scholarly journals Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating

2011 ◽  
Vol 114 (6) ◽  
pp. 1654-1661 ◽  
Author(s):  
Caitlin W. Burke ◽  
Alexander L. Klibanov ◽  
Jason P. Sheehan ◽  
Richard J. Price
Keyword(s):  
Tumor Growth ◽  
Duty Cycle ◽  
Focused Ultrasound ◽  
C6 Glioma ◽  
High Intensity Focused Ultrasound ◽  
C6 Glioma Cells ◽  
Low Duty Cycle ◽  
Duty Cycles ◽  
Glioma Growth ◽  
Rag 1

Object In this study, the authors sought determine whether microbubble (MB) destruction with pulsed low duty cycle ultrasound can be used to reduce brain tumor perfusion and growth through nonthermal microvascular ablation. Methods Studies using C57BLJ6/Rag-1 mice inoculated subcutaneously with C6 glioma cells were approved by the institutional animal care and use committee. Microbubbles were injected intravenously, and 1 MHz ultrasound was applied with varying duty cycles to the tumor every 5 seconds for 60 minutes. During treatment, tumor heating was quantified. Following treatment, tumor growth, hemodynamics, necrosis, and apoptosis were measured. Results Tumor blood flow was significantly reduced immediately after treatment, with posttreatment flow ranging from 36% (0.00002 duty cycle) to 4% (0.01 duty cycle) of pretreatment flow. Seven days after treatment, tumor necrosis and apoptosis were significantly increased in all treatment groups, while treatment with ultrasound duty cycles of 0.005 and 0.01 inhibited tumor growth by 63% and 75%, respectively, compared with untreated tumors. While a modest duty cycle–dependent increase in intratumor temperature was observed, it is unlikely that thermal tissue ablation occurred. Conclusions In a subcutaneous C6 glioma model, MB destruction with low–duty cycle 1-MHz ultrasound can be used to markedly inhibit growth, without substantial tumor tissue heating. These results may have a bearing on the development of transcranial high-intensity focused ultrasound treatments for brain tumors that are not amenable to thermal ablation.

scholarly journals Effects of varying duty cycle and pulse width on high-intensity focused ultrasound (HIFU)-induced transcranial thrombolysis

2013 ◽  
Vol 1 (1) ◽  
pp. 18 ◽  
Author(s):  
Thilo Hölscher ◽  
Rema Raman ◽  
David J Fisher ◽  
Golnaz Ahadi ◽  
Eyal Zadicario ◽  
...  
Keyword(s):  
Duty Cycle ◽  
High Intensity ◽  
Pulse Width ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound

Programmable Ultrasound Phased Array Therapy System

2017 ◽  
Author(s):  
Yiying I. Zhu ◽  
Timothy L. Hall ◽  
Oliver D. Kripfgans
Keyword(s):  
High Power ◽  
Duty Cycle ◽  
Focused Ultrasound ◽  
Continuous Wave ◽  
Low Cost ◽  
Uterine Fibroids ◽  
High Intensity Focused Ultrasound ◽  
Center Frequency ◽  
Tissue Ablation ◽  
Waveform Generator

There has been an emerging interest in high intensity focused ultrasound (HIFU) for therapeutic applications. By means of its thermal or mechanical effects, HIFU is able to serve as a direct tool for tissue ablation, or an indirect moderating medium to manipulate microbubbles or perform heating (hyperthermia) for the purpose of targeted drug delivery. The development and testing of HIFU based phased arrays is favorable as their elements allow for individual phasing to steer and focus the beam. While FDA has already approved tissue ablation by HIFU for the treatment of uterine fibroids (2004) and pain from bone metastases (2012), development continues on other possible applications that are less forgiving of incomplete treatment, such as thermal necrosis of malignant masses. Ideally, each element, of such an array must have its own fully programmable electrical driving channel, which allows the control of delay, phase, and amplitude of the output from each element. To enable full control, each channel needs a waveform generator, an amplification device, and an impedance matching circuit between driver and acoustic element. Similar projects utilizing this approach to drive therapeutic arrays include a 512-channel therapy system which was built at the University of Michigan using low cost Field-Programmable Gate Arrays (FPGA) microcontroller and highly efficient MOSFET switching amplifiers [1]. However, this system lacks the ability to drive both, continuous wave (CW) and transient short duty-cycle high power pulses. This paper presents a hybrid system, which is able to perform CW and transient short duty-cycle high power excitation. In the following we will describe the design, programming, fabrication, and evaluation of this radiofrequency (RF) driver system as used in our laboratory for a 1.5 MHz center frequency, 298-element array (Imasonic SA, Besancon, France) [2], FPGA-controlled amplifier boards and matching circuitry. Advantages of our design include: 1. Inexpensive components (<$15/channel); 2. Ability to program/drive individual output channels independently; 3. Sufficient time and amplitude resolution for various acoustic pattern design; 4. Capability of hybrid switching between low power CW and short duty cycle, high instantaneous power.

