Scientific article
Open access

Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers

Published inInternational journal of hyperthermia, vol. 37, no. 1, p. 1116-1130
Publication date2020

Background: High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-core sonosensitizers have been previously suggested to enhance the thermal energy deposition at the focal area and to lower the near-/far-field heating. We are investigating the therapeutic potential of PFOB-FTAC micro-droplets in a perfused tissue-mimicking model and postmortem excised organs.

Method: A custom-made in vitro perfused tissue-mimicking model, freshly excised pig kidneys (n = 3) and liver (n = 1) were perfused and subjected to focused ultrasound generated by an MR-compatible HIFU transducer. PFOB-FTAC sonosensitizers were injected in the perfusion fluid up to 0.235% v/v ratio. Targeting and on-line PRFS thermometry were performed on a 3 T MR scanner. Assessment of the fluid perfusion was performed with pulsed color Doppler in vitro and with dynamic contrast-enhanced (DCE)-MRI in excised organs.

Results: Our in vitro model of perfused tissue demonstrated re-usability. Sonosensitizer concentration and perfusion rate were tunable in situ. Differential heating under equivalent HIFU sonications demonstrated a dramatic improvement in the thermal deposition due to the sonosensitizers activity. Typically, the energy deposition was multiplied by a factor between 2.5 and 3 in perfused organs after the administration of micro-droplets, while DCE-MRI indicated an effective perfusion.

Conclusion: The current PFOB-FTAC micro-droplet sonosensitizers provided a large and sustained enhancement of the HIFU thermal deposition at the focal area, suggesting solutions for less technological constraints, lower risk for the near-/far- field heating. We also report a suitable experimental model for other MRgHIFU studies.

  • micro-droplets
  • perfused model
  • sonosensitizers
  • thermal deposition
  • Animals
  • Fluorocarbons
  • High-Intensity Focused Ultrasound Ablation
  • Hydrocarbons, Brominated
  • Magnetic Resonance Imaging
  • Swine
  • Thermometry
Citation (ISO format)
LORTON, Orane et al. Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers. In: International journal of hyperthermia, 2020, vol. 37, n° 1, p. 1116–1130. doi: 10.1080/02656736.2020.1817575
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Article (Published version)
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ISSN of the journal0265-6736

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