63 results on '"Jean-Louis Mestas"'
Search Results
2. Ultrasound Molecular Imaging for the Guidance of Ultrasound-Triggered Release of Liposomal Doxorubicin and Its Treatment Monitoring in an Orthotopic Prostatic Tumor Model in Rat
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Frédéric Padilla, Thierry Bettinger, Alexandre Helbert, Mathew A. Von Wronski, Isabelle Tardy, Jean-Louis Mestas, Cyril Lafon, and Jean-Marc Hyvelin
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Male ,Vascular Endothelial Growth Factor A ,Drug ,Acoustics and Ultrasonics ,media_common.quotation_subject ,Confocal ,Biophysics ,Polyethylene Glycols ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Doxorubicin ,media_common ,Liposome ,Radiological and Ultrasound Technology ,Chemistry ,business.industry ,Ultrasound ,Prostatic Neoplasms ,Ultrasound molecular imaging ,Kinase insert domain receptor ,Molecular Imaging ,Rats ,Liposomes ,business ,Treatment monitoring ,medicine.drug ,Biomedical engineering - Abstract
Liposome encapsulation of drugs is an interesting approach in cancer therapy to specifically release the encapsulated drug at the desired treatment site. In addition to thermo-, pH-, light-, enzyme- or redox-responsive liposomes, which have had promising results in (pre-) clinical studies, ultrasound-triggered sonosensitive liposomes represent an exciting alternative to locally trigger the release from these cargos. Localized drug release requires precise tumor visualization to produce a targeted and ultrasound stimulus. We used ultrasound molecular imaging (USMI) with BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasound contrast agent, to guide ultrasound-triggered release of sonosensitive liposomes encapsulating doxorubicin (L-DXR) in an orthotopic prostatic rodent tumor model. Forty-eight hours after L-DXR injection, local release of doxorubicin was triggered with a confocal ultrasound device with two focused transducers, 1.1-MHz center frequency, and peak positive and negative pressures of 20.5 and 13 MPa at focus. Tumor size decreased by 20% in 2 wk with L-DXR alone (n = 9) and by 70% after treatment with L-DXR and confocal ultrasound (n = 7) (p0.01). The effect of doxorubicin on perfusion/vascularity and VEGFR2 expression was evaluated by USMI and immunohistochemistry of CD31 and VEGFR2 and did not reveal differences in perfusion or VEGFR2 expression in the absence or after the triggered release of liposomes. USMI can provide precise guidance for ultrasound-triggered release of liposomal doxorubicin mediated by a confocal ultrasound device; moreover, the combination of B-mode imaging and USMI can help to follow the response of the tumor to the therapy.
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- 2021
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3. DNA Double-Strand Breaks in Murine Mammary Tumor Cells Induced by Combined Treatment with Doxorubicin and Controlled Stable Cavitation
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Jacqueline Ngo, Maxime Lafond, Cécile Fant, Frédéric Padilla, Jean-Louis Mestas, Cyril Lafon, Nicolas Foray, and Adeline Granzotto
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Mammary tumor ,Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,Cell Survival ,Chemistry ,DNA damage ,Biophysics ,Antineoplastic Agents ,DNA ,Mice ,chemistry.chemical_compound ,Doxorubicin ,Cell culture ,Extracellular ,Bystander effect ,Cancer research ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Viability assay ,DNA Damage ,medicine.drug - Abstract
Chemotherapeutic agents such as doxorubicin induce cell cytotoxicity through induction of DNA double-strand breaks. Recent studies have reported the occurrence of DNA double-strand breaks in different cell lines exposed to cavitational ultrasound. As ultrasound stable cavitation can potentiate the therapeutic effects of cytotoxic drugs, we hypothesized that combined treatment with unseeded stable cavitation and doxorubicin would lead to increased DNA damage and would reduce cell viability and proliferation in vitro. In this study, we describe how we determined, using 4T1 murine mammary carcinoma as a model cell line, that unseeded stable cavitation combined with doxorubicin leads to additive DNA double-strand break induction. Combined treatment with doxorubicin and unseeded stable cavitation significantly reduced cell viability and proliferation at 72 h. A mechanistic study of the potential mechanisms of action of the combined treatment identified the presence of cavitation necessary to increase early DNA double-strand break induction, likely mediated by a bystander effect with release of extracellular calcium.
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- 2021
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4. Evaluation of a Three-Hydrophone Method for 2-D Cavitation Localization
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Nicolas Asquier, Alexandre Carpentier, Maxime Lafond, Jean-Louis Mestas, Cyril Lafon, and Shin-ichiro Umemura
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Beamforming ,Meat ,Acoustics and Ultrasonics ,Computer science ,Acoustics ,Models, Biological ,01 natural sciences ,Displacement (vector) ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Histotripsy ,0302 clinical medicine ,Position (vector) ,Region of interest ,0103 physical sciences ,Animals ,Computer Simulation ,Electrical and Electronic Engineering ,010301 acoustics ,Instrumentation ,Hydrophone ,Phantoms, Imaging ,business.industry ,Ultrasound ,Water ,Equipment Design ,Cavitation ,High-Intensity Focused Ultrasound Ablation ,business ,Chickens - Abstract
Cavitation is a critical parameter in various therapeutic applications involving ultrasound (US) such as histotripsy, lithotripsy, drug delivery, and cavitation-enhanced hyperthermia. A cavitation exposure outside the region of interest may lead to suboptimal treatment efficacy or in a worse case, to safety issues. Current methods of localizing cavitation are based on imaging approaches, such as beamforming the cavitation signals received passively by a US imager. These methods, although efficient, require expensive equipment, which may discourage potential future developments. We propose a three-hydrophone method to localize the cavitation cloud source. First, the delays between the three receptors are measured by detecting the maximum of their intercorrelations. Then, the position of the source is calculated by either minimizing a cost function or solving hyperbolic equations. After a numerical validation, the method was assessed experimentally. This method was able to track a source displacement with accuracy similar to the size of the cavitation cloud (2-4 mm). This light and versatile method provides interesting perspectives since localization can be executed in real time, and the extension to 3-D localization seems straightforward.
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- 2018
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5. Numerical study of a confocal ultrasonic setup for cavitation creation
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Fabrice Prieur, Maxime Lafond, Jean-Louis Mestas, Cyril Lafon, and Françoise Chavrier
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Absorption (acoustics) ,Focal point ,Materials science ,Acoustics and Ultrasonics ,business.industry ,Confocal ,Acoustics ,01 natural sciences ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Cardinal point ,Optics ,Transducer ,Nonlinear acoustics ,Arts and Humanities (miscellaneous) ,Cavitation ,0103 physical sciences ,otorhinolaryngologic diseases ,Ultrasonic sensor ,business ,010301 acoustics - Abstract
Acoustic cavitation has found a wide range of applications in the last few decades. For potential applications involving cavitation, the acoustic characteristics of a confocal ultrasonic setup are studied: two high-intensity focused ultrasound transducers are mounted so that their focal points overlap. A mathematical simulator is developed that takes into account nonlinear propagation, absorption, and diffraction. Each one of these physical effects is solved in the frequency domain for successive planes. Comparing the confocal setup with equivalent single transducer setups, it is shown that, with the confocal configuration, nonlinear distortion of the waveform is reduced, resulting in a greater peak rarefactional pressure and a lower peak positive pressure. Furthermore, additional features are investigated for confocal configurations such as a greater spatial stability for the focal point, which can be maintained while increasing the pressure level, and a focal region consisting of interference acting as an acoustic trap.
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- 2017
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6. Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast Agents
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Maxime Lafond, Cyril Lafon, Kamel Chettab, Charles Dumontet, Jean-Louis Mestas, Djamel Eddine Saadna, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Application des ultrasons à la thérapie ( LabTAU ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 14, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
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Programmed cell death ,Cell Survival ,medicine.medical_treatment ,Contrast Media ,Pharmaceutical Science ,Antineoplastic Agents ,Tumor cells ,02 engineering and technology ,Pharmacology ,doxorubicin ,Suspension culture ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,cavitation ,Cell Line, Tumor ,Drug Discovery ,polycyclic compounds ,medicine ,Humans ,Ultrasonics ,Doxorubicin ,Ultrasonography ,business.industry ,Chemistry ,Ultrasound ,021001 nanoscience & nanotechnology ,High-intensity focused ultrasound ,3. Good health ,cell death ,030220 oncology & carcinogenesis ,Molecular Medicine ,0210 nano-technology ,business ,Sonoporation ,Intracellular ,medicine.drug - Abstract
International audience; Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents. The device was used to potentiate the delivery of active doxorubicin into both adherent and suspended cell lines. Combining doxorubicin with ultrasound resulted in a significant enhancement of doxorubicin intracellular delivery and a decrease in cell viability at 48 and 72 h, in comparison to doxorubicin alone. More importantly and unlike previous investigations, our procedure does not require the addition of contrast agents to generate acoustic cavitation and to achieve high levels of doxorubicin delivery. The successful translation of this approach for an in vivo application may allow a significant reduction in the dosage and the adverse effects of doxorubicin therapy in patients.
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- 2017
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7. Ultrasound-mediated ocular delivery of therapeutic agents: a review
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Cyril Lafon, Jean-Louis Mestas, Florent Aptel, and Maxime Lafond
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Eye Diseases ,medicine.medical_treatment ,Pharmaceutical Science ,Bioinformatics ,Cornea ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,In vivo ,medicine ,Humans ,Sound wave ,Ultrasonography ,Corneal epithelium ,business.industry ,Ultrasound ,Macular degeneration ,medicine.disease ,High-intensity focused ultrasound ,030104 developmental biology ,medicine.anatomical_structure ,Pharmaceutical Preparations ,030220 oncology & carcinogenesis ,Drug delivery ,business ,Ex vivo - Abstract
Due to numerous anatomical and physiological barriers, ocular drug delivery remains a major limitation in the treatment of diseases such as glaucoma, macular degeneration or inflammatory diseases. To date, only invasive approaches provide clinically effective results. Ultrasound can be defined as the propagation of a high-frequency sound wave exposing the propagation media to mechanical and thermal effects. Ultrasound has been proposed as a non-invasive physical agent for increasing therapeutic agent delivery in various fields of medicine. Areas covered: An update on recent advances in transscleral and transcorneal ultrasound-mediated drug delivery is presented. Efficient drug delivery is achieved in vitro, ex vivo and in vivo for various types of materials. Numerous studies indicate that efficacy is related to cavitation. Although slight reversible effects can be observed on the corneal epithelium, efficient drug delivery can be performed without causing damage to the cornea. Expert opinion: Recent developments prove the potential of ultrasound-mediated ocular drug delivery. Cavitation appears to be a preponderant mechanism, opening a way to treatment monitoring by cavitation measurement. Even if no clinical studies have yet been performed, the promising results summarized here are promoting developments toward clinical applications, particularly in assessing the safety of the technique.
