• Title/Summary/Keyword: Focused Ultrasound

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Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

  • 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.

A Study on the Efficiency Evaluation of Ultrasound Therapy Using Varicose Vein Simulated Tissue Phantom and Tissue Equivalent Phantom (하지정맥류 모사 생체조직 팬텀과 조직등가 팬텀을 이용한 초음파 치료효과 평가에 관한 연구)

  • Kim, Ju-Young;Jung, Tae-Woong;Shin, Kyoung-Won;Noh, Si-Cheol;Choi, Heung-Ho
    • Journal of the Korean Society of Radiology
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    • v.12 no.3
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    • pp.427-433
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    • 2018
  • Because of the expectation of the non-invasive treatment effect, Various studies on the treatment of varicose veins using focused ultrasound are reported. In this study, the bio-tissue phantom and tissue equivalent phantom that can be applied to estimation of ultrasonic varicose veins treatment effect. Each phantom was evaluated for its usefulness by evaluating the acoustic characteristics and the shrinkage rate according to the ultrasonic irradiation. A multi-layer structure phantom with three layers of skin, fat, and muscle was constructed considering the structure of the tissue where the varicose veins occurred. The materials constituting each layer were made to have characteristics similar to human body. In addition, the multi-layered phantoms with blood vessel mimic tube, with bovine blood vessel, and with animal tissue were fabricated. The degree of shrinkage of blood vessel mimic material and vascular tissue according to ultrasonic irradiation was evaluated using B-mode image. As the results of this study, it was thought that the proposed phantom could be used effectively in the evaluation of ultrasonic varicose veins treatment. In addition, it is thought that these phantoms could be applied to the development of varicose vein treatment device using the focused ultrasound and the verification of the therapeutic effect.

A Study on the Implementation of Ultrasonic Guidance Algorithm for Improving Safety of Ultrasonic Varicose Vein Treatment (초음파 하지정맥류 치료의 안전성 개선을 위한 초음파 유도 알고리즘 구현에 관한 연구)

  • Kim, Seong-Cheol;Kim, Ju-Young;Noh, Si-Cheol;Choi, Heung-Ho
    • Journal of the Korean Society of Radiology
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    • v.12 no.3
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    • pp.435-441
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    • 2018
  • In this study, we performed to design an image guiding algorithm to improve the efficiency and safety of treatment of varicose vein by focused ultrasound. The algorithm was suggested by different guiding images according to the location of varicose veins. In the case of deep-seated varicose veins, the target area was marked on the surface of the blood vessel in the obtained cross-sectional blood vessel ultrasound image. In the case of the superficial varicose vein, A guiding system based on image segmentation algorithm of the vascular region was suggested and designed two different algorithms according to varicose veins progression degree. as a results, the algorithm based on ultrasound image show a small error with $830{\mu}m$ at maximum. However, the algorithm based on charge coupled device image has a maximum error of 8.3 mm in some data. Therefore, it is expected that additional study is needed for superficial varicose vein image guiding algorithm, and it is expected that the accuracy of blood vessel tracking should be evaluated by constructing simple system.

Comparative Study on Transcatheter Arterial Chemoembolization, Portal Vein Embolization and High Intensity Focused Ultrasound Sequential Therapy for Patients

  • Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Wu, Xing-Jun;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6257-6261
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    • 2012
  • Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.

Animal Skin Irritation and Skin Sensitization Tests of High Intensity Focused Ultrasound System Cartridges (집속형초음파자극시스템 카트리지의 동물실험을 통한 피부자극시험 및 피부 감작성시험)

  • Jun-tae, Kim;Ju-hee, Kim;Kyu-tai, Joo;Kyung-ah, Kim;Ahnryul, Choi;Jae-hyun, Jo;Jin-houng, Jeong
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.15 no.6
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    • pp.477-484
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    • 2022
  • In this study, the cartridge part of the focused ultrasound stimulation system was used as a sample to conduct a skin irritation test and a skin sensitization test through animal experiments among the tests related to GLP (Good Laboratory Practice), a medical device safety evaluation standard. The test was conducted after IACUC approval using 6 female New Zeland White Rabbits. The polar and non-polar stimulation indices were all '0.0'. In addition, in the case of skin sensitization evaluation, 30 guinea pigs approved by IACUC were divided into control and experimental groups, and all induction and induction steps were applied using the eluate itself without separate dilution of the test sample and blank test solution. As a result of the experiment, the skin reaction grade of the control animal was 0 grade, and there was no animal showing more than 1 grade in the skin reaction of the test animal. As a result of both tests, no abnormal skin symptoms were observed, and when applied to the human body to treat patients, the test materials used in the tests will investigate the stability of whether any diseases that cause skin abnormal symptoms will occur.

