Effects of breast structure on high-intensity focused ultrasound focal error.

BACKGROUND: The development of imaging technologies and breast cancer screening allowed early detection of breast cancers. High-intensity focused ultrasound (HIFU) is a non-invasive cancer treatment, but the success of HIFU ablation was depending on the system type, imaging technique, ablation protocol, and patient selection. Therefore, we aimed to determine the relationship between breast tissue structure and focal error during breast cancer HIFU treatment. METHODS: Numerical simulations of the breast cancer HIFU ablation were performed using digital breast phantoms constructed using the magnetic resonance imaging data obtained from 12 patients. RESULTS: The focal shapes were distorted despite breast tissue representing soft tissue. Focal errors are caused by the complex distribution of fibroglandular tissue, and they depend on the target position and the arrangement of the transducer. We demonstrated that the focusing ratio increases with the decrease in the local acoustic inhomogeneity, implying that it may be used as an indicator to reduce the HIFU focal error depending on the breast structure. CONCLUSIONS: The obtained results demonstrated that the focal error observed during the breast cancer HIFU treatment is highly dependent on the structure of fibroglandular tissue. The optimal arrangement of the transducer to the target can be obtained by minimizing the local acoustic inhomogeneity before the breast cancer HIFU treatment.

Hyperthermal molecular beam source using a non-diaphragm-type small shock tube.

We have developed a hyperthermal molecular beam source employing a non-diaphragm-type small shock tube for gas-surface interaction studies. Unlike conventional shock-heated beam sources, the capability of repetitive beam generation without the need for replacing a diaphragm makes our beam source suitable for scattering experiments, which require signal accumulation for a large number of beam pulses. The short duration of shock heating alleviates the usual temperature limit due to the nozzle material, enabling the generation of a molecular beam with higher translational energy or that containing dissociated species. The shock-heated beam is substantially free from surface-contaminating impurities that are pronounced in arc-heated beams. We characterize the properties of nitrogen and oxygen molecular beams using the time-of-flight method. When both the timing of beam extraction and the supply quantity of nitrogen gas are appropriately regulated, our beam source can generate a nitrogen molecular beam with translational energy of approximately 1 eV, which corresponds to the typical activation energy of surface reactions. Furthermore, our beam source can generate an oxygen molecular beam containing dissociated oxygen atoms, which can be a useful probe for surface oxidation. The dissociation fraction along with the translational energy can be adjusted through the supply quantity of oxygen gas.

Focused Ultrasound and Lithotripsy.

Shock wave lithotripsy has generally been a first choice for kidney stone removal. The shock wave lithotripter uses an order of microsecond pulse durations and up to a 100 MPa pressure spike triggered at approximately 0.5-2 Hz to fragment kidney stones through mechanical mechanisms. One important mechanism is cavitation. We proposed an alternative type of lithotripsy method that maximizes cavitation activity to disintegrate kidney stones using high-intensity focused ultrasound (HIFU). Here we outline the method according to the previously published literature (Matsumoto et al., Dynamics of bubble cloud in focused ultrasound. Proceedings of the second international symposium on therapeutic ultrasound, pp 290-299, 2002; Ikeda et al., Ultrasound Med Biol 32:1383-1397, 2006; Yoshizawa et al., Med Biol Eng Comput 47:851-860, 2009; Koizumi et al., A control framework for the non-invasive ultrasound the ragnostic system. Proceedings of 2009 IEEE/RSJ International Conference on Intelligent Robotics and Systems (IROS), pp 4511-4516, 2009; Koizumi et al., IEEE Trans Robot 25:522-538, 2009). Cavitation activity is highly unpredictable; thus, a precise control system is needed. The proposed method comprises three steps of control in kidney stone treatment. The first step is control of localized high pressure fluctuation on the stone. The second step is monitoring of cavitation activity and giving feedback on the optimized ultrasound conditions. The third step is stone tracking and precise ultrasound focusing on the stone. For the high pressure control we designed a two-frequency wave (cavitation control (C-C) waveform); a high frequency ultrasound pulse (1-4 MHz) to create a cavitation cloud, and a low frequency trailing pulse (0.5 MHz) following the high frequency pulse to force the cloud into collapse. High speed photography showed cavitation collapse on a kidney stone and shock wave emission from the cloud. We also conducted in-vitro erosion tests of model and natural kidney stones. For the model stones, the erosion rate of the C-C waveform showed a distinct advantage with the combined high and low frequency waves over either wave alone. For optimization of the high frequency ultrasound intensity, we investigated the relationship between subharmonic emission from cavitation bubbles and stone erosion volume. For stone tracking we have also developed a non-invasive ultrasound theragnostic system (NIUTS) that compensates for kidney motion. Natural stones were eroded and most of the resulting fragments were less than 1 mm in diameter. The small fragments were small enough to pass through the urethra. The results demonstrate that, with the precise control of cavitation activity, focused ultrasound has the potential to be used to develop a less invasive and more controllable lithotripsy system.