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- 2016
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8. Abstract LB-078: Effect of a combined immune checkpoint inhibitor and mechanical focused ultrasound treatment on intratumoral immune response in a MC38 preclinical model
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Doriane Mathe, Cyril Lafon, Loic Daunizeau, Morgane Denis, Stéphane Depil, Christophe Caux, Cécile Fant, Jean-Louis Mestas, Pierre-Antoine Choffour, Frederic Padilla, Chloé Grasselly, and Charles Dumontet
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Cancer Research ,education.field_of_study ,LAG3 ,Myeloid ,business.industry ,Population ,FOXP3 ,Immune system ,medicine.anatomical_structure ,Oncology ,Antigen ,TIGIT ,Cancer research ,medicine ,Tumor necrosis factor alpha ,business ,education - Abstract
Recent preclinical and clinical data suggest that Focused ultrasound (FUS) can enhance host antitumor immune response. FUS is a minimally invasive therapy focusing beams of high power ultrasound to locally induce tissue damage such as thermal necrosis or apoptosis, approved for treatment of some solid malignancies. As a result, there is an interest in combining FUS and immune checkpoint inhibitors (ICI) to enhance ICI response. However, the effect of such combined treatment on the immune response remains unclear. We have evaluated the combination of anti-PD1 and FUS in the MC38 preclinical colon cancer model. FUS was delivered using a confocal device generating and monitoring mechanical cavitational ultrasound (peak negative pressure -20.5MPa). Mice were treated each week with FUS three days before injections of anti-PD1 antibodies. A longitudinal follow-up of tumor growth and overall survival was performed. Lymphoid and myeloid intratumoral immune cells were assessed by flow cytometry on days one, three and six after the start of the combined treatment, including expression levels of co-inhibitory and co-stimulatory molecules such as PD1, PDL-1, TIGIT, LAG3, TIM3 and ICOS. Combined treatment of FUS and ICI led to significant increased survival (up to three-fold for the combination compared to control) and improved tumor growth control. Flow cytometry revealed various changes in lymphoid as well as myeloid populations. The CD8+ TNFa+ / CD4+ FoxP3+ cells ratio was increased for combined group compared to non-treated, the fraction of CD11b+ cells in treated groups was increased and could be explained by an increase in the granulocyte population. Moreover, ICI and FUS combination may lead to increased antigen priming as increased CD11c+ CMHIIhigh conventional dendritic cells (DC), activated CD8- and Sirpa-CD24- subpopulations were found. As for co-inhibitory and co-stimulatory molecules expression at cell surface, flow cytometry showed increased PD1 and LAG3 expression by CD8+ cells on day 1 (respectively two- and three-fold increases for combined group compared to control); an increased TIM3 expression by CD4+ cells for combined group on day 3;an increased PD1 expression by CD4+ cells for FUS-treated groups and by tumor cells for combined group on day 6; increased PDL1 and TIGIT expression by CD8+ cells on day 6. Combination of therapeutic ultrasound and anti PD1 results in a significant improvement in tumor growth control and survival, possibly through significant changes in immune infiltrate such as increased activated CD8+ cells / inhibitory CD4+ cells ratio, an important clinical biomarker of response, increased granulocyte cell populations and an increased DC-mediated response. However, the combined treatment led to increased PD1 expression, as well as of other co-inhibitory molecules, by CD4+, CD8+ and tumor cells possibly explaining the transient effect of the combination. Our observation carries important implications for future FUS/ICI therapies at clinical and mechanistic levels. Citation Format: Cécile Fant, Chloé Grasselly, Morgane Denis, Doriane Mathé, Pierre-Antoine Choffour, Loic Daunizeau, Jean-Louis Mestas, Cyril Lafon, Christophe Caux, Stéphane Depil, Charles Dumontet, Frédéric Padilla. Effect of a combined immune checkpoint inhibitor and mechanical focused ultrasound treatment on intratumoral immune response in a MC38 preclinical model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-078.
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- 2020
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9. Evaluation of a Three Hydrophones Method for 2-Dimensional Cavitation Localization
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Maxime, Lafond, Nicolas, Asquier, Jean-Louis, Mestas, Alexandre, Carpentier, Shin-Ichiro, Umemura, and Cyril, Lafon
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Cavitation is a critical parameter in various therapeutic applications involving ultrasound (US) such as histotrispy, lithothripsy, drug delivery, and cavitation-enhanced hyperthermia. A cavitation exposure outside the region of interest may lead to suboptimal treatment efficacy or in a worse case, to safety issues. Current methods of localizing cavitation are based on imaging approaches, such as beamforming the cavitation signals received passively by a US imager. These methods, although efficient, require expensive equipment, which may discourage potential future developments. We propose a threehydrophone method to localize the cavitation cloud source. Firstly, the delays between the three receptors are measured by detecting the maximum of their inter-correlations. Then, the position of the source is calculated by either minimizing a cost function or solving hyperbolic equations. After a numerical validation, the method was assessed experimentally. This method was able to track a source displacement with accuracy similar to the size of the cavitation cloud (2-4 millimeters). This light and versatile method provides interesting perspectives since localization can be executed in real time and the extension to three-dimensional localization seems straightforward.
- Published
- 2018
10. Feasibility and main mechanisms underlying in vivo ultrasound neurostimulation of the ventral nerve cord's giant axons of lumbricus terrestris
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Jeremy Vion-Bailly, W. Apoutou N'Djin, Jean-Louis Mestas, and Jean-Yves Chapelon
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- 2017
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11. International Society for Therapeutic Ultrasound Conference 2016
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Brian Fowlkes, Pejman Ghanouni, Narendra Sanghvi, Constantin Coussios, Paul C. Lyon, Michael Gray, Christophoros Mannaris, Marie de Saint Victor, Eleanor Stride, Robin Cleveland, Robert Carlisle, Feng Wu, Mark Middleton, Fergus Gleeson, Jean-Franҫois Aubry, Kim Butts Pauly, Chrit Moonen, Jacob Vortman, Shirley Sharabi, Dianne Daniels, David Last, David Guez, Yoav Levy, Alexander Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Zion Zibly, Yael Mardor, Sagi Harnof, Michael Plaksin, Yoni Weissler, Shy Shoham, Eitan Kimmel, Omer Naor, Nairouz Farah, Dong-Guk Paeng, Zhiyuan Xu, John Snell, Anders H. Quigg, Matthew Eames, Changzhu Jin, Ashli C. Everstine, Jason P. Sheehan, Beatriz S. Lopes, Neal Kassell, Thomas Looi, Vera Khokhlova, Charles Mougenot, Kullervo Hynynen, James Drake, Michael Slayton, Richard C. Amodei, Keegan Compton, Ashley McNelly, Daniel Latt, John Kearney, David Melodelima, Aurelien Dupre, Yao Chen, David Perol, Jeremy Vincenot, Jean-Yves Chapelon, Michel Rivoire, Wei Guo, Guoxin Ren, Guofeng Shen, Michael Neidrauer, Leonid Zubkov, Michael S. Weingarten, David J. Margolis, Peter A. Lewin, Nathan McDannold, Jonathan Sutton, Natalia Vykhodtseva, Margaret Livingstone, Thiele Kobus, Yong-Zhi Zhang, Michael Schwartz, Yuexi Huang, Nir Lipsman, Jennifer Jain, Martin Chapman, Tejas Sankar, Andres Lozano, Robert Yeung, Christakis Damianou, Nikolaos Papadopoulos, Omer Brokman, Eyal Zadicario, Ori Brenner, David Castel, Shih-Ying Wu, Julien Grondin, Wenlan Zheng, Marc Heidmann, Maria Eleni Karakatsani, Carlos J. Sierra Sánchez, Vincent Ferrera, Elisa E. Konofagou, Marinos Yiannakou, HongSeok Cho, Hwayoun Lee, Mun Han, Jong-Ryul Choi, Taekwan Lee, Sanghyun Ahn, Yongmin Chang, Juyoung Park, Nicholas Ellens, Ari Partanen, Keyvan Farahani, Raag Airan, Alexandre Carpentier, Michael Canney, Alexandre Vignot, Cyril Lafon, Jean-yves Delattre, Ahmed Idbaih, Henrik Odéen, Bradley Bolster, Eun Kee Jeong, Dennis L. Parker, Pooja Gaur, Xue Feng, Samuel Fielden, Craig Meyer, Beat Werner, William Grissom, Michael Marx, Hans Weber, Valentina Taviani, Brian Hargreaves, Jun Tanaka, Kentaro Kikuchi, Ayumu Ishijima, Takashi Azuma, Kosuke Minamihata, Satoshi Yamaguchi, Teruyuki Nagamune, Ichiro Sakuma, Shu Takagi, Mathieu D. Santin, Laurent Marsac, Guillaume Maimbourg, Morgane Monfort, Benoit Larrat, Chantal François, Stéphane Lehéricy, Mickael Tanter, Gesthimani Samiotaki, Shutao Wang, Camilo Acosta, Eliza