News

Professor Gail ter Haar, PhD, is a renowned expert who works at the intersection of focused ultrasound and physics and leads the therapeutic ultrasound team at The Institute for Cancer Research (ICR), where her work centers on understanding how ultrasound interacts with tissue. Her most recent research has involved developing devices and protocols for ultrasound-based treatments of cancer, investigating focused ultrasound for immune stimulation, and using focused ultrasound to treat liver and kidney tumours. In 2014, her team at ICR – along with colleagues at the Royal Marsden Hospital – were recognized as the first Focused Ultrasound Center of Excellence in Europe. Currently, her team is involved in a Foundation-funded trial aiming to use focused ultrasound to resolve twin-twin transfusion syndrome (TTTS). Prof. ter Haar is the founding President of the International Society for Therapeutic Ultrasound (ISTU), and she leads the UK-based ThUNDDAR (Therapy Ultrasound Network for Drug Delivery and Ablation Research) network, which promotes collaboration between British and European groups working with therapeutic ultrasound. She is also an honorary member of the British Medical Ultrasound Society (BMUS) and the Society of Thermal Medicine (STM), honorary fellow of the American Institute for Ultrasound in Medicine (AIUM), and fellow of the Acoustical Society of America (ASA), the Institute of Physics and Engineering in Medicine (IPEM), and the Institute of Physics (IoP). Prof. ter Haar studied physics at the University of Oxford and received her master’s degree in medical physics from Aberdeen University. She earned her PhD in physics at Guy’s Hospital and holds a DSc in clinical medicine from Oxford. She has recently been awarded both a Visionary Award by the Focused Ultrasound Foundation and the Peter Mansfield silver medal by the IoP in recognition of her work in therapeutic ultrasound. Read the following Q&A to learn more. When and how did you get interested in focused ultrasound?I was drawn to ultrasound because of its versatility. There is no other form of energy that can be used not only to form sophisticated images and stimulate beneficial functional responses in tissue, but also to ablate localized targets, all noninvasively. I got into the field early on in my academic career working on the fundamental principles of high-intensity focused ultrasound (HIFU) before we treated our first patient in 1996 at The Royal Marsden Hospital with a homemade system. It has been a privilege to be able to work in this field, which requires an understanding of thermal and mechanical effects, and to help develop techniques that have a very real impact on patients’ lives. What are your areas of interest in focused ultrasound?My team is working in several areas: Exploring the potential for cavitation-based treatments to treat pancreatic cancer, especially through stimulating the immune response and enhancing the uptake of oncolytic viruses Investigating the use of HIFU to occlude the anastomoses involved in TTTS Investigating therapy ultrasound’s potential to improve drug delivery to the paediatric brain for the treatment of diffuse midline glioma Ensuring that therapy ultrasound exposures are properly quantified and described in order that treatment descriptions can be standardized Conducting preclinical studies to optimize histotripsy Raising funds to begin treating head and neck cancer What is the goal of your work?My overarching goal is to get therapy ultrasound into the clinic in order that anyone who can benefit has access to it. I believe it has a huge potential that has still to be realised. We just need to identify the conditions in which therapy ultrasound will have the greatest impact. What are your funding sources?Our work has been funded by the Focused Ultrasound Foundation, the UK Research and Innovation Engineering and Physical Sciences Research Council (EPSRC), the UK Research and Innovation Medical Research Council (MRC), and The Cure Starts Now. Who are your team members and your internal and external collaborators?I have a small team, but their expertise is extraordinary. Dr. Ian Rivens (who did his PhD with me) is a physicist expert in technical aspects of therapy ultrasound research. Richards Symonds-Tayler is a systems engineer expert responsible for building the new devices we develop. Dr. Petros Mouratidis is an expert in immunotherapy, working primarily on pancreatic cancer treatments. We currently have three PhD students as well. What are your greatest achievements? Any major disappointments?Getting HIFU treatments into the clinic, especially those delivered using devices designed and made at the ICR, has been a great achievement. Our recently started clinical trial for the treatment of TTTS is particularly exciting. The biggest disappointments come from not being able to progress to the next stage of a trial due to lack of funding. What do you see as impediments to your success?The lack of funding, especially for transitional stages of clinical treatments, is an impediment. There is also a lack of clinical research time for our clinical colleagues due to the stringencies of the current NHS. What is on your research wish list? Funding to develop the treatment of head and neck tumours by therapy ultrasound Funding to establish a 5-year fellowship for Ian Rivens to support the technology involved in our therapy ultrasound work, as any good team needs someone in this role A system to investigate histotripsy clinically and preclinically Does the Foundation play a role in your work?Very much so. In addition to our Center of Excellence status, we have also had several small grants for pilot projects. Without these we would not have made the progress we have. How many patients have you treated?We have treated approximately 65 patients in four different clinical trials at ICR, and approximately 30 patients with the Oxford HIFU team. Do you have any clinical or clinical research highlights?Most recently, our first treatment of TTTS has been a clinical research highlight.

