Peter Bevan - Academia.edu (original) (raw)

Papers by Peter Bevan

IEEE Ultrasonics Symposium, 2005.

ABSTRACT

IEEE Ultrasonics Symposium, 2004

Page 1. Microbubble Potentiated Changes in Cell Permeability and Viability Raffi Karshafian, Pete... more Page 1. Microbubble Potentiated Changes in Cell Permeability and Viability Raffi Karshafian, Peter D. Bevan, Peter N. Burns Department of Medical Biophysics, University of Toronto Sunnybrook &Women's College Health Sciences ...

Ultrasonics, 2010

This work investigates whether the application of sonoporation is limited by the size of a macrom... more This work investigates whether the application of sonoporation is limited by the size of a macromolecule being delivered and by the ability of cells to proliferate following uptake. KHT-C cells in suspension were exposed to variations in ultrasound pressure (0-570 kPa) and microbubble shell-type (lipid and protein) at fixed settings of 500 kHz centre frequency, 32 micros pulse duration, 3 kHz pulse repetition frequency and 2 min insonation. Reversible permeability (P(R)), defined as the number of cells stained with FITC-dextran and unstained with propidium iodide (i.e., PI-viable), was measured with flow cytometry for marker molecules ranging from 10 kDa to 2 MDa in size. Viable permeability (P(V)) defined as the number of permeabilised cells that maintained their ability to proliferate, was measured by clonogenic assay. Comparable intracellular delivery of all sizes of molecules was achieved, indicating that intracellular delivery of common therapeutic drugs may not be limited by m...

Ultrasound in Medicine & Biology, 2006

Submicrometer particles filled with liquid perfluorocarbon have been shown to increase the ultras... more Submicrometer particles filled with liquid perfluorocarbon have been shown to increase the ultrasound reflectivity of surfaces onto which they bind and, consequently, are seen as potential targeted contrast agents. The objective of this study is to explain the reflectivity enhancement as a result of the presence of randomly distributed particles on a surface. A model is presented where the diffraction-weighted scattering of all particles is summed over the exposed surface. Experiments were performed at frequencies ranging from 15 MHz to 60 MHz, with glass microbeads and perfluorohexane particles deposited on the surface of agar and Aqualene, a rubber closely matched to water, to confirm the validity of the model. Results showed that the model predicts the surface density and the frequency dependence of the reflectivity enhancement up to a density corresponding to twice the maximum packing of spheres on a surface (200% confluence fraction) for glass beads and a fifth (20% confluence fraction) for perfluorohexane particles. This suggests the possibility of predicting signal enhancement due to a bound contrast agent in simple geometries.

IEEE Ultrasonics Symposium, 2004

The goal of this study was to assess the threshold of disruption and the time-course of the subse... more The goal of this study was to assess the threshold of disruption and the time-course of the subsequent acoustic response of four agents comprising gas encapsulated within a polymer shell. The four agents shared the same bubble diameter (∼4 μm), contained the same gas (N2) but had shell thicknesses that varied by a factor of 5. The time-course of the response was assessed by applying a series of pulses to a diluted suspension of these agents. Measurements showed that the pre-disruption response of the agents decreased with increasing shell thickness. Above the disruption threshold for the agents, highly echogenic, nonlinear scatterers were observed and persisted for a mean half-life of about 12 ms, which is consistent with the free diffusion of N2 in water. This suggests a picture wherein the shell is disrupted, releasing the gas contained within the bubble, generating free gas bubbles. This release is followed by diffusion of the gas into solution and resonant, high amplitude nonlinear scattering. The optimum bubble tested combined a shell thickness which produced a well-defined disruption threshold within the diagnostic range and a gas which dissolved relatively rapidly, thus increasing the decorrelation signal obtainable for disruption diagnostic imaging.

