Key Points

  • University Medical Center (UMC) Utrecht is the latest Focused Ultrasound Center of Excellence. Watch the virtual opening event >
  • Read the profile to learn about its research and clinical medicine – from technical to adult and pediatric applications.

The Focused Ultrasound Foundation recently named University Medical Center Utrecht (UMC Utrecht) in The Netherlands as the latest Focused Ultrasound Center of Excellence. UMC Utrecht is the fourth European Center of Excellence and the tenth worldwide.

This comprehensive and dynamic site truly exemplifies the Foundation’s Centers of Excellence programmatic goal to serve as a hub for collaboration while bringing together academia, industry, and the Foundation to showcase focused ultrasound technology. Read on to learn about the breadth and depth of research and clinical medicine – from technical to adult and pediatric applications – taking place at their site and worldwide.

Representatives from UMC Utrecht and the Foundation held a virtual opening event on Tuesday, January 19, 2021, to share the site’s latest research and plans for future projects. 

Background Information

UMC Utrecht building 600The UMC Utrecht Center of Excellence is strategically poised to benefit patients and the therapeutic ultrasound community by providing efficient translation of novel high-intensity focused ultrasound (HIFU) approaches to the clinical community. UMC Utrecht is a leader in developing technical advances, performing preclinical and veterinary studies, and conducting clinical trials.

In the realm of technical developments, the team at UMC Utrecht has created novel phased-array transducers, studied histotripsy for immunomodulation, and developed ultrasound-microbubble combinations for safe, transient, blood-brain barrier (BBB) disruption. They have also built on past and current innovations in MR thermometry, real-time image processing, real-time temperature control, volumetric HIFU ablations, and codeveloped the Sonalleve system.

The team’s preclinical and veterinary studies have centered around drug and radiosensitizer delivery and immunomodulation.

Recent clinical studies conducted at UMC Utrecht include the ongoing Phase 3 FURTHER project comparing MR-HIFU and radiotherapy for pain palliation in patients with bone metastases in a three-arm randomized controlled trial, and ongoing breast cancer applications. New trials are planned for drug delivery in pediatric and adult brain tumors.

Beyond the Center of Excellence, UMC Utrecht is among the top academic hospitals in Europe and has defined image-guided therapies as one of its main research fields. The medical center has shown institutional leadership in creating a Center of Imaging Sciences (CIS) and providing a large building infrastructure for image-guided therapies, including MR-HIFU as one of three main research lines. As one of the largest public health care institutions in the Netherlands, UMC Utrecht has more than 11,000 employees and almost 1,000 PhD students.

UMC Utrecht has demonstrated its vision for increasing synergy between image-guided therapies by bringing together nuclear medicine, radiotherapy, radiology, and oncology into a single division, resulting in a global leading role in this field. The recent opening of the Princess Maxima Pediatric Oncology Center (PMC) adjacent to the UMC Utrecht, and its initial researching funding of 8 million Euros, created the opportunity to conduct collaborative research and acquire the InSightec Exablate Neuro low-frequency focused ultrasound system for BBB applications in the clinic. The Exablate system will be installed at UMC Utrecht in 2021, and together with the existing Profound Sonalleve system for body applications and the prototype Profound Sonalleve breast HIFU system, UMC Utrecht is well equipped with clinical HIFU systems.

UMC Utrecht is associated with Utrecht University, which was founded in 1636. Located in the heart of the Netherlands, it is one of Europe's leading research universities and recognized internationally for a high-quality, innovative approach to research and teaching. The University of Utrecht has a total student body of approximately 30,000 students and 12 Nobel prize winners. It is ranked first in the Netherlands, 16th in Europe, and 75th worldwide on the Shanghai Ranking. Utrecht University offers 147graduate programs (MSc, MA) and 49 Bachelor (BSc, BA, LLM) programs. Most classes are taught in English and cover a wide range of academic disciplines, including Natural Sciences, Law, Governance, Life Sciences, Humanities, Social Sciences and Earth Sciences. Utrecht University has 8 Graduate Schools. The MR-HIFU program is associated with the Graduate School of Life Sciences.