Prof. Wladyslaw “Wady” Gedroyc, MBBS, MRCP, FRCR is a consultant radiologist at St. Mary’s Hospital, Imperial College National Health Service (NHS) Trust, and has been a champion of focused ultrasound for more than 20 years. He has used focused ultrasound to treat over 800 patients, beginning with women with uterine fibroids for many years and, more recently, patients with essential tremor and tremor-dominant Parkinson’s disease. We interviewed Prof. Gedroyc to learn more about his pioneering career in focused ultrasound. Read the following Q&A to hear how he first learned about focused ultrasound, his long-term research, and his fruitful collaborations. When and how did you get interested in focused ultrasound?I was first involved with MR-guided interventional work using an MR scanner to carry out a variety of percutaneous thermal ablation procedures. The work we were doing in this area in fibroids was obviously applicable to the newly emerging field of MR-guided focused ultrasound, and it was our original work in percutaneous thermal ablation of fibroids that led me to suggest that focused ultrasound could also be used for this purpose. We then treated the world’s first uterine fibroid patient with focused ultrasound in the year 2000. Having seen first-hand the potential of focused ultrasound to replace a great deal of conventional invasive therapeutic procedures for the great benefit of our patients, I became deeply engaged in this field. What are your areas of interest in focused ultrasound?I am interested in using focused ultrasound for uterine fibroid treatment, facet joint treatment, liver treatment, and brain applications, such as treatment of essential tremor and tremor dominant Parkinson’s disease. I am also studying the use of focused ultrasound in the activation of drugs at local sites within the body, including the brain, to be able to treat brain tumours and possibly Alzheimer’s disease in the future. What mechanisms and clinical indications do you study?Most of my initial work in focused ultrasound has involved studying thermal ablation procedures and their clinical results, and this remains a primary goal and interest. However, now we are purely doing brain work, which is an area of unmet need and profoundly successful. For the brain, we are studying the following clinical indications: Essential tremor thalamotomy (unilateral and bilateral) Parkinson’s dyskinesia pallidotomy Drug delivery for oncology (preclinical research) Importantly, we have a large backlog of patients who are seeking treatment for movement disorders. However, over the last years I have been deeply involved in a variety of projects looking at focused ultrasound for local drug applications and in using focused ultrasound to increase the uptake of drugs within tumours. This work has led to the patenting of several new drug formulations that have been developed within my group. We expect the evolution to first-in-human work to happen over the next few years, followed by commercialization of these developments. What is the goal of your work?My goal is to convert many currently utilized surgical and interventional procedures into completely non-interventional outpatient procedures, which would immensely benefit our patients in terms of greatly reduced morbidity and mortality. This will also benefit patients by keeping them out of hospitals and reduce the cost and burden on our financially strapped health services. Now focusing on the brain, we can offer noninvasive treatments for conditions that so far are treated with deep brain stimulation or open surgery to patients who no longer respond to medication. Apparently, this is a great relief for these patients and very gratifying to see as a treating physician. What are your funding sources?All our research funding is from the NHS Trust, industry partners, and charitable donations – especially for the capital equipment. Imperial College NHS Trust charity very generously funded the purchase of our focused ultrasound brain system. We are now in positive discussions with them to also fund the low frequency brain system that would enable us to advance our work to deliver drugs to the brain. We do not have a budget designated specifically for focused ultrasound. Part of our ongoing brain clinical work is now funded directly by the NHS for patients with refractory essential tremor. Some of the cases that we do are private pay. Who are your team members and your internal and external collaborators?Although none of us work full time in focused ultrasound, we have a group of nine professionals who are currently a part of the focused ultrasound program, including the following individuals: Professor Wladyslaw Gedroyc, MBBS, MRCP, FRCR (consultant