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ABSTRACT: Current, minimally invasive, treatments for cardiac arrhythmia use a transvenous radio-frequency (RF) catheter to ablate the malfunctioning cardiac muscle regions. The paper proposes a noninvasive transesophageal cardiac thermal ablation using focused ultrasound. A planar phased array (1 MHz, 60×10 mm<sup>2</sup>, 0.525 mm element center-to-center distance, 2280 elements) was put in the esophagus. Using electronic beam steering, a matrix of 5×3×5 foci in the cardiac muscle was defined in three planes parallel to the transducer surface at short, medium and long (20, 40 and 60 mm) radial ranges and different steering angles. The transmitted ultrasound pressure distribution in a volume of 20×20×20 mm<sup>3</sup> centered at each focus was calculated using a multilayer acoustic wave transmission model. The thermal lesions due to the acoustic energy absorption in cardiac muscle were simulated using the bioheat transfer equation. For short, medium and long (1-, 10- and 20-second) sonications, the acoustic powers needed to achieve 60°C and 70°C peak temperatures in the cardiac muscle were 89-725, 25-125, 20-86 W and 128-1040, 36-179, 28-123 W, respectively. The simulated tissue lesion (thermal dose >240 min at 43°C) lengths at these foci were 2-10, 5-12, 6-14 mm and 3-13, 7-15, 9-17 mm, respectively. The lesion widths were 2-8, 3-10, 4-11 mm and 3-11, 4-12, 5-13 mm, respectively. The simulations show that noninvasive transesophageal cardiac ablation with a planar phased ultrasound array is feasible.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: The radiation force incident on an object in an ultrasound field has been utilized to create local displacements for making elastographic measurements. This study looks at the combined pressure field from two ultrasound transducers in a dual-frequency system to determine the radiation pressure field incident on an object in the focal plane. The combined pressure fields from a concentric-element transducer and a separate-element system with intersecting foci are analyzed. First, the combined pressure fields are calculated using a computer simulation of the summed linear fields. Then, the simulation results are shown to be in close agreement with experimental measurement of the pressure fields. Finally, the simulations are expanded to compute the radiation pressures for various target sizes and transducer geometries. A more thorough understanding of the resulting time-varying radiation pressure fields, as presented in this paper, facilitates the optimization of the dual-frequency set-up for radiation force imaging by providing general design guidelines for a dual-frequency imaging system.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: The use of cavitation-enhanced MRI-guided focused ultrasound (FUS) to disrupt the blood-brain barrier (BBB) locally and enhance drug delivery to the brain was investigated in rats with an intact skull. Contrast-enhanced MR images of 50 rat brains exposed in multiple locations to FUS in the presence of microbubbles were analyzed to determine the minimum focal pressure amplitude needed to achieve BBB opening, The images indicated that localized BBB opening was consistently achieved by applying FUS at estimated peak focal pressure amplitudes of 1.2 MPa or greater. In addition, the uptake of liposome-encapsulated doxorubicin in the brain tissue of six rats with and without exposure to FUS was quantified by fluorometry. Preliminary results indicated that FUS-enhanced drug delivery increased the uptake of liposomal doxorubicin by 53% compared to unexposed tissue. The successful delivery of molecules as large as 100 nm in diameter across the BBB indicates the clinical potential of FUS-enhanced drug delivery in the treatment of brain tumors.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: A practical method for sub-millimeter imaging in vivo would provide considerable benefits to both laboratory investigations and clinical diagnosis. Consequently, numerous imaging modalities have sought to achieve this high-resolution. Ultrasound is a viable candidate for such imaging, due to its ability to penetrate deeply and safely into tissues. However, previous studies have approached the problem by using increasingly higher ultrasound frequencies. The unfortunate tradeoff for higher frequencies is a simultaneous increase in the level of ultrasound attenuation, which has allowed imaging only a few millimeters deep. Our investigation proposes a new method that could allow sub-millimeter in vivo imaging at substantially lower frequencies than previously reported, thus allowing significantly greater depth penetration. To achieve this, we introduce a new superresolution imaging technique designed to resolve objects significantly smaller than the imaging wavelength. Our method exploits unique properties of ultrasound in order to provide additional information than achieved with related optical techniques. Presently, we outline the method and then demonstrate the procedure by reconstructing images of a human hair, which is more than one order of magnitude smaller then the source wavelength.