Molecular beam study of the scattering behavior of water molecules from a graphite surface.

Gas flow in nanospaces is greatly affected by the scattering behavior of gas molecules on solid surfaces, resulting in unique mass transport properties. In this paper, the molecular beam scattering experiment of water molecules on a graphite surface was conducted to understand their scattering dynamics in an incident energy range that corresponds to their thermal velocity distribution at room temperature (35-130 meV). Because of the large adsorption energy (∼100 meV), the scattering behavior is quite sensitive to the incident energy even within this narrow energy range. For relatively large incident energies, the direct-inelastic and trapping-desorption channels have comparable contributions to the scattering process on the surface at 300 K. In contrast, when the incident energy decreases well below the adsorption energy on the surface, the trapping-desorption channel becomes dominant, changing the scattering pattern from directional to diffusive scattering. As a result, the tangential momentum accommodation coefficient (TMAC), which significantly impacts the mass transport in nanospaces, largely depends on the incident energy. A decrease in the incident energy from 130 to 35 meV doubles the TMAC (0.42 to 0.86). In addition to the incident energy, the TMAC shows a strong dependence on the surface temperature. With increasing the surface temperature from 300 to 500 K, the scattering becomes more directional because of the increasing contribution of the direct-inelastic channel, which reduces the TMAC for the incident beam energy of 35 meV to 0.48.

Temperature distributions measurement of high intensity focused ultrasound using a thin-film thermocouple array and estimation of thermal error caused by viscous heating.

To improve the throughput of high intensity focused ultrasound (HIFU) treatment, we have considered a focus switching method at two points. For this method, it is necessary to evaluate the thermal distribution under exposure to ultrasound. The thermal distribution was measured using a prototype thin-film thermocouple array, which has the advantage of minimizing the influence of the thermocouple on the acoustic and temperature fields. Focus switching was employed to enlarge the area of temperature increase and evaluate the proposed evaluation parameters with respect to safety and uniformity. The results indicate that focus switching can effectively expand the thermal lesion while maintaining a steep thermal boundary. In addition, the influence caused by the thin-film thermocouple array was estimated experimentally. This thermocouple was demonstrated to be an effective tool for the measurement of temperature distributions induced by HIFU.

Localized elasticity measurement for detection of coagulation during HIFU therapy.

High intensity focused ultrasound (HIFU) treatment is one minimally invasive treatment method for cancer. Visualizing the internal treatment area of a body during HIFU treatment is required in order to achieve appropriate beam positioning and HIFU dosage. The objective of this work is to develop an ultrasound monitoring system for thermally induced coagulation. Localized motion imaging (LMI) is a monitoring method used to detect a localized mechanical response that is dependent on changes in tissue stiffness caused by thermal coagulation. In LMI, amplitude modulated HIFU causes oscillation of tissues in the HIFU focal area. The elastic modulus at a coagulated area increases and can be detected as an area with decreased oscillation amplitude., Localized control of the oscillation by changing the modulation frequency was conducted to increase the detection sensitivity for small coagulated areas in porcine liver. 2 and 7.5 MHz transducers were employed for HIFU and imaging, respectively. The amplitude modulation frequency was changed in the range from 50 to 200 Hz. The acoustic intensity of HIFU was 2.0 kW/cm2 at the focus and the exposure time was 45 s. The decrease in the amplitude of tissue oscillation at the focal point was detected within 5-10 s of HIFU exposure at the highest modulation frequency. The detected amplitude was decreased to 0.2, which indicates that for LMI, a high modulation frequency is suitable for the detection of small coagulation areas or areas of initial coagulation.

