The influence of bone model geometries on the determination of skull acoustic properties.

In this study, we investigated the impact of various simulated skull bone geometries on the determination of skull speed of sound and acoustic attenuation values via optimization using transmitted pressure amplitudes beyond the bone. Using the hybrid angular spectrum method (HAS), we simulated ultrasound transmission through four model sets of different geometries involving sandwiched layers of diploë and cortical bone in addition to three models generated from CT images of ex-vivo human skull-bones. We characterized cost-function solution spaces for each model and, using optimization, found that when a model possessed appreciable variations in resolvable layer thickness, the predefined attenuation coefficients could be found with low error (RMSE < 0.

Influence of cerebrospinal fluid on power absorption during transcranial magnetic resonance-guided focused ultrasound treatment.

Background: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy.

Purpose: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments.

Magnetic resonance shear wave elastography using transient acoustic radiation force excitations and sinusoidal displacement encoding.

A magnetic resonance (MR) shear wave elastography technique that uses transient acoustic radiation force impulses from a focused ultrasound (FUS) transducer and a sinusoidal-shaped MR displacement encoding strategy is presented. Using this encoding strategy, an analytic expression for calculating the shear wave speed in a heterogeneous medium was derived. Green's function-based simulations were used to evaluate the feasibility of calculating shear wave speed maps using the analytic expression.

Development and characterization of a tissue mimicking psyllium husk gelatin phantom for ultrasound and magnetic resonance imaging.

To develop and characterize a tissue-mimicking phantom that enables the direct comparison of magnetic resonance (MR) and ultrasound (US) imaging techniques useful for monitoring high-intensity focused ultrasound (HIFU) treatments. With no additions, gelatin phantoms produce little if any scattering required for US imaging. This study characterizes the MR and US image characteristics as a function of psyllium husk concentration, which was added to increase US scattering.

Efficient shear wave elastography using transient acoustic radiation force excitations and MR displacement encoding.

Purpose: To present a novel MR shear wave elastography (MR-SWE) method that efficiently measures the speed of propagating wave packets generated using acoustic radiation force (ARF) impulses.

Methods: ARF impulses from a focused ultrasound (FUS) transducer were applied sequentially to a preselected set of positions and motion encoded MRI was used to acquire volumetric images of the propagating shear wavefront emanating from each point. The wavefront position at multiple propagation times was encoded in the MR phase image using a train of motion encoding gradient lobes.

Rapid full-wave phase aberration correction method for transcranial high-intensity focused ultrasound therapies.

Background: Non-invasive high-intensity focused ultrasound (HIFU) can be used to treat a variety of disorders, including those in the brain. However, the differences in acoustic properties between the skull and the surrounding soft tissue cause aberrations in the path of the ultrasonic beam, hindering or preventing treatment.

Methods: We present a method for correcting these aberrations that is fast, full-wave, and allows for corrections at multiple treatment locations.

MR thermometry for focused ultrasound monitoring utilizing model predictive filtering and ultrasound beam modeling.

Background: A major challenge in using magnetic resonance temperature imaging (MRTI) to monitor focused ultrasound (FUS) applications is achieving high spatio-temporal resolution over a large field of view (FOV). This is important to accurately monitor all ultrasound (US) power depositions. Magnetic resonance (MR) subsampling in conjunction with thermal model-based reconstruction of the MRTI utilizing Pennes bioheat transfer equation (PBTE) is one promising approach.

Phase aberration simulation study of MRgFUS breast treatments.

Purpose: This simulation study evaluates the effects of phase aberration in breast MR-guided focused ultrasound (MRgFUS) ablation treatments performed with a phased-array transducer positioned laterally to the breast. A quantification of these effects in terms of thermal dose delivery and the potential benefits of phase correction is demonstrated in four heterogeneous breast numerical models.

Methods: To evaluate the effects of varying breast tissue properties on the quality of the focus, four female volunteers with confirmed benign fibroadenomas were imaged using 3T MRI.

