High resolution 3D flow mapping in tumors

Tumor biologists indicate that angiogenesis is required for tumor growth beyond about 1 mm ³. Furthermore, regions of increased and decreased vascular density are each on the order of 500 μm. Therefore, it is for tumors whose size is on the order of 1 mm ³ that we would like to detect this increased vascular density, and a resolution of at least 500 μm is critical. In a small clinical study we were able to detect localized vasculature in all malignant masses of diameter 1 cm ³ or greater, with associated vessels of a size 300 μm or greater. In order to detect very low velocity blood flow in vessels of diameter less than 300 gin, we evaluate the feasibility of both nominal 50 MHz color flow mapping without contrast, and 7 MHz color flow mapping with contrast agent. We tested these strategies with LNCaP athymic mice, a human prostate tumor model. In a very high frequency study, we detected low velocity flow in vessels as small as 50 μm within and surrounding the tumor. In our a 7 MHz contrast study, vessels less than 200 μm were not detected with color flow without a contrast agent. With a contrast agent, the dense vasculature within and surrounding the tumors was detected, however, individual vessels can not be resolved. These tumor models are a new tool to evaluate imaging systems, with both development and morphology being similar to human tumors. We have detected both high speed flow in A-V shunts and low velocity flow in these tumor models. In this paper, we establish the feasibility of 7 MHz contrast assisted imaging for detection of smaller vessels, with the goal of detecting angiogenesis in its earliest stages (i.e. for a 1 mm ³ tumor).