A non-diaphragm type small shock tube for application to a molecular beam source.

A non-diaphragm type small shock tube was developed for application to a molecular beam source, which can generate beams in the energy range from 1 to several electron volts and beams containing dissociated species such as atomic oxygen. Since repetitive high-frequency operation is indispensable for rapid signal acquisition in beam scattering experiments, the dimensions of the shock tube were miniaturized to reduce the evacuation time between shots. The designed shock tube is 2-4 mm in diameter and can operate at 0.5 Hz. Moreover, a high shock Mach number at the tube end is required for high-energy molecular beam generation. To reduce the shock attenuation caused by the wall boundary layer, which becomes significant in small-diameter tubes, we developed a high-speed response valve employing the current-loop mechanism. The response time of this mechanism is about 100 µs, which is shorter than the rupture time of conventional diaphragms. We show that the current-loop valve generates shock waves with shorter formation distances (about 200-300 mm) than those of conventional shock tubes. In addition, the converging geometry efficiently accelerates shock wave in the small-diameter tubes. The optimal geometry of the shock tube yields shock Mach number around 7, which indicates that the translation energy of molecular beams can exceed 1 eV even in the presence of the real gas effect.

Mechanical clot damage from cavitation during sonothrombolysis.

Recent studies have shown that high intensity focused ultrasound (HIFU) accelerates thrombolysis for ischemic stroke. Although the mechanisms are not fully understood, cavitation is thought to play an important role. The goal of this paper is to investigate the potential for cavitation to cause mechanical damage to a blood clot. The amount of damage to the fiber network caused by a single bubble expansion and collapse is estimated by two independent approaches: One based on the stretch of individual fibers and the other based on the energy available to break individual fibers. The two methods yield consistent results. The energy method is extended to the more important scenario of a bubble outside a blood clot that collapses asymmetrically creating an impinging jet. This leads to significantly more damage compared to a bubble embedded within the clot structure. Finally, as an example of how one can apply the theory, a simulation of the propagation of HIFU waves through model calvaria of varying density is explored. The maximum amount of energy available to cause damage to a blood clot increases as the density of the calvaria decreases.

A novel high intensity focused ultrasound robotic system for breast cancer treatment.

High intensity focused ultrasound (HIFU) is a promising technique for cancer treatment owing to its minimal invasiveness and safety. However, skin burn, long treatment time and incomplete ablation are main shortcomings of this method. This paper presents a novel HIFU robotic system for breast cancer treatment. The robot has 4 rotational degrees of freedom with the workspace located in a water tank for HIFU beam imaging and ablation treatment. The HIFU transducer combined with a diagnostic 2D linear ultrasound probe is mounted on the robot end-effector, which is rotated around the HIFU focus when ablating the tumor. HIFU beams are visualized by the 2D probe using beam imaging. Skin burn can be prevented or alleviated by avoiding long time insonification towards the same skin area. The time cost could be significantly reduced, as there is no need to interrupt the ablation procedure for cooling the skin. In addition, our proposed robot control strategies can avoid incomplete ablation. Experiments were carried out and the results showed the effectiveness of our proposed system.

Ultrasound-mediated gene transfection in vitro: effect of ultrasonic parameters on efficiency and cell viability.

Ultrasound (US)-mediated gene transfection in the presence of microbubbles is a recently developed and promising non-viral gene delivery method. Optimising the parameters used in ultrasonic transfection is urgently required in order to realise higher transfection efficiencies in clinical settings. This study examined the effect of ultrasound exposure parameters on plasmid DNA transfection in mouse embryonic fibroblast cell lines using perfluorobutane bubbles. Variations in US intensity (0-11 W/cm2), pulse repetition frequency (PRF, 50-50,000 Hz), duty ratio (10 to 50%), exposure time (0-120 s) and microbubble volume concentration (0 to 10%) were tested, and the microbubble volume concentration was also monitored during exposure. Through the experiments, the mechanism of how variations in parameters influence US-mediated gene transfection was discussed, which can provide a basis for future applications of ultrasound mediated transfection.