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: The accuracy of a resonance ultrasound method is determined when used towards resolving the acoustic phase shifts in single- and three-layer plastic plates, and in pig skull samples ex vivo at oblique angles. The investigation is conducted with a single, broadband nonfocused transducer at frequency range from 0.45 to 1.45 MHz while the angle of incidence of the sound beam is varied by rotating the studied plate by 0-15°. Acoustic phase shifts are calculated using the resonance frequencies of the plates resolved from the reflected spectrum. These phase shifts are compared to those measured directly with hydrophone. Materials include 20 pieces of acrylic, six pieces of polycarbonate plastic (PC), and two pig's skull bone samples ex vivo. Ten acrylic and three PC plates are bent to model the shape of the human skull. Further, the four thinnest acrylic plates and all PC plates are used in three-layer stacks to model the layered structure of skull bone. Results show that with flat single-layer plates, 70% of the measured phase shifts (of altogether 416) deviate by less than 30° from those measured with the hydrophone; after bending the similar performance is about 61% (of 208), and about 58% (of 192) with the flat three-layer phantoms. Few measurements show deviation of higher than 90° between the methods. With curved three-layer plates and bone samples the discrepancy increased, showing a difference of less than 30° in 23% (of 192) for curved three-layered plates, and in 17% (of 64) for bone samples, respectively. In general the increase in the discrepancy is due to the destruction of the resonance pattern at higher angles of incidence as sound beam is reflected away from the transducer and uncertainty in resolving the resonance frequencies increases.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: Ultrasound-stimulated vibro-acoustography (USVA) is one of the recent noninvasive techniques that have been developed to explore mechanical properties of soft tissues. USVA is based on the interference of two focused ultrasound beams that have a slightly different frequency. This interference produces time variation to the acoustic radiation force that vibrates the joint focal region at the difference frequency. In this paper, we have simulated displacement amplitudes in the blood vessel using different difference frequencies and elasticity parameters. The difference frequency was varied between 300 Hz and 2.5 kHz, and two different stiffness parameters (60 kPa and 120 kPa) for the blood vessel wall were used. The stimulation transducer used in the simulations consists of two concentric and focused ring elements whose base frequency is 0.75 MHz. The stimulation fields have been computed in a homogeneous domain using the Rayleigh integral. The simulations of the vibrations have been computed using the finite element method. The displacement simulations are computed in an inhomogeneous domain that consists of soft tissue and a blood vessel. From the simulations, it can be seen that USVA is sensitive to the mechanical properties of vessel wall and that the displacements are highly dependent on the difference frequency and the material parameters.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: An ultrasound contrast agent (Optison<sup>®</sup>) was use with focused ultrasound to target the vasculature directly and produce localized lesions in the brain at low power levels. Also, MRI was tested to detect the induced temperature rise and the resulting lesions. Fifty-seven locations in the brains of 15 rabbits were sonicated using 1.5 MHz focused transducer (ROC/D=8 cm/10 cm). The 10 s or 20 s sonications were performed with either continuous wave (CW, 23 locations) or at a 50% duty cycle (PRF 1 Hz, 34 locations). Peak pressure amplitudes ranged from 1.6 to 9.8 MPa (in water). MRI was used to monitor the temperature rise during sonication and to detect tissue effects. At 4 h or 48 h after sonication, the animals were sacrificed and the brains were examined under light microscopy. Focal lesions were produced, with the necrosis appearing to result from a cessation of the blood supply within the sonicated regions. The lesions were seen in contrast-enhanced MRI and matched the shape of the MRI-mapped temperature distributions. In some cases (mostly CW sonications), damage along the ultrasound beam path was observed. This method may be useful for destroying tumors by targeting blood vessels directly. The threshold for tissue effects was reduced by approximately a factor of ten below that found in the same experimental conditions without the contrast agent. MRI thermometry appears useful for guiding such sonications.