To learn more, we asked Professor Chrit Moonen and the UMC Utrecht team to provide responses to the following questions:

When was the UMC Utrecht focused ultrasound program started, who started it, and why?
MR thermometry was started at Utrecht in 2005 by Wilbert Bartels (after receiving a Dutch grant). MR-HIFU was started in 1995 by Chrit Moonen at the National Institute of Health (NIH) in Bethesda, Maryland, USA -- initially with the objective of controlling gene expression based on the heat shock protein (hsp) promoter. In 1998, Dr. Moonen continued this work at the University of Bordeaux and the French National Center for Scientific Research (CNRS). The MR-HIFU group at Bordeaux then collaborated closely with Philips Healthcare and produced major technological developments, at first at Bordeaux, then at Utrecht, in the areas of:

  • Real-time, automatic, feedback coupling of MR thermometry and HIFU
  • Volumetric HIFU ablation methods
  • Rapid MR thermometry
  • Motion correction methods in MR-HIFU
  • Novel Phased-Array transducer design

These technical developments led to the creation of a start-up company, Image-guided Therapy, under the direction of Erik Dumont, and to the decision in 2006 by Philips Healthcare to co-develop the Sonalleve platform, in close collaboration with the MR-HIFU group. In 2008, the first uterine fibroid patient was treated with the Sonalleve system at Bordeaux.

The MR-HIFU group also initiated new applications, such as MR guidance of local drug delivery with temperature sensitive liposomes and local control of gene expression based on MR-HIFU and the hsp70 promotor.

In the meantime, the interventional radiology program at the UMC Utrecht, led by Willem Mali, in collaboration with Wilbert Bartels, initiated a program toward clinical translation of MR-HIFU, in collaboration with Philips Healthcare and the Bordeaux group of Chrit Moonen. In 2009, a large grant named VOLTA by the Dutch government at Utrecht, in collaboration with Chrit Moonen, led to the start of the clinical MR-HIFU program at Utrecht. In 2011, Chrit Moonen and members of his Bordeaux team moved to Utrecht.

What is the center’s vision and mission?
Vision: To improve current cancer therapy with MR-guided focused ultrasound, often in combination with other image-guided procedures, such as radiotherapy, chemotherapy, and immunotherapy, leading to higher efficacy, fewer side effects, and lower costs.

Mission: To develop MR-HIFU as a pillar of image-guided therapies as part of precision medicine at the UMC Utrecht Center of Imaging Sciences (CIS).

What types of facilities, space, and equipment does the site have?
CIS Overview
The MR-HIFU group is embedded within UMC Utrecht’s CIS. The CIS has three main image-guided therapy research lines:

  • MR-HIFU
  • Radiotherapy
  • Theranostics (using one radioactive drug to diagnose a cancer followed by a second radioactive drug to deliver therapy to treat its main tumor and any metastatic tumors)

For radiotherapy, UMC Utrecht invented the MR-guided linear accelerator (LinAc), a product that is now marketed by Elekta and Philips Healthcare. Three MR-LinAcs are currently installed at UMC Utrecht in collaboration with these companies. The theranostics translational research program includes image-guided radioembolization. UMC Utrecht also invented holmium-labeled microspheres for liver tumors, which led to the creation of a start-up company called Quirem.

To facilitate the development of the CIS, UMC Utrecht extended its main hospital building with a new, 5,000-square-meter building with five new treatment rooms and the following imaging equipment:

  • A total of 12 clinical LinAcs, including three new clinical MR-LinAcs and two cone beam CT (CBCT) LinAcs.
  • A total of X MRI scanners dedicated to research, including two 3T, four 1.5T, one shielded intervention 1.5T (brachytherapy), and one human research 7T scanner, which are available for clinical and research imaging. The addition of a second 7T MRI is under development.
  • A total of seven MRI systems dedicated solely for therapy, including a wide-bore 1.5T HIFU system, wide-bore 1.5T and 3T radiotherapy treatment simulators, three MR-LinAcs, and a dedicated wide-bore 1.5T Philips Ingenia system for MRI-guided brachytherapy.
  • Nuclear medicine facilities, including the newest PET/CT and a PET/MRI system under development.

Focused Ultrasound Equipment
The MR-HIFU group at the UMC Utrecht is equipped with the CE-labeled Sonalleve platform, a prototype Sonalleve breast HIFU system, various phased-array Sonalleve HIFU transducers, and homemade preclinical systems for BBB research in mice and HIFU studies in small rodents.