Orientation and internal flow of a vesicle in tank-treading motion in shear flow.

Deformation, orientation and internal flow of lipid bilayer vesicles in linear shear flows are investigated using phase contrast microscopy. We construct a rotating-cylinder apparatus, which can generate a linear shear flow with constant shear rates. Vesicles are prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) by the gentle hydration method. When visualizing internal flows, polystyrene tracer particles are mixed with the hydration water solution. In our observation, vesicles deform to steady ellipsoidal shapes and show constant orientations given by θ(i), which is the angle between the major axis and the flow direction. The tracer particles inside a vesicle rotate around the center of the vesicle along ellipsoidal orbits, which are homothetic to the shape of the vesicle. It is shown that the relationship between θ(i) and the swelling ratio (volume/surface ratio) S(w) agrees quantitatively with the experimental result of Abkarian et al. [Biophys. J.89, 1055 (2005)], which was obtained with vesicles in wall-bounded shear flows. It also agrees with a theoretical analysis of Keller and Skalak [J. Fluid Mech.120, 27 (1982)] and other numerical simulations. It is also shown that angular velocities of the particles near the membrane change periodically and agree quantitatively with the experimental result for the motion of a particle adhering to the membrane of a tank-treading vesicle [Kantsler and Steinberg, Phys. Rev. Lett.95, 258101 (2005)]. A statistical analysis indicates that the velocity of the internal fluid close to the membrane is not constant along the circumference, which implies the possibility of a three-dimensional flow field of the lipid molecules or an apparent stretching motion of the membrane by the effect of hidden surface area due to thermal fluctuation.

Visual servoing for a US-guided therapeutic HIFU system by coagulated lesion tracking: a phantom study.

BACKGROUND: Applying ultrasound (US)-guided high-intensity focused ultrasound (HIFU) therapy for kidney tumours is currently very difficult, due to the unclearly observed tumour area and renal motion induced by human respiration. In this research, we propose new methods by which to track the indistinct tumour area and to compensate the respiratory tumour motion for US-guided HIFU treatment. METHODS: For tracking indistinct tumour areas, we detect the US speckle change created by HIFU irradiation. In other words, HIFU thermal ablation can coagulate tissue in the tumour area and an intraoperatively created coagulated lesion (CL) is used as a spatial landmark for US visual tracking. Specifically, the condensation algorithm was applied to robust and real-time CL speckle pattern tracking in the sequence of US images. Moreover, biplanar US imaging was used to locate the three-dimensional position of the CL, and a three-actuator system drives the end-effector to compensate for the motion. Finally, we tested the proposed method by using a newly devised phantom model that enables both visual tracking and a thermal response by HIFU irradiation. RESULTS: In the experiment, after generation of the CL in the phantom kidney, the end-effector successfully synchronized with the phantom motion, which was modelled by the captured motion data for the human kidney. The accuracy of the motion compensation was evaluated by the error between the end-effector and the respiratory motion, the RMS error of which was approximately 2 mm. CONCLUSION: This research shows that a HIFU-induced CL provides a very good landmark for target motion tracking. By using the CL tracking method, target motion compensation can be realized in the US-guided robotic HIFU system.

Three-dimensional computer-controlled acoustic pressure scanning and quantification of focused ultrasound.

We propose an automated needle hydrophone-based scanning system to measure high-resolution 3-D acoustic pressure distributions generated by high-intensity focused ultrasound (HIFU). The hardware consists of a host computer, subsystems for HIFU generation, and an oscilloscope to sample the pressure response from a sensor in a water tank. Software was developed to control the hardware subsystems, to search for the initial scan position, and to design the scanning path and volume. A preoperative scanning plan with three perpendicular planes is used to manipulate the position of the HIFU transducer and to automate the acquisition of the spatial acoustic pressure distribution. The post-processing process displays the scanning results, compensates time delays caused by continuous linear scans, and quantifies the focal region. A method to minimize the displacement error induced by the time delay improves the scanning speed of a conventional needle hydrophone-based scanning system. Moreover, a noise-robust, automatic-focus searching algorithm using Gaussian function fitting reduces the total number of iterations and prevents the initial scanning position search from diverging. Finally, the minimum-volume enclosing ellipsoid approximation is used to quantify the size and orientation of the 3-D focal region thresholded by the minimum pressure of interest for various input conditions and to test the reproducibility of the scanning system.