Kinetics of Ultrasonic Drug Delivery from Targeted Micelles.

To minimize the adverse side effects of conventional chemotherapy, a targeted micellar drug carrier was investigated that retains hydrophobic drugs in its core and then releases the drug via ultrasonic activation. This paper compares the percent drug release from folated versus non-folated micelles by insonation at 70 kHz and different acoustic power densities. The encapsulated drug is Doxoru- bicin (Dox).

Characterization and evaluation of tissue-mimicking gelatin phantoms for use with MRgFUS.

Background: A tissue-mimicking phantom that accurately represents human-tissue properties is important for safety testing and for validating new imaging techniques. To achieve a variety of desired human-tissue properties, we have fabricated and tested several variations of gelatin phantoms. These phantoms are simple to manufacture and have properties in the same order of magnitude as those of soft tissues.

A simulation technique for 3D MR-guided acoustic radiation force imaging.

Purpose: In magnetic resonance-guided focused ultrasound (MRgFUS) therapies, the in situ characterization of the focal spot location and quality is critical. MR acoustic radiation force imaging (MR-ARFI) is a technique that measures the tissue displacement caused by the radiation force exerted by the ultrasound beam. This work presents a new technique to model the displacements caused by the radiation force of an ultrasound beam in a homogeneous tissue model.

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy.

Purpose: Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up.

Materials And Methods: The controller realises time savings by modelling the heated treatment cell's future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell.

Treatment envelope evaluation in transcranial magnetic resonance-guided focused ultrasound utilizing 3D MR thermometry.

Background: Current clinical targets for transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) are all located close to the geometric center of the skull convexity, which minimizes challenges related to focusing the ultrasound through the skull bone. Non-central targets will have to be reached to treat a wider variety of neurological disorders and solid tumors. Treatment envelope studies utilizing two-dimensional (2D) magnetic resonance (MR) thermometry have previously been performed to determine the regions in which therapeutic levels of FUS can currently be delivered.

The accuracy and precision of two non-invasive, magnetic resonance-guided focused ultrasound-based thermal diffusivity estimation methods.

Purpose: The use of correct tissue thermal diffusivity values is necessary for making accurate thermal modelling predictions during magnetic resonance-guided focused ultrasound (MRgFUS) treatment planning. This study evaluates the accuracy and precision of two non-invasive thermal diffusivity estimation methods, a Gaussian temperature method and a Gaussian specific absorption rate (SAR) method.

Materials And Methods: Both methods utilise MRgFUS temperature data obtained during cooling following a short (<25 s) heating pulse.

Investigating the acoustic release of doxorubicin from targeted micelles.

The main problem associated with the administration of anti-cancer medication is that the drug is delivered throughout the body causing undesirable side effects. Therefore, it is important to synthesize drug carriers capable of minimizing the adverse side effects of chemotherapy by preferentially targeting tumor cells both actively (e.g.

Thermal sensitivity of endothelial cells on synthetic vascular graft material.

Purpose: The goal is to identify thermal exposures capable of reducing or eliminating cell survival on expanded polytetrafluoroethylene (ePTFE), in an effort to develop a mild hyperthermia treatment of neointimal hyperplasia in ePTFE vascular grafts.

Materials And Methods: Viable and dead bovine aortic endothelial cells were quantified following different thermal exposure conditions: cells on collagen-coated ePTFE sheets or tissue culture polystyrene dishes were heated at 42° and 45°C to determine their thermal sensitivity on different surfaces, and cells cultured on collagen-coated ePTFE sheets were heated at 43-50°C for various durations, followed by incubation at 37°C for 0 and 20 h, respectively. Significant cell death was set to be 50%.

Extension of the angular spectrum method to calculate pressure from a spherically curved acoustic source.

