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Author: Klazina Kooiman
Time: 11H00
Language: English
Place: Conference Room at LabTAU

Abstract: Ultrasound-activated vibrating microbubbles (1-10 µm in size) have shown preclinical potential to boost drug therapy and reduce side-effects for treating cardiovascular disease and cancer because drugs are delivered locally. Recently, safety of the treatment was demonstrated in several clinical trials. Despite the advances in the field, the underlying mechanism of microbubble-mediated drug delivery are poorly understood. One of the reasons for this is the huge range in time scales involved. The time scale of the microbubble vibration is 2 million times per second in a 2 MHz ultrasound field (microseconds), which is many orders of magnitude smaller than the time scale of physiological effects (milliseconds), let alone that of biological effects (seconds to minutes) and clinical relevance (days to months). To allow the investigation of the microbubble-cell-drug interaction at a microsecond and micrometer resolution, unique technology was created by coupling an ultra-high-speed camera (~20 million frames per second recordings) to a custom-built confocal microscope. In this seminar, I will describe new insights gained into the microbubble-cell-drug interaction by using this technology for two different cell types: endothelial cells that line blood vessels and bacteria. For endothelial cells, the focus will be on the microbubble behavior in relation to the drug delivery pathways sonoporation (i.e., cell membrane poration), tunnel formation and cell-cell contact opening, as well as how the cytoskeleton F-actin plays a role. Novel microbubble-mediated treatments for the life-threatening disease bacterial infective endocarditis, either on native heart valves or cardiac devices such as pacemakers, are the focus for the bacteria biofilm work.

Abstract: The Internationnal Tissue Elasticity Conference  (ITEC) was held in Lyon from 21 to 23 October. With a total of around 100 participants, it was a great success and a pleasure to share recent advances in elastography. We look forward to seeing you in Seattle at the end of June 2025. Stefan Catheline, for the organising committee.

Mr. Thomas BISCALDI, PhD student at the Laboratory of Therapeutic Applications of Ultrasound (LabTAU, French National Institute of Health and Medical Research, University Claude Bernard of Lyon, France), recently received the International Society of Therapeutic Ultrasound's (ISTU) Nadine BARRIE SMITH Award at the 23^rd International Symposium for Therapeutic Ultrasound. ISTU's most prestigious student award was established in 2011 in honor of Dr. Nadine BARRIE SMITH's dedication to students in therapeutic ultrasound and recognizes exemplary student achievements at the ISTU Annual Symposium. This fund allows continued recognition of Dr. BARRIE SMITH's legacy as a mentor, and to encourage others to do the same.

The ISTU24 event was held in Taipei (Taiwan) from Sept. 19 to 22, 2024, at the Taipei International Convention Center (TICC) located right in the heart of Taipei City in the international Xinyi business district. Following ISTU tradition, the student award winners were selected by the ISTU Student Awards Committee after pre-selection of abstracts and presentations of their works at either the "Student Award Talks" Session or the "Student Award Posters" Session. Three awards were then given for Best Poster, Best Oral Presentation, and the Nadine BARRIE SMITH Award at the final "Student Award Announcements" session. This year, Mr. Thomas BISCALDI (LabTAU, INSERM, CLB, University Claude Bernard of Lyon, France) shared this session with Ms. Mahsa MOKHLESABADI (Sunnybrook Research Institute, Toronto, Canada) and Ms. Vanessa DREVENAKOVA (Imperial College London, UK) who respectively received the awards for Best Oral and Best Poster Presentations.

Thomas BISCALDI gave a presentation entitled "Dual-Mode US Interstitial Catheter for Robotic US-Navigation-guided Conformal HIFU therapy: in-vitro experimental validation" highlighting their recent contributions to the development of 3D image-guided robot-assisted ultrasound therapy in interventional radiology, in the context of HepatoCellular Carcinoma (HCC) ablation.

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Lauréats du Prix de Thèse 2023 en GBM

La Société Française de Génie Biologique et Médical et l'Alliance pour le Génie Biologique et Médical, avec le soutien de la Communauté Stic-Santé, ont décerné leurs prix de thèse 2023 à l'occasion des RITS 2024 à l'Université Clermont-Auvergne.

Les quatre finalistes ont présenté leurs travaux lors d'une session spéciale devant le Jury présidé par la Professeur Frédéric Patat, et le choix des membres du Jury a été le suivant :

Le prix Recherche a été décerné à Gabrielle LALOY-BORGNA, pour ses travaux au LabTau (INSERM U1032, Université Lyon1) intitulés "Micro-élastographie : caractérisation mécanique de la cellule par ondes élastiques".

Le prix Innovation a été décerné à Marion TACONNE, pour ses travaux au LTSI (INSERM U642, Université de Rennes) intitulés “Hybrid approach, combining computational and machine-learning models, for the analysis of myocardial strain and cardiac function evaluation”.

Une mention spéciale Recherche a été décernée à Ling HUANG, pour ses travaux au laboratoire Heudiasyc (CNRS UMR 7253, UTC) et à l'Université de Rouen-Normandie intitulés “Medical Image Segmentation with Belief Function Theory and Deep Learning” .

Enfin une mention spéciale Innovation a été décernée à Paul NOBRE, pour ses travaux au Laboratoire CREATIS (CNRS UMR 5220, INSERM U1294, INSA Lyon) intitulés “Sondes et capteurs de champs électromagnétiques à liaisons optiques pour la sécurité en IRM” .

Cette année, le jury était présidé par Frédéric Patat et avait pour membres Olivier Beuf (Responsable d’organisation), Su Ruan, Véronique Migonney et Daniel Racoceanu (SFGBM), Guirec Hillion (AGBM) et Emmanuel Blanc (anciennement CTO EDAP TMS).

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Prix jeunes chercheurs / jeunes chercheuses aux RITS 2024

La SFGBM a récompensé deux jeunes chercheurs lors des journées RITS 2024 qui se sont déroulées à l'Université Clermont-Auvergne.

Clément FOULLOUNOUX (LabTAU, INSERM U1032, Centre Léon Bérard, Université Claude Bernard Lyon 1) a reçu le prix Jeune Chercheur de la meilleure communication orale, intitulée "Étude du déclenchement de la cavitation dans le cristallin en vue de traiter la presbytie".

Tom AUBIER (LabTAU, INSERM U1032, Centre Léon Bérard, Université Claude Bernard Lyon 1) a reçu le prix Jeune Chercheur de la meilleure communication affichée, intitulée "In vitro investigation of the biophysical mechanisms underlying ultrasound neurostimulation".

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Author: Anam Bhatti
Time: 11H00
Language: English
Place: Conference Room at LabTAU

Abstract: 

In response to any cutaneous disease, the morphology and functionality of superficial vasculatures in skin being deteriorated. Superficial vasculatures are characterized as the tortuous and branched structures anastomosed around the diseased tissue. Therefore, visualization of these vessels plays a crucial role in diagnosis and prognosis of cutaneous disorders. Traditionally, high-frequency ultrasound has been used in dermatology for dermal morphological observation, its limited Doppler sensitivity poses challenges for micro-vessels visualization. This study addresses this limitation by employing the ultrafast acquisition techniques of ultrasound and advanced clutter filtering approaches based on singular value decomposition to map the micro-circulation in dermal superficial vasculatures effectively in 2D and 3D imaging.

A novel approach using region-based SVD clutter filtering was proposed to extract the blood flow signals in vasculatures of different dimensions, densities, and flow speed across different layers of the skin. Additionally, a 3D volumetric imaging method was introduced to visualize the superficial vasculatures from various perspectives, using continuous mechanical translation to scan the imaging area and the section-wise region-based SVD processing was proposed to extracts the blood flow signal efficiently. Post-processing algorithms such as top-hat transform morphological filter and non-local means filter were implemented to remove the noises and enhance the image quality.

The effectiveness of the proposed approaches was evaluated using custom-designed micro-flow phantoms mimicking different types of superficial micro-vessels. In-vivo experiments on healthy subject demonstrated the visualization of micro-vessels with a minimum diameter of 51 μm in the dermal layers. Acquired in-vitro and in-vivo results highlights the efficacy of the proposed 2D and 3D approaches to visualize the superficial micro-vessels for an effective diagnosis of cutaneous diseases.

Author: Jessica Gannon
Time: 11H00
Language: English
Place: Conference Room at LabTAU

Abstract: 

Ultrasound-Guided Non-Invasive Pancreas Ablation Using Histotripsy: Feasibility Studies in Porcine Models

Pancreatic cancer is an aggressive disease that is typically diagnosed late-stage leading to poor prognosis and overall survival. Even with advances in treatment, the five-year survival rate for patients is only 12.5% with only 20% of patients presenting with resectable tumors. Histotripsy is a non-invasive, non-thermal, and non-ionizing focused ultrasound ablation method that has recently been FDA approved for treating hepatic tumors and is currently being investigated for other malignancies. This study expands upon prior work by our group investigating the feasibility of non-invasive pancreas ablation using ultrasound-guided histotripsy in a healthy chronic porcine model. Additional work by our group includes the development of an immunocompromised porcine model allowing us to surgically inject and grow human Panc-01 tumors orthotopically to target with histotripsy. While results from these studies are promising, they also highlight the challenges of targeting the pancreas through an extracorporeal approach due to overlying gas-filled tissues. Therefore, we are also investigating the development of endoscopic histotripsy devices for minimally invasive tissue ablation which has led to the collaboration between our two labs.

Author: Adrien Rohfritsch
Time: 11H00
Language: French/English
Place: Conference Room at LabTAU

Abstract: 

La connaissance précise des propriétés acoustiques d’un milieu hétérogène est d’une importance majeure dans de nombreux domaines d’application, tels que l’imagerie, le contrôle non destructif, le développement de métamatériaux ou la thérapie par ultrasons focalisés. La propagation des ultrasons dans un tel milieu est régie à la fois par les propriétés de l’onde incidente, la taille des hétérogénéités du milieu, leurs propriétés acoustiques et leur distribution spatiale. La prise en compte de tous ces facteurs est un défi qui limite la plupart du temps le champ d’application d’une ´étude numérique ou d’un modèle théorique. Nous présentons un code de calcul récent, MuScat, qui permet de pallier ces problèmes. Il rend possible le calcul du champ formé par l’interaction de l’onde incidente avec un milieu peuplé de plusieurs milliers de diffuseurs cylindriques ou sphériques. Ce code fréquentiel prend en compte les effets de diffusion multiple `a tous les ordres ainsi que la taille des particules, leurs propriétés mécaniques et leurs positions. Ce dernier point permet de modéliser exactement n’importe quel type de microstructure (i.e. la distribution spatiale des diffuseurs dans l’espace). La diffusion par une particule est modélisée par la matrice de diffusion décomposée sur la base modale, et les interactions entre particules sont décrites à l’aide de la théorie de la diffusion multiple linéaire.

