Biaxial Excitation and Reception Method Applied to Ultrasound Imaging.

The biaxial method consists of the utilization of orthogonal electric fields in single-element piezoceramics both in transmission and reception. This study demonstrates the application of the biaxial method to broadband transducers. We developed a three-element biaxial transducer array to demonstrate the feasibility of biaxial method in imaging applications.

Biaxial ultrasound driving technique for small animal blood-brain barrier opening.

Biaxial driving can more efficiently convert electrical power to forward acoustic power in piezoelectric materials, and the interaction between the orthogonal electric fields can produce a combination of extensional and shear deformations as a function of the phase difference between them to allow dynamic steering of the beam with a single-element. In this study, we demonstrate for the first time the application of a single-element biaxially driven ring transducerfor blood-brain barrier opening in mice, and compare it to that achieved with a conventional single-element highly focused (F# = 0.7) spherical transducer operating at a similar frequency.

Higher harmonics dynamic focalization in single-element ring transducers using biaxial driving.

Biaxial driving is a new driving technique that allows the steering of the ultrasound field generated by a single-element piezoceramic transducer. Because of their natural axisymmetric geometry, ultrasound generation with ring transducers can take advantage of the biaxial driving to change the focus of the beam generated by this type of transducer using only two driving signals. In this study, we applied the biaxial driving technique into a single-element PZT ring transducer operating at 500 kHz to produce a change in size and position of the focal spot while using the 1st (482 kHz), 3rd (1.

Comparing Phantom and Animal Metrics Applied in the Determination of Focused Ultrasound Stable and Inertial Cavitation Levels.

Objective: The opening of the blood-brain barrier (BBB) to allow therapeutic drug passage can be achieved by inducing microbubble cavitation using focused ultrasound (FUS). This approach can be monitored through analysis of the received signal to distinguish between stable cavitation associated with safe BBB opening and inertial cavitation associated with blood vessel damage. In this study, FUS phantom and animal studies were used to evaluate the experimental conditions that generate several cross-consistent metrics having the potential to be combined for the reliable, automatic control of cavitation levels.

Passive Directivity Detection Using Individual Biaxial Ultrasound Transducers.

Biaxial transducers are an emerging technology that can steer generated ultrasound waves using a single piezoceramic component. Simulations have also shown that biaxial transducers can passively estimate the direction of arrival (DOA) of sound waves when operating in the receive mode. This research seeks to experimentally verify biaxial directivity estimates and establish directivity as an independent parameter detected by biaxial transducers.

Aptamer-Functionalized Microbubbles Targeted to P-selectin for Ultrasound Molecular Imaging of Murine Bowel Inflammation.

Purpose: Our objectives were to develop a targeted microbubble with an anti-P-selectin aptamer and assess its ability to detect bowel inflammation in two murine models of acute colitis.

Procedures: Lipid-shelled microbubbles were prepared using mechanical agitation. A rapid copper-free click chemistry approach (azide-DBCO) was used to conjugate the fluorescent anti-P-selectin aptamer (Fluor-P-Ap) to the microbubble surface.

Investigation of hardware and software techniques to enhance the characteristics of focused ultrasound (FUS) spectra.

. Microbubble cavitation generated by focused ultrasound () can induce safe blood-brain-barrier () opening allowing therapeutic drug passage. Spectral changes in the hydrophone sensor signal are currently used to distinguish stable cavitation from inertial cavitation that can damage theGibbs' ringing, peak intensity loss and peak width increase are well-known distortions evident when using the discrete Fourier transform () to transform data containing a few hundred points.

Rapid Copper-free Click Conjugation to Lipid-Shelled Microbubbles for Ultrasound Molecular Imaging of Murine Bowel Inflammation.

Microbubbles are ultrasound contrast agents that can adhere to disease-related vascular biomarkers when functionalized with binding ligands such as antibodies or peptides. The biotin-streptavidin approach has predominantly been used as the microbubble labeling approach in preclinical imaging. However, due to the immunogenicity of avidin in humans, it is not suitable for clinical translation.

