Subharmonic phase-inversion for tumor perfusion estimation

A perfusion estimation scheme based on the destruction and wash-in of ultrasound contrast agents enables the estimation of microvascular flow velocities below those estimated by traditional Doppler and colorflow methods. The observation of low-flow microvascular beds is useful in the monitoring of therapy in a research setting. Perfusion estimation may be described in four steps: bubble destruction, non-destructive imaging, detection, and estimation. The destructive and non-destructive imaging modes are implemented in real-time on a modified clinical ultrasound scanner (Siemens, Issaquah, WA). In-vivo results in a chronic tumor study show that the system is capable of detecting microvascular flow that is otherwise undetectable with Doppler or colorflow imaging methods. The resulting maps of increased vascular density correlate with regions of active tumor cells on histology. Maps of increased blood flow correlate with computed tomography. Microvascular heterogeneities on the scale of 800 μm are observed in tumors, with a ring of perfusion developing as the tumor grows. Vascular regions in the periphery of the tumor require less than 4 seconds to achieve 80% perfusion, while other regions in the tumor require up to 30 seconds.