Study of ultrasound stiffness imaging methods using tissue mimicking phantoms

A pilot study was carried out to investigate the performance of ultrasound stiffness imaging methods namely Ultrasound Elastography Imaging (UEI) and Acoustic Radiation Force Impulse (ARFI) Imaging. Specifically their potential for characterizing different classes of solid mass lesions was analyzed using agar based tissue mimicking phantoms. Composite tissue mimicking phantom was prepared with embedded inclusions of varying stiffness from 50 kPa to 450 kPa to represent different stages of cancer. Acoustic properties such as sound speed, attenuation coefficient and acoustic impedance were characterized by pulse echo ultrasound test at 5 MHz frequency and they are ranged from (1564 ± 88 to 1671 ± 124 m/s), (0.6915 ± 0.123 to 0.8268 ± 0.755 db cm^-1 MHz^-1) and (1.61×10⁶ ± 0.127 to 1.76 × 10⁶ ± 0.045 kg m^-2 s^-1) respectively. The elastic property Young’s Modulus of the prepared samples was measured by conducting quasi static uni axial compression test under a strain rate of 0.5 mm/min upto 10 % strain, and the values are from 50 kPa to 450 kPa for a variation of agar concentration from 1.7% to 6.6% by weight. The composite phantoms were imaged by Siemens Acuson S2000 (Siemens, Erlangen, Germany) machine using linear array transducer 9L4 at 8 MHz frequency; strain and displacement images were collected by UEI and ARFI. Shear wave velocity 4.43 ± 0.35 m/s was also measured for high modulus contrast (18 dB) inclusion and X.XX m/s was found for all other inclusions. The images were pre processed and parameters such as Contrast Transfer Efficiency and lateral image profile were computed and reported. The results indicate that both ARFI and UEI represent the abnormalities better than conventional US B mode imaging whereas UEI enhances the underlying modulus contrast into improved strain contrast. The results are corroborated with literature and also with clinical patient images.     

Noninvasive electromechanical wave imaging and conduction-relevant velocity estimation in vivo

Electromechanical wave imaging is a novel technique for the noninvasive mapping of conduction waves in the left ventricle through the combination of ECG gating, high frame rate ultrasound imaging and radio-frequency (RF)-based displacement estimation techniques. In this paper, we describe this new technique and characterize the origin and velocity of the wave under distinct pacing schemes. First, in vivo imaging (30 MHz) was performed on anesthetized, wild-type mice (n = 12) at high frame rates in order to take advantage of the transient electromechanical coupling occurring in the myocardium. The RF signal acquisition in a long-axis echocardiographic view was gated between consecutive R-wave peaks of the mouse electrocardiogram (ECG) and yielded an ultra-high RF frame rate of 8000 frames/s (fps). The ultrasound RF signals in each frame were digitized at 160 MHz. Axial, frame-to-frame displacements were estimated using 1D cross-correlation (window size of 240 μm, overlap of 90%). Three pacing protocols were sequentially applied in each mouse: (1) sinus rhythm (SR), (2) right-atrial (RA) pacing and (3) right-ventricular (RV) pacing. Pacing was performed using an eight-electrode catheter placed into the right side of the heart with the capability of pacing from any adjacent bipole. During a cardiac cycle, several waves were depicted on the electromechanical wave images that propagated transmurally and/or from base to apex, or apex to base, depending on the type of pacing and the cardiac phase. Through comparison between the ciné-loops and their corresponding ECG obtained at different pacing protocols, we were able to identify and separate the electrically induced, or contraction, waves from the hemodynamic (or, blood-wall coupling) waves. In all cases, the contraction wave was best observed along the posterior wall starting at the S-wave of the ECG, which occurs after Purkinje fiber, and during myocardial, activation. The contraction wave was identified based on the fact that it changed direction only when the pacing origin changed, i.e., it propagated from the apex to the base at SR and RA pacing and from base to apex at RV pacing. This reversal in the wave propagation direction was found to be consistent in all mice scanned and the wave velocity values fell within the previously reported conduction wave range with statistically significant differences between SR/RA pacing (0.85 ± 0.22 m/s and 0.84 ± 0.20 m/s, respectively) and RV pacing (−0.52 ± 0.31 m/s; p < 0.0001). This study thus shows that imaging the electromechanical function of the heart noninvasively is feasible. It may therefore constitute a unique noninvasive method for conduction wave mapping of the entire left ventricle. Such a technology can be extended to 3D mapping and/or used for early detection of dyssynchrony, arrhythmias, left-bundle branch block, or other conduction abnormalities as well as diagnosis and treatment thereof.     

