Phantom investigation of phase-inversion-based dual-frequency excitation imaging for improved contrast display

Objective

The goal of this work is to examine the effects of pulse-inversion (PI) technique in combination with dual-frequency (DF) excitation method to separate the high-order nonlinear responses from microbubble contrast agents for improvement of image contrast. DF excitation method has been previously developed to induce the low-frequency ultrasound nonlinear responses from bubbles by using the composition of two high-frequency sinusoids (f₁ and f₂).

Motivation

Although the simple filtering was conventionally utilized to provide signal separation, the PI approach is better in the sense that it minimizes the mutual interferences among these high-order nonlinear responses in the presence of spectral overlap. The novelty of the work is that, in addition to the common PI summation, the PI subtraction was also applied in DF excitation method.

Methods

DF excitation pulses having an envelope frequency of 3 MHz (i.e., f₁ = 8.5 MHz and f₂ = 11.5 MHz) with pulse lengths of 3-10 μs and the pressure amplitudes from 0.5 to 1.5 MPa were used to interrogate the nonlinear responses of SonoVue™ microbubbles in the phantom experiments. The high-order nonlinear responses in the DF excitation were extracted for contrast imaging using PI summation for even-order nonlinear components or PI subtraction for odd-order nonlinear ones.

Results

Our results indicated that, as compared to the conventional filtering technique, the PI processing effectively increases the contrast-to-tissue ratio (CTR) of the third-order nonlinear response at 5.5 MHz and the fourth-order nonlinear response at 6 MHz by 2-5 dB. For these high-order nonlinear components, the CTR increase varies with the transmission pressures from 0.5 to 1.5 MPa due to the microbubbles’ displacement induced by the radiation force of DF excitation.

Conclusions

For DF excitation technique, the PI processing can help to extract either the odd-order or the even-order nonlinear components for higher CTR estimates.     

Diagnostic value of elastosonography for thyroid microcarcinoma

Objective

To assess the diagnostic value of elastosonography for thyroid microcarcinoma (TMC), particularly with regard to elasticity score (ES) and strain ratio (SR).

Methods

Conventional ultrasound and elastosonography were performed for 487 thyroid micronodules before surgery. We set the histology as the reference standard. The ES and SR values, as well as their diagnostic threshold and efficiency, were compared and analyzed by the receiver-operating characteristic (ROC) curve. Additional comparisons between TMC patients with and without extracapsular extension were also performed.

Results

Statistically significant differences (P < 0.05) in both ES and SR values were detected among the TMC and benign groups. The area under the ROC curve of SR was significantly greater than that of ES (0.956 and 0.844, respectively; P < 0.05). Using ES ? 3 and SR ? 3.65 as diagnostic threshold values, the diagnostic sensitivity, specificity, and accuracy of ES for differentiating benign and malignant nodules were 79.9%, 72.3%, and 80.5%, respectively, whereas those of SR were 86.6%, 85.3%, and 89.4%, respectively. The maximum diameter, microcalcification status, aspect ratio, bilateral cervical lymph node metastasis, and SR values of nodules with extracapsular extension (A1 subgroup) were greater than those of nodules without extracapsular extension (A2 subgroup).

Conclusions

Elasticity imaging technology not only can help differentiate between benign and malignant thyroid micronodules but also allow SR values to provide accurate and objective information on tissue hardness and to predict TMC extracapsular extension or even bilateral cervical lymph node metastasis.     

Dual-high-frequency ultrasound excitation on microbubble destruction volume

Objective and motivation

The goal of this work was to test experimentally that exposing air bubbles or ultrasound contrast agents in water to amplitude modulated wave allows control of inertial cavitation affected volume and hence could limit the undesirable bioeffects.

Methods

Focused transducer operating at the center frequency of 10 MHz and having about 65% fractional bandwidth was excited by 3 μs 8.5 and 11.5 MHz tone-bursts to produce 3 MHz envelope signal. The 3 MHz frequency was selected because it corresponds to the resonance frequency of the microbubbles used in the experiment. Another 5 MHz transducer was used as a receiver to produce B-mode image. Peak negative acoustic pressure was adjusted in the range from 0.5 to 3.5 MPa. The spectrum amplitudes obtained from the imaging of SonoVue^TM contrast agent when using the envelope and a separate 3 MHz transducer were compared to determine their cross-section at the - 6 dB level.

