- Rajiv Chopra, PhD, is a pioneering focused ultrasound researcher and a dynamic entrepreneur who has started several companies with the goal of putting focused ultrasound technology in the hands of physicians and researchers.
- His research has advanced the technology for prostate treatment and countless other applications.
- Now, he is planning to build a network of outpatient imaging clinics that offer therapeutic ultrasound as a treatment option.
In his academic career at the University of Toronto and Sunnybrook Health Sciences Centre that continued at the University of Texas Southwestern (UTSW) Medical Center in Dallas, Texas, Rajiv Chopra, PhD, led pioneering preclinical research and eventually helped implement newly created focused ultrasound clinical services. His early research led to the creation of Profound Medical, a company that has treated over 2,000 patients with therapeutic ultrasound around the globe. His preclinical research has contributed to discoveries on blood-brain barrier (BBB) opening and drug and gene delivery for Alzheimer’s disease and other neurodegenerative disorders. Most recently, his efforts at UTSW Medical Center have led to a robust multidisciplinary focused ultrasound Program offering both prostate and brain treatments to patients in North Texas.
Beyond conducting research, mentoring young investigators, and implementing new patient services, Dr. Chopra is a dynamic entrepreneur who has started several companies. After co-founding Profound Medical with Michael Bronskill, PhD, he also launched FUS Instruments and more recently Solenic Medical. Always pushing the boundaries of the field, his newest endeavor is launching and growing Perigon Imaging, a company that is building a network of diagnostic and image-guided therapy centers in Texas and Oklahoma offering MRI-guided focused ultrasound for the treatment of localized prostate cancer.
As he transitions out of academia, we interviewed Dr. Chopra to learn more about his amazing career that has always pushed the boundaries of focused ultrasound to new levels.
Focused Ultrasound Work
When and how did you get interested in focused ultrasound?
I completed my undergraduate degree in physics at McMaster University. When I began graduate school in the late 1990s at the University of Toronto and Sunnybrook Health Sciences Centre, I wanted to use my physics background in an applied area and was attracted to magnetic resonance imaging (MRI). Around that time, there were early advances in the field of MRI-guided focused ultrasound, and the group in Toronto recognized the potential of the technology. The physicists and engineers there had a long history of developing MRI, ultrasound, and x-ray diagnostic imaging technology, and some of the scientists were exploring the expansion of traditional diagnostic imaging into image-guided interventions. MRI-guided focused ultrasound was a good fit. My PhD advisor, Michael Bronskill, PhD, and I began investigating whether minimally invasive focused ultrasound devices could be integrated with MRI and, if so, for which medical interventions this technology was well suited. The research environment at that time within Sunnybrook was very conducive to making rapid progress, and we did.
What are your areas of interest in focused ultrasound?
My primary interest has always been in the development of technology for image-guided interventions, and most of my efforts have been in the area of focused ultrasound. Over the years, my laboratories have developed new devices for high-intensity focused ultrasound (HIFU) prostate treatment, preclinical focused ultrasound systems, and other technology that can be used in the MRI environment. Beyond device development, my preclinical research interests are in BBB opening and drug and gene therapy delivery.
I am also passionate about clinical translation. A number of my research efforts have been translated to commercial and clinical applications – through the creation of companies such as Profound Medical and FUS Instruments. I started Profound Medical because I was convinced that this approach to treating prostate cancer had the potential be a standard of care, and could benefit patients, physicians, and payors. I co-founded FUS Instruments with my colleague Kullervo Hynynen, PhD, to disseminate focused ultrasound into the hands of researchers all around the world to accelerate development and discovery.
There is so much potential at the intersection of acoustic and electromagnetic energy. MRI-guided focused ultrasound is perfect example of that. More recently my group has shown that we can also flip that switch and use magnetic fields as the therapeutic energy source with acoustics serving as the sensor/receiver for treatment of infected metal implants in the body. Others have described clever combinations of these energies at the cellular scale. I am confident there are many more applications within this space, and I look forward to more of these being discovered in the future.
What mechanisms and clinical indications have you studied?
- Tissue Hyperthermia
Most of my research in the area of thermal bioeffects of ultrasound has been focused on the application of prostate tissue ablation and prostate therapy. We demonstrated that by controlling focused ultrasound with real-time MR thermometry in a closed-loop fashion, very precise tissue ablation could be achieved, and this has held true from our preclinical studies to more than 2,000 patients. The other important demonstration from this work has been that simple disposable ultrasound transducers are capable of delivering very complex heating patterns in tissue in a very efficient manner, and they are superior to laser, RF, or microwave devices. They perform as well as externally focused transducers for bulk ablation and can offer significant economic advantages because of cost and time savings. These observations are what led to the formation of Profound Medical.
