Non-invasive assessment of the spatial and temporal distributions of interstitial fluid pressure, fluid velocity and fluid flow in cancers in vivo

Interstitial fluid pressure (IFP), interstitial fluid velocity (IFV), interstitial permeability (IP) and vascular permeability (VP) are cancer mechanopathological parameters of great clinical significance. To date, there is a lack of non-invasive techniques that can be used to estimate these parameters in vivo. In this study, we designed and tested new ultrasound poroelastography methods capable of estimating the magnitude and spatial distribution of fluid pressure, fluid velocity and fluid flow inside tumors. We theoretically proved that fluid pressure, velocity and flow estimated using poroelastography from a tumor under creep compression are directly related to the underlying IFP, IFV and fluid flow, respectively, differing only in peak values. We also proved that, from the spatial distribution of the fluid pressure estimated using poroelastography, it is possible to derive: the parameter alpha, which quantifies the spatial distribution of the IFP; the ratio between VP and IP and the ratio between the peak IFP and effective vascular pressure in the tumor. Finally, we demonstrated that axial strain time constant (TC) elastograms are directly related to VP and IP in tumors. Our techniques were validated using finite element and ultrasound simulations, while experiments on a human breast cancer animal model were used to show the feasibility of these methods in vivo.