Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology.

Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child's life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (LPS) to pregnant females is a widely used paradigm. Previous studies have reported that a model of 'emotional stress', involving chronic exposure of rodents to ultrasonic frequencies, induces neuroinflammation, aberrant neuroplasticity, and behavioral deficits. In this study, we explored whether this model is a suitable paradigm for maternal stress and promotes neurodevelopmental abnormalities in the offspring of stressed females. Pregnant dams were exposed to ultrasound stress for 21 days. A separate group was injected with LPS on embryonic days E11.5 and E12.5 to mimic prenatal infection. The behavior of the dams and their female offspring was assessed using the sucrose test, open field test, and elevated plus maze. Additionally, the three-chamber sociability test and Barnes maze were used in the offspring groups. ELISA and qPCR were used to examine pro-inflammatory changes in the blood and hippocampus of adult females. Ultrasound-exposed adult females developed a depressive-like syndrome, hippocampal overexpression of GSK-3ß, IL-1ß, and IL-6 and increased serum concentrations of IL-1ß, IL-6, IL-17, RANTES, and TNFα. The female offspring also displayed depressive-like behavior, as well as cognitive deficits. These abnormalities were comparable to the behavioral changes induced by LPS. The ultrasound stress model can be a promising animal paradigm of neurodevelopmental pathology associated with prenatal 'emotional stress'.

Reduction of Platinum(IV) Prodrug Hemoglobin Nanoparticles with Deeply Penetrating Ultrasound Radiation for Tumor-Targeted Therapeutically Enhanced Anticancer Therapy.

The development of PtIV prodrugs that are reduced into the therapeutically active PtII species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of PtIV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of PtIV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.

Shear Elastic Coefficient of Normal and Fibrinogen-Deficient Clotting Plasma Obtained with a Sphere-Motion-Based Acoustic-Radiation-Force Approach.

Blood coagulation is a process involving several chemical reactions governed by coagulation factors, during which the shear elastic coefficient, µ, varies as the medium transitions from liquid to gel phase. This work used ultrasound to measure µ during the clotting of human plasma samples by tracking the motion of a glass sphere located inside a cuvette filled with the plasma. A 2.03 MHz ultrasonic system generated an impulsive acoustic radiation force acting on the sphere, and a 4.89 MHz pulse-echo ultrasonic system tracked the sphere displacement induced by that force. Measurements of µ were determined by fitting a µ-dependent theoretical model to the motion waveform of the sphere immersed in clotting normal plasma and plasma samples with fibrinogen (FI) concentrations of 1.2 (FI-deficiency) and 3.6 (FI-normal) g/L. For normal plasma, µ started at 14.22 Pa and increased rapidly until 2 min, then slowly until it reached 210.23 Pa at 35 min after the clotting process started. A similar trend was exhibited in plasma samples with FI concentrations of 1.2 and 3.6 g/L, with µ reaching 120.55 and 679.42 Pa, respectively. A theoretical model, related to the kinetics of clot-structure formation, describes the time changes of µ for the clotting plasma samples. The sphere-motion-based acoustic-radiation-force approach allowed us to measure the shear elastic coefficient during the coagulation process of plasma samples with normal and deficient FI concentrations. Our results suggest that the method used in this study is capable of being used to detect bleeding disorders.

Experimental investigation of flow boiling heat transfer enhancement under ultrasound fields in a minichannel heat sink.

Ultrasound is considered to be an effective active heat transfer enhancement method, which is widely used in various fields. But there is no clear understanding of flow boiling heat transfer characteristics in micro/mini-channels under ultrasonic field since the studies related are limited up to now. In this paper, a novel minichannel heat exchanger with two ultrasonic transducers inside the inlet and outlet plenum respectively is designed to experimentally investigate the impacts of ultrasound on flow boiling heat transfer enhancement in a minichannel heat sink. Flow visualization analyses reveal that ultrasound can promote rapid bubble motion, bubble detachment from heating wall surface and thereby new bubble generation, and decrease the length of confined bubble. Furthermore, the flow boiling experiments are initiated employing working fluid R141b at different ultrasonic parameters (e.g., frequency, power, angle of radiation) and heat flux under three types of ultrasound excitations: no ultrasound (NU), single inlet ultrasound (IU), inlet and outlet ultrasound (IOU). The results indicate that ultrasound has obvious augmentation effects on flow boiling heat transfer even though the intensification effects will be limited with the heat flux increases. The higher ultrasonic power, the lower ultrasonic frequency and the higher ultrasonic radiation angle, the better intensification efficiency. The maximum enhancement ratio of have in the saturated boiling section reaches 1.88 at 50 W, 23 kHz and 45° under the experimental conditions. This study will be beneficial for future applications of ultrasound on flow boiling heat transfer in micro/mini-channels.

