Transdermal drug delivery mediated by acoustic vortex beam.

Ultrasound-mediated transdermal drug delivery exhibits various advantages such as biocompatibility, controllability and safety, which attracts plenty of interests within biomedical field. Current researches mostly emphasizes the acoustic cavitation generated by planar or focused waves while neglecting other physics that occur during transportation. Our experimental study illustrates the presence of an acoustic vortex (AV) beam that exhibits a lower acoustic intensity and typically means a lower dose of inertial cavitation, yet achieves a more efficient delivery. Such a result calls for the fundamental mechanism of ultrasound-mediated transdermal transfer using the AV beam. In this work, according to our knowledge, the AV beam is firstly introduced to ultrasound-mediated transdermal medication delivery. The transversal acoustic radiation force (T-ARF), which is the primary characteristic carried by the acoustic vortex beam, and its contribution to the transport enhancement are investigated. It is shown that a focused AV (FAV) beam with a maximal acoustic pressure of 200 kPa induces a pN-level T-ARF, which promotes the enlargement of pores on the stratum corneum and thereby enhances the permeability, as compared with a zero-order (non-vortex) counterpart. This contribution of the T-ARF is validated by the experimental transport on the cellulose membrane, which exhibits a significantly increased membrane porosity and delivery efficiency. The favorable results introduce the new degree of freedom into the ultrasound-mediated transdermal drug transport based on AV beam, and thereby promotes the development of a combined control strategy for more precise and efficient transdermal drug delivery in conjunction with the administration of acoustic cavitation.

Perfect Acoustic-Vortexes Constructed by the Fourier Transform of Quasi-Bessel Beams Based on the Simplified Ring Array of Sectorial Planar Transducers.

Benefiting from the independence of the vortex radius on the topological charge (TC), the perfect acoustic-vortex (PAV) with an angular phase gradient exhibits important perspectives in acoustic applications. However, the practical implementation is still restricted by the limited accuracy and flexibility of the phase control for large-scaled source arrays. An applicable scheme of constructing PAVs by the spatial Fourier transform of quasi-Bessel AV (QB-AV) beams is developed using the simplified ring array of sectorial transducers. The principle of PAV construction is derived based on the phase modulation of the Fourier and saw-tooth lenses. Numerical simulations and experimental measurements are carried out for the ring array with the continuous and discrete phase spirals. The construction of PAVs is demonstrated by the annuli at an almost identical peak pressure with the vortex radius independent of the TC. The vortex radius is proved to increase linearly with the increase of the rear focal length and the radial wavenumber, which are determined by the curvature radii and the acoustic refractive index of the Fourier lens and the bottom angle of the saw-tooth lens, respectively. The improved PAV with a more continuous high-pressure annulus and lower concentric disturbances can be constructed by the ring array of more sectorial sources and the Fourier lens of a bigger radius. The favorable results demonstrate the feasibility of constructing PAVs by the Fourier transform of QB-AV beams and provide an implementable technology in the fields of acoustic manipulation and communication.

General principle and optimization of magneto-acousto-electrical tomography based on image distortion evaluation.