Une première étude d´démontre la possibilité de tirer profit des corrélations spatiales à courte portée (appelées SRC pour Short Range Correlation) et longue portée (SHU, pour Stealth Hyperuniform) afin de fabriquer des matériaux aux propriétés surprenantes et très prometteuses pour le d´développement de m´métamatériaux de nouvelle génération. Une seconde ´étude se focalise sur la détection de lésions créées par ultrasons focalisés de haute intensité (HIFU) à l’intérieur du tissu hépatique. Le passage du faisceau focalisé créé une anisotropie locale dans le réseau cellulaire, qui modifie le signal rétrodiffusé par le milieu. Nous quantifions ce phénomène grâce à des simulations numériques et le corrélons à l´évolution du facteur de structure de la zone traitée. Nous montrons pour finir de premiers résultats expérimentaux ouvrant la voie à un nouveau moyen de suivi temps réel des traitements thermiques par HIFU.

Author: Myléva DAHAN
Time: 2 PM
Language: French
Place: Conference Room at LabTAU

Résumé: 
L'utilisation des ultrasons thérapeutiques, de l'immunothérapie, et de la délivrance de médicaments via des nanoparticules représente une avancée significative dans le domaine de la recherche en oncologie. Chacune de ces modalités thérapeutiques offre des avantages distincts pour le traitement du cancer, mais leur combinaison promet une approche révolutionnaire pour lutter contre cette maladie dévastatrice. En combinant plusieurs modalités, nous visons à créer une réponse thérapeutique améliorée et synergique pour lutter contre le cancer. Cette approche polyvalente tire parti des avantages spécifiques de chaque méthode pour obtenir des résultats plus efficaces. La conception et la caractérisation de l’appareil ultrasonore confocal multimodal dédié aux applications pré-cliniques a fait l’objet d’un premier travail. Cette plateforme offre une polyvalence pour différentes modalités de traitement préclinique, une robustesse et une stabilité permettant la personnalisation et la facilité de comparaison de différentes approches thérapeutiques ultrasonores,

telles que la cavitation inertielle, l’histotripsie et l’ablation thermique.

Ensuite, dans une seconde partie, des nanoparticules à base de liposome et complexées à un agent immunostimulant ont été développées afin de booster le système immunitaire. Ces nanoparticules, capables de complexer l'agoniste TLR3 PolyIC, se sont révélées non cytotoxiques et stables, préservant l'activité du PolyIC et peuvent activer efficacement les cellules dendritiques, offrant des opportunités de combinaisons thérapeutiques.

Enfin, dans une dernière partie, trois combinaisons distinctes ont été examinées sur des modèles pré-cliniques : (1) l'utilisation d'ultrasons mécaniques en conjonction avec des nanoparticules, (2) l'application d'ultrasons thermiques combinée à un inhibiteur de point de contrôle, à savoir l'anti-PD1, et (3) l'association d'ultrasons mécaniques, d'un inhibiteur de point de contrôle (anti-PD1) et d'une hormonothérapie à base de Tamoxifène, chacune présentant ses avantages et inconvénients. Des pistes d'amélioration sont également proposées pour ces approches combinées.

Title: « Therapeutic ultrasound for oncology applications : Optimization of thermal and mechanical therapies with a confocal system for combined treatments, and development of nanoparticles for immune activation »

Abstract:
The use of therapeutic ultrasound, immunotherapy, and drug delivery via nanoparticles represents a significant advancement in the field of oncology research. Each of these therapeutic modalities offers distinct advantages for cancer treatment, but their combination promises a revolutionary approach to combat this devastating disease. By combining different modalities, our goal is to create an enhanced and synergistic therapeutic response to fight cancer. This versatile approach leverages the specific benefits of each method to achieve more effective results. The design and characterization of a multimodal confocal ultrasound device dedicated to preclinical applications were the focus of the initial work. This platform provides versatility for various preclinical treatment modalities, robustness, and stability, allowing for customization and easy comparison of different ultrasound therapeutic approaches, including inertial cavitation, histotripsy and thermal ablation.

In the second part, nanoparticles based on liposomes and complexed with an immunostimulant agent were developed to boost the immune system. These nanoparticles, capable of complexing the TLR3 agonist PolyIC, have proven to be non- cytotoxic and stable, preserving the activity of PolyIC. They can effectively activate dendritic cells, providing opportunities for therapeutic combinations.

Finally, in the last part, three distinct combinations were examined in preclinical models: (1) the use of mechanical ultrasound in conjunction with nanoparticles, (2) the application of thermal ultrasound combined with a checkpoint inhibitor, namely anti- PD1, and (3) the combination of mechanical ultrasound, a checkpoint inhibitor (anti- PD1), and Tamoxifen-based hormonal therapy, each presenting its own advantages and disadvantages. Suggestions for improvement are also proposed for these combined approaches.

Jeudi 12 octobre le LabTAU a eu l'honneur d’accueillir M. Didier Samuel (Président Directeur Général de l’Inserm) accompagné de M. Frédéric Fleury (Président de l’Université Lyon 1) pour une présentation des différentes activités du Laboratoire.
Ce fut l’occasion d’une démonstration par nos chercheurs de l’utilisation des ultrasons à la thérapie.

Place: Lyon (Palais de la Bourse) - Satellite of ISTU/EUFUS 2023

It is with great enthusiasm that we announce the arrival of the 2nd edition of HIFUture which will be held following the ISTU/EUFUS 2023 international symposium, at the Palais de la Bourse in Lyon, on Friday April 21, 2023.

LabTAU and the Hospices Civils de Lyon invite you to this day dedicated to meetings between clinicians, engineers and industrials involved in ultrasound treatments in France and abroad.

The symposium program will include presentations by clinical and academic leaders on : i) a prospective of therapeutic ultrasound with a special focus on the future of HIFU in Interventional Radiology; ii) the physics of ultrasound and the key clinical applications of this technology; iii) the latest clinical innovations and those to come in various medical specialties.

The event will take place in person and can also be followed remotely (virtual part). After the success of the 2021 edition, we are expecting you on April 21, 2023 for this 2nd edition.

To participate to HIFUture 2023 : HIFUture2023

Organizers : Gil Dubernard & Cyril Lafon. Secretaries : Charles-André Philip & W. Apoutou N’Djin

Author: Christina Tsarsitalidou
Time: 11H00
Language: French/English
Place: Conference Room at LabTAU

Abstract: Seismic imaging constitutes a fundamental building block of Earth Science research as the obtained
images or snapshots of our planet’s interior challenge our understanding of plate tectonics, yield
information on fault zone environments and inform many near-surface engineering applications. In
this work, we explore the imaging potential of refocusing surface waves reconstructed from noise
correlation functions so as to estimate the seismic velocity. At zero lag-time, converging surface
wave fields create a large amplitude feature at the origin referred to as focal spot. Its properties are
governed by local medium properties and have long been used in medical imaging approaches such
as passive elastography. We treat dense seismic arrays equivalent to medical ultrasound transducers
that allow the reconstruction of focal spots at near-field distances. We focus on demonstrating the
general applicability of the method using the USArray dataset, but we also investigate the biasing
effects of ambient wave field properties on our estimates, like impinging body wave energy and
non-isotropic energy flux.

Author: Dr Laura CURIEL - Assistant Professor - Department of Electrical and Software Engineering University of Calgary
Time: 11H00
Language: French
Place: Conference Room at LabTAU

Abstract: Le pilotage multiaxial est une nouvelle méthode d’excitation des matériaux piézoélectriques qui utilise une combination des modes de vibration extensionnel et latéral pour moduler le faisceau ultrasonore produit. Il a été démontré que cette méthode peut produire différents effets : une modulation de l’efficacité électroacoustique, une déflection de l’axe d’émission sans avoir à utiliser multiples éléments piézoélectriques, et un control et réduction de la taille focale, en particulier quand un réseau d’éléments multiaxial est utilisé. Dans ce séminaire on discutera les principes du pilotage multiaxial des transducteurs, ses avantages et les applications initiales explorées par notre groupe de recherche. Ensuite, une introduction sur les applications émergentes de la méthode en ce qui concerne des dispositives animaux, ou la réduction de la taille focale présente des avantages, seront décrites.

Author: Tristan Jaouen 
Time: 14H00
Language: French
Place: LabTAU Conference Room / Visio Microsoft Teams
Link: https://teams.microsoft.com/l/meetup-join/19%3ameeting_YTcwOTlhMTEtOWU1OS00YjVkLTg1MzktZjRmZmE5MWRlYzAy%40thread.v2/0?context=%7b%22Tid%22%3a%2299dde8fb-92f6-414d-bc5e-44ffa3e2419c%22%2c%22Oid%22%3a%2206fbf2f7-63eb-4935-8487-1fe7674caef4%22%7d

Abstract: 

We developed a region of interest-based (ROIs) computer-aided diagnosis system (CAD) to characterize International Society of Urological Pathology grade (ISUP) ≥2 prostate cancers at multiparametric MRI (mp-MRI). Image parameters from two multi-vendor datasets of 265 pre-prostatectomy and 112 pre-biopsy MRIs were combined using logistic regression. The best models used the ADC 2nd percentile (ADC2) and normalized wash-in rate (WI) in the peripheral zone (PZ) and the ADC 25th percentile (ADC25) in the transition zone (TZ). They were combined in the CAD system.

The CAD was retrospectively assessed on two multi-vendor datasets containing respectively 158 and 105 pre-biopsy MRIs from our institution (internal test dataset) and another institution (external test dataset). Two radiologists independently outlined lesions targeted at biopsy. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score prospectively assigned at biopsy and the CAD score were compared to biopsy findings. At patient level, the areas under the Receiver Operating Characteristic curve (AUC) of the PI-RADSv2 score were 82% (95% CI: 74-87) and 85% (95% CI: 79-91) in the internal and external test datasets respectively. For both radiologists, the CAD score had similar AUC results in the internal (82%, 95% CI: 76-89, p=1; 84%, 95% CI: 78-91, p=1) and external (82%, 95% CI: 76-89, p=0.82; 86%, 95% CI: 79-93, p=1) test datasets. Combining PI-RADSv2 and CAD findings could have avoided 41-52% of biopsies while missing 6-10% of ISUP≥2 cancers.

The CAD system confirmed its robustness showing good discrimination of ISUP ≥2 cancers in a multicentric study involving 22 different scanners with highly heterogeneous image protocols. In per patient analysis, the CAD and the PI-RADSv2 had similar AUC values (76%, 95% CI: 70-82 vs 79%, 95% CI: 73-86; p=0.34) and sensitivities (86%, 95% CI: 76-96 vs 89%, 95% CI: 79-98 for PI-RADSv2 ≥4). The specificity of the CAD (62%, 95% CI: 53-70 vs 49%, 95% CI: 39-59 for PI-RADSv2 ≥4) could be used to complement the PI-RADSv2 score and potentially avoid 50% of biopsies, while missing 13% of ISUP ≥2 cancers. These findings were very similar to those reported in the single center test cohorts. Given its robustness, the CAD could then be exploited in more specific applications.