Results

The conventional 3 MHz tone-burst excitation resulted in the region of interest (ROI) cross-section of 2.47 mm while amplitude modulated, dual-frequency excitation with difference frequency of 3 MHz produced cross-section equal to 1.2 mm.

Conclusion

These results corroborate our hypothesis that, in addition to the considerably higher penetration depth of dual-frequency excitation due to the lower attenuation at 3 MHz than that at 8.5 and 11.5 MHz, the sample volume of dual-frequency excitation is also smaller than that of linear 3-MHz method for more spatially confined destruction of microbubbles.     

Modelling and simulation of high-frequency (100 MHz) ultrasonic linear arrays based on single crystal LiNbO3

Background

High-frequency ultrasonic transducer arrays are essential for high resolution imaging in clinical analysis and Non-Destructive Evaluation (NDE). However, the fabrication of conventional backing-layer structure, which requires a pitch (distance between the centers of two adjacent elements) of half wavelength in medium, is really a great challenge.

Objective and method

Here we present an alternative buffer-layer structure with a silicon lens for volumetric imaging. The requirement for the size of the pitch is less critical for this structure, making it possible to fabricate high-frequency (100 MHz) ultrasonic linear array transducers. Using silicon substrate also makes it possible to integrate the arrays with IC (Integrated Circuit). To compare with the conventional backing-layer structure, a finite element tool, COMSOL, is employed to investigate the performances of acoustic beam focusing, the influence of pitch size for the buffer-layer configuration, and to calculate the electrical properties of the arrays, including crosstalk effect and electrical impedance.

Results

For a 100 MHz 10-element array of buffer-layer structure, the ultrasound beam in azimuth plane in water could be electronically focused to obtain a spatial resolution (a half-amplitude width) of 86 μm at the focal depth. When decreasing from half wavelength in silicon (42 μm) to half wavelength in water (7.5 μm), the pitch sizes weakly affect the focal resolution. The lateral spatial resolution is increased by 4.65% when the pitch size decreases from 42 μm to 7.5 μm. The crosstalk between adjacent elements at the central frequency is, respectively, −95 dB, −39.4 dB, and −60.5 dB for the 10-element buffer, 49-element buffer and 49-element backing arrays. Additionally, the electrical impedance magnitudes for each structure are, respectively, 4 kΩ, 26.4 kΩ, and 24.2 kΩ, which is consistent with calculation results using Krimholtz, Leedom, and Matthaei (KLM) model.

Conclusion

These results show that the buffer-layer configuration is a promising alternative for the fabrication of high-frequency ultrasonic linear arrays dedicated to volumetric imaging.     

Third harmonic transmit phasing for SNR improvement in tissue harmonic imaging with Golay-encoded excitation

Background

Ultrasound tissue harmonic signal generally provides superior image quality as compared to the linear signal. However, since the generation of the tissue harmonic signal is based on finite amplitude distortion of the propagating waveform, the penetration and the sensitivity in tissue harmonic imaging are markedly limited because of the low signal-to-noise ratio (SNR).

Methods

The method of third harmonic (3f₀) transmit phasing can improve the tissue harmonic SNR by transmitting at both the fundamental (2.25 MHz) and the 3f₀ (6.75 MHz) frequencies to achieve mutual enhancement between the frequency-sum and the frequency-difference components of the second harmonic signal. To further increase the SNR without excessive transmit pressure, coded excitation can be incorporated in 3f₀ transmit phasing to boost the tissue harmonic generation.

Results

Our analyses indicate that the phase-encoded Golay excitation is suitable in 3f₀ transmit phasing due to its superior transmit bandwidth efficiency. The resultant frequency-sum and frequency-difference components of tissue harmonic signal can be simultaneously Golay-encoded for SNR improvement. The increase of the main-lobe signal with the Golay excitation in 3f₀ transmit phasing are consistent between the tissue harmonic measurements and the simulations. B-mode images of the speckle generating phantom also demonstrate the increases of tissue harmonic SNR for about 11 dB without noticeable compression artifacts.

Conclusion

For tissue harmonic imaging in combination with the 3f₀ transmit phasing method, the Golay excitation can provide further SNR improvement. Meanwhile, the axial resolution can be effectively restored by pulse compression while the lateral resolution remains unchanged.     