BACKGROUND: As a novel non-invasive multi-physics imaging methodology, the magneto-acousto-electrical (MAE) technology is capable of detecting electric conductivity changes for biological tissues, exhibiting prosperous perspectives in medical applications. However, the acoustic beam was often simplified to a straight line or a focused one, being perpendicular to layered boundaries of tissues in previous studies. Linear-scanning measurements were carried out to reconstruct B-mode MAE images for layered models without considering the radiation pattern of transducers. Obvious image distortions in both shape and brightness were observed in experiments without any reasonable explanation. PURPOSE: This study aims to establish a general physical model for MAE measurements and solve the problem of B-mode image distortion, and hence provide theoretical and technical supports for the improvement of MAE imaging in practical applications. METHODS: By considering the radiation pattern of actual transducers and the inclined angle of electric conductivity boundaries, a general principal of MAE measurements applicable for objects of arbitrary shapes is proposed based on the theories of acoustic radiation, Hall Effect and electrical detection. The influences of inclined conductivity boundaries and transducer directivities are numerically analyzed with Matlab programming and also demonstrated by experimental measurements. To evaluate the degree of B-mode image distortion, the deformation length (3 dB amplitude decrease) of approximate straight lines for a circular model is defined as L = dtan(ßm /2), with d and ßm being the measurement distance and the half radiation angle of the main-lobe, respectively. The rotary-scanning-based MAE tomography (MAET) is employed to reduce the image distortion, and the rotation angle step is further optimized based on the criterion of the boundary radius fluctuation coefficient <0.01 mm. RESULTS: The experimental results of MAE signals and B-mode images as well as MAETs show good agreements with simulations. It is demonstrated that, as the increase of the inclined angle, the MAE decreases rapidly with an extended time interval and reaches the 20 dB amplitude decrease when the angle exceeds 12°. Meanwhile, the deformation length of B-mode MAE imaging increases with the increase of the radiation angle for the transducer with a weaker radiation pattern, and hence results in a more serious image distortion. A smaller rotation angle step should be adopted to the MAET system with a longer deformation length, and the optimized maximum angle step of 12° is also achieved for the omnidirectional radiation of point sources with a long deformation length. CONCLUSION: The image distortion is originated from the amplitude decrease, the time shift and the time interval expansion of MAE signals introduced by the deformation length and the incident angle. The favorable results demonstrate that the fast high-resolution imaging can be accomplished by the minimum rotations of the rotary-scanning-based MAET using an actual transducer, and also provide an optimized scheme for the rotary-based MAET without scanning using a linear array of point sources.

Phase-Dislocation-Mediated High-Dimensional Fractional Acoustic-Vortex Communication.

With unlimited topological modes in mathematics, the fractional orbital angular momentum (FOAM) demonstrates the potential to infinitely increase the channel capacity in acoustic-vortex (AV) communications. However, the accuracy and stability of FOAM recognition are still limited by the nonorthogonality and poor anti-interference of fractional AV beams. The popular machine learning, widely used in optics based on large datasets of images, does not work in acoustics because of the huge engineering of the 2-dimensional point-by-point measurement. Here, we report a strategy of phase-dislocation-mediated high-dimensional fractional AV communication based on pair-FOAM multiplexing, circular sparse sampling, and machine learning. The unique phase dislocation corresponding to the topological charge provides important physical guidance to recognize FOAMs and reduce sampling points from theory to practice. A straightforward convolutional neural network considering turbulence and misalignment is further constructed to achieve the stable and accurate communication without involving experimental data. We experimentally present that the 32-point dual-ring sampling can realize the 10-bit information transmission in a limited topological charge scope from ±0.6 to ±2.4 with the FOAM resolution of 0.2, which greatly reduce the divergence in AV communications. The infinitely expanded channel capacity is further verified by the improved FOAM resolution of 0.025. Compared with other milestone works, our strategy reaches 3-fold OAM utilization, 4-fold information level, and 5-fold OAM resolution. Because of the extra advantages of high dimension, high speed, and low divergence, this technology may shed light on the next-generation AV communication.

Quasi-Bessel Acoustic-Vortex Beams Constructed by the Line-Focused Phase Modulation for a Ring Array of Sectorial Planar Transducers.

Acoustic Bessel beams are commonly used as ideal sources to study the characteristics for acoustic-vortex (AV) beams, exhibiting prosperous perspectives in contactless object manipulations and acoustic communications. However, accurate Bessel beams are difficult to construct using 2-D arrays in practical applications. By integrating active phase control and passive phase modulation to a ring array of sectorial planar transducers, quasi-Bessel AV (QB-AV) beams of arbitrary order are built by the line focus of AV fields in the current study. Based on Snell's refraction law, a circular sawtooth lens of phase modulation is designed to converge incident waves toward the beam axis at the same deflection angle. QB-AV beams constructed by the main lobes of the sectorial sources are demonstrated by theoretical derivations, numerical simulations, and quality evaluations, while those created by the sidelobes are neglected to avoid the pressure fluctuations in the near field. Experimental measurements for AV beams of different orders coincide basically with the simulations, demonstrating that line-focused QB-AV beams can be generated along the beam axis across the pressure peak. With the increase of the topological charge, the peak pressure of the beam decreases accordingly with a reduced effective axial range. The favorable results prove that, as a special kind of diffraction sources, the adjustable QB-AV beams may enable more important biomedical applications where Bessel beams are necessary, especially for the line-focused manipulation of biological and drug particles.

