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1.
莫润阳  林书玉  王成会 《物理学报》2011,60(11):114306-114306
理论和实验研究了超声空化场中的H-22型肝癌细胞产生可逆声孔效应的剪应力阈值.本文用1.37 MHz的聚焦声场,当超顺磁性纳米氧化铁在细胞悬液中的终浓度为410 μg/mL,换能器负载电功率为2 W,超声辐照60 s,细胞存活率90%以上时,有45.9±13.5%的细胞显示普鲁士蓝染阳性,暗示超声作用下,这些细胞表面曾出现可逆性微孔而使磁性微粒由此进入细胞内.利用无界自由空间微泡运动方程的球对称稳态解对实验条件下细胞膜表面的切变应力进行数值估算,结果表明,使H-22细胞产生可逆性声孔效应的微流剪应力阈值为697 Pa. 关键词: 声孔效应 磁性标记 微流 剪应力  相似文献   

2.
In this work we determine conditions to produce cell samples for imaging with detection of the modification of the magnetic field by maghemite (Fe2O3) nanoparticles acting as a high sensitivity magnetic bio-sensor based on the giant magneto-impedance (GMI) effect. Mat Ly Lu cells are grown for 24 h with various maghemite nanoparticles concentrations (from 0 to 6 mg/ml). The percentage of viable cells is determined by counting labeled cells with trypan blue under an optical microscope. The quantity of nanoparticles internalized into the cells is evaluated by X-ray fluorescence analysis and expressed in iron moles per cell. The GMI bio-sensor was tested with the various samples. We observed that the best sensitivity of the GMI bio-sensor was obtained at a frequency of 1 MHz. To confirm these results in the presence of cell samples, four measurement frequencies were pre-selected (from 1 to 100 MHz) and tested. Cell growth conditions compatible with an acceptable percentage of cell viability for various concentrations of nanoparticles were also determined. These experiments allow us to conclude that cell growth with 0.1 mg/ml of nanoparticles for 24 h shows modifications of the magnetic field detectable optimally at 1 MHz frequency.  相似文献   

3.
Xu J  Xia X  Leung AW  Xiang J  Jiang Y  Yu H  Bai D  Li X  Xu C 《Ultrasonics》2011,51(4):480-484
Sonodynamic therapy with pyropheophorbide-a methyl ester (MPPa) presents a promising aspect in treating liver cancer. The present study aims to investigate the mitochondrial damage of liver cancer cells induced by MPPa-mediated sonodynamic action. Mouse hepatoma cell line H22 cells were incubated with MPPa (2 μM) for 20 h and then exposed to ultrasound with an intensity of 0.97 W/cm2 for 8 s. Cytotoxicity was investigated 24 h after sonodynamic action using MTT assay and light microscopy. Mitochondrial membrane potential (ΔΨm) was analyzed using flow cytometry with rhodamine 123 staining and ultrastructural changes were observed using transmission electron microscopy (TEM).The cytotoxicity of MPPa-mediated SDT on H22 cell line was 73.00 ± 3.42%, greater than ultrasound treatment alone (28.12 ± 5.19%) significantly while MPPa treatment alone had no significant effect on H22 cells. Moreover, after MPPa-mediated SDT cancer cells showed swollen mitochondria under TEM and a significant collapse of mitochondrial membrane potential. Our findings demonstrated that MPPa-mediated SDT could remarkably induce cell death of H22 cells, and highlighted that mitochondrial damage might be an important cause of cell death induced by MPPa-mediated SDT.  相似文献   

4.
The primary objective of this work was to develop and optimize the calibration techniques for ultrasonic hydrophone probes used in acoustic field measurements up to 100 MHz. A dependable, 100 MHz calibration method was necessary to examine the behavior of a sub-millimeter spatial resolution fiber optic (FO) sensor and assess the need for such a sensor as an alternative tool for high frequency characterization of ultrasound fields. Also, it was of interest to investigate the feasibility of using FO probes in high intensity fields such as those employed in HIFU (high intensity focused ultrasound) applications. In addition to the development and validation of a novel, 100 MHz calibration technique the innovative elements of this research include implementation and testing of a prototype FO sensor with an active diameter of about 10 μm that exhibits uniform sensitivity over the considered frequency range and does not require any spatial averaging corrections up to about 75 MHz. The results of the calibration measurements are presented and it is shown that the optimized calibration technique allows the sensitivity of the hydrophone probes to be determined as a virtually continuous function of frequency and is also well suited to verify the uniformity of the FO sensor frequency response. As anticipated, the overall uncertainty of the calibration was dependent on frequency and determined to be about ±12% (±1 dB) up to 40 MHz, ±20% (±1.5 dB) from 40 to 60 MHz and ±25% (±2 dB) from 60 to 100 MHz. The outcome of this research indicates that once fully developed and calibrated, the combined acousto-optic system will constitute a universal reference tool in the wide, 100 MHz bandwidth.  相似文献   

