Perfusion/Permeability 1: Tracer Kinetic Modeling Using Contrast Agents

• Agents originally developed to enhance contrast-to-noise in anatomic images following intravenous administration. • Their principal mode of action is to increase the relaxation rates (1/T1, 1/T2, 1/T2*) of nearby water molecules thereby modifying local signal intensity. • Extracellular agents (such as Gd-DTPA) accumulate in the interstitium of many tissues (e.g. muscle) but do not cross the blood-brain-barrier (BBB) in normal brain tissue. • Gd-DTPA is particularly useful for identifying breakdown of the BBB in conditions such as cancer, multiple sclerosis and ischemia. • Extracellular agents are by far the most common contrast agents in use today. Others exist and numerous agents are in development but this discussion is limited to Gd-DTPA and its like. o Functional information may be obtained by treating Gd-DTPA as a tracer and following its kinetics (as opposed to the conventional approach, inject wait – image once). o After intravenous administration (normally in the form of a bolus) Gd-DTPA transits the venous and arterial system leaking from capillary beds wherever the endothelial cell junctions allow. It is excreted via the kidneys [1]. • The choice of imaging method is crucially dependent on what is to be measured and the rate of tracer delivery and uptake.