Spectrum Decomposition-Based Orbital Angular Momentum Communication of Acoustic Vortex Beams Using Single-Ring Transceiver Arrays.

The orbital angular momentum (OAM)-based acoustic vortex (AV) communication has been proven to provide a topological spinning characteristics for data transmission with an improved channel capacity, exhibiting good application prospects in underwater acoustic communications. To improve the accuracy and efficiency of data communication, the spectrum decomposition of OAM modes for OAM-multiplexed AV beams is studied with a simplified structure of single-ring transceiver arrays. The principle of spectrum decomposition for the single-OAM or OAM-multiplexed AV beams is derived based on the phase-coded approach and the orthogonal property of AVs. With the single-ring arrays of 16 transducers and 16 receivers, numerical studies and experimental measurements of eight-OAM-multiplexed AV beams transmitting ASCII codes are conducted. The formation of OAM-multiplexed AV beams is demonstrated by the cross-sectional scanning measurements, and the OAM modes are decoded successfully with a 16-point circular sampling. Compared with the traditional orthogonality-based decoding algorithm, the spectrum decomposition can be realized using a rotational measurement without the multiple premeasurements of single-OAM AV beams. The favorable results demonstrate the feasibility of the spectrum decomposition-based OAM communication for AV beams using a simplified structure of single-ring transceiver arrays, which would facilitate the practical application in underwater communications.

Effects of Clematis chinensis Osbeck mediated by low-intensity pulsed ultrasound on transforming growth factor-ß/Smad signaling in rabbit articular chondrocytes.

PURPOSE: Clematis chinensis Osbeck (CCO) is an essential herb that has been shown to promote the biological functions of cartilage cells. In this study, we aimed to explore whether and how low-intensity pulsed ultrasound (LIPUS) enhanced CCO delivery into chondrocytes and stimulated biological activity in vitro. METHODS: Chondrocytes were isolated from knee articular cartilage of 2-week-old rabbits and treated with LIPUS plus CCO or recombinant transforming growth factor beta 1 (TGF-ß1; 0.5 ng/mL), with or without anti-TGF-ß1 antibodies (10 µg/mL), for 3 days. Cell proliferation was assessed by Cell-Counting Kit-8 assays. Immunocytochemistry, western blotting, and quantitative polymerase chain reaction were applied to detect the expression of type II collagen and some molecules in the TGF-ß1 signal pathway. RESULTS: LIPUS plus 0.1 mg/mL CCO solution promoted chondrocyte proliferation and type II collagen and TGF-ß1 expression synergistically in vitro (P < 0.05). In addition, treatment with anti-TGF-ß1 antibodies blocked this effect (P < 0.01), but not completely. CCO plus LIPUS also showed more enhanced effects on promoting TGF-ß receptor II and Smad2 signaling and reducing Smad7 signaling than either intervention separately (P < 0.05). CONCLUSIONS: CCO plus LIPUS promoted extracellular matrix deposition by accelerating the TGF-ß/Smad-signaling pathway in chondrocytes.

Noninvasive Treatment-Efficacy Evaluation for HIFU Therapy Based on Magneto-Acousto-Electrical Tomography.