R. Feinberg, Zsofia I. Kovacs, Tsang-Wei Tu, Georgios Z. Papadakis, William C. Reid, Dima A. Hammoud, Joseph A. Frank, Zsofia i. Kovacs, Saejeong Kim, Neekita Jikaria, Michele Bresler, Farhan Qureshi, Jingjing Xia, Po-Shiang Tsui, Hao-Li Liu, Juan C. Plata, Bragi Sveinsson, Vasant A. Salgaonkar, Matthew Adams, Chris Diederich, Eugene Ozhinsky, Matthew D. Bucknor, Viola Rieke, Andrew Mikhail, Lauren Severance, Ayele H. Negussie, Bradford Wood, Martijn de Greef, Gerald Schubert, Mario Ries, Megan E. Poorman, Mary Dockery, Vandiver Chaplin, Stephanie O. Dudzinski, Ryan Spears, Charles Caskey, Todd Giorgio, Marcia M. Costa, Efthymia Papaevangelou, Anant Shah, Ian Rivens, Carol Box, Jeff Bamber, Gail ter Haar, Scott R. Burks, Matthew Nagle, Ben Nguyen, Blerta Milo, Nhan M. Le, Shaozhen Song, Kanheng Zhou, Ghulam Nabi, Zhihong Huang, Shmuel Ben-Ezra, Shani Rosen, Senay Mihcin, Jan Strehlow, Ioannis Karakitsios, Nhan Le, Michael Schwenke, Daniel Demedts, Paul Prentice, Sabrina Haase, Tobias Preusser, Andreas Melzer, Jean-Louis Mestas, Kamel Chettab, Gustavo Stadthagen Gomez, Charles Dumontet, Bettina Werle, Fabrice Marquet, Pierre Bour, Fanny Vaillant, Sana Amraoui, Rémi Dubois, Philippe Ritter, Michel Haïssaguerre, Mélèze Hocini, Olivier Bernus, Bruno Quesson, Amit Livneh, Dan Adam, Justine Robin, Bastien Arnal, Mathias Fink, Mathieu Pernot, Tatiana D. Khokhlova, George R. Schade, Yak-Nam Wang, Wayne Kreider, Julianna Simon, Frank Starr, Maria Karzova, Adam Maxwell, Michael R. Bailey, Jonathan E. Lundt, Steven P. Allen, Jonathan R. Sukovich, Timothy Hall, Zhen Xu, Philip May, Daniel W. Lin, Charlotte Constans, Thomas Deffieux, Jean-Francois Aubry, Eun-Joo Park, Yun Deok Ahn, Soo Yeon Kang, Dong-Hyuk Park, Jae Young Lee, J. Vidal-Jove, E. Perich, A. Ruiz, A. Jaen, N. Eres, M. Alvarez del Castillo, Rachel Myers, James Kwan, Christian Coviello, Cliff Rowe, Calum Crake, Sean Finn, Edward Jackson, Antonios Pouliopoulos, Caiqin Li, Marc Tinguely, Meng-Xing Tang, Valeria Garbin, James J. Choi, Lisa Folkes, Michael Stratford, Sandra Nwokeoha, Tong Li, Navid Farr, Samantha D’Andrea, Kayla Gravelle, Hong Chen, Donghoon Lee, Joo Ha Hwang, Sophie Tardoski, Jacqueline Ngo, Evelyne Gineyts, Jean-Pau Roux, Philippe Clézardin, Allegra Conti, Rémi Magnin, Matthieu Gerstenmayer, François Lux, Olivier Tillement, Sébastien Mériaux, Stefania Della Penna, Gian Luca Romani, Erik Dumont, Tao Sun, Chanikarn Power, Eric Miller, Oleg Sapozhnikov, Sergey Tsysar, Petr V. Yuldashev, Victor Svet, Dongli Li, Antonio Pellegrino, Nik Petrinic, Clive Siviour, Antoine Jerusalem, Peter V. Yuldashev, Bryan W. Cunitz, Barbrina Dunmire, Claude Inserra, Matthieu Guedra, Cyril Mauger, Bruno Gilles, Maxim Solovchuk, Tony W. H. Sheu, Marc Thiriet, Yufeng Zhou, Esra Neufeld, Christian Baumgartner, Davnah Payne, Adamos Kyriakou, Niels Kuster, Xu Xiao, Helen McLeod, Christopher Dillon, Allison Payne, Vera A. Khokhova, Ilya Sinilshchikov, Yulia Andriyakhina, Andrey Rybyanets, Natalia Shvetsova, Alex Berkovich, Igor Shvetsov, Caroline J. Shaw, John Civale, Dino Giussani, Christoph Lees, Valery Ozenne, Solenn Toupin, Vasant Salgaonkar, Elena Kaye, Sebastien Monette, Majid Maybody, Govindarajan Srimathveeravalli, Stephen Solomon, Amitabh Gulati, Mario Bezzi, Jürgen W. Jenne, Thomas Lango, Michael Müller, Giora Sat, Christine Tanner, Stephan Zangos, Matthias Günther, Au Hoang Dinh, Emilie Niaf, Flavie Bratan, Nicolas Guillen, Rémi Souchon, Carole Lartizien, Sebastien Crouzet, Olivier Rouviere, Yang Han, Thomas Payen, Carmine Palermo, Steve Sastra, Kenneth Olive, Johanna M. van Breugel, Maurice A. van den Bosch, Benjamin Fellah, Denis Le Bihan, Luis Hernandez-Garcia, Charles A. Cain, Erasmia Lyka, Delphine Elbes, Chunhui Li, Satoshi Tamano, Hayato Jimbo, Shin Yoshizawa, Keisuke Fujiwara, Kazunori Itani, Shin-ichiro Umemura, Dan Stoianovici, Zulfadhli Zaini, Ryo Takagi, Shenyan Zong, Ron Watkins, Aurea Pascal-Tenorio, Peter Jones, Kim Butts-Pauly, Donna Bouley, Yazhu Chen, Chung-Yin Lin, Han-Yi Hsieh, Kuo-Chen Wei, Camille Garnier, Gilles Renault, Reza Seifabadi, Emmanuel Wilson, Avinash Eranki, Peter Kim, Dennis Lübke, Peter Huber, Joachim Georgii, Caroline V. Dresky, Julian Haller, Pavel Yarmolenko, Karun Sharma, Haydar Celik, Guofeng Li, Weibao Qiu, Hairong Zheng, Meng-Yen Tsai, Po-Chun Chu, Taylor Webb, Urvi Vyas, Matthew Walker, Jidan Zhong, Adam C. Waspe, Mojgan Hodaie, Feng-Yi Yang, Sin-Luo Huang, Yuval Zur, Benny Assif, Christian Aurup, Hermes Kamimura, Antonio A. Carneiro, Sven Rothlübbers, Julia Schwaab, Graeme Houston, Haim Azhari, Noam Weiss, Jacob Sosna, S. Nahum Goldberg, Victor Barrere, Kee W. Jang, Bobbi Lewis, Xiaotong Wang, Visa Suomi, David Edwards, Zahary Larrabee, Arik Hananel, Boaz Rafaely, Rasha Elaimy Debbiny, Carmel Zeltser Dekel, Michael Assa, George Menikou, Petros Mouratidis, José A. Pineda-Pardo, Marta Del Álamo de Pedro, Raul Martinez, Frida Hernandez, Silvia Casas, Carlos Oliver, Patricia Pastor, Lidia Vela, Jose Obeso, Paul Greillier, Ali Zorgani, Stefan Catheline, Vyacheslav Solovov, Michael O. Vozdvizhenskiy, Andrew E. Orlov, Chueh-Hung Wu, Ming-Kuan Sun, Tiffany T. Shih, Wen-Shiang Chen, Fabrice Prieur, Arnaud Pillon, Valerie Cartron, Patrick Cebe, Nathalie Chansard, Maxime Lafond, Pauline Muleki Seya, Jean-Christophe Bera, Tanguy Boissenot, Elias Fattal, Alexandre Bordat, Helene Chacun, Claire Guetin, Nicolas Tsapis, Kazuo Maruyama, Johan Unga, Ryo Suzuki, Cécile Fant, Bernadette Rogez, Mercy Afadzi, Ola Finneng Myhre, Siri Vea, Astrid Bjørkøy, Petros Tesfamichael Yemane, Annemieke van Wamel, Sigrid Berg, Rune Hansen, Bjørn Angelsen, and Catharina Davies
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0301 basic medicine ,medicine.medical_specialty ,Therapeutic ultrasound ,business.industry ,Tel aviv ,medicine.medical_treatment ,02 engineering and technology ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,030104 developmental biology ,Ophthalmology ,medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,0210 nano-technology ,business - Published
- 2017
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12. Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model
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Esben A. Nilssen, Tove J. Evjen, Sigrid L. Fossheim, Sabrina Chesnais, Lucie Somaglino, Alexei Moussatov, Jean-Louis Mestas, Jacqueline Ngo, R. Andrew Fowler, Cyril Lafon, and Sibylla Røgnvaldsson
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Pathology ,medicine.medical_specialty ,Ultrasonic Therapy ,Confocal ,Pharmaceutical Science ,Pharmacology ,Random Allocation ,Drug Delivery Systems ,Pharmacokinetics ,In vivo ,medicine ,Animals ,Doxorubicin ,Ultrasonography ,Liposome ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,business.industry ,Chemistry ,Ultrasound ,Neoplasms, Experimental ,Rats ,Liposomes ,Toxicity ,Drug delivery ,business ,medicine.drug - Abstract
The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.
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- 2014
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13. In vivo monitoring of liposomal release in tumours following ultrasound stimulation
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Alexei Moussatov, Cyril Lafon, Jean-Louis Mestas, Esben A. Nilssen, R. Andrew Fowler, Eirik Hagtvet, Sibylla Røgnvaldsson, and Tove J. Evjen
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Male ,Indoles ,Time Factors ,Confocal ,Analytical chemistry ,Pharmaceutical Science ,Isoindoles ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Optical imaging ,Chlorides ,In vivo ,Phosphatidylcholine ,Animals ,Ultrasonics ,Fluorescent Dyes ,Mice, Inbred BALB C ,Liposome ,Microscopy, Confocal ,Chemistry ,Phosphatidylethanolamines ,General Medicine ,Fluorescence ,In vitro ,Liposomes ,Drug delivery ,Biophysics ,Sulfonic Acids ,Aluminum ,Biotechnology - Abstract
Dioeleoylphosphatidylethanolamine (DOPE)-based liposomes were recently reported as a new class of liposomes for ultrasound (US)-mediated drug delivery. The liposomes showed both high stability and in vitro US-mediated drug release (sonosensitivity). In the current study, in vivo proof-of-principle of US triggered release in tumoured mice was demonstrated using optical imaging. Confocal non-thermal US was used to deliver cavitation to tumours in a well-controlled manner. To detect in vivo release, the near infrared fluorochrome Al (III) Phthalocyanine Chloride Tetrasulphonic acid (AlPcS₄) was encapsulated into both DOPE-based liposomes and control liposomes based on hydrogenated soy phosphatidylcholine (HSPC). Encapsulation causes concentration dependent quenching of fluorescence that is recovered upon AlPcS₄ release from the liposomes. Exposure of tumours to US resulted in a significant increase in fluorescence in mice administered with DOPE-based liposomes, but no change in the mice treated with HSPC-based liposomes. Thus, DOPE-based liposomes showed superior sonosensitivity compared to HSPC-based liposomes in vivo.