A Biodegradable Magnetic Nanocomposite as a Superabsorbent for the Simultaneous Removal of Selected Fluoroquinolones from Environmental Water Matrices: Isotherm, Kinetics, Thermodynamic Studies and Cost Analysis.

The application of a magnetic mesoporous carbon/ß-cyclodextrin-chitosan (MMPC/Cyc-Chit) nanocomposite for the adsorptive removal of danofloxacin (DANO), enrofloxacin (ENRO) and levofloxacin (LEVO) from aqueous and environmental samples is reported in this study. The morphology and surface characteristics of the magnetic nanocomposite were investigated by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) adsorption-desorption and Fourier transform infrared spectroscopy (FTIR). The N2 adsorption-desorption results revealed that the prepared nanocomposite was mesoporous and the BET surface area was 1435 m2 g-1. The equilibrium data for adsorption isotherms were analyzed using two and three isotherm parameters. Based on the correlation coefficients (R2), the Langmuir and Sips isotherm described the data better than others. The maximum monolayer adsorption capacities of MMPC/Cyc-Chit nanocomposite for DANO, ENRO and LEVO were 130, 195 and 165 mg g-1, respectively. Adsorption thermodynamic studies performed proved that the adsorption process was endothermic and was dominated by chemisorption.

Ultrasound Radiation Force for the Assessment of Bone Fracture Healing in Children: An In Vivo Pilot Study.

Vibrational characteristics of bone are directly dependent on its physical properties. In this study, a vibrational method for bone evaluation is introduced. We propose a new type of quantitative vibro-acoustic method based on the acoustic radiation force of ultrasound for bone characterization in persons with fracture. Using this method, we excited the clavicle or ulna by an ultrasound radiation force pulse which induces vibrations in the bone, resulting in an acoustic wave that is measured by a hydrophone placed on the skin. The acoustic signals were used for wave velocity estimation based on a cross-correlation technique. To further separate different vibration characteristics, we adopted a variational mode decomposition technique to decompose the received signal into an ensemble of band-limited intrinsic mode functions, allowing analysis of the acoustic signals by their constitutive components. This prospective study included 15 patients: 12 with clavicle fractures and three with ulna fractures. Contralateral intact bones were used as controls. Statistical analysis demonstrated that fractured bones can be differentiated from intact ones with a detection probability of 80%. Additionally, we introduce a "healing factor" to quantify the bone healing progress which successfully tracked the progress of healing in 80% of the clavicle fractures in the study.

Neuroinflammation and aberrant hippocampal plasticity in a mouse model of emotional stress evoked by exposure to ultrasound of alternating frequencies.

Emotional stress is a form of stress evoked by processing negative mental experience rather than an organic or physical disturbance and is a frequent cause of neuropsychiatric pathologies, including depression. Susceptibility to emotional stress is commonly regarded as a human-specific trait that is challenging to model in other species. Recently, we showed that a 3-week-long exposure to ultrasound of unpredictable alternating frequencies within the ranges of 20-25 kHz and 25-45 kHz can induce depression-like characteristics in laboratory mice and rats. In an anti-depressant sensitive manner, exposure decreases sucrose preference, elevates behavioural despair, increases aggression, and alters serotonin-related gene expression. To further investigate this paradigm, we studied depression/distress-associated markers of neuroinflammation, neuroplasticity, oxidative stress and the activity of glycogen synthase kinase-3 (GSK-3) isoforms in the hippocampus of male mice. Stressed mice exhibited a decreased density of Ki67-positive and DCX-positive cells in the subgranular zone of hippocampus, and altered expression of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and anti-apoptotic protein kinase B phosphorylated at serine 473 (AktpSer473). The mice also exhibited increased densities of Iba-1-positive cells, increased oxidative stress, increased levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) in the hippocampus and plasma, and elevated activity of GSK-3 isoforms. Together, the results of our investigation have revealed that unpredictable alternating ultrasound evokes behavioural and molecular changes that are characteristic of the depressive syndrome and validates this new and simple method of modeling emotional stress in rodents.

Effects and mechanism of diclofenac degradation in aqueous solution by US/Zn0.

A system of ultrasound radiation coupled with Zn0 was applied to degrade diclofenac. The effects of initial pH, dosage of Zn0 and ultrasound density were investigated. To further explore the mechanism of the microcosmic reaction, the fresh and used Zn0 powders were characterized by SEM, XRD and XPS. Radical scavengers were used to determine the oxidation performance of strong oxidizing free radicals on diclofenac, including hydroxyl radicals and superoxide radicals. The results showed that the optimum removal of diclofenac reached to over 85% at pH of 2.0 in 15min, with Zn0 dosage of 0.1g/L and ultrasound density of 0.6W/cm3. TOC removal of 72.6% in 15min and dechlorination efficiency of diclofenac reached 70% in 30min. Characterization results showed that a ZnO membrane was generated on the surface of Zn particles after use. According to the mass spectrometry results, several possible pathways of diclofenac degradation were proposed, and most diclofenac was turned into micro-molecules or CO2 finally. The synergistic effect of US/Zn0 in the reactions led to a proposed degradation mechanism in which zinc could directly attack the target contaminant diclofenac because of its good reducibility with the auxiliary functions of ultrasonic irradiation, mechanical shearing and free radical oxidation.

