Ji Yoon Kim;Un Chul Shin;Ji Yong Park;Ran Ji Yoo;Soeku Bae;Tae Hyeon Choi;Kyuwan Kim;Young Chan Ann;Jin Sil Kim;Yu Jin Shin;Hokyu Lee;Yong Jin Lee;Kyo Chul Lee;Suhng Wook Kim;Yun-Sang Lee
Journal of Radiopharmaceuticals and Molecular Probes
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v.9
no.1
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pp.9-16
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2023
Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.
Transdermal permeation enhancer has been used to increased skin absorption. External control of drug release and skin absorption can also be achieved by iontophoresis or phonophoresis. However, because several problems with iontophoresis are that it has a risk to skin damage because of the change of pH and the increase of current density in applying it and that it can be applied only in the form of water solution, This study is to enhance drug permeation via skin following application of ultrasound. For this goal, in gel containing piroxicam, the degree of skin permeation in vitro and anti-inflammatory effect in in vivo were investigated. Permeation study using hairless mouse skin was performed at 37 $^{\circ}C$ using buffer saline as the receptor solution. The amount of piroxicam were quantified using a HPLC system consisting of solvent delivery system. Following adoption of ultrasound 1 MHZ, it showed relatively high permeation rate where it was compared with non treated by ultrasound. The influence of duty cycle having an effect on skin permeation rate was slight higher in the case of using pulsed mode. Skin permeation increase attended by intensity of ultrasound, the permeation of trice was accelerated at 2.0 W/$cm^{2}$ than 1.0 W/$cm^{2}$. The skin permeation of piroxicam was substantially influenced by ultrasound. Anti-inflammatory effects were determined using carrageenan-induced paw swelling method in SD rat. Paw swelling tests showed that pulsed phonophoresis group was more effective than control group and only gel application group. The conclusion of phonophoresis was found to improve significantly the skin permeation in vitro and the anti-inflammatory effect in vivo.
Purpose: The aim of present study is to evaluate a possibility of clinical application for the effect of low intensity ultrasound stimulation (LIUS) in mechanical characteristics of bone on osteoporotic fractures prevention. Materials and Methods: Eight virgin ICR mice (14 weeks old, approximate weight 25g) were ovariectomized (OVX) to induce osteoporosis. The right hind limbs were then stimulated with LIDS (US Group), whereas left hind limbs were not stimulated (CON Group). Both hind limbs of all mice were scanned by in-vivo micro-CT to acquire two-dimensional (2D) images at 0 week before stimulation and 3 weeks and 6 weeks after stimulation. Three-dimensional (3D) finite element (FE) models generated by scanned 2D images were used to determine quantitatively the effect of LIUS on strength related to bone structure. Additionally, distributions of Hounsfield units and elastic moduli, which are related to the bone quality, for the bones in the US and CON groups were determined to analyze quantitatively a degree of improvement of bone qualities achieved by LIUS. Results: The result of FE analysis showed that the structural strength in US Group was significantly increased over time (p<0.05), while that in CON Group was statistically constant over time (p>0.05). High values of Hounsfield units obtained from voxels on micro-CT images and high values of elastic moduli converted from the Hounsfield units were dominantly appeared in US Group compared with those in CON Group. Conclusion: These finding indicated that LIUS would improve the mechanical characteristics of osteoporotic bone via the effects of bone structure (bone strength) and quality (Hounsfield unit and elastic modulus). Therefore, the LIUS may decrease effectively the risk of osteoporotic fracture in clinics.
Ultrasound brain stimulation is spot-lighted by its capability of inducing brain cell activation in a localized deep brain region and ultimately treating impaired brain function while the efficiency and directivity of neural modulation are highly dependent on types of stimulus waveforms. Therefore, to optimize the types of stimulation parameters, we propose a cell-cultivable ultrasonic transducer having a series stack of a spin-coated polymer piezoelectric element (Poly-vinylidene fluoride-trifluorethylene, PVDF-TrFE) and a parylene insulating layer enhancing output acoustic pressure on a glass-coverslip which is commonly used in culturing cells. Due to the uniformity and high accuracy of stimulus waveform, tens of neuronal cell responses located on the transducer surface can be recorded simultaneously with fluorescence microscopy. By averaging the cell response traces from tens of cells, small changes to the low intensity ultrasound stimulations can be identified. In addition, the reduction of stimulus distortions made by standing wave generated from reflections between the transducers and other strong reflectors can be achieved by placing acoustic absorbers. Through the proposed ultrasound transducer, we could successfully observe the calcium responses induced by low-intensity ultrasound stimulation of 6 MHz, 0.2 MPa in astrocytes cultured on the transducer surface.