Major funding has been secured for acquiring the Insightec Exablate low frequency focused ultrasound system for clinical BBB applications. UMC Utrecht has a dedicated MR suite and an adjacent laboratory space for focused ultrasound research. The latter is equipped with facilities for high resolution mapping of the pressure field, acoustics development, and basic physics and chemistry analyses.

MR-HIFU in the body: Through a fruitful collaboration – initially with Philips Healthcare (leading to the development of the Sonalleve platform) then with Profound Medical – UMC Utrecht has dedicated HIFU platforms for pelvis, abdomen (Sonalleve’s CE-labelled HIFU system), and breast (a prototype Sonalleve breast HIFU platform), all compatible with the 1.5T Achieva MRI. UMC Utrecht is one of the national centers for breast, liver, and pancreas cancer. The radiation oncology and interventional radiology department provide the clinical expertise. This will allow UMC Utrecht access to patients for the clinical translational tasks. A close collaboration has been established with one of the largest non-academic hospitals in the Netherlands, Isala Zwolle, where an identical Sonalleve platform is installed (research leader Dr. Martijn Boomsma), and they are partnering in the FURTHER bone metastasis project. Isala Zwolle Hospital is also collaborating in a large trial (the MYCHOICE project) to hopefully make MR-HIFU uterine fibroid treatment a reimbursed standard of care. The Focused Ultrasound Foundation is also a partner in this endeavor.

MR-HIFU in the brain: A research facility that will be centered around a state-of-the-art transcranial MR-guided focused ultrasound (MRgFUS) system for noninvasive BBB disruption is now under construction. Our brain program will focus on the development of an innovative drug delivery strategy to the brain parenchyma and noninvasive methods to retrieve information from the brain to ascertain both therapy response and resistance. The MRgFUS research facility will be operational for early phase clinical trials in patients with brain tumors by mid-2021.The InSightec Exablate Neuro transcranial system uses a low-frequency option for BBB disruption.

Preclinical MR-HIFU: A dedicated small animal system is available for MR-HIFU at 1.5T and includes temperature control and gas anesthesia. This unit summons a rich technological ecosystem with MR-physicists, biomedical engineers, and image processing experts. The presence of the Utrecht University test animal facility and the unique Faculty of Veterinary Medicine of Utrecht University (the only one in the Netherlands) ensures that small and large animal trials can successfully be performed.

Where does the funding come from, and what is your annual budget?
Our current and past funding sources have included salaries for permanent academic staff, grants by the Center for Translational Molecular Medicine (CTMM), the European Commission, the European Research Council, the domain Applied and Engineering Sciences of the Dutch Research Council (NWO), the Focused Ultrasound Foundation, the Dutch Cancer Society (KWF), the Friends of the UMC Utrecht Foundation, and EuroNanoMed.

The annual budget for the MR-HIFU translational research program is estimated to be about 2 million euros.

Investigators

How many total staff do you have, and what are their positions?
Our current list of staff and their positions are:

  • Judith Bouwens Secretary
  • Chrit Moonen, PhD, Professor of MR-HIFU
  • Clemens Bos, PhD, Associate Professor, MR physicist
  • Wilbert Bartels, PhD, Associate Professor, MR physicist
  • Mario Ries, PhD, Assistant Professor, MR physicist
  • Roel Deckers, PhD, Assistant Professor, MR physicist
  • Greet Bouwman, MR Technician (Trained on HIFU)
  • Niels Blanken, MR Technician (Trained on HIFU)
  • Jurgen Mensinga, MR Technician (Trained on HIFU)
  • Manon Braat, radiologist
  • Evert-Jan Vonken, radiologist
  • Cyril Ferrer, postdoctoral fellow, physics
  • Josanne de Maar, PhD candidate, medicine
  • Inez Verpalen, PhD candidate, medicine
  • Beatrice Lena, PhD candidate, physics
  • Helen Besse, PhD candidate, biology
  • Isabell Bones, PhD candidate, physics
  • Suzanne Franklin, PhD candidate, physics
  • Avinash Eranki, recent PhD (2019), Guest researcher, biomedical engineering

Who are your key investigators?

Mario Ries, PhD, obtained his PhD in physics in 2001 and pursues research in diagnostic MR-imaging, real time guidance of HIFU-cancer therapy, MR-thermometry, mathematical modeling, and acoustic experimentation. He has published more than 50 peer-reviewed articles in fields relevant to MR-HIFU. Dr. Ries’s recent research activities are mainly focused on method development toward MR-HIFU ablations in challenging target areas, such as the kidney and liver, as well as drug delivery in the brain.