radiologist) Peter Bain, MBBS, MA (Oxon), MD, FRCS, a neurologist Dipankar Nandi, MBBS, a neurosurgeon Brynmor Jones, MBBS, a neuroradiologist Ayesha Jameel, MBBS, MRgFUS clinical research fellow Four radiography technicians who operate the focused ultrasound systems Furthermore, we have our imaging research coordinators and nurses, who are extremely helpful and without whom we would be lost. The people who fill these roles are vital to our program. In the drug activation program, we work closely with Professor Maya Thanou, PhD, and her group at King’s College London. What are your greatest achievements? Any major disappointments?Initiating the fibroid focused ultrasound work was immensely gratifying because it has been taken up and expanded on a worldwide basis. More recently, making the case for reimbursement of focused ultrasound treatment of essential tremor and pushing it through the NHS bureaucracy has been extremely nerve wracking and time consuming. But eventually succeeding to secure reimbursement and being able to help these patients has been equally rewarding. Our immensely promising work in drug activation, which will potentially change the way we deliver therapy to patients with malignancies, is also exciting. We have encountered our share of disappointments along the way as well. Our centre faced a difficult internal political situation for a few years, which decreased the size of my research team, tightened financial constraints, and stalled our work in using focused ultrasound to treat facet joint pain and uterine fibroids. These challenges stifled innovation and creativity, but the situation has evolved, and we are now poised for progress. What do you see as impediments to your success?Ongoing financial ...

Professor Constantin Coussios, PhD, is the Director of the Institute of Biomedical Engineering and the Statutory Chair of Biomedical Engineering at the University of Oxford. He received the Silver Medal of the Royal Academy of Engineering in 2017 for his contributions to the clinical translation of novel technologies and was subsequently elected a Fellow of the Royal Academy of Engineering (FREng) in 2019. He was appointed an Officer of the Most Excellent Order of the British Empire (OBE) for his services to biomedical engineering as part of the Honours List during Queen Elizabeth’s Jubilee Birthday. Prof. Coussios holds BA, Meng, and PhD degrees in engineering from the University of Cambridge. Following postdoctoral appointments in Cincinnati and Boston, he moved to Oxford in 2004 to take up the very first faculty position in biomedical engineering in the university. Research and Training Laboratory At Oxford, Prof. Coussios founded and still leads the Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory (BUBBL), a multidisciplinary research and training environment for combinational engineering of biology, chemistry, and medical devices to improve noninvasive therapies and drug delivery under a single roof. The BUBBL team recently moved into a dedicated 2,000-square-meter building with state-of-the art facilities for therapeutic ultrasound research that is adjacent to Oxford’s clinical focused ultrasound unit. Today, BUBBL has grown to include seven principal investigators and more than 50 postdoctoral, doctoral, and clinical researchers working on a wide array of therapeutic ultrasound applications, ranging from noninvasive surgery and drug delivery to sonodynamic therapy, immune-modulation, transdermal vaccination, and stimulus-responsive tissue engineering. Scientific Discovery To date, Professor Coussios and colleagues, Profs. Eleanor Stride, Robert Carlisle, Robin Cleveland, Malavika Nair, and Drs. Michael Gray and Dario Carugo have filed more than 30 patents in the field of therapeutic ultrasound. These discoveries have been licensed and thus far led to the creation of four spin-out companies: OxSonics Therapeutics is focused on cavitation-enhanced oncological drug delivery. OrthoSon Ltd. is using ultrasound-mediated fractionation for the minimally invasive replacement of intervertebral discs. Avrox Technologies specializes in the development of ingestible and injectable oxygen nanobubbles for therapy. SonoTarg is developing sonodynamic therapy for the treatment of pancreatic cancer. This team has also overseen the clinical translation of several technologies into first-in-human clinical trials, ranging from kidney and liver ablation to targeted drug release and enhanced drug delivery to treat solid tumours. In the following Q&A, Prof. Coussios further describes his background, basic and clinical research projects, and vision for the future of therapeutic ultrasound. Focused Ultrasound Work When and how did you get interested in focused