Breast tissue mimicking phantoms for combined ultrasound and microwave imaging.

We present a new formulation for a breast tissue-mimicking phantom for combined microwave and ultrasound imaging to assist breast cancer detection. Formulations based on coconut oil, canola oil, agar and glass beads were used to mimic skin and fat tissues. First, 36 recipes were fabricated, and properties were measured to determine the relationship and possible interaction between ingredients with the ultrasound and microwave properties.

Steering single-element lead zirconate titanate ultrasound transducers using biaxial driving.

Previous work has shown that biaxial driving using two phase-offset orthogonal electric fields (propagation and lateral) improves the efficiency of ferroelectric materials by reducing coercivity and, hence, energy dissipation. In the current investigation, we demonstrated the capability of the biaxial method to steer ultrasound waves in single-element piezoceramic transducers made of prismatic lead zirconate titanate (PZT). We conducted finite element analysis simulations for 133 kHz (model 1) and 470 kHz biaxial (model 2) transducers models.

Superposition method for modelling boundaries between media in viscoelastic finite difference time domain simulations.

Finite-difference time domain (FDTD) techniques are widely used to model the propagation of viscoelastic waves through complex and heterogeneous structures. However, in the specific case of media mixing liquid and solid, attempts to model continuous media onto a Cartesian grid produces errors when the liquid-solid interface between different media do not align precisely with the Cartesian grid. The increase in spatial resolution required to eliminate this grid staircasing effect can be computationally prohibitive.

Targeting feasibility evaluation of magnetic resonance-guided focused ultrasound in the management of osteomyelitis: a virtual treatment planning study in 75 patients.

Osteomyelitis is one of the most serious complications linked to diabetes and increases the possibility of limb amputation considerably. There exists an important clinical need to improve management of osteomyelitis, especially for diabetic patients who are more susceptible to failures, relapses and chronicity of multiple bone infections. Magnetic resonance-guided focused ultrasound (MRgFUS) can offer a clinical management option for patients with osteomyelitis by providing a non-surgical and potentially rapid-recovery treatment option.

Quasi Class-DE Driving of HIFU Transducer Arrays.

Recently, a method was proposed to determine the parameters for each Class DE driver in high-intensity focused ultrasound arrays for efficient operation and to compensate for variations in the impedance of each array element. This work extends that method to consider the effect of switch resistance and to provide limited control on the power delivered to the transducers with a constant supply voltage while keeping a good efficiency. The method is experimentally validated using an integrated driver developed by the authors.

Development of custom RF coils for use in a small animal platform for magnetic resonance-guided focused ultrasound hyperthermia compatible with a clinical MRI scanner.

Three different magnetic resonance imaging (MRI) coils were developed and assessed for use with an experimental platform designed to generate hyperthermia in mice using magnetic resonance-guided focused ultrasound (MRgFUS). An ergonomic animal treatment bed was integrated with MRI coils. Three different coil designs optimized for small targets were tested, and performance in targeting and conducting accurate temperature imaging was evaluated.

A viscoelastic model for the prediction of transcranial ultrasound propagation: application for the estimation of shear acoustic properties in the human skull.

A better understanding of ultrasound transmission through the human skull is fundamental to develop optimal imaging and therapeutic applications. In this study, we present global attenuation values and functions that correlate apparent density calculated from computed tomography scans to shear speed of sound. For this purpose, we used a model for sound propagation based on the viscoelastic wave equation (VWE) assuming isotropic conditions.

Sonoporation efficacy on SiHa cells in vitro at raised bath temperatures-experimental validation of a prototype sonoporation device.

Background: A device was devised which aimed to reduce the time and expertise required to perform sonoporation on adherent cell cultures. This prototype device was used to examine the superficial effect of bath temperature on sonoporation efficacy.

