Site Profile: Physics for Medicine Paris

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logotype Physics for Medicine smPhysics for Medicine Paris was created in January 2019, under the direction of Mickael Tanter, PhD, as the result of the designation of the former research team “Wave Physics for Medicine and Biology” from Langevin Institute as an independent laboratory Inserm Unit U1273 “Physics for Medicine Paris.” Our researchers have thus worked together on the same team since 2007.

It is affiliated with four institutions: Inserm (the French equivalent to the National Institutes of Health in the United States), ESPCI Paris (a high ranked Engineering School), PSL University (Paris-Sciences-Lettres University), and CNRS (the French equivalent to the National Science Foundation).

We spoke with the Center of Excellence’s Scientific Director, Jean-François Aubry, PhD, to learn more about their work.

What is the organization’s vision and/or mission?
Physics for Medicine Paris gathers biologists and physicists with expertise in ultrasound. The laboratory’s mission is to invent innovative technologies for medical imaging and therapy. Our researchers are very keen to translate fundamental physics ideas into preclinical and clinical devices. We develop applications to target three main fields of medicine: cancer, cardiovascular diseases, and neurosciences. Our research philosophy is to conduct transdisciplinary research through collaboration with experts in various fields of medicine and biology that will lead to major biomedical advances.

Physics for Medicine buildingWhat types of focused ultrasound facilities, space, and equipment do you have at Physics for Medicine Paris?
The site occupies a 1,200 m2 space located in the heart of Paris, France, where we develop and test all the prototypes, with all the needed engineering equipment and calibration tools. This central location allows close collaborations with an extended network of top-notch hospitals and research centers in Paris. Physics for Medicine Paris has a unique research platform for biomedical ultrasound, including 38 diagnostic systems (18 Verasonics VantageTM systems, 16 Aixplorer® ultrafast scanners, four 3D-ultrafast scanner prototypes [1024 channels]) and eight therapeutic systems (one MR-guided small preclinical system, three whole-body MR-guided systems – one clinical and two preclinical, two neuronavigated systems, and two ultrasound-guided systems. The experimental rooms are mostly dedicated to fundamental research, technology development, and small animal experiments. Clinical experiments are conducted in partnering hospitals.

Where does the funding come from, and what is your annual budget?
Our laboratory is funded by French, European, and international grants, as well as philanthropic foundations like the AXA Research Fund and the Bettencourt Schueller Foundation. Our annual budget in 2019 was about 3 million euros (not including tenured researchers’ salaries), the equivalent of $3.3 million US.

Investigators

How many total staff do you employ, and who are your key investigators?
Physics for Medicine Paris consists of 60 lab members, including nine permanent researchers (mostly physicists and a few biologists), 12 engineers and technicians, about 30 PhD students and postdocs, and interns. The laboratory trains students from various backgrounds, in either physics or biomedical engineering, as well as medical doctors who wish to conduct a PhD.

The senior investigators in therapeutic ultrasound are:

portrait mtanterMickael Tanter, PhD
Research Director at INSERM
Director of Physics for Medicine Paris, ESPCI, INSERM, CNRS, PSL research university France

Mickael Tanter received an Engineering degree from Supelec Gif-sur-Yvette, France, in 1994, and the PhD degree in physics from the Paris 7 University, Paris, France, in 1999. In 2006, he co-founded Supersonic Imagine (Aix-en-Provence, France) with M. Fink, J. Souquet, and C. Cohen-Bacrie. In 2014, he co-founded Cardiawave (Ile-de-France, France). In 2016, he co-founded Iconeus (Paris, France). He co-invented several major innovations in biomedical ultrasound, including transient elastography, ultrafast ultrasound, functional ultrasound imaging of brain activity, and ultrasound localization microscopy. Since 2016, he has been the Director of the first Technological Research Accelerator with the Institut National de la Santé Et de la Recherche Médicale (Inserm), Paris, dedicated to biomedical ultrasound, and created by Inserm to foster the translation of the laboratory’s innovation into prototypes for biomedical research. He is currently a Research Professor with Inserm, and the Director of the Team Inserm U979 “Physics for Medicine” (Inserm/CNRS/ESPCI Paris). He has authored more than 220 peer-reviewed papers and book chapters and holds 40 international patents. Dr. Tanter is a member of the Technical Program Committee of the IEEE International Ultrasonics Symposium and the Administrative Committee of the IEEE UFFC Society. He received multiple international scientific distinctions, including the Grand Prize of the French Foundation for Medical Research in 2016, the Roberts Prize of Physics in Medicine and Biology for the best paper of the year 2015, and the Honored Lecture of the Radiology Society of North America in 2012. He was awarded the prestigious European Research Council Advanced Grant in 2013 to develop functional ultrasound imaging and its applications. He is an Associate Editor of the IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

portrait mpernotMathieu Pernot, PhD
Research Director at INSERM
Deputy director of Physics for Medicine Paris, ESPCI, INSERM, CNRS, PSL research university France