Effect of dual-frequency clutter suppression in harmonic Doppler detection

Background

High-frequency Doppler imaging is highly potential for detection of blood flow in microcirculation. In a swept-scan system, however, the spectral broadening of tissue clutter limits the detectability of low-velocity flow signal. Conventionally, the scanning speed of transducer has to be reduced to alleviate the clutter interference but at the cost of imaging frame rate. For example, the blood velocity of 0.5 mm/s becomes detectable only with a scanning speed lower than 1 mm/s. In this study, an alternative method is examined by suppressing the clutter magnitude to reduce the interference to flow signal without sacrificing scanning speed.

Methods

The method of third harmonic (3f₀) transmit phasing can suppress the tissue harmonic clutter by transmitting at the fundamental and the additional 3f₀ frequencies to achieve mutual cancellation between the frequency-sum and the frequency-difference components of the second harmonic signal. With 3f₀ transmit phasing, the cut-off frequency of wall filtering can be reduced to preserve low-velocity flow without compromising the frame rate.

Results

Our results indicate that the 3f₀ transmit phasing effectively reduces the harmonic clutter magnitude and thus improves the flow signal-to-clutter ratio. Compared to the conventional counterpart, the clutter-suppressed color flow and power Doppler images show fewer clutter artifacts and is capable of detecting more low-velocity flow of microbubbles. The resultant color-pixel-density also improves with clutter suppression.

Conclusion

For the swept-scan high-frequency (>20 MHz) system, 3f₀ transmit phasing is capable of providing effective clutter suppression. With the same achievable scanning speed, the resultant Doppler image has higher sensitivity for low-velocity flow and is less susceptible to clutter artifacts.     

Characterization of mediastinal lymphadenopathy with diffusion-weighted imaging

Purpose

To predict malignancy of mediastinal lymphadenopathy with diffusion-weighted imaging.

Material and methods

A prospective study was conducted on 35 patients with mediastinal lymphadenopathy (28 malignant and seven benign nodes). They underwent echoplanar diffusion-weighted magnetic resonance imaging of the mediastinum with b-factors of 0, 300 and 600 s/mm². The apparent diffusion coefficient (ADC) values of the mediastinal lymph nodes were calculated. The ADC values were correlated with the biopsy results and statistical analysis was done. A value of P<.05 was considered significant.

Results

The mean ADC value of malignant mediastinal lymphadenopathy (1.06±0.3×10⁻³ mm²/s) was significantly lower (P=.001) than that of benign lymphadenopathy (2.39±0.7×10⁻³ mm²/s). There was an insignificant difference in the ADC values between metastatic and lymphomatous mediastinal lymph nodes (P=.32) as well as within benign nodes (P=.07). When an ADC value of 1.85×10⁻³ mm²/s was used as a threshold value for differentiating malignant mediastinal nodes from benign nodes, the best results were obtained with an accuracy of 83.9%, a sensitivity of 96.4%, a specificity of 71.4%, a negative predictive value of 95.2% and a positive predictive value of 77.1%. The area under the curve was 0.98.

Conclusion

Diffusion weighted magnetic resonance imaging is a promising noninvasive imaging modality that can be used for characterization of mediastinal lymphadenopathy and differentiation of malignant from benign mediastinal lymph nodes.     

Numerical and experimental investigation of kerf depth effect on high-frequency phased array transducer

Background

High-frequency ultrasonic transducer arrays are essential for high resolution imaging in clinical analysis and Non-Destructive Evaluation (NDE). However, the structure design and fabrication of the kerfed ultrasonic array is quite challenging when very high frequency (?100 MHz) is required.

Objective and method

Here we investigate the effect of kerf depth on the performances of array transducers. A finite element tool, COMSOL, is employed to simulate the properties of acoustic field and to calculate the electrical properties of the arrays, including crosstalk effect and electrical impedance. Furthermore, Inductively Coupled Plasma (ICP) deep etching process is used to etch 36°/Y-cut lithium niobate (LiNbO₃) crystals and the limitation of etching aspect ratio is studied. Several arrays with different profiles are realized under optimized processes. At last, arrays with a pitch of 25 μm and 40 μm are fabricated and characterized by a network analyzer.

