Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers. (1st January 2020)

• Record Type: Journal Article
• Authors: Lorton, Orane; Guillemin, Pauline C.; Holman, Ryan; Desgranges, Stéphane; Gui, Laura; Crowe, Lindsey A.; Terraz, Sylvain; Nastasi, Antonio; Lazeyras, François; Contino-Pépin, Christiane; Salomir, Rares
• Is Part Of: International journal of hyperthermia. Volume 37:Number 1(2020)
• Page Start: 1116
• Page End: 1130
• Publication Date: 2020-01-01
• Subjects: MRgHIFU -- sonosensitizers -- micro-droplets -- perfused model -- thermal deposition; Thermotherapy -- Periodicals; 615.832
• DOI: 10.1080/02656736.2020.1817575
• Languages: English
• ISSNs: 0265-6736

Abstract

Abstract: 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