- Published
- 2013
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14. Feasibility study of cavitation-induced liposomal doxorubicin release in an AT2 Dunning rat tumor model
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Guillaume Bouchoux, Jacqueline Ngo, Sigrid L. Fossheim, Cyril Lafon, Jean-Louis Mestas, Esben A. Nilssen, Jean-Yves Chapelon, Jean Martial Mari, Sabrina Chesnais, and Lucie Somaglino
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Drug ,Liposome ,business.industry ,media_common.quotation_subject ,Therapeutic effect ,Ultrasound ,Pharmaceutical Science ,Neoplasms, Experimental ,Pharmacology ,Rats ,Disease Models, Animal ,Drug Delivery Systems ,Pharmacokinetics ,Doxorubicin ,In vivo ,Drug delivery ,medicine ,Animals ,Feasibility Studies ,Ultrasonics ,business ,medicine.drug ,media_common - Abstract
Background Targeted and triggered release of liposomal drug using heat or ultrasound represents a promising treatment modality able to increase the therapeutic-totoxicity ratio of encapsulated drugs. Purpose To study the ability for high-intensity focused ultrasound to induce liposomal drug release mainly by focused inertial cavitation in vitro and in an animal model. Methods A 1 MHz ultrasound setup has been developed for in vitro and in vivo drug release from a specific liposomal doxorubicin formulation at a target cavitation dose. Results Controlled cavitation at 1 MHz was applied within the tumors 48 hours after liposome injection according to preliminary pharmacokinetic study. A small non-significant therapeutic effect of US-liposomal treatment was observed compared to liposomes alone suggesting no beneficial effect of ultrasound in the current setup. Conclusion The in vitro study provided a suitable ultrasound setup for delivering a cavitation dose appropriate for safe liposomal drug release. However, when converting to an in vivo model, no therapeutic benefit was observed. This may be due to a number of reasons, one of which may be the difficulty in converting in vitro findings to an in vivo model. In light of these findings, we discuss important design features for future studies.
- Published
- 2012
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15. In vitro sonodynamic cytotoxicity in regulated cavitation conditions
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Laurent Alberti, Jean-Louis Mestas, Jhony El Maalouf, D. Cathignol, and Jean-Christophe Béra
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Ultrasound device ,Acoustics and Ultrasonics ,Cell Survival ,Acoustics ,Antineoplastic Agents ,In Vitro Techniques ,Cell Line ,chemistry.chemical_compound ,Tumor Cells, Cultured ,Animals ,Ultrasonics ,Cytotoxicity ,Hematoporphyrin ,Cytotoxins ,business.industry ,Sonodynamic therapy ,Ultrasound ,Equipment Design ,In vitro ,Rats ,chemistry ,Cavitation ,Biophysics ,Regression Analysis ,Dihematoporphyrin Ether ,business - Abstract
Sonodynamic toxicity has always been linked to the cavitation phenomenon. In this work, sonodynamic effect with Photofrin was evaluated with a new ultrasound device: a regulated cavitation generator. In this way, acoustic intensity was substituted with cavitation level as ultrasound parameter. Photofrin potentiated significantly the cavitation cytotoxicity even for low setpoints where no inertial cavitation appeared. Therefore sonodynamic mechanism was principally mechanical, facilitated by the Photofrin insertion in cellular cytoplasmic membranes. This assertion was also supported by the fact that sonodynamic cytotoxicity was independent from the Photofrin presence or absence in the extracellular medium. Reproducible sonodynamic efficiency was perfectly obtained with this new regulated cavitation generator.
- Published
- 2009
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16. Observation of a cavitation cloud in tissue using correlation between ultrafast ultrasound images
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Cyril Lafon, Rémi Souchon, Stefan Catheline, Maxime Lafond, Fabrice Prieur, Ali Zorgani, and Jean-Louis Mestas
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Materials science ,Acoustics and Ultrasonics ,business.industry ,Acoustics ,Ultrasound ,Transducers ,Signal Processing, Computer-Assisted ,Equipment Design ,Signal-To-Noise Ratio ,Frame rate ,Models, Biological ,Speckle pattern ,Transducer ,Optics ,Cavitation ,Animals ,Imaging Signal ,Electrical and Electronic Engineering ,business ,Muscle, Skeletal ,Instrumentation ,Decorrelation ,Ultrashort pulse ,Chickens ,Ultrasonography - Abstract
The local application of ultrasound is known to improve drug intake by tumors. Cavitating bubbles are one of the contributing effects. A setup in which two ultrasound transducers are placed confocally is used to generate cavitation in ex vivo tissue. As the transducers emit a series of short excitation bursts, the evolution of the cavitation activity is monitored using an ultrafast ultrasound imaging system. The frame rate of the system is several thousands of images per second, which provides several tens of images between consecutive excitation bursts. Using the correlation between consecutive images for speckle tracking, a decorrelation of the imaging signal appears due to the creation, fast movement, and dissolution of the bubbles in the cavitation cloud. By analyzing this area of decorrelation, the cavitation cloud can be localized and the spatial extent of the cavitation activity characterized.
- Published
- 2015
17. Enhancement of Fluorescent Probe Penetration into Tumors In Vivo Using Unseeded Inertial Cavitation
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Maxime Lafond, Fabrice Prieur, Cyril Lafon, Valérie Cartron, Nathalie Chansard, Arnaud Pillon, Patrick Cèbe, and Jean-Louis Mestas
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Materials science ,Acoustics and Ultrasonics ,Sonication ,Biophysics ,Cancer therapy ,Melanoma, Experimental ,Mice, Nude ,Nanotechnology ,02 engineering and technology ,01 natural sciences ,Mice ,In vivo ,0103 physical sciences ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,010301 acoustics ,Fluorescent Dyes ,Radiological and Ultrasound Technology ,business.industry ,Ultrasound ,Penetration (firestop) ,Equipment Design ,021001 nanoscience & nanotechnology ,Fluorescence ,Disease Models, Animal ,Ultrasonic Waves ,Cavitation ,Female ,0210 nano-technology ,business ,Sonoporation ,Biomedical engineering - Abstract
Ultrasound-induced cavitation has found many applications in the field of cancer therapy. One of its beneficial effects is the enhancement of drug intake by tumor cells. Our group has developed a device that can create and control unseeded cavitation in tissue using ultrasound. We conducted experiments on tumor-bearing mice using our device to assess the impact of sonication on the penetration of fluorescent probes into tumor cells. We studied the influence of pressure level, timing of sonication and sonication duration on treatment efficiency. Our results indicate that fluorescent probes penetrate better into tumors exposed to ultrasound. The best results revealed an increase in penetration of 61% and were obtained when sonicating the tumor in presence of the probes with a peak negative pressure at focus of 19 MPa. At this pressure level, the treatment generated only minor skin damage. Treatments could be significantly accelerated as equivalent enhanced penetration of probes was achieved when multiplying the initial raster scan speed by a factor of four.
- Published
- 2015
18. Unseeded Inertial Cavitation for Enhancing the Delivery of Chemotherapies: A Safety Study
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Maxime Lafond, Fabrice Prieur, Philippe Clézardin, Kamel Chettab, Cyril Lafon, Sandra Geraci, and Jean-Louis Mestas
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Pathology ,medicine.medical_specialty ,Acoustics and Ultrasonics ,Confocal ,Biophysics ,Breast Neoplasms ,02 engineering and technology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Drug Delivery Systems ,Medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Doxorubicin ,Ultrasonics ,Mice, Inbred BALB C ,Antibiotics, Antineoplastic ,Radiological and Ultrasound Technology ,business.industry ,Ultrasound ,021001 nanoscience & nanotechnology ,medicine.disease ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer cell ,Drug delivery ,Immunohistochemistry ,Female ,Bone marrow ,0210 nano-technology ,business ,medicine.drug - Abstract
Acoustic cavitation can improve local drug delivery in tumors. Without injected external nucleation agents, initiating inertial cavitation requires high negative pressures, which can lead to biological damage. In the present study, unseeded inertial cavitation was obtained in vivo using confocal beams, and the effect of these exposure conditions was assessed on drug structure and activity, shallow tissues and growth of breast tumors. No change was observed in the structure and cytotoxicity of doxorubicin. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histologic analyses at 72 h and 2 weeks post-treatment demonstrated a modest impact on tissues. Syngeneic 4 T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that ultrasound did not impact vascular density, proliferation and apoptosis of cancer cells. In addition, ultrasound did not negatively modify cancer cell spreading to the lungs and bone marrow. This provides evidence that these particular parameters can be used safely in vivo.
- Published
- 2015
19. Numerical study of a confocal ultrasonic setup for creation of cavitation
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Françoise Chavrier, Cyril Lafon, Fabrice Prieur, Maxime Lafond, and Jean-Louis Mestas
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Materials science ,business.industry ,Confocal ,Acoustics ,Rarefaction ,Sound power ,Histotripsy ,Transducer ,Optics ,Distortion ,Cavitation ,otorhinolaryngologic diseases ,Ultrasonic sensor ,business - Abstract
Acoustic cavitation is used for various therapeutic applications such as local enhancement of drug delivery, histotripsy or hyperthermia. One of the utmost important parameter for cavitation creation is the rarefaction pressure. The typical magnitude of the rarefaction pressure required to initiate cavitation from gas dissolved in tissue is beyond the range of the megapascal. Because nonlinear effects need to be taken into account, a numerical simulator based on the Westervelt equation was used to study the pressure waveform and the acoustic field generated by a setup for creation of cavitation consisting of two high intensity focused ultrasound transducers mounted confocally. At constant acoustic power, simulations with only one and both transducers from the confocal setup showed that the distortion of the pressure waveform due to the combined effects of nonlinearity and diffraction is less pronounced when both confocal transducers are used. Consequently, the confocal setup generates a greater peak negat...
- Published
- 2015
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20. Développement d’un dispositif expérimental ultrasonore pour le largage ciblé et contrôlé d’une chimiothérapie encapsulée
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Cyril Lafon, Guillaume Bouchoux, Sabrina Chesnais, A. Matias, Lucie Somaglino, Jean-Yves Chapelon, and Jean-Louis Mestas
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Gynecology ,medicine.medical_specialty ,Chemistry ,Biomedical Engineering ,Biophysics ,medicine - Abstract
Resume L’application d’ultrasons a des liposomes sonosensibles charges de chimiotherapie offre de nouvelles perspectives dans le traitement du cancer. Dans ce travail, des essais in vitro ont permis de definir un indice de cavitation pour permettre le suivi des traitements. Cet indice permet egalement d’evaluer la sonosensibilite de liposomes prototypes. Des experimentations ont ete conduites chez des rats porteurs de tumeurs sous-cutanees. Le temps de 48 heures apres injection a ete choisi pour l’application des ultrasons. Concernant le traitement, les liposomes ralentissent significativement la dynamique tumorale. Les ultrasons combines aux liposomes semblent contribuer au ralentissement du developpement de la tumeur. Cependant, la grande efficacite des liposomes seuls et la possible faible interaction avec les ultrasons ne permettent pas de garantir que l’effet des ultrasons est significatif.
