Acoustic cavitation can improve local drug delivery in tumors. Without injected external nucleati... more 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.
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2015
The local application of ultrasound is known to improve drug intake by tumors. Cavitating bubbles... more 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.
The Journal of the Acoustical Society of America, 2013
ABSTRACT Inertial cavitation has been shown to be useful in many therapeutic applications; thus, ... more ABSTRACT Inertial cavitation has been shown to be useful in many therapeutic applications; thus, controlling this phenomenon is of great therapeutic interest. However, the stochastic nature of cavitation often proves problematic for predicting its location and extent. Traditional solutions to this problem are the of use dedicated detection apparatuses, or to use injectable microbubbles (MBs), which act as nuclei for the initiation of cavitation. We hypothesize here that cavitation can be reliably controlled without the use of MBs using a confocal system, which produces a lobular focal zone due to acoustic interference. This interference pattern was studied both in simulation and hydrophone measurement. Cavitation extent was confirmed chemometrically with an assay for hydroxyl radical formation, and by passive cavitation detection with a hydrophone. A high speed camera was used to image the initiation of cavitation within the focal zone, the evolution of the bubble cloud, and the subsequent bubble rebound after pulse cessation. The experiments in this work confirm that cavitation is produced more reliably in the confocal setup as opposed to a single transducer, as well as illuminating the mechanisms for this enhancement. [Work supported by the European Union through the Eurostars program (project E!6173) and Caviskills SAS.].
Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleatio... more Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleation agents are injected, high negative pressures are required for initiating inertial cavitation, which can lead to biological damages. 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 on structure and cytotoxicity of doxorubicin after sonication. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histological analyses at 72 hours and 2 weeks post-treatment demonstrated only a modest impact on tissues, mainly resulting in mild skin damages. Finally, 4T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that the exposures of mammary tumors did not impact vascular density, proliferation, nor the proliferation and apoptosis of cancer cells. Moreover, ultrasound did not negatively impact on the spreading of cancer cells to the lungs and bone marrow. Thus, our study provides experimental evidence that these particular ultrasound parameters can be used safely for unseeded inertial cavitation in vivo.
Acoustic cavitation can improve local drug delivery in tumors. Without injected external nucleati... more 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.
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2015
The local application of ultrasound is known to improve drug intake by tumors. Cavitating bubbles... more 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.
The Journal of the Acoustical Society of America, 2013
ABSTRACT Inertial cavitation has been shown to be useful in many therapeutic applications; thus, ... more ABSTRACT Inertial cavitation has been shown to be useful in many therapeutic applications; thus, controlling this phenomenon is of great therapeutic interest. However, the stochastic nature of cavitation often proves problematic for predicting its location and extent. Traditional solutions to this problem are the of use dedicated detection apparatuses, or to use injectable microbubbles (MBs), which act as nuclei for the initiation of cavitation. We hypothesize here that cavitation can be reliably controlled without the use of MBs using a confocal system, which produces a lobular focal zone due to acoustic interference. This interference pattern was studied both in simulation and hydrophone measurement. Cavitation extent was confirmed chemometrically with an assay for hydroxyl radical formation, and by passive cavitation detection with a hydrophone. A high speed camera was used to image the initiation of cavitation within the focal zone, the evolution of the bubble cloud, and the subsequent bubble rebound after pulse cessation. The experiments in this work confirm that cavitation is produced more reliably in the confocal setup as opposed to a single transducer, as well as illuminating the mechanisms for this enhancement. [Work supported by the European Union through the Eurostars program (project E!6173) and Caviskills SAS.].
Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleatio... more Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleation agents are injected, high negative pressures are required for initiating inertial cavitation, which can lead to biological damages. 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 on structure and cytotoxicity of doxorubicin after sonication. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histological analyses at 72 hours and 2 weeks post-treatment demonstrated only a modest impact on tissues, mainly resulting in mild skin damages. Finally, 4T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that the exposures of mammary tumors did not impact vascular density, proliferation, nor the proliferation and apoptosis of cancer cells. Moreover, ultrasound did not negatively impact on the spreading of cancer cells to the lungs and bone marrow. Thus, our study provides experimental evidence that these particular ultrasound parameters can be used safely for unseeded inertial cavitation in vivo.
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Papers by Maxime Lafond