Development of Various Pilot Scale's Ultrasound Systems and Sonodegradation of Naphthalene in Water (다양한 형태의 Pilot Scale 초음파 시스템 개발 및 나프탈렌 분해효율 검증)

  • Park, Jong-Sung;Lee, Ha-Yun;Han, Jong-Hun;Her, Nam-Guk
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.4
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    • pp.281-288
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    • 2011
  • Recently, researches that a variety of contaminants in water are removed by sonolysis technology with oxidation and pyrolysis process from cavitation were conducted. However, there are few studies for sonochemical treatment by a pilot-scale ultrasound system. This research focused on developing pilot-scale ultrasound systems, which could be an continuously effective treatment for a large volumes of contaminants, and demonstrating the feasibility of utilizing these systems to remove naphthalene from groundwater. V-120 type reactor was found to be 1.4~2.2 times higher effective than the normal type. A total of three different pilot scale's systems consisted of installing effluent and irrigation water in order to be a continuos system, including supplemental additives, and applying a V-120 type reactor and a external cooling cycle system. Naphthalene levels treated by three systems were lower than a recommended guideline of naphthalene for drinking water in EPA. Especially, the naphthalene removal efficiencies of PS1 and PS2 systems were over 97%. The pilot-scale continuous ultrasound clean-up system delivered over 84~95% naphthalene removal efficiency for treatment of 10~20 liter of groundwater. In addition, the ultrasound system could be successfully applied to the conditions of artificial and genuine groundwater contaminated with naphthalene.

Drug Release from Thermosensitive Liposomes by High-Intensity Focused Ultrasound (고강도 집속 초음파에 의한 온도민감성 리포솜으로부터 약물 방출)

  • Jeon, Ye Won;Cho, Sun Hang;Han, Hee Dong;Shin, Byung Cheol
    • Journal of the Korean Chemical Society
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    • v.58 no.6
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    • pp.575-579
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    • 2014
  • Development of liposomes has been actively studied for effective delivery of drug at tumor site. However, despite their preferential accumulation at tumor site, the therapeutic efficacy of such liposomal drug has been limited because of low drug release. Therefore, we developed a temperature-sensitive liposome (TSL), which can be made to maximize release of drug by external stimulation such as ultrasound. Doxorubicin (DOX) as a model drug was encapsulated into TSL by a pH gradient method. The particle size of the TSL was $142.0{\pm}6.24nm$. Surface charge was $-10.55{\pm}1.12mV$. Release of drug from TSLs was up to 80% within 15 min at over $42^{\circ}C$ measured by fluorescence intensity. Cytotoxicity of released DOX from TSLs with ultrasound was highly increased compared to TSLs without ultrasound. Taken together, we demonstrate that temperature sensitive drug release from TSLs with ultrasound, which may be useful for cancer therapy to increase drug concentration at tumor site by external stimulation.

Effects of a video education program for patients with benign uterine tumors receiving high-intensity focused ultrasound treatment (고강도 집속 초음파 치료를 받는 자궁양성종양 환자의 동영상 교육프로그램 효과)

  • Hong, Mi Suk;Park, Hyoung Sook;Cho, Young Suk
    • Women's Health Nursing
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    • v.26 no.2
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    • pp.151-160
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    • 2020
  • 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.

Effect of High Intensity Ultrasonic Wave on the Degradation Characteristics of PEO (고강도 초음파에 의한 PEO의 분해특성에 관한 연구)

  • 김형수;김미화
    • Polymer(Korea)
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    • v.26 no.3
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    • pp.353-359
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    • 2002
  • High intensity ultrasound has been applied to a series of poly(ethylene oxide) (PEO)/water systems having different molecular weights of PEO. Major interest was focused on the effect of ultrasonic wane on the melt viscosity chemical structure and thermal properties of PEO. The expected role of ultrasound used in this study was to generate macroradicals of PEO chains by the formation and subsequent collapse of bubbles. It was found that the melt viscosity and chemical structure of PEO change significantly depending on the sonication time. For the prolonged sonication, PEO chains were significantly degraded and new end groups were formed by the interplay of various radical species. When the molecular weight of PEO was relatively higher, the crystallization rate was decreased and the intensity of the melting peak was reduced.

The Effect of Distance between Two Transducers on Sonochemical Reactions in Dual Irradiation Systems (이중 초음파 조사 시스템에서 진동부 사이의 거리가 초음파 화학 반응에 미치는 영향)

  • Kim, Eunkyung;Son, Younggyu
    • Journal of Soil and Groundwater Environment
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    • v.18 no.5
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    • pp.39-45
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    • 2013
  • Many researchers have studied the effectiveness of ultrasound in chemical and environmental engineering fields including material synthesis, pollutant removal, cleaning, extraction, and disinfection. Acoustic cavitation induced by ultrasound irradiation in aqueous phase can cause various sonophysical and sonochemical reactions without any chemicals. However most of the previous studies focused only on the relationships between ultrasonic conditions and the results of sonochemical reactions in lab-scale sonoreactors. As a results of this, only a few studies have been devoted to design and optimization of industrial scale sonoreactors. In this study, the effect of the distance between two opposite transducer modules on sonochemical reactions was investigated in single and dual irradiation systems (334 kHz) for four distances including 50, 100, 150, and 200 mm using KI dosimetry. It was found that the dual irradiation systems provided higher performance in terms of the zeroth reaction coefficient and the cavitation yield compared to the single irradiation systems. The sonochemiluminescence (SCL) images for the visualization of the cavitation field showed that cavitation active zone was larger and sonochemical reaction intensity was much higher in the dual irradiation system than in the single irradiation system.