- Published
- 2009
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21. Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery
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Aurélie Béglé, Fabrice Romano, David Clement, Alain Birer, Françoise Chavrier, Jean-Louis Mestas, Jean-Yves Chapelon, Arash Razavi, R. Andrew Fowler, and Cyril Lafon
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Materials science ,genetic structures ,Acoustics and Ultrasonics ,medicine.medical_treatment ,Biophysics ,In Vitro Techniques ,Sonication ,Optics ,Drug Delivery Systems ,medicine ,Low permeability ,Animals ,Radiology, Nuclear Medicine and imaging ,Radiological and Ultrasound Technology ,Therapeutic ultrasound ,Pulse (signal processing) ,business.industry ,eye diseases ,In vitro ,Sclera ,medicine.anatomical_structure ,Permeability (electromagnetism) ,Cavitation ,Drug delivery ,Fluorescein ,sense organs ,Rabbits ,business ,Biomedical engineering - Abstract
In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5–5.4 W (6.8–12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.
- Published
- 2013
22. Le principe de l'électrosection monopolaire appliquée en résection endoscopique
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Jean Louis Mestas, M. Devonec, J Jossinet, and Dominique Cathignol
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Gynecology ,medicine.medical_specialty ,Electric energy ,business.industry ,medicine ,Endoscopic surgery ,Prostate disease ,business ,Applied Microbiology and Biotechnology ,Biotechnology ,Resection - Abstract
Resume Les generateurs de frequences radiofrequences (RF) sont employes couramment en bloc operatoire. Ils sont generalement utilises comme source d'energie des resecteurs endoscopiques pour l'ablation de l'adenome prostatique. L'etude presentee decrit la physique de l'electrochirurgie avec l'utilisation des courants de frequence elevee pour la coupe et la coagulation, l'interface electrode-tissu d'electrodes dispersives (plaques) et d'electrodes actives (anses) et l'impedance electrique des tissus profonds. Les principales caracteristiques electriques des generateurs RF pour la coupe et l'hemostase sont illustrees par des mesures sur un appareil du commerce. L'energie delivree par le generateur inclut l'energie absorbee par l'interface plaque-peau et l'energie dissipee dans des circuits paralleles associes aux fuites de courant. Les differentes pertes electriques sont susceptibles d'engendrer des risques pour le patient et l'operateur. Les risques rencontres en resection endo-uretrale de la prostate sont recapitules afin d'en assurer un controle optimal.
- Published
- 1996
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23. Non-invasive magnetic resonance imaging follow-up of sono-sensitive liposome tumor delivery and controlled release after high-intensity focused ultrasound
- Author
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Sigrid L. Fossheim, Emmanuelle Canet-Soulas, Cyril Lafon, Jacqueline Ngo, Jean-Louis Mestas, and Robert A. Fowler
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Gadolinium DTPA ,Male ,Acoustics and Ultrasonics ,Gadolinium ,Confocal ,medicine.medical_treatment ,Biophysics ,chemistry.chemical_element ,Contrast Media ,Sensitivity and Specificity ,Nuclear magnetic resonance ,In vivo ,Cell Line, Tumor ,medicine ,Organometallic Compounds ,Animals ,Radiology, Nuclear Medicine and imaging ,Liposome ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Relaxation (NMR) ,Prostatic Neoplasms ,Reproducibility of Results ,Magnetic resonance imaging ,Pentetic Acid ,Controlled release ,Magnetic Resonance Imaging ,High-intensity focused ultrasound ,Rats ,Treatment Outcome ,chemistry ,Delayed-Action Preparations ,Liposomes ,High-Intensity Focused Ultrasound Ablation ,Follow-Up Studies - Abstract
This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1).
- Published
- 2012
24. Design and characterization of a shock wave generator using canalized electrical discharge: Application to lithotripsy
- Author
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Maurice Bourlion, Francois Lacoste, Dominique Cathignol, Paul Dancer, and Jean-Louis Mestas
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Shock wave ,Focal point ,Materials science ,law ,Acoustics ,Electrode ,Electric discharge ,Plasma ,Spark plug ,Instrumentation ,Electrical conductor ,Voltage ,law.invention - Abstract
During recent years, much work has focused on breaking urinary and biliary stones using extracorporeal shock wave devices. Up to now, in terms of fragmentation efficacy, the ‘‘electrohydraulic’’ principle is the gold standard. In an electrohydraulic shock wave generator, a plasma is created by a high‐voltage electrical discharge between two underwater electrodes. This kind of shock wave generator has a significant drawback because of the large variations of pressure pulses. Moreover, the wear of the electrodes is considerable, leading to nonconstant electrical discharge conditions all along the treatment. A new method to canalize the plasma between the electrodes, using highly conductive liquid, was investigated. Based on this principle a new spark plug was designed. This paper deals with the description and the characterization of this new type of spark plug. The electrical and geometrical parameters are presented. Measurements of the focal point pressure amplitude, of the spatial pressure distribution using different voltage settings, are reported. The acoustic energy in the focal zone is computed. We show that using this principle, the wear of the electrodes has been tremendously reduced. A comparison of in vitro results with other shock wave technologies shows that this new spark plug represents a significant breakthrough in terms of stone fragmentation efficacy. This spark plug is not only useful in the medical field, but it should also be of great interest to laboratories.
- Published
- 1994
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25. Feedback loop process for controlling inertial cavitation: experimental evidence
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Claude Inserra, Abbas Sabraoui, Lina Reslan, Jean-Christophe Bera, Bruno Gilles, Jean-Louis Mestas, Yoichiro Matsumoto, Lawrence A. Crum, and Gail Reinette ter Haar
- Subjects
Standing wave ,Work (thermodynamics) ,Materials science ,Sonication ,Cavitation ,Acoustics ,Feedback loop ,Sonoporation ,Sound intensity ,Sonochemistry - Abstract
Applications involving cavitation mechanisms, such as sonoporation, are irreproducible in the case of a fixed‐intensity sonication, due to the non‐stationary behavior of cavitation. We then propose to work at a fixed‐cavitation level instead of under fixed‐intensity sonication conditions. For this purpose a regulated cavitation generator has been developed in a stationary wave field configuration, which allows regulation of the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop based on acoustic cavitation measurements. The cavitation level indicator was quantified by the broadband spectrum noise level relative to inertial cavitation events. This generated inertial cavitation was characterized by both acoustic and chemical measurements, quantifying hydroxyl radicals produced by water sonolysis. While the cavitation level is obtained with a 40% standard deviation for fixed applied acoustic intensities in the range [0.01 3.44] W/cm2, the regulated generator ...
- Published
- 2011
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26. Texture Analysis of Ultrasonic Images of the Prostate by Means of Co-occurrence Matrices
- Author
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Jean-Louis Mestas
- Subjects
Radiological and Ultrasound Technology ,Radiology, Nuclear Medicine and imaging - Published
- 1993
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27. Feedback loop process to control acoustic cavitation
- Author
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Claude Inserra, Abbas Sabraoui, Jean-Louis Mestas, Bruno Gilles, and Jean-Christophe Béra
- Subjects
Materials science ,Time Factors ,Acoustics and Ultrasonics ,Acoustics ,Phthalic Acids ,Signal ,Feedback ,Inorganic Chemistry ,Standing wave ,Chemical Engineering (miscellaneous) ,Environmental Chemistry ,Radiology, Nuclear Medicine and imaging ,Ultrasonics ,Hydrophone ,business.industry ,Hydroxyl Radical ,Spectrum Analysis ,Organic Chemistry ,Ultrasound ,Reproducibility of Results ,Sound intensity ,Intensity (physics) ,Cavitation ,Gases ,business ,Sonoporation - Abstract
Applications involving acoustic cavitation mechanisms, such as sonoporation, are often poorly reproducible because of the unstationary behavior of cavitation. For this purpose, this study proposes to work at a fixed cavitation level instead of a fixed acoustic intensity. A regulated cavitation generator has been developed in an in vitro configuration of standing wave field. This system implements the regulation of the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop based on acoustic measurements. The experimental setup consists of a plane piezoelectric transducer for sonication (continuous wave, frequency 445 kHz) and a hydrophone pointing to the sonicated medium. The cavitation level is quantified every 5 ms from a spectral analysis of the acoustic signal. The results show that the regulation device generates reproducible mean cavitation levels with a standard deviation lower than 1.6% in the applied intensity range (from 0.12 to 3.44 W/cm 2 ), while this standard deviation can reach 76% without regulation. The feedback loop process imposes precise cavitation level even in low applied acoustic intensity.
- Published
- 2010
28. Validation of an acoustic cavitation dose with hydroxyl radical production generated by inertial cavitation in pulsed mode: application to in vitro drug release from liposomes
- Author
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Jean-Louis Mestas, Cyril Lafon, Lucie Somaglino, and Guillaume Bouchoux
- Subjects
Pulse repetition frequency ,Time Factors ,Acoustics and Ultrasonics ,Sonication ,Chemistry, Pharmaceutical ,Analytical chemistry ,Phthalic Acids ,Sonochemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,Chemical Engineering (miscellaneous) ,Environmental Chemistry ,Radiology, Nuclear Medicine and imaging ,Ultrasonics ,Dosimeter ,Chemistry ,business.industry ,Hydroxyl Radical ,Organic Chemistry ,Ultrasound ,Pulse duration ,Nanostructures ,Doxorubicin ,Cavitation ,Liposomes ,Hydroxyl radical ,Gases ,business - Abstract
The purpose of this study was to define and validate an inertial cavitation dose (CD) based on the detection of broadband noise, designed to monitor ultrasound-mediated drug release from liposomes. The validation consists of using the terephthalate dosimeter to quantify by fluorescence measurements the extent of hydroxyl radical ( OH) production during inertial cavitation. Sonication of samples was performed using tone bursts (pulse repetition frequency (PRF): 10 Hz −1 kHz, duty cycle (dc): 5–25%, Isppa: 4100–12,200 W/cm 2 ) generated by a 1 MHz focused transducer. Three sets of ultrasound parameters with different PRF and dc were selected to be more precisely compared. Results demonstrated an excellent correlation between OH radical production and CD for each set of parameters, but significant differences in hydroxyl radical levels were observed among the sets of parameters. The results were compared with other studies, and the same tendency of variation with pulse duration was demonstrated. Results also showed that the CD was not distorted by peak intensity variations and was a much more reliable indicator than sonication time. Consequently, one validated parameter was selected to monitor drug release from two liposome formulations, and compare their ultrasound sensitivity.