scholarly journals Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

2012 ◽  
Vol 101 (12) ◽  
pp. 124102 ◽  
Author(s):  
Juan Tu ◽  
Joo Ha Hwang ◽  
Tao Chen ◽  
Tingbo Fan ◽  
Xiasheng Guo ◽  
...  
Keyword(s):  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Duty Cycles

Differential efficacy of SSTR1, -2, and -5 agonists in the inhibition of C6 glioma growth in nude mice

2009 ◽  
Vol 297 (5) ◽  
pp. E1078-E1088 ◽  
Author(s):  
Federica Barbieri ◽  
Alessandra Pattarozzi ◽  
Monica Gatti ◽  
Cinzia Aiello ◽  
Ana Quintero ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
Somatostatin Receptors ◽  
C6 Glioma ◽  
Synergistic Activity ◽  
Ki 67 ◽  
Glioma Growth ◽  
Simultaneous Activation

Somatostatin receptors (SSTR1–5) mediate antiproliferative effects. In C6 rat glioma cells, somatostatin is cytostatic in vitro via phosphotyrosine phosphatase-dependent inhibition of ERK1/2 activity mediated by SSTR1, -2, and -5. Here we analyzed the effects of SSTR activation on C6 glioma growth in vivo and the intracellular mechanisms involved, comparing somatostatin effects with selective agonists for SSTR1, -2, and -5 (BIM-23745, BIM-23120, BIM-23206) or receptor biselective compounds (SSTR1 and -2, BIM-23704; and SSTR2 and -5, BIM-23190). Nude mice subcutaneously xenografted with C6 cells were treated with somatostatin, SSTR agonists (50 μg, twice/day), or vehicle. Tumor growth was evaluated every 3 days for 19 days. The intracellular pathways responsible of SSTR effects in vivo were evaluated measuring Ki-67, phospho-ERK1/2, and p27kip1 expression by immunohistochemistry in sections from explanted tumors. Somatostatin and SSTR1, -2, and -5 agonists strongly inhibited in vivo C6 tumor growth, intratumoral neovessel formation, Ki-67 expression, and ERK1/2 phosphorylation and induced upregulation of p27Kip1, whereas only a modest activation of caspase-3 was observed. Somatostatin (acting on SSTR1, -2, and -5) displayed the highest efficacy; SSTR5 selective agonist showed a stronger effect than SSTR1 agonist, and SSTR2 agonist was less effective. On the other hand, SSTR1 and -2 agonists maximally reduced tumor neovascularization. The combined activation of SSTR1 and -2 showed a synergistic activity, reaching a higher efficacy than BIM-23206, whereas the simultaneous activation of SSTR2 and -5 resulted in a response resembling SSTR5 effects. Thus the simultaneous activation of different SSTRs inhibits glioma cell proliferation in vivo through both direct cytotostatic and antiangiogenic effects.

scholarly journals Differential Polarization of Tumor-Associated Macrophages/Microglia Drives the Aggressiveness of Gliomas

2021 ◽  
Author(s):  
Nai-Wei Yao ◽  
Hsiu-Ting Lin ◽  
Ya-Lin Lin ◽  
Khamushavalli Geeviman ◽  
Fang Liao ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Wistar Rats ◽  
Tumor Development ◽  
C6 Glioma ◽  
Sprague Dawley ◽  
Tumor Associated Macrophages ◽  
Sd Rats ◽  
Glioma Growth

Abstract Background: Glioblastoma is the most aggressive subtype of brain tumors. The major component of tumor microenvironment in glioblastoma is tumor-associated macrophages (TAMs), which are associated with enhanced malignancy of glioblastoma. The polarization of macrophages to the pro-inflammatory M1 or anti-inflammatory M2 subtypes governed by the context of tumor microenvironment may dictate the aggressiveness and outcome of glioblastoma. Given that the immune responses to tumors vary distinctively among individuals due to intrinsic, environmental and genetic factors and that TAMs display a high level of diversity and plasticity, we aimed to examine the effects of differential polarization of TAMs on the glioblastoma development by implanting C6 glioma into brains of Sprague–Dawley (SD) and Wistar rats; these two rats have different genetic background and host microenvironment during tumor development. Methods: Sprague–Dawley (SD) and Wistar rats were implanted with C6 glioma in the brain. The measurement of tumor volumes, tumor morphology and tumor growth in C6 glioma implanted brains were measured by multi-parametric magnetic resonance imaging (MRI). Immunofluorescence staining was performed to analyze tumor angiogenesis and M1 and M2 TAMs in C6 gliomas. Results: By multi-parametric MRI measurement, C6 gliomas developed in the SD rats were characterized with enlarged tumors, accompanied with shorter animal survival. In comparison to the gliomas in Wistar rats, the accelerated tumor growth in SD rats was associated with greater extent of angiogenesis accompanied with higher levels of VEGF/VEGFR2. In support, C6 gliomas in SD rats were filtrated with TAMs characterized with a higher M2/M1 ratio, in contrast to the TAMs of a high M1/M2 ratio in Wistar rats. Attempts were made to shift the M2/M1 balance. Administration of the cytokine IFN-γ that induces M1 TAMs to SD rats greatly suppressed glioma formation, accompanied with a remarkable increase of M1 TAMs. Administration of the cytokines IL-4 plus IL-10 that induces M2 TAMs significantly promoted glioma growth in the Wistar rats, associated with an increase in the M2 TAMs. Conclusions: These results demonstrate an important role of TAMs in glioma pathogenesis and the crucial role of microenvironment in dictating the polarization of TAMs, suggesting that targeting or repolarization of TAMs may serve as an effective intervention for gliomas.