- Targeted Drug Delivery
My group used focused ultrasound—based hyperthermia to help deliver thermosensitive liposomes (TSLs) containing doxorubicin into the body, and we have also had projects to deliver drugs, antibodies, and other gene therapies to the brain. This work has been extremely promising in preclinical studies by my group and others. Commercial development in this field has been slow, however, and the future is uncertain from my perspective.
- BBB Opening
I have maintained a program studying the unique capability of focused ultrasound to open the BBB, work I started in collaboration with Kullervo Hynynen when we were colleagues at Sunnybrook Research Institute. At UTSW, I’ve focused on a few unique areas. On the technology side, I built and tested a stereotactic focused ultrasound system for brain studies in rodents (primarily because I didn’t have access to an MRI for the first two years of my time there!), and then worked with FUS instruments to make this commercially available to researchers. It’s currently in more than 20 labs around the globe.
I also explored the ability to open the BBB using nanobubbles (2-300 nm diameter) instead of microbubbles, something I didn’t believe would work until we did the studies. We have pointed out that infusion of microbubbles during BBB opening produces more consistent results and also makes the use of acoustic control more reliable. Finally, I stumbled across a discovery that Nitrous Oxide (N2O), a commonly used inhalant anesthetic, has a dramatic impact on BBB opening with focused ultrasound. The mechanism is complex, and involves interplay between the gas, the microbubbles, and blood vessel response, but the effect is unmistakable. It can amplify the effect of microbubble activity by 10-100x, which creates the possibility to reduce acoustic pressures or microbubble concentrations. I will not continue this research as I leave academia, but I hope our publications – which are under review – will stimulate others to further investigate and refine this bioeffect. In my opinion, there are even opportunities in diagnostic contrast imaging that could be exploited through the use of N2O.
What is the goal of your work?
If I had to assign a broad theme to my work, it would be to improve healthcare delivery using image-guided therapies. This can be achieved by using new technologies to create treatments that are less invasive or less harmful to patients and also more efficient and economical to physicians and payors. I have done this this through the development of medical devices that combine acoustic and magnetic energy for non-ionizing and noninvasive therapies.
Tell us about your research space.
The focused ultrasound research group at UTSW occupies about 1,800 square feet of laboratory space in the Department of Radiology. It is open bench space that is suitable for the development and testing of ultrasound devices and systems. I also have a footprint across campus in the Department of Infectious Disease with my collaborator David Greenberg, MD. In addition to UTSW, I have access to laboratory space in Canada at the companies I started and, during the pandemic, I created a laboratory at the back of my home (when research activity virtually shut down across the globe). I have maintained this home-based laboratory and operate a company now with some talented engineers I have had the good fortune of meeting. Recently I opened a laboratory in Oklahoma City associated with a nuclear cyclotron, related to new forays I am making into this field.
What type of focused ultrasound equipment does UTSW have?
When I arrived at UTSW, there was no infrastructure to conduct focused ultrasound research, so I invested a few years setting up the laboratory. Initially the primary clinical equipment was a Sonalleve MR-HIFU system attached to a 3T Philips research MRI. This was used as part of a clinical trial I led to treat uterine fibroids. We also had several preclinical focused ultrasound systems, including a Verasonics research system and a FUS Instruments RK100. The lab was supported by a suite of in-house test and measurement equipment and facilities (radiation force balance, hydrophone scan tanks, electronics and machine shops, and degassers).
Over the past few years, the focused ultrasound program at UTSW has matured to offer the technology as a clinical service as devices achieved regulatory approval. Today we have the Insightec Brain system at our main hospital attached to a 3T Siemens scanner with both the high and low frequency system. We also have the Profound Medical TULSA-PRO system attached to a 3T Philips MRI in the same hospital. We have treated close to 100 prostate cancer patients, and over 100 essential tremor patients. The response from patients and physicians is overwhelming, and I anticipate these programs will only grow in magnitude and scale as awareness of the technology grows.
What funding sources have you used for your research?
Over the years, I have had research funding from the US National Institutes of Health (NIH), the Canadian Institutes for Health Research (CIHR), the Cancer Prevention and Research Institute of Texas, private foundations and private donors. I also received industry funding for research projects from Philips Healthcare, Profound Medical, FUS Instruments, Solenic Medical, Johnson & Johnson, Celsion, Monteris Medical, and several other companies. Early seed funding for prostate studies from the Ontario Institute for Cancer Research (OICR) helped spur the commercialization of Profound Medical.