Clemens Bos, PhD, has 20 years of experience in MRI. He obtained his PhD (Cum Laude) on MR-guided intravascular interventions and then received NWO talent and Marie Curie grants for a 2-year cell therapy postdoctoral fellowship in Bordeaux. After working at Philips Healthcare for 8 years to expand his network and develop experience with public-private partnerships, innovation roadmaps, and product development, he returned to UMC Utrecht in 2011 for an image-guided therapy faculty position.

L.W. “Wilbert” Bartels, PhD, graduated in Applied Physics from Eindhoven University of Technology and received his PhD from Utrecht University after defending his thesis entitled "Magnetic Resonance Imaging for Guidance and Evaluation of Endovascular Therapy." He is currently the director of the Image Sciences Institute (www.isi.uu.nl), a large research group in the field of medical image acquisition and image analysis at UMC Utrecht. Dr. Bartels has supervised more than 20 PhD candidates along with many master’s and undergraduate students and has coauthored over 100 peer reviewed journal papers. He is the director of the PhD program for Medical Imaging of the Graduate School of Life Sciences at Utrecht University/UMC Utrecht. He also leads the master’s program in Medical Imaging that is offered at UMC Utrecht in close collaboration with Eindhoven University of Technology. His main research interests are quantitative MRI and MRI methods for planning, guidance, and evaluation of therapy, in particular MRI-guided high intensity focused ultrasound therapy. Dr. Bartels has been active as a researcher in the MR-HIFU field since the mid 2000s.

Chrit Moonen, PhD, completed his master’s degree in molecular sciences and his PhD in biophysics at Wageningen University and also worked alongside Nobel Laureate Wüthrich in Zürich, Switzerland. He completed a postdoctoral position at the University of Oxford (Sir Georg Radda) and then worked at the University of California, Davis as a visiting research scientist before becoming leading the In vivo NMR Research Center from 1987-1996 at the National Institutes of Health (NIH). He moved back to Europe (Bordeaux, France) in 1996 to direct the “Molecular and Functional Imaging: from Physiology to Therapy” laboratory until 2011. He is currently a professor in the Division of Imaging at UMC Utrecht and has coauthored more than 250 scientific papers. Dr. Moonen has served as President of the International Society of Magnetic Resonance in Medicine (2006) and the Society for Molecular Imaging (2009). He received the European Magnetic Resonance Award in 2000, and is a Fellow of numerous societies, including the International Society of Magnetic Resonance in Medicine, the European Society of Magnetic Resonance in Medicine and Biology, and the World Molecular Imaging Society. His recent work mainly concentrates on molecular and cellular imaging, MRI-guided focused ultrasound, and image-guided drug delivery. He recently (2019) received the prestigious Fry Award (Gold medal) from the International Society for Therapeutic Ultrasound.

Roel Deckers, PhD, graduated in Biomedical Engineering from Eindhoven University of Technology and received his PhD from Université Bordeaux (France) after defending his thesis entitled “The role of ultrasound, MRI, and optical imaging in local gene activation and local drug delivery.” His main research interests are focused ultrasound therapy of breast cancer and ultrasound-mediated drug delivery. He is currently involved in two clinical studies for the thermal ablation of breast cancer and local temperature-triggered drug delivery in breast tumors. Furthermore, he is supervising several PhD students who ae working on ultrasound-mediated drug delivery for applications such as head and neck cancer and ocular diseases.

Manon Braat, MD, completed a radiology residency and a fellowship in abdominal and breast radiology. She is a tenured staff member in the department of radiology at UMC Utrecht and has been part of the clinical HIFU team since 2013, treating more than 90 patients with HIFU (including patients with uterine fibroids, bone metastases, breast cancer and desmoids). Dr. Braat participates in the FURTHER trial for bone metastases and serves as the Principal Investigator for a breast cancer ablation trial.

Evert-Jan Vonken, MD, PhD, graduated in Applied Physics from Eindhoven University of Technology and received his medical degree from UMC Utrecht, where he also earned his PhD by studying quantitative MR perfusion. Following his radiology residency, Dr. Vonken completed a fellowship in MR physics in Baltimore and became an interventional radiologist at UMC Utrecht. He is currently participating in several studies where the common denominator is the application of new technology using an image-guided therapy.

