scholarly journals Pulsed Ultrasound Assisted Thermo-Therapy for Subsurface Tumor Ablation: A Numerical Investigation

2021 ◽  
Vol 13 (4) ◽  
Author(s):  
Gajendra Singh ◽  
Abhijit Paul ◽  
Himanshu Shekhar ◽  
Anup Paul
Keyword(s):  
Focused Ultrasound ◽  
Numerical Study ◽  
Thermal Response ◽  
High Intensity Focused Ultrasound ◽  
Acoustic Properties ◽  
Pressure Amplitude ◽  
Thermal Dose ◽  
Pulsed Ultrasound ◽  
Layered Model

Abstract High-intensity focused ultrasound (HIFU) is a promising therapy for thermal ablation and hyperthermia, characterized by its non-invasiveness and high penetration depth. Effective HIFU thermo-therapy requires the ability to accurately predict temperature elevation and corresponding thermal dose distribution in target tissues. We report a parametric numerical study of the thermal response and corresponding of thermal dose in a soft tissue in response to ultrasound. We compared the predictions of tissue models with two, three, and seven layers, to ultrasound-induced heating at duty cycles ranging from 0.6 and 0.9. Further, two tumor sizes and transducer powers (10 W and 15 W) were considered. The inhomogeneous Helmholtz equation was coupled with the Pennes bio-heat equation to predict heating in response to pulsed ultrasound. Necrotic lesion size was calculated using the cumulative equivalent minute (CEM) thermal dose function. In-vitro experiments were performed with agar-based tissue phantoms as a preliminary validation of the numerical results. The simulations conducted with the seven-layered model predicted up to 33.5% lower peak pressure amplitude than the three-layered model. As the ultrasound pulse width decreased with the equivalent sonication time fixed, the corresponding magnitude of the peak temperature and the rate of temperature rise decreased. Pulsed ultrasound resulted in the increased volume of necrotic lesions for an equivalent time of sonication. The findings of this study highlight the dependence of HIFU-induced heating on target geometry and acoustic properties and could help guide the choice of suitable ultrasound exposure parameters for further studies.

scholarly journals Adjuvant Biophysical Therapies in Osteosarcoma

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 348 ◽  
Author(s):  
Valeria Carina ◽  
Viviana Costa ◽  
Maria Sartori ◽  
Daniele Bellavia ◽  
Angela De Luca ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Technological Development ◽  
Bone Sarcoma ◽  
High Intensity Focused Ultrasound ◽  
In Vivo Studies ◽  
Patient Treatment ◽  
Limb Amputation ◽  
Pulsed Ultrasound

Osteosarcoma (OS) is a primary bone sarcoma, manifesting as osteogenesis by malignant cells. Nowadays, patients’ quality of life has been improved, however continuing high rates of limb amputation, pulmonary metastasis and drug toxicity, remain unresolved issues. Thus, effective osteosarcoma therapies are still required. Recently, the potentialities of biophysical treatments in osteosarcoma have been evaluated and seem to offer a promising future, thanks in this field as they are less invasive. Several approaches have been investigated such as hyperthermia (HT), high intensity focused ultrasound (HIFU), low intensity pulsed ultrasound (LIPUS) and sono- and photodynamic therapies (SDT, PDT). This review aims to summarize in vitro and in vivo studies and clinical trials employing biophysical stimuli in osteosarcoma treatment. The findings underscore how the technological development of biophysical therapies might represent an adjuvant role and, in some cases, alternative role to the surgery, radio and chemotherapy treatment of OS. Among them, the most promising are HIFU and HT, which are already employed in OS patient treatment, while LIPUS/SDT and PDT seem to be particularly interesting for their low toxicity.

scholarly journals Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage

2021 ◽  
Author(s):  
Xinrui Zhang ◽  
Mariana Bobeica ◽  
Michael Unger ◽  
Anastasia Bednarz ◽  
Bjoern Gerold ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Metabolic Activity ◽  
Focused Ultrasound ◽  
Double Strand Breaks ◽  
High Intensity Focused Ultrasound ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

Abstract Purpose High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40–47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. Methods An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X‑ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST‑1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). Results The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. Conclusion Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

Minimization of treatment time for in vitro 1.1MHz destruction of Pseudomonas aeruginosa biofilms by high-intensity focused ultrasound

Ultrasonics ◽  
2012 ◽  
Vol 52 (5) ◽  
pp. 668-675 ◽  
Author(s):  
Jin Xu ◽  
Timothy A. Bigelow ◽  
Larry J. Halverson ◽  
Jill M. Middendorf ◽  
Ben Rusk
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Treatment Time ◽  
High Intensity Focused Ultrasound

Nonlinear Derating of High-Intensity Therapeutic Ultrasound Beams Using Gaussian Modal Sums

2013 ◽  
Author(s):  
Seyed Ahmad Reza Dibaji ◽  
Matthew R. Myers ◽  
Joshua E. Soneson ◽  
Rupak K. Banerjee
Keyword(s):  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Nonlinear Propagation ◽  
Tissue Temperature ◽  
Medical Procedure ◽  
Pressure Amplitude ◽  
Pressure Trace ◽  
The Difference ◽  
Semi Empirical