Ultrasound in Medicine & Biology, 2008

Bubble disruption is associated with the response of ultrasound contrast agents (UCAs) exposed to... more Bubble disruption is associated with the response of ultrasound contrast agents (UCAs) exposed to high acoustic pressures. This behavior is important for bubble detection techniques as well as flow quantitation and some proposed therapeutic applications. Previous work has measured acoustically the disruption threshold and postdisruption echo from populations of microbubbles. This suggests a model for UCA disruption whereby ultrasound breaks their shell, leaving free gas bubbles. Diffusion of gas causes the bubbles to shrink and, consequently, reduces the measured backscatter echo over time. In this work, similar bubbles containing three different gases were measured and their echo behavior with time compared with a simple simulation based on diffusion of gas out of the bubble. It was found that, in general, the simulations and experiments compared well at low disruption pressures. Incorporating bubble fragmentation in the simulation model brought its results closer to experiment.

Ultrasound in Medicine & Biology, 2006

Submicron particles filled with liquid perfluorocarbon are currently being studied as a potential... more Submicron particles filled with liquid perfluorocarbon are currently being studied as a potential ultrasound-targeted contrast agent. The objective of this study was to evaluate the scattering properties of these particles. Sets of perfluorohexane-filled particles of different average sizes (300 nm to 1000 nm) were produced with a constant total volume fraction. The attenuation coefficient was measured in the 15-to 50-MHz frequency range and was found to increase smoothly with frequency and to be independent of the amplitude and bandwidth of the transmitted pulse. The values range from 0.31 to 0.64 dB/mm at 30 MHz for mean particle size ranging from 970 to 310 nm, respectively. The backscattering spectra of the particle solutions were measured and showed no sign of nonlinear scattering. The backscattering coefficient increased with the power 3.9 ؎ 0.3 of the frequency. These results confirm that liquid perfluorocarbon droplets behave as linear Rayleigh scatterers.

Ultrasound in Medicine & Biology, 2001

Thermal therapy is an experimental procedure to treat localised tumours in the prostate, liver, k... more Thermal therapy is an experimental procedure to treat localised tumours in the prostate, liver, kidney or breast. Monitoring is important to ensure complete tumour destruction while sparing adjacent sensitive structures. Previous work demonstrated that, when biological tissues are heated above 65 degrees C, ultrasound (US) attenuation increases due to thermal coagulation of tissue. This study examined the feasibility of a B-scan, envelope-based attenuation estimation method to monitor thermal therapy. The slope of the log of the signal envelope was used to estimate attenuation. It is shown that this method is able to demonstrate, from simulated and phantom data, a limited ability to differentiate attenuation levels that correspond to thermally coagulated and uncoagulated beef liver. In ex vivo bovine liver, however, issues due to signal-to-noise ratio (SNR) of the signal envelope prevented the visulisation of a 2-cm diameter thermally coagulated inclusion. The limitations of this method are extended to the multinarrow-band (MNB) technique.

Physics in Medicine and Biology, 2008

Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at on... more Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at one-half the driving frequency. At ultrasound frequencies in the 20-40 MHz range, the subharmonic offers the potential to differentiate the blood in the microcirculation from the surrounding tissue. It is unknown whether current contrast agents, manufactured to be resonant between 2 and 12 MHz, are ideal for subharmonic imaging at higher frequencies. We performed numerical simulations of the Keller-Miksis model for the behavior of a single bubble and experimental investigations of Definity microbubbles in water. The results supported the hypothesis that off-resonant bubbles, excited at their second harmonic, may be primarily responsible for the observed subharmonic energy. For frequencies between 20 and 32 MHz and 32 and 40 MHz, the optimal bubble diameters for the generation of subharmonics in vitro were determined experimentally to be 1.2-5 µm and less than 1.2 µm, respectively. Definity may be a suitable ultrasound contrast agent for subharmonic imaging at 20 MHz with peak-negative pressures between 380 and 590 kPa and pulses greater than or equal to four cycles in duration.