Describe your team members at UTSW.
The research teams I’ve built at UTSW and elsewhere tend to be very multidisciplinary. I’ve always had graduate students, post-doctoral fellows, and research staff with engineering or science backgrounds, veterinary technicians, medical residents and fellows, and junior faculty.
Who are your internal and external collaborators?
- Brain Projects
Bhavya Shah, MD, is the neuroradiologist who I mentored and worked with to build the clinical HIFU program for movement disorders. He learned the techniques for BBB opening in my laboratory, and has been very successful at building collaborations with investigators in the Brain Sciences campus. I have been impressed to see his leadership on the clinical translational side and he has built one of the best clinical focused ultrasound brain programs I have seen. He is advancing the field as he shows the superior clinical outcomes his targeting with advanced diffusion tensor imaging achieves. I look forward to his continued success after I leave.
- Prostate Projects
The Radiology Department, in particular the Body MRI group, has spearheaded the introduction and growth of prostate MRI for imaging and therapy at UTSW since they arrived 10 years ago. Doing MRI-guided prostate ablation with the Profound Medical TULSA-PRO system was a natural evolution in their program development and it has been a success. Today, the TULSA-PRO program is a joint effort between Urology and Radiology, and Drs Xiaosong Meng and Daniel Costa have demonstrated their leadership in growing this program at UTSW.
- Preclinical Projects
This is a very long list of people because of the large number of projects my group has been involved in. I’m sure there are people I have missed.
- Advanced Imaging Research Center: Ian Corbin, PhD, Jae Mo Park, PhD, Dean Sherry, PhD
- Radiation Oncology: Brian Hrycushko, PhD, Paul Medin, PhD, Debabrata Saha, PhD
- Pediatric Oncology: Ted Laetsch, MD, Noelle Williams, PhD
- Radiology: Ananth Madhuranthakam, PhD, Matthew Lewis, PhD, Xiankai Sun, PhD, Ralph Mason, PhD, Avneesh Chhabra, MD
From my time at Sunnybrook, I enjoyed fruitful scientific collaborations with Kullervo Hynynen, PhD, David Goertz, PhD, Stuart Foster, PhD, Peter Burns, PhD, Don Plewes, PhD, Martin Yaffe, PhD, Apoutou N’Djin, PhD, and Michael Bronskill, PhD.
I appreciate the clinical partnership I built with Laurence Klotz, MD, Linda Sugar, MD, and Masoom Haider, MD, as we embarked on the first human studies with MRI-guided transurethral prostate ablation.
Robert Staruch, PhD, and Mathieu Burtnyk, PhD, are former students who joined Profound Medical and remain collaborators as we push the technology toward a standard of care for prostate cancer treatment.
Beyond my direct internal and external partnerships, I consider all the users of focused ultrasound technology from FUS Instruments as scientific collaborators. We have installed approximately 50 systems around the globe in laboratories, academic medical centers, and pharmaceutical companies, and each of these groups is doing research.
Have you had a role in education?
As my career has advanced, I have mentored several younger investigators who have started their own research laboratories around the world, which has been extremely rewarding. I have never had major teaching responsibilities in my career. However, the one program for students I am proud of having co-founded with Kullervo Hynynen, is a high-school summer internship in Toronto we launched back in 2008, which has exposed over 20 students each year to research and has influenced over 200 bright young minds to consider academic medical research as a future career path. The impact of this program may outweigh the impact of our research!
What are your greatest professional achievements?
I’m proud of how far Profound Medical has come. When I co-founded it with Michael Bronskill back in 2008, I felt the technology had potential but couldn’t predict what would happen as it was commercialized. It has been rewarding to see it grow through the stages of clinical trials and regulatory approval. Today the TULSA-PRO system is available at around 20 sites around the world to patients who desire treatment of their prostate cancer or enlarged prostate without all the side effects associated with conventional treatments. I enjoy seeing physicians use the technology and develop new, clever ways to use it to treat prostate disease more effectively. It has been very rewarding. Many of my former students work at Profound Medical. I feel I have a surrogate family there.
Any major disappointments?
I have worked on incredibly promising research that just could not make it out into clinical practice. For example, the work we did with temperature-sensitive liposomal drug delivery work at UTSW had phenomenal results in preclinical studies. Unfortunately, the commercial development and regulatory approval of these drugs has been slow, which has hampered clinical trials of the agents across a wide range of cancers. Further, the technology to do ultrasound hyperthermia is not yet available, or is still very complex and not ready for routine clinical use. I don’t know where this field will go, but I hope it can find a way forward because it is a powerful way to localize drugs in the body.