5.
We report on the magnetic hyperthermia properties of chemically synthesized ferromagnetic 11 and 16 nm Fe(0) nanoparticles of cubic shape displaying the saturation magnetization of bulk iron. The specific absorption rate measured on 16 nm nanocubes is 1690±160 W/g at 300 kHz and 66 mT. This corresponds to specific losses-per-cycle of 5.6 mJ/g, largely exceeding the ones reported in other systems. A way to quantify the degree of optimization of any system with respect to hyperthermia applications is proposed. Applied here, this method shows that our nanoparticles are not fully optimized, probably due to the strong influence of magnetic interactions on their magnetic response. Once protected from oxidation and further optimized, such nano-objects could constitute efficient magnetic cores for biomedical applications requiring very large heating power.  相似文献   

6.
Tang W  Fan W  Liu Q  Zhang J  Qin X 《Ultrasonics》2011,51(7):777-785
p53 plays a pivotal role in apoptosis. In addition, p53 is currently extensively investigated as a promising strategy for highly specific anticancer therapy in chemotherapeutics and photodynamic therapy. However, the role of p53 in the response of tumor cells to sonodynamic therapy treatment is still unclear. In this study, we aim to investigate the activation of p53 in sonodynamic therapy. Three murine tumor models with distinct aggressiveness (S180, H-22 and EAC) were treated with 1.75 MHz continuous ultrasound at an acoustic intensity (ISATA) of 1.4 W for 3 min in the presence of 20 μg/ml hematoporphyrin. The DNA fragment and nuclear damage were observed by TUNEL and single cell gel electrophoresis. Western blotting and RT-PCR were used to analyze the expression of p53, PUMA, Bax and Fas. Then we checked the translocation of p53 by confocal microscopy. DNA sequencing was used to determine the status of p53 gene in three tumor cell lines. Our results indicated that the level of p53 protein and mRNA increased significantly, and p53 activated the expression of its downstream pro-apoptosis gene PUMA, Bax and Fas in the S180 and H-22 cells. Meanwhile, p53 protein translocated onto mitochondria. In the EAC cells, expression and translocation of p53 was not found; the level of PUMA, Bax and Fas remained unaltered. The S180 cells showed most serious DNA fragment and nuclear damage with 77.43% TDNA; H-22 cells in the middle with 58.85% TDNA; whereas EAC cells appeared less nuclear material lost with just 15.82% TDNA. The results of DNA sequencing showed that the sequences of exons 5-8 of the p53 gene of S180, H-22 and EAC cells were the same with the sequences of wild-type p53 provided by NCBI. These results primarily demonstrated that: (1) p53 was activated to promote SDT-induced apoptosis through extrinsic and intrinsic signaling pathways in the S180 and H-22 cells; (2) cellular responses of different cells to SDT were distinct, the aggressive S180 cells were much more sensitive than H-22, whereas EAC cells were relatively less sensitive. The discrepancy among the cell lines may be due to different activation time of p53 protein.  相似文献   

7.
三种肿瘤细胞对超声结合血卟啉敏感性的实验研究   总被引:2,自引:0,他引:2       下载免费PDF全文
实验采用频率为1.6MHz,强度为1W/cm^2、3W/cm^2、5W/cm^2、7W/cm^2的聚焦超声结合血卟啉分别对腹水型小鼠S180细胞(Sarcomal80,S180)、艾氏腹水瘤细胞(Ehrlich Ascites Tumor,EAT)及H-22肝癌细胞进行杀伤效应研究,利用台盼蓝拒染法检测处理后细胞存活率的变化。实验结果表明,不同类型的细胞对超声结合血卟啉的敏感性不同,声照条件相同时,三种细胞对1.6MHz频率超声的敏感性依次为:S18〉EAT〉H-22,且对超声结合血卟啉敏感性明显大于单纯超声。无论是单纯超声组还是超声结合血卟啉组,三种细胞的存活率均随超声强度的增加而下降。  相似文献   