The angular spectrum method is an accurate and computationally efficient method for modeling acoustic wave propagation. The use of the typical 2D fast Fourier transform algorithm makes this a fast technique but it requires that the source pressure (or velocity) be specified on a plane. Here the angular spectrum method is extended to calculate pressure from a spherical transducer-as used extensively in applications such as magnetic resonance-guided focused ultrasound surgery-to a plane.

Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts.

Background: Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating.

The effect of electronically steering a phased array ultrasound transducer on near-field tissue heating.

Purpose: This study presents the results obtained from both simulation and experimental techniques that show the effect of mechanically or electronically steering a phased array transducer on proximal tissue heating.

Methods: The thermal response of a nine-position raster and a 16-mm diameter circle scanning trajectory executed through both electronic and mechanical scanning was evaluated in computer simulations and experimentally in a homogeneous tissue-mimicking phantom. Simulations were performed using power deposition maps obtained from the hybrid angular spectrum (HAS) method and applying a finite-difference approximation of the Pennes' bioheat transfer equation for the experimentally used transducer and also for a fully sampled transducer to demonstrate the effect of acoustic window, ultrasound beam overlap and grating lobe clutter on near-field heating.

In-plane parallel scanning: a microarray technology for point-of-care testing.

A new microarray technology is described for rapid, inexpensive, multiplex diagnostics assays. Referred to as "in-plane parallel scanning" (IPPS), this technology replaces expensive laser scanning with a grid of 100-μm-wide waveguides embedded in the chip's substrate, enabling real-time quantification of molecular complex formation on the chip's surface. Compared to conventional microarray technology, IPPS has advantages of shorter assay time and lower instrument cost and complexity so that the platform can potentially be used in point-of-care (POC) settings.

Cavitation properties of block copolymer stabilized phase-shift nanoemulsions used as drug carriers.

Cavitation properties of block copolymer stabilized perfluoropentane nanoemulsions have been investigated. The nanoemulsions were stabilized by two biodegradable amphiphilic block copolymers differing in the structure of the hydrophobic block, poly(ethylene oxide)-co-poly(L-lactide) (PEG-PLLA) and poly(ethylene oxide)-co-polycaprolactone (PEG-PCL). Cavitation parameters were measured in liquid emulsions and gels as a function of ultrasound pressure for unfocused or focused 1-MHz ultrasound.

Microbubble Generation in Phase-Shift Nanoemulsions used as Anticancer Drug Carriers.

The paper describes droplet-to-bubble transition in block copolymer stabilized perfluoropentane nanoemulsions. Three physical factors that trigger droplet-to-bubble transition in liquid emulsions and gels were evaluated, namely heat, ultrasound, and injections through fine-gauge needles. Among those listed, ultrasound irradiation was found the most efficient factor.

Degradation kinetics of stabilized Pluronic micelles under the action of ultrasound.

The majority of research in the area of acoustically-activated drug delivery from stabilized micelles has been focused on the rapid release of chemotherapy drugs from the core of such nano-carriers. Previous publications have shown that low-frequency ultrasound is able to release approximately 2% of Doxorubicin (Dox) from the core of Pluronic P105 micelles stabilized using a cross-linked network of N,N-diethylacrylamide (NanoDeliv) within 2 s of applying 70-kHz ultrasound. Here we use a custom-made ultrasound exposure chamber with fluorescence detection to measure the long-term fluorescence emissions of Dox from the NanoDeliv after 2 h of exposure to two ultrasound frequencies, 70 and 476 kHz, at a mechanical index of 0.

Dependence of aortic arch morphogenesis on intracardiac blood flow in the left atrial ligated chick embryo.

Partial left atrial ligation before cardiac septation redistributes intracardiac blood flow and produces left ventricular hypoplasia in the chick. We hypothesized that redistributed intracardiac blood flow adversely alters aortic arch development. We ligated the left atrial appendage with a 10-0 nylon suture at stage 21 chick embryos, then reincubated up to stage 34.