Results

Kerf depth plays an important role in the performance of the transducer array. The crosstalk is proportional to kerf depth. When kerf depth is more than 13 μm, the array with crosstalk less than −20 dB, which is acceptable for the real application, could provide a desired resolution. Compared to beam focusing, kerf depth exhibits more effect on the beam steering/focusing. The lateral pressure distribution is quantitatively summarized for four types of arrays with different kerf depth. The results of half-cut array are similar to those of the full-cut one in both cases of focusing and steering/focusing. The Full-Width-at-Half-Maximum (FWHM) is 55 μm for the half-cut array, and is 42 μm for the full-cut one. The 5-μm-cut array, suffering from severe undesired lobes, demonstrates similar behaviors with the no-cut one. ICP process is used to etch the 36°/Y-cut LiNbO₃ film. The aspect ratio of etching profile increases with the kerf width decreasing till it stops by forming a V-shaped groove, and the positive tapered profile angle ranges between 62° and 80°. If the mask selectivity does not limit the process in terms of achievable depth, the aspect ratio is limited to values around 1.3. The measurement shows the electrical impedance and crosstalk are consistent with the numerical calculation.

Conclusion

The numerical results indicate that half-cut array is a promising alternative for the fabrication of high-frequency ultrasonic linear arrays. In fact, the minimum pitch that could be obtained is around 25 μm, equivalent to a pitch of 1.6λ, with a kerf depth of 16 μm under the optimized ICP parameters.     

Continuous-wave ultrasound reflectometry for surface roughness imaging applications

Background

Measurement of surface roughness irregularities that result from various sources such as manufacturing processes, surface damage, and corrosion, is an important indicator of product quality for many nondestructive testing (NDT) industries. Many techniques exist, however because of their qualitative, time-consuming and direct-contact modes, it is of some importance to work out new experimental methods and efficient tools for quantitative estimation of surface roughness.

Objective and method

Here we present continuous-wave ultrasound reflectometry (CWUR) as a novel nondestructive modality for imaging and measuring surface roughness in a non-contact mode. In CWUR, voltage variations due to phase shifts in the reflected ultrasound waves are recorded and processed to form an image of surface roughness.

Results

An acrylic test block with surface irregularities ranging from 4.22 μm to 19.05 μm as measured by a coordinate measuring machine (CMM), is scanned by an ultrasound transducer having a diameter of 45 mm, a focal distance of 70 mm, and a central frequency of 3 MHz. It is shown that CWUR technique gives very good agreement with the results obtained through CMM inasmuch as the maximum average percent error is around 11.5%.

Conclusion

Images obtained here demonstrate that CWUR may be used as a powerful non-contact and quantitative tool for nondestructive inspection and imaging of surface irregularities at the micron-size level with an average error of less than 11.5%.     

Hypocrellin B-mediated sonodynamic action induces apoptosis of hepatocellular carcinoma cells

Objective

The present study aims to investigate apoptosis of hepatocellular carcinoma cells induced by hypocrellin B-mediated sonodynamic action.

Methods

The hypocrellin B concentration was kept constant at 2.5 μM and cells from the hepatocellular carcinoma HepG2 cell line were exposed to ultrasound with an intensity of 0.46 W/cm² for 8 s. Cell cytotoxicity was quantified using an MTT assay 24 h after sonodynamic therapy (SDT) of hypocrellin B. Apoptosis was investigated using a flow cytometry with Annexin V-FITC and propidium iodine staining. Intracellular reactive oxygen species (ROS) levels were detected using a flow cytometry with 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA) staining.

Results

The cytotoxicity of hypocrellin B-mediated sonodynamic action on HepG2 cells was significantly higher than those of other treatments including ultrasound alone, hypocrellin B alone and sham treatment. Flow cytometry showed that hypocrellin B-induced sonodynamic action markedly enhanced the apoptotic rate of HepG2 cells. Increased ROS was observed in HepG2 cells after being treated with hypocrellin B-mediated sonodynamic action.

Conclusions

Our data demonstrated that hypocrellin B-mediated sonodynamic action remarkably induced apoptosis of HepG2 cells, suggesting that apoptosis is an important mechanism of cell death induced by hypocrellin B-mediated SDT.     