scholarly journals MR Guided Pulsed High Intensity Focused Ultrasound Enhancement of Docetaxel Combined with Radiotherapy for Prostate Cancer Treatment

2018 ◽  
Author(s):  
Lili Chen ◽  
Alan Pollack
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Tumor Growth ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Tumor Growth Inhibition ◽  
Prostate Cancer Treatment ◽  
Ultrasound Enhancement ◽  
Enhance Tumor Growth

This project will determine whether (1) HIFU increases the cellular update of docetaxel in vivo, and (2) the increased uptake of docetaxel combined with RT will enhance tumor growth inhibition. We will determine the optimal HIFU parameters, quantify the update of docetaxel using a radioactive tritiated docetaxel and evaluate the efficacy of docetaxel+RT in inhibiting prostate tumor growth in vivo. This research has the potential to improve local control and may also have effects on distant microscopic disease by promoting immune response, which will also lay the foundation for other tumor models and studies on gene therapy and thrombolytic drugs.

scholarly journals Acoustic Cavitation Enhances Focused Ultrasound Ablation with Phase-Shift Inorganic Perfluorohexane Nanoemulsions: AnIn VitroStudy Using a Clinical Device

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Lu-Yan Zhao ◽  
Jian-Zhong Zou ◽  
Zong-Gui Chen ◽  
Shan Liu ◽  
Jiao Jiao ◽  
...  
Keyword(s):  
Phase Shift ◽  
Focused Ultrasound ◽  
Continuous Wave ◽  
Acoustic Cavitation ◽  
High Intensity Focused Ultrasound ◽  
Inertial Cavitation ◽  
Hifu Ablation ◽  
Duty Cycles ◽  
Ultrasound Ablation ◽  
Phosphate Buffered Saline

Purpose.To investigate whether acoustic cavitation could increase the evaporation of a phase-shift inorganic perfluorohexane (PFH) nanoemulsion and enhance high intensity focused ultrasound (HIFU) ablation.Materials and Methods.PFH was encapsulated by mesoporous silica nanocapsule (MSNC) to form a nanometer-sized droplet (MSNC-PFH). It was added to a tissue-mimicking phantom, whereas phosphate buffered saline (PBS) was added as a control (PBS-control). HIFU (Pac=150 W,t=5/10 s) exposures were performed in both phantoms with various duty cycles (DC). US images, temperature, and cavitation emissions were recorded during HIFU exposure. HIFU-induced lesions were measured and calculated.Results.Compared to PBS-control, MSNC-PFH nanoemulsion could significantly increase the volume of HIFU-induced lesion (P<0.01). Peak temperatures were 78.16 ± 5.64°C at a DC of 100%, 70.17 ± 6.43°C at 10%, 53.17 ± 4.54°C at 5%, and 42.00 ± 5.55°C at 2%, respectively. Inertial cavitation was much stronger in the pulsed-HIFU than that in the continuous-wave HIFU exposure. Compared to 100%-DC exposure, the mean volume of lesion induced by 5 s exposure at 10%-DC was significantly larger, but smaller at 2%-DC.Conclusions.MSNC-PFH nanoemulsion can significantly enhance HIFU ablation. Appropriate pulsed-HIFU exposure could significantly increase the volume of lesion and reduce total US energy required for HIFU ablation.

scholarly journals Delay-constrained flooding in extremely low-duty-cycle sensor networks

2019 ◽  
Vol 15 (3) ◽  
pp. 155014771984022
Author(s):  
Zuzhi Fan
Keyword(s):  
Sensor Networks ◽  
Duty Cycle ◽  
Large Scale ◽  
Power Level ◽  
Transmission Power ◽  
Delay Bound ◽  
Data Packets ◽  
Low Duty Cycle ◽  
Duty Cycles ◽  
Extra Energy

Flooding is a fundamental function for the network-wide dissemination of command, query, and code update in wireless sensor networks. However, it is challenging to enable fast and energy-efficient flooding in sensor networks with low-duty cycles because it is rare that multiple neighboring nodes wake up at the same time, making broadcast instinct of wireless radio unavailable. The unreliability of wireless links deteriorates the situation. In this work, we study the delay-constrained flooding problem in order to disseminate data packets to all nodes within given expected delivery delay. In particular, a transmission power control–based flooding algorithm is proposed to reduce the flooding delay in such low-duty-cycle sensor networks. According to the soft delay bound, each node can locally adjust its transmission power level. To alleviate transmission conflicts, the backoff method with transmission power adaptive mechanism has been proposed. Based on the large-scale simulations, we validate that our design can reduce flooding delay with small extra energy expenditure compared with conventional flooding schemes.

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