Arabinoxylans matrixes as a potential material for drug delivery systems development - A bibliometric analysis and literature review.

Arabinoxylans (AX) have become a focal point in the pharmaceutical sector owing to their physicochemical, biological, and functional properties. The purpose of this paper was to present a summary of the utilization of AX as drug release matrices through a bibliometric analysis (BA) and a literature review to spotlight the AX functional characteristics and their technological applications to promote this line of research. The BA was carried out using data from a Web of Science database research, specifically emphasizing the analysis of authors' keywords. This approach was chosen due to its significance in comprehensively understanding a particular research field and its relevance for in-depth knowledge of a research field. The BA outcomes revealed limited information concerning the AX applications in both release matrices and as excipients in the formulation and development of drug delivery systems (DDS), so there is a need for additional scientific and technological research in these areas to address the existing information gaps. However, the literature review shows that the native and modified AX from different delivery release systems, such as macrogels (including films, tablets, and hard gelatin capsules) and multi-particulate systems (including micro and nanogels), present an excellent potential as release matrices of biomolecules and drugs, such as doxorubicin, diclofenac sodium, caffeine, gentamicin, tizanidine hydrochloride, and insulin. In conclusion, AX have a wide potential for application in the pharmaceutical industry, so this work is expected to be a reference point for future research by scientists, technologists, and entrepreneurs who cope with the subject.

Evaluating the application of an arabinoxylan-rich fraction from brewers' spent grain as a release modifier of drugs.

This study evaluated the possible use of a fraction of brewers' spent grain rich in arabinoxylans (BSG-AX) as an excipient that modifies the release of class III drugs (Biopharmaceutics Classification System), by determining the release profile of metformin hydrochloride (MH), in a water medium. The cumulative percentage of MH release showed the best linear fit when modeled with the cumulative distribution function (CDF) of the Weibull distribution (R2 = 0.993 ± 0.001). According to the Korsmeyer-Peppas model, the first stage of MH release is regulated by a super case-II transport mechanism controlled by the expansion and relaxation of BSG-AX. Finally, with the Hixson-Crowell model, a release rate (kHC) of 0.350 ± 0.026 h-13 was obtained (R2 = 0.996 ± 0.007). BSG-AX constitutes a suitable material for producing prolonged drug release vehicles; however, additional research is required to provide a better encapsulation of the active ingredients to ensure their optimal applicability and performance.

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. Finite element analysis was used to model the response of a single transducer element. An electric characterization was performed at each transducer element to determine their driving frequency. Each transducer was driven at 6.25 MHz and tested in different phases to determine the phase that produced the maximum pressure amplitude and shortest pulsewidth. Both simulations and experimental results showed that the acoustic pressure and half-pulsewidth followed a sinusoidal response as a function of the difference in phase applied to the lateral electrodes, as it has been described in our previous work. An imaging test was performed by placing a 0.36-mm diameter nylon wire 20 mm away from the transducer while driving and receiving each element with different combinations of conventional and biaxial driving. By applying a biaxial rephasing at the receiving electrodes during the data analysis, we obtained a maximum reduction in the axial resolution from 4.6 to 1.3 mm and signal-to-noise ratio (SNR) improvements from 15.2 to 24.4 dB, when compared to conventional driving.

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 transducerin vivofor 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. Transcranial focused ultrasound (0.45 MPa, 10 ms pulse length, 1 Hz repetition frequency, 30 s duration) was applied bilaterally to mice with a 40µl/kg bolus of DefinityTMmicrobubbles, employing either a single-element biaxial ring (1.482 MHz, 10 mm inner diameter, 13.75 mm outer diameter) or spherical (1.5 MHz, 35 mm diameter, F# = 0.7; RK50, FUS Instruments) transducer on each side. Follow-up MRI scans (T1 pre- and post- 0.2 mmol/kg Gd injection, T2) were acquired to assess blood-brain barrier opening volume and potential damage. Compared to blood-brain barrier opening achieved with a conventional single-element spherical focused transducer, the opening volume achieved with a single-element biaxial ring transducer was 35% smaller (p= 0.002) with a device of a ring diameter of 40% the aperture size. Axial refocusing was further demonstrated with the single-element biaxial ring transducer, yielding a 1.63 mm deeper, five-fold larger opening volume (p= 0.048) relative to its small-focus mode. The biaxial ring transducer achieved a more localized opening compared to the spherical focused transducer under the same parameters, and further enabled dynamic axial refocusing with a single-element transducer with a smaller fabrication footprint.