OBJECTIVE: As a novel noninvasive modality of oncotherapy or stroke treatment, high-intensity focused ultrasound (HIFU) has drawn more and more attention in the past decades. Whereas, real-time temperature monitoring and treatment-efficacy evaluation are still the key issues for HIFU therapy. METHODS: Based on the temperature-conductivity relation of tissues with a sharp conductivity variation of irreversible thermocoagulation at 69 °C, a noninvasive method of treatment-efficacy evaluation for HIFU ablation using the magneto-acousto-electrical tomography (MAET) technology is theoretically studied. By applying the nonlinear Khokhlov-Zabolotskaya-Kuznetsov equation and Pennes equation, a cylindrical model is established to simulate the distributions of pressure, temperature, and conductivity with the consideration of harmonic components. RESULTS: The MAET signals are simulated to analyze the characteristics of the peak amplitude and the axial interval of the two clusters generated by the conductivity boundary of HIFU ablation. CONCLUSION: The axial interval can be used as the indictor to evaluate the size of HIFU ablation with the minimum axial width of one wavelength. SIGNIFICANCE: The favorable results demonstrate the feasibility of real-time treatment-efficacy evaluation for HIFU therapy using the MAET technology and suggest potential applications in clinical practice.

Conductivity Anisotropy Influence on Acoustic Sources for Magnetoacoustic Tomography With Magnetic Induction.

OBJECTIVE: As the multi-physics imaging approach, magnetoacoustic tomography with magnetic induction (MAT-MI) attracts more and more attentions, focusing on image reconstruction for conductivity isotropic tissues. METHODS: By introducing vector analyses to electromagnetic stimulation and magnetoacoustic excitation for a single-layer cylindrical conductivity anisotropic model, the acoustic source strength (ASS) of MAT-MI is derived in explicit formula and the influence of the anisotropic conductivity tensor is also analyzed. RESULTS: Theoretical and numerical studies demonstrate that the ASS generated at the tissue boundary is composed of an alternating current (AC) fluctuation and a direct current (DC) bias, where the distribution of the AC fluctuation with respect to the spatial angle exhibits a double-period cosine function, and the DC bias remains constant at each angle. The dependences of the AC fluctuation and the DC bias on the anisotropic component ratio (ACR) and the conductivity tensor are proved by numerical results, which are also verified by the special cases of the zero AC fluctuation for the conductivity isotropic medium and the negative DC bias of the low-conductivity medium. CONCLUSION: With the measurements of the ASS around the model, the anisotropic conductivity tensor can be reconstructed by the amplitudes of the AC fluctuation and the DC bias with the conductivity of the isotropic surrounding medium. SIGNIFICANCE: The favorable results provide a new method for anisotropic conductivity measurement, and suggest the application potential of MAT-MI in biomedical imaging and nondestructive testing for conductivity anisotropic tissues.

Magneto-acousto-electrical Measurement Based Electrical Conductivity Reconstruction for Tissues.

OBJECTIVE: Based on the interaction of ultrasonic excitation and magnetoelectrical induction, magneto-acousto-electrical (MAE) technology was demonstrated to have the capability of differentiating conductivity variations along the acoustic transmission. By applying the characteristics of the MAE voltage, a simplified algorithm of MAE measurement based conductivity reconstruction was developed. METHODS: With the analyses of acoustic vibration, ultrasound propagation, Hall effect, and magnetoelectrical induction, theoretical and experimental studies of MAE measurement and conductivity reconstruction were performed. The formula of MAE voltage was derived and simplified for the transducer with strong directivity. MAE voltage was simulated for a three-layer gel phantom and the conductivity distribution was reconstructed using the modified Wiener inverse filter and Hilbert transform, which was also verified by experimental measurements. RESULTS: The experimental results are basically consistent with the simulations, and demonstrate that the wave packets of MAE voltage are generated at tissue interfaces with the amplitudes and vibration polarities representing the values and directions of conductivity variations. With the proposed algorithm, the amplitude and polarity of conductivity gradient can be restored and the conductivity distribution can also be reconstructed accurately. CONCLUSION: The favorable results demonstrate the feasibility of accurate conductivity reconstruction with improved spatial resolution using MAE measurement for tissues with conductivity variations, especially suitable for nondispersive tissues with abrupt conductivity changes. SIGNIFICANCE: This study demonstrates that the MAE measurement based conductivity reconstruction algorithm can be applied as a new strategy for nondestructive real-time monitoring of conductivity variations in biomedical engineering.

Enhanced porosity and permeability of three-dimensional alginate scaffolds via acoustic microstreaming induced by low-intensity pulsed ultrasound.