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: The paper explores the feasibility of using low frequency image guided focused ultrasound as a noninvasive method to temporarily disrupt the blood-brain barrier (BBB) at targeted locations. This method could provide a means for targeted delivery of therapeutic or diagnostic agents to the brain. Brains of rabbits were targeted with 20 s burst sonications (10 ms, repetition frequency, 1 Hz.) using a focused ultrasound transducer (frequency, 260 kHz; diameter, 10 cm; radius of curvature, 8 cm) in a clinical magnetic resonance imaging (MRI) scanner. The peak rarefactional pressure amplitude during the burst was varied between 0.2 and 0.9 MPa. Each sonication was performed 10 s after an intravenous injection of an ultrasound contrast agent (Optison<sup>®</sup>). The disruption of the BBB was evaluated by injecting MRI contrast agent (Magnevist<sup>®</sup>). The animals were sacrificed at different times between 4 h and 5 weeks, after which histology or electron microscopy evaluation was performed. The results demonstrated that low frequency ultrasound bursts could induce local, reversible disruption of the BBB without undesired long-term effects. Electron microscopy showed that a large particle (horseradish peroxidase; molecular weight 40 kDa) could be delivered through the BBB disruption. This frequency is desirable since it can be focused through the intact skull without significant distortion of the ultrasound beam.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: Inertial cavitation has been implicated as the primary mechanism for a host of emerging applications. In all these applications, the main concern is to induce cavitation in perfectly controlled locations in the field, this means specifically to be able to achieve cavitation threshold at the geometrical focus of the transducer without stimulating its near field. In this study, we develop dual-frequency methods to preferentially lower the cavitation threshold at the focus relative to the rest of the field. One family of dual-frequency driving waveforms is evaluated in a bubble model incorporating rectified diffusion. Results are then verified by experiment. Finally, the performance of the rest of the acoustic field in suppressing cavitation when cavitation is induced at the focus is investigated theoretically and checked experimentally. This study shows that dual-frequency phased arrays could be used to precisely control cavitation. The cavitation threshold is proved to be almost 1.3 times higher in the near field than at the focus. The concept of cavitation field is introduced and complements cavitation studies concentrating on the focal behavior only.
Ultrasonics Symposium, 2004 IEEE; 09/2004
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ABSTRACT: A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.
The Journal of the Acoustical Society of America 07/2004; 115(6):3235-43. · 1.55 Impact Factor
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ABSTRACT: The technique of harmonic motion imaging (HMI) uses the localized stimulus of the oscillatory ultrasonic radiation force as produced by two overlapping beams of distinct frequencies, and estimates the resulting harmonic displacement in the tissue in order to assess its underlying mechanical properties. In this paper, we studied the relationship between measured displacement and stiffness in gels and tissues in vitro. Two focused ultrasound transducers with a 100 mm focal length were used at frequencies of 3.7500 MHz and either 3.7502 (or 3.7508 MHz), respectively, in order to produce an oscillatory motion at 200 Hz in the gel or tissue. A 1.1 MHz diagnostic transducer (Imasonics, Inc.) was also focused at 100 mm and acquired 5 ms RF signals (pulse repetition frequency (PRF)=3.5 kHz) at 100 MHz sampling frequency during radiation force application. First, three 50x50 mm(2) acrylamide gels were prepared at concentrations of 4%, 8% and 16%. The resulting displacement was estimated using crosscorrelation techniques between successively acquired RF signals with a 2 mm window and 80% window overlap at 1260 W/cm(2). A normal 1-D indentation instrument (TeMPeST) applied oscillatory loads at 0.1-200 Hz with a 5 mm-diameter flat indenter. Then, 12 displacement measurements in 6 porcine muscle specimens (two measurements/case, as above) were made in vitro, before and after ablation which was performed for 10 s at 1260 W/cm(2). In all gel cases, the harmonic displacement was found to linearly increase with intensity and exponentially decrease with gel concentration. The TeMPeST measurements showed that the elastic moduli for the 4%, 8% and 16% gels equaled 3.93+/-0.06, 17.1+/-0.2 and 75+/-2 kPa, respectively, demonstrating that the HMI displacement estimate depends directly on the gel stiffness. Finally, in the tissues samples, the mean displacement amplitude showed a twofold decrease between non-ablated and ablated tissue, demonstrating a correspondence between the HMI response and an increase in stiffness measured with the TeMPeST instrument.