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 (1.362 MHz) and 5th (2.62 MHz) harmonic excitation. The transducer had a thickness of 2.85 mm, an inner diameter of 9.75 mm and a ring width of 2.0 mm, and two pairs of electrodes as required for biaxial driving. Simulation and experimental results showed that both the focal area and the distance at which the focal area centre was located changed as a function of the phase and power difference between the two driving signals. Experimental results showed that the focal area could be reduced from 31.6 mm2 (conventional driving) to 3.4 mm2 (89 % reduction) when using the first harmonic excitation. For the third harmonic, the focal area could be reduced from 4.0 mm2 (conventional driving) to 3.3 mm2 (17.5 % reduction). For the fifth harmonic, the focal area could be reduced from 1.7 mm2 (conventional driving) to 1 mm2 (41.7 % reduction). Results also demonstrated the centre of the focus could be displaced between 3.0 mm and 9.3 mm from the surface of the transducer when using the first harmonic, between 7.3 mm and 8.4 mm at the third harmonic, and between 4.9 mm and 8.2 mm at the fifth harmonic. The reduction in the focus area, as well as the possibility to displace the focus dynamically will be advantageous for preclinical applications of focused ultrasound, especially on drug delivery and neuromodulation studies in small rodents.

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. METHODS: Typical metrics for cavitation monitoring involve observing changes in the spectrum generated by applying the discrete Fourier transform (DFT) to the time domain signal detected using a hydrophone during FUS. A confocal hydrophone was used to capture emissions during a 10 ms FUS burst, sampled at 32 ns intervals, to produce 321,500 points and a high-resolution spectrum when transformed. The FUS spectra were analyzed to show the impact that equipment-transients and well-known DFT-related distortions had on the metrics used for cavitation control. A new approach, physical sparsification (PH-SP), was introduced to sharpen FUS spectral peaks and minimize the effect of these distortions. DISCUSSION: It was demonstrated that the general spectral signal-to-noise ratio (SNR) could be improved by removing the initial noisy phantom hydrophone signal transient. Minor changes in the transient length digitally removed from the sampled values significantly changed the spectral bandwidths of all the harmonically related FUS signals. We evaluated signal processing techniques to minimize the impact these DFT-related distortions on area-under-the-curve (AUC) metric calculations, and we identified the advantages of using PH-SP and proposed new metrics when characterizing FUS spectral properties. The results show many second, third and sub-harmonic metrics provide cross-consistent evidence of changes between stable and inertial cavitation levels. Removing the first harmonic signal component with a hardware low-pass filter allowed the hydrophone gain to be boosted without introducing distortion, leading to an improved analysis of the sub-harmonic signal orders of magnitude smaller in intensity. Metrics that optimized the energy in the real component of the complex-valued PH-SP spectra provided a 32% increase in the sub-harmonic sensitivity compared to standard metrics. CONCLUSION: A preliminary investigation of existing and proposed metrics showed that system noise could be large enough to mask the transition between stable and inertial cavitation. Strong narrowing of sub-harmonic peak shapes on applying physical sparsification (PH-SP) were seen in both phantom and animal studies. However, validating equivalent trends of the metrics with pressure were limited by the increased system noise level in the animal study combined with the natural variability between subjects studied. The combined use of hardware low-pass filters and physical sparsification to selectively removing distortions in the spectrum allowed the optimization of metrics for cavitation monitoring by improving the sub-harmonic sensitivity.

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. Bowel inflammation was chemically induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in both Balb/C and interleukin-10-deficient (IL-10 KO) mice. Mouse bowels were imaged using non-linear contrast mode following an i.v. bolus of 1 × 108 microbubbles. Each mouse received a bolus of aptamer-functionalized and non-targeted microbubbles. Mouse phenotypes and the presence of P-selectin were validated using histology and immunostaining, respectively. RESULTS: Microbubble labelling of Fluor-P-Ap was complete after 20 min at 37 ̊C. We estimate approximately 300,000 Fluor-P-Ap per microbubble and confirmed fluorescence using confocal microscopy. There was a significant increase in ultrasound molecular imaging signal from both Balb/C (p = 0.003) and IL-10 KO (p = 0.02) mice with inflamed bowels using aptamer-functionalized microbubbles in comparison to non-targeted microbubbles. There was no signal in healthy mice (p = 0.4051) using either microbubble. CONCLUSIONS: We constructed an aptamer-functionalized microbubble specific for P-selectin using a clinically relevant azide-DBCO click reaction, which could detect bowel inflammation in vivo. Aptamers have potential as a next generation targeting agent for developing cost-efficient and clinically translatable targeted microbubbles.

