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Focused ultrasound-induced cell apoptosis for the treatment of tumours.

ABSTRACT: Cancer is a serious public health problem worldwide. Traditional treatments, such as surgery, radiotherapy, chemotherapy, and immunotherapy, do not always yield satisfactory results; therefore, an efficient treatment for tumours is urgently needed. As a convenient and minimally invasive modality, focused ultrasound (FUS) has been used not only as a diagnostic tool but also as a therapeutic tool in an increasing number of studies. FUS can help treat malignant tumours by inducing apoptosis. This review describes the three apoptotic pathways, apoptotic cell clearance, and how FUS affects these three apoptotic pathways. This review also discusses the role of thermal and cavitation effects on apoptosis, including caspase activity, mitochondrial dysfunction, and Ca²⁺ elease. Finally, this article reviews various aspects of FUS combination therapy, including sensitization by radiotherapy and chemotherapy, gene expression upregulation, and the introduction of therapeutic gases, to provide new ideas for clinical tumour therapy.

SUBMITTER: Wang N

PROVIDER: S-EPMC11344538 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Focused ultrasound-induced cell apoptosis for the treatment of tumours.

Wang Na N Luo Li L Xu Xinzhi X Zhou Hang H Li Fang F

PeerJ 20240821

Cancer is a serious public health problem worldwide. Traditional treatments, such as surgery, radiotherapy, chemotherapy, and immunotherapy, do not always yield satisfactory results; therefore, an efficient treatment for tumours is urgently needed. As a convenient and minimally invasive modality, focused ultrasound (FUS) has been used not only as a diagnostic tool but also as a therapeutic tool in an increasing number of studies. FUS can help treat malignant tumours by inducing apoptosis. This r ...[more]

PMID: 39184389

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Project description:The success of any minimally invasive treatment procedure can be enhanced significantly if combined with a robust noninvasive imaging modality that can monitor therapy in real time. Quantitative ultrasound (QUS) imaging has been widely investigated for monitoring various treatment responses such as chemotherapy, radiation, and thermal therapy. Previously, we demonstrated the feasibility of using spectral-based QUS parameters to monitor high-intensity focused ultrasound (HIFU) treatment of in situ tumors in euthanized rats [Ultrasonic Imaging 36(4), 239-255, 2014]. In the present study, we examined the use of spectral-based QUS parameters to monitor HIFU treatment of in vivo rat mammary adenocarcinoma tumors (MAT) where significant tissue motion was present. HIFU was applied to tumors in rats using a single-element transducer. During the off part of the HIFU duty cycle, ultrasound backscatter was recorded from the tumors using a linear array co-aligned with the HIFU focus. A total of 10 rats were treated with HIFU in this study with an additional sham-treated rat. Spectral parameters from the backscatter coefficient, i.e., effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were estimated. The changes of each parameter during treatment were compared with a temperature profile recorded by a fine-needle thermocouple inserted into the tumor a few millimeters behind the focus of the HIFU transducer. The mean ESD changed from 121 ±6 to [Formula: see text], and the EAC changed from 33 ±2 to [Formula: see text] during HIFU exposure as the temperature increased on average from 38.7 ±1.0 (°)C to 64.2 ±2.7 (°)C. The changes in ESD and EAC were linearly correlated with the changes in tissue temperature during the treatment. When HIFU was turned off, the ESD increased from 81 ±8 to [Formula: see text] and the EAC dropped from 46 ±3 to 36±2 dB/cm(3) as the temperature decreased from 64.2 ±2.7 (°)C to 45 ±2.7 (°)C. QUS was demonstrated in vivo to track temperature elevations caused by HIFU exposure.

Project description:Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p- ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p- at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.

Dataset Information

Focused ultrasound-induced cell apoptosis for the treatment of tumours.

Publications

Focused ultrasound-induced cell apoptosis for the treatment of tumours.

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