8.
In this paper, water-soluble magnetite nanoparticles have been directly synthesized by thermal decomposition of iron (III) acetylacetonate, Fe(acac)3 in tri(ethyleneglycol). Size and morphology of the nanoparticles are determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements while the crystal structure is identified using X-ray diffraction (XRD). Surface charge and surface coating of the nanoparticles are recognized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectra (XPS) and zeta potential measurements. Magnetic properties are determined using vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements. The results show that as-prepared magnetite nanoparticles are relatively monodisperse, single crystalline and superparamagnetic in nature with the blocking temperature at around 100 K. The magnetite nanoparticles are found to be highly soluble in water due to steric and electrostatic interactions between the particles arising by the surface adsorbed tri(ethyleneglycol) molecules and associated positive charges, respectively. Cytotoxicity studies on human cervical (SiHa), mouse melanoma (B16F10) and mouse primary fibroblast cells demonstrate that up to a dose of 80 μg/ml, the magnetic nanoparticles are nontoxic to the cells. Specific absorption rate (SAR) value has been calculated to be 885 and 539 W/gm for samples with the iron concentration of 1 and 0.5 mg/ml, respectively. The high SAR value upon exposure to 20 MHz radiofrequency signifies the applicability of as-prepared magnetite nanoparticles for a feasible magnetic hyperthermia treatment.  相似文献   

9.
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, = 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.  相似文献   

10.
Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO2) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO2 NPs activated by external ultrasound irradiation (called TiO2/US treatment). The present study first examined the uptake behavior of TiO2 NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24 h. It took 6 h for sufficient uptake of the TiO2 NPs by the cells. Next, the effect of the TiO2/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm2, 30 s) to the cells which incorporated the TiO2 NPs. Apoptosis was observed at 6 h after the TiO2/US treatment. Although no apparent cell-injury was observed until 24 h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO2/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO2 (0.1 mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm2 for 60 s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions.  相似文献   

11.
Aqueous colloidal suspension of iron oxide nanoparticles has been synthesized. Z-potential of iron oxide nanoparticles stabilized by citric acid was −35±3 mV. Iron oxide nanoparticles have been characterized by the light scattering method and transmission electron microscopy. The polyelectrolyte/iron oxide nanoparticle thin films with different numbers of iron oxide nanoparticle layers have been prepared on the surface of silicon substrates via the layer-by-layer assembly technique. The physical properties and chemical composition of nanocomposite thin films have been studied by atomic force microscopy, magnetic force microscopy, magnetization measurements, Raman spectroscopy. Using the analysis of experimental data it was established, that the magnetic properties of nanocomposite films depended on the number of iron oxide nanoparticle layers, the size of iron oxide nanoparticle aggregates, the distance between aggregates, and the chemical composition of iron oxide nanoparticles embedded into the nanocomposite films. The magnetic permeability of nanocomposite coatings has been calculated. The magnetic permeability values depend on the number of iron oxide nanoparticle layers in nanocomposite film.  相似文献   

12.
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.  相似文献   

13.
Fe-doped Au nanoparticles are ideal for biological applications over magnetic oxides due to their conjugation chemistry, optical properties, and surface chemistry. We present an AC magnetic field heating study of 8 nm Fe-doped Au nanoparticles which exhibit magnetic behavior. Magnetic heating experiments were performed on stable aqueous solutions of the nanoparticles at room temperature. The nanoparticles exhibit magnetic field heating, with a specific absorption rate (SAR) of 1.84 W/g at 40 MHz and H=100 A/m. The frequency dependence of the heating follows general trends predicted by power loss equations and is similar to traditional materials.  相似文献   

14.
Multifunctional magnetic microcapsules (MMCs) for the combined cancer cells hyperthermia and chemotherapy in addition to MR imaging are successfully developed. A classical layer‐by‐layer technique of oppositely charged polyelectrolytes (poly(allylamine hydrochloride) (PAH) and poly(4‐styrene sulfonate sodium) (PSS)) is used as it affords great controllability over the preparation together with enhanced loading of the chemotherapeutic drug (doxorubicin, DOX) in the microcapsules. Superparamagnetic iron oxide (SPIOs) nanoparticles are layered in the system to afford MMC1 (one SPIOs layer) and MMC2 (two SPIOs layers). Most interestingly, MMC1 and MMC2 show efficient hyperthermia cell death and controlled DOX release although their magnetic saturation value falls below 2.5 emu g?1, which is lower than the 7–22 emu g?1 reported to be the minimum value needed for biomedical applications. Moreover, MMCs are pH responsive where a pH 5.5 (often reported for cancer cells) combined with hyperthermia increases DOX release predictably. Both systems prove viable when used as T2 contrast agents for MR imaging in HeLa cells with high biocompatibility. Thus, MMCs hold a great promise to be used commercially as a theranostic platform as they are controllably prepared, reproducibly enhanced, and serve as drug delivery, hyperthermia, and MRI contrast agents at the same time.  相似文献   