Fractal dimension of 40 MHz intravascular ultrasound radio frequency signals

Objective

Fully automatic tissue characterization in intravascular ultrasound systems is still a challenge for the researchers. The present work aims to evaluate the feasibility of using the Higuchi fractal dimension of intravascular ultrasound radio frequency signals as a feature for tissue characterization.

Methods

Fractal dimension images are generated based on the radio frequency signals obtained using mechanically rotating 40 MHz intravascular ultrasound catheter (Atlantis SR Plus, Boston Scientific, USA) and compared with the corresponding correlation images.

Conclusion

An inverse relation between the fractal dimension images and the correlation images was revealed indicating that the hard or slow moving tissues in the correlation image usually have low fractal dimension and vice-versa. Thus, the present study suggests that fractal dimension images may be used as a feature for intravascular ultrasound tissue characterization and present better resolution then the correlation images.     

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.     

Ultrasound induces cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin

Objectives

Curcumin, a natural pigment from the traditional Chinese herb, has shown promise as an efficient enhancer of ultrasound. The present study aims to investigate ultrasound-induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin in vitro.

Methods

Nasopharyngeal carcinoma cell line CNE2 cells were incubated by 10 μm curcumin and then were treated by ultrasound for 8 s at the intensity of 0.46 W/cm². Cytotoxicity was evaluated using MTT assay and light microscopy. Mitochondrial damage was analyzed using a confocal laser scanning microcopy with Rhodamine 123 and ultrastructural changes were observed using a transmission electron microscopy (TEM).

Results

MTT assay showed that cytotoxicity induced by ultrasound treatment alone and curcumin treatment alone was 18.16 ± 2.37% and 24.93 ± 8.30%, respectively. The cytotoxicity induced by the combined treatment of ultrasound and curcumin significantly increased up to 86.67 ± 7.78%. TEM showed that microvillin disappearance, membrane blebbing, chromatin condensation, swollen mitochondria, and mitochondrial myelin-like body were observed in the cells treated by ultrasound and curcumin together. The significant collapse of mitochondrial membrane potential (MMP) was markedly observed in the CNE2 cells after the combined treatment of curcumin and ultrasound.

Conclusions

Our findings demonstrated that ultrasound sonication in the presence of curcumin significantly killed the CNE2 cells and induced ultrastructural damage and the dysfunction of mitochondria, suggesting that ultrasound treatment remarkably induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin.     

Parametric harmonic-to-fundamental ratio contrast echocardiography: a novel approach to identification and accurate measurement of left ventricular area under variable levels of ultrasound signal attenuation

Objectives

We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation.

Background

Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography.

Methods

RF data from short axis systolic and diastolic scans were obtained from 14 open-chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7 dB or 14 dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0 dB, 7 dB and 14 dB attenuation conditions, and LV area obtained by summation of “LV cavity pixels”. A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts.

Results

Correlation of the HFR-defined and reference areas at systole was R = 0.95, R = 0.94, and R = 0.91 for 0 dB, 7 dB and 14 dB levels of attenuation, respectively, and at diastole was R = 0.95 for 0 dB, 7 dB and 14 dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm² (i.e. negligible) in all attenuation settings.

Conclusion

Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals.     

Effects of therapeutic pulsed ultrasound and dimethylsulfoxide phonophoresis on oxidative stress parameters after injury induced by eccentric exercise

Introduction

The aim of the study was to evaluate the effects of TPU together with DMSO on oxidative stress parameters after eccentric exercise.

Methods

Thirty and six animals were divided in control; eccentric exercise (EE); EE + saline gel 0.9%; EE + TPU 0.8 W/cm²; EE + DMSO gel; EE + TPU + DMSO gel and submitted to one 90-min downhill run (1.0 km h⁻¹). TPU was used 2, 12, 24, 46 h after exercise session and 48 h after the animals were killed and the gastrocnemius muscles were surgically removed. Production of superoxide anion, creatine kinase (CK) levels, lipoperoxidation, carbonylation, and antioxidants enzymes were analyzed.

Results

Showed that TPU and gel-DMSO improved muscle healing. Moreover, superoxide anion production, TBARS level and protein carbonyls levels, superoxide dismutase and catalase activity were all decreased in the group TPU plus gel-DMSO.

