Estimation of Vascular Permeability in Irregularly Shaped Cancers Using Ultrasound Poroelastography

Objective: Vascular permeability (VP) is a mechanical parameter which plays an important role in cancer initiation, metastasis, and progression. To date, there are only a few non-invasive methods that can be used to image VP in solid tumors. Most of these methods require the use of contrast agents and are expensive, limiting widespread use. Methods: In this paper, we propose a new method to image VP in tumors, which is based on the use of ultrasound poroelastography. Estimation of VP by poroelastography requires knowledge of the Young's modulus (YM), Poisson's ratio (PR), and strain time constant (TC) in the tumors. In our method, we find the ellipse which best fits the tumor (regardless of its shape) using an eigen-system-based fitting technique and estimate the YM and PR using Eshelby's elliptic inclusion formulation. A Fourier method is used to estimate the axial strain TC, which does not require any initial guess and is highly robust to noise. Results: It is demonstrated that the proposed method can estimate VP in irregularly shaped tumors with an accuracy of above \text{80}\% using ultrasound simulation data with signal-to-noise ratio of 20 dB or higher. In vivo feasibility of the proposed technique is demonstrated in an orthotopic mouse model of breast cancer. Conclusion: The proposed imaging method can provide accurate and localized estimation of VP in cancers non-invasively and cost-effectively. Significance: Accurate and non-invasive assessment of VP can have a significant impact on diagnosis, prognosis, and treatment of cancers.