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

中文翻译：

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使用微米级 FTAC 稳定的 PFOB 核心血管内声敏剂增强灌注组织模型中的 HIFU 热疗法

摘要

背景

高强度聚焦超声 (HIFU) 在临床上被接受用于治疗实体瘤，但由于散热器效应，在高灌注组织中仍然具有挑战性。血管内液体核心声敏剂先前已被建议用于增强焦点区域的热能沉积并降低近/远场加热。我们正在研究 PFOB-FTAC 微滴在灌注组织模拟模型和死后切除器官中的治疗潜力。

方法

定制的体外灌注组织模拟模型、新鲜切除的猪肾脏 ( n  = 3) 和肝脏 ( n  = 1) 被灌注并接受由 MR 兼容的 HIFU 换能器产生的聚焦超声。PFOB-FTAC 声敏剂以高达 0.235% v/v 的比例注入灌注液中。在 3 T MR 扫描仪上进行靶向和在线 PRFS 测温。用体外脉冲彩色多普勒和切除器官的动态对比增强 (DCE)-MRI对液体灌注进行评估。

结果

我们的体外灌注组织模型证明了可重复使用性。声敏剂浓度和灌注率可原位调节。由于声敏剂的活性，等效 HIFU 超声处理下的差异加热表明热沉积有显着改善。通常，在施用微滴后，灌注器官中的能量沉积乘以 2.5 到 3 之间的系数，而 DCE-MRI 表明有效灌注。

结论

当前的 PFOB-FTAC 微液滴声敏剂在焦点区域提供了大而持续的 HIFU 热沉积增强，提出了减少技术限制、降低近/远场加热风险的解决方案。我们还报告了适用于其他 MRgHIFU 研究的实验模型