Discussion

Our results show that DMSO is effective in the reduction of the muscular lesion and in the oxidative stress after eccentric exercise only when used with TPU.     

Assessment of pulmonary artery pulse wave velocity in children: An MRI pilot study

Purpose

To assess the feasibility of measuring pulmonary artery (PA) pulse wave velocity (PWV) in children breathing ambient air and 12% oxygen.

Methods

Velocity-encoded phase-contrast MR images of the PA were acquired in 15 children, aged 9–12 years, without evidence of cardiac or pulmonary diseases. PWV was derived as the ratio of flow to area changes during early systole. Each child was scanned twice, in air and after at least 20 minutes into inspiratory hypoxic challenge. Intra-observer and inter-observer variability and repeatability were also compared.

Results

PA PWV, which was successfully measured in all subjects, increased from 1.31 ± 0.32 m/s in air to 1.61 ± 0.58 m/s under hypoxic challenge (p = 0.03). Intra- and inter-observer coefficients of variations were 9.0% and 15.6% respectively. Good correlation within and between observers of r = 0.92 and r = 0.72 respectively was noted for PA PWV measurements. Mean (95% limit of agreement) intra- and inter-observer agreement on Bland–Altman analysis were − 0.02 m/s (− 0.41–0.38 m/s) and -0.28 m/s (− 1.06–0.49 m/s).

Conclusion

PA PWV measurement in children using velocity-encoded MRI is feasible, reproducible and sufficiently sensitive to detect differences in PA compliance between normoxia and hypoxia. This technique can be used to detect early changes of PA compliance and monitor PAH in children.     

Characterization of ultrasound-mediated destruction of drug-loaded microbubbles using an improved in vitro model

Introduction

Ultrasound mediated destruction of microbubbles (MBs) has become a promising tool for site specific drug and gene delivery. One of the most important properties of drug-loaded MBs is their destructibility by ultrasound. Therefore, the aim of this study was to establish a new in vitro model that allows evaluation of the kinetics of ultrasound-mediated MB destruction at near physiological conditions.In this work, a newly developed drug-loaded MB formulation was compared with unloaded MBs in order to assess the influence of drug-loading on their acoustic destructibility. Furthermore, drug-loaded MBs were compared to acoustically active lipospheres (AALs), comprising an additional layer of triacetin, as well as to a marketed MB contrast agent (SonoVue^®, Bracco Diagnostics, USA), used as standard.

Methods

MBs with phospholipid monolayer shells were produced by mechanical agitation of liposomal dispersions and octafluoropropane gas. AALs were accordingly produced by agitation of phospholipid-stabilized aqueous triacetin microemulsions with gas.The in vitro experimental setup for acoustic destructibility testing comprised a membrane cell, pressurized and brought to 37 °C in order to imitate human blood pressure and body temperature. The optimized egg-like cell shape provided optimal flow conditions and a minimized dead volume.Ultrasound with frequencies of 1 and 3 MHz and intensities, varying from 1 to 4 W/cm², was applied through a silicone membrane window to the cell. MB size distribution and concentration were measured by light blockage in equal time intervals during the sonication.

Results

The optimized in vitro setup demonstrated differences in the ultrasound destructibility of the MB formulations used. The fastest decay upon ultrasound exposure was found for SonoVue^®. Unloaded and drug-loaded MBs appeared to be comparably destructible to SonoVue^®. AALs were about 4.5-fold more stable than SonoVue^®. MB destructibility was also found to depend on particle diameter, corresponding to theoretical models described in the literature.

Conclusion

The optimized in vitro setup has rendered a fast and reliable laboratory tool for characterization of MB formulations.     

Surface modification with fibronectin or collagen to improve the cell adhesion

Objective

The surface of biomaterials plays a critical role in determining bioactivity. The aim of this study was to evaluate the cell adhesion and proliferation of ADSCs on the surface of biomaterial which is modified with fibronectin or collagen.

Materials and methods

Adipose-derived stromal cells (ADSCs) were obtained from SD rats, expanded in culture, and seeded onto scaffold surface-modified with fibronectin or collagen. To characterize cellular attachment, cells were incubated on scaffold for 1 and 2 h and then counted the cells attached onto the scaffold. The MTT assay was chosen to evaluate the proliferation at days 1, 4, 7 and 14. After 7 d of culture, scanning electron microscope was chosen to observe cell morphology and attachment of ADSCs on the scaffolds.

