Enhanced ultrasound transmission through the human skull using shear mode conversion

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.     

Forced linear oscillations of microbubbles in blood capillaries

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 effect of wave reflection and refraction at soft tissue interfaces during ultrasound hyperthermia treatments.

An improved numerical model for calculating the ultrasonic power deposition in layered medium was developed and experimentally tested. The new model takes into account the ultrasound wave reflection and refraction at the tissue interfaces thereby providing improved accuracy in ultrasound hyperthermia treatment planning. The model was compared with a simplified model to evaluate when the tissue interfaces could be ignored in the hyperthermia treatment planning and evaluation. The effect of variations in water and tissue temperatures, the fat layer thicknesses, and the beam entrance angle were also investigated to establish guidelines for treatment execution. It was found that in most cases the effects of the soft tissue interfaces can be ignored. However, in some instances the acoustic focus may be shifted several millimeters off axis in layered medium. This is important when sharply focused transducers are used for ultrasound surgery or under the condition of pulsed, high-temperature hyperthermia treatments.     

Progress and problems in the application of focused ultrasound for blood-brain barrier disruption

Advances in neuroscience have resulted in the development of new diagnostic and therapeutic agents for potential use in the central nervous system (CNS). However, the ability to deliver the majority of these agents to the brain is limited by the blood-brain barrier (BBB), a specialized structure of the blood vessel wall that hampers transport and diffusion from the blood to the brain. Many CNS disorders could be treated with drugs, enzymes, genes, or large-molecule biotechnological products such as recombinant proteins, if they could cross the BBB. This article reviews the problems of the BBB presence in treating the vast majority of CNS diseases and the efforts to circumvent the BBB through the design of new drugs and the development of more sophisticated delivery methods. Recent advances in the development of noninvasive, targeted drug delivery by MRI-guided ultrasound-induced BBB disruption are also summarized.     

The use of ultrasound-stimulated acoustic emission in the monitoring of modulus changes with temperature

It has been previously shown that the amplitude of the ultrasound-stimulated acoustic emission (USAE) signal is sensitive to tissue temperature and, therefore, can help detect it. Its amplitude, however, is sensitive to both acoustical and mechanical parameters, that at most frequencies have opposite effects due to temperature. In this paper, we explore the feasibility of using a frequency shift of the resonant peaks of the USAE signal for monitoring the tissue stiffness variation with temperature. In a numerical simulation, the variation of the frequency shift at different temperatures is shown. Then, in a series of experiments involving a gel phantom and porcine muscle tissue, the frequency shift variation is shown to follow the known stiffness changes due to temperature. It is also shown that this shift indicates reversible changes as well as the onset of thermal coagulative necrosis. The necrosis is marked by a monotonically increasing positive frequency shift. It was thus shown that the USAE spectrum peaks undergo a negative shift (or, downshift) when the stiffness decreases and a positive shift (or, upshift) when the stiffness increases. The experimental frequency shifted around a peak at 22.1-22.5 kHz within a range of -250 to 80 Hz and -200 to 250 Hz for the gel and muscle tissue for the temperatures of 25-70 and 30-70 degrees C, respectively. Simulation and ex vivo experimental results indicate that the USAE frequency shift method can help decouple the mechanical from the acoustical parameter dependence as well as detect the onset of thermal coagulative necrosis.     

Estimating localized oscillatory tissue motion for assessment of the underlying mechanical modulus

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.     

The potential of transskull ultrasound therapy and surgery using the maximum available skull surface area

Based on previous studies, the transskull ultrasound field is re-examined by utilizing the maximum available skull surface area. The source is assumed to be in direct contact with the skull outer surface, and phase correction is adopted to obtain a sharp focus at a desired location. A digitized skull profile was obtained from Magnetic Resonance (MR) scan images of a volunteer. Two driving frequencies (0.5 and 1.0 MHz) within the appropriate frequency range for transskull ultrasound therapy and surgery are investigated. With no phase correction, there is no apparent transskull focus. With phase correction, a sharp transskull focus is obtained at the desired location. Both pressure and specific absorption rate (SAR) gains (ratios of pressure amplitude and SAR at the focal point compared to those on the outer skull surface) are examined, and it is shown that the skull heating problem can be overcome by utilizing the maximum available skull surface area. By specifying the phase correction for different locations, the focus can be successfully moved inside the deep brain volume without significantly compromising the pressure and SAR gains; however, the sidelobes may be of concern at superficial sites.     

Additive‐like amounts of HDPE prevent creep of molten LDPE: Phase‐behavior and thermo‐mechanical properties of a melt‐miscible blend

Low‐density polyethylene (LDPE) is the preferred type of polyolefin for many medical and electrical applications because of its superior purity and cleanliness. However, the inferior thermo‐mechanical properties as compared to, for example, high‐density polyethylene (HDPE), which arise because of the lower melting temperature of LDPE, constitute a significant drawback. Here, we demonstrate that the addition of minute amounts of HDPE to a LDPE resin considerably improves the mechanical integrity above the melting temperature of LDPE. A combination of dynamic mechanical analysis and creep experiments reveals that the addition of as little as 1 to 2 wt% HDPE leads to complete form stability above the melting temperature of LDPE. The investigated LDPE/HDPE blend is found to be miscible in the melt, which facilitates the formation of a solid‐state microstructure that features a fine distribution of HDPE‐rich lamellae. The absence of creep above the melting temperature of LDPE is rationalized with the presence of tie chains and trapped entanglements that connect the few remaining crystallites. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 146–156     

MRI-guided focused ultrasound treatments

Focused ultrasound (FUS) allows noninvasive focal delivery of energy deep into soft tissues. The focused energy can be used to modify and eliminate tissue for therapeutic purposes while the energy delivery is targeted and monitored using magnetic resonance imaging (MRI). MRI compatible methods to deliver these exposures have undergone rapid development over the past 10 years such that clinical treatments are now routinely performed. This paper will review the current technical and clinical status of MRI-guided focused ultrasound therapy and discuss future research and development opportunities.     

Simulations of lesion detection using a combined phased array LHMI-technique

Ultrasound based elasticity imaging techniques have been developed during the past decades. Some of these techniques are based on an internal radiation force stimulation in which a transient or dynamic radiation force is produced by using a single or dual-frequency sonication. In addition, sonication and data acquisition can be implemented using combined or separate transducers. In this simulation study of lesion detection using localized harmonic motion imaging (LHMI), we used a combined phased array designed for simultaneous thermal ablation and lesion detection. In the sonication mode, a focused single-frequency amplitude-modulated sonication is used to induce harmonic motion and in the tracking mode, some of the array elements are used for pulse-echo tracking of the induced displacements. The results showed that the size of the lesion affected the induced displacement around the sonication point. The displacement tracking simulations demonstrated that these changes in the displacement distributions can be detected using only a few of the array elements in the tracking mode but the exact size of the lesion can not be detected accurately. The simulations also showed that two lesions having the radius of 2.5mm can be distinguished if distance between these lesions is at least 2.5mm.