As the lead clinician at the University of California, San Francisco (UCSF) School of Medicine in performing focused ultrasound treatments, Matthew Bucknor, MD, Assistant Professor of Radiology, has used the technology to perform more than 30 procedures on 20 patients. This, combined with his prior work at Stanford, makes him one of the most experienced physicians in the country who is treating patients with musculoskeletal diseases using focused ultrasound. Using his focused ultrasound expertise and his sub-specialization in musculoskeletal radiology, he has recently initiated a new clinical trial comparing focused ultrasound to CT-guided radiofrequency ablation for treatment of specific bone tumors. He also has convincing ideas for combining focused ultrasound with cancer immunotherapy to create a dramatically larger impact. Although Dr. Bucknor could be considered a young investigator by some measures, he has developed a large number of highly productive collaborations and has received awards similar to long-experienced researchers. We recently interviewed Dr. Bucknor for this investigator profile.
Q & A with Dr. Matthew Bucknor
Focused Ultrasound Work
Q. When and how did you get interested in focused ultrasound?
I was a radiology resident at UCSF when Dr. Fergus Coakley (now Chairman at Oregon Health Sciences University), helped lead an effort to bring a focused ultrasound system to our institution. When I first heard about focused ultrasound technology, it seemed, to borrow the words of Steve Jobs, “insanely great.” I was uncertain whether or not I wanted to pursue academic medicine, but when I began to imagine the potential of this technology, I knew it was a field that I wanted to help drive forward. I was able to obtain an NIH grant to further study the technology as part of my final year of radiology residency training. My project centered on what happens to bone when it is targeted with focused ultrasound. I led a team studying how different focused ultrasound technical parameters lead to changes in bone structure. We were particularly interested in trying to identify ways to stimulate new bone formation, which had been reported in some patients who had been treated for bone metastases. Those basic science studies were published in JMRI and Radiology.
Q. What are your areas of interest in focused ultrasound?
I am a musculoskeletal radiologist and interested in all potential musculoskeletal applications of focused ultrasound, including treatment of benign and malignant tumors of bone and soft tissue. The technology is ideal for treating the musculoskeletal system because disease processes within muscles and bones can be easily targeted and generally don’t move (with the exception of the ribs).
I am also interested in innovating within the larger sphere of oncology. I have been collaborating with other investigators to combine focused ultrasound with novel immunotherapies to improve patient outcomes. In cases where advanced disease is not responding to chemotherapy, patients are increasingly offered immunotherapy for an ever growing list of different types of cancer. These new medications can have dramatic results, but benefits are limited to a minority of patients. There is good early data to suggest focused ultrasound might improve responses to these medications. We would like to develop clinical trials within this sphere and hopefully modify the function of existing, widely available focused ultrasound devices for improved disease control.
Q. What is the goal of your work?
In general, I want to help fully realize the potential of focused ultrasound, particularly for treatment of benign and malignant tumors. In the near term, I hope our recently initiated clinical trial will lead to the first FDA-approved indication for focused ultrasound in children—currently there is no approved pediatric indication. A first approval would dramatically lower the barriers to treating many more kinds of diseases in our younger patients. And because focused ultrasound is non-invasive and free of ionizing radiation (which can increase cancer risk in children), they are one of the groups that stands to benefit the most.
Overall, we want to be a part of this paradigm shift with the technology–a part of the force that figures out where the technology is best used and how it can positively benefit the most people.
Q. What are your funding sources?
Our work is currently funded by grants from the Focused Ultrasound Foundation, the National Institutes of Health, along with UCSF institutional grants. I was also recently awarded an Association of University Radiologists (AUR) GE Radiology Research Academic Fellowship (GERRAF) for the next two years. This award is for junior faculty academic radiologists committed to careers in clinical research. The goals of the program are to strengthen the research interest of radiologist-investigators by broadening their opportunities for continuing scholarship and to foster original clinical and health services research in technology assessment, health and economic outcome methods, and decision analysis.
Q. Who are your team members?
Our technical director of focused ultrasound is Viola (Rieke) Tognina, PhD, who is an MRI physicist and Associate Professor of Radiology in the UCSF School of Medicine. She works closely with Eugene Ozhinsky, PhD, who is also an MRI physicist at UCSF. Our post-doctoral fellow is Rutwik Shah, MD. We also have a team of specialized anesthesiologists, MRI technologists, and nursing staff working with us, along with a medical student, Gabriela Beroukhim.
Q. Who are your internal and external collaborators?
We are currently working with several collaborators at UCSF and I expect this group to grow:
- Rosanna Wustrack, MD, Assistant Professor, Orthopedic Oncology
- Richard O’Donnell, MD, Professor and Chief of Orthopedic Oncology
- Thierry Jahan, MD, Clinical Professor, Department of Medicine, Thoracic Oncology
- Ross Okimoto, MD, Adjunct Instructor, Department of Medicine, Medical Oncology
- Lawrence Fong, MD, Leader of the Cancer Immunotherapy Program, Co-leader of the Cancer Immunology Program, and Distinguished Professor in Cancer Biology
Outside of UCSF, we have been working with the following:
- Pejman Ghanouni, MD, PhD, at Stanford, a co-investigator on the osteoid osteoma clinical trial
- Michael Temple, MD, and James Drake, BSE, MBBCh, MSc, at SickKids in Toronto, as part of the pediatric registry
- Karun Sharma, MD, PhD at Children’s National Health System, sharing case experiences of our treatments for tumors including desmoid tumors and osteoid osteomas
Q. What are your greatest professional achievements? Any major disappointments?
As a radiology resident, I received a Radiological Society of North America (RSNA) research trainee prize for my early focused ultrasound work. As a faculty member, we were the first center in the US to treat an osteoid osteoma patient with the Insightec Exablate device. I was also thrilled to receive the GERRAF award, which is very competitive and only given to three radiologist-investigators each year. I’ve been fortunate to not have any major disappointments. I have barriers to my work. But that’s how I know that I’m in the right field – because despite those barriers, I still feel committed to my work and want to keep pushing forward because the potential is too great.