Physics in Medicine and Biology, 2011

IEEE Ultrasonics Symposium, 2005.

ABSTRACT

IEEE Ultrasonics Symposium, 2004

Page 1. Microbubble Potentiated Changes in Cell Permeability and Viability Raffi Karshafian, Pete... more Page 1. Microbubble Potentiated Changes in Cell Permeability and Viability Raffi Karshafian, Peter D. Bevan, Peter N. Burns Department of Medical Biophysics, University of Toronto Sunnybrook &Women's College Health Sciences ...

Ultrasonics, 2010

This work investigates whether the application of sonoporation is limited by the size of a macrom... more This work investigates whether the application of sonoporation is limited by the size of a macromolecule being delivered and by the ability of cells to proliferate following uptake. KHT-C cells in suspension were exposed to variations in ultrasound pressure (0-570 kPa) and microbubble shell-type (lipid and protein) at fixed settings of 500 kHz centre frequency, 32 micros pulse duration, 3 kHz pulse repetition frequency and 2 min insonation. Reversible permeability (P(R)), defined as the number of cells stained with FITC-dextran and unstained with propidium iodide (i.e., PI-viable), was measured with flow cytometry for marker molecules ranging from 10 kDa to 2 MDa in size. Viable permeability (P(V)) defined as the number of permeabilised cells that maintained their ability to proliferate, was measured by clonogenic assay. Comparable intracellular delivery of all sizes of molecules was achieved, indicating that intracellular delivery of common therapeutic drugs may not be limited by m...

Ultrasound in Medicine & Biology, 2006

Submicrometer particles filled with liquid perfluorocarbon have been shown to increase the ultras... more Submicrometer particles filled with liquid perfluorocarbon have been shown to increase the ultrasound reflectivity of surfaces onto which they bind and, consequently, are seen as potential targeted contrast agents. The objective of this study is to explain the reflectivity enhancement as a result of the presence of randomly distributed particles on a surface. A model is presented where the diffraction-weighted scattering of all particles is summed over the exposed surface. Experiments were performed at frequencies ranging from 15 MHz to 60 MHz, with glass microbeads and perfluorohexane particles deposited on the surface of agar and Aqualene, a rubber closely matched to water, to confirm the validity of the model. Results showed that the model predicts the surface density and the frequency dependence of the reflectivity enhancement up to a density corresponding to twice the maximum packing of spheres on a surface (200% confluence fraction) for glass beads and a fifth (20% confluence fraction) for perfluorohexane particles. This suggests the possibility of predicting signal enhancement due to a bound contrast agent in simple geometries.

IEEE Ultrasonics Symposium, 2004

The goal of this study was to assess the threshold of disruption and the time-course of the subse... more The goal of this study was to assess the threshold of disruption and the time-course of the subsequent acoustic response of four agents comprising gas encapsulated within a polymer shell. The four agents shared the same bubble diameter (∼4 μm), contained the same gas (N2) but had shell thicknesses that varied by a factor of 5. The time-course of the response was assessed by applying a series of pulses to a diluted suspension of these agents. Measurements showed that the pre-disruption response of the agents decreased with increasing shell thickness. Above the disruption threshold for the agents, highly echogenic, nonlinear scatterers were observed and persisted for a mean half-life of about 12 ms, which is consistent with the free diffusion of N2 in water. This suggests a picture wherein the shell is disrupted, releasing the gas contained within the bubble, generating free gas bubbles. This release is followed by diffusion of the gas into solution and resonant, high amplitude nonlinear scattering. The optimum bubble tested combined a shell thickness which produced a well-defined disruption threshold within the diagnostic range and a gas which dissolved relatively rapidly, thus increasing the decorrelation signal obtainable for disruption diagnostic imaging.