Ultrasonics 05/2004; 42(1-9):951-6. · 1.84 Impact Factor
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ABSTRACT: A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snell's critical angle experience a mode conversion from an incident longitudinal wave into a shear wave in the bone layers and then back to a longitudinal wave in the brain. The skull's shear speed provides a better impedance match, less refraction, and less phase alteration than its longitudinal counterpart. Therefore, the idea of utilizing a shear wave for focusing ultrasound in the brain is examined. Demonstrations of the phenomena, and numerical predictions are first studied with plastic phantoms and then using an ex vivo human skull. It is shown that at a frequency of 0.74 MHz the transskull shear method produces an amplitude on the order of--and sometimes higher than--longitudinal propagation. Furthermore, since the shear wave experiences a reduced overall phase shift, this indicates that it is plausible for an existing noninvasive transskull focusing method [Clement, Phys. Med. Biol. 47(8), 1219-1236 (2002)] to be simplified and extended to a larger region in the brain.
The Journal of the Acoustical Society of America 04/2004; 115(3):1356-64. · 1.55 Impact Factor
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ABSTRACT: A planar forward projection algorithm is combined with ray theory to describe longitudinal propagation through an arbitrary number of randomly oriented isotropic layers. This method first measures the space-time pressure field in a plane, then uses wavevector frequency-domain methods to project the field through layered media and to an arbitrary new plane, not necessarily parallel to the initial plane. The approach is valid for longitudinal propagation through liquid layers and in solids, such as soft tissues, that can be approximated as viscous liquids. The algorithm is verified by propagating the field from a 0.5 MHz planar transducer through a combination of rubber, plastic, and water layers. Hydrophone measurements indicate correlation between measured and simulated fields for angles below the longitudinal critical angles of the layered materials.
IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 01/2004; · 1.69 Impact Factor
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ABSTRACT: Needle and spot-poled membrane hydrophones using polyvinylidene fluoride (PVDF) sensors are widely used for characterization of biomedical ultrasound fields. It is known that, in measurements of continuous-wave (CW) fields, standing waves may be generated between the transducer and the hydrophone, distorting the field and possibly alternating the signal of the hydrophone. This study uses a three-dimensional, full-wave method to computationally simulate the distortion in the CW field caused by needle and membrane hydrophones. The physical model used in simulations is based on the linear time-harmonic wave equation, which therefore neglects the effects of nonlinear wave propagation. The significance of the distortion is examined by comparing fields emitted by 0.5-5.0 MHz planar circular transducers in the absence and presence of the hydrophones. In addition, the effect of the field distortions on the signal of the hydrophones is studied with simulated measurements. The simulations showed an observable standing wave pattern between the source and the needle hydrophone if the diameter of the needle was larger than a half of the wavelength. However, the standing waves had no clear effect on the signal of the hydrophone. The presence of membrane hydrophone in the CW field generated notable standing waves. Furthermore, the standing waves caused a periodic distortion to the signal of the membrane hydrophone.
IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 12/2003; · 1.69 Impact Factor
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ABSTRACT: Efficient and controlled delivery is one of the largest obstacles towards effective clinical use of gene therapy. In this study, we investigate the use of MRI-monitored ultrasound to induce enhanced expression of luciferase after local injection of the gene construct Ad-HSP-Luc, an adenoviral vector containing a human hsp70B promoter and a transgene for the firefly luciferase gene. Using a construct that includes an hsp promoter allows us to activate the associated transgene only in areas that are subsequently heated after injection. Using ultrasound imaging, 1mL of purified virus was injected into both lobes of the prostates of three beagles. 48 hours later, under MRI guidance, we heated the left lobe of the prostate using a 1.5MHz ultrasound transducer driven by a multi-channel, RF driving system. Left lobe prostate temperature was maintained at or above 42°C for periods of 25 minutes as measured by thermocouples placed in the prostate. After 12 hours, the dogs were sacrificed and the lobes were analyzed for luciferase activity. Increased luciferase expression was observed in areas that were exposed to ultrasonic heating. This study demonstrates the feasibility of using ultrasonic heating to spatially control transgene expression using a minimally invasive approach.