- Published
- 2010
29. Transfection of cells in suspension by ultrasound cavitation
- Author
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Stéphanie Herveau, Lina Reslan, Charles Dumontet, Jean-Louis Mestas, and Jean-Christophe Béra
- Subjects
Genetic enhancement ,bcl-X Protein ,Pharmaceutical Science ,Mice, SCID ,Gene delivery ,Biology ,Transfection ,Flow cytometry ,Mice ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Ultrasonics ,Viability assay ,RNA, Small Interfering ,Lymphoma, Follicular ,Cells, Cultured ,medicine.diagnostic_test ,Genetic transfer ,DNA ,Equipment Design ,Molecular biology ,Leukemia, Lymphoid ,Cell culture ,Female ,Sonoporation ,Plasmids - Abstract
Sonoporation holds many promises in developing an efficient, reproducible and permanent gene delivery vector. In this study, we evaluated sonoporation as a method to transfect nucleic acids in suspension cells, including the human follicular lymphoma cell line RL and fresh human Chronic Lymphocytic Leukemia (CLL) cells. RL and CLL cells were exposed to continuous ultrasound waves (445 kHz) in the presence of either plasmid DNA coding for green fluorescent protein (GFP) or fluorescent siRNA directed against BCL2L1. Transfection efficiency and cell viability were assessed using fluorescent microscopy and flow cytometry analysis, respectively. Knock-down of target protein by siRNA was assessed by immunoblotting. Moreover, sonoporation was used to stably transfect RL cells with a plasmid coding for luciferase (pGL3). These cells were then used for the non-invasive monitoring of tumorigenesis in immunodeficient SCID mice. Sonoporation allows a highly efficient transfection of nucleic acid in suspension cells with a low rate of mortality, both in a tumor cell line and in fresh human leukemic cells. It also allowed efficient transfection of BCL2L1 siRNA with efficient reduction of the target protein level. In conclusion, ultrasound cavitation represents an efficient method for the transfection of cells in suspension, including fresh human leukemic cells.
- Published
- 2009
30. Sonodynamic Cytotoxicity In Controlled Cavitation Conditions
- Author
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Jhony El Maalouf, Arnaud Salvador, Laurent Alberti, Sabrina Chesnais, Izella Saletes, Jean-Christophe Béra, Jean-Louis Mestas, and Emad S. Ebbini
- Subjects
chemistry.chemical_classification ,Reactive oxygen species ,chemistry ,Cavitation ,Biophysics ,Analytical chemistry ,Cytotoxicity - Abstract
Sonodynamic cytotoxicity was always linked to the inertial cavitation phenomenon. In this work, sonodynamic effects with Photofrin® were evaluated in controlled cavitation conditions.Photofrin® potentiated significantly the cavitation cytoxicity even for low setpoints where no inertial cavitation appeared. Moreover, the use of antioxidant histidine (10 mM) did not prevent the sonodynamic toxicity when inertial cavitation was preponderant. This was confirmed by mass spectrometry data showing no histidine transformation due to reactive oxygen species during sonodynamic experiments. The results show that sonodynamic mechanism would be principally mechanical, facilitated by the Photofrin® insertion in cellular cytoplasmic membranes.
- Published
- 2009
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31. Volume measurement by ultrasonic transverse or sagittal cross-sectional scanning
- Author
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Olivier Basset, Dominique Cathignol, Jean Louis Mestas, M. Devonec, Gérard Gimenez, Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Applications des ultrasons à la thérapie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
- Subjects
Male ,Materials science ,Acoustics and Ultrasonics ,Biophysics ,Volume estimation ,01 natural sciences ,Agar gel ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Optics ,Volume measurement ,0103 physical sciences ,Image Processing, Computer-Assisted ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,010301 acoustics ,ComputingMilieux_MISCELLANEOUS ,Ultrasonography ,Radiological and Ultrasound Technology ,business.industry ,Prostate ,Centroid ,Acoustics ,Reference Standards ,modelisationₚb_inverses ,Sagittal plane ,Models, Structural ,Transverse plane ,medicine.anatomical_structure ,categₘixte ,Ultrasonic sensor ,business ,Volume (compression) ,Biomedical engineering - Abstract
A technique is described that provides an accurate estimation of the volume of an organ from its ultrasonic cross-sectional images. The technique is applied to two types of ultrasonic investigation, one providing transverse and the other sagittal images. The organ outline has to be traced on each scan. The computer first calculates the area and then the volume from the vector areas and the centroids of a series of sections. The technique has been tested with phantoms of various shapes and volumes made with agar gel. These experiments show that the error in the volume estimation is less than 10% and the variability of measurements is less than 2%.
- Published
- 1991
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32. Extracorporeal lithotripsy of bile duct stones using ultrasonography for stone localization
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Alan N. Barkun, Thierry Ponchon, Jean-Louis Mestas, Christian Boustière, Xavier Martin, and Annick Chavaillon
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Bile Duct Diseases ,Lithotripsy ,Cholangiography ,Cholelithiasis ,medicine ,Humans ,Fluoroscopy ,Saline ,Aged ,Ultrasonography ,Aged, 80 and over ,Hepatology ,medicine.diagnostic_test ,Common bile duct ,business.industry ,Bile duct ,Gastroenterology ,Middle Aged ,Surgery ,Major duodenal papilla ,medicine.anatomical_structure ,Evaluation Studies as Topic ,Biliary tract ,Female ,Bile Ducts ,business - Abstract
In 19 patients, extraction of bile duct stones through the papilla using a Dormia basket or a mechanical lithotripter was not possible following endoscopic sphincterotomy. After the insertion of a nasobiliary drain, extracorporeal lithotripsy was performed with intravenous sedation using an ultrasonographic stone localization system. The number and location of stones were first determined by retrograde cholangiography. At the time of lithotripsy, saline was injected in the bile ducts to modify the acoustic impedance of tissues surrounding the stones, and subsequent ultrasonography was effective in localizing all stones present in 4 of 5 (80%) patients with intrahepatic stones, and 13 of 14 (93%) with common bile duct stones. In 10 patients (53%), fragmentation was satisfactory and the bile ducts were cleared completely. The mean single stone diameter was significantly smaller in successful cases of fragmentation compared with failures (22.8 ± 6.6 mm vs. 40 ± 10 mm). The results in patients with multiple stones were significantly worse than those in patients with single stones of similar size (25% vs. 100% successful fragmentation). Reasons for this difference in results included the small size of the focal area and the reduced ability of ultrasonography (1) to adequately visualize multiple calculi individually and (2) to assess the degree of stone destruction. Care was taken to first await the resolution of infection or the correction of coagulation abnormalities when present; no morbidity following extracorporeal lithotripsy was observed. Despite its 3-step approach (endoscopic sphincterotomy, lithotripsy, and endoscopic extraction), the need for only intravenous sedation and the absence of patient immersion in water render this technique attractive for elderly and frail patients.
- Published
- 1990
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- View/download PDF
33. INFLUENCE DE LA CONDUCTIVITÉ DE L'EAU SUR LA GÉNÉRATION DES ONDES DE CHOC
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P. Dancer, Jean-Louis Mestas, M. Bourlion, and Dominique Cathignol
- Subjects
General Engineering - Abstract
Le generateur electrohydraulique utilise en lithotritie est constitue d'un bol ellipsoidal rempli d'eau au foyer duquel sont disposees deux electrodes reliees a un condensateur par l'intermediaire d'un interrupteur. A la fermeture, un arc s'etablit, liberant une energie suffisante pour creer une onde de choc. L'etablissement du regime d'arc est un phenomene peu reproductible induisant des variations importantes de la valeur de la pression generee. Nous montrons que l'utilisation d'un liquide fortement conducteur a la place de l'eau permet de reduire l'ecart type sur les valeurs de pression mesurees de 30 a 2 %. La mesure des parametres electriques suggere que la decharge du condensateur ne se fait plus par l'intermediaire d'un arc mais par l'intermediaire de la resistance formee par le liquide situe entre les electrodes dont la valeur est proche de la resistance critique.
- Published
- 1990
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34. CAPTEURS DE PRESSION POUR LE CONTRÔLE DE GÉNÉRATEURS D'ONDES DE CHOC ÉLECTROHYDRAULIQUE
- Author
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Dominique Cathignol and Jean-Louis Mestas
- Subjects
Physics ,General Engineering - Published
- 1990
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- View/download PDF
35. A novel method to control P+/P- ratio of the shock wave pulses used in the extracorporeal piezoelectric lithotripsy (EPL)
- Author
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Jean-Louis Mestas, Dominique Cathignol, Peter A. Lewin, Jean-Yves Chapelon, and Alain Birer
- Subjects
Shock wave ,Ceramics ,Materials science ,Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,business.industry ,medicine.medical_treatment ,Acoustics ,Biophysics ,Lithotripsy ,Extracorporeal shock wave lithotripsy ,Extracorporeal ,Shock (mechanics) ,Pulse (physics) ,Optics ,Cavitation ,Harmonics ,Pressure ,medicine ,Humans ,Ultrasonics ,Radiology, Nuclear Medicine and imaging ,business - Abstract
There is growing evidence that acoustic cavitation plays an important role in stone fragmentation during extracorporeal shock wave lithotripsy (ESL) treatment. In addition, side effects of the treatment, such as the hemorrhage and destruction of the tissue in the vicinity of the stone are also ascribed to cavitation phenomenon. Since cavitation is associated with the maximum negative pressure in the shock pulse, it would thus appear that possibility of controlling this pressure would be desirable in ESL applications. This paper describes a novel technique developed to control the ratio of compressional peak (P+) to rarefactional peak pressure (P-) of the shock wave for use in lithotripsy treatment. The procedure is based on the finite amplitude wave generation by focused piezoelectric transducers and subsequent interaction of the shocked waves in the common focal region. The highly asymmetrical shock wave is produced in the focal region by providing an appropriate time delay to each of the high voltage electrical excitation signals which drive the transducers. The degree of relative reduction of negative halfcycles and the corresponding positive halfcycles amplification increases with the number of the acoustic sources used. The practical implementation of the shock wave generator was obtained by using 5 cm diameter, focused 1 MHz transmitter, and additional transducers of identical construction having frequencies corresponding to the harmonics and subharmonics of the 1 MHz frequency. The importance of the results for the future development of lithotripters, and stone treatment efficiency is pointed out.
