Effect of pulse repetition frequency of high-intensity focused ultrasound on in vitro thrombolysis

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.

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Histologische Morphologie von Läsionen nach MR-gesteuerter high-intensity focused ultrasound (MR-HIFU)-Ablation: in-vitro Untersuchung an Putenbrust

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren ◽

10.1055/s-0030-1268301 ◽

2010 ◽

Vol 182 (11) ◽

Author(s):

M Karul ◽

A Neumann ◽

H Merz ◽

J Barkhausen ◽

P Hunold

Keyword(s):

High Intensity ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound ◽

Hifu Ablation

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Effects of Non-thermal Ultrasound on a Fibroblast Monolayer Culture: Influence of Pulse Number and Pulse Repetition Frequency

Sensors ◽

10.3390/s21155040 ◽

2021 ◽

Vol 21 (15) ◽

pp. 5040

Author(s):

Silvia Ronda Peñacoba ◽

Mar Fernández Gutiérrez ◽

Julio San Román del Barrio ◽

Francisco Montero de Espinosa

Keyword(s):

Short Pulse ◽

Pulse Repetition Frequency ◽

Pulse Number ◽

Repetition Frequency ◽

Pulse Repetition ◽

Treatment Protocols ◽

Culture Plate ◽

New Treatment ◽

Long Pulse

Despite the use of therapeutic ultrasound in the treatment of soft tissue pathologies, there remains some controversy regarding its efficacy. In order to develop new treatment protocols, it is a common practice to carry out in vitro studies in cell cultures before conducting animal tests. The lack of reproducibility of the experimental results observed in the literature concerning in vitro experiments motivated us to establish a methodology for characterizing the acoustic field in culture plate wells. In this work, such acoustic fields are fully characterized in a real experimental configuration, with the transducer being placed in contact with the surface of a standard 12-well culture plate. To study the non-thermal effects of ultrasound on fibroblasts, two different treatment protocols are proposed: long pulse (200 cycles) signals, which give rise to a standing wave in the well with the presence of cavitation (ISPTP max = 19.25 W/cm2), and a short pulse (five cycles) of high acoustic pressure, which produces a number of echoes in the cavity (ISPTP = 33.1 W/cm2, with Pmax = 1.01 MPa). The influence of the acoustic intensity, the number of pulses, and the pulse repetition frequency was studied. We further analyzed the correlation of these acoustic parameters with cell viability, population, occupied surface, and cell morphology. Lytic effects when cavitation was present, as well as mechanotransduction reactions, were observed.

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

Ultrasonics ◽

10.1016/j.ultras.2012.01.013 ◽

2012 ◽

Vol 52 (5) ◽

pp. 668-675 ◽

Cited By ~ 24

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

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

Pharmaceutics ◽

10.3390/pharmaceutics12060536 ◽

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.

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