The CAD first provided good discrimination of ISUP ≥2 cancers in patients under Active Surveillance. Its AUC (80%, 95% CI: 74-86) was similar to that of the PI-RADS score prospectively assigned by specialized uro-radiologists at the time of biopsy (81%, 95% CI: 74-87; p=0.96). After dichotomization, the CAD was more specific than the PI-RADS ≥3 (p<0.001) and the PI-RADS ≥4 scores (p<0.001). It could offer a solution to select patients who could safely avoid confirmatory or follow-up biopsy during Active Surveillance (25%), while missing 5% of ISUP≥2 cancers.

Finally, the CAD was tested with the pre-prostatectomy mp-MRIs of 56 Japanese patients, from a population which is geographically distant from its training population and which is of interest because of its low prostate cancer incidence and mortality. The CAD obtained an AUC similar to the PI-RADSv2 score assigned by an experience radiologist in the PZ (80%, 95% CI: 71-90 vs 80%, 95% CI: 71-89; p=0.886) and in the TZ (79%, 95% CI: 66-90 vs 93%, 95%CI: 82-96; p=0.051).

These promising and robust results across heterogeneous datasets suggest that the CAD could be used in clinical routine as a second opinion reader to help select the patients who could safely avoid biopsy. This CAD may assist less experience readers in the characterization of prostate lesions.

Author: Tristan Deruelle
Time: 13h30
Language: English
Place: Conference Room at LabTAU and video (need registration by clicking the button above)

Abstract: 
Prostate cancer is the second most prevalent cancer in men worldwide. It is suspected when the PSA density is high or/and the superficial prostate feels hard during digital rectal examination. Multiparametric MRI is now recommended prior biopsy when detecting for cancer. However, image interpretation is challenging, even for specialists, and brings many false-positive. Elastography is a technique to assess tissue stiffness by inducing small vibrations. It could provide a 3D map of the stiffness of the prostate. We believe that MR elastography could complement the current multiparametric MRI. Given prostate location and consitution, wave propagation is difficult though. The current work presents the design of a non-invasive wave generation device for the prostate. Then, a new field separation algorithm is presented. This algorithm provides a better estimation of the stiffness, and the correction of artefact generated by common vibrators. Finally, this algorithm can have applications in porous media. Indeed, in poro-elastic materials, a slow compression wave propagates. We observe such a wave in an agar gel, in a foam phantom, and in vivo in human kidney graft. In addition to the classic shear wave velocity estimation, it is now possible to estimate the compression wave velocity. This is an additional piece of information that the operator can use in its diagnostic. In the future, more porous parameters could be derived.

Author: Jérôme Sallet & Clément Hebert
Time: 11H00
Language: French/English
Place: Conference Room at LabTAU

Abstract: Part 1:  The development of wireless and battery free sensors for biomedical applications is a fast growing research and industrial field. It promises to greatly improve the patient’s comfort during the diagnosis but also in the treatment of chronic diseases. While the standard technologies have been based for the last decade on electromagnetic waves, ultrasonic powering and communication is a very interesting way to reduce the size of the sensor in order to develop minimally invasive implantable technology. In this context, the Wireless Neural Interface team of the Grenoble Institute for Neuroscience is developing a new type of ultrasound-based sensor for biosensing and neural recording. The presentation will show the mm-sized prototype that was used to establish the transfer curve that links the amplitude of the Echo signal to an electric potential in a physiological solution. This curve represents the first step toward real time recording.

Part 2: Abstract: Transcranial ultrasonic stimulation (TUS) is an emerging method whereby low-intensity ultrasound is delivered through the skull to brain tissue resulting in reversible disruption of neuronal activity at the targeted site. Although the exact mechanisms by which ultrasound effects neuromodulation are not fully characterized, the goal of this presentation is to show that the technique is safe and can be used to modulate brain activity and behaviour with a good anatomical precision. TUS neuromodulatory effects were measured by examining relationships between activity in each targeted area and the rest of the brain using resting-state functional magnetic resonance imaging (fMRI) collected under anaesthesia. Importantly those targeted regions could either be superficial cortical areas (e.g. medial premotor, frontopolar cortex), or deep subcortical structures (e.g. Amygdala, Hippocampus, Basal Forebrain). With the specific protocol used, dissociable and focal effects on neural activity could not be explained by auditory confounds. Furthermore, offline effects were shown to last for more than two hours post-stimulation. With such long lasting effect, we were able to test in separate experiments for the specific contribution of perigenual cingulate cortex to counterfactual reasoning, of the lateral orbitofrontal cortex to credit assignment and of the mid-superior temporal sulcus to computing social prediction in primates.

Author: Jade Robert
Time: 14h00
Language: French
Place: Conference Room at LabTAU

Abstract: 

            Les arythmies cardiaques sont, aujourd’hui encore, un enjeu de santé publique majeur. Certains types d’arythmies affectent plusieurs dizaines de millions de personnes dans le monde, tandis que d’autres sont la cause principale de mort subite cardiaque. Dans les cas les plus sévères, il est impératif de recourir à un traitement, afin de préserver l’intégrité du patient. Or, les méthodes interventionnelles, de guidage et de suivi de ce traitement, sont limitées, menant ainsi à un taux de récurrence parfois élevé, en fonction du type d’arythmie. Cette thèse s’intéresse alors au développement de modalités d’imagerie ultrarapide ultrasonore, pouvant pallier ces limitations. Ces modalités sont l’imagerie de l’onde électromécanique et l’élastographie passive, et pourraient offrir des informations pertinentes, jusqu’alors indisponible en clinique.

            Dans un premier temps, des études ex-vivo, sur cœurs isolés travaillants, ont été conduites afin d’évaluer le potentiel de l’imagerie de l’onde électromécanique. Une étude en aveugle a permis de démontrer qu’il était possible de détecter avec précision le type de stimulation et la source de contraction dans 79% des cas. Puis, deux études in-vivo, sur modèle porcin ont permis d’étudier la faisabilité de l’imagerie de l’onde électromécanique sur deux types de sondes, plus adaptées à un contexte interventionnel. Des ondes pouvant être associées à la contraction cardiaque ont été visualisées dans les deux études. Néanmoins, la visualisation dynamique de l’onde de contraction a été plus complexe dans un contexte in-vivo, puisqu’elle nécessite une interprétation, nécessairement subjective, d’un lecteur expérimenté.

            Pour répondre à cette limitation, une nouvelle méthode d’analyse temps-fréquence des données ultrasonores a été mise en place afin d’aboutir à une représentation plus objective de la contraction cardiaque, et ne nécessitant pas d’utilisateur expérimenté. La méthode a été validée, qualitativement et quantitativement, sur données ex-vivo, vis-à-vis de la méthode de référence utilisée en imagerie de l’onde électromécanique dans la littérature. En appliquant la méthode aux données des études in-vivo, il a pu être démontré que les schémas de contraction décrits sont similaires entre deux stimulations consécutives, et que la source de contraction est correctement positionnée lorsque la sonde de stimulation est située dans le plan. Notamment, la zone de contraction observée était cohérente avec la zone de stimulation dans le plan d’imagerie dans 81% des cas, lors des acquisitions réalisées à l’aide d’une sonde intracardiaque.

            Des études ex-vivo, sur échantillons cardiaques, ont été mises en place afin d’évaluer la faisabilité de détection des lésions simples et des schémas de lésions thermiques par élastographie passive. Il a été démontré sur un grand nombre d’échantillons (41 sur n = 51, 80% sur deux études) qu’une augmentation locale de la rigidité des zones lésées (d’un facteur 1.6 à 2.5 en moyenne), était visible par élastographie. Les répartitions des lésions détectées sont cohérentes et les dimensions correctement estimées (manuellement, 1.1 à 2.8 mm d’erreur absolue, en moyenne), bien que les surfaces de lésions obtenues par élastographie passive soient encore approximatives. Finalement, une étude in-vivo sur modèle porcin a permis de démontrer la faisabilité de détecter des lésions thermiques individuelles ou en ligne par élastographie passive.

Author: Gabriel Regnault
Time: 14H00
Language: French
Place: École Centrale de Lyon, Amphi 201, Bâtiment W1

Abstract: 

Acoustic bubbles are known to allow a contactless and localized action on a surrounding body, as for example in ultrasound therapies or for engineering applications. These bubbles are often encountered as more or less dense groups, called bubble clouds. The behavior of such clouds are driven by acoustic and fluid interactions. The work presented in this dissertation aims at studying the streaming flow induced by such oscillating bubbles as well as the interactions undergone by a bubble couple. 

Under specific conditions on the size of the bubbles and the acoustic pressure amplitude they are submitted to, a bubble interface can demonstrate shape oscillations. Such deformations give rise to a slow mean flow around the bubble: the so-called microstreaming. A recent theoretical approach is used to understand the diversity of microstreaming patterns that are observed experimentally around bubbles trapped in a resonant water tank. It is shown that the cross-like patterns (large scale action) are linked to self interaction of the main triggered mode and that lobe-like patterns (local action) are associated to the cross-interaction between the breathing mode and the parametrically excited one.

The study of a large variety of bubble couples is achieved through the use of a bi-frequency acoustic levitation chamber. Bubbles are maintained at controlled distances in an infinite fluid. Such a technique allows the quantification of the secondary radiation force acting on each bubble, their spherical or nonspherical oscillations, the acoustic coupling at the ultrasonic time scale and the fluid flow they generate. It is shown that the triggering of nonspherical oscillations induce an additional hydrodynamic force which modifies the bubble pair equilibrium. The inversion of the secondary radiation force is evidenced when the bubbles sufficiently attract and migrate to a specific equilibrium location in the trapping field. At this location, the presence of shape modes has been shown to be responsible for bouncing between the bubbles. The acoustic coupling is also studied. Two regimes are evidenced: either the bubbles are both smaller than the resonance size for the chosen excitation frequency and hence the coupling is constructive or they are greater than this resonance size and hence the coupling is destructive. While nonspherical oscillations do not seem to have a huge impact on this coupling, they are at the origin of a large scale hydrodynamic interaction. In this case, the shear stress induced in the bulk is quantified, and appears greater than the threshold required to induce biological effects on cell membranes.