The preliminary evaluation of a 1 MHz ultrasound probe for measuring the elastic anisotropy of human cortical bone

Our objective is to evaluate an ultrasound probe for measurements of velocity and anisotropy in human cortical bone (tibia). The anisotropy of cortical bone is a known and mechanically relevant property in the context of osteoporotic fracture risk. Current in vivo quantitative ultrasound devices measuring the velocity of ultrasound in long bones can only be applied in the axial direction. For anisotropy measurements a second direction for velocity measurements preferably perpendicular to the axial direction is necessary. We developed a new ultrasound probe which permits axial transmission measurements with a simultaneous second perpendicular direction (tangential). Anisotropy measurements were performed on isotropic and anisotropic phantoms and two excised human female tibiae (age 63 and 82). Anisotropy ratios (AI; ratio of squared ultrasound velocities in the two directions) were for the isotropic phantom 1.06 ± 0.01 and for the anisotropic phantom 1.14 ± 0.03 (mean ± standard deviation). AI was 1.83 ± 0.29 in the tibia from the older donor and 1.37 ± 0.18 in the tibia from the younger donor. The AIs were in the expected range and differed significantly (p < 0.05, t-test) between the tibiae. Measured sound velocities were reproducible (mean standard deviation of short time precision of both channels for phantom measurements 31 m/s) and in agreement with reported velocities of the phantom material. Our results document the feasibility of anisotropy measurements at long bones using a single probe. Further improvements in the design of the probe and tests in vivo are warranted. If this approach can be evaluated in vivo an additional tool for assessing the bone status is available for clinical use.     

Ultrasound frame rate requirements for cardiac elastography: experimental and in vivo results

Cardiac elastography using radiofrequency echo signals can provide improved 2D strain information compared to B-mode image data, provided data are acquired at sufficient frame rates. In this paper, we evaluate ultrasound frame rate requirements for unbiased and robust estimation of tissue displacements and strain. Both tissue-mimicking phantoms under cyclic compressions at rates that mimic the contractions of the heart and in vivo results are presented. Sinusoidal compressions were applied to the phantom at frequencies ranging from 0.5 to 3.5 cycles/sec, with a maximum deformation of 5% of the phantom height. Local displacements and strains were estimated using both a two-step one-dimensional and hybrid two-dimensional cross-correlation method. Accuracy and repeatability of local strains were assessed as a function of the ultrasound frame rate based on signal-to-noise ratio values.The maximum signal-to-noise ratio obtained in a uniformly elastic phantom is 20 dB for both a 1.26 Hz and a 2 Hz compression frequency when the radiofrequency echo acquisition is at least 12 Hz and 20 Hz respectively. However, for compression frequencies of 2.8 Hz and 4 Hz the maximum signal-to-noise ratio obtained is around 16 dB even for a 40 Hz frame rate. Our results indicate that unbiased estimation of displacements and strain require ultrasound frame rates greater than ten times the compression frequency, although a frame rate of about two times the compression frequency is sufficient to estimate the compression frequency imparted to the tissue-mimicking phantom. In vivo results derived from short-axis views of the heart acquired from normal human volunteers also demonstrate this frame rate requirement for elastography.     