- Published
- 1990
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36. The role of serum on photodynamic and sonodynamic cytotoxicity with Photofrin®
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Sabrina Chesnais, Jean Paul Steghens, Jhony El Maalouf, Dominique Cathignol, Jean-Louis Mestas, and Laurent Alberti
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Chemistry ,Cancer research ,Cytotoxicity - Published
- 2007
- Full Text
- View/download PDF
37. Development of a confocal ultrasound device using an inertial cavitation control for transfection in-vitro
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Cyril Lafon, S Roux, Fabrice Prieur, Kamel Chettab, Maxime Lafond, Charles Dumontet, and Jean-Louis Mestas
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History ,medicine.diagnostic_test ,business.industry ,Ultrasound ,Nucleofection ,Transfection ,Gene delivery ,Biology ,Computer Science Applications ,Education ,Flow cytometry ,chemistry.chemical_compound ,chemistry ,In vivo ,medicine ,Propidium iodide ,business ,Sonoporation ,Biomedical engineering - Abstract
Sonoporation using low-frequency high-pressure ultrasound (US) is a non-viral approach for in vitro and in vivo gene delivery. We developed a new sonoporation device designed for spatial and temporal control of ultrasound cavitation. This device was evaluated for the in vitro transfection efficiency of a plasmid coding for Green Fluorescent Protein (peGFP- C1) in adherent and non-adherent cell lines. The frequency spectrum of the signal receive by a hydrophone is used to compute a cavitation index (CI) representative of the inertial cavitation activity. The influence of the CI on transfection efficiency, as well as reproducibility were determined. A real-time feedback loop control on CI was integrated in the process to regulate the cavitation level during sonoporation. In both adherent and non-adherent cell lines, the sonoporation device produced a highly efficient transfection of peGFP-C1 (40-80%), as determined by flow cytometry analysis of GFP expression, along with a low rate of mortality assessed by propidium iodide staining. Moreover, the sonoporation of non-adherent cell lines Jurkat and K562 was found to be equivalent to nucleofection in terms of efficiency and toxicity while these two cell lines were resistant to transfection with lipofection.
- Published
- 2015
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38. Correlation of the exposed-cell mortality with the transient cavitation noise in vitro
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Sabrina Chesnais, Dominique Cathignol, Jean-Louis Mestas, J.-Y. Blay, L. Alverti, and L. Villeneuve
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On cells ,Araldite ,Materials science ,Transducer ,Tray ,Correlation coefficient ,Hydrophone ,Cavitation ,Acoustics ,Analytical chemistry ,Ultrasonic sensor - Abstract
The cavitation noise is a suitable and accurate indicator of the cavitation activity induced in a liquid. Frohly (2000) proposed a quantitative indicator of the transient cavitation calculated as a cavitation spectrum integration in a logarithmic scale and called CNP cavitation noise power indicator. This work studied the relation between a new indicator CMS based on CNP and the exposed-cell mortality in the following conditions. The cell suspension to be insonified (prostatic cells AT2 at 2.5 10/sup 6/ cells/mL) is placed in a medium sample tray (12 wells/tray, 2 mL/well, well diameter: 20 mm). This tray is submerged at mid-depth in degassed water and positioned 5 mm above the face of a flat ultrasonic transducer (diameter 22 mm, frequency: 445.5 kHz; intensity: 0.08-1.09 W/cm/sup 2/, exposure time: 30 sec-4 min). This technical configuration was admitted to be conducive to standing-wave generation through reflection at the air/medium interface in the well thus enhancing the cavitation phenomenon. Laterally to the transducer, a homemade hydrophone (PVDF film of 10 min diameter molded in araldite AY103) was oriented to receive the acoustical signal from the bubbles. From this spectral signal (0.1 to 7.1 MHz bandwidth) recorded every 3 sec on a computer during the exposure condition, CNP was calculated. Its mean value was compared to the cell mortality measured just after ultrasound exposure with a flow cytometer (FACScan) by counting 10000 events. This was accomplished by adding 7AAD solution (Via-Probe kit). Ten exposure conditions were chosen. Two of them corresponded to the experimental limits: no effects on cells (i.e. 0.08 W/cm/sup 2/; 4 min) - complete destruction of cells (i.e. 1.09 W/cm/sup 2/; 30 sec). 3 to 8 measures were realized for each exposure condition. The mortality due to cavitation effect varied from 0.1% to 85.5% and was compared to CMS mean given in relative value (from 3.8% to 97.5%). A simply linear relation between these parameters was given by a correlation coefficient of r/sup 2/=0.81. This correlation coefficient came better when exposed times were considered (for 1 min r/sup 2/=0.82 and for 2 min r/sup 2/=0.95). These results show that CNP is a good indicator of the effect induced by the cavitation phenomenon in cell culture medium in vitro.
- Published
- 2005
- Full Text
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39. Determination of the acoustic pressure at and the reflection coefficient of a target through measurements of the absorbed power and the emitter voltage
- Author
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P. Lenz, Jean-Louis Mestas, and Dominique Cathignol
- Subjects
Acoustics and Ultrasonics ,Acoustics ,Transducers ,Models, Biological ,Sensitivity and Specificity ,Standing wave ,Optics ,Image Interpretation, Computer-Assisted ,Electric Impedance ,Transducers, Pressure ,Scattering, Radiation ,Electrical and Electronic Engineering ,Reflection coefficient ,Sound pressure ,Instrumentation ,Common emitter ,Ultrasonography ,Physics ,business.industry ,Phantoms, Imaging ,Reproducibility of Results ,Acoustic wave ,Equipment Design ,Equipment Failure Analysis ,Acoustic emission ,Energy Transfer ,Reflection (physics) ,Physics::Accelerator Physics ,Acoustic impedance ,business ,Algorithms - Abstract
A harmonic acoustic wave, fed back by a reflecting target, modifies the electric impedance of the emitter. This effect is studied using a tightly focused beam and various flat targets with known reflection coefficients, which are placed at pressure maxima or minima of the standing wave in the focal zone. It is possible to establish relationships that allow one to determine, for flat targets with unknown acoustic properties, the acoustic impedance and reflection coefficient of the target as well as the acoustic pressure present at the target, only from measurements of the absorbed power and the emitter voltage.
- Published
- 2004
40. Long-lasting stable cavitation
- Author
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Dominique Cathignol, Peter W. Lenz, and Jean-Louis Mestas
- Subjects
Long lasting ,Materials science ,Acoustics and Ultrasonics ,Arts and Humanities (miscellaneous) ,Cavitation ,Excited state ,Abrasive ,Composite material ,FOIL method ,Beam (structure) ,Grain size ,Sonochemistry - Abstract
Stable cavitation is produced on the surface of a special target, i.e., an abrasive foil with a grain size of about 15 microm, insonified by a 473 kHz focused beam. Cavitation bubbles are first created by a pressure of about 2 MPa. Progressive reduction of the pressure to about 100 kPa leads to a state of stable cavitation characterized by strong stable emission of the half-order subharmonic. This state can be maintained for five hours if the defining parameters (position and pressure) are optimized and constant to within a few percent. There is strong evidence for the presence of "latent" cavitation bubbles, which can persist for a few minutes without being excited.
- Published
- 2003
41. Improvement of the reproducibility in electrohydraulic generators by using conducting liquid (medical US lithotripsy)
- Author
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Dominique Cathignol, P. Lenz, Francisco Gómez, P. Dancer, Jean-Louis Mestas, and M. Bourlion
- Subjects
Shock wave ,Materials science ,business.industry ,Plasma ,law.invention ,Pulse (physics) ,Generator (circuit theory) ,Capacitor ,Optics ,Amplitude ,law ,business ,Voltage ,Electronic circuit - Abstract
In an electrohydraulic generator, two underwater metal electrodes are connected in series with a capacitor charged to a high voltage. When the circuit is switched on, a plasma occurs reaching temperatures of thousands of degrees Celsius and resulting in a compressive pressure pulse. The formation of the plasma is a particular nonreproducible phenomenon inducing great variations in the pressure pulse values. Measurements obtained by triangulation show that the origin of the plasma changes and that the center of the spherical divergent shock wave can be located largely outside the interelectrode gap when tap water is used. However, the center of the shock wave is always located at the same place when electrolyte is used. The plasma duration was also photographed to better study the nonreproducibility of the shock-wave amplitudes. >
- Published
- 2002
- Full Text
- View/download PDF
42. Motorised resection device for transurethral resection of the prostate: a laboratory evaluation
- Author
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Françoise Chavrier, Jean-Louis Mestas, M. Devonec, and D. Cathignol
- Subjects
Male ,medicine.medical_specialty ,Adenoma ,medicine.medical_treatment ,Biomedical Engineering ,Prostatic Hyperplasia ,Common method ,Models, Biological ,Transurethral prostatectomy ,Resection ,Blood loss ,medicine ,Humans ,Ultrasonography, Interventional ,Transurethral resection of the prostate ,Prostatectomy ,business.industry ,medicine.disease ,Prostatic enlargement ,Computer Science Applications ,Surgery ,Agar ,Evaluation Studies as Topic ,business ,Nuclear medicine - Abstract
Transurethral resection of the prostate is the most common method of relieving urinary outflow obstruction secondary to prostatic enlargement. However, this procedure can be responsible for various complications, including irrigant-fluid absorption and blood loss, both of which are strongly dependent on operation duration time. To reduce the latter, a new resection device has been designed for transurethral prostatectomy. The device basically consists of a rotating cutting loop controlled externally, with three degrees of freedom, to fit the adenoma shape. Its performance is assessed in vitro by drilling conical and semi-ellipsoidal cavities in agar gel models. The mean difference between the calculated and obtained cavity volumes is 3% (SD = 0.9%). The volume cutting rate, found to be independent of the type of cavity drilled, is equal to 2.9 +/- 0.3 cm3 min-1. The advantages of this motorised resection device prototype are reduction in operation duration and accuracy of the resected volume. In vivo resection of a 20 cm3 adenoma in less than 15 min can be expected.