Quantitative analysis of liver fibrosis in rats with shearwave dispersion ultrasound vibrometry: comparison with dynamic mechanical analysis.

Ultrasonic elastography, a non-invasive technique for assessing the elasticity properties of tissues, has shown promising results for disease diagnosis. However, biological soft tissues are viscoelastic in nature. Shearwave dispersion ultrasound vibrometry (SDUV) can simultaneously measure the elasticity and viscosity of tissue using shear wave propagation speeds at different frequencies. In this paper, the viscoelasticity of rat livers was measured quantitatively by SDUV for normal (stage F0) and fibrotic livers (stage F2). Meanwhile, an independent validation study was presented in which SDUV results were compared with those derived from dynamic mechanical analysis (DMA), which is the only mechanical test that simultaneously assesses the viscoelastic properties of tissue. Shear wave speeds were measured at frequencies of 100, 200, 300 and 400 Hz with SDUV and the storage moduli and loss moduli were measured at the frequency range of 1-40 Hz with DMA. The Voigt viscoelastic model was used in the two methods. The mean elasticity and viscosity obtained by SDUV ranged from 0.84±0.13 kPa (F0) to 1.85±0.30 kPa (F2) and from 1.12±0.11 Pa s (F0) to 1.70±0.31 Pa s (F2), respectively. The mean elasticity and viscosity derived from DMA ranged from 0.62±0.09 kPa (F0) to 1.70±0.84 kPa (F2) and from 3.38±0.32 Pa s (F0) to 4.63±1.30 Pa s (F2), respectively. Both SDUV and DMA demonstrated that the elasticity of rat livers increased from stage F0 to F2, a finding which was consistent with previous literature. However, the elasticity measurements obtained by SDUV had smaller differences than those obtained by DMA, whereas the viscosities obtained by the two methods were obviously different. We suggest that the difference could be related to factors such as tissue microstructure, the frequency range, sample size and the rheological model employed. For future work we propose some improvements in the comparative tests between SDUV and DMA, such as enlarging the harmonic frequency range of the shear wave to highlight the role of viscosity, finding an appropriate rheological model to improve the accuracy of tissue viscoelasticity estimations.

Radiofrequency ablation combined with low frequency ultrasound radiation with microbubble for the treatment of malignant liver neoplasms / 中华消化外科杂志

Objective To investigate the clinical efficacy and safety of radiofrequency ablation (RFA)combined with low frequency ultrasound radiation with microbubble for the treatment of malignant liver neoplasms.Methods The clinical data of 25 patients with malignant liver neoplasms who received RFA combined with low frequency ultrasound radiation with microbubble at the Kunming General Hospital from January 2010 to June 2011 were retrospectively analyzed.RFA was firstly performed with ultrasonic guidance,and then low frequency ultrasound radiation with microbubble was performed according to the results of ultrasound contrast examination 1 week after RFA.Ultrasound contrast examination was performed and the hepatic function and serum alpha fetoprotein (AFP) were assayed before operation,3 and 6 months after operation,respectively.All data were analyzed using the t test or chi-square test.Results The gross tumor volumes of 16 patients reduced by 30％ at 3 months after operation when compared with that before operation.The gross tumor volumes of 17 patients reduced by 50％ at 6 months after operation when compared with that before operation.The gross tumor volume of 7 patients reduced,but tissues surrounding tumors showed the signal of bloodstream.The gross tumor volume of 1 patient did not reduce.The levels of aspartate aminotransferase (AST),total bilirubin (TBil) and alpha fetoprotein (AFP) at 3 months after operation were significantly lower than those before operation (t =23.51,13.79,257.07,P ＜0.05).The levels of alanine aminotransferase (ALT),AST,TBil and AFP at 6 months after operation were significantly lower than those before operation (t =5.67,27.19,21.02,333.46,P ＜ 0.05).No local recurrence was detected during a follow-up of 6 months.The scores of quality of life (QOL) were very good in 21 (84.0％) patients,good in 2 (8.0％) patients,fair in 1 (4.0％) patient and poor in 1 (4.0％) patient.The scores of Karnofsky (KPS)were improved in 19 (76.0％) patients,stable in 5 (20.0％) patients and aggravated in 1 (4.0％) patient.There were significant differences in QOL and KPS between pre-and postoperation (x2=41.600,18.960,P ＜0.05).Conclusion RFA combined with low frequency ultrasound radiation with microbubble is effective in reducing the tumor size and protect the hepatic function for patients with malignant liver neoplasms.