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Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

ABSTRACT: High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent magnetic resonance imaging.Iron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with perfluoropentane and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor-bearing athymic nude mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation.Ex vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 s without nanoshells and only 2 s with nanoshells administered IV before sacrifice. Nanoshells administered IV into nude mice with xenograft tumors were activated in vivo by HIFU 24 h after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm(3) bubble cloud with the IV injected particles and no bubble cloud without particles.Iron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.

SUBMITTER: Liberman A

PROVIDER: S-EPMC4141695 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

Liberman Alexander A Wu Zhe Z Barback Christopher V CV Viveros Robert D RD Wang James J Ellies Lesley G LG Mattrey Robert F RF Trogler William C WC Kummel Andrew C AC Blair Sarah L SL

The Journal of surgical research 20140510 2

<h4>Background</h4>High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, ...[more]

PMID: 24972734

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Project description:BackgroundHigh-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy.Methods and findingsClinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0-280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58-44.38%, p<0.0001) and benign lesions (1.67-17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions.ConclusionThe frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared with MRgFU.

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.

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Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

Publications

Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

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