Mathieu Pernot, PhD, is a research director at the French National Institute of Health and Medical Research (INSERM) and deputy director of Physics for Medicine Paris, France. His main research activities are focused on the development of wave physics for biomedical imaging and therapy including ultrafast ultrasound imaging in cardiology, neuroscience and therapeutic ultrasound. He has been granted 26 patents in the field of ultrasonic therapy and imaging and has published more than 120 peer-reviewed papers in international journals. In 2012, he received a prestigious award from the European Research Council (ERC starting grant) for his research on ultrafast imaging of the human heart and early diagnosis of heart failure. He and his co-authors received the IEEE UFFC Outstanding Paper Award in 2010 and 2016, the Robert’s prize in 2015, and the Rotblat Medal in 2019. In 2014, he co-founded Cardiawave, a startup company that develops the first clinical ultrasound device for noninvasive therapy of aortic calcified valves, and Iconeus, in 2017, a startup company that develops an ultrasound imaging platform for neuroscience.

portrait jfaubryJean-François (Jeff) Aubry, PhD
Research Director at CNRS
Scientific Director of the Center of Excellence

Jean-François (Jeff) Aubry, PhD, is a director of research at France’s National Center for Scientific Research (CNRS). He is a member of the medical team of the Physics for Medicine lab in Paris, France, and he is an invited associate professor at the University of Virginia’s Department of Radiation Oncology. His main research interests are MR-guided transcranial brain therapy and ultrasound-guided transcostal liver therapy, but he has also worked on ultrasonic motion detection and motion correction, high resolution cavitation mapping, and ultrasonic brain imaging. Aubry holds four patents on adaptive focusing and has been a consultant for Supersonic Imagine (Aix en Provence, France) on MR-guided brain therapy. He has given 54 invited talks at international conferences and published more than 75 papers in international scientific journals. In 2011, Dr. Aubry received the Frederic Lizzi Early Career Award from the International Society of Therapeutic Ultrasound and the 2011 CNRS bronze medal. Aubry is a member of the editorial board of the Journal of Therapeutic Ultrasound and associate editor of the journal IEEE UFFC. He is a member of the Focused Ultrasound Foundation’s Research Advisory Committee. He has been president of the International Society for Therapeutic Ultrasound (2015-2018).

Who are your internal and external collaborators?
We currently have ongoing research collaborations with three companies for therapeutic applications (Insightec, Theraclion and Cardiawave) and six companies for ultrasound imaging (BF Systems, Iconeus, Moduleus, Vermon, Aenitis, and L’Oréal).

Physics for Medicine Paris collaboration mapWe also have a longstanding collaboration with the Institute for Brain and Spinal Cord (Paris, France) for brain therapy applications, as well as the Hôpital Européen Georges Pompidou (Paris, France) for cardiac therapy applications. Overall, we have an ongoing collaboration with 13 hospitals and five research institutes in Paris (see map).

Projects

Which focused ultrasound applications and biomechanisms are being investigated?
Our projects cover a large span of biomechanisms: thermal ablation for neurological disease and the treatment of varicose veins, mechanical softening for the treatment of calcified aortic stenosis, mechanical neurostimulation, and blood-brain barrier opening for drug delivery.

How many different focused ultrasound studies are being conducted at Physics for Medicine Paris?
We develop applications to target three main fields of medicine: cancer, cardiovascular diseases, and neurosciences.

What are your ongoing projects?
We always continue to develop innovative imaging and therapeutic methods for diagnosis and targeted therapy using ultrasound. We have more than 10 projects ongoing for cardiovascular diseases and neuroscience. We also have two ongoing clinical trials: one on calcified aortic stenosis and one on essential tremor.