The shear stress resulting from the microstreaming induced by low-intensity pulsed ultrasound (LIPUS) has been often used to improve the permeability of cell membrane or porous engineering scaffolds. In the present study, three-dimensional (3-D) scaffold culture systems were constituted to simulate the in vivo microenvironment, providing benefits for cell growth. In order to investigate the mechanism underlying the enhanced porosity and permeability of the 3-D alginate scaffolds by using LIPUS with varied acoustic intensities, two quantitative imaging techniques (i.e. scanning electron microscopy, and laser con-focal imaging) were used to evaluate the porosity and permeability of the 3-D alginate scaffolds. The results suggested that the porosity and permeability of the scaffolds were enhanced by the microbubble-induced microstreaming, and increased with the increasing LIPUS driving intensity. Furthermore, the cell proliferation assessments verified that HeLa cell grew better in the treated 3-D alginate scaffolds, since the LIPUS exposures can improve the scaffold porosity and permeability, leading to better cell growth space and nutrition supply.

Characterization of mechanical properties of hybrid contrast agents by combining atomic force microscopy with acoustic/optic assessments.

Multi-parameter fitting algorithms, which are currently used for the characterization of coated-bubbles, inevitably introduce uncertainty into the results. Therefore, a better technique that can accurately determine the microbubbles' mechanical properties is urgently needed. A comprehensive technology combining atomic force microscopy, optical, and acoustic measurements with simulations of coated-bubble dynamics was developed. Using this technique, the mechanical parameters (size distribution, shell thickness, elasticity, and viscosity) of hybrid (ultrasound/magnetic-resonance-imaging) contrast microbubbles and their structure-property relationship were determined. The measurements indicate that when more superparamagnetic iron oxide nanoparticles are embedded in the microbubbles' shells, their mean diameter and effective viscosity increase, and their elastic modulus decreases. This reduces the microbubbles' resonance frequency and thus enhances acoustic scattering and attenuation effects.

Low intensity pulse ultrasound stimulate chondrocytes growth in a 3-D alginate scaffold through improved porosity and permeability.

A 3-D scaffold culture system has been used to promote in producing functional chondrocytes for repairing damaged cartilage. In the present study, the low intensity pulse ultrasound (LIPUS) (P(-)=0, 0.055, 0.085 and 0.11 MPa) was applied to improve the porosity and permeability of a 3-D alginate scaffold which was beneficial for the nutrition supply and metabolism during cell growth in 3-D alginate scaffold. The porosity and permeability of the scaffold was quantitatively analyzed based on scanning electron microscopy examination and fluorescence image observation. The results suggest that, for the scaffold exposed to LIPUS, its porosity and permeability could be significantly enhanced by the increasing LIPUS amplitude, which might be induced by the microstreaming shear stress generated by ultrasound-driven microbubble oscillations. Furthermore, the assessments of cell proliferation and collagen II expression confirmed that chondrocytes growth could be effectively promoted in 3-D alginate scaffolds treated by LIPUS, because of the improved scaffold porosity and permeability might benefit cell growth space and nutrition supply. It should also be noticed that appropriate LIPUS driving parameters should be adapted to achieve optimized chondrocytes culture effect in 3-D alginate scaffold.

Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents.

Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml(-1). The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

Ultrasound-assisted permeability improvement and acoustic characterization for solid-state fabricated PLA foams.

In the present study, power ultrasound is applied to improve the permeability of the solid-state fabricated PLA foams with different cell sizes. It is experimentally proved that cell interconnection and the permeability is improved with the increasing of power ultrasound radiation intensity. Furthermore, an insert-substitution testing approach is put forward to perform acoustic measurement and property characterization for the PLA foams before and after ultrasound radiation. The experimental results indicate that the attenuation coefficient of the close-celled PLA foams decreases exponentially with respect to the saturation pressure and it shows linear behavior with respect to the ultrasound radiation intensity. The favorable results suggest the feasibility of the proposed technologies of ultrasound-assisted permeability improvement and acoustic characterization for the application of the solid-state foamed PLA foams in tissue engineering.