In vivo characterization of the aortic wall stress-strain relationship

Arterial stiffness has been shown to be a good indicator of arterial wall disease. However, a single parameter is insufficient to describe the complex stress-strain relationship of a multi-component, non-linear tissue such as the aorta. We therefore propose a new approach to measure the stress-strain relationship locally in vivo noninvasively, and present a clinically relevant parameter describing the mechanical interaction between aortic wall constituents. The slope change of the circumferential stress-strain curve was hypothesized to be related to the contribution of elastin and collagen, and was defined as the transition strain (). A two-parallel spring model was employed and three Young’s moduli were accordingly evaluated, i.e., corresponding to the: elastic lamellae (E₁), elastin-collagen fibers (E₂) and collagen fibers (E₃). Our study was performed on normal and Angiotensin II (AngII)-treated mouse abdominal aortas using the aortic pressure after catheterization and the local aortic wall diameters change from a cross-correlation technique on the radio frequency (RF) ultrasound signal at 30 MHz and frame rate of 8 kHz. Using our technique, the transition strain and three Young’s moduli in both normal and pathological aortas were mapped in 2D. The slope change of the circumferential stress-strain curve was first observed in vivo under physiologic conditions. The transition strain was found at a lower strain level in the AngII-treated case, i.e., 0.029 ± 0.006 for the normal and 0.012 ± 0.004 for the AngII-treated aortas. E₁, E₂ and E₃ were equal to 69.7 ± 18.6, 214.5 ± 65.8 and 144.8 ± 55.2 kPa for the normal aortas, and 222.1 ± 114.8, 775.0 ± 586.4 and 552.9 ± 519.1 kPa for the AngII-treated aortas, respectively. This is because of the alteration of structures and content of the wall constituents, the degradation of elastic lamella and collagen formation due to AngII treatment. While such values illustrate the alteration of structure and content of the wall constituents related to AngII treatment, limitations regarding physical assumptions (isotropic, linear elastic) should be kept in mind. The transition strain, however, was shown to be a pressure independent parameter that can be clinically relevant and noninvasively measured using ultrasound-based motion estimation techniques. In conclusion, our novel methodology can assess the stress-strain relationship of the aortic wall locally in vivo and quantify important parameters for the detection and characterization of vascular disease.     

In vitro ultrasonic and mechanic characterization of the modulus of elasticity of children cortical bone

The assessment of elastic properties in children’s cortical bone is a major challenge for biomechanical engineering community, more widely for health care professionals. Even with classical clinical modalities such as X-ray tomography, MRI, and/or echography, inappropriate diagnosis can result from the lack of reference values for children bone. This study provides values for elastic properties of cortical bone in children using ultrasonic and mechanical measurements, and compares them with adult values. 18 fibula samples from 8 children (5–16 years old, mean age 10.6 years old ±4.4) were compared to 16 fibula samples from 3 elderly adults (more than 65 years old). First, the dynamic modulus of elasticity (E_dyn) and Poisson’s ratio (ν) are evaluated via an ultrasonic method. Second, the static modulus of elasticity (E_sta) is estimated from a 3-point microbending test. The mean values of longitudinal and transverse wave velocities measured at 10 MHz for the children’s samples are respectively 3.2 mm/μs (±0.5) and 1.8 mm/μs (±0.1); for the elderly adults’ samples, velocities are respectively 3.5 mm/μs (±0.2) and 1.9 mm/μs (±0.09). The mean E_dyn and the mean E_sta for the children’s samples are respectively 15.5 GPa (±3.4) and 9.1 GPa (±3.5); for the elderly adults’ samples, they are respectively 16.7 GPa (±1.9) and 5.8 GPa (±2.1). E_dyn, ν and E_sta are in the same range for children’s and elderly adults’ bone without any parametric statistical difference; a ranking correlation between E_dyn and E_sta is shown for the first time.     

Noninvasive estimation of the ocular elastic modulus for age-related macular degeneration in the human eye using sequential ultrasound imaging

Introduction

Elastic modulus estimation may be an important clinical criterion, as it seems to affect such eye parameters as intraocular pressure, ocular pulsation, blood flow, effect of topical medications, and post-refractive surgery complications. The purpose of this study was to examine the differences in elasticity in the ocular axial length, posterior wall thickness (posterior pole), and retina-choroid thickness under normal and aged-related macular degeneration (AMD) conditions in the human eye by directly estimating the elastic modulus with sequential and noninvasive ultrasound image processing.

Materials and Methods

In this study, 25 healthy subjects and 20 patients with non-neovascular AMD participated in the experiment. The deformation of the ocular axial length, posterior wall thickness and retina-choroid complex thickness was captured using high-resolution ultrasonography before and after loading. The B-mode (20 MHz) and A-mode (8 MHz) frames were obtained and processed with an echo tracking technique. The elastic modulus was estimated using changes in ocular axial length, posterior wall thickness and retina-choroid complex thickness and with applied stress measurements.