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. Three cuboid ( 3.84×3.84×5.92 mm) biaxial piezoceramics with two pairs of orthogonal electrodes (one pair applied laterally and one pair applied in the polling direction) were manufactured and characterized. Each transducer was placed in a water tank where an independent hemispherical source was attached to a moveable arm and operated at 250 kHz. Terminal voltages were recorded for 81 source positions in a plane parallel to the transducer's front face and at a depth of approximately 9 cm. Collection was repeated three times per transducer to ensure reproducibility. In silico results were compared with the experimental results. Two derived metrics were then calculated using both the forward and lateral terminal voltages: the phase difference and amplitude ratio. Biaxial transducers demonstrate an ability to estimate the DOA of incident sound waves, independently of any time-of-flight (TOF) information. The phase difference and amplitude ratio complement each other to provide statistically significant and repeatable estimates over a range of 48° (from -24° to +24°). These results can be used to augment a variety of medical, geophysical, and industrial passive ultrasound imaging techniques.

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

Objective. Microbubble cavitation generated by focused ultrasound (FUS) can induce safe blood-brain-barrier (BBB) 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 theBBB.Gibbs' ringing, peak intensity loss and peak width increase are well-known distortions evident when using the discrete Fourier transform (DFT) to transform data containing a few hundred points. We investigate overcoming the fact thatFUStime signals (10 ms providing 312 500 points sampled at 32 ns intervals) can generate such sharp spectral peaks that variations in theirDFT-related distortions can significantly impact the values of the key metrics used for cavitation characterization.Approach. We introduce low-pass filter hardware to improve how the analogue to digital convertor handles high-frequency noise components and the orders of magnitude differences betweenFUSharmonic intensities. We investigate the enhancedFUSspectral stability and resolution obtained from a new technique, physical sparsification(PH-SP),customized to thea-prioriinformation that all keyFUScomponents are harmonically related. Results are compared with standardDFToptimizations involving time data windowing and Fourier interpolation.Main results. A new simulation model showed peak intensity, widths and metrics modified by small changes in the transformed signal's length when removing the noisy starting transient of theFUShydrophone signal or following minor excitation frequency or sampling rate adjustments. 25%-60% area-under-the-curve changes occurred in phantom studies at different pressure levels. Spectral peak sharpness was best optimized and stabilized withPH-SP.Significance. SpecialFUScharacteristics mean starting transients and minor variations in experimental procedures lead to significant changes in the spectral metrics used to monitor cavitation levels. CustomizingPH-SPto these characteristics led to sharper, more stable spectra with the potential to track the impact of microbubble environment changes.

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. What would aid clinical translation is a simple and effective microbubble functionalization approach that could be directly translated from animals to humans. We developed a targeted microbubble to P-selectin, a vascular inflammatory marker, labeled using a strain-promoted [3 + 2] azide-alkyne (azide-DBCO) reaction, comparing its ability to detect bowel inflammation to that of P-selectin targeted microbubbles labeled with a traditional biotin-streptavidin approach. Bowel inflammation was chemically induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in Balb/C mice. Each mouse received both non-targeted and P-selectin targeted microbubbles (either biotin-streptavidin or azide-DBCO). Using the biotin-streptavidin reaction, there was a significant increase in the ultrasound molecular imaging signal in inflamed mice using P-selectin targeted (2.30 ± 0.91 a.u.) compared to isotype control microbubbles (1.14 ± 0.7 a.u.) (p = 0.009). Using the azide-DBCO reaction, there was a similar increase in the ultrasound molecular imaging signal in inflamed mice (2.54 ± 0.56 a.u) compared to the isotype control (0.44 ± 0.25 a.u) (p = 0.009). There were no significant differences between the two labeling approaches between non-targeted and P-selectin targeted microbubbles. Mouse inflammatory phenotypes and expression of P-selectin were validated using histology and immunostaining. We constructed P-selectin targeted microbubbles using an azide-DBCO click reaction, which could detect bowel inflammation in vivo. This reaction generated a similar ultrasound molecular imaging signal to biotin-strepavidin-labeled microbubbles. These data show the potential of click chemistry conjugation (azide-DBCO) as a quick, cost-efficient, and clinically translatable approach for developing targeted microbubbles.