Methods: The prototype device consisted of six ultrasound transducers affixed beneath an Opticell stage.

Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique.

Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU) or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al.

Class-DE Ultrasound Transducer Driver for HIFU Therapy.

This paper presents a practical implementation of an integrated MRI-compatible CMOS amplifier capable of directly driving a piezoelectric ultrasound transducer suitable for high-intensity focused ultrasound (HIFU) therapy. The amplifier operates in Class DE mode without the need for an output matching network. The integrated amplifier has been implemented with the AMS AG H35 CMOS process.

Focused ultrasound treatment of abscesses induced by methicillin resistant Staphylococcus aureus: feasibility study in a mouse model.

Purpose: To study the therapeutic effect of focused ultrasound on abscesses induced by methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a major nosocomial pathogen where immunocompromised patients are prone to develop infections that are less and less responsive to regular treatments. Because of its capability to induce a rise of temperature at a very precise location, the use of focused ultrasound represents a considerable opportunity for therapy of localized MRSA-related infections.

Development and characterization of an antibody-labeled super-paramagnetic iron oxide contrast agent targeting prostate cancer cells for magnetic resonance imaging.

In this study we developed, characterized and validated in vitro a functional superparagmagnetic iron-oxide based magnetic resonance contrast agent by conjugating a commercially available iron oxide nanoparticle, Molday ION Rhodamine-B Carboxyl (MIRB), with a deimmunized mouse monoclonal antibody (muJ591) targeting prostate-specific membrane antigen (PSMA). This functional contrast agent is intended for the specific and non-invasive detection of prostate cancer cells that are PSMA positive, a marker implicated in prostate tumor progression and metastasis. The two-step carbodiimide reaction used to conjugate the antibody to the nanoparticle was efficient and we obtained an elemental iron content of 1958 ± 611 per antibody.

High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality.

Influence of cell line and cell cycle phase on sonoporation transfection efficiency in cervical carcinoma cells under the same physical conditions.

Using cervical-carcinoma-derived cells as a model, the present study investigates the effects cell line and cell cycle phase have on sonoporation transfection efficiency under the same physical conditions. A plasmid expressing green fluorescent protein (GFP) was used to measure transfection efficiency. To evaluate the effect of cell type, CaSki, HeLa, and SiHa cells were sonoporated using an acoustic pressure of 1 MPa for 30 s with a duty cycle of 4.

Sonoporation delivery of monoclonal antibodies against human papillomavirus 16 E6 restores p53 expression in transformed cervical keratinocytes.

High-risk types of human papillomavirus (HPV), such as HPV16, have been found in nearly all cases of cervical cancer. Therapies targeted at blocking the HPV16 E6 protein and its deleterious effects on the tumour suppressor pathways of the cell can reverse the malignant phenotype of affected keratinocytes while sparing uninfected cells. Through a strong interdisciplinary collaboration between engineering and biology, a novel, non-invasive intracellular delivery method for the HPV16 E6 antibody, F127-6G6, was developed.

Localized harmonic motion imaging for focused ultrasound surgery targeting.

Recently, an in vivo real-time ultrasound-based monitoring technique that uses localized harmonic motion (LHM) to detect changes in tissues during focused ultrasound surgery (FUS) has been proposed to control the exposure. This technique can potentially be used as well for targeting imaging. In the present study, we evaluated the potential of using LHM to detect changes in stiffness and the feasibility of using it for imaging purposes in phantoms and in vivo tumor detection.

Local harmonic motion monitoring of focused ultrasound surgery--a simulation model.

In this paper, a computational model for localized harmonic motion (LHM) imaging-based monitoring of high-intensity focused ultrasound surgery (FUS) is presented. The LHM technique is based on a focused, time-varying ultrasound radiation force excitation, which induces local oscillatory motions at the focal region. These vibrations are tracked, using pulse-echo imaging, and then, used to estimate the mechanical properties of the sonication region.