Lowering of the Interstitial Fluid Pressure as a Result of Tissue Compliance Changes during High Intensity Focused Ultrasound Exposure: Insights from a Numerical Model

Interstitial fluid pressure (IFP) is elevated in tumors. This may constitute a significant physiological barrier to drug delivery to solid tumors. Owing to this elevated IFP, the interstitial fluid velocity (IFV) is negligible throughout the tumor but significant near the tumor margin. Any therapeutic strategy that can lower the IFP will likely improve drug convection within the tumor and decrease convection of drugs from the tumor margin. High intensity focused ultrasound (HIFU) operated in thermal mode has been shown to reduce the IFP and to improve the penetration of therapeutics in tumors. We have used a mathematical model to simulate the effect of HIFU on the IFP and IFV. We have shown that a reduction of the IFP as a result of HIFU exposure facilitates fluid convection and macromolecule distribution within the exposed area and reduces fluid convection and macromolecule wash out at its margin.