Author: Jonathan Mamou and Cameron Hoerig
Time: 11H00
Language: English
Place: Conference Room at LabTAU

Abstract: High-frequency ultrasound provides a means of investigating the anatomical changes in soft tissues at the microscale that accompany many disease processes. Of particular interest to our group are the effects of myopia on the posterior sclera, where microstructure changes occur that underly eye elongation and staphyloma formation.  We will first describe how quantitative ultrasound (QUS) methods applied at high frequencies (80MHz) can detect changes in tissue structure on the scale of 30micro caused by myopia. Then, from complementary studies, we will demonstrate how quantitative acoustic microscopy (QAM) methods (>250MHz) can be used to infer the mechanical properties of ocular tissues at <7micro resolution and how those properties relate to collagen microstructure. Following these in-depth discussions – and if time allows – we will present a lightning round of QUS applications in lymph nodes, thyroid, lung, and liver tissues

All the videos of HIFUture presentations are available on our new youtube channel dedicated to HIFUture symposiums

Author: Apoutou N'Djin
Time: 14H00
Language: French
Place: Conference Room at LabTAU (registration required for non-LabTAU members to participate in visio with the button above)

Résumé (Abstract)

Les ultrasons (US) thérapeutiques sont en constante évolution. Pour améliorer les soins aux patients, des thérapies personnalisées - focales ou conformationnelles - doivent permettre de mieux cibler les sites pathologiques. Ces stratégies restent complexes à implémenter, car elles nécessitent un contrôle avancé : de l’émission US ; des interactions biophysiques « US/tissus ». Pour guider ces procédures, la bimodalité US (imagerie/thérapie) et l’imagerie multimodale(ex : US, IRM, modélisation, fusion) sont prometteuses. Nos recherches transversales ont été réparties selon 3 thèmes : 1)nouvelles stratégies de ciblage ; 2) technologie MEMs émergente ; 3) ouverture aux neurosciences.
Thème 1 – En chirurgie ouverte, nous avons proposé une focalisation ultrasonore - torique - pour la thérapie focale des métastases hépatiques par ultrasons focalisés de haute intensité guidés sous imagerie US. Les ablations tissulaires obtenues en préclinique étaient volumineuses, peu affectées par la vascularisation et les mouvements physiologiques (épilogue : Phases I-IIa cliniques). En radiologie interventionnelle, l'étude d’expositions ultrasonores collimatées - mono- puis bi-fréquentielles - permettait la génération d’ablations conformationnelles sous IRM (préclinique ; Phase 0 clinique), pour la thérapie transurétrale du cancer localisé de la prostate (épilogue : études multicentriques). Nous travaillons aujourd’hui sur des méthodes de visualisation temps-réel et de guidage multimodale (navigation, fusion), qui pourraient offrir de nouvelles perspectives de ciblage, mais également nécessiter une transition technologique.
Thème 2 – Pour envisager de nouvelles approches thérapeutiques avec une technologie MEMs émergente de - Transducteur Ultrasonore Capacitif Micro-usiné (CMUT) -, nous étudions la mécanotransduction (à l’échelle cellulaire) et les performances acoustiques de différents designs de réseaux d’éléments CMUTs. Outre les avantages connus (miniaturisation, multifréquence), la capacité de cette technologie à émettre des ultrasons de puissance a été démontrée. Des investigations sont en cours, avec le développement de nouvelles générations de prototypes hautement intégrés. Les thérapies ultrasonores de basse énergie pourraient aussi bénéficier de ces innovations, mais nécessitent parfois d’abord une ouverture à d’autres disciplines.
Thème 3 – Pour comprendre les mécanismes de neurostimulation par ultrasons de basse énergie, nous avons dû intégrer des techniques électrophysiologiques avancées issues des neurosciences. Dès lors, une approche comparative multi-modèle multi-échelle suggérait un rôle prépondérant de la force de radiation, dans le déclenchement des réponses neuronales. La maitrise de ces phénomènes pourrait déboucher sur de nouvelles formes de thérapies - fonctionnelles -.

Les technologies ultrasonores émergentes et les méthodes issues des computer-/neuro- sciences continueront à inspirer nos recherches, pour maitriser certains mécanismes biophysiques et proposer des approches médicales personnalisées innovantes.

Therapeutic ultrasound (US) is constantly evolving. To improve patient care, personalized therapies - focal or conformal - must allow better targeting of pathological sites. These strategies remain complex to implement, as they require advanced control: of the US emission; of “US/tissue” biophysical interactions. To guide these procedures, US bimodality(imaging / therapy) and multimodal imaging (e.g. US, MRI, modeling, fusion) are promising. Our transversal research was divided into 3 themes: 1) new targeting strategies; 2) emerging MEMs technology; 3) openness to neurosciences.
Theme 1 - In open surgery, we have proposed a - toroidal - ultrasound focusing for the focal therapy of liver metastases by high intensity focused ultrasound guided under US imaging. Tissue ablations obtained preclinically were voluminous, little affected by vascularization and physiological movements (epilogue: clinical Phases I-IIa). In interventional radiology, the study of - single then dual-frequency - collimated ultrasound exposures allowed the generation of conformal ablations under MR guidance (preclinical; clinical Phase 0), for the transurethral therapy of localized prostate cancer (epilogue: multicenter studies). We are currently working on real-time visualization and multimodal guidance methods (navigation, fusion), which could offer new targeting perspectives, but also require a technological transition.
Theme 2 - To consider new therapeutic approaches with an emerging MEMs technology of - Micro-machined Capacitive Ultrasonic Transducer (CMUT) -, we are studying the mechanotransduction (at the cellular level) and the acoustic performances of different designs of CMUT element arrays. In addition to the known advantages (miniaturization, multi-frequency), the capacity of this technology to emit high-power ultrasound has been demonstrated. Investigations are underway, with the development of new generations of highly integrated prototypes. Low-energy ultrasound therapies could also benefit from these innovations, but sometimes require opening up to other disciplines first.
Theme 3 - To understand the mechanisms of low-energy ultrasound neurostimulation, we had to integrate advanced electrophysiological techniques from neurosciences. Therefore, a multi-model multi-scale comparative approach suggested a preponderant role of the radiation force in triggering neuronal responses. The mastery of these phenomena could lead to new forms of - functional - therapies.

Emerging ultrasound technologies and methods from computer-/neuro- sciences will continue to inspire our research, to master certain biophysical mechanisms and to propose innovative personalized medical approaches.

Résumé en image (Graphical abstract)
 

Author: samuel Pichardo
Time: 14H00
Language: French/English
Place: Conference Room at LabTAU

Abstract: 

Dans cet exposé, nous présenterons les bases et les applications de la méthode multiaxiale dans les matériaux piézocéramiques dans la formation et la détection des ultrasons. La méthode multiaxiale consiste principalement à placer des paires d'électrodes dans une piece de matériau piézocéramique où les paires d'électrodes sont orthogonales entre elles. Pour la génération d'ultrasons, nous avons découvert qu'un champ électrique de rotation généré par un signal déphasé (mais à la même fréquence) peut contrôler la direction des ultrasons générés par la piece piézocéramique. Cette approche permettra de concevoir des sondes multi-élément où les éléments de la sonde peuvent être placés avec une distance inter-élément plus grande que les sondes traditionnelles. En mode réception, nous avons découvert que les signaux collectés par les paires d'électrodes orthogonales peuvent être combinés pour améliorer la qualité d'imagerie d’une sonde multi-élément. La méthode multiaxiale offrira des opportunités très importantes pour développer une nouvelle génération d'applicateurs et de détecteurs à ultrasons.

Video available on our youtube channel: https://youtu.be/hFuawmbiUSg

Author: adrien Rohfritsch
Time: 11H00
Language: French
Place: Conference Room at LabTAU

Abstract: 

Nous nous intéressons à la propagation d'une onde incidente à l'intérieur d'un milieu hétérogène a diffuseurs élastiques discrets. Le champ moyen, appelé onde cohérente, est caractérise par un nombre d'onde effectif complexe, qui est le cœur de notre étude. L'influence des propriétés statistiques du désordre sur ce nombre d'onde est étudiée précisément. Pour ce faire, un code numérique à hautes performances, développé au cours de ma thèse, est utilisé [1]. Cet outil permet de traiter des problèmes de plusieurs milliers de particules et prend en compte les positions réelles des diffuseurs ainsi que toutes les interactions. Ces résultats numériques sont comparés a des modèles statistiques issus de la littérature ainsi qu'à des résultats expérimentaux. Deux types de corrélation, a courte [2] et longue [3] portées, sont étudiés successivement. Ce dernier type de corrélation nous amène a considérer de nouveaux matériaux, appelés hyper uniformes [4, 5]. Des modifications très significatives des propriétés effectives sont observées qui dépendent du régime fréquentiel. Ces modifications sont en accord avec certaines théories d'homogénéisation prenant en compte la microstructure. Le travail présente ouvre la voie a la compréhension fine et a l'optimisation de matériaux fonctionnels de nouvelle génération.

[1] A. Rohfritsch, J.-M. Conoir, R. Marchiano et T. Valier-Brasier, Numerical simulation of two-dimensional multiple scattering of sound by a large number of circular cylinders, The Journal of the Acoustical Society of America, 145(6), 3320{3329, 2019.

[2] A. Rohfritsch, J.-M. Conoir, T. Valier-Brasier et R. Marchiano, Inuence of the microstructure of two dimensional random heterogeneous media on propagation of acoustic coherent waves, Phys. Rev. E, 101, 023001, 2020.

[3] A. Rohfritsch, J.-M. Conoir, T. Valier-Brasier et R. Marchiano, Impact of particle size and multiple scattering on the propagation of waves in stealthy-hyperuniform media, Phys. Rev. E, 102, 053001, 2020.

[4] O. U. Uche, F. H. Stillinger et S. Torquato, Constraints on collective density variables: Two dimensions, Phys. Rev. E, 70, 046122, 2004.

[5] Y. Jiao, T. Lau, H. Hatzikirou, M. Meyer-Hermann, J. C. Corbo et S. Torquato, Avian photoreceptor patterns represent a disordered hyperuniform solution to a multiscale packing problem, Phys. Rev. E, 89, 022721, 2014.

Author: Cécile Fant
Time: 14H00
Language: French
Place: Visioconference (need to send a request to participate at the visio with the button below the abstact)

Abstract: 
Cancer is recognized as one of today's major international health issues. Among recent advances, the rise of immunotherapies has profoundly changed the therapeutic approach. However, a sometimes partial response to treatment, the rate of recurrence or the high toxicity of certain anti-cancer agents such as radiotherapy or chemotherapy are all elements limiting the complete cure of patients. Surpassing these toxicities or improving their effectiveness are therefore crucial clinical needs. Therapeutic focused ultrasound is currently used through its thermal ablation effect to treat different types of cancer. However, its wide range of possible biological effects at the organism, tissue, cellular or molecular level, as well as its low side effects, make it a preferred modality for combination with other anti-cancer treatments to overcome their limitations. In particular, the potentiation of chemotherapy agents by focused ultrasound is an active research topic. In recent years, the study of the combination of focused ultrasound with immunotherapies has also been in full boom. In this thesis, we have studied the effect of cavitational focused ultrasound in combination with a chemotherapy agent, doxorubicin, or immunotherapies, anti-PD-1 anti-CTLA-4. A synergistic in vitro effect of the combination of ultrasound and doxorubicin was demonstrated in a mouse breast tumor model. After investigation of the underlying mechanisms, we demonstrated an additive effect of this combination on the induction of DNA double-strand breaks. This induction of DNA damage seems to occur through the release of calcium into the extracellular medium. We also studied the impact of a combination of cavitational ultrasound and immunotherapy in different in vivo mouse tumor models with partial sensitivities to different immunotherapies. After demonstrating a synergy of the combination on the control of tumor growth and the increase of overall survival in these preclinical models, an exploration of the underlying immune mechanisms was performed, highlighting the involvement of the adaptive immune system via CD8+ T lymphocytes and the increased activation of dendritic cells within the tumor environment.

