Combination of HIFU therapy with contrast-enhanced sonography for quantitative assessment of therapeutic efficiency on tumor grafted mice

The objective was to evaluate treatment efficiency of a new high-intensity focused ultrasound (HIFU) prototype combining a therapeutic transducer with a sonographic probe. The optimal HIFU sequence was defined on ex vivo samples before in vivo evaluation of tumor ablation was performed by perfusion quantification after contrast agent injection. The original feature of this prototype is a 9-MHz sonographic probe in a HIFU device and connected to an Aplio (Toshiba®) sonograph. Acoustical power and treatment time were determined on ex vivo livers to generate 1-cm-long lesions. Lesion reproducibility was assessed for the power and treatment time selected. The gap between lesions and HIFU displacement shot procedures were optimized to ablate a 1-cm3 volume. The optimized protocol was applied to five murine tumors in vivo. Tumor ablation was quantified according to (1) contrast uptake (CU) after HIFU using perfusion software (Toshiba®) in “vascular recognition imaging” mode and Sonovue (Bracco®) contrast agent, and (2) the percentage of necrosis quantified on histologic slides. Ex vivo results: optimized settings, at 442 W/cm2 applied during three cycles (3 s on/5 s off) generated 10 identical elementary lesions measuring 9.78 (±0.66) * 2.11 (±0.33) mm2. A 4-mm gap between adjacent lesions and a 2-min pause between shot lines were found optimal. In vivo results: 60 % (±22) mean reduction in CU after HIFU and tumor necrosis histologically estimated at 58 % (±5.7) were quantified for the five animals. The therapeutic potential of this HIFU prototype was demonstrated in vivo through objective quantification of tumor ablation based on CU. (E-mail: rouffiac@igr.fr)