Results

Attachment at 1 and 2 h of cells on scaffold modified with fibronectin was significantly greater than in control, but not with collagen. The MTT assay revealed that ADSCs proliferation tendency was nearly parallel to that in control. The scanning electron microscope (SEM) showed that ADSCs in experiment expanded thoroughly and excreted much extracellular materials.

Conclusions

Surface modification with fibronectin or collagen can enhance the attachment of cultured ADSCs on the scaffold, but it had not evident effect to proliferation.     

In vitro comparative study of vibro-acoustography versus pulse-echo ultrasound in imaging permanent prostate brachytherapy seeds

Background

Permanent prostate brachytherapy (PPB) is a common treatment for early stage prostate cancer. While the modern approach using trans-rectal ultrasound guidance has demonstrated excellent outcome, the efficacy of PPB depends on achieving complete radiation dose coverage of the prostate by obtaining a proper radiation source (seed) distribution. Currently, brachytherapy seed placement is guided by trans-rectal ultrasound imaging and fluoroscopy. A significant percentage of seeds are not detected by trans-rectal ultrasound because certain seed orientations are invisible making accurate intra-operative feedback of radiation dosimetry very difficult, if not impossible. Therefore, intra-operative correction of suboptimal seed distributions cannot easily be done with current methods. Vibro-acoustography (VA) is an imaging modality that is capable of imaging solids at any orientation, and the resulting images are speckle free.

Objective and methods

The purpose of this study is to compare the capabilities of VA and pulse-echo ultrasound in imaging PPB seeds at various angles and show the sensitivity of detection to seed orientation. In the VA experiment, two intersecting ultrasound beams driven at f₁ = 3.00 MHz and f₂ = 3.020 MHz respectively were focused on the seeds attached to a latex membrane while the amplitude of the acoustic emission produced at the difference frequency 20 kHz was detected by a low frequency hydrophone.

Results

Finite element simulations and results of experiments conducted under well-controlled conditions in a water tank on a series of seeds indicate that the seeds can be detected at any orientation with VA, whereas pulse-echo ultrasound is very sensitive to the seed orientation.

Conclusion

It is concluded that vibro-acoustography is superior to pulse-echo ultrasound for detection of PPB seeds.     

Interaction of a high-order Bessel beam with a submerged spherical ultrasound contrast agent shell - Scattering theory

Background and objective

Acoustic scattering properties of ultrasound contrast agents are useful in extending existing or developing new techniques for biomedical imaging applications. A useful first step in this direction is to investigate the acoustic scattering of a new class of acoustic beams, known as helicoidal high-order Bessel beams, to improve the understanding of their scattering characteristics by an ultrasound contrast agent, which at present is very limited.

Method

The transverse acoustic scattering of a commercially available albuminoidal ultrasound contrast agent shell filled with air or a denser gas such as perfluoropropane and placed in a helicoidal Bessel beam of any order is examined numerically. The shell is assumed to possess an outer radius a = 3.5 microns and a thickness of ∼105 nm. Moduli of the total and resonance transverse acoustic scattering form functions are numerically evaluated in the bandwidth 0 < ka? 3, which corresponds to a frequency bandwidth of 0-205 MHz that covers a wide range of applications for imaging with contrast agents. Particular attention is paid to the shell’s material, the content of its interior hollow region and the fluid surrounding its exterior. The contrast agent shell is assumed to be immersed in an ideal compressible fluid so the viscous corrections are not considered. Analytical equations are derived and numerical calculations of the total and resonance form functions are performed with particular emphasis on the effect of varying the half-cone angle, the order of the helicoidal Bessel beam as well as the fluid that fills the interior hollow space.

Results and conclusion

It is shown that shell wave resonance modes can be excited on an encapsulated micro-bubble. The forward and backscattering vanish for a helicoidal high-order Bessel beam. Additionally, the fluid filling the inner core affects the shell’s response significantly. Moreover, there is no monopole contribution to the axial scattering of a helicoidal Bessel beam of order m ? 1 so that the dynamics of contrast agents would be significantly altered. The main finding of the present theory is the suppression or enhancement for a particular resonance that may be used to advantage in imaging with ultrasound contrast agents for clinical applications.