Author: Marine Sanchez
Time: 15H00
Language: French
Place: Visioconference (need to subscribe with the button below the summary)

Summary: 
High Intensity Focused Ultrasound (HIFU) is a technique commonly used in the medical field for the treatment of solid tumors. This therapeutic strategy allows for the localized destruction of biological tissue by temperature elevation. This manuscript describes the design and utilization of a therapeutic system and a novel, patented focalization technique for non-invasive treatment of mammary adenocarcinomas. In a first instance, an existing device that has been previously used for intraoperative treatment of hepatic metastases, and one that is currently undergoing clinical trials, was used. An ex vivo study on human mammary samples demonstrated the possibility of applying pressures on deep tissue layers in a non-invasive manner. Based on this study, the development of a new focalization modality was developed to provide larger treated volumes while yielding treatment times under a minute and eliminating the need for mechanical steering of the device. This new modality provided treated volumes 30% larger than those produced by the existing device with no changes to treatment time. Given the limitations of the existing device, in addition to the need of integrating the new focalization strategy, a new device was designed and specifically fabricated to meet the demands for treating mammary adenocarcinomas. The natural focalization of this novel transducer allows for depositing pressure deep in tissue. When the new focalization modality is used, a larger pressure field produces increased treated volumes. The performance provided by the novel probe was first characterized through modeling studies. These results were then validated through preliminary in vitro studies on hepatic tissues as well as in ex vivo studies on human mammary tissue samples. This work represents the first stage of development of a HIFU treatment for mammary adenocarcinomas using a novel, non-invasive and image-guided HIFU device that can be used manually.

Author: Charles-André PHILIP- Praticien Hospitalier
Service de Gynécologie-Obstetrique
CHU Lyon Croix-Rousse, 69004 LYON
Location: Conference Room - LAbTAU INSERM 1032- 151 Crs Albert Thomas 69003 Lyon;
Summary: 

OBJECTIVES: In this thesis, we describe a new technique for the management of rectosigmoid endometriosis by transrectal ultrasound-guided high intensity focused ultrasound ultrasound (TR-USgHIFU). We also review several limiting factors of this technique before assessing several modifications to improve the feasibility and the efficacy of the procedure.

METHODS: We first conducted a phase I clinical trial to test the feasibility of TR-USgHIFU treatment using the FocalOne® device. We then carried out a study on anatomical specimens to assess the limiting factors of the FocaleOne® probe and to test another HIFU probe, which has smaller transducer and which is mounted on a flexible endoscope. We also performed an observational clinical study to measure the acoustic attenuation of rectosigmoid endometriosis lesions and that of normal bowel. Finally, we have developed a murine model of subcutaneous endometriosis to assess the pathophysiological effects of HIFU on endometriosis.

RESULTS: We included 23 patients in the phase I clinical trial between June 2015 and October 2019. Treatment was carried out in 20 of these patients (87% feasibility). No serious adverse events have been reported. We did not find a significant morphological effect at 6 months, but we report a significant improvement on digestive and gynecological symptoms as well as on patients’ quality of life. Studies on anatomical specimens and on MRI pictures demonstrated the role of the sacrum and the recto-sigmoid hinge in the mechanical limitations of the FocalOne® probe. The use of a smaller probe with a shorter focal could be interesting in order to increase the feasibility of the treatment. Our study on 13 patients treated surgically for rectum or sigmoid endometriosis nodule, showed that attenuation of digestive endometriosis at 3 MHz is 50.2 Np / m. This value was significantly higher than attenuation of the normal bowel (32.8; p <0.001). We finally showed that the heterologous subcutaneous murine model "BALB / c-nude # Ishikawa" was reliable and efficient to study the effects of HIFU on digestive endometriosis, as the acoustic attenuation of its nodules are remarkably close to that of endometriosis lesions. Thanks to this model, we reported that HIFU lesions are associated with a higher rate of ischemic and coagulation necrosis.

CONCLUSIONS: Treatment with TR-USgHIFU in rectosigmoid endometriosis is feasible and safe. Its morphological efficacy remains to be demonstrated, but its significant clinical efficacy is promising. It could become be a minimally invasive alternative to replace surgical treatment in this indication, especially for rectal lesions.

Charles-André PHILIP was born in Lyon, France, in 1986. He obtained is MD degree from University Claude Bernard (Lyon, France), in 2014 and is specialized in Obstetrics and Gynecology. He obtained his Master of Science in Oncology from Lyon 1 University (Lyon, France) during his fellowship in the Lady Davis Institute for Medical Research at McGill University (Montreal, Canada) in 2015. 
His main clinical and research fields are endometriosis and oncology. He completed a 2 years fellowship in Gynecology-Obstetric in Croix-Rousse University Hospital (HCL, Lyon, France) and contributed with Pr. Gil Dubernard to the description and evaluation of 3D-Rectosonography, a new procedure combining tridimensional sonography and intra-rectal contrast for the diagnosis of rectal endometriosis

Author: Francesco Prada
Time: 11:00
Place: Salle de conférence 151 Cours Albert Thomas, 69003 Lyon

Summary: 

Dr. Prada earned his degrees and residency at the “Università degli Studi” of Milan, Italy, perfectioning his training in major centers worldwide.

He is currently neurosurgeon in the Department of Neurosurgery at the Fondazione IRCCS Istituto Neurologico C.Besta in Milan, Italy, where he shared his interests between clinical practice, mainly focusing in skull base/pituitary surgery and neuro-oncology, and research, studying intra-operative applications of ultrasound for the treatment of cerebral and spinal tumor and vascular lesions and advanced ultrasound techniques such as Fusion Imaging for Virtual Navigation, contrast enhanced ultrasound (CEUS) and elasto-sonography.

He is now the Director of the “Ultrasound Neuro-Imaging and Therapy Lab” (UNIT-Lab), performing pre-clinical, clinical and technical research in ultrasound imaging and therapy for various neurological conditions.

He is also founder and developer of In.Tra. and Neuro-stream, start-ups related to the application of ultrasound to the brain.

Dr. Francesco Prada joined the Focused Ultrasound Foundation in Charlottesville (USA) in July 2017 where he was recipient of the Merkin Fellowship. Since July 2018 he has also been named in Brain Program Director of the Focused Ultrasound Foundation.

He is currently Visiting Professor in the Department of Neurological Surgery, University of Virginia Health Science Center in Charlottesville, Virginia (USA) where he is conducting clinical and pre-clinical researches in the field of focused ultrasound.

Dr. Prada earned his degrees and residency at the “Università degli Studi” of Milan, Italy, perfectioning his training in major centers worldwide.

He is currently neurosurgeon in the Department of Neurosurgery at the Fondazione IRCCS Istituto Neurologico C.Besta in Milan, Italy, where he shared his interests between clinical practice, mainly focusing in skull base/pituitary surgery and neuro-oncology, and research, studying intra-operative applications of ultrasound for the treatment of cerebral and spinal tumor and vascular lesions and advanced ultrasound techniques such as Fusion Imaging for Virtual Navigation, contrast enhanced ultrasound (CEUS) and elasto-sonography.

He is now the Director of the “Ultrasound Neuro-Imaging and Therapy Lab” (UNIT-Lab), performing pre-clinical, clinical and technical research in ultrasound imaging and therapy for various neurological conditions.

He is also founder and developer of In.Tra. and Neuro-stream, start-ups related to the application of ultrasound to the brain.

Dr. Francesco Prada joined the Focused Ultrasound Foundation in Charlottesville (USA) in July 2017 where he was recipient of the Merkin Fellowship. Since July 2018 he has also been named in Brain Program Director of the Focused Ultrasound Foundation.

He is currently Visiting Professor in the Department of Neurological Surgery, University of Virginia Health Science Center in Charlottesville, Virginia (USA) where he is conducting clinical and pre-clinical researches in the field of focused ultrasound.

Author: Nicolas Asquier
Time: 10:00
Place: Rockefeller Theses Room

Summary: 

The blood-brain barrier (BBB) is a natural protection of the central nervous system. However, it limits the delivery of many drugs to the brain tissues. It can be temporarily disrupted by ultrasound exposure combined with intravenous injection of microbubbles. In this manuscript, BBB disruption with an implantable unfocused ultrasound device is studied.
An automatic method for quantifying the volume of BBB disruption using MR images from a phase 1/2a clinical study in patients with reccurent glioblastoma was assessed and validated. A correlation between the probability of disruption and the local acoustic pressure was found.
Microbubbles cavitation activity was studied in vitro to better understand its effect on BBB disruption. The uncertainty on the amplitudes of cavitation signals recorded with a passive single-element detector (PCD) through the skull was quantified. A position-based correction of the PCD signal was assessed and validated.
The effect of the volume of a cavitation cloud in the unfocused ultrasound field on the signal amplitude recorded by the PCD during the clinical treatment was discussed. Two methods for localizing and discriminating cavitation sources in a transcranial context were evaluated by simulations and in vitro.

Author: Dr Mario Ries – Image Sciences Institute-University Medical Center Ultrecht
Time: 2 PM
Place: LabTAU – Conference Room

Summary: 
While therapeutic HIFU applications in the linear pressure regime have meanwhile established their place in numerous clinical applications, non-linear acoustic phenomena have despite their considerable potential so far been left largely unexploited.
Here we contrast the in-vivo experience of the UMC-Utrecht with non-linear acoustic applications for local control vs systemic therapy. Shock wave enhanced HIFU thermotherapy can hereby overcome the typical limitations of HIFU ablations in high perfused organs such as the liver, while mechanical tissue fractionation allows transforming immunologically 'cold' Neuroblastoma tumors into responsive 'hot' tumors, which in combination with immune checkpoint inhibitors lead to a systemic response.

Author: Claude INSERRA
Summary:  Contrôle de la dynamique spatiotemporelle de bulles de cavitation ultrasonore -

Une bulle acoustique est un oscillateur non linéaire, excité par un champ ultrasonore, qui possède un grand nombre d'avantages pour certaines applications thérapeutiques, en tant que vecteur localisé de l'énergie acoustique, avec une forte échogénicité, et aidant au transport de médicament au sein de cellules ou tissus biologiques. Les localiser in vivo, et détecter/quantifier leur activité de cavitation est primordial pour assurer une meilleure efficacité des traitements ultrasonores. Afin de les détecter de manière extra-corporelle, des signatures acoustiques propres à la bulle sont classiquement utilisées. Ces signatures sont (i) le bruit large bande, caractéristique de l'implosion de bulles, qui identifie le régime de cavitation inertielle et (ii) la composante sous-harmonique (entre autres composantes) de la fréquence fondamentale, dont les origines sont diverses, mais qui identifie un régime temporellement stable d'oscillations (ou d'implosions périodiques d’un nuage de bulles). A l'aide d'une écoute passive de ces signatures, on peut distinguer l'activité de cavitation selon ces deux régimes.