What do you see as impediments to your success?
I have been in academia for about 25 years. It has been a great environment for discovery and early clinical evaluation. However, it is not the best environment for rapid growth and expansion of clinical treatments. I want to make technologies like TULSA-PRO available to every man who wants it within 100 miles of their home. If this can be achieved, there is no doubt in my mind it will become a standard of care. This type of expansion can’t be done in the confines of the academic medical center, so I am embarking on a new journey to achieve this goal.
What is on your research wish list?
Recently I co-invented a new treatment for removing biofilm on infected metal implants (such as prosthetic joints.) The method works by exposing these implants to alternating magnetic fields, which can be applied noninvasively to heat the implant surface where biofilm is located. We discovered that 1) Heat combined with standard of care antibiotics is very potent at removing biofilm from metal implants, 2) Coils can be designed that uniformly heated complex implants like a knee, and 3) Acoustic sensors can be used to noninvasively monitor the procedure. While on the face of it, this technology is unrelated to MRI-guided focused ultrasound, it uses the same combination of magnetic and acoustic energy, just in the opposite way. I am working hard to translate this technology to human trials, and started Solenic Medical in Texas, which recently received a breakthrough medical device designation from the FDA. My wishlist is to see more medical applications combining acoustic and magnetic fields become established in medicine, across a broad range of disease states. I would encourage the Foundation to also be receptive to new ideas that combine these common energy sources.
Has the Focused Ultrasound Foundation played a role in your work?
The Foundation’s symposium has been very helpful, and I have met a lot of valuable people through the Foundation. Just by its existence, the Foundation has connected me with many research, industry, and clinical partners. It has played an incredibly important role in the field.
What clinical treatments are now being done at UTSW?
UTSW entered the clinical scene for focused ultrasound two years ago, in 2020, when it purchased the Profound Medical prostate HIFU system. The first patients were treated in October 2020. With UTSW scanning 1,500 men for prostate cancer each year with MRI and conducting about 200 MRI-guided biopsies, a minimally invasive option for focal treatment of cancer was in demand. High patient volumes combined with an experienced and established team create a good environment for this technology at UTSW. Offering the TULSA-PRO technology is a nice continuum, because patients come in, are diagnosed with cancer, then undergo a fusion biopsy to determine the grade of cancer. And now, with prostate HIFU, they can receive a localized treatment.
With respect to brain, a generous donor enabled UTSW to purchase the Insightec ablation and BBB systems, and the medical center began initiating clinical programs just over a year ago, in the spring of 2021. Dr. Shah has built strong connections between neurology, neurosurgery, and radiology, and the wheels are in motion to establish clinics, billing, referral patterns and treatment protocols. In parallel with using the platform for treatment of tremor, Insightec has invited UTSW to be part of an Alzheimer’s disease clinical trial evaluating the safety of BBB opening.
How did UTSW fund the development of these clinical programs?
There was growing interest from the wider donor community and hospital leadership about the potential of focused ultrasound to be a shining example of how UTSW is defining the future of medicine. The interest from Dallas-based donors was awe inspiring. There is a strong generosity in Dallas, and an even stronger desire to facilitate UTSW having the latest technology for Dallas residents. I have been amazed at the magnitude of philanthropic good will in Dallas compared to previous cities where I lived.
Do you have a favorite clinical treatment story or highlight?
The first NIH-funded clinical trials that my laboratory conducted with MRI-guided transurethral ultrasound therapy were at Sunnybrook. These were collaborative, investigator-initiated trials performed by my group in collaboration with urologists, radiologists, and pathologists. The entire treatment system was built in-house at Sunnybrook Hospital. The trial design was to treat men diagnosed with prostate cancer with the transurethral system, prior to their scheduled radical prostatectomy. We obtained their prostate glands after surgery and evaluated at the tissue level with pathology whether we accurately treated the region of prostate tissue we targeted with imaging. The men who participated in this study knew that they would have no benefit from our treatment, but they were still willing to undergo the procedure for our work. In particular, I remember one man who was of Jamaican origin who was a pilot. He got prostate cancer in his 50s, and his father had also had prostate cancer. He said that if he could shed some knowledge and help the field move forward for future generations, then he was happy. That was what a lot of these men did, and it was admirable.
What is next for you?
I will be working primarily to help advance the mission of the companies I’ve created over the past 20 years. With Perigon Imaging, I will work with my partners to expand the footprint of treatment centers for TULSA-PRO. Stay tuned for updates as the first centers open this fall and the first patients begin to be treated!
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