Effect of Continuous High Intensity Focused Ultrasound in a Squamous Cell Carcinoma Tumor Model Compared to Muscle Tissue Evaluated by MRI, Histology, and Gene Expression

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Abstract

The purpose of this study was to investigate the effect of the continuous mode of high intensity focused ultrasound (HIFU) in a mouse head and neck cancer model (SCCVII) compared to muscle tissue. HIFU was applied to SCCVII tumors and to muscle tissue in C3H/Km mice using a dual ultrasound system (imaging 6 MHz/therapeutic 1 MHz). A continuous HIFU mode (total time 20 sec, intensity 6730.6 W/cm2) was applied. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images, and a diffusion-wt STEAM sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle tissue was taken out for histology and functional genomic analysis.

T2 images showed increased signal intensity, post-contrast T1 showed a decreased contrast uptake in the central parts in the tumor tissue as well as in the muscle tissue. In addition a significant higher diffusion coefficient was found in both tissue types. Histological evaluation (H&E, Immunohistochemistry) of the tumors and the muscle tissue revealed areas of significant necrosis. In the tumor tissue 23 genes were up-regulated (> 2 fold change) and 4 genes were down-regulated (< −2 fold change). In the muscle tissue 29 genes were up-regulated and 17 genes down-regulated. Thirteen genes were up-regulated in both tissue types, 8 genes only in the SCCVII tissue, and 11 genes only in the muscle tissue. The use of HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression. The expression of some genes are tissue specific, the expression of other genes are independent of the tissue type.

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