Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model

Tatiana D. Khokhlova, Yak Nam Wang, Julianna Simon, Bryan W. Cunitz, Frank Starr, Marla Paun, Lawrence A. Crum, Michael R. Bailey, Vera A. Khokhlova

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extra-corporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

Original languageEnglish (US)
Pages (from-to)8161-8166
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number22
DOIs
StatePublished - Jun 3 2014

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Swine
Liver
Heating
Blood Vessels
Hot Temperature
Ribs
Therapeutics
Cell- and Tissue-Based Therapy
Connective Tissue
Pressure

All Science Journal Classification (ASJC) codes

  • General

Cite this

Khokhlova, Tatiana D. ; Wang, Yak Nam ; Simon, Julianna ; Cunitz, Bryan W. ; Starr, Frank ; Paun, Marla ; Crum, Lawrence A. ; Bailey, Michael R. ; Khokhlova, Vera A. / Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 22. pp. 8161-8166.
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Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model. / Khokhlova, Tatiana D.; Wang, Yak Nam; Simon, Julianna; Cunitz, Bryan W.; Starr, Frank; Paun, Marla; Crum, Lawrence A.; Bailey, Michael R.; Khokhlova, Vera A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 22, 03.06.2014, p. 8161-8166.

Research output: Contribution to journalArticle

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AU - Khokhlova, Tatiana D.

AU - Wang, Yak Nam

AU - Simon, Julianna

AU - Cunitz, Bryan W.

AU - Starr, Frank

AU - Paun, Marla

AU - Crum, Lawrence A.

AU - Bailey, Michael R.

AU - Khokhlova, Vera A.

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AB - The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extra-corporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

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