Results

There was a significant difference (p < 0.05) in the ocular axial length elastic modulus between the AMD and healthy subjects (AMD patients: 95.165 ± 26.431 kPa, vs. healthy subjects: 49.539 ± 25.867 kPa). Moreover, there was a statistically significant difference (p < 0.05) in the posterior wall thickness elastic modulus between AMD patients and healthy subjects (AMD patients: 50.519 ± 12.295 kPa, vs. healthy subjects: 20.519 ± 11.827 kPa). However, no statistically significant difference (p-value > 0.05) was found in the retina-choroid complex elastic modulus between the two groups (AMD patients: 20.134 ± 3.898 kPa, vs. healthy subjects: 15.630 ± 4.250 kPa).

Conclusion

Although the results were obtained examining a relatively low number of patients, it would appear that noninvasive ultrasound estimation of the local elastic moduli of ocular axial length and posterior wall thickness is suited to aid in detection of the non-exudative AMD thus manifesting its potential as a screening tool in symptom-free individuals.     

Novel device to measure critical point "Onset" of capillary wave and interpretation of Faraday instability wave by numerical analysis

A capillary wave was created on a surface by vibrating from the bottom of a container. When the amplitude of the container vibration approached the critical point, called the onset state, the surface broke up and bursted into very small drops on the air. The numerical analysis was used to determine the amplitude of the onset. The onset point was found to be 0.349 μm at f = 500 kHz. The critical amplitude h_cr was determined by using a multi-Fourier horn nozzle (MFHN) device. The onset point was measured to be 0.37 μm using a laser Doppler vibrometer (LDV) with the MFHN at f = 486 kHz. These drops indicate that particle size distributions of 10.8 μm and 7.0 μm were produced by the MFHN at f = 289 kHz and f = 486 kHz, respectively. These results agreed with those obtained using Kelvin’s equation, which predicted D = 0.34λ.     

Relative contributions of porosity and mineralized matrix properties to the bulk axial ultrasonic wave velocity in human cortical bone

Velocity of ultrasound waves has proved to be a useful indicator of bone biomechanical competence. A detailed understanding of the dependence of ultrasound parameters such as velocity on bone characteristics is a key to the development of bone quantitative ultrasound (QUS). The objective of this study is to investigate the relative contributions of porosity and mineralized matrix properties to the bulk compressional wave velocity (BCV) along the long bone axis. Cross-sectional slabs from the diaphysis of four human femurs were included in the study. Seven regions of interest (ROIs) were selected in each slab. BCV was measured in through-transmission at 5 MHz. Impedance of the mineralized matrix (Z_m) and porosity (Por) were obtained from 50 MHz scanning acoustic microscopy. Por and Z_m had comparable effects on BCV along the bone axis (R = −0.57 and R = 0.72, respectively).     

The effect of geometry and post-annealing on surface acoustic wave characteristics of AlN thin films prepared by magnetron sputtering

This paper describes experimental relationship between surface acoustic wave (SAW) properties of two-port SAW resonators based on polycrystalline aluminum nitride (AlN) thin films grown on Si substrates by using a pulsed reactive magnetron sputtering system and their geometry's parameters. Moreover, the influence of post-deposition heat treatment on SAW properties of AlN thin films was investigated at different annealing temperature (600 °C and 900 °C). The measurement results show the number of the inter-digital transducers (IDT) finger pairs (N), the number of reflectors grating pairs (R) and the IDT center-to-center distance (L) related to insertion loss of SAW resonators. The best result of insertion loss was 15.6 dB for SAW resonators with R = 160 pair, N = 5 pair and L = 750 μm. At the same geometry parameters, the SAW velocity and insertion loss were improved slightly after annealing at 600 °C and were worse for the films annealed at 900 °C by changes in the surface morphology and stress on the film.     