Dans une première partie de ce mémoire le contrôle temps-réel de l'activité de cavitation d'un nuage de bulles est présenté. Ce contrôle permet de s'affranchir du caractère stochastique de la cavitation ultrasonore, et d'assurer un niveau de cavitation reproductible, temporellement stable. Deux stratégies de contrôle sont présentées, une sur l'indice de cavitation inertielle, l'autre sur l'indice de cavitation stable. Elles reposent sur la modulation en temps-réel de la tension électrique appliquée aux transducteurs ultrasonores. Cette modulation est régie par un processus proportionnel de contrôle afin d'assurer un niveau de cavitation donné par l'opérateur. Grâce à une programmation sous FPGA (Field Programmable Gate Array), des temps de rétroaction inférieurs à la milliseconde ont permis le contrôle de cavitation au sein de tirs ultrasonores pulsés. Il est montré que la stratégie de contrôle permet de s'affranchir de l'utilisation d'agents de contraste ultrasonore, au moins in vitro. Les taux de sonoporation/transfection obtenus lors de l'utilisation du contrôle sont généralement plus reproductibles que ceux obtenus en séquences ultrasonores à intensité acoustique fixe. L'utilisation du contrôle de cavitation stable a mis en évidence la possibilité de sonoporer des cellules tout en minimisant la mortalité cellulaire. Afin de saisir l'origine physique de la sonoporation cellulaire (en termes d'interaction bulle-cellule), il est nécessaire de différencier les régimes de cavitation stable et inertiel dans les phénomènes cellulaires étudiés.

Dans une seconde partie de ce mémoire mes travaux sur la dynamique temporelle de bulle unique sont présentés. Après des balbutiements sur la dynamique de bulles présentant des couplages translation/oscillation radiale en champ acoustique intense, une étude analytique sur la dynamique de bulle en excitation bifréquentielle est réalisée. Cette étude permet de démontrer l'intérêt de la génération de nouvelles composantes fréquentielles proches de la fréquence de résonance de la bulle, qui se décale par effet non linéaire. Une démarche expérimentale a été initiée pour vérifier ces travaux théoriques avec la conception d'une chambre de lévitation acoustique où une bulle unique est piégée sur un ventre de pression du champ ultrasonore. L'intérêt de cette configuration est d'obtenir les oscillations d'une bulle loin de toute paroi, et de faciliter les observations par caméra rapide. En utilisant un champ acoustique modulé en amplitude, une déviation des oscillations radiales de la bulle est observée. L'interface se déforme selon des modes de surface qui sont périodiquement déclenchés, maintenus puis annihilés. Ce déclenchement périodique des modes de surface de bulle a mis en évidence le couplage non linéaire existant entre les modes de volume, de translation et de surface de la bulle. L'ensemble des observations expérimentales a ainsi permis de valider les plus récents modèles théoriques prenant en compte ces couplages.  Les oscillations non sphériques de bulle ont finalement été maîtrisées par utilisation d'une technique de coalescence entre deux bulles filles. Cette technique a permis le contrôle de l'orientation des déformations non sphériques, ainsi que la mise en place d'un régime permanent des modes de surface. Profitant de ce régime permanent, l'ensemencement de particules dans la chambre de lévitation acoustique permet l'observation des écoulements fluides induits par les oscillations de bulles. Les motifs d'écoulements observés sont reliés à la dynamique de la bulle, mais aussi à la position de la bulle dans la zone d'instabilité des modes de surface. Des motifs confinés (proche de l'interface de la bulle) ou en croix (très étendu jusqu'à plusieurs diamètres de bulle) sont relevés. Pour expliquer ces motifs, un modèle analytique des écoulements induits par une bulle axisymétrique oscillant sur ses modes de volume, translation et de surface, est réalisé. Il permet le calcul exact du champ de vitesse moyen de l'écoulement induit. Une classification des motifs expérimentaux à l'aide de ce modèle analytique est en cours.
Time:13:30
Place:Salle de Conférence de l'INSERM, 151 Cours Albert Thomas, LYON

Author: Francis Bessiere
Summary: 

A la croisée des chemins entre médecine et physique des ultrasons, ce travail de thèse s’est intéressé à l’apport de solutions diagnostiques et de thérapeutiques novatrices dans le domaine de l’électrophysiologie cardiaque.

Un système capable de délivrer des ultrasons focalisés dans le cœur par voie transoesophagienne sous guidage par ultrasons a été développé et testé in vivo chez 6 porcs. Les tirs HIFU ont été délivrés sur les oreillettes et les ventricules. Lors de l'autopsie, une analyse visuelle a démontré la présence de lésions thermiques dans les zones ciblées chez 3 animaux. Ces lésions ont été confirmées par analyse histologique (taille moyenne: 5,5 mm2 x 11 mm2). Aucune lésion thermique œsophagienne n'a été observée. Un animal a présenté une bradycardie due à un bloc auriculo-ventriculaire, ce qui a permis de confirmer une réelle interaction entre les tirs HIFU et le tissu nodal cardiaque. Nous avons cependant observé un manque de précision, principalement lié aux mouvements cardiaques ainsi qu’aux structures anatomiques situées entre les zones ciblées et le transducteur de thérapie. Ces difficultés ont été principalement reliées à l’anatomie du modèle porcin, loin de celle de l’être humain. La recherche d'un meilleur modèle a conduit à des tests d'imagerie concluants sur des babouins.

Des expériences supplémentaires ont été conduites afin d'améliorer la cartographie des arythmies ventriculaires et le suivi de la formation de lésions pendant l'ablation.

Des expériences ont été menées sur les ventricules gauches de quatre coeurs de porcs en mode travaillant. Le protocole visait à démontrer que différents modèles d'activation mécanique pouvaient être observés, que le ventricule soit en rythme sinusal, stimulé depuis l'épicarde ou l'endocarde. Des acquisitions d’imagerie de déformation électromécanique (EWI) ont été enregistrées sur les faces antérieures, latérales et postérieures du ventricule gauche. Elles ont été ensuite analysées à l’aveugle par deux lecteurs indépendants.

Les interprétations des séquences EWI étaient correctes dans 89% des cas. Le taux de concordance globale entre les deux lecteurs était de 83%. Dans un ventricule stimulé, l'origine du front d'onde était focale et provenait de l'endocarde ou de l'épicarde stimulé. En rythme sinusal, le front d'onde était activé depuis tout l'endocarde, en direction de l'épicarde, à une vitesse de 1,7 ± 0,28 m.s-1. Les vitesses du front d'onde ont été mesurées respectivement lorsque l'endocarde ou l'épicarde étaient stimulés à une vitesse de 1,1 ± 0,35 m.s -1 et 1,3 ± 0,34 m.s-1 (p = NS).

Nous avons aussi démontré sur des échantillons ex-vivo que l'imagerie trans oesophagienne par analyse des ondes de cisaillement (élastographie) pouvait cartographier l'étendue des lésions HIFU.

Des tirs HIFU ont été réalisés à l'aide de la sonde trans oesophagienne sur des échantillons de blanc de poulet (n = 3), puis sur un modèle porcin ex vivo d'oreillette (gauche, n = 2) et de ventricule gauche (n = 1). L’élastographie a fourni des cartes de rigidité des tissus avant et après l'ablation. Les zones des lésions ont été obtenues par analyse et quantification des changements de couleur des tissus puis ont été comparées aux images par élastographie.

Dans le blanc de poulet, la rigidité est passée en moyenne de 4.8±1.1 kPa à 20.5±10.0 kPa (ratio 5.0±3.2). Dans le ventricule gauche, la rigidité est passée en moyenne de 21.2±3.3kPa à 73.8±13.9kPa (ratio 3.7±1.2). Dans l’oreillette gauche, la rigidité est passée en moyenne de 12.2±4.3 kPa à 30.3±10.3 (ratio 3.2±2.0). En histologie, la taille des lésions variait de 0.1 à 1.5 cm2 dans la zone du plan d'imagerie. Les caractéristiques morphométriques étaient similaires entre histologie et élastographie.
Time:14:00
Place:Salle de conférence de l''INSERM, 151 Cours Albert Thomas, LYON

Author: Sarah Clève
Summary: Microbubbles find use in several domains, one of them being medical ultrasound applications. Different characteristics of those bubbles such as their acoustic resonance or their destructive effect during inertial cavitation can be exploited. Another phenomenon induced around acoustically excited bubbles is microstreaming, that means a relatively slow mean flow with respect to the fast bubble oscillations. Microstreaming and its associated shear stresses are commonly agreed to play a role in the permeabilization of cell membranes, a detailed understanding of the induced flows is however missing. To acquire basic physical knowledge, this work focuses on the characterization of streaming induced around an air bubble in water, more precisely around
a single acoustically trapped and excited, nonspherically oscillating bubble. The experimental part consists of two steps. First, the bubble dynamics, in particular the triggered shape mode and the orientation of the bubble have to be controlled. For this, the use of bubble coalescence proves to be an adequate method. In a second step, the microstreaming is recorded in parallel to bubble dynamics. This allows to correlate the obtained streaming patterns to the respective shape oscillations. The large number of obtained pattern types can be classified, in particular with respect to the mode number and bubble size. A close investigation of the bubble dynamics allows furthermore deducing the important physical mechanisms which lead to such a variety of streaming patterns. In order to confirm the experimental findings, an analytical model has been developed. It is based upon time-averaged second-order fluid mechanics equations and the experimentally obtained bubble dynamics serves as input parameters. Supplementary to the microstreaming work, this manuscript contains a short section on directed jetting of contrast agent microbubbles, which might appear at high acoustic driving. The impact of those microjets on cell membranes presents another mechanism made responsible for the permeabilization of cell membranes.
Time: 13h30
Place: Ecole Centrale Lyon - Bâtiment W1 Amphi201

More info here

Dr. W. Apoutou N’DJIN, Ph.D., Research Associate in Biomedical Engineering & Physics at the Laboratory of Therapeutic Applications of Ultrasound (LabTAU, French National Institute of Health and Medical Research, University of Lyon, France), was recently presented the International Society of Therapeutic Ultrasound’s (ISTU) Frederic LIZZI Early Career Award at the 19th International Symposium for Therapeutic Ultrasound. One of ISTU’s most prestigious awards, the Frederic LIZZI Early Career Award was established in 2008 to honor Dr. Frederic L. LIZZI, a pioneer in advanced diagnostic and therapeutic applications of ultrasound. Since then, it is presented to one recipient annually (except in special circumstances) for their contributions to therapeutic ultrasound. The recipient should be within 10 years of their terminal degree and is selected among a pool of nominees by ISTU’s Organizing Committee and Board.

The event was held in Barcelona (Spain) at the occasion of the first joint meeting of the ISTU Society and the European Focused Ultrasound Charitable Society (EUFUS). The Symposium has been held at the historic building of the Universitat de Barcelona, one of the most emblematic sites in the city centre, which was constructed in 1863 by the architect Elies Rogent.

This year’s LIZZI Award was shared by two researchers, Dr. W. Apoutou N’DJIN, Ph.D. (LabTAU, INSERM, CLB, Univ Lyon, France) and Dr. Kevin J. HAWORTH, Ph.D. (College of Medicine, University of Cincinnati, United States). Following ISTU tradition, LIZZI award recipients delivered the LIZZI Award Lecture and shared a dedicated session with the 2019 FRY Award (Pr. Chrit MOONEN, Ph.D., Division of Imaging, Uninversity Mecial Center Utrecht, Netherland) and the 2019 PIONEER Award (Pr. Leonid GAVRILOV, Ph.D., Andreyev Acoustics Institute, Physical Acoustics, University of Moscow, Russia).