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. Based on these results, the formulae were developed to mimic different tissues found in breast, including skin, fat, fibroglandular, and tumour tissues. All phantoms contained a base of agar and glass beads at different proportions depending on the tissue mimicked. Tumour and fibroglandular tissues were best mimicked by adding polyvinylpyrrolidone (PVP), while using coconut oil for skin and canola oil for fat produced the best results. Five final phantoms with different internal structures were fabricated and imaged using B-mode ultrasound and a microwave transmission system. Microwave permittivity maps were obtained from the microwave system and compared to ultrasound images. The structure and composition of the phantoms were all confirmed through this microwave and ultrasound imaging.

Toward understanding the signals of bacteriocin production by Streptococcus spp. and their importance in current applications.

Microorganisms have developed quorum sensing (QS) systems to detect small signaling molecules that help to control access to additional nutrients and space in highly competitive polymicrobial niches. Many bacterial processes are QS-regulated; two examples are the highly related traits of the natural genetic competence state and the production of antimicrobial peptides such as bacteriocins. The Streptococcus genus is widely studied for its competence and for its ability to produce bacteriocins, as these antimicrobial peptides have significant potential in the treatment of infections caused by multiple-resistant pathogens, a severe public health issue. The transduction of a two-component system controls competence in streptococci: (1) ComD/E, which controls the competence in the Mitis and Anginosus groups, and (2) ComR/S, which performs the same function in the Bovis, Mutans, Salivarius, and Pyogenic groups. The cell-to-cell communication required for bacteriocin production in the Streptococcus groups is controlled mainly by a paralog of the ComD/E system. The relationships between pheromone signals and induction pathways are related to the bacteriocin production systems. In this review, we discuss the recent advances in the understanding of signaling and the induction of bacteriocin biosynthesis by QS regulation in streptococci. This information could aid in the design of better methods for the development and production of these antimicrobial peptides. It could also contribute to the analysis and emerging applications of bacteriocins in terms of their safety, quality, and human health benefits.

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. We performed experimental validation with biaxially driven single-element transducers (n = 3) operating at an average frequency of 131 kHz with the same characteristics as model 1. For both models, we found non-symmetric steering that was a function of both the phase and power of the second electric field. At a constant electrical power (1 W) on the propagation electrodes, simulations for the 133 kHz model predicted maximal steering of 10.3°, 22.6°, and 30.9° for lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Experimentally, for model 1, the maximal steering was 11.7° ± 1.9°, 23.5° ± 3.5°, and 30.2° ± 4.4° for the lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Simulations for the 470 kHz model predicted maximal steering of 8.8°, 16.1°, and 27° for lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Simulations showed that the cause of the steering asymmetry was a non-uniform shear deformation associated with the slightly off-resonance lateral electric field driving frequency. This is the first demonstration of ultrasound steering using a single-element transducer, which can have important applications for ultrasound focusing with phased arrays.

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

Purpose: 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. Material and Methods: A retrospective study with patients with confirmed osteomyelitis (n = 75) was performed at evaluating the feasibility to target bone infection sites with a clinically approved MRgFUS device (Sonalleve, Profound Medical, Mississauga, ON, Canada). The developed methodology allows using preexisting diagnostic magnetic resonance imaging (MRI) or computed tomography (CT) scans to evaluate the treatment feasibility directly using a MRgFUS treatment planning software. Results: 74.7% of the cases included in our study passed the targetability criteria. Cases were deemed non-targetable if the target was less than 1 cm from the skin or close to a neuro-vascular bundle, metallic implants, or in the way of a defect in the overlying skin. For cases that passed the targetability criteria, an average among patients of 92.7 ± 5.2% of the gross treatment volume could be reached using treatment cells available at the Sonalleve system. Conclusion: The retrospective study presented here is the first step to demonstrate the feasibility of utilizing MRgFUS for the thermal treatment of osteomyelitis.

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. Here, a modification to the Virieux staggered-grid FDTD scheme called the superposition method is presented. This method is intended to reduce this staircasing effect while keeping a manageable computational time. The method was validated by comparing low-spatial-resolution simulations against simulations with sufficiently high resolution to provide reasonably accurate results at any incident angle. The comparison of the root-mean-square of the stress amplitude maps showed that the amplitude of artifactual waves could be reduced by several orders of magnitude when compared to the Virieux staggered-grid FDTD method and that the superposition method helped to significantly reduce the staircasing effect in FDTD simulations.