Effect of wood properties on within-tree variation in ultrasonic wave velocity in softwood

The radial variations in the velocity of longitudinal waves propagating through Japanese cedar and Japanese cypress were experimentally investigated. In addition, the tracheid length (TL), microfibril angle (MFA), air-dried density (AD), and moisture content (MC) were measured in order to determine the effect of wood properties on velocity variations within the wood trunk. For both species, the longitudinal wave velocities measured in the longitudinal direction (V_L) exhibited minimum values near the pith. For Japanese cedar, V_L increased from 3600 m/s toward the bark and soon attained a constant value (=4500 m/s). On the other hand, for Japanese cypress, V_L kept increasing from 4000 m/s near the pith to 4800 m/s at the bark. These radial variations in V_L coincided with those in the tracheid length. V_L exhibited strong correlations with TL and MFA with a significant level of (p < 0.01). These findings suggest that the TL and MFA greatly affect the radial variation in the ultrasonic wave velocity in softwood.     

Acoustic backscattering enhancements resulting from the interaction of an obliquely incident plane wave with an infinite cylinder

Background and objective

The analysis of the acoustic backscattering enhancements from tilted cylinders is of particular importance in determining some of the (visco)elastic properties of the cylinder, and/or its surrounding fluid in ultrasonic non-destructive evaluation (NDE) and imaging (NDI) applications. Previous related investigations on an aluminum cylinder limited to incidence angles varying from 0° to 40°, revealed the existence of an anomalous “pseudo-Rayleigh” mode (above the critical Rayleigh angle) identified as the rigid-body translational dipole (n = 1) mode. The objective here is to provide a complete investigation on the backscattering enhancements for incidence angles larger than 40° for various elastic and viscoelastic cylinder materials.

Method

Using the partial-wave series solution for the linear scattering by an infinite circular cylinder, the acoustic backscattering from isotropic elastic and viscoelastic (polymer-type) cylinders excited by an obliquely incident plane acoustic wave is investigated. Total and resonance backscattering form functions are calculated for several elastic and viscoelastic cylinder materials immersed in water versus the angle of incidence 0° ? α < 90°. The “pure” resonance peaks are isolated by subtracting a rigid background from the total form function, so the associated resonance modes are properly identified.

Results and conclusion

The plots of the partial-wave series reveal acoustic backscattering enhancements (not shown in previous investigations) generally occurring at ka? 0.1 at a critical angle α_c bounded by the longitudinal and shear waves coupling angles θ_L=sin^-1(c/c_L) and θ_S=sin^-1(c/c_S) such that θ_L<α_c<θ_S (where c_L and c_S are the phase velocities of the longitudinal and shear waves inside the elastic cylinder, and c is the speed of sound in the surrounding medium). It is shown here that the backscattering enhancements with a critical angle θ_L<α_c<θ_S result from the excitation of the monopole (n = 0) resonance mode. Moreover, additional acoustic backscattering enhancements still occur in the range 1 ?ka? 6 even though the angle of tilt is greater than the Rayleigh wave coupling angle θ_R=sin^-1(c/c_R) (where c_R is the Rayleigh wave velocity in an elastic half-space). The resonance scattering theory shows that such additional enhancements are associated with the excitation of a dipole (n = 1) resonance mode which may result from the interference of meridional and/or helical waves propagating along the cylinder’s surface. It is therefore essential to consider tilt angles ranging from normal to end-on incidence for a complete analysis of the backscattering by elastic and viscoelastic cylinders.     

Nanoindentation analysis of the pop-in events on SiGe single layer

The growth of metastable silicon germanium (Si_0.8Ge_0.2) thin film on Si(1 0 0) by ultrahigh-vacuum chemical vapor deposition has been subjected to residual indentation studies. A nanoindentation system has been applied to analyze SiGe film after different annealing treatments. A number of phenomena have been found for the heteroepitaxial growth of SiGe film at the critical thickness of 350 nm, including single discontinuity (the so-called “pop-in” event) as well as the elastic/plastic contact translation. Atomic force microscopy is employed to investigate the surface impression. Pop-in events in the load-indentation depth curves of 400 and 500 °C and no nano-cracks in the vicinity regions are found. The values of H ranging from 13.13±0.9, 21.66±1.3, 18.52±1.1, 14.47±0.7 GPa and the values of E ranging from 221.8±5.3, 230.7±6.4, 223.5±4.6, 156.7±3.8 GPa, are obtained. The elastic/plastic contact translation of the SiGe film occurs at different annealing conditions, with h_f/h_max values in the range of 0.501, 0.392, 0.424, and 0.535 for samples are treated at RT, 400, 500, and 600 °C, respectively. The mechanism responsible for the pop-in event in such crystal structure is due to the interaction of the indenter tip with the pre-existing threading dislocations, since the release of the indentation load is bound to be reflected in the directly compressed volume.     

