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Cascade-amplified ultrasound focal ablation (CAMUS)

English title Cascade-amplified ultrasound focal ablation (CAMUS)
Applicant Salomir Rares
Number 162722
Funding scheme Interdisciplinary projects
Research institution Service de Radiologie Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Experimental Cancer Research
Start/End 01.01.2016 - 31.12.2019
Approved amount 375'144.00
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All Disciplines (5)

Discipline
Experimental Cancer Research
Organic Chemistry
Other disciplines of Engineering Sciences
Biomedical Engineering
Other disciplines of Physics

Keywords (6)

liquid core microparticles; core evaporation; in vitro proof of concept; in vivo validation; hybrid MRI and ultrasonography; focus ultrasound ablation

Lay Summary (French)

Lead
Les tumeurs du foie, rein et pancréas représente un enjeu de santé publique par leur fréquence et leur mauvais pronostique. Leur localisation les rendent souvent inopérables. La recherche de nouvelles approches thérapeutiques est donc fortement souhaitable, et plus spécialement les approches minimalement invasives. Notre projet cherche à apporter des réponses novatrices à cette question.
Lay summary

Contenu et objectifs du travail de recherche

Les ultrasons focalisés de haute intensité sous guidage IRM (MRgHIFU) représente une technologie de pointe destinée au traitement non-invasifs de tumeurs localisées ou de pathologies fonctionnelles. Elle a été utilisée avec succès lors d'essais thérapeutiques concernant le cancer du sein et les métastases osseuses. Cependant, l'application des MRgHIFU aux organes abdominaux (foie, rein, pancréas) se heurte simultanément aux trois problèmes : le mouvement respiratoire, le refroidissement tissulaire par l'apport de sang et les obstacles à la propagation. Nous cherchons ainsi de faciliter la thermo-ablation MRgHIFU abdominale par un apport externe de "catalyseur thermique" qui permettra d'accentuer l'effet d’échauffement au niveau de la cible sans augmenter le risque de lésion dans les structures avoisinantes. L’évaporation de micro-gouttes circulantes dans le sang devra se produire à un endroit précis, grâce au cumul de conditions physiques de pression et température contrôlés en temps réel. Ll’équipe de recherche dirigée par le Dr. Rares Vincent Salomir, affiliée aux HUG et à l’Université de Genève, dispose d’une plateforme technologique haut de gamme.  Le projet vise la mise au point sur plan physico-chimique du « catalyseur thermique », la preuve de concept ex vivo sur rein isolé perfusé, et finalement in vivo.

Contexte scientifique et social du projet de recherche

Les nouvelles thérapies guidées par imagerie dans le contexte du traitement du cancer ont pour but à la fois d’augmenter l’efficacité, réduire les effets secondaires et réduire ainsi les coûts de prise en charge de malades. Le projet relève de la recherche translationnelle. Nous souhaitons apporter la preuve pré-clinique de l’intérêt à longue terme de cette nouvelle méthode. Les résultats devraient ouvrir la voie pour l’élargissement du domaine d’applicabilité de cette méthode de traitement dont le potentiel technologique et médical est encore loin d’être valorisé pratiquement.

Direct link to Lay Summary Last update: 04.11.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Micron-sized PFOB liquid core droplets stabilized with tailored-made perfluorinated surfactants as a new class of endovascular sono-sensitizers for focused ultrasound thermotherapy
Desgranges Stéphane, Lorton Orane, Gui-Levy Laura, Guillemin Pauline, Celicanin Zarko, Hyacinthe Jean-Noel, Breguet Romain, Crowe Lindsey A., Becker Christoph D., Soulié Marine, Taulier Nicolas, Contino-Pépin Christiane, Salomir Rares (2019), Micron-sized PFOB liquid core droplets stabilized with tailored-made perfluorinated surfactants as a new class of endovascular sono-sensitizers for focused ultrasound thermotherapy, in Journal of Materials Chemistry B, 2019(7), 927-939.

Datasets

Data supporting the conclusions of peer review articles

Author SALOMIR, Rares
Publication date 09.04.2020
Persistent Identifier (PID) DOI : 10.26037/yareta:nccbros2z5dxzj4nyo4vy6xiee
Repository DOI : 10.26037/yareta:nccbros2z5dxzj4nyo4vy6xiee
Abstract
Standard Matlab matrices of MRI magnitude, phase and temperature for MR monitored sonications without and with sonosensitizers; experimental conditions: semi-rigid gel, perfused tissue mimicking gel, ex vivo excised and perfused organs.Standard DICOM files for the MRI DCE of perfused ex vivo organs.