Ultrasound in Medicine & Biology, 2008

Bubble disruption is associated with the response of ultrasound contrast agents (UCAs) exposed to... more Bubble disruption is associated with the response of ultrasound contrast agents (UCAs) exposed to high acoustic pressures. This behavior is important for bubble detection techniques as well as flow quantitation and some proposed therapeutic applications. Previous work has measured acoustically the disruption threshold and postdisruption echo from populations of microbubbles. This suggests a model for UCA disruption whereby ultrasound breaks their shell, leaving free gas bubbles. Diffusion of gas causes the bubbles to shrink and, consequently, reduces the measured backscatter echo over time. In this work, similar bubbles containing three different gases were measured and their echo behavior with time compared with a simple simulation based on diffusion of gas out of the bubble. It was found that, in general, the simulations and experiments compared well at low disruption pressures. Incorporating bubble fragmentation in the simulation model brought its results closer to experiment.

Ultrasound in Medicine & Biology, 2006

Submicron particles filled with liquid perfluorocarbon are currently being studied as a potential... more Submicron particles filled with liquid perfluorocarbon are currently being studied as a potential ultrasound-targeted contrast agent. The objective of this study was to evaluate the scattering properties of these particles. Sets of perfluorohexane-filled particles of different average sizes (300 nm to 1000 nm) were produced with a constant total volume fraction. The attenuation coefficient was measured in the 15-to 50-MHz frequency range and was found to increase smoothly with frequency and to be independent of the amplitude and bandwidth of the transmitted pulse. The values range from 0.31 to 0.64 dB/mm at 30 MHz for mean particle size ranging from 970 to 310 nm, respectively. The backscattering spectra of the particle solutions were measured and showed no sign of nonlinear scattering. The backscattering coefficient increased with the power 3.9 ؎ 0.3 of the frequency. These results confirm that liquid perfluorocarbon droplets behave as linear Rayleigh scatterers.

Ultrasound in Medicine & Biology, 2001

Thermal therapy is an experimental procedure to treat localised tumours in the prostate, liver, k... more Thermal therapy is an experimental procedure to treat localised tumours in the prostate, liver, kidney or breast. Monitoring is important to ensure complete tumour destruction while sparing adjacent sensitive structures. Previous work demonstrated that, when biological tissues are heated above 65 degrees C, ultrasound (US) attenuation increases due to thermal coagulation of tissue. This study examined the feasibility of a B-scan, envelope-based attenuation estimation method to monitor thermal therapy. The slope of the log of the signal envelope was used to estimate attenuation. It is shown that this method is able to demonstrate, from simulated and phantom data, a limited ability to differentiate attenuation levels that correspond to thermally coagulated and uncoagulated beef liver. In ex vivo bovine liver, however, issues due to signal-to-noise ratio (SNR) of the signal envelope prevented the visulisation of a 2-cm diameter thermally coagulated inclusion. The limitations of this method are extended to the multinarrow-band (MNB) technique.

Physics in Medicine and Biology, 2008

Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at on... more Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at one-half the driving frequency. At ultrasound frequencies in the 20-40 MHz range, the subharmonic offers the potential to differentiate the blood in the microcirculation from the surrounding tissue. It is unknown whether current contrast agents, manufactured to be resonant between 2 and 12 MHz, are ideal for subharmonic imaging at higher frequencies. We performed numerical simulations of the Keller-Miksis model for the behavior of a single bubble and experimental investigations of Definity microbubbles in water. The results supported the hypothesis that off-resonant bubbles, excited at their second harmonic, may be primarily responsible for the observed subharmonic energy. For frequencies between 20 and 32 MHz and 32 and 40 MHz, the optimal bubble diameters for the generation of subharmonics in vitro were determined experimentally to be 1.2-5 µm and less than 1.2 µm, respectively. Definity may be a suitable ultrasound contrast agent for subharmonic imaging at 20 MHz with peak-negative pressures between 380 and 590 kPa and pulses greater than or equal to four cycles in duration.

Physics in Medicine and Biology, 2011