The hydroxyl radical (·OH) and superoxide anion radical (·O2- ) generated by the shock wave generated during ultrasonic cavitation collapse in TiO2 suspension are highly useful because they can sterilize and disinfect. For practical use as a sterilization method without any chemicals, in this study, we proposed a method for evaluating the generation of radicals generated by high-intensity ultrasound emitted to titanium dioxide suspension. In the proposed method, the sonoluminescence phenomenon, which emits light by ultrasonic cavitation decay energy, was utilized, and the degree of radical generation was evaluated through the amount of light energy by sonoluminescence. As a result, even at a low concentration of titanium dioxide of 0.02 wt%, light energy 5 times higher than in the absence of titanium dioxide was received. After that, as the concentration increased by 0.1 wt%, the luminous intensity of sonoluminescence increased linearly by about 14.8 × 10-12 lm. Therefore, it was confirmed that the radicals generated by radiating high-intensity ultrasound to the titanium dioxide suspension increased linearly as the concentration of titanium dioxide increased within a given concentration range.
Purpose: The purpose of this study was to examine the effects of a video education program in women receiving high-intensity focused ultrasound (HIFU) treatment. Methods: This was a quasi-experimental study with a nonequivalent control group non-synchronized design. The participants were 54 patients who had benign uterine tumors and adenomyosis. The data were collected from June to August 2018. A 10-minute video education program on HIFU and post-procedural care was developed based on the literature. The experimental group was provided the video education program with a question-and-answer session for 10 minutes after viewing the video. The control group received usual care (i.e., verbal instructions on post-procedural self-care). The questionnaire survey was conducted twice: before the educational program and before being discharged from the hospital. Differences in uncertainty, emotions, and self-efficacy among patients were analyzed. Data were analyzed using the chi-square test, Shapiro-Wilk test, paired t-test, and t-test with SPSS version 23.0. Results: The participants in the experimental group showed a decrease in uncertainty (t=4.33, p<.001), improvements in anxiety (t=-4.07, p<.001) and depression (t=-3.55, p<.001), and an enhancement of self-efficacy (t=-4.39, p<.001) compared to the control group. Conclusion: This nursing intervention was effective at reducing uncertainty, improving emotions, and enhancing self-efficacy. This intervention is feasible for use in nursing practice as an aid for patients when considering treatment methods.
As many people are westernizing their life style and food consumption habits, a number of patients who have malignant tumors which grow very rapidly and hazardously destroy the human body are increasing. Ultrasonic hyperthermia is not only one of the tumor treatment methods which employs the non-radioactive ultrasonic waves to increase the temperature at the tumor region up to $40\sim45^{\circ}C$ to destroy and suppress tumor cells but also has been proved by many studies. Due to the rapid development of High Intensity Focused Ultrasound(HIFU), the ultrasound hyperthemia extensively boosts its applications in clinical field. For those reasons, Computed simulation factor should be needed before inspection to patients. To prove efficiency of ultrasonic hyperthermia, precise acoustic field measurement considering tissue characteristics and a heating experiment with tissue mimicking material phantom were conducted for effectiveness of simulation program. Finally, in this study, the computer simulation program verified the anticipated temperature effects induced by ultrasound hyperthermia. In the near future, it is hoped that this simulation program could be utilized to improve the efficiency of ultrasound hyperthermia.
Jung, Hyun Ho;Chang, Won Seok;Kim, Se Joo;Kim, Chan-Hyung;Chang, Jin Woo
Journal of Korean Neurosurgical Society
/
v.61
no.4
/
pp.427-433
/
2018
Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.
High intensity ultrasound was irradiated to induce mechano-chemical degradation during melt processing of polycarbonate (PC) and styrene-co-acrylonitrile (SAN) in an intensive mixer. It was found that macroradicals of PC and SAM can be generated during ultrasound assisted melt processing; which, in turn, provides a useful route to achieve in-situ compatibilization for the blends of PC and SAM by their mutual coupling. Effectiveness of compatibilization was assessed by investigating phase morphology and mechanical properties of the blends. It was observed that domain size was reduced and the stability of morphology was well maintained even after annealing treatment of the blends. In audition, the enhancement of mechanical properties such as elongation at break and tensile strength was evident, which added further confirmation on the desirable feature that sonication of melt-blends is able to enhance intermolecular interaction by promoting chemical bonds between dissimilar polymers without use of any compatibilizers.
Jung, Na Young;Rachmilevitch, Itay;Sibiger, Ohad;Amar, Talia;Zadicario, Eyal;Chang, Jin Woo
Journal of Korean Neurosurgical Society
/
v.62
no.6
/
pp.712-722
/
2019
Objective : Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. Methods : For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. Results : Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). Conclusion : This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.
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