Q. What do you see as impediments to your success?
Some of the diseases that we are treating have very well established treatment paradigms. It can be difficult to set up new trials that disrupt traditional therapies, no matter the potential. Building relationships and getting people to see how a newer therapy like focused ultrasound might be in the patient’s best interest has been challenging, but we are making progress.
Regulatory processes can be very inefficient and at times can dramatically slow the momentum behind a really good idea.
Finally, trying to obtain insurance coverage for treatments requires a huge amount of time. I’m always willing to fight for the best possible treatment for my patients. But it is frustrating when insurance companies deny coverage without reviewing a lot of very good focused ultrasound clinical research performed over the last decade.
Q. What is on your research wish list?
It would be great to have more lasting or endowed support for my work. Because many grants are relatively brief in duration, we have to focus on finding near-term results. I wonder if we are sometimes missing high risk/high reward opportunities that could have a dramatic impact, but that require a longer upfront investment.
On the technical side of things, I would love to have a single focused ultrasound device that combined some of the properties that are currently found in several devices: some are good for soft tissue, some are good for bone, some are better at reaching high temperatures quickly, some are better for shaking tissue at very high frequencies. If all of those modes could be combined into a single device, we may find that certain combinations of these properties produce better treatment outcomes.
Q. Did the Foundation play a role in your work?
Yes, the Foundation played a role very early on when I was first learning about focused ultrasound. As I was pursuing those early research studies, having a centralized resource where I could see what was happening across the entire field was very powerful for me. Moving forward, the Foundation has given me invaluable opportunities to present my work, get input from colleagues, and, most recently, receive direct support for my research efforts. In those ways, the Foundation has been one of the most important entities helping me to move forward at every step.
I have not yet attended any Foundation workshops, but I have attended several Symposiums. I have met many great collaborators from all over the world at the Symposium, including Alessandro Napoli, MD and Karun Sharma, MD. Interestingly, one of my colleagues here at UCSF, Lawrence Fong, MD, attended a Foundation workshop on cancer immunotherapy a few years ago. During the workshop, he found out about my research here at UCSF. We were each in our respective silos, interested in the same technology, but had never met. Now, thanks to the Foundation, we have a powerful collaboration.
Q. How many patients have you treated?
I have performed approximately 50 focused ultrasound procedures on 30 patients (some of them with Dr. Pejman Ghanouni at Stanford). I completed a musculoskeletal radiology fellowship at Stanford, where I spent one day a week working with him. Here at UCSF, I have treated about 20 patients. Most of our treatments are for patients with desmoid tumors.
Q. Do you have any clinical research stories or highlights?
The first patient that I treated with focused ultrasound was a 7-year-old boy with a desmoid tumor in his thigh. The tumor was the size of his entire thigh. He and his parents had tried many other approaches: surgery, radiation, and chemotherapy, all before age 7, but the tumor recurred to this very large size. Chemotherapy had caused him to suffer from severe and painful dermatitis over his entire body. When he was referred to me, the tumor was too large to treat in one setting because we wanted to avoid a long anesthesia time. Now he is 11 years old and we have been managing his tumor entirely with periodic focused ultrasound treatments. These tumors often recur, but with focused ultrasound we are able to extend the time between his treatments. Most recently he went 18 months between sessions. I hardly recognized him from how much he had grown. In his short life, he had never had that much time off between medical visits. It has been great for the family to have this treatment option. It’s given them hope.
Q. What comes next?
We are actively recruiting for our current clinical trials. Our osteoid osteoma trial has begun enrolling. We have a post-approval trial for bone metastases. We are looking toward initiating some immunotherapy clinical trials.
Bucknor MD, Ozhinsky E, Shah R, Krug R, Rieke V. Effect of Sonication Duration and Power on Ablation Depth During MR-Guided Focused Ultrasound of Bone. J Magn Reson Imaging 2017 Nov;46(5):1418-22.
Ghanouni P, Dobrotwir A, Bazzocchi A, Bucknor M, Bitton R, Rosenberg J, Telischak K, Busacca M, Ferrari S, Albisinni U, Walters S, Gold G, Ganjoo K, Napoli A, Pauly KB, Avedian R. Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. Eur Radiol 2017 Feb;27(2):732-40.
Ozhinsky E, Han M, Bucknor M, Krug R, Rieke V. T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound. J Ther Ultrasound 2016 Nov 17;4:26. eCollection 2016.
Temple MJ, Waspe AC, Amaral JG, Napoli A, LeBlang S, Ghanouni P, Bucknor MD, Campbell F, Drake JM. Establishing a clinical service for the treatment of osteoid osteoma using magnetic resonance-guided focused ultrasound: overview and guidelines. J Ther Ultrasound 2016 May 20;4:16. Review.
Bucknor MD, Rieke V, Seo Y, Horvai AE, Hawkins RA, Majumdar S, Link TM, Saeed M. Bone remodeling after MR imaging-guided high-intensity focused ultrasound ablation: evaluation with MR imaging, CT, Na(18)F-PET, and histopathologic examination in a swine model. Radiology 2015 Feb;274(2):387-94.
Bucknor MD, Rieke V, Do L, Majumdar S, Link TM, Saeed M. MRI-guided high-intensity focused ultrasound ablation of bone: evaluation of acute findings with MR and CT imaging in a swine model. J Magn Reson Imaging 2014 Nov;40(5):1174-80.