CT imaging of angiogenesis

Tumor angiogenesis has significant implications in the diagnosis and treatment of various solid tumors. With the advent of fast, multi-slice CT scanners, CT imaging techniques capable of qualitative and quantitative analysis of tumor angiogenesis have been the subject of extensive investigation in the past 2 decades. The fundamental bases for CT imaging of angiogenesis are both the transport by blood flow of intravenously administered iodinated contrast material to tissue and the exchange by diffusion of these contrast molecules between the intravascular space and the extravascular interstitial space. With current fast CT scanners both tissue and vascular enhancement can be measured and traced over time at small time intervals to allow detailed modeling of the distribution of contrast agent in tissue. Both compartmental and distributed parameter models for contrast transport and exchange have been developed to quantify from the CT data the following angiogenesis related parameters: tissue blood flow, blood volume, mean transit time, contrast arrival time, capillary permeability surface area product and hepatic arterial fraction in case of the liver. This review addresses the following aspects of CT imaging of angiogenesis: 1) basic concepts related to the understanding of both compartmental and distributed parameter models; 2) comparison between both types of models; 3) practical issues with respect to the measurement of the arterial input function, which is required for the solution of both types of models; and, 4) illustration of the application of a distributed parameter model, the Johnson and Wilson model, in a number of experimental studies.