W. Apoutou N’DJIN delivered a LIZZI Lecture entitled " A healthy future for focal conformal therapeutic ultrasound" and highlighted some of their contributions in the development of new ultrasound targeting strategies and technologies in surgery and interventional radiology, as well as their openness to methods coming from neurosciences for studying ultrasound neurostimulation.

Author: Jeremy Vion
Summary: Focused ultrasound (US) are considered as a promising tool to develop a new modality of therapeutic neurostimulation. An in vivo invertebrate nervous model (system of giant fibers of the common earthworm, Lumbricus terrestris) has been proposed to study the biophysical mechanisms underlying the phenomenon of US neurostimulation. After proving the feasibility, the nervous responses associated with different stimulation modalities (mechanical, electrical, US) were characterized and compared together. Following a causal approach of interpretation, the afferent nerves were deduced to be the locus of interaction between the nervous system and the US stimulus (pulsed, 1.1 MHz, 2% DT, 2.5 kW/cm²). The respective influences of each acoustic parameter on the neurostimulation success rate were evaluated. Results suggest afferent nerves are sensitive to the value of the ‘mean radiation force’ carried by the US stimulus, whatever combination of parameters leading to it. Complementarily, the role played by cavitation in the phenomenon of US neurostimulation was investigated, using both the monitoring of cavitation indexes and ultra-fast imaging. It was concluded that neither the occurrence of stable cavitation nor particularly high levels of inertial cavitation were necessary conditions for the occurrence of US-induced nervous responses. A new experimental campaign was launched, aiming to apply the methodology developed for the invertebrate nervous model to a nervous model of higher complexity. The feasibility of using Microelectrode Arrays (MEA) to record US-induced nervous responses from mouse cortical slices was demonstrated, and further trials are currently undertaken.
Time: 13h
Place: LabTAU Conference Room

Dear all

The 12th course composing the MOOC is now available. This clinical presentation is given by Professor Florent APTEL on «HIFU for treating glaucoma»

Note that this is the last of the 12 courses composing this first MOOC dedicated to therapeutic ultrasound but that all courses remain available online 

Note that this is the last of this first MOOC dedicated to therapeutic ultrasound and that all the courses will still be available on-line after March 4.

You can register on Claroline by clicking here
We hope you enjoyed the presentations and again we wanted to thank you for showing your interest in the first MOOC dedicated to therapeutic ultrasound.

If you have any suggestion for further Courses on therapeutic ultrasound please let us know!
We are looking forward to your feedback.

Thank you 
 

Dear all

The 11th course composing the MOOC is now available. This clinical presentation is given by Professor Franco ORSI on «Application of HIFU in oncology »

It will be followed on March 4 by a course given by Professor Florent APTEL on «HIFU for treating glaucoma». 

You can register on Claroline by clicking here

Hope you’ll enjoy the presentation!

We are looking forward to your feedback.

Thank you for showing your interest in the first MOOC dedicated to therapeutic ultrasound

Dear all

The 9th course composing the MOOC is now available. This technical presentation is given by Professor Bruno QUESSON on «MRI for guiding HIFU treatment».

It will be followed on February 4 by a course given by Professor Pejman GHANOUNI on «MR guided high intensity focused ultrasound : A pediatric application»

You can register on Claroline by clicking here

Hope you’ll enjoy the presentation!

We are looking forward to your feedback.

Thank you for showing your interest in the first MOOC dedicated to therapeutic ultrasound
 

Dear all

The 7th course of the first MOOC on therapeutic ultrasound is now available. This technical presentation is given by Professor Lawrence A. CRUM on «What is cavitation?».
It will be followed in January by a course given by Professor A. CARPENTIER entitled «Opening the BBB by ultrasound».

You can register on Claroline using the following link: clarolineconnect.univ-lyon1.fr.

Hope you’ll enjoy the presentation

We are looking forward to your feedback and will be back in January with more courses.

Thank you and wishing you all a very happy festive season!
 

Dear all

The 6th course is now available. It is a technical presentation given by Pr. Chrit MOONEN on «Drug delivery by ultrasound».

It will be followed by a course given by Dr Lawrence A. CRUM entitled «What is cavitation ?». We will then be back in January with more courses.

You can register on Claroline using the following link: clarolineconnect.univ-lyon1.fr. 

Hope you’ll enjoy the presentation

We are looking forward to your feedback!

Thank you
 

Author: Stephane Marinesco
Summary: Ce séminaire passera en revue les différents modèles de traumatisme crânien modéré et sévère chez le rat ainsi que les difficultés particulières liées à l’induction d’un trauma sévère chez l’animal. Les mécanismes lésionnels aboutissant à des lésions neurologiques et des déficits comportements seront également discutés.
Time:11:00
Place: Salle de réunion du LabTAU 151 Cours A.Thomas LYON

Dear all

An increasing number of participants has been registering on of the first MOOC on therapeutic ultrasound.

The 4^th course is now available. It is a clinical presentation given by Pr Sébastien Crouzet on the use of «HIFU for treating prostate cancer».

In two weeks, it will be followed by the 5^th course which will be given by Pr. Shin-Ichiro UMEMURA on «Ultrasound imaging for high intensity focused ultrasound treatment»

You can register on Claroline using the following link: https://clarolineconnect.univ-lyon1.fr/

Hope you’ll enjoy the presentation

Thank you

Thesis defense: Time reversal elastography, mechanical characterization of biological tissues by shear- wave phased array
Date: Tuesday, October 30th, 2018 at 14h
Author: Chadi ZEMZEMI
Location: Conference room, INSERM – Cours Albert Thomas Lyon 3

follow this link for more information 

Author: Alexander Doinikov
Time: 14H
Place: AMPHI EST, BÂT HUMANITÉS, INSA DE LYON
Summary: When a body in a fluid is subjected to an acoustic wave field, the scattered wave from the body interacts with the incident wave, giving rise to the co-called acoustic radiation force. This force makes the body migrate in space, and in the case of two or more bodies, causes repulsion or attraction between them. An understanding of this motion is important to applications such as acoustomicrofluidics and medical ultrasonics. The history of theoretical studies of acoustic radiation forces (...)

It’s a big pleasure to invite you to for the 23nd scientific day of EDISS, which will take place on Thursday, 11th October at Villeurbanne. 

This day will be the occasion to welcome new PhD students and to present them the organization of the doctoral school. It is therefore obligatory for the 1st year PhD students and their supervisors to participate.

To participate, you need to subscribe via https://jediss2018.sciencesconf.org/.

This day is also the occasion for PhD students to present their work via oral communications or posters. We remind you that you have to make a presentation at least once during your PhD. 

We hope to see you all!

Les nœuds franciliens, Paris Centre et Paris Sud, du réseau national France Life Imaging, FLI vous invitent à leur journée scientifique le jeudi 27 septembre 2018 à l’Institut de Myologie à Paris.

Cette quatrième édition sera consacrée aux avancées des techniques d'acquisition multimodales en imagerie médicale.

Télécharger le programme ici

Pour participer, inscrivez-vous jusqu’au 24 septembre inclus à cette adresse : https://fli-pariscentre.sciencesconf.org/

Nous contacter 

Kahina Abbas pour le comité d'organisation : Olivier Couture, Luc Darrasse, Esther Heinrich, Vincent Lebon, Bernard Van Beers.

Author: Karla P. Mercado-Shekhar, Ph.D.
Summary: Clot stiffness is inversely correlated with rt-PA thrombolytic efficacy in vitro  -Predicting thrombolytic susceptibility to recombinant tissue plasminogen activator (rt-PA) a priori could help guide clinical decision-making during acute ischemic stroke treatment and avoid adverse off-target lytic effects. Prior research has shown that the composition and structure of clots impact their mechanical properties and rt-PA thrombolytic efficacy. The goal of the current research was to determine the relationship between clot elasticity and rt-PA thrombolytic efficacy in vitro. Human and porcine mildy and highly retracted clots were fabricated in glass pipettes. The rt-PA thrombolytic efficacy was evaluated in vitro using the percent clot mass loss. A second set of clots were embedded in agar phantoms. Subsequently, the Young’s modulus of each clot was estimated using single-track-location shear wave elasticity imaging. The imaging sequence was implemented using a Verasonics Vantage 256 system equipped with an L7-4 linear array. The results revealed an inverse relationship between the Young’s moduli and clot mass loss, indicating that stiffer clots are more difficult to lyse with rt-PA. This work suggests that clot stiffness may serve as a predictive metric for rt-PA thrombolytic efficacy. Additionally, this presentation will briefly discuss ongoing projects at the Image-guided Ultrasound Therapeutics Laboratories in the University of Cincinnati. These projects include ultrasound-assisted thrombolysis, ultrasound-triggered bioactive gas delivery, and passive cavitation image guidance and monitoring of ultrasound therapeutics.
Time:11:00
Place: Salle de conférence

Author: Jonathan Mamou
Summary: High-frequency ultrasound (HFU, >20 MHz) and scanning acoustic microscopy (SAM, >200 MHz) offer a means of investigating biological tissue at the microscopic level with spatial resolutions better than 100 μm or 10 μm, respectively. After a brief review of conventional ultrasound imaging, this talk will introduce HFU imaging and present two HFU examples and one SAM example.
Novel HFU imaging methods to form three-dimensional (3D) images of the brain of developing mouse embryos: Many genetically-engineered mice display abnormal development of the central nervous system (CNS) at early embryonic ages and HFU offers great potential for in vivo imaging and characterization. A 34 MHz, five-element annular array was excited using chirp-coded excitation. In utero, in vivo 3D data sets were acquired from more than 100 embryos over five stages, from embryonic days E10.5 to E14.5, and CNS volume renderings were obtained.
The second HFU study focuses on 3D imaging and characterization of lymph nodes freshly-excised from cancer patients. Quantitative-ultrasound (QUS) images were formed and used to detect metastases using a transducer that has a 26-MHz center frequency. Classification results suggest that these QUS methods may provide a clinically-important means of identifying small metastatic foci that might not be detected using standard pathology procedures.
The SAM study focuses on using a novel microscopy system as well as dedicated signal-processing methods to form quantitative images of thin sections of tissue using transducers ranging from 250 MHz to 500 MHz. These techniques yield spatial resolutions better than 8 μm and can be used to assess morphological, acoustical and mechanical tissue properties quantitatively. Data obtained from excised eyes from a guinea pig model of myopia will be presented.
Time:11:00
Place:Salle de réunion duLabTAU u1032 151 Cours A.Thomas , Lyon

Une conférence de Mickael TANTER, de l'Institut Langevin (ESPCI Paris),  qui sera donnée dans le cadre des conférences du CRNL.
Elle sera accomapgnée par une présentation de Ludovic LECOINTRE, de ICONEUS, une spin-off spécialiste en neuro-imagerie fonctionnelle, notamment par ultrason.