Who are your internal and external collaborators?
We collaborate with medical specialists at UMC Utrecht and our primary collaborating hospitals, which are the Princess Maxima Center (PMC, Pediatric Oncology), Community Hospital Isala Zwolle, the Antonie van Leeuwenhoek (AvL) specialized cancer center, Radboud University Medical Center (RUMC) in Nijmegen, Alexander Monro Breast Clinic Hospital in Bilthoven, and Diakonessenhuis in Utrecht.

Internationally, we collaborate with the NIH in Bethesda, MD, Children’s National Hospital (CNH) in Washington, DC, Stanford University, and European hospitals collaborating on the treatment of pancreatic cancer (the iPaCT project) and bone metastases (the FURTHER project).

Neurology: Neurosurgeons Professor Pierre Grobe (UMC Utrecht) and Professor Eelco Hoving (UMC Utrecht and PMC), neurologist professor Tom Snijder (UMC Utrecht), and neuro-oncologist Dr. Dannis van Vuurden (PMC).

Head and Neck: Surgeon Professor Remco de Bree and radiotherapist Professor Chris ter Haard (UMC Utrecht). We also collaborate with veterinary medicine radiologist Dr. Stefanie Veraa and veterinary oncologist Dr. Maurice Zandvliet.

Abdominal: Oncologists Dr. Karijn Suijkerbuijk (UMC Utrecht), Dr. Max van Noesel (PMC), and Dr. Miranda Dierselhuis (PMC), surgeons Professor Theo Ruers (AvL) and Dr. Anthony Sandler (CNH), radiologist Dr. Bradford Wood (NIH), interventional radiologist Dr. Karun Sharma (CNH), and gastroenterologist Professor Joo Ha Hwang (Stanford University).

Immunotherapy: Immunologists Professor Juergen Kuball (UMC Utrecht), Dr. Stefan Nerkens (UMC Utrecht), and Professor Gosse Adema (RUMC).

Breast: Oncologists Professor Elsken van der Wall (UMC Utrecht) and Dr. Britt Suelmann (UMC Utrecht), surgeons Dr. Arjen Witkamp (UMC Utrecht) and Dr. Thijs van Dalen (Diakonessenhuis), and oncologist Professor Sabine Linn (AvL).

Bone: Surgeon Professor Jorrit-Jan Verlaan (UMC Utrecht); epidemiologist Professor Lenny Verkooijen (UMC Utrecht trial bureau), radiologists Dr. Alessandro Napoli (Rome, Italy), Dr. Alberto Bazzocchi (Bologna, Italy), Professor Roberto Blanco (Turku, Finland), and Professor Nandita DeSouza (London, UK).

Desmoid: Oncologist Dr. Hans Merks (PMC).

Uterine Fibroids: Radiologist Dr. Martijn Boomsma (Isala Zwolle) and gynecologists Professor Bas Veersema (UMC Utrecht) and Professor Arie Franx (Erasmus University Medical Center, Rotterdam).

Pathology: Professor Paul van Diest (UMC Utrecht).

Anesthesiology: Dr. Paul Vaessen (UMC Utrecht).

Projects

Which focused ultrasound applications and biomechanisms are being investigated?
1) Clinical translation of histotripsy and immune checkpoint inhibition
2) Breast cancer clinical trials using ablation and drug delivery
3) BBB disruption for pediatric and adult brain tumors
4) Pain palliation for patients suffering from painful bone metastases
5) Ablation of desmoid tumors
6) Ablation of uterine fibroids

Biomechanisms
1) Membrane permeabilization with HIFU in combination with microbubbles
2) Disruption of the BBB with HIFU in combination with microbubbles
3) Hyperthermia-related mechanisms
4) Heat ablation
5) Histotripsy for immune stimulation

What is the infrastructure for conducting clinical trials?
Within the CIS, a dedicated group under Professor Lenny Verkooijen supports numerous clinical studies. The team provides data management, trial design, and monitoring services to the CIS, as well as services to be compliant with the legal requirements on ethics and confidentiality pertaining to running clinical trials. Professor Verkooijen is also the PI of the FURTHER study, as described below. A major objective of the Imaging/Cancer Center at the UMC Utrecht is to conduct research that translates laboratory discovery into the clinical setting for the benefit of cancer patients, with an emphasis on personalized medicine. It has an outstanding international reputation in basic and clinical cancer research as well as in diagnostic imaging.