- Published
- 1998
43. High-efficiency shock-wave generator for extracorporeal lithotripsy
- Author
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D. Cathignol, P. Broyer, Y. Theillere, and Jean-Louis Mestas
- Subjects
Materials science ,business.industry ,Electrical engineering ,Biomedical Engineering ,Spark gap ,Acoustics ,Characteristic impedance ,Computer Science Applications ,Inductance ,Electrolytes ,Electricity ,Rise time ,Lithotripsy ,Electrode ,Optoelectronics ,Humans ,Electric discharge ,Coaxial ,business ,Voltage - Abstract
In extracorporeal lithotripsy, the electro-acoustic efficiency of electrohydraulic generators is limited by the inductance of the electrical discharge circuit. A new shock-wave generator is described that uses a coaxial discharge line enabling electro-acoustic efficiency to be greatly increased. The line is built using a para-electric ceramic with a relative dielectric constant of 1700, manufactured for use in high-voltage impulse mode. A coaxial spark gap, with minimal inductance, has been developed to obtain the triggered breakdown of the discharge line. Shock waves are created with a coaxial electrode plugged directly into the spark gap and immersed in an electrolyte of degassed saline. Electrode gap and electrolyte resistivity are adjusted to match the resistivity of the electrolyte volume between the underwater electrodes to the characteristic impedance of the line. The discharge line generates in the medium a rectangular current pulse with an amplitude of about 6000 A and a rise time of 50 ns. Compared with conventional generators, measurements of the expansive peak pressure pulse show an increase of 105% at 10 kV, 86.5% at 12 kV and 34.5% at 14 kV charging voltage. Electro-acoustic efficiency is found to be 11% instead of 5.5% for a conventional discharge circuit.
- Published
- 1996
44. Stable inertial cavitation with a confocal ultrasonic device for drug release from nongaseous sonosensitive liposomes
- Author
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Jacqueline Ngo, Jean-Louis Mestas, Sabrina Chesnais, Lucie Somaglino, Cyril Lafon, Jean-Yves Chapelon, Jean Martial Mari, and Esben A. Nilssen
- Subjects
Liposome ,Acoustics and Ultrasonics ,Chemistry ,business.industry ,Confocal ,Ultrasound ,Ultrasonic device ,chemistry.chemical_compound ,Arts and Humanities (miscellaneous) ,Phosphatidylcholine ,Cavitation ,Drug delivery ,medicine ,Doxorubicin ,business ,Biomedical engineering ,medicine.drug - Abstract
Encapsulating chemotherapeutic agents in liposomes improves targeting and efficacy of treatments against some tumors. The present work aims at evaluating if sonosensitive liposomes combined with cavitation for drug delivery enhance efficacy and reduce toxicity. Two focused beams were combined for stabilizing the cavitation cloud and an imaging probe used for guidance. Each 1MHz focused transducer had a 5cm diameter and focal length. Exposure conditions were 10.8kW/cm2 Isppa, 250Hz PRF and 1% duty cycle. Phosphatidylcholine-based nongaseous liposomes were loaded with Doxorubicin. To control for mechanical tissue damage, AT2 Dunning tumors on rats were first exposed to ultrasound only. Treatment induced temperature rose below 0.5° C. The tumor growth was not significantly slowed down by ultrasound, but histological examination of tumors evidenced large areas of necrosis which resorbed one week after ultrasound. The new liposomes were compared with conventional HSPC-based liposomes in terms of efficacy and t...
- Published
- 2012
- Full Text
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45. New discharge circuit using high voltage transmission line for efficient shock wave generation: application to lithotripsy
- Author
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P. Broyer, Y. Theillere, Jean-Louis Mestas, and Dominique Cathignol
- Subjects
Inductance ,Shock wave ,Electric power transmission ,Materials science ,Transmission line ,Acoustics ,Pulse generator ,Spark gap ,Line (electrical engineering) ,Voltage - Abstract
In extracorporeal shock wave lithotripsy (ESWL), spreading wave amplitude is limited by the inductance of the discharge circuit. The goal of this study is to demonstrate the possibility of increasing pressure wave amplitude by using a low inductance transmission line. A high voltage transmission line has been constructed using a ferroelectric ceramic with relative dielectric constant equal to 1700 to give a total capacitance of 100 nF. A coaxial spark gap, with minimal inductance, has been developed to obtain triggered breakdown of the charged line. This new discharge circuit generates a high voltage rectangular pulse between underwater electrodes and then creates a spreading wave. Pressure amplitude and electroacoustic efficiency compared to conventional generators results demonstrate qualities of this new generator
- Published
- 1994
- Full Text
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46. Corrigendum to 'Validation of an acoustic cavitation dose with hydroxyl radical production generated by inertial cavitation in pulsed mode: Application to in vitro drug release from liposomes' [Ultrasonics Sonochemistry 18 (2011) 577–588]
- Author
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Lucie Somaglino, Cyril Lafon, Guillaume Bouchoux, and Jean-Louis Mestas
- Subjects
Liposome ,Acoustics and Ultrasonics ,Organic Chemistry ,Analytical chemistry ,Photochemistry ,Sonochemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Cavitation ,Drug release ,Chemical Engineering (miscellaneous) ,Environmental Chemistry ,Pulsed mode ,Radiology, Nuclear Medicine and imaging ,Hydroxyl radical - Abstract
1350-4177/$ see front matter 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.ultsonch.2010.12.007 DOI of original article: 10.1016/j.ultsonch.2010.07.009 ⇑ Corresponding author at: Universite de Lyon, Lyon F-69003, France. E-mail address: lucie.somaglino@yahoo.fr (L. Somaglino). 4th paragraph (line 35 of the Section), the line ‘‘off-time duration induced a decrease of hydroxyl radical production’’ should read as follows
- Published
- 2011
- Full Text
- View/download PDF
47. Three-dimensional reconstruction of the prostate from transverse or sagittal ultrasonic images
- Author
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Jean Louis Mestas, I. Dautraix, Olivier Basset, and Gérard Gimenez
- Subjects
business.industry ,Triangulation (computer vision) ,Image segmentation ,3D modeling ,Sagittal plane ,medicine.anatomical_structure ,Parametric surface ,Digital image processing ,medicine ,Computer vision ,Artificial intelligence ,business ,Rotation (mathematics) ,Mathematics ,Envelope (motion) - Abstract
A device devoted to the 3-D representation of the prostate has been developed. It operates with either sagittal or transverse images. On each selected image, an operator outlines the prostate (and/or an eventual pathological area), by means of a digitizing tablet. These contours are then described by a limited number of points. From these points, belonging to the object envelope, two 3-D representation techniques have been implemented: the B-spline parametric surface and the triangulation method. The main advantage of the triangulation algorithm is its rapidity, contrary to the one using the parametric surfaces. Moreover, it allows satisfying representations of simple anatomic shapes like the prostate. The understanding of the geometry of the object is improved by a fast rotation of the whole object.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
- Published
- 1993
- Full Text
- View/download PDF
48. 69: Chronic Lymphocytic Leukemia and anti-CD20 monoclonal antibodies
- Author
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Cindy Tournebize, Charles Dumontet, Stéphane Dalle, Reslan Lina, and Jean-Louis Mestas
- Subjects
CD20 ,Cancer Research ,biology ,medicine.drug_class ,business.industry ,Chronic lymphocytic leukemia ,Hematology ,General Medicine ,medicine.disease ,Monoclonal antibody ,Oncology ,Immunology ,biology.protein ,medicine ,Radiology, Nuclear Medicine and imaging ,Anti cd20 ,business - Published
- 2010
- Full Text
- View/download PDF
49. Combined effect of ultrasound and liposomal doxorubicin on AT2 Dunning tumor growth in rats: Preliminary results
- Author
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Jean-Louis Mestas, Anis Amdouni, Jean-Yves Chapelon, Sabrina Chesnais, Guillaume Bouchoux, Sigrid L. Fossheim, Esben A. Nilssen, Cyril Lafon, and Lucie Somaglino
- Subjects
Liposome ,Acoustics and Ultrasonics ,business.industry ,Liposomal Doxorubicin ,Ultrasound ,Focused ultrasound ,Arts and Humanities (miscellaneous) ,Pharmacokinetics ,In vivo ,Medicine ,Tumor growth ,Doxorubicin ,Nuclear medicine ,business ,medicine.drug - Abstract
Previous in vitro studies conducted in our group have shown the feasibility of monitoring drug release from liposomes by an inertial acoustic cavitation index. We currently report in vivo experiments utilizing the cavitation index in combined treatment of AT2 Dunning tumor grafted rats with focused ultrasound and liposomal doxorubicin. Sixty‐three rats were allocated into seven groups: control, low level ultrasound treatment, high level ultrasound treatment, free doxorubicin+high level ultrasound treatment, and liposomal doxorubicin, liposomal doxorubicin+low level ultrasound treatment, and liposomal doxorubicin+high level ultrasound treatment. Based on pharmacokinetic studies, it was decided to apply ultrasound to the tumor 48 h after drug injection. An experimental setup was built to perform repeatable and rapid sonications of tumors monitored by the cavitation index. Tumor growth was assessed for a period of 35 days after tumor inoculation. Results showed that liposomal doxorubicin significantly slowed...
- Published
- 2009
- Full Text
- View/download PDF
50. Influence of water conductivity on the efficiency and the reproducibility of electrohydraulic shock wave generation
- Author
-
Dominique Cathignol, Francisco Gómez, P. Lenz, and Jean-Louis Mestas
- Subjects
Shock wave ,medicine.medical_specialty ,Materials science ,Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,Biophysics ,Electric Conductivity ,Reproducibility of Results ,Water ,Mechanics ,Plasma ,Electrolyte ,Efficiency ,Conductivity ,Surgery ,Pulse (physics) ,Amplitude ,Lithotripsy ,Electrode ,medicine ,Radiology, Nuclear Medicine and imaging ,Electric discharge - Abstract
In an electrohydraulic generator, two underwater metal electrodes are connected with a capacitor charged to a high voltage. When the circuit is switched on, a plasma is generated reaching temperatures of thousands of K, resulting in a compressive pressure pulse. The formation of the plasma is a nonreproducible phenomenon inducing great variations of the pressure pulse. When the electrodes are immersed in an electrolyte instead of degassed water, the conditions of electrical discharge are dramatically modified. The latency time and the amplitude of the oscillations of the discharge current decrease as the conductivity of the electrolyte increases. For a conductivity of 7 Ωcm, there is no latency, and the critically damped discharge is achieved. The expanding pressure wave is increased by 10%, and the mean peak pressure value over 120 shocks at the second focus after focalization is increased by 50%. The relative standard deviation of the pressure value at the second focus is only 5%, while it is about 30% in ordinary water. The fragmentation efficiency is considerably increased because total fragmentation is obtained in 220 shocks instead of 450 shocks in ordinary water when standard stones are used, and in 131 shocks instead of 304 shocks when gallstones are used. Last, we show that the wear of the electrodes is reduced by a factor 8 when electrolyte is used. The improvement is supposed to have two causes: First, the energy is delivered into the medium in a shorter time, and, second, the center of the shock wave is always located at the same place. The decreased wear should make it possible to treat a much greater number of patients without changing electrodes, and the enhancement of the pressure should increase the efficiency of the fragmentation of the gallstones without aggravating the patient's pain.
- Published
- 1991
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