Lundi 2 juillet 2018 11h30
Lieu: Amphitheâtre M Hemingway, Bâtiment IDEE, Pôle Hospitalier Lyon Est Bron

En savoir plus :  Mickael_TANTER_Conference_CRNL.pdf

                          ICONEUS.pdf

Source : Les conférences du CRNL

Author: Pejman Ghanouni
Summary: Discussion of clinical applications of MR guided focused ultrasound in use or in development at Stanford Hospital
Time:13:30
Place:Salle de réunion du LabTAU, Inserm 151 Cours A.Thomas, Lyon

Afin de promouvoir le rayonnement de son Université et de valoriser les activités de recherche de ses chercheurs(ses), la Métropole de Lyon organise en partenariat avec l’Université de Lyon,  le Prix Jeune Chercheur(se) remis à 3 lauréat(e)s distingué(e)s, selon les champs thématiques suivants :

1. Thème « biosanté et société», où les enjeux dépassent largement les seuls aspects technologiques, notamment dans les secteurs du cancer et des vaccins, traditionnellement en pointe à Lyon, avec la médecine personnalisée, la croissance de pathologies émergentes, la nécessité de développer des approches avancées de modélisation et simulation.
2. Thème « sciences et ingénierie », avec des enjeux comme les industries du futur pour qui les aspects de durabilité et de soutenabilité sont au centre des préoccupations, le partage de l'énergie, les transports.
3. Thème « humanités et urbanité », dans une compréhension des métropoles où la technologie, les politiques publiques et les organisations sont tournées vers l'humain. L’analyse des sociétés dans une compréhension de la modernité, du religieux et de la laïcité, de la gestion des croissances économiques et des risques sont étudiés comme des enjeux majeurs.

Date limite de participation : 31 mai 2018.

Author: Emilie Franceschini
Summary: Cette présentation porte sur les techniques de spectroscopie ultrasonore permettant d’estimer les structures cellulaires au sein des tissus. Ces techniques permettent de différencier des tissus sains et pathologiques ou de faire le suivi de thérapie. Les tumeurs cancéreuses résultent souvent d'une prolifération de cellules anormales formant une masse  qui grossit. Les modèles classiques de diffusion ultrasonore utilisés par les techniques classiques supposent que les diffuseurs sont distribués de façon aléatoire (i.e. des milieux dilués), alors que les tumeurs sont des milieux à fortes concentrations cellulaires. Déterminer les modèles de diffusion adaptés à un amas dense de cellules et identifier les structures cellulaires responsables de la diffusion sont les deux thématiques principales que je développerai. Nous comparons différents modèles de diffusion et discutons de leurs limites à travers des expériences hautes fréquences (10-45 MHz) sur des biofantômes de cellules vivantes ou apoptotiques.
Time:11:00
Place:Salle de réunion, LabTAU u1032 151 Cours A.Thomas, LYON

Author: Lawrence A. Crum Professor of Bioengineering and Electrical Engineering, Center for Industrial and Medical Ultrasound, University of Washington, Seattle, USA

Dr. Lawrence A. Crum is currently Principal Physicist and Chair of the Department of Acoustics and Electromagnetics in the Applied Physics Laboratory, and Research Professor of Bioengineering and Electrical Engineering at the University of Washington. He has held previous positions at Harvard University, the U. S. Naval Academy and the University of Mississippi, where he was F. A. P. Barnard Distinguished Professor of Physics and Director of the National Center for Physical Acoustics. He has published over 180 articles in professional journals, presented over 200 papers at professional meetings, and holds an honorary doctorate from the Universite Libre de Bruxelles. He is Past President of the Acoustical Society of America and current President of the Board of the International Commission for Acoustics. In June of 2000, he was awarded the Helmholtz-Rayleigh Interdisciplinary Silver Medal of the Acoustical Society of America.
Summary: Acoustic cavitation is a phenomenon that involves the interaction of an acoustic field with a gas bubble in a liquid. Since a bubble has a compressibility many orders of magnitude more than a liquid, the gas bubble can act as a means of concentrating the energy of the acoustic field to a restricted region of time and space. Concentrations of energy on the order of eleven orders of magnitude have been reported. This lecture will introduce cavitation as a physical phenomenon and describe some applications of cavitation to current topics in medical ultrasound.
Time:11:00
Place:Conference room, LabTAU, INSERM 151 Cours Albert Thomas

Author: Jeff Elias

William Jeffrey Elias was born in Durham, North Carolina, in 1968. He grew up in Roanoke as the son of a neurologist. He attended Wake Forest University and pursued a Bachelor of Arts degree in chemistry while also playing junior varsity tennis. While in college, he was awarded a scholarship for undergraduate research in chemistry and he graduated Phi Beta Kappa. He attended the University of Virginia for medical school and neurosurgical training. During neurosurgical training, he completed intramural fellowships in neuropathology and spinal surgery before spending a year in Plymouth, England, as a senior registrar. Following residency, he pursued additional training in stereotactic and functional neurosurgery at the Oregon Health Sciences University. In 2002, Dr. Elias returned to the University of Virginia where he is currently the director of stereotactic and functional neurosurgery with a large multidisciplinary program in the surgical treatment of movement disorders, epilepsy and spasticity. He currently sits on the medical advisory board of the International Essential Tremor Foundation (IETF). Dr. Elias’ clinical team includes Caroline Metsch, PAC, Kathy Maynard, RN, and Karen Osteen.

Summary: Therapeutic uses of FUS in the brain.

In the 1950s, neuroscientists and neurosurgeons became interested in using ultrasound to treat disorders deep in the brain.  This never gained favor because of the difficulty transmitting acoustic energy through the intact skull.  Recent advances in ultrasound transducer technology now enable the precise transmission of ultrasound, through the skull, to deep regions inside the brain.  An increasing number of clinical trials now demonstrate the potential efficacy of MRI-guided focused ultrasound for the treatment of movement disorders and other neurologic conditions.  This talk will review the current status of focused ultrasound therapy in human brain.

Time:16:00
Place:Conference room

La médaille de l’innovation a été décernée au Docteur Albert Gelet le 10 janvier 2017 par l’académie de chirurgie validant une activité de recherche fondamentale et clinique qui s’est étalée sur plus de 25 ans concernant le traitement du cancer de la prostate par ultrasons focalisés.

Le traitement du cancer localisé de la prostate par ultrasons focalisés est un traitement mini invasif qui a été développé à partir de 1990 grâce à une collaboration entre 4 partenaires tous basés à Lyon : le service d’urologie et de chirurgie de la transplantation de l’Hôpital Edouard Herriot (Hospices Civils de Lyon), le service de radiologie urinaire de l’Hôpital Edouard Herriot,  l’unité INSERM 1032 (application des ultrasons à la thérapie) université Lyon 1, et la société EDAP-TMS. L’objectif était la mise au point d’un traitement aussi peu invasif que possible du cancer localisé de la prostate rendu nécessaire par l’augmentation drastique de son incidence liée à son  dépistage par le dosage du PSA (400 000 nouveaux cas en Europe par an dont 70 000 en France) .La plupart  des cancers sont maintenant détectés à un stade précoce et un grande nombre de patients présente des cancers dont le risque  évolutif  à 10 ans  (apparition de métastases) est faible  ou modéré .Ces patients reçoivent actuellement un traitement radical d’emblée (avec des risques de séquelles urinaires et sexuelles) ou bien sont placés en surveillance active avec traitement différé en cas de progression (avec le risque de réaliser dans certains cas le traitement trop tardivement comme l’a montré l’étude anglaise Protect). L’objectif principal du traitement HIFU est de proposer une alternative à la fois au traitement radical et à le surveillance active à des patients dont la tumeur a été bien évaluée grâce à la combinaison d’une IRM multiparamétrique et de biopsies guidées par l’imagerie IRM.

Thesis title: Ultrasound Microbubbles for Molecular Imaging and Drug Delivery: Detection of Netrin-1 in Breast Cancer & Immunomodulation in Hepatocellular Carcinoma
Summary: Ultrasound has an important role in cancer diagnosis and was further developed for cancer therapy. Diagnostic approaches are required to analyze molecular profiles and enable personalized medicine and therapeutic approaches have to be tumor-specific reducing off-site delivery and side effects. Ultrasound molecular imaging uses microbubbles as ultrasound contrast agents which are functionalized with targeting ligands. Upon intravenous injection, targeted microbubbles bind to molecular markers presented on the tumor endothelium and enable the non-invasive assessment cancer-related biomarkers. In the present thesis, ultrasound molecular imaging was developed for detection of netrin-1, which is upregulated in 70% of metastatic breast cancer and promotes cell survival. A newly developed netrin-1 interference therapy requires the identification of patients who overexpress the target protein and, could benefit from anti-netrin-1 therapy. In vivo imaging of netrin-1 showed a significantly increased imaging signal in netrin-1-positive breast tumors compared to netrin-1-negative breast tumors and normal mammary glands. The results suggest that ultrasound molecular imaging allows accurate detection of netrin-1 on the endothelium of netrin-1-positive tumors and has the potential to become a companion diagnostic for netrin-1 interference therapy in breast cancer patients. Ultrasound-targeted microbubble destruction triggers cavitation and sonoporation thereby permeabilizing the tissue and facilitating local drug delivery. Further, immune cell infiltration and tumor antigen release are induced and trigger anti-tumor immune responses. In the present thesis, ultrasound-targeted microbubble destruction-mediated delivery of anti-cancer microRNA-122 and anti-microRNA-21 is studied for immune response activation in hepatocellular carcinoma, in which the immune microenvironment is deregulated. Tumor lymph nodes showed pro-tumor cytokine downregulation and anti-tumor cytokine upregulation, suggesting an overall positive therapy response with regard to the tumor immunology. The results identified ultrasound-targeted microbubble destruction-mediated miRNA delivery as a potent immuno-modulatory therapeutic approach. In conclusion, ultrasound molecular imaging and ultrasound-targeted microbubble destruction turned out to be powerful techniques that can significantly improve diagnosis and therapy of different types of carcinomas.

Author: Professor Chrit Moonen de « lmage Sciences Institute » at Utrecht.
Summary: The Centre for Image Guided Oncological Interventions (CIGOI) of the UMC Utrecht is an initiative of the Division of Imaging at the University Medical Center, Utrecht, the Netherlands with the central objective to provide real-time image guidance for high precision in the treatment of localized tumors. Within the CIGOI a range of unique image-guided treatment techniques have been developed such as MRI controlled 'High Intensity Focused Ultrasound (MRI guided HIFU), MRI-driven linear accelerator (first prototype installed at UMCU), MRI guided robotic brachytherapy, and intra-arterial radio-embolization with holmium microspheres.

Author: Emily White MD Director of operations, Charlottesville, USA
Summary: Emily White, MD joined the Foundation in 2016 as Director of Operations. Prior to joining the Foundation, Dr. White was a private consultant working in operations and business development support in the healthcare and medical start-up space. Her clients have included everything from a 4,000+ employee, publically traded, health care company to a brand new start-up with two employees. Her background includes training in general surgery, leadership positions in several highly technical start-up companies with federal clients, non-profit executive management and over 25 years of grant writing experience. She completed her undergraduate degree in Biology & Anthropology at Smith College, holds certification for Community Conflict Resolution from Loyola Law School, and is a University of Virginia School of Medicine graduate.