How many different focused ultrasound studies are being conducted at this site?
Prior to 2011, during the “Bordeaux period,” the MR-HIFU group concentrated on technological developments and preclinical work and started clinical work in collaboration with Philips Healthcare leading to the development of the Sonalleve MR-HIFU system. The first patient, suffering from uterine fibroids, was successfully treated in 2008 at Bordeaux using the Sonalleve system.

From 2009, at Utrecht, an increasing number of clinical applications have been pursued. Early phase clinical studies are mostly performed at UMC Utrecht, while for more widespread clinical adoption, we collaborate very closely with the community hospital Isala Zwolle. All applications in the neuro-oncology field are planned in close collaboration with the Princess Maxima Center (PMC), the unique pediatric oncology center that is located adjacent to UMC Utrecht. The PMC started activities in 2018.

How many patients have been treated with focused ultrasound at UMC Utrecht or in collaboration with your regional clinical partners?
From 2011 through 2020, we treated a total of 273 patients, as follows:

  • Uterine fibroids: 233
  • Bone metastasis: 21
  • Breast cancer: 10
  • Desmoid: 4
  • Endometriosis: 4
  • Hemangioma: 1

What are your preclinical projects?
Our initial technical projects in Bordeaux led to the creation of Image-Guided Therapy with Erik Dumont and the development of the Sonalleve platform with Philips Healthcare. The MR-HIFU group moved from the University of Bordeaux, France, to UMC Utrecht in 2011. Following the move to the UMC Utrecht, the MR-HIFU group interacted very closely with the radiology group (Professors Willem Mali and Maurice van den Bosch) and the radiotherapy group (Professors Jan Lagendijk, Bas Raaijmakers), as MRI guidance shares many features with MR-LinAc: Planning and monitoring of therapeutic efficacy by MRI is similar for both treatment modalities. Highlights of this collaboration include the following research projects.

  • SORTS, or Systems of Real-Time Systems: A European ITEA2 project with Philips and Elekta that took place from 2014-2017 to develop real-time systems (i.e., imaging and therapy systems) to enable more automated combination (“more than human interaction”) of imaging, therapy, and motion compensation for target tumor tissue via a guaranteed latency of the image and control data between the systems. This research is applicable to the three treatment modalities: MR-LinAc, MR-guided brachytherapy, and MR-HIFU.
  • “OnTrack:” A joint effort between MR-HIFU and MR-LinAc research groups toward real-time motion characterization, allowing target tracking of tumors in mobile abdominal organs with a minimum time lag (latency) between image acquisition and energy deposition.
  • VOLTA and HIFU-CHEM: Translational MR-HIFU approaches toward tumor ablation in breast and liver, as well as a drug delivery platform, were developed from these large Dutch grants (more than 15 million Euros from the Center for Translational Molecular Medicine). These grants were important for developing major MR-HIFU hardware.
  • Image-guided pancreatic cancer therapy (iPaCT): This European project used MR-HIFU methods for drug delivery in the pancreas. A novel transducer design was developed, colloquially known as the sunflower design.
  • Histotripsy Immunomodulation: This collaboration with the group of Dr. Bradford Wood at the NIH and Drs. Karun Sharma, Anthony Sandler, and Peter Kim at Children’s National Hospital led to the development of a novel immunomodulation technique in a mouse model of neuroblastoma (i.e., histotripsy combined with checkpoint inhibition). The results were published in Clinical Cancer Research in 2020. This method has tremendous potential for clinical translation.

Does your group have a role in device commercialization?
Our MR-HIFU group has an active collaboration with Profound Medical as the manufacturer of the Sonalleve platforms (see ongoing clinical trials).

In the past, the MR-HIFU group collaborated closely with Philips Healthcare in the development of the Sonalleve system before Philips sold the Sonalleve platform to Profound Medical. We still have a close collaboration with Philips Healthcare, but it is now concentrated on MRI for planning, real-time guidance, and follow-up of MR-HIFU.

UMC Utrecht, together with the Princess Maxima pediatric oncology center, has acquired the Insightec low-frequency Exablate system. We will develop a research collaboration with InSightec in the field of drug delivery in the brain.

