Estimation of vascular density and blood velocity in tumors

We have completed a series of validation studies to demonstrate that ultrasound with a contrast agent and perfusion estimator is a reliable, accurate, and non-invasive method of measuring blood flow. A subharmonic phase-inversion detection scheme (Chomas et al.) was implemented on a Siemens Elegra scanner. A fluorescent microsphere study was completed in which high correlation was found between the spatial integral of flow obtained from ultrasound derived parameters and the microsphere measurement of ml of flow/minute/gram of tissue. We seek to further validate our results by showing a high degree of spatial correlation between US images and those acquired using histological analysis. In addition, contrast-enhanced ultrasound imaging studies were completed using a rat mammary adenocarcinoma model to evaluate the performance of an anti-angiogenic drug. Mean replenishment times and integrated enhancement values were calculated and differences between treated and control tumors were evaluated. The spatial extent of flow and the spatial integral of flow were calculated from the histograms of integrated enhancement and provide a method of comparison between tumors treated with the anti-angiogenic drug and control tumors. These parameters demonstrate a significant difference between the treated and control groups (P<0.05). A significant difference was not present in these parameters between groups prior to the onset of treatment (P>0.1).