Retardation calculation for achromatic and apochromatic quarter and half wave plates of gypsum based birefringent crystal

This paper presents retardation calculations for achromatic and apochromatic half and quarter wave retarders of gypsum based birefringent crystal. The calculations indicate that an achromatic wave plates can be obtained by combining gypsum crystal with KDP, ADP, MgF₂, sapphire and calcite birefringent crystals. The residual variation percentages of retardations as a function of wavelength for gypsum/KDP, gypsum/ADP, gypsum/MgF₂, gypsum/sapphire and gypsum/calcite were found to be ± 1.7%, ± 3%, ± 12.2%, ± 12.0% and ± 7.2%, respectively. To reduce the spectral variation of retardations, a third layer (apochromatic) of birefringet material is added to the aforementioned achromatic wave plates. The proposed apochromatic wave plates are gypsum/KDP/quartz, gypsum/ADP/quartz, MgF₂/ADP/gypsum, MgF₂/KDP/gypsum and gypsum/sapphire/MgF₂. The addition of a third layer has reduced spectral residual variation percentages of retardations of the aforementioned apochromatic designs to ± 0.27, ± 0.33, ± 0.3, ± 0.17 and ± 0.45, respectively.     

Laser shock wave consolidation of nanodiamond powders on aluminum 319

A novel coating approach, based on laser shock wave generation, was employed to induce compressive pressures up to 5 GPa and compact nanodiamond (ND) powders (4-8 nm) on aluminum 319 substrate. Raman scattering indicated that the coating consisted of amorphous carbon and nanocrystalline graphite with peaks at 1360 cm⁻¹ and 1600 cm⁻¹ respectively. Scanning electron microscopy revealed a wavy, non-uniform coating with an average thickness of 40 μm and absence of thermal effect on the surrounding material. The phase transition from nanodiamond to other phases of carbon is responsible for the increased coating thickness. Vicker's microhardness test showed hardness in excess of 1000 kg_f/mm² (10 GPa) while nanoindentation test indicated much lower hardness in the range of 20 MPa to 2 GPa. Optical surface profilometry traces displayed slightly uneven surfaces compared to the bare aluminum with an average surface roughness (R_a) in the range of 1.5-4 μm depending on the shock wave pressure and type of confining medium. Ball-on-disc tribometer tests showed that the coefficient of friction and wear rate were substantially lower than the smoother, bare aluminum sample. Laser shock wave process has thus aided in the generation of a strong, wear resistant, durable carbon composite coating on aluminum 319 substrate.     

Effect of ultrasound therapy on the repair of gastrocnemius muscle injury in rats

The aim of this study was to evaluate the effect of the pulsed ultrasound therapy (PUT) in stimulating myoregeneration and collagen deposition in an experimental model of lacerative gastrocnemius muscle lesion in 30 Wistar rats. Fifteen rats were treated (TG) daily with 1 MHz pulsed ultrasound (50%) at 0.57 W/cm² for 5 min, and 15 were control animals (CG). Muscle samples were analyzed on postoperative days 4, 7 and 14 through H&E, Picrosirius-polarization and immunohistochemistry for desmin. The lesions presented similar inflammatory responses in both treated and control groups. The areal fraction of fibrillar collagen was larger in the TG at 4 days post-operatively (17.53 ± 6.2% vs 6.79 ± 1.3%, p = 0.0491), 7 days (31.07 ± 7.45% vs 12.57 ± 3.6%, p = 0.0021) and 14 days (30.39 ± 7.3% vs 19.13 ± 3.51%, p = 0.0118); the areal fraction of myoblasts and myotubes was larger in the TG at 14 days after surgery (41.66 ± 2.97% vs 34.83 ± 3.08%, p = 0.025). Our data suggest that the PUT increases the differentiation of muscular lineage cells, what would favor tissue regeneration. On the other hand, it is also suggested that there is a larger deposition of collagenous fibers, what could mean worse functional performance. However, the percentage of fibers seems to have stabilized at day 7 in TG and kept increasing in CG. Furthermore, the collagen supramolecular organization achieved by the TG is also significant according to the Sirius red staining results.     