We also have collaborations with Bracco on the use of MBs for therapeutic purposes, Celsion Corporation on the use of their ThermoDox doxorubicin-containing thermosensitive liposomal formulation, and Imasonic SA on transducer design.

What is on your wish list to increase your impact?
Our emphasis will be on clinical translation, in Phase I, II, III clinical trials in the fields of ablation, drug delivery, and immune stimulation.

Education

What is your role in education?
Our Focused Ultrasound Foundation Center of Excellence will become a state-of-the-art resource for patients, clinicians, and researchers. It will house a skills laboratory for advanced MR-HIFU training with dedicated clinical specialists, interdisciplinary scientists, and ongoing clinical trials. It will be modeled after our MR-guided radiotherapy laboratory in which we collaborate with Elekta and Philips. The advanced MR-HIFU training, in collaboration with industry partners, will shorten the path from fundamental research to widespread clinical acceptance.

The MR-HIFU group is a major participant in UMC Utrecht’s medical imaging PhD program in the Utrecht Graduate School of Life Sciences. The program, with more than 150 PhD students, is led by program director Wilbert Bartels, PhD. It provides extensive scientific courses on all aspects of medical imaging, MRI physics, MRI for radiotherapy, MRI for HIFU, ultrasound and HIFU physics, radiotherapy physics, and advanced radiotherapy techniques. The MR-HIFU group also participates in the training of master’s students from the MSc program in Medical Imaging at Utrecht University and from other MSc programs in disciplines such as (bio)physics, medical physics, pharmaceutical sciences, and technical medicine. A list of individuals who obtained their PhD degree in MR-HIFU from 2011-2020 is shown below.

At the national level, the MR-HIFU group participates annually in the training of clinical physicists. We contributed to the Massive Online Open Course (MOOC) dedicated to therapeutic ultrasound that was organized by the LabTau group in Lyon, France, by providing its initial lecture. Our MR-HIFU group will organize a hands-on training in MR-HIFU during the International Congress of Hyperthermic Oncology (ICHO) and participate in advanced training during several scientific meetings, including the International Society for Therapeutic Ultrasound (ISTU), the International Society for Magnetic Resonance in Medicine (ISMRM), and the American Association of Physicists in Medicine (AAPM). We also participate in AAPM’s efforts to produce a phantom, procedures for MR-HIFU quality assurance, and a white paper on MR-HIFU. The AAPM group meets on a regular basis to provide recommendations on MR-HIFU quality assurance and standard operating procedures.

The following individuals were enrolled in the Medical Imaging PhD program, specializing in MR-HIFU from 2009-2020: Sara Sprinkhuizen, Paul Baron, Marlijne Ikink, Marianne Voogt, Marjolein van Breugel, Joost Wijlemans, Bart Lammertink, Cyril Lorenzato, Marc Derieppe, Miekee Lam, Pascal Ramaekers, Laura Merckel, Floor Knuttel, Merel Huisman, Cornel Zachiu, Pim Borman, Yulia Shcherbakova, Cyril Ferrer, and Avinash Eranki. The following individuals participated in postdoctoral training in the MR-HIFU group in this period: Roel Deckers, JeanMichel Escoffre, Noburu Sasaki, Pierre Smirnov, Martijn de Greef, Ivan Dmitriev, and Cyril Ferrer (following his PhD at UMC Utrecht).

UMC Utrecht Selected MR-HIFU Publications

Verpalen IM, Bartels LW, Heijman E, Anneveldt KJ, Nijholt IM, van ’t Veer-ten Kate M, de Boer E, van den Hoed RD; Franx A, Moonen CTW, Boomsma MF. Diffusion-Weighted Imaging for monitoring of the Non-Perfused Volume during Magnetic Resonance guided Focused Ultrasound Fibroid Ablation therapy. Submitted for publication 2021.

Verpalen IM, Anneveldt KJ, Vos PC, Edens MA, Heijman E, Nijholt IM, Dijkstra JR, Schutte JM, Franx A, Bartels LW, Moonen CTW, Boomsma MF. Use of multiparametric MRI to characterize uterine fibroid tissue types. MAGMA 2020 Oct;33(5):689-700.

