The aim of this chapter is to provide an overview about models and methodologies used for the Dynamic Contrast Enhancement (DCE) analysis. DCE is a non-invasive methodology aimed to diagnostic the nature of a lesion on the base of the perfusion’s dynamic of specific contrast agents. The idea at the base of DCE is that, in several pathological tissues, including tumors and inflammatory diseases, the angiogenic process is abnormal, hence the characterization of vascularisation structure may be used to support the diagnosis. In this chapter, we will describe the basic DCE procedures and introduce some of its most innovative evolution based on the pharmacokinetic analysis technique (PK), and the empirical model (EM). Even if DCE is still a medical research topic, there is large interest for this type of approach in biomedical applications as witnessed by the availability of specific tools in the last generation top-class US, CT and MR machines.
Quantitative characterization of microvascular structure using DCE is a powerful tool, able to provide valuable information for clinical purposes and/or for therapeutic trials. One goal of DCE is to characterize tissue regions, since some of their features (blood flow, vascular characteristics, or tissue integrity) are expected to vary in pathological tissue with respect to normal one.
In a typical DCE study, the dynamic information shows the rate at which tissue “enhances”, and subsequently the rate at which Contrast Agent (CA) washes out. The enhancement is thought to be the result of the CA arriving via the system blood flown and diffusing into the interstitial space around these vessels (which is known as the extravascular extracellular space - EES). The rate and the amplitude of enhancement depend on the density and permeability of the microvasculature and on the relative size of the EES. The degree of enhancement is, therefore, related to the distribution and concentration of the CA in the vessels and in the ESS; hence the shape of the enhancement curve, then, reflects blood flow, vascular volume, extravascular volume and vessel permeability (Srikanchana et al., 2004).
The CA is used generally as an intravascular marker while the leakage into the interstitial space is generally ignored. In practice the kinetics of CA distribution are more complex and additional data can be obtained from explicit modelling of the contrast (enhancement) leakage process. In the presence of leaky capillary endothelial membranes, intravascular CA will pass into the ESS, causing enhancement. The leakage rate depends on the surface area of leaky endothelium, on the permeability of the endothelium itself and on the concentration gradient of the CA across the vessel wall. It has become apparent that quantification of contrast leakage may be a powerful indicator of the state of neo-vascular angiogenesis in pathologies, such as tumors and inflammatory processes. As for cancer research, this is very appealing, since the inhibition of angiogenesis presents new therapeutic chances of targeting of newly formed vessels, with the final aim at inhibiting their onset and growth.
Key Terms in this Chapter
Pharmacokinetics (PK): It is referred to the evalutation of chemical compounds distribution in body over time.
Transfer Constant (Ktrans): Formally called volume transfer constant is the transfer constant related to “wash in” of the CA into the tissue
Contrast Agent (CA): Contrast Media perfuses into the tissue
Contrast Enhancement (CE): Tissue Contrast Concentration: the shape of an Enhancement Curve reflects blood flow, vascular volume, extravascular volume and vessel permeability
Area Under Curve (AUC): Represents the area under the CE Curve; it measures the quantity of CA absorbed by the tissue, hence it yields an estimation of blood flow that diffuses into the specific region
Arterial Input Factor (AIF): Is the Input Function and it measures the Plasma Contrast Concentration (of a Contrast Agent)
Extravascular Extracelllar Space (EES): Interstitial space (around vessels)
General Kinetic Model (GKM): Is the basic model often used to simplifies the human anatomy into two functional components (two compartments).
Transfer Constant (kep): Is the transfer constant related with the “wash-out” of the CA from the tissue; formally is the flux rate constant between the ESS and blood plasma and can be derived from the shape of the tracer concentration vs volume data
Dynamic Contrast Enhancement (DCE): The perfusion’s dynamic of specific Contrast Agent insight the tissues;