Cardiovascular Molecular Imaging Imaging Techniques and Quantification

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in the western world and developing countries. Diseases affecting the cardiovascular system are expected to be the main cause of death globally within the next 20 years. This is due to the rising prevalence of CVD in the eastern parts of Europe, developing countries and an increasing incidence of obesity and diabetes in the western world 1. Molecular imaging with targeted contrast agents using MRI refers to the noninvasive visualization of biological processes at the cellular and molecular level with MRI in vivo to improve characterization and detection of normal and diseased tissues. Compared to other molecular imaging modalities (e.g. SPECT, PET), MRI provides excellent spatial resolution, unique soft tissue contrast and has the ability to simultaneously assess anatomy, function and biological processes at the cellular and molecular level. 2 The disadvantage of MRI is its relatively low sensitivity for contrast agents (~50μ), which makes imaging of low abundance targets challenging. Several classes of molecular MR contrast agent exist, which include small molecular weight contrast agents and nanoparticles. MR contrast agents can be used to shorten local T1 and T2 relaxation times. Gadolinium (Gd) based contrast agents cause an increase in the longitudinal relaxation rate (R1), due to their paramagnetic properties. The increase in R1 is found to be directly proportional to the contrast agent concentration and can be calculated by measuring the intrinsic relaxation rate R1 before and after contrast agent injection. Contrast agents, however, also influence and shorten the T2 relaxation time 3. Due to the low abundance of certain molecular imaging targets, longitudinal and transverse relaxivity, r1 and r2, are essential for the design of target specific contrast agents and will be discussed later. Signal intensity in MRI primarily depends on the local values of longitudinal and transverse relaxation rates of water protons. Gadolinium and iron oxide based MR contrast agents are therefore not directly detectable, but only indirectly by their effect on surrounding water protons. Usually a threshold for a local concentration of a contrast agent (typically μM to mM for agents having a r1 between 4-80 mM-1s-1) has to be reached to alter relaxation rate of water protons sufficiently for detectable signal effects. MR imaging sequences can be divided into spin echo (SE) and gradient echo (GRE) sequences (Table 1). Several types of SE or GRE imaging sequences can be used for optimal contrast …