The deformation behavior of multiple red blood cells in a capillary vessel.

The deformation of multiple red blood cells in a capillary flow was studied numerically. The immersed boundary method was used for the fluid red blood cells interaction. The membrane of the red blood cell was modeled as a hyperelastic thin shell. The numerical results show that the apparent viscosity in the capillary flow is more sensitive to the change of shear coefficient of the membrane than the bending coefficient and surface dilation coefficient, and the increase in the shear coefficient results in an increase in the pressure drop in the blood flow in capillary vessels in order to sustain the same flux rate of red blood cells.

High intensity focused ultrasound lithotripsy with cavitating microbubbles.

In the medical ultrasound field, microbubbles have recently been the subject of much interest. Controlling actively the effect of the microbubbles, a novel therapeutic method has been investigated. In this paper, our works on high intensity focused ultrasound (HIFU) lithotripsy with cavitating microbubbles are reviewed and the cavitation detection method to optimize the HIFU intensity is investigated. In the HIFU lithotripsy, collapse of the cloud cavitation is used to fragment kidney stones. Cloud cavitation is potentially the most destructive form of cavitation. When the cloud cavitation is acoustically forced into a collapse, it has the potential to concentrate a very high pressure. For the control of the cloud cavitation collapse, a novel two-frequency wave (cavitation control [C-C] waveform) is designed; a high-frequency ultrasound pulse (1-4 MHz) to create the cloud cavitation and a low-frequency trailing pulse (500 kHz) following the high-frequency pulse to force the cloud into collapse. High-speed photography showed the cavitation collapse on the stone and the shock-wave emission from the cloud. In vitro erosion tests of model and natural stones were also conducted. In the case of model stones, the erosion rate of the C-C waveform showed a distinct advantage with the combined high- and low-frequency waves over either wave alone. For the optimization of the high-frequency ultrasound intensity, the subharmonic acoustic pressure was examined. The results showed relationship between the subharmonic pressure from cavitating bubbles induced by the high-frequency ultrasound and eroded volume of the model stones. Natural stones were eroded and most of the resulting fragments were less than 1 mm in diameter. The method has the potential to provide a novel lithotripsy system with small fragments and localized cavitating bubbles on a stone.

A molecular dynamics study on heat transfer characteristics at the interfaces of alkanethiolate self-assembled monolayer and organic solvent.

In this paper, we present molecular dynamics (MD) simulations of interfaces composed of self-assembled monolayers (SAMs) and solvents in order to investigate the heat transfer characteristics at the interface. Two typical normal alkylthiolate SAMs with different chain lengths, i.e., 1-propanethiol C(3)H(7)SH and 1-dodecanethiol (C(12)H(25)SH) chemically adsorbed on Au(111) substrate surfaces, were used, and toluene was adopted as the organic solvent. In addition to the SAM systems, an interface composed of the bare solid substrate and solvent (without SAMs) was analyzed for comparison. Nonequilibrium MD simulations, in which a temperature gradient perpendicular to the interface was imposed, were performed and the difference in thermal boundary resistance in the interface systems was discussed. We observed that the SAM interfaces have smaller thermal resistance when compared with that of the bare solid interface. In order to understand the mechanisms of the small resistance at the SAM-solvent interfaces, the vibrational character of molecules in each phase, which contacted each other at the interface was analyzed and a detailed adsorbed structure of solvent molecule in the interface region was extracted. As a result, a clear difference in these characters was found between the SAM interfaces and bare solid interface.

Inhomogeneous decomposition of ultrathin oxide films on Si(100): application of Avrami kinetics to thermal desorption spectra.

