WE‐E‐17A‐09: Modulation of the Interstitial Fluid Pressure by High Intensity Focused Ultrasound as a Way to Alter Local Fluid and Solute Movement: Insights From a Mathematical Model

Abstract

Purpose:To investigate and quantify the mechanisms responsible for the increased uptake of macromolecules observed in tissue exposed to pulsed high‐intensity focused ultrasound (HIFU) guided by MRI in preclinical studies.Methods:A mathematical model describing the transport of fluid and macromolecules in normal and tumor tissue is presented. The tissue is treated as a porous‐permeable, isotropic and linearly elastic medium. The model calculates the changes in the interstitial fluid pressure (IFP) and the interstitial fluid velocity (IFV) immediately after HIFU exposure. T2 weighted MR images taken a few minutes after a pulsed HIFU exposure of a rabbit thigh have been employed to estimate the fluid content in the tissue. A typical HIFU exposure is about 60s long and results in a temperature increase (hottest pixel) of about 140C as measured by MRI thermometry. The IFP and the IVF are then inserted into a macroscopic solute transport equation to determine the tissue concentration profiles of macromolecules. The model equations have been solved numerically using a finite element technique.Results:In both normal and tumor tissue, the model shows that in the focal region, immediately after HIFU exposure, there is a decrease in the IFP and the IVF is directed inward. Furthermore, the solution of the solute transport equation predicts a significant accumulation in the interstitium of large macromolecule solutes such as IgG which has a molecular weight of 150,000 Da.Conclusion:Efficient delivery of therapeutic agents in targeted tissues still remains a significant challenge in medicine. HIFU guided by MRI has been shown to improve targeted drug delivery in preclinical studies. The results of our simulation suggest improved fluid convection and macromolecule distribution during the initial lowering of the IFP resulting from HIFU exposure. This model offers valuable guidance for developing strategies that employ MRI‐guided HIFU for improving targeted drug delivery.