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Mechanical decellularization of tissue while sparing extracellular matrix using boiling histotripsy Abstract Bookтезисы доклада
- Авторы: Y-N Wang, Khokhlova T., Maxwell A., Kreider W., Ari Partanen, Navid Farr, Schade G., Bailey M., Khokhlova V.
- Сборник: Abstract Book of 14th International Symposium for Therapeutic Ultrasound (April 2-5, 2014, Las Vegas, Nevada, USA)
- Тезисы
- Год издания: 2014
- Место издания: Las Vegas, Nevada, USA
- Аннотация: Background: HIFU is rapidly advancing as an alternative therapy for non-invasively treating specific cancers and other pathological tissues mainly through thermal ablation. Recently, a new types of HIFU therapy aiming at mechanical fractionation of tissue into subcellular fragments showed great promise – cavitation-cloud histotripsy and boiling histotripsy (BH). BH uses millisecond-long bursts of HIFU waves containing shock fronts to induce repetitive boiling at the focus; the interaction of the the incident HIFU waves with boiling bubble fractionates tissue. It has been shown that the degree of mechanical tissue damage induced by both types of histotripsy depends on the tissue type; in general, the more collagenous structures are more resistant to mechanical disruption and cells have been found to be the most sensitive. This effect shows much promise in the clinic, since many applications require the need to spare critical tissues such as vessels and ducts adjacent to or within the treatment site. In this study we have demonstrated that BH can be used to decellularize large tissue volumes while sparing extracellular matrix, vessels and similar structures. Methods: Degassed ex-vivo bovine liver samples were sonicated using a clinical a clinical MR-HIFU system (Sonalleve, Philips Healthcare, Vantaa, Finland). The BH lesions were produced by the 256-element array operating at the frequency of 1.2 MHz with 10-ms long pulses and pulse repetition frequencies (PRFs) of 1-10 Hz to cover a range of effects from pure mechanical fractionation to thermal ablation. The peak acoustic power was 250 W, corresponding to the estimated in situ shock front amplitude of 65 MPa. The HIFU focus position was electronically steered at the depth of 20 mm in tissue across the treatment volume within 8-16 mm range with 2 mm separation of the neighboring spots, so that each treatment spot received 30 HIFU pulses. Large circular lesions of 10-20 mm diameter and 10 mm thickness were obtained. After treatment, the lesions contained in the samples were either processed for histological analysis or cut open for gross analysis and to carefully remove the contents for protein analysis. Results: The treatments performed with PRFs of 1, 3, 5, and 10 Hz resulted in fractionated lesions with increasing amounts of thermal damage to the tissue as evident in the protein analysis. These results were similar to those previously found for single lesions. Histological evaluation revealed that vascular structures, with a range of diameters, and supporting extracellular matrix were spared in lesions formed with 1, 3, and 5 Hz. These structures could be observed macroscopically in samples bisected and washed immediately after treatment (Figure 1). However, finer vascular structures were more sensitive to treatments at the higher PRFs. At 1Hz, the remaining structures were surrounded by finely homogenized tissue. As with single lesions, the homogenate in the volumetric lesions became less complete with increasing PRFs. At 10 Hz, a dense thermal paste with vaporized cavities was formed inside the volumetric lesion. Conclusion: This study demonstrates that large volumes of liver tissue can be decellularized by BH in a clinical HIFU system while leaving certain 3-D tissue structures like vessels intact without any thermal damage. With further tailoring of the parameters of the pulsing scheme, this treatment modality could potentially be utilized for different applications where selective removal of tissue is required such as in tumor treatment and the decellularization of organs for tissue engineering applications.
- Добавил в систему: Хохлова Вера Александровна