The physician treating the patient said that popping was good because we know we are killing tissue, but I also saw that it was producing a lot of bubbles, which prevented propagation into the distal region, so I thought cavitation was to be avoided. Then Ron Roy discovered cavitation-enhanced heating and I thought it might be useful but did not realize its exciting potential until the Michigan group discovered histotripsy. Incidentally, I observed histotripsy several years before the Michigan group. I was HIFUing a kidney with Shahram Vaezy and when we picked up the kidney the one end dropped off – we had cut the kidney in two with cavitation-induced mechanical ablation. But I didn't recognize it as a potential application at that time.

All of the pioneers in the field seem to have a moment when they "discovered" focused ultrasound or realized its potential. Can you tell us about your "aha moment" with the technology?
It was when I saw the patients being treated for BPH in 1994, which led to my acoustic hemostasis proposal a couple years later to DARPA.

What stands out as the most exciting moments? Any noteworthy disappointments?
Naren Sanghvi, along with Frank Fry, developed the HIFU system that was used to treat BPH. Naren and I have been working together since 1994. An exciting moment was when Shahram Vaezy (who was then a graduate student) and Roy Martin (an engineer in UW's anesthesiology department) showed me that HIFU could induce acoustic hemostasis. That was the "aha moment" that led to the DARPA grant. I was disappointed when all of the successes we had with acoustic hemostasis were not commercialized. I have a lecture that I give called "How Not to Commercialize Products," which is about the mistakes that academic researchers make when attempting to develop and transfer their intellectual property.

How about the places you've visited? The field of focused ultrasound is global and collegial – what stands out to you in this regard?
I have enjoyed going to ISTU meetings to see the wonderful research that is going on and to connect with the many colleagues and friends that I have made through the organization. Focused ultrasound is truly an international venture and staying current means knowing what's going on around the world – and getting to know the principals.

Do you have anything to say about the impact that the Focused Ultrasound Foundation has had on the field?
When Neal Kassell first announced the formation of the Focused Ultrasound Foundation, I thought it was the end of ISTU because he said that he wasn't interested in basic science – he wanted to see clinical translations. But we worked it out, and now both organizations are stronger because we are working together. Actually, without the Foundation, the field might well have died. Through the Foundation, Neal has done more than anyone else in the community to show that this field has a tremendous future.

Where do you think the technology is headed? What is on the horizon? What is most realistically achievable in terms of a mainstream application? And what's the most ambitious aspiration for where focused ultrasound might ultimately go?
Of course, the work in the brain is phenomenal – revolutionary, and it is where medicine will go in the future. I'm convinced that brain tumors (and others as well) will soon be widely treated. I thought neuromodulation was a farce until I saw some of the latest results – tremendous potential there. And possibly histotripsy has a future as well. Indeed, I think if this field continues to grow and show progress as it has in the last five years, there should be a Nobel Prize for someone – maybe Kullervo Hynynen.

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