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. This paper also shows that the frequency range for efficient electrical operation is close to the frequency where the transducer array presents a peak in the conversion efficiency.

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. Two transmit/receive surface coils of different diameters (4 and 7 cm) and a transmit-only/receive-only (TORO) coil were used. A software platform was developed to provide real-time targeting and temperature maps and to deliver controlled ultrasound exposure. MR thermometry was conducted on different targets, including fresh chicken breasts and mouse cadavers. Multiple experiments were performed in which tissues were targeted with high reproducibility. The TORO coil was the most resilient to temperature drift, resulting in an increase in the calculated temperature of 0.29 ± 0.12 °C, compared to 1.27 ± 0.13 °C and 0.47 ± 0.04 °C for the medium and small coils, respectively. Controlled closed-loop hyperthermia exposure was successfully performed with all three coils. Considering all assessments, the TORO coil exhibited the best overall performance for thermometry acquisition when accounting for stability, precision, temperature spread and resilience to temperature drift. B1 maps of the three coils confirmed that the TORO coil exhibited the most homogeneous B1 field, which explained the improved thermometry performance. The use of coils specifically designed for small targets within the proposed experimental platform allowed accurate thermometry during hyperthermia.

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. The model was validated using a series of measurements with plates of different plastic materials and angles of incidence of 0°, 15° and 50°. The optimal functions for transcranial ultrasound propagation were established using the VWE, scan measurements of transcranial propagation with an angle of incidence of 40° and a genetic optimization algorithm. Ten (10) locations over three (3) skulls were used for ultrasound frequencies of 270 kHz and 836 kHz. Results with plastic materials demonstrated that the viscoelastic modeling predicted both longitudinal and shear propagation with an average (±s.d.) error of 9(±7)% of the wavelength in the predicted delay and an error of 6.7(±5)% in the estimation of transmitted power. Using the new optimal functions of speed of sound and global attenuation for the human skull, the proposed model predicted the transcranial ultrasound transmission for a frequency of 270 kHz with an expected error in the predicted delay of 5(±2.7)% of the wavelength. The sound propagation model predicted accurately the sound propagation regardless of either shear or longitudinal sound transmission dominated. For 836 kHz, the model predicted accurately in average with an error in the predicted delay of 17(±16)% of the wavelength. Results indicated the importance of the specificity of the information at a voxel level to better understand ultrasound transmission through the skull. These results and new model will be very valuable tools for the future development of transcranial applications of ultrasound therapy and imaging.

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. A class DE amplifier design methodology for driving unmatched piezoelectric loads is presented along with simulation and experimental results. The proposed design achieves approximately 90% efficiency with over 800 mW of output power at 1010 kHz. The total die area including pads is 2 mm(2). Compatibility with MRI was validated with B1 imaging of a phantom and the amplifier circuit.

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. Six transducers with nominal diameters of 20 mm were constructed and the acoustic field of each was characterized using hydrophone scanning. A near field treatment plane was chosen for each transducer to minimize field heterogeneity in the near field. Cervical cancer-derived SiHa cells were exposed to nine different treatments in the presence of plasmid DNA-expressing green fluorescent protein (GFP). Ultrasound treatment with Definity ultrasound contrast agent (US+UCA) present, ultrasound treatment without contrast agent present (US), and a sham ultrasound treatment in the presence of ultrasound contrast agent (CA) were each performed at bath temperatures of 37, 39.5, and 42 °C. Each treatment was performed in biological triplicate. GFP expression and PARP expression following treatment were measured using fluorescent microscopy and digital image processing. Cell detachment was measured using phase contrast microscopy before and after treatment. RESULTS: Mean (± s.d.) transfection rates for the US+UCA treatment were 5.4(±0.92), 5.8(±1.3), and 5.3(±1.1) % at 37, 39.5, and 42 °C, respectively. GFP expression and cell detachment were both significantly affected by the presence of ultrasound contrast agent (p < 0.001, p < 0.001). Neither GFP expression, PARP expression, or detachment differed significantly between bath temperatures. CONCLUSIONS: Bath temperature did not impact the efficacy of sonoporation treatment on SiHa cells in vitro. The prototype device was found to be suitable for performing sonoporation on adherent cell cultures and will reduce the time and expertise required for conducting sonoporation experiments on adherent cell cultures in the future.