Describe how your work has impacted the commercial industry.
Our group holds 45 patents families in the fields of ultrasound and wave physics. Four startup companies have originated from the work of our researchers:

Physics for Medicine Paris startups

Three of them are ultrasonic imaging companies: Echosens (founded in 2001) is commercializing the Fibroscan® device; SuperSonic Imagine (founded in 2007) is commercializing the Explorer® device; and Iconeus (founded in 2016) is commercializing a real-time portable functional ultrasound neurological imaging system. One therapeutic ultrasound company, Cardiawave, was created in 2014.

What are your most noteworthy successes?
Over the past 20 years, the team has achieved two major advances in the field of biomedical ultrasound imaging by surpassing the intrinsic limitations of ultrasound: we have increased the frame rate of ultrasound scanners from 50 frames/second to 10,000 frames/second, and we have improved the spatial resolution from typically 500 µm all the way down to 5 µm.

In therapy, our main achievements have been to allow precise targeting in the most technologically challenging organs:

  • For brain therapies: performing CT-based (Aubry et al, J Acoust Soc Am 2003) and MR-based (Marsac et al, Medical Physics 2012) adaptive focusing to compensate from the defocusing effect of the human skull.
  • For liver and cardiac therapies: achieving trans-costal focusing and performing motion detection and motion compensation (Aubry et al, Phys Med Biol 2008).

In the late 1990s, we were part of the handful group of pioneers, including Kullervo Hynynen’s team members, who believed that noninvasive high-intensity transcranial therapy should be feasible. Breaking the technological barriers one by one was a long but exciting and rewarding scientific adventure.

The laboratory now has all the expertise to transfer these innovations to the clinic by achieving all of the necessary steps: demonstrating new fundamental concepts, prototyping medical instruments, and finally, disseminating them to labs, clinics, and industry.

See all our publications >

What role does the Foundation play in your work?
The Foundation has been instrumental in encouraging our group to brainstorm with the leading teams in therapeutic ultrasound to accelerate the development of the technology. A striking example was the 2009 Brain Workshop, just before transcranial brain therapy took off. At that time, it was critical for the key opinion leaders to confront their views, and for the community to set a roadmap. Our group participated in all the follow-up workshops on various topics such as enlarging the treatment envelope, blood-brain barrier opening, brain therapy, and others to further advance the technology and clinical translation.

In the past ten years, two of our projects have been funded by the Foundation’s external program (MR acoustic radiation force imaging and transcranial simulation), as well as two internships in Paris and summer internships in Charlottesville for one of our PhD students, Guillaume Maimbourg.

On a more personal note, I would like to thank the Foundation and Richard Merkin for giving me (Aubry) the fantastic opportunity to spend one year at the University of Virginia. It has been a memorable journey for my family, and a very fruitful collaboration, with more than 12 scientific papers published and a successful ongoing collaboration.

Education

In what ways does Physics for Medicine Paris prioritize education?
From 2012 to 2018, our team mentored 36 PhD students (defended or ongoing), including 17 in quantification and biomarkers, 11 in functional imaging, and 8 in therapeutic ultrasound.

Our lab has organized five winter schools on therapeutic ultrasound. Jean-François Aubry, Gail ter Haar (Institute for Cancer Research, UK) and Vera Khokhlova (University of Washington and Moscow State University) co-direct the school. Mathieu Pernot and Thomas Deffieux are co-organizers, and our lab manages the school’s registrations and general finances.

We are happy to announce that the next Winter School will take place March 7–12, 2021, in Les Houches (French Alps). We will be happy to welcome anyone wishing to learn more about therapeutic ultrasound.

Past Coverage

Company Profile: Cardiawave October 2019

Focused Ultrasound and Gene Therapy Provide Hope for Parkinson’s June 2019

Cardiawave Begins First Human Aortic Stenosis Clinical Trial May 2019

Notable Student Research Awards June 2017

2016 Summer Intern: Guillaume Maimbourg September 2016

Research Site Profile: Institut Langevin December 2015

Webinar: A Brief History of Focused Ultrasound Brain Therapy: From Old Dreams to New Hopes August 2015

2015 Summer Intern: Guillaume Maimbourg August 2015

Webinar: Transient Ultrasonic Modulation of the Brain: From Remote Palpation to Action Potential Triggering August 2015

Worldwide Neuromodulation Research June 2014

Ultrasonic Brain Therapy Expert, Jean-Francois Aubry, PhD, to be Visiting Associate Professor at UVA July 2012

ISTU Names Annual Award Winners June 2012

Breast System Project Leads to International Collaborations on MR Thermometry for Liver and Brain Indications April 2012