In-vitro investigation of the relationship between microvascular structure and ultrasound contrast agent dynamics

Prostate cancer (PCa) is the second leading cause of cancer mortality in men in western countries. Tumor-driven angiogenesis is a recognized hallmark of cancer. Typical features of angiogenic vasculature include increased microvascular density (MVD), smaller vessel diameter and higher tortuosity, resulting in complex blood-flow patterns. Dynamic contrast-enhanced ultrasound (DCE-US) widely provides a noninvasive diagnostic tool for PCa detection with the passage of ultrasound contrast agents (UCAs) through the prostate. Analysis of the UCA dispersion kinetics in the tumor vasculature has shown promise for PCa diagnostics, but a clear link between the estimated kinetics parameters and the underlying microvascular structure is still lacking. In this work, modeling the prostate microvasculature as a porous medium, we developed tissue-mimicking phantoms with variable pore size, representing different MVD and vessel diameter. The UCA flow through the phantoms was recorded by DCE-US, and UCA velocity and dispersion coefficient were estimated by model-based deconvolution. In general, phantoms reproducing increased MVD and smaller vessel diameter lead to increased velocity and decreased dispersion coefficient. This is line with our in-vivo findings in PCa patients. Further validation will be performed by insilico simulation and more complex in-vitro phantoms in the future.