Ultrasound biomicroscopy measurement of skin thickness change induced by cosmetic treatment with ultrasound stimulation

Moisturizing creams and lotions are commonly used in daily life for beauty and treatment of different skin conditions such as dryness and wrinkling, and ultrasound stimulation has been used to enhance the delivery of ingredients into skin. However, there is a lack of convenient methods to study the effect of ultrasound stimulation on lotion absorption by skin in vivo. Ultrasound biomicroscopy was adopted as a viable tool in this study to investigate the effectiveness of ultrasound stimulation on the enhancement of lotion delivery into skin. The forearm skin of 10 male and 10 female young subjects was tested at three different sites, including two lotion treatment sites with (Ultrasound Equipment – UE ON) and without (UE OFF) ultrasound stimulation and a control site without any lotion treatment. 1 MHz ultrasound with a duty cycle of 1.7%, a spatial peak temporal peak pressure of 195 kPa and an average power of 0.43 W was used for the stimulation. The skin thickness before, immediately after (0 min), and 15 and 30 min after the treatment was measured by an ultrasound biomicroscopic system (55 MHz). It was found that the skin thickness significantly increased immediately after the lotion treatment for both UE ON (from 1.379 ± 0.187 mm to 1.466 ± 0.182 mm, p < 0.001) and UE OFF (from 1.396 ± 0.193 mm to 1.430 ± 0.194 mm, p < 0.001) groups. Further comparison between the two groups revealed that the skin thickness increase of UE ON group was significantly larger than that of UE OFF group (6.5 ± 2.4% vs. 2.5 ± 1.3%, p < 0.001). Furthermore, it was disclosed that the enhancement of lotion delivery by ultrasound stimulation was more effective for the female subjects than the male subjects (7.6 ± 2.3% vs. 5.4 ± 2.0% immediately after treatment, p = 0.017). In conclusion, this study demonstrated that ultrasound biomicroscopy was a feasible method for studying the effectiveness of lotion treatment in vivo, and ultrasound stimulation was effective to enhance the rate of lotion absorption into skin.     

Reconstructing 3-D maps of the local viscoelastic properties using a finite-amplitude modulated radiation force

A modulated acoustic radiation force, produced by two confocal tone-burst ultrasound beams of slightly different frequencies (i.e. 2.0 MHz ± Δf/2, where Δf is the difference frequency), can be used to remotely generate modulated low-frequency (Δf ? 500 Hz) shear waves in attenuating media. By appropriately selecting the duration of the two beams, the energy of the generated shear waves can be concentrated around the difference frequency (i.e., Δf ± Δf/2). In this manner, neither their amplitude nor their phase information is distorted by frequency-dependent effects, thereby, enabling a more accurate reconstruction of the viscoelastic properties. Assuming a Voigt viscoelastic model, this paper describes the use of a finite-element-method model to simulate three-dimensional (3-D) shear-wave propagation in viscoelastic media containing a spherical inclusion. Nonlinear propagation is assumed for the two ultrasound beams, so that higher harmonics are developed in the force and shear spectrum. Finally, an inverse reconstruction algorithm is used to extract 3-D maps of the local shear modulus and viscosity from the simulated shear-displacement fields based on the fundamental and second-harmonic component. The quality of the reconstructed maps is evaluated using the contrast between the inclusion and the background and the contrast-to-noise ratio (CNR). It is shown that the shear modulus can be accurately reconstructed based on the fundamental component, such that the observed contrast deviates from the true contrast by a root-mean-square-error (RMSE) of only 0.38 and the CNR is greater than 30 dB. If the second-harmonic component is used, the RMSE becomes 1.54 and the corresponding CNR decreases by approximately 10–15 dB. The reconstructed shear viscosity maps based on the second harmonic are shown to be of higher quality than those based on the fundamental. The effects of noise are also investigated and a fusion operation between the two spectral components is applied to enhance the reconstruction quality. Finally, a modified shear-wave spectroscopy technique, shown to be more robust to noise, is described for the estimation of the viscoelastic properties inside and outside the spherical inclusion under conditions of increased noise.     