Verpalen IM, de Boer JP, Linstra M, Pol RLI, Nijholt IM, Moonen CTW, Bartels LW, Franx A, Boomsma MF, Braat MNG. The Focused Ultrasound Myoma Outcome Study (FUMOS); a retrospective cohort study on long-term outcomes of MR-HIFU therapy. Eur Radiol 2020 May;30(5):2473-2482.

Eranki A, Srinivasan P, Ries M, Kim A, Lazarski CA, Rossi CT, Khokhlova TD, Wilson E, Knoblach SM, Sharma KV, Wood BJ, Moonen C, Sandler AD, Kim PCW. High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy. Clin Cancer Res 2020;26:1152–1161.

Verpalen IM, van 't Veer-Ten Kate M, de Boer E, van den Hoed RD, Schutte JM, Dijkstra JR, Franx A, Bartels LW, Moonen CTW, Boomsma MF. Development and clinical evaluation of a 3-step modified manipulation protocol for MRI-guided high-intensity focused ultrasound of uterine fibroids. Eur Radiol 2020 July;30(7);3869-3878.

Stehouwer BL, Braat MNG, Veersema S. Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound is a Noninvasive Treatment Modality for Patients with Abdominal Wall Endometriosis. J Minim Invasive Gynecol 2018 Nov - Dec;25(7):1300-1304.

Knuttel FM, Huijsse SEM, Feenstra TL, Moonen CTW, van den Bosch MAAJ, Buskens E, Greuter MJW, de Bock GH. Early health technology assessment of magnetic resonance-guided high intensity focused ultrasound ablation for the treatment of early-stage breast cancer. J Ther Ultrasound 2017 Aug 1;5:23.

Merckel LG, Knuttel FM, Deckers R, van Dalen T, Schubert G, Peters NH, Weits T, van Diest PJ, Mali WP, Vaessen PH, van Gorp JM, Moonen CT, Bartels LW, van den Bosch MA. First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation. Eur Radiol 2016 Nov;26(11):4037-4046.

Huisman M, Lam MK, Bartels LW, Nijenhuis RJ, Moonen CT, Knuttel FM, Verkooijen HM, van Vulpen M, van den Bosch MA. Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases. J Ther Ultrasound 2014 Oct 10;2:16.

Ikink ME, Voogt MJ, Verkooijen HM, Lohle PN, Schweitzer KJ, Franx A, Mali WP, Bartels LW, van den Bosch MA. Mid-term clinical efficacy of a volumetric magnetic resonance-guided high-intensity focused ultrasound technique for treatment of symptomatic uterine fibroids. Eur Radiol 2013 Nov;23(11):3054-61.

Voogt MJ, van Stralen M, Ikink ME, Deckers R, Vincken KL, Bartels LW, Mali WP, van den Bosch MA. Targeted vessel ablation for more efficient magnetic resonance-guided high-intensity focused ultrasound ablation of uterine fibroids. Cardiovasc Intervent Radiol 2012 Oct;35(5):1205-10.

Voogt MJ, Trillaud H, Kim YS, Mali WP, Barkhausen J, Bartels LW, Deckers R, Frulio N, Rhim H, Lim HK, Eckey T, Nieminen HJ, Mougenot C, Keserci B, Soini J, Vaara T, Köhler MO, Sokka S, van den Bosch MA. Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy. Eur Radiol 2012 Feb;22(2):411-7.

Past Coverage

University Medical Center Utrecht Named Focused Ultrasound Center of Excellence January 2021
ISMRM Meeting Report August 2020
Foundation-Funded Research Update: Drug Delivery Strategies May 2020
ISTU Meeting Report June 2019
Therapeutic Ultrasound Course (MOOC) Now Available Online September 2018
IEEE Meeting Report July 2018
Second Quarter Research Award June 2018
STM Meeting Report May 2017
Research Roundup March 2016
Celsion Focused Ultrasound Symposium Highlights Cancer Studies January 2015
European Congress of Radiology Meeting Report March 2014
Focused Ultrasound Breast Research Update December 2013
New Research Center Launched at University Medical Center in Utrecht November 2013
Breast Cancer Study with New Focused Ultrasound System Begins at Utrecht Medical Center November 2012
Focused Ultrasound Foundation Interview with Roel Deckers about Breast Cancer Study November 2012
University Medical Center of Utrecht and Philips Start Pilot Study for New Treatment of Breast Cancer October 2012

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