ultrasound?My interest in ultrasound started following my undergraduate studies in engineering at the University of Cambridge, where I was given the opportunity to complete my PhD under the supervision of Prof. Shon Ffowcs Williams, a world-leading expert in acoustics who was also one of the designers of the Concorde. Under his supervision, I began investigating the interactions between ultrasound and red blood cells – both experimentally and theoretically – and I came to realize that exciting interactions occurred between cells and sound waves at higher amplitudes than those conventionally used in diagnostic ultrasound. My discoveries led me to seek a first postdoctoral fellowship in therapeutic ultrasound under Prof. Christy Holland at the University of Cincinnati, who introduced me to drug delivery, sonothrombolysis, and theranostic agents (e.g., liposomes and microbubbles). Under the Hunt Fellowship of the Acoustical Society of America, I then moved to Boston University to work with Profs. Ron Roy, Glynn Holt, and Robin Cleveland, where I had the opportunity to train in theoretical and experimental aspects of ultrasound-induced cavitation, active and passive cavitation detection, nonlinear acoustics, and ultrasonically induced heating. What are your areas of interest in focused ultrasound?I am interested in all applications of acoustics and bubbles in noninvasive therapy and drug delivery. My three current focus areas are oncological drug delivery using both cavitational and thermal ultrasound mechanisms; the use of ultrasound and novel stimulus-responsive particles for immuno-modulation – both in the context of cancer and for transdermal vaccination; and the further development of clinically relevant methods for real-time treatment monitoring, including passive acoustic mapping for cavitation imaging. What mechanisms and clinical indications do you study?My primary expertise is in the seeding, generation, mapping, and control of acoustic cavitation for therapeutic applications. Our research group is currently investigating clinical indications for oncological drug delivery and immune-modulation across the liver, kidney, and pancreas; thermal ablation and cavitation-enhanced thermal ablation of the liver, kidney, and pancreas; and emerging applications of cavitation-mediated delivery, including intracellular and transdermal drug delivery. What is the goal of your work?Everything we do is ultimately patient centric. As a research group, we seek to develop new platform technologies for delivering, optimizing, and monitoring focused ultrasound treatments that can be readily translated to the clinic by virtue of maximizing safety, efficacy, and cost effectiveness. We are particularly interested in indications that demand the precision and noninvasiveness of focused ultrasound. Beyond oncology, we also like to stray into novel applications, including orthopaedic applications, transdermal vaccination, and tissue engineering. What are your funding sources?Our mechanistic and technology development studies are primarily supported by the UK’s Engineering and Physical Sciences Research Council, including under a national program grant supporting the Oxford Centre for Drug Delivery Devices (OxCD3). Our clinical translation work is primarily supported by the UK’s National Institute for Health and Care Research (NIHR), as well as several charities, including Cancer Research UK and the generous support of several private donors. Research Details Who are your team members?BUBBL research is led by seven principal investigators (Constantin Coussios, Eleanor Stride, Robin Cleveland, Robert Carlisle, Mike Gray, Malavika Nour, and Dario Carugo) and conducted by approximately 50 postdoctoral and doctoral researchers. Our expanded clinical team includes focused ultrasound specialists Prof. Feng Wu and Prof. David Cranston, leading interventional radiologists Prof. Fergus Gleeson and Mr. Paul Lyon, leading oncologists Prof. Mark Middleton and Dr. Rachel Kerr, clinical academic anaesthetist Mr. Shaun Scott, and a number of clinical research fellows, including Ms. Laura Spiers and Mr. Jeffrey Rubasingham. Who ...

BBC Click recently featured a patient named Peter whose neuroendocrine cancer has caused tumors throughout his body, including his liver. He took part in a focused ultrasound clinical trial in the UK that is exploring histotripsy – a non-thermal method of using focused ultrasound to mechanically destroy target tissue – to noninvasively destroy liver tumors. The cancer is now stable, so researchers will monitor Peter to see whether the histotripsy triggers an immune response.The #HOPE4LIVER trial is being sponsored in the US and Europe by HistoSonics. Learn more about the trial >