Ultrasonics, 2003 IEEE Symposium on; 11/2003
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ABSTRACT: Therapeutic ultrasound phased arrays show great promise in the treatment of brain disorders and deep-seated tumors where precise beam steering and controlled power deposition are needed as stated in D. Daum et al. (1999) and G.T. Clement et al. (2000). In addition, cavitation and mechanical effects, which are fast becoming essential elements of these therapies, could potentially be better controlled with phased array systems that employ multi-frequency techniques according to S. Umemura and K. Kawabata (1996) and J.Y. Chapelon et al. (1996). However, these recent therapeutic ultrasound applications increase the demands on the phased array hardware, both the ultrasound transducer and the multi-channel electronic driving system. First, large scale (greater than 200 elements) high-density (elements on the order of 1/2 or less), broadband ultrasound phased array transducers capable of generating high power fields are required. Second, multi-channel amplifier systems that are capable of fully utilizing these large-scale, high-density, broadband arrays need to be developed. With the advent of high power piezocomposites according to T.R. Shrout et al. (1980) and T.R. Gururaja et al. (1980) broadband high-density transducers are now available for therapy; however, the current driving system technology still falls short. In this paper, we describe the design, construction, and evaluation for a multi-channel broadband phased array amplifier system capable of driving large-scale therapeutic phased arrays.
Ultrasonics, 2003 IEEE Symposium on; 11/2003
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ABSTRACT: The technique of harmonic motion imaging (HMI) utilizes the localized stimulus of the oscillatory ultrasonic radiation force as produced by two overlapping beams of distinct frequencies, and estimates the resulting harmonic displacement in the tissue in order to assess its underlying mechanical properties. In this paper, we studied the relationship between the measured displacement and the gel/tissue stiffness. Two focused transducers with a 100 mm focus were used at the frequencies of 3.7500 MHz and 3.7502 MHz (or 3.7508 MHz depending on the case), respectively, in order to produce an oscillatory motion at 200 Hz in the gel (or, 800 Hz in the tissue). A 1.1 MHz diagnostic transducer (Imasonics Inc.) was also focused at 100 mm and acquired RF signals of 5 ms in total duration (PRF=3.5 kHz) at 100 MHz sampling frequency during radiation force application. First, three acrylamide gels of 50×50 mm<sup>2</sup> were prepared at concentrations of 4%, 8% and 16%. The resulting displacement was estimated using crosscorrelation techniques between successively acquired RF signals with a 2 mm window and 80% window overlap at 1260 W/cm<sup>2</sup>. A 1-D normal indentation instrument (TeMPeST) applied oscillatory loads at 0.5-200 Hz with a 5 mm-diameter flat indenter. Then, 12 displacement measurements in six ex vivo porcine muscle specimens (2 measurements/case) were made using 1260 W/cm<sup>2</sup>, before and after ablation for 10s at 1260 W/cm<sup>2</sup>. In all gel cases, the harmonic displacement was found to steadily decrease with gel concentration. The TeMPeST measurements showed that the elastic moduli for the 4%, 8% and 16% gels equaled 3.93+/-0.06kPa, 17.1+/-0.2kPa and 75+/-2kPa, respectively; demonstrating, thus, that the HMI displacement estimate depends directly on the gel stiffness. Finally, in the ex vivo tissues, the mean displacement amplitude showed a two-fold decrease between non-ablated and ablated tissue; depicting thus the stiffness dependence of the HMI response in tissues.
Ultrasonics, 2003 IEEE Symposium on; 11/2003
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P E Huber,
M J Mann,
L G Melo,
A Ehsan,
D Kong,
L Zhang,
M Rezvani,
P Peschke,
F Jolesz,
V J Dzau, K Hynynen
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ABSTRACT: The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.
Gene Therapy 10/2003; 10(18):1600-7. · 3.71 Impact Factor
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ABSTRACT: The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R(2)) of 0.6694 and bovine fat resulted in an R(2) of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R(2) of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery.
Ultrasound in Medicine & Biology 03/2003; 29(2):293-9. · 2.29 Impact Factor
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ABSTRACT: In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand while rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MRT2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI thermometry closely correlated with the resulting lesion as examined by T2-weighted imaging. The lesions created with the gas-bubble-enhanced heating exposures were 2-3 times larger by volume, consistently more spherical in shape and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo. MRI thermometry techniques were successfully used to monitor the thermal effects mediated by the bubble-enhanced exposures.
Physics in Medicine and Biology 02/2003; 48(2):223-41. · 2.83 Impact Factor