Collaboration

Group / person Country
Types of collaboration
Radiological Physics, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Max Mousseron Institute of Biomolecules (IBMM), Avignon France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Laboratory of Biomedical Imaging, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Charitable Focused Ultrasound Foundation (EUFUS) 2019 Talk given at a conference HIFU thermal contrast enhancement in ex-­vivo pig kidneys using a new class of endovascular sono-sensitizers 17.06.2019 Barcelona, Spain Guillemin Pauline Coralie; Desgranges Stéphane; Lazeyras François; Breguet Romain; Lorton Orane; Salomir Rares;
International Society for Magnetic Resonance in Medicine (ISMRM) 2019 Poster Enhancement of the HIFU thermal effect in ex-vivo kidneys using a new class of endovascular sono-sensitizer 11.05.2019 Montreal, Canada Salomir Rares; Desgranges Stéphane; Guillemin Pauline Coralie; Breguet Romain; Lazeyras François; Lorton Orane;
The European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2017 Poster 19F MR characterization of molecular oxygen affinity of a new concept of theragnostic nano- and micro-droplets, applied to the in situ mapping of oxygen partial pressure 19.10.2017 Barcelona, Spain Hyacinthe Jean-Noël; Lorton Orane; Desgranges Stéphane; Salomir Rares; Lazeyras François;
European Charitable Focused Ultrasound Foundation (EUFUS) 2017 Talk given at a conference Enhancement of thermal contrast in HIFU treatments by perfluorocarbon microparticles 26.09.2017 Leipzig, Germany Lorton Orane; Salomir Rares; Desgranges Stéphane;


Communication with the public

Communication Title Media Place Year
Media relations: radio, television Cancer, une thérapie prometteuse RTS Western Switzerland 2017

Associated projects

Number Title Start Funding scheme
152045 Sonoactivable Nanotheragnostics for Cancer Treatment (ERANet EuroNanoMed2 SonoTherag) 01.04.2014 ERA-Euro-NanoMed
170155 Novel theranostic approaches for stroke based on hyperpolarized Magnetic Resonance Imaging 01.09.2017 Project funding (Div. I-III)

Abstract

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU, or MRgFUS) is consi-dered to be a promising treatment for localized cancer. Depending on the anatomical target, com-monly recognized challenges for the transfer of this technology towards the clinical routine are: acoustic obstacles (bones, air filled cavities, calcifications, scars), tissue motion (respiratory and cardiac) and heat sink in perfused organs (requiring sustained sonication). An increasing number of recent publications tried to address these issues, individually or simultaneously. However, based on our own long term experience with MRgHIFU in vivo studies with upper abdomen applications, it appears that a challenging complication of HIFU ablation is the far field heating of hard acoustic interfaces, for instance spinal bone structures or tissue-to-air interfaces, that represent a severe and frequent side effect. Indeed, any HIFU transducer forms an energy beam that is first concentrated at a focus then continues its post-focal propagation while losing the spatial control-lability as a consequence of diffraction. That is, the spatial profile of the acoustic intensity in the far field loses its correlation with the emission pattern at the surface of the transducer and there is little or no possibility of manipulating the HIFU source in order to directly reduce the far field energy deposition, unlike the near field situation. There is a substantial need to search for new methods to enhance the thermal contrast achievable between the focus and the far field areas. Various solutions to this problem were suggested: use of shock waves with non-linear enhance-ment of focal absorption, thermally induced boiling core of water steam, or use of ultrasound con-trast agents as adjuvants. Despite potential interest, it seems yet unlikely these methods to be applied “as is” in a realistic clinical scenario. We propose an alternative method of MRgFUS me-diated ablation in highly perfused tumours that should not have the same drawbacks as previously suggested approaches. It consists of using specially designed exogenous fluid microparticles as a source of in situ boiling core induction at/around the focal point of the HIFU beam. These mi-croparticles are perfluorocarbon droplets stabilized with fluorinated surfactants, whose vaporiza-tion at ultrasound focal area is triggered using low to moderate HIFU energy, as a joint effect of temperature and acoustic pressure. The evaporation process is expected to induce a cascade of positive-feedback (“chain reaction”, or “self-amplified”) energy deposition that will result in the use of lower energy to perform ablation and reduced HIFU side effects. Due to the fact that the blood will continuously deliver new droplets, which will be activated as they pass the “hot” initial bubble could, a self-amplifying chain reaction is estimated (cascade effect). The vaporized microparticles would cause bubble cloud acting as a strong reflector for the incident beam, hence protecting or-gans or bones located behind the focus in the far field by partly blocking the forward propagation of the wave (that is, back scattering). Bubble cloud would also enhance local absorption by non-linear attenuation. Superposition of the incident and reflected wave may help re-triggering the evaporation of new particles freshly supplied by the blood flow and ultimately self-maintaining the process until the sonication stops or the renewal of the particles stops. Our goal in this project is to achieve a proof-of-concept for cascade-amplified focal ultrasound ablation, first in tissue mi-micking gels, then in ex vivo perfused kidney, and eventually in living animal liver. The applicants and their international partners involved will take advantage of the complementary skills and available resources, covering the chemistry and physics of microparticle synthesis and characteri-zation, hybrid ultrasonography and MR imaging and thermometry for simultaneous monitoring of cascade-amplified focal ultrasound ablation treatments, and animal research facilities for in vivo proof of concept.
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