High intensity focused ultrasound (HIFU) is a noninvasive medical procedure during which a large amount of energy is deposited in a short duration which causes sudden localized rise in tissue temperature, and ultimately, cell necrosis. In assessing the influence of HIFU on biological tissue, semi-empirical mathematical models can be useful for predicting thermal effects. These models require values of the pressure amplitude in the tissue of interest, which can be difficult to obtain experimentally. One common method for estimating the pressure amplitude in tissue is to operate the HIFU transducer in water, measure the pressure amplitude, then multiply by a scaling factor that accounts for the difference in attenuation between water and tissue. This procedure can be accurate when the ultrasound amplitude is low, and the pressure trace in tissue is proportional to that in water. Because of this proportionality, the procedure for reducing the amplitude from water to tissue is called linear derating. At higher intensities, however, harmonics of the fundamental frequency are generated due to nonlinear propagation effects. Higher harmonics are attenuated differently in water and tissue (Hamilton and Blackstock [1]), and the pressure waves in water and tissue are no longer proportional to one another. Techniques for nonlinearly transforming pressure amplitudes measured in water to values appropriate for tissue are therefore desirable when bioeffects of higher intensity procedures are being studied. These techniques are labeled “nonlinear derating”.

scholarly journals A Doxorubicin-Glucuronide Prodrug Released from Nanogels Activated by High-Intensity Focused Ultrasound Liberated β-Glucuronidase

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 536
Author(s):  
Helena C. Besse ◽  
Yinan Chen ◽  
Hans W. Scheeren ◽  
Josbert M. Metselaar ◽  
Twan Lammers ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Anticancer Drugs ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Anticancer Therapy ◽  
High Intensity Focused Ultrasound ◽  
Low Molecular Weight ◽  
Chemotherapeutic Drug ◽  
The Poor

The poor pharmacokinetics and selectivity of low-molecular-weight anticancer drugs contribute to the relatively low effectiveness of chemotherapy treatments. To improve the pharmacokinetics and selectivity of these treatments, the combination of a doxorubicin-glucuronide prodrug (DOX-propGA3) nanogel formulation and the liberation of endogenous β-glucuronidase from cells exposed to high-intensity focused ultrasound (HIFU) were investigated in vitro. First, a DOX-propGA3-polymer was synthesized. Subsequently, DOX-propGA3-nanogels were formed from this polymer dissolved in water using inverse mini-emulsion photopolymerization. In the presence of bovine β-glucuronidase, the DOX-propGA3 in the nanogels was quantitatively converted into the chemotherapeutic drug doxorubicin. Exposure of cells to HIFU efficiently induced liberation of endogenous β-glucuronidase, which in turn converted the prodrug released from the DOX-propGA3-nanogels into doxorubicin. β-glucuronidase liberated from cells exposed to HIFU increased the cytotoxicity of DOX-propGA3-nanogels to a similar extend as bovine β-glucuronidase, whereas in the absence of either bovine β-glucuronidase or β-glucuronidase liberated from cells exposed to HIFU, the DOX-propGA3-nanogels hardly showed cytotoxicity. Overall, DOX-propGA3-nanogels systems might help to further improve the outcome of HIFU-related anticancer therapy.

scholarly journals Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Heikki J. Nieminen ◽  
Eetu Lampsijärvi ◽  
Gonçalo Barreto ◽  
Mikko A. J. Finnilä ◽  
Ari Salmi ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Articular Cartilage ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Pulse Repetition Frequency ◽  
High Intensity Focused Ultrasound ◽  
Positive Pressure ◽  
Mechanical Index ◽  
Localized Delivery

Abstract Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.

Robotic Platform for High-Intensity Focused Ultrasound Surgery Under Ultrasound Tracking: The FUTURA Platform

2017 ◽  
Vol 02 (03) ◽  
pp. 1740010 ◽  
Author(s):  
Selene Tognarelli ◽  
Gastone Ciuti ◽  
Alessandro Diodato ◽  
Andrea Cafarelli ◽  
Arianna Menciassi
Keyword(s):  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Ultrasound Surgery ◽  
Ultrasound Monitoring ◽  
Focused Ultrasound Surgery ◽  
Set Up ◽  
Framework Programme Project ◽  
Static Conditions ◽  
Ultrasound Tracking

Focused Ultrasound Therapy Using Robotic Approaches (FUTURA) is a European seventh research framework programme project aimed at creating an innovative platform for Focused Ultrasound Surgery (FUS). Merging robotics together with noninvasive ultrasound monitoring and therapy has the goal to improve flexibility, precision and accuracy of the intervention, thus enabling a large use of FUS for the treatment of different pathologies. The FUTURA platform, based on FUS therapy under US tracking, has been set up with the first clinical target of kidney cancer treatment. Experiments for assessing the accuracy of the FUS delivery with the FUTURA platform have been carried out under in vitro static conditions and presented here as preliminary outcomes of this study.

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