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, interstitial fluid velocity and related parameters are of great clinical significance for cancer diagnosis, prognosis and treatment. A limited number of non-invasive techniques can be used to estimate these mechanopathological parameters in cancers in vivo. In this study, we designed and tested newultrasound poroelastography methods capable of estimating the magnitude and spatial distribution of fluid pressure, fluid velocity and fluid flow inside tumors under external compression. We theoretically proved that fluid pressure, velocity and flow estimated using poroelastography from a tumor under creep compression are directly related to the underlying interstitial fluid pressure, interstitial fluid velocity and fluid flow, respectively, differing only in peak values. Furthermore, by knowledge of the spatial distribution of the fluid pressure estimated using poroelastography, it is possible to derive: the parameter ff, which quantifies the spatial distribution of the interstitial fluid pressure, the vascular permeability to interstitial permeability ratio and the peak interstitial fluid pressure to effective vascular pressure ratio in the tumor. Our techniques were validated using finite element and ultrasound simulations for a variety of simulated phantoms. Excellent qualitative agreement was found between the fluid pressure and velocity obtained using the finite element models and the corresponding fluid pressure and fluid velocity obtained using the proposed models. The estimated parameter ff was found to differ from the corresponding theoretical value by less than 10%. Experiments on a human breast cancer animal model were used as proof-of-principle of the feasibility of the proposed methods in vivo

Automated summary

Interstitial fluid pressure, interstitial fluid velocity and related parameters play a crucial role in cancer diagnosis, prognosis and treatment. Non-invasive techniques have been developed to estimate these mechanopathological parameters in cancers in vivo. The new ultrasound poroelastography methods were able to accurately estimate fluid pressure, fluid velocity and fluid flow inside tumors under external compression, with validation through finite element and ultrasound simulations.