15.
This paper presents a study on the line-width and wavelength stability of a single mode narrow line-width (≈ 100 MHz) dye laser pumped by a copper vapour laser, with and without precision temperature control of dye solution. The single mode dye laser system was based on a specially designed SS metal dye cell and grazing incidence grating (GIG) dye resonator with intra-cavity double prism beam expander and etalon. A high precision wavelength-meter was used to record the line-width and frequency stability data. With the coarse dye solution temperature control of 23 ± 2 °C, dye laser line-width varied in a periodic fashion (in every 30 s) between 100 and 770 MHz. Frequency stability was ± 215 MHz (1 min). This is attributed to switching from single to double mode due to temperature induced cavity length change. For the precise dye solution control of 23 ± 0.1 °C, the periodic variation of the line-width was removed completely and the line-width was always ≤ 100 MHz. The frequency stability also improved to ± 42 MHz (1 min). It is established that the dye temperature control is very crucial for achieving, highly frequency stable single axial mode operation.  相似文献   

16.
Chen CK  Wan YL  Tsui PH  Chiu WT  Jui F 《Ultrasonics》2012,52(5):663-667
The objective of this study is to explore the feasibility of using ultrasound to detect mastoid effusion (ME). In the past, ultrasound has been used to measure middle ear effusion (MEE) by injecting water into the external ear canal to measure echoes from the tympanic membrane, which is uncomfortable for the patient. It has been shown that air cells in the mastoid of patients with MEE are filled with fluid, which implies that ME could be a useful indicator of MEE. This study suggests using ultrasound to detect ME as a potentially noninvasive approach for MEE detection. In vitro experiments were performed on ten cadaver samples of the human ear. A single-element 1 MHz transducer was used to measure the mastoid of each cadaver before and after injecting water into the mastoid. The experimental results showed that the relative amplitudes of ultrasonic signals differed significantly between before (0.24 ± 0.09, mean ± standard deviation) and after (0.15 ± 0.03) the water injection (p < 0.05, t-test), demonstrating that the ultrasonic reflection can be used to detect ME. The location of the human mastoid under the skin behind the ear allows external measurements, and hence ultrasound-based ME detection may be an alternative, noninvasive diagnostic approach to detecting MEE in the future, providing an examination that avoids discomfort.  相似文献   

17.
Low density and thin thickness are essential for electromagnetic (EM) wave absorbers. In this study, we fabricated a novel micro-tubular iron nanocomposite (MTIC) that composed of carbon microtubes and monodisperse iron nanoparticles (NPs). The bulk density of MTIC is only 0.35±0.04 g cm−3 due to its micro-tubular structure. The presence of iron NPs increased the magnetic loss significantly and therefore enhanced the reflection loss (RL) of MTIC/paraffin composite. The optimum thickness for the composite is 1.5-1.8 mm, with maximum bandwidth of 7.6 GHz for RL<−5 dB and 3.6 GHz for RL<−10 dB. The corresponding frequency at this thickness is 10-18 GHz. Because of low density and broad bandwidth at thin thickness, MTIC is a promising light-weight absorber for EM wave absorption or microwave shielding. This study will also provide new ideas for fabricating microwave absorbers with low density and thin thickness.  相似文献   

18.
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.  相似文献   

19.
Rhenium sulfide nanoparticles are associated with magnetic iron oxide through coprecipitation of iron salts with tetramethylammonium hydroxide. Sizes of the formed magnetic rhenium sulfide composite particles are in the range 5.5-12.5 nm. X-ray diffraction and energy-dispersive analysis of X-rays spectra demonstrate the coexistence of Fe3O4 and ReS2 in the composite particle, which confirm the formation of the magnetic rhenium sulfide composite nanoparticles. The association of rhenium sulfide with iron oxide not only keeps electronic state and composition of the rhenium sulfide nanoparticles, but also introduces magnetism with the level of 24.1 emu g-1 at 14 kOe. Surface modification with monocarboxyl-terminated poly(ethylene glycol) (MPEG-COOH) has the role of deaggregating the composite nanoparticles to be with average hydrodynamic size of 27.3 nm and improving the dispersion and the stability of the composite nanoparticles in water.  相似文献   

20.
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.  相似文献   

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