Thermal decomposition of ultrathin oxide layers on silicon surface was investigated with temperature programed desorption. Oxide layers were formed on Si(100) at 400 degrees C by exposure to O(2) molecular beam. Desorption spectrum for oxygen coverages between 1.7 and 2.6 ML exhibits a single dominant peak with an additional broad peak at lower temperatures. The former peak corresponds to stable binding states of O atoms at dimer bridge sites and dimer backbond sites. The high peak intensity indicates that most O atoms are at stable states. The latter peak corresponds to an unstable binding state, where O atoms are presumably trapped at dangling bonds. The SiO desorption rate from the stable binding states is well described by Avrami kinetics, suggesting that the decomposition process is spatially inhomogeneous with void formation and growth. The rate-determining step is the reaction at void perimeter even if the overlap between voids becomes quite large. The Avrami exponents determined from our experiment indicate that the increase in the initial coverage makes the oxide layer more stable and suppresses the rate of void formation at the potential nucleation sites.

The effects of surfactant on the multiscale structure of bubbly flows.

It is well known that a bubble in contaminated water rises much slower than one in purified water, and the rising velocity in a contaminated system can be less than half that in a purified system. This phenomenon is explained by the so-called Marangoni effect caused by surfactant adsorption on the bubble surface. In other words, while a bubble is rising, there exists a surface concentration distribution of surfactant along the bubble surface because the adsorbed surfactant is swept off from the front part and accumulates in the rear part by advection. Owing to this surfactant accumulation in the rear part, a variation of surface tension appears along the surface and this causes a tangential shear stress on the bubble surface. This shear stress results in the decrease in the rising velocity of the bubble in contaminated liquid. More interestingly, this Marangoni effect influences not only the bubble's rising velocity but also its lateral migration in the presence of mean shear. Together, these influences cause a drastic change of the whole bubbly flow structures. In this paper, we discuss some experimental results related to this drastic change in bubbly flow structure. We show that bubble clustering phenomena are observed in an upward bubbly channel flow under certain conditions of surfactant concentrations. This cluster disappears with an increase in the concentration. We explain this phenomenon by reference to the lift force acting on a bubble in aqueous surfactant solutions. It is shown that the shear-induced lift force acting on a contaminated bubble of 1mm size can be much smaller than that on a clean bubble.

Fluoroscopic bone fragment tracking for surgical navigation in femur fracture reduction by incorporating optical tracking of hip joint rotation center.

A new method for fluoroscopic tracking of a proximal bone fragment in femoral fracture reduction is presented. The proposed method combines 2-D and 3-D image registration from single-view fluoroscopy with tracking of the head center position of the proximal femoral fragment to improve the accuracy of fluoroscopic registration without the need for repeated manual adjustment of the C-arm as required in stereo-view registrations. Kinematic knowledge of the hip joint, which has a positional correspondence with the femoral head center and the pelvis acetabular center, allows the position of the femoral fragment to be determined from pelvis tracking. The stability of the proposed method with respect to fluoroscopic image noise and the desired continuity of the fracture reduction operation is demonstrated, and the accuracy of tracking is shown to be superior to that achievable by single-view image registration, particularly in depth translation.

Microbubble-induced increase in ablation of liver tumors by high-intensity focused ultrasound.

We studied the possibility of using high-intensity focused ultrasound (HIFU) together with a microbubble agent to treat hepatocellular carcinoma. Development of liver tumors in rats was induced by administration of Dimethylnitrosamin (100ppm). Rats with liver tumors were anesthetized, underwent laparotomy, and were given the microbubble agent Levovist or saline intravenously. After the injection, the liver was exposed to HIFU for 30s (2.18MHz, 600W/cm(2), 40mm in diameter). Immediately after HIFU exposure, ultrasound images of the HIFU area were evaluated. Then the liver was excised and the volume of coagulated tissue was measured. The mean volumes of hyperechoic areas after HIFU were as follows (mm(3), Levovist versus saline: 355.3+/-180.7 versus 47.4+/-35.6, P<0.001, n=13). The volumes of liver tissue coagulated by HIFU were as follows (mm(3), Levovist versus saline: 275.3+/-120.0 versus 60.1+/-23.6, P<0.001, n=13). On microscopic examination of areas exposed to HIFU, implosion cysts were seen, and many cancer cells were found to have been destroyed completely (loss of cell membranes or nuclei). In conclusion, the microbubble agent Levovist can increase the volume of tissue coagulated by HIFU.