Periodic shock-emission from acoustically driven cavitation clouds: A source of the subharmonic signal

Single clouds of cavitation bubbles, driven by 254 kHz focused ultrasound at pressure amplitudes in the range of 0.48–1.22 MPa, have been observed via high-speed shadowgraphic imaging at 1 × 10⁶ frames per second. Clouds underwent repetitive growth, oscillation and collapse (GOC) cycles, with shock-waves emitted periodically at the instant of collapse during each cycle. The frequency of cloud collapse, and coincident shock-emission, was primarily dependent on the intensity of the focused ultrasound driving the activity. The lowest peak-to-peak pressure amplitude of 0.48 MPa generated shock-waves with an average period of 7.9 ± 0.5 μs, corresponding to a frequency of f₀/2, half-harmonic to the fundamental driving. Increasing the intensity gave rise to GOC cycles and shock-emission periods of 11.8 ± 0.3, 15.8 ± 0.3, 19.8 ± 0.2 μs, at pressure amplitudes of 0.64, 0.92 and 1.22 MPa, corresponding to the higher-order subharmonics of f₀/3, f₀/4 and f₀/5, respectively. Parallel passive acoustic detection, filtered for the fundamental driving, revealed features that correlated temporally to the shock-emissions observed via high-speed imaging, p(two-tailed) < 0.01 (r = 0.996, taken over all data). Subtracting the isolated acoustic shock profiles from the raw signal collected from the detector, demonstrated the removal of subharmonic spectral peaks, in the frequency domain. The larger cavitation clouds (>200 μm diameter, at maximum inflation), that developed under insonations of peak-to-peak pressure amplitudes >1.0 MPa, emitted shock-waves with two or more fronts suggesting non-uniform collapse of the cloud. The observations indicate that periodic shock-emissions from acoustically driven cavitation clouds provide a source for the cavitation subharmonic signal, and that shock structure may be used to study intra-cloud dynamics at sub-microsecond timescales.     

Hyperpolarized He diffusion MRI and histology of secreted frizzled related protein-1 (SFRP1) deficient lungs in a Murine model

Secreted frizzled related protein-1 (SFRP1) plays a key role in many diverse processes, including embryogenesis, tissue repair, bone formation, and tumor genesis. Previous studies have shown the effects of the SFRP1 gene on lung development using the SFRP1 knockout mouse model via histological and physiological studies. In this study, the feasibility of ADC (acquired via HP ³He) to detect altered lung structure in the SFRP1 knockout (SFRP1^−/−) mice was investigated, and compared to analysis by histology. This study consisted of two groups, the wild-type (WT) mice and the knockout (KO) mice with n = 6 mice for each group. ³He ADC MRI and histology were performed on all of the animals. The global L_m values of WT and KO mice were 35.0 ± 0.8 μm and 38.4 ± 3.8 μm, respectively, which translated to an increase of 9.58% in the L_m of KO mice. The mean global ADCs for the WT and KO mice were 0.12 ± 0.01 cm²/s and 0.13 ± 0.01 cm²/s, respectively, which equated to a relative increase of 8.0% in the KO mice compared to the WT mice. In the sub-analysis of the anterior, medial and posterior lung regions, L_m increased by 10.50%, 6.66% and 11.84% in the KO mice, respectively, whereas the differences in ADC between the two groups in the anterior, medial, and posterior regions were 7.3%, 8.3%, and 4.6%, respectively. These results suggest that HP MRI measurements can be used as a suitable substitute for histology to obtain valuable information about lung geometry non-invasively. This technique is also advantageous as regional measurements can be performed, which can identify lung destruction more precisely. Most importantly, this approach extends far beyond the specific pathology analyzed in this study, as